Sample records for modulate motor cortex

  1. Monoaminergic Modulation of Motor Cortex Function

    PubMed Central

    Vitrac, Clément; Benoit-Marand, Marianne

    2017-01-01

    Elaboration of appropriate responses to behavioral situations rests on the ability of selecting appropriate motor outcomes in accordance to specific environmental inputs. To this end, the primary motor cortex (M1) is a key structure for the control of voluntary movements and motor skills learning. Subcortical loops regulate the activity of the motor cortex and thus contribute to the selection of appropriate motor plans. Monoamines are key mediators of arousal, attention and motivation. Their firing pattern enables a direct encoding of different states thus promoting or repressing the selection of actions adapted to the behavioral context. Monoaminergic modulation of motor systems has been extensively studied in subcortical circuits. Despite evidence of converging projections of multiple neurotransmitters systems in the motor cortex pointing to a direct modulation of local circuits, their contribution to the execution and learning of motor skills is still poorly understood. Monoaminergic dysregulation leads to impaired plasticity and motor function in several neurological and psychiatric conditions, thus it is critical to better understand how monoamines modulate neural activity in the motor cortex. This review aims to provide an update of our current understanding on the monoaminergic modulation of the motor cortex with an emphasis on motor skill learning and execution under physiological conditions. PMID:29062274

  2. Signals from the ventrolateral thalamus to the motor cortex during locomotion

    PubMed Central

    Marlinski, Vladimir; Nilaweera, Wijitha U.; Zelenin, Pavel V.; Sirota, Mikhail G.

    2012-01-01

    The activity of the motor cortex during locomotion is profoundly modulated in the rhythm of strides. The source of modulation is not known. In this study we examined the activity of one of the major sources of afferent input to the motor cortex, the ventrolateral thalamus (VL). Experiments were conducted in chronically implanted cats with an extracellular single-neuron recording technique. VL neurons projecting to the motor cortex were identified by antidromic responses. During locomotion, the activity of 92% of neurons was modulated in the rhythm of strides; 67% of cells discharged one activity burst per stride, a pattern typical for the motor cortex. The characteristics of these discharges in most VL neurons appeared to be well suited to contribute to the locomotion-related activity of the motor cortex. In addition to simple locomotion, we examined VL activity during walking on a horizontal ladder, a task that requires vision for correct foot placement. Upon transition from simple to ladder locomotion, the activity of most VL neurons exhibited the same changes that have been reported for the motor cortex, i.e., an increase in the strength of stride-related modulation and shortening of the discharge duration. Five modes of integration of simple and ladder locomotion-related information were recognized in the VL. We suggest that, in addition to contributing to the locomotion-related activity in the motor cortex during simple locomotion, the VL integrates and transmits signals needed for correct foot placement on a complex terrain to the motor cortex. PMID:21994259

  3. Engagement of the Rat Hindlimb Motor Cortex across Natural Locomotor Behaviors.

    PubMed

    DiGiovanna, Jack; Dominici, Nadia; Friedli, Lucia; Rigosa, Jacopo; Duis, Simone; Kreider, Julie; Beauparlant, Janine; van den Brand, Rubia; Schieppati, Marco; Micera, Silvestro; Courtine, Grégoire

    2016-10-05

    Contrary to cats and primates, cortical contribution to hindlimb locomotor movements is not critical in rats. However, the importance of the motor cortex to regain locomotion after neurological disorders in rats suggests that cortical engagement in hindlimb motor control may depend on the behavioral context. To investigate this possibility, we recorded whole-body kinematics, muscle synergies, and hindlimb motor cortex modulation in freely moving rats performing a range of natural locomotor procedures. We found that the activation of hindlimb motor cortex preceded gait initiation. During overground locomotion, the motor cortex exhibited consistent neuronal population responses that were synchronized with the spatiotemporal activation of hindlimb motoneurons. Behaviors requiring enhanced muscle activity or skilled paw placement correlated with substantial adjustment in neuronal population responses. In contrast, all rats exhibited a reduction of cortical activity during more automated behavior, such as stepping on a treadmill. Despite the facultative role of the motor cortex in the production of locomotion in rats, these results show that the encoding of hindlimb features in motor cortex dynamics is comparable in rats and cats. However, the extent of motor cortex modulations appears linked to the degree of volitional engagement and complexity of the task, reemphasizing the importance of goal-directed behaviors for motor control studies, rehabilitation, and neuroprosthetics. We mapped the neuronal population responses in the hindlimb motor cortex to hindlimb kinematics and hindlimb muscle synergies across a spectrum of natural locomotion behaviors. Robust task-specific neuronal population responses revealed that the rat motor cortex displays similar modulation as other mammals during locomotion. However, the reduced motor cortex activity during more automated behaviors suggests a relationship between the degree of engagement and task complexity. This relationship emphasizes the importance of the behavioral procedure to engage the motor cortex during motor control studies, gait rehabilitation, and locomotor neuroprosthetic developments in rats. Copyright © 2016 the authors 0270-6474/16/3610440-16$15.00/0.

  4. Motor cortex plasticity can indicate vulnerability to motor fluctuation and high L-DOPA need in drug-naïve Parkinson's disease.

    PubMed

    Kishore, Asha; James, Praveen; Krishnan, Syam; Yahia-Cherif, Lydia; Meunier, Sabine; Popa, Traian

    2017-02-01

    Motor cortex plasticity is reported to be decreased in Parkinson's disease in studies which pooled patients in various stages of the disease. Whether the early decrease in plasticity is related to the motor signs or is linked to the future development of motor complications of treatment is unclear. The aim of the study was to test if motor cortex plasticity and its cerebellar modulation are impaired in treatment-naïve Parkinson's disease, are related to the motor signs of the disease and predict occurrence of motor complications of treatment. Twenty-nine denovo patients with Parkinson's disease were longitudinally assessed for motor complications for four years. Using transcranial magnetic stimulation, the plasticity of the motor cortex and its cerebellar modulation were measured (response to paired-associative stimulation alone or preceded by 2 active cerebellar stimulation protocols), both in the untreated state and after a single dose of L-DOPA. Twenty-six matched, healthy volunteers were tested, only without L-DOPA. Patients and healthy controls had similar proportions of responders and non-responders to plasticity induction. In the untreated state, the more efficient was the cerebellar modulation of motor cortex plasticity, the lower were the bradykinesia and rigidity scores. The extent of the individual plastic response to paired associative stimulation could indicate a vulnerability to develop early motor fluctuation but not dyskinesia. Measuring motor cortex plasticity in denovo Parkinson's disease could be a neurophysiological parameter that may help identify patients with greater propensity for early motor fluctuations. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Non-Invasive Electrical Brain Stimulation Montages for Modulation of Human Motor Function.

    PubMed

    Curado, Marco; Fritsch, Brita; Reis, Janine

    2016-02-04

    Non-invasive electrical brain stimulation (NEBS) is used to modulate brain function and behavior, both for research and clinical purposes. In particular, NEBS can be applied transcranially either as direct current stimulation (tDCS) or alternating current stimulation (tACS). These stimulation types exert time-, dose- and in the case of tDCS polarity-specific effects on motor function and skill learning in healthy subjects. Lately, tDCS has been used to augment the therapy of motor disabilities in patients with stroke or movement disorders. This article provides a step-by-step protocol for targeting the primary motor cortex with tDCS and transcranial random noise stimulation (tRNS), a specific form of tACS using an electrical current applied randomly within a pre-defined frequency range. The setup of two different stimulation montages is explained. In both montages the emitting electrode (the anode for tDCS) is placed on the primary motor cortex of interest. For unilateral motor cortex stimulation the receiving electrode is placed on the contralateral forehead while for bilateral motor cortex stimulation the receiving electrode is placed on the opposite primary motor cortex. The advantages and disadvantages of each montage for the modulation of cortical excitability and motor function including learning are discussed, as well as safety, tolerability and blinding aspects.

  6. Dopamine Promotes Motor Cortex Plasticity and Motor Skill Learning via PLC Activation

    PubMed Central

    Rioult-Pedotti, Mengia-Seraina; Pekanovic, Ana; Atiemo, Clement Osei; Marshall, John; Luft, Andreas Rüdiger

    2015-01-01

    Dopaminergic neurons in the ventral tegmental area, the major midbrain nucleus projecting to the motor cortex, play a key role in motor skill learning and motor cortex synaptic plasticity. Dopamine D1 and D2 receptor antagonists exert parallel effects in the motor system: they impair motor skill learning and reduce long-term potentiation. Traditionally, D1 and D2 receptor modulate adenylyl cyclase activity and cyclic adenosine monophosphate accumulation in opposite directions via different G-proteins and bidirectionally modulate protein kinase A (PKA), leading to distinct physiological and behavioral effects. Here we show that D1 and D2 receptor activity influences motor skill acquisition and long term synaptic potentiation via phospholipase C (PLC) activation in rat primary motor cortex. Learning a new forelimb reaching task is severely impaired in the presence of PLC, but not PKA-inhibitor. Similarly, long term potentiation in motor cortex, a mechanism involved in motor skill learning, is reduced when PLC is inhibited but remains unaffected by the PKA inhibitor. Skill learning deficits and reduced synaptic plasticity caused by dopamine antagonists are prevented by co-administration of a PLC agonist. These results provide evidence for a role of intracellular PLC signaling in motor skill learning and associated cortical synaptic plasticity, challenging the traditional view of bidirectional modulation of PKA by D1 and D2 receptors. These findings reveal a novel and important action of dopamine in motor cortex that might be a future target for selective therapeutic interventions to support learning and recovery of movement resulting from injury and disease. PMID:25938462

  7. Inter-cortical Modulation from Premotor to Motor Plasticity.

    PubMed

    Huang, Ying-Zu; Chen, Rou-Shayn; Fong, Po-Yu; Rothwell, John C; Chuang, Wen-Li; Weng, Yi-Hsin; Lin, Wey-Yil; Lu, Chin-Song

    2018-06-11

    Plasticity is involved in daily activities but abnormal plasticity may be deleterious. In this study, we found that motor plasticity could be modulated by suppressing the premotor cortex with the theta burst form of repetitive transcranial magnetic stimulation. Such changes in motor plasticity were associated with reduced learning of a simple motor task. We postulate that the premotor cortex adjusts the amount of motor plasticity to modulate motor learning through heterosynaptic metaplasticity. The present results provide an insight into how the brain physiologically coordinates two different areas to bring them into a functional network. This concept could be employed to intervene in diseases with abnormal plasticity. Primary motor cortex (M1) plasticity is known to be influenced by the excitability and prior activation history of M1 itself. However, little is known about how its plasticity is influenced by other areas of the brain. In the present study on humans of either sex who were known to respond to theta burst stimulation from previous studies, we found plasticity of M1 could be modulated by suppressing the premotor cortex with the theta burst form of repetitive transcranial magnetic stimulation. Motor plasticity was distorted and disappeared 30 min and 120 min respectively after premotor excitability was suppressed. Further evaluation revealed that such changes in motor plasticity were associated with impaired learning of a simple motor task. We postulate that the premotor cortex modulates the amount of plasticity within M1 through heterosynaptic metaplasticity, and that this may impact on learning of a simple motor task previously shown to be directly affected by M1 plasticity. The present results provide an insight into how the brain physiologically coordinates two different areas to bring them into a functional network. Furthermore, such concepts could be translated into therapeutic approaches for diseases with aberrant plasticity. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  8. Cleveland Clinic Rehabilitation Research Program

    DTIC Science & Technology

    2015-12-01

    Study 1: The penicillin-induced seizure animal model has been generated by acute focal intracortical injection of penicillin in the motor cortex of rats ... motor cortex of rats . The effects of transcranial magnetic stimulation (TMS) on penicillin-induced seizure have been investigated using behavioral...electroencephalographic (EEG) recording. Study 2: The motor cortex (M1) and the corticospinal tracts (CST) will be directly modulated using brain stimulation

  9. [Transcranial magnetic stimulation and motor cortex stimulation in neuropathic pain].

    PubMed

    Mylius, V; Ayache, S S; Teepker, M; Kappus, C; Kolodziej, M; Rosenow, F; Nimsky, C; Oertel, W H; Lefaucheur, J P

    2012-12-01

    Non-invasive and invasive cortical stimulation allows the modulation of therapy-refractory neuropathic pain. High-frequency repetitive transcranial magnetic stimulation (rTMS) of the contralateral motor cortex yields therapeutic effects at short-term and predicts the benefits of epidural motor cortex stimulation (MCS). The present article summarizes the findings on application, mechanisms and therapeutic effects of cortical stimulation in neuropathic pain.

  10. Subthalamic Nucleus Stimulation Modulates Motor Cortex Oscillatory Activity in Parkinson's Disease

    ERIC Educational Resources Information Center

    Devos, D.; Labyt, E.; Derambure, P.; Bourriez, J. L.; Cassim, F.; Reyns, N.; Blond, S.; Guieu, J. D.; Destee, A.; Defebvre, L.

    2004-01-01

    In Parkinson's disease, impaired motor preparation has been related to an increased latency in the appearance of movement-related desynchronization (MRD) throughout the contralateral primary sensorimotor (PSM) cortex. Internal globus pallidus (GPi) stimulation improved movement desynchronization over the PSM cortex during movement execution but…

  11. Self-modulation of primary motor cortex activity with motor and motor imagery tasks using real-time fMRI-based neurofeedback

    PubMed Central

    Berman, Brian D.; Horovitz, Silvina G.; Venkataraman, Gaurav; Hallett, Mark

    2011-01-01

    Advances in fMRI data acquisition and processing have made it possible to analyze brain activity as rapidly as the images are acquired allowing this information to be fed back to subjects in the scanner. The ability of subjects to learn to volitionally control localized brain activity within motor cortex using such real-time fMRI-based neurofeedback (NF) is actively being investigated as it may have clinical implications for motor rehabilitation after central nervous system injury and brain-computer interfaces. We investigated the ability of fifteen healthy volunteers to use NF to modulate brain activity within the primary motor cortex (M1) during a finger tapping and tapping imagery task. The M1 hand area ROI (ROIm) was functionally localized during finger tapping and a visual representation of BOLD signal changes within the ROIm fed back to the subject in the scanner. Surface EMG was used to assess motor output during tapping and ensure no motor activity was present during motor imagery task. Subjects quickly learned to modulate brain activity within their ROIm during the finger-tapping task, which could be dissociated from the magnitude of the tapping, but did not show a significant increase within the ROIm during the hand motor imagery task at the group level despite strongly activating a network consistent with the performance of motor imagery. The inability of subjects to modulate M1 proper with motor imagery may reflect an inherent difficulty in activating synapses in this area, with or without NF, since such activation may lead to M1 neuronal output and obligatory muscle activity. Future real-time fMRI-based NF investigations involving motor cortex may benefit from focusing attention on cortical regions other than M1 for feedback training or alternative feedback strategies such as measures of functional connectivity within the motor system. PMID:21803163

  12. Abnormal dopaminergic modulation of striato-cortical networks underlies levodopa-induced dyskinesias in humans

    PubMed Central

    Haagensen, Brian N.; Christensen, Mark S.; Madsen, Kristoffer H.; Rowe, James B.; Løkkegaard, Annemette; Siebner, Hartwig R.

    2015-01-01

    Dopaminergic signalling in the striatum contributes to reinforcement of actions and motivational enhancement of motor vigour. Parkinson's disease leads to progressive dopaminergic denervation of the striatum, impairing the function of cortico-basal ganglia networks. While levodopa therapy alleviates basal ganglia dysfunction in Parkinson's disease, it often elicits involuntary movements, referred to as levodopa-induced peak-of-dose dyskinesias. Here, we used a novel pharmacodynamic neuroimaging approach to identify the changes in cortico-basal ganglia connectivity that herald the emergence of levodopa-induced dyskinesias. Twenty-six patients with Parkinson's disease (age range: 51–84 years; 11 females) received a single dose of levodopa and then performed a task in which they had to produce or suppress a movement in response to visual cues. Task-related activity was continuously mapped with functional magnetic resonance imaging. Dynamic causal modelling was applied to assess levodopa-induced modulation of effective connectivity between the pre-supplementary motor area, primary motor cortex and putamen when patients suppressed a motor response. Bayesian model selection revealed that patients who later developed levodopa-induced dyskinesias, but not patients without dyskinesias, showed a linear increase in connectivity between the putamen and primary motor cortex after levodopa intake during movement suppression. Individual dyskinesia severity was predicted by levodopa-induced modulation of striato-cortical feedback connections from putamen to the pre-supplementary motor area (Pcorrected = 0.020) and primary motor cortex (Pcorrected = 0.044), but not feed-forward connections from the cortex to the putamen. Our results identify for the first time, aberrant dopaminergic modulation of striatal-cortical connectivity as a neural signature of levodopa-induced dyskinesias in humans. We argue that excessive striato-cortical connectivity in response to levodopa produces an aberrant reinforcement signal producing an abnormal motor drive that ultimately triggers involuntary movements. PMID:25882651

  13. Defective cerebellar control of cortical plasticity in writer’s cramp

    PubMed Central

    Hubsch, Cecile; Roze, Emmanuel; Popa, Traian; Russo, Margherita; Balachandran, Ammu; Pradeep, Salini; Mueller, Florian; Brochard, Vanessa; Quartarone, Angelo; Degos, Bertrand; Vidailhet, Marie; Kishore, Asha

    2013-01-01

    A large body of evidence points to a role of basal ganglia dysfunction in the pathophysiology of dystonia, but recent studies indicate that cerebellar dysfunction may also be involved. The cerebellum influences sensorimotor adaptation by modulating sensorimotor plasticity of the primary motor cortex. Motor cortex sensorimotor plasticity is maladaptive in patients with writer’s cramp. Here we examined whether putative cerebellar dysfunction in dystonia is linked to these patients’ maladaptive plasticity. To that end we compared the performances of patients and healthy control subjects in a reaching task involving a visuomotor conflict generated by imposing a random deviation (−40° to 40°) on the direction of movement of the mouse/cursor. Such a task is known to involve the cerebellum. We also compared, between patients and healthy control subjects, how the cerebellum modulates the extent and duration of an ongoing sensorimotor plasticity in the motor cortex. The cerebellar cortex was excited or inhibited by means of repeated transcranial magnetic stimulation before artificial sensorimotor plasticity was induced in the motor cortex by paired associative stimulation. Patients with writer’s cramp were slower than the healthy control subjects to reach the target and, after having repeatedly adapted their trajectories to the deviations, they were less efficient than the healthy control subjects to perform reaching movement without imposed deviation. It was interpreted as impaired washing-out abilities. In healthy subjects, cerebellar cortex excitation prevented the paired associative stimulation to induce a sensorimotor plasticity in the primary motor cortex, whereas cerebellar cortex inhibition led the paired associative stimulation to be more efficient in inducing the plasticity. In patients with writer’s cramp, cerebellar cortex excitation and inhibition were both ineffective in modulating sensorimotor plasticity. In patients with writer’s cramp, but not in healthy subjects, behavioural parameters reflecting their capacity for adapting to the rotation and for washing-out of an earlier adaptation predicted the efficacy of inhibitory cerebellar conditioning to influence sensorimotor plasticity: the better the online adaptation, the smaller the influence of cerebellar inhibitory stimulation on motor cortex plasticity. Altered cerebellar encoding of incoming afferent volleys may result in decoupling the motor component from the afferent information flow, and also in maladjusted sensorimotor calibration. The loss of cerebellar control over sensorimotor plasticity might also lead to building up an incorrect motor program to specific adaptation tasks such as writing. PMID:23801734

  14. rTMS with Motor Training Modulates Cortico-Basal Ganglia-Thalamocortical Circuits in Stroke Patients

    PubMed Central

    Chang, Won Hyuk; Kim, Yun-Hee; Yoo, Woo-Kyoung; Goo, Kyoung-Hyup; Park, Chang-hyun; Kim, Sung Tae; Pascual-Leone, Alvaro

    2013-01-01

    Background and Purpose Repetitive transcranial magnetic stimulation (rTMS) may enhance plastic changes in the human cortex and modulation of behavior. However, the underlying neural mechanisms have not been sufficiently investigated. We examined the clinical effects and neural correlates of high-frequency rTMS coupled with motor training in patients with hemiparesis after stroke. Methods Twenty-one patients were randomly divided into two groups, and received either real or sham rTMS. Ten daily sessions of 1,000 pulses of real or sham rTMS were applied at 10 Hz over the primary motor cortex of the affected hemisphere, coupled with sequential finger motor training of the paretic hand. Functional MRIs were obtained before and after training using sequential finger motor tasks, and performances were assessed. Results Following rTMS intervention, movement accuracy of sequential finger motor tasks showed significantly greater improvement in the real group than in the sham group (p<0.05). Real rTMS modulated areas of brain activation during performance of motor tasks with a significant interaction effect in the sensorimotor cortex, thalamus, and caudate nucleus. Patients in the real rTMS group also showed significantly enhanced activation in the affected hemisphere compared to the sham rTMS group. Conclusion According to these results, a 10 day course of high-frequency rTMS coupled with motor training improved motor performance through modulation of activities in the cortico-basal ganglia-thalamocortical circuits. PMID:22555430

  15. Cerebellar-M1 Connectivity Changes Associated with Motor Learning Are Somatotopic Specific.

    PubMed

    Spampinato, Danny A; Block, Hannah J; Celnik, Pablo A

    2017-03-01

    One of the functions of the cerebellum in motor learning is to predict and account for systematic changes to the body or environment. This form of adaptive learning is mediated by plastic changes occurring within the cerebellar cortex. The strength of cerebellar-to-cerebral pathways for a given muscle may reflect aspects of cerebellum-dependent motor adaptation. These connections with motor cortex (M1) can be estimated as cerebellar inhibition (CBI): a conditioning pulse of transcranial magnetic stimulation delivered to the cerebellum before a test pulse over motor cortex. Previously, we have demonstrated that changes in CBI for a given muscle representation correlate with learning a motor adaptation task with the involved limb. However, the specificity of these effects is unknown. Here, we investigated whether CBI changes in humans are somatotopy specific and how they relate to motor adaptation. We found that learning a visuomotor rotation task with the right hand changed CBI, not only for the involved first dorsal interosseous of the right hand, but also for an uninvolved right leg muscle, the tibialis anterior, likely related to inter-effector transfer of learning. In two follow-up experiments, we investigated whether the preparation of a simple hand or leg movement would produce a somatotopy-specific modulation of CBI. We found that CBI changes only for the effector involved in the movement. These results indicate that learning-related changes in cerebellar-M1 connectivity reflect a somatotopy-specific interaction. Modulation of this pathway is also present in the context of interlimb transfer of learning. SIGNIFICANCE STATEMENT Connectivity between the cerebellum and motor cortex is a critical pathway for the integrity of everyday movements and understanding the somatotopic specificity of this pathway in the context of motor learning is critical to advancing the efficacy of neurorehabilitation. We found that adaptive learning with the hand affects cerebellar-motor cortex connectivity, not only for the trained hand, but also for an untrained leg muscle, an effect likely related to intereffector transfer of learning. Furthermore, we introduce a novel method to measure cerebellar-motor cortex connectivity during movement preparation. With this technique, we show that, outside the context of learning, modulation of cerebellar-motor cortex connectivity is somatotopically specific to the effector being moved. Copyright © 2017 the authors 0270-6474/17/372377-10$15.00/0.

  16. After-effects of anodal transcranial direct current stimulation on the excitability of the motor cortex in rats.

    PubMed

    Koo, Ho; Kim, Min Sun; Han, Sang Who; Paulus, Walter; Nitche, Michael A; Kim, Yun-Hee; Kim, Hyoung-Ihl; Ko, Sung-Hwa; Shin, Yong-Il

    2016-09-21

    Transcranial direct current stimulation (tDCS) is increasingly seen as a useful tool for noninvasive cortical neuromodulation. A number of studies in humans have shown that when tDCS is applied to the motor cortex it can modulate cortical excitability. It is especially interesting to note that when applied with sufficient duration and intensity, tDCS can enable long-lasting neuroplastic effects. However, the mechanism by which tDCS exerts its effects on the cortex is not fully understood. We investigated the effects of anodal tDCS under urethane anesthesia on field potentials in in vivo rats. These were measured on the skull over the right motor cortex of rats immediately after stimulating the left corpus callosum. Evoked field potentials in the motor cortex were gradually increased for more than one hour after anodal tDCS. To induce these long-lasting effects, a sufficient duration of stimulation (20 minutes or more) was found to may be required rather than high stimulation intensity. We propose that anodal tDCS with a sufficient duration of stimulation may modulate transcallosal plasticity.

  17. TMS-Induced Modulation of Action Sentence Priming in the Ventral Premotor Cortex

    ERIC Educational Resources Information Center

    Tremblay, Pascale; Sato, Marc; Small, Steven L.

    2012-01-01

    Despite accumulating evidence that cortical motor areas, particularly the lateral premotor cortex, are activated during language comprehension, the question of whether motor processes help mediate the semantic encoding of language remains controversial. To address this issue, we examined whether low frequency (1 Hz) repetitive transcranial…

  18. High-Definition Transcranial Direct Current Stimulation Enhances Conditioned Pain Modulation in Healthy Volunteers: A Randomized Trial.

    PubMed

    Flood, Andrew; Waddington, Gordon; Cathcart, Stuart

    2016-05-01

    Transcranial direct current stimulation (tDCS) is a form of brain stimulation that allows for the selective increase or decrease in the cortical excitability of a targeted region. When applied over the motor cortex it has been shown to induce changes in cortical and subcortical brain regions involved in descending pain inhibition or conditioned pain modulation (CPM). The aim of the current study was to assess whether activation of pain inhibitory pathways via tDCS of the motor cortex facilitates the CPM response. Elevated CPM after active tDCS of the motor cortex was hypothesized. Thirty healthy male volunteers attended 2 experimental sessions separated by 7 days. Both sessions consisted of CPM assessment after 20 minutes of either active or sham (placebo) tDCS over the motor cortex. CPM capacity was assessed via the pain-inhibits-pain protocol; CPM responses were shown to be elevated after active compared with sham tDCS. This report concludes that tDCS of the motor cortex enhances the CPM response in healthy men. This finding supports the potential utility of tDCS interventions in clinical pain treatment. The use of noninvasive brain stimulation over the motor cortex was shown to enhance the CPM effect. This finding supports the use of tDCS in the treatment of chronic pain, particularly in sufferers exhibiting maladaptive CPM. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

  19. From the motor cortex to the movement and back again.

    PubMed

    Teka, Wondimu W; Hamade, Khaldoun C; Barnett, William H; Kim, Taegyo; Markin, Sergey N; Rybak, Ilya A; Molkov, Yaroslav I

    2017-01-01

    The motor cortex controls motor behaviors by generating movement-specific signals and transmitting them through spinal cord circuits and motoneurons to the muscles. Precise and well-coordinated muscle activation patterns are necessary for accurate movement execution. Therefore, the activity of cortical neurons should correlate with movement parameters. To investigate the specifics of such correlations among activities of the motor cortex, spinal cord network and muscles, we developed a model for neural control of goal-directed reaching movements that simulates the entire pathway from the motor cortex through spinal cord circuits to the muscles controlling arm movements. In this model, the arm consists of two joints (shoulder and elbow), whose movements are actuated by six muscles (4 single-joint and 2 double-joint flexors and extensors). The muscles provide afferent feedback to the spinal cord circuits. Cortical neurons are defined as cortical "controllers" that solve an inverse problem based on a proposed straight-line trajectory to a target position and a predefined bell-shaped velocity profile. Thus, the controller generates a motor program that produces a task-specific activation of low-level spinal circuits that in turn induce the muscle activation realizing the intended reaching movement. Using the model, we describe the mechanisms of correlation between cortical and motoneuronal activities and movement direction and other movement parameters. We show that the directional modulation of neuronal activity in the motor cortex and the spinal cord may result from direction-specific dynamics of muscle lengths. Our model suggests that directional modulation first emerges at the level of muscle forces, augments at the motoneuron level, and further increases at the level of the motor cortex due to the dependence of frictional forces in the joints, contractility of the muscles and afferent feedback on muscle lengths and/or velocities.

  20. Development of closed-loop neural interface technology in a rat model: combining motor cortex operant conditioning with visual cortex microstimulation.

    PubMed

    Marzullo, Timothy Charles; Lehmkuhle, Mark J; Gage, Gregory J; Kipke, Daryl R

    2010-04-01

    Closed-loop neural interface technology that combines neural ensemble decoding with simultaneous electrical microstimulation feedback is hypothesized to improve deep brain stimulation techniques, neuromotor prosthetic applications, and epilepsy treatment. Here we describe our iterative results in a rat model of a sensory and motor neurophysiological feedback control system. Three rats were chronically implanted with microelectrode arrays in both the motor and visual cortices. The rats were subsequently trained over a period of weeks to modulate their motor cortex ensemble unit activity upon delivery of intra-cortical microstimulation (ICMS) of the visual cortex in order to receive a food reward. Rats were given continuous feedback via visual cortex ICMS during the response periods that was representative of the motor cortex ensemble dynamics. Analysis revealed that the feedback provided the animals with indicators of the behavioral trials. At the hardware level, this preparation provides a tractable test model for improving the technology of closed-loop neural devices.

  1. Underlying neural mechanisms of mirror therapy: Implications for motor rehabilitation in stroke.

    PubMed

    Arya, Kamal Narayan

    2016-01-01

    Mirror therapy (MT) is a valuable method for enhancing motor recovery in poststroke hemiparesis. The technique utilizes the mirror-illusion created by the movement of sound limb that is perceived as the paretic limb. MT is a simple and economical technique than can stimulate the brain noninvasively. The intervention unquestionably has neural foundation. But the underlying neural mechanisms inducing motor recovery are still unclear. In this review, the neural-modulation due to MT has been explored. Multiple areas of the brain such as the occipital lobe, dorsal frontal area and corpus callosum are involved during the simple MT regime. Bilateral premotor cortex, primary motor cortex, primary somatosensory cortex, and cerebellum also get reorganized to enhance the function of the damaged brain. The motor areas of the lesioned hemisphere receive visuo-motor processing information through the parieto-occipital lobe. The damaged motor cortex responds variably to the MT and may augment true motor recovery. Mirror neurons may also play a possible role in the cortico-stimulatory mechanisms occurring due to the MT.

  2. Heterogeneous Attractor Cell Assemblies for Motor Planning in Premotor Cortex

    PubMed Central

    Pani, Pierpaolo; Mirabella, Giovanni; Costa, Stefania; Del Giudice, Paolo

    2013-01-01

    Cognitive functions like motor planning rely on the concerted activity of multiple neuronal assemblies underlying still elusive computational strategies. During reaching tasks, we observed stereotyped sudden transitions (STs) between low and high multiunit activity of monkey dorsal premotor cortex (PMd) predicting forthcoming actions on a single-trial basis. Occurrence of STs was observed even when movement was delayed or successfully canceled after a stop signal, excluding a mere substrate of the motor execution. An attractor model accounts for upward STs and high-frequency modulations of field potentials, indicative of local synaptic reverberation. We found in vivo compelling evidence that motor plans in PMd emerge from the coactivation of such attractor modules, heterogeneous in the strength of local synaptic self-excitation. Modules with strong coupling early reacted with variable times to weak inputs, priming a chain reaction of both upward and downward STs in other modules. Such web of “flip-flops” rapidly converged to a stereotyped distributed representation of the motor program, as prescribed by the long-standing theory of associative networks. PMID:23825419

  3. Multiple Transient Signals in Human Visual Cortex Associated with an Elementary Decision

    PubMed Central

    Nolte, Guido

    2017-01-01

    The cerebral cortex continuously undergoes changes in its state, which are manifested in transient modulations of the cortical power spectrum. Cortical state changes also occur at full wakefulness and during rapid cognitive acts, such as perceptual decisions. Previous studies found a global modulation of beta-band (12–30 Hz) activity in human and monkey visual cortex during an elementary visual decision: reporting the appearance or disappearance of salient visual targets surrounded by a distractor. The previous studies disentangled neither the motor action associated with behavioral report nor other secondary processes, such as arousal, from perceptual decision processing per se. Here, we used magnetoencephalography in humans to pinpoint the factors underlying the beta-band modulation. We found that disappearances of a salient target were associated with beta-band suppression, and target reappearances with beta-band enhancement. This was true for both overt behavioral reports (immediate button presses) and silent counting of the perceptual events. This finding indicates that the beta-band modulation was unrelated to the execution of the motor act associated with a behavioral report of the perceptual decision. Further, changes in pupil-linked arousal, fixational eye movements, or gamma-band responses were not necessary for the beta-band modulation. Together, our results suggest that the beta-band modulation was a top-down signal associated with the process of converting graded perceptual signals into a categorical format underlying flexible behavior. This signal may have been fed back from brain regions involved in decision processing to visual cortex, thus enforcing a “decision-consistent” cortical state. SIGNIFICANCE STATEMENT Elementary visual decisions are associated with a rapid state change in visual cortex, indexed by a modulation of neural activity in the beta-frequency range. Such decisions are also followed by other events that might affect the state of visual cortex, including the motor command associated with the report of the decision, an increase in pupil-linked arousal, fixational eye movements, and fluctuations in bottom-up sensory processing. Here, we ruled out the necessity of these events for the beta-band modulation of visual cortex. We propose that the modulation reflects a decision-related state change, which is induced by the conversion of graded perceptual signals into a categorical format underlying behavior. The resulting decision signal may be fed back to visual cortex. PMID:28495972

  4. Self-regulation of primary motor cortex activity with motor imagery induces functional connectivity modulation: A real-time fMRI neurofeedback study.

    PubMed

    Makary, Meena M; Seulgi, Eun; Kyungmo Park

    2017-07-01

    Recent developments in data acquisition of functional magnetic resonance imaging (fMRI) have led to rapid preprocessing and analysis of brain activity in a quasireal-time basis, what so called real-time fMRI neurofeedback (rtfMRI-NFB). This information is fed back to subjects allowing them to gain a voluntary control over their own region-specific brain activity. Forty-one healthy participants were randomized into an experimental (NFB) group, who received a feedback directly proportional to their brain activity from the primary motor cortex (M1), and a control (CTRL) group who received a sham feedback. The M1 ROI was functionally localized during motor execution and imagery tasks. A resting-state functional run was performed before and after the neurofeedback training to investigate the default mode network (DMN) modulation after training. The NFB group revealed increased DMN functional connectivity after training to the cortical and subcortical sensory/motor areas (M1/S1 and caudate nucleus, respectively), which may be associated with sensorimotor processing of learning in the resting state. These results show that motor imagery training through rtfMRI-NFB could modulate the DMN functional connectivity to motor-related areas, suggesting that this modulation potentially subserved the establishment of motor learning in the NFB group.

  5. Transformation of Cortex-wide Emergent Properties during Motor Learning.

    PubMed

    Makino, Hiroshi; Ren, Chi; Liu, Haixin; Kim, An Na; Kondapaneni, Neehar; Liu, Xin; Kuzum, Duygu; Komiyama, Takaki

    2017-05-17

    Learning involves a transformation of brain-wide operation dynamics. However, our understanding of learning-related changes in macroscopic dynamics is limited. Here, we monitored cortex-wide activity of the mouse brain using wide-field calcium imaging while the mouse learned a motor task over weeks. Over learning, the sequential activity across cortical modules became temporally more compressed, and its trial-by-trial variability decreased. Moreover, a new flow of activity emerged during learning, originating from premotor cortex (M2), and M2 became predictive of the activity of many other modules. Inactivation experiments showed that M2 is critical for the post-learning dynamics in the cortex-wide activity. Furthermore, two-photon calcium imaging revealed that M2 ensemble activity also showed earlier activity onset and reduced variability with learning, which was accompanied by changes in the activity-movement relationship. These results reveal newly emergent properties of macroscopic cortical dynamics during motor learning and highlight the importance of M2 in controlling learned movements. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Rapid treatment-induced brain changes in pediatric CRPS.

    PubMed

    Erpelding, Nathalie; Simons, Laura; Lebel, Alyssa; Serrano, Paul; Pielech, Melissa; Prabhu, Sanjay; Becerra, Lino; Borsook, David

    2016-03-01

    To date, brain structure and function changes in children with complex regional pain syndrome (CRPS) as a result of disease and treatment remain unknown. Here, we investigated (a) gray matter (GM) differences between patients with CRPS and healthy controls and (b) GM and functional connectivity (FC) changes in patients following intensive interdisciplinary psychophysical pain treatment. Twenty-three patients (13 females, 9 males; average age ± SD = 13.3 ± 2.5 years) and 21 healthy sex- and age-matched controls underwent magnetic resonance imaging. Compared to controls, patients had reduced GM in the primary motor cortex, premotor cortex, supplementary motor area, midcingulate cortex, orbitofrontal cortex, dorsolateral prefrontal cortex (dlPFC), posterior cingulate cortex, precuneus, basal ganglia, thalamus, and hippocampus. Following treatment, patients had increased GM in the dlPFC, thalamus, basal ganglia, amygdala, and hippocampus, and enhanced FC between the dlPFC and the periaqueductal gray, two regions involved in descending pain modulation. Accordingly, our results provide novel evidence for GM abnormalities in sensory, motor, emotional, cognitive, and pain modulatory regions in children with CRPS. Furthermore, this is the first study to demonstrate rapid treatment-induced GM and FC changes in areas implicated in sensation, emotion, cognition, and pain modulation.

  7. Auditory-Motor Processing of Speech Sounds

    PubMed Central

    Möttönen, Riikka; Dutton, Rebekah; Watkins, Kate E.

    2013-01-01

    The motor regions that control movements of the articulators activate during listening to speech and contribute to performance in demanding speech recognition and discrimination tasks. Whether the articulatory motor cortex modulates auditory processing of speech sounds is unknown. Here, we aimed to determine whether the articulatory motor cortex affects the auditory mechanisms underlying discrimination of speech sounds in the absence of demanding speech tasks. Using electroencephalography, we recorded responses to changes in sound sequences, while participants watched a silent video. We also disrupted the lip or the hand representation in left motor cortex using transcranial magnetic stimulation. Disruption of the lip representation suppressed responses to changes in speech sounds, but not piano tones. In contrast, disruption of the hand representation had no effect on responses to changes in speech sounds. These findings show that disruptions within, but not outside, the articulatory motor cortex impair automatic auditory discrimination of speech sounds. The findings provide evidence for the importance of auditory-motor processes in efficient neural analysis of speech sounds. PMID:22581846

  8. Altered cortical processing of motor inhibition in schizophrenia.

    PubMed

    Lindberg, Påvel G; Térémetz, Maxime; Charron, Sylvain; Kebir, Oussama; Saby, Agathe; Bendjemaa, Narjes; Lion, Stéphanie; Crépon, Benoît; Gaillard, Raphaël; Oppenheim, Catherine; Krebs, Marie-Odile; Amado, Isabelle

    2016-12-01

    Inhibition is considered a key mechanism in schizophrenia. Short-latency intracortical inhibition (SICI) in the motor cortex is reduced in schizophrenia and is considered to reflect locally deficient γ-aminobutyric acid (GABA)-ergic modulation. However, it remains unclear how SICI is modulated during motor inhibition and how it relates to neural processing in other cortical areas. Here we studied motor inhibition Stop signal task (SST) in stabilized patients with schizophrenia (N = 28), healthy siblings (N = 21) and healthy controls (n = 31) matched in general cognitive status and educational level. Transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) were used to investigate neural correlates of motor inhibition. SST performance was similar in patients and controls. SICI was modulated by the task as expected in healthy controls and siblings but was reduced in patients with schizophrenia during inhibition despite equivalent motor inhibition performance. fMRI showed greater prefrontal and premotor activation during motor inhibition in schizophrenia. Task-related modulation of SICI was higher in subjects who showed less inhibition-related activity in pre-supplementary motor area (SMA) and cingulate motor area. An exploratory genetic analysis of selected markers of inhibition (GABRB2, GAD1, GRM1, and GRM3) did not explain task-related differences in SICI or cortical activation. In conclusion, this multimodal study provides direct evidence of a task-related deficiency in SICI modulation in schizophrenia likely reflecting deficient GABA-A related processing in motor cortex. Compensatory activation of premotor areas may explain similar motor inhibition in patients despite local deficits in intracortical processing. Task-related modulation of SICI may serve as a useful non-invasive GABAergic marker in development of therapeutic strategies in schizophrenia. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Low-Frequency Repetitive Transcranial Magnetic Stimulation Targeted to Premotor Cortex Followed by Primary Motor Cortex Modulates Excitability Differently Than Premotor Cortex or Primary Motor Cortex Stimulation Alone.

    PubMed

    Chen, Mo; Deng, Huiqiong; Schmidt, Rebekah L; Kimberley, Teresa J

    2015-12-01

    The excitability of primary motor cortex (M1) can be modulated by applying low-frequency repetitive transcranial magnetic stimulation (rTMS) over M1 or premotor cortex (PMC). A comparison of inhibitory effect between the two locations has been reported with inconsistent results. This study compared the response secondary to rTMS applied over M1, PMC, and a combined PMC + M1 stimulation approach which first targets stimulation over PMC then M1. Ten healthy participants were recruited for a randomized, cross-over design with a one-week washout between visits. Each visit consisted of a pretest, an rTMS intervention, and a post-test. Outcome measures included short interval intracortical inhibition (SICI), intracortical facilitation (ICF), and cortical silent period (CSP). Participants received one of the three interventions in random order at each visit including: 1-Hz rTMS at 90% of resting motor threshold to: M1 (1200 pulses), PMC (1200 pulses), and PMC + M1 (600 pulses each, 1200 total). PMC + M1 stimulation resulted in significantly greater inhibition than the other locations for ICF (P = 0.005) and CSP (P < 0.001); for SICI, increased inhibition (group effect) was not observed after any of the three interventions, and there was no significant difference between the three interventions. The results indicate that PMC + M1 stimulation may modulate brain excitability differently from PMC or M1 alone. CSP was the assessment measure most sensitive to changes in inhibition and was able to distinguish between different inhibitory protocols. This work presents a novel procedure that may have positive implications for therapeutic interventions. © 2015 International Neuromodulation Society.

  10. Cortico-cortical and motor evoked potentials to single and paired-pulse stimuli: An exploratory transcranial magnetic and intracranial electric brain stimulation study.

    PubMed

    Boulogne, Sébastien; Andre-Obadia, Nathalie; Kimiskidis, Vasilios K; Ryvlin, Philippe; Rheims, Sylvain

    2016-11-01

    Paired-pulse (PP) paradigms are commonly employed to assess in vivo cortical excitability using transcranial magnetic stimulation (TMS) to stimulate the primary motor cortex and modulate the induced motor evoked potential (MEP). Single-pulse cortical direct electrical stimulation (DES) during intracerebral EEG monitoring allows the investigation of brain connectivity by eliciting cortico-cortical evoked potentials (CCEPs). However, PP paradigm using intracerebral DES has rarely been reported and has never been previously compared with TMS. The work was intended (i) to verify that the well-established modulations of MEPs following PP TMS remain similar using DES in the motor cortex, and (ii) to evaluate if a similar pattern could be observed in distant cortico-cortical connections through modulations of CCEP. Three patients undergoing intracerebral EEG monitoring with electrodes implanted in the central region were studied. Single-pulse DES (1-3 mA, 1 ms, 0.2 Hz) and PP DES using six interstimulus intervals (5, 15, 30, 50, 100, and 200 ms) in the motor cortex with concomitant recording of CCEPs and MEPs in contralateral muscles were performed. Finally, a navigated PP TMS session targeted the intracranial stimulation site to record TMS-induced MEPs in two patients. MEP modulations elicited by PP intracerebral DES proved similar among the three patients and to those obtained by PP TMS. CCEP modulations elicited by PP intracerebral DES usually showed a pattern comparable to that of MEP, although a different pattern could be observed occasionally. PP intracerebral DES seems to involve excitatory and inhibitory mechanisms similar to PP TMS and allows the recording of intracortical inhibition and facilitation modulation on cortico-cortical connections. Hum Brain Mapp 37:3767-3778, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. Assessment and modulation of neuroplasticity in rehabilitation with transcranial magnetic stimulation

    PubMed Central

    Bashir, Shahid; Mizrahi, Ilan; Weaver, Kayleen; Fregni, Felipe; Pascual-Leone, Alvaro

    2013-01-01

    Despite intensive efforts towards the improvement of outcomes after acquired brain injury functional recovery is often limited. One reasons is the challenge in assessing and guiding plasticity after brain injury. In this context, Transcranial Magnetic Stimulation (TMS) - a noninvasive tool of brain stimulation - could play a major role. TMS has shown to be a reliable tool to measure plastic changes in the motor cortex associated with interventions in the motor system; such as motor training and motor cortex stimulation. In addition, as illustrated by the experience in promoting recovery from stroke, TMS a promising therapeutic tool to minimize motor, speech, cognitive, and mood deficits. In this review, we will focus on stroke to discuss how TMS can provide insights into the mechanisms of neurological recovery, and can be used for measurement and modulation of plasticity after an acquired brain insult. PMID:21172687

  12. Auditory and audio-vocal responses of single neurons in the monkey ventral premotor cortex.

    PubMed

    Hage, Steffen R

    2018-03-20

    Monkey vocalization is a complex behavioral pattern, which is flexibly used in audio-vocal communication. A recently proposed dual neural network model suggests that cognitive control might be involved in this behavior, originating from a frontal cortical network in the prefrontal cortex and mediated via projections from the rostral portion of the ventral premotor cortex (PMvr) and motor cortex to the primary vocal motor network in the brainstem. For the rapid adjustment of vocal output to external acoustic events, strong interconnections between vocal motor and auditory sites are needed, which are present at cortical and subcortical levels. However, the role of the PMvr in audio-vocal integration processes remains unclear. In the present study, single neurons in the PMvr were recorded in rhesus monkeys (Macaca mulatta) while volitionally producing vocalizations in a visual detection task or passively listening to monkey vocalizations. Ten percent of randomly selected neurons in the PMvr modulated their discharge rate in response to acoustic stimulation with species-specific calls. More than four-fifths of these auditory neurons showed an additional modulation of their discharge rates either before and/or during the monkeys' motor production of the vocalization. Based on these audio-vocal interactions, the PMvr might be well positioned to mediate higher order auditory processing with cognitive control of the vocal motor output to the primary vocal motor network. Such audio-vocal integration processes in the premotor cortex might constitute a precursor for the evolution of complex learned audio-vocal integration systems, ultimately giving rise to human speech. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Motor cortex guides selection of predictable movement targets

    PubMed Central

    Woodgate, Philip J.W.; Strauss, Soeren; Sami, Saber A.; Heinke, Dietmar

    2016-01-01

    The present paper asks whether the motor cortex contributes to prediction-based guidance of target selection. This question was inspired by recent evidence that suggests (i) recurrent connections from the motor system into the attentional system may extract movement-relevant perceptual information and (ii) that the motor cortex cannot only generate predictions of the sensory consequences of movements but may also operate as predictor of perceptual events in general. To test this idea we employed a choice reaching task requiring participants to rapidly reach and touch a predictable or unpredictable colour target. Motor cortex activity was modulated via transcranial direct current stimulation (tDCS). In Experiment 1 target colour repetitions were predictable. Under such conditions anodal tDCS facilitated selection versus sham and cathodal tDCS. This improvement was apparent for trajectory curvature but not movement initiation. Conversely, where no predictability of colour was embedded reach performance was unaffected by tDCS. Finally, the results of a key-press experiment suggested that motor cortex involvement is restricted to tasks where the predictable target colour is movement-relevant. The outcomes are interpreted as evidence that the motor system contributes to the top-down guidance of selective attention to movement targets. PMID:25835319

  14. Cellular mechanisms underlying behavioral state-dependent bidirectional modulation of motor cortex output.

    PubMed

    Schiemann, Julia; Puggioni, Paolo; Dacre, Joshua; Pelko, Miha; Domanski, Aleksander; van Rossum, Mark C W; Duguid, Ian

    2015-05-26

    Neuronal activity in primary motor cortex (M1) correlates with behavioral state, but the cellular mechanisms underpinning behavioral state-dependent modulation of M1 output remain largely unresolved. Here, we performed in vivo patch-clamp recordings from layer 5B (L5B) pyramidal neurons in awake mice during quiet wakefulness and self-paced, voluntary movement. We show that L5B output neurons display bidirectional (i.e., enhanced or suppressed) firing rate changes during movement, mediated via two opposing subthreshold mechanisms: (1) a global decrease in membrane potential variability that reduced L5B firing rates (L5Bsuppressed neurons), and (2) a coincident noradrenaline-mediated increase in excitatory drive to a subpopulation of L5B neurons (L5Benhanced neurons) that elevated firing rates. Blocking noradrenergic receptors in forelimb M1 abolished the bidirectional modulation of M1 output during movement and selectively impaired contralateral forelimb motor coordination. Together, our results provide a mechanism for how noradrenergic neuromodulation and network-driven input changes bidirectionally modulate M1 output during motor behavior. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Altered Modulation of Silent Period in Tongue Motor Cortex of Persistent Developmental Stuttering in Relation to Stuttering Severity.

    PubMed

    Busan, Pierpaolo; Del Ben, Giovanni; Bernardini, Simona; Natarelli, Giulia; Bencich, Marco; Monti, Fabrizio; Manganotti, Paolo; Battaglini, Piero Paolo

    2016-01-01

    Motor balance in developmental stuttering (DS) was investigated with Transcranial Magnetic Stimulation (TMS), with the aim to define novel neural markers of persistent DS in adulthood. Eleven DS adult males were evaluated with TMS on tongue primary motor cortex, compared to 15 matched fluent speakers, in a "state" condition (i.e. stutterers vs. fluent speakers, no overt stuttering). Motor and silent period thresholds (SPT), recruitment curves, and silent period durations were acquired by recording tongue motor evoked potentials. Tongue silent period duration was increased in DS, especially in the left hemisphere (P<0.05; Hedge's g or Cohen's dunbiased = 1.054, i.e. large effect size), suggesting a "state" condition of higher intracortical inhibition in left motor cortex networks. Differences in motor thresholds (different excitatory/inhibitory ratios in DS) were evident, as well as significant differences in SPT. In fluent speakers, the left hemisphere may be marginally more excitable than the right one in motor thresholds at lower muscular activation, while active motor thresholds and SPT were higher in the left hemisphere of DS with respect to the right one, resulting also in a positive correlation with stuttering severity. Pre-TMS electromyography data gave overlapping evidence. Findings suggest the existence of a complex intracortical balance in DS tongue primary motor cortex, with a particular interplay between excitatory and inhibitory mechanisms, also in neural substrates related to silent periods. Findings are discussed with respect to functional and structural impairments in stuttering, and are also proposed as novel neural markers of a stuttering "state" in persistent DS, helping to define more focused treatments (e.g. neuro-modulation).

  16. Altered Modulation of Silent Period in Tongue Motor Cortex of Persistent Developmental Stuttering in Relation to Stuttering Severity

    PubMed Central

    Busan, Pierpaolo; Del Ben, Giovanni; Bernardini, Simona; Natarelli, Giulia; Bencich, Marco; Monti, Fabrizio; Manganotti, Paolo; Battaglini, Piero Paolo

    2016-01-01

    Motor balance in developmental stuttering (DS) was investigated with Transcranial Magnetic Stimulation (TMS), with the aim to define novel neural markers of persistent DS in adulthood. Eleven DS adult males were evaluated with TMS on tongue primary motor cortex, compared to 15 matched fluent speakers, in a “state” condition (i.e. stutterers vs. fluent speakers, no overt stuttering). Motor and silent period thresholds (SPT), recruitment curves, and silent period durations were acquired by recording tongue motor evoked potentials. Tongue silent period duration was increased in DS, especially in the left hemisphere (P<0.05; Hedge’s g or Cohen’s dunbiased = 1.054, i.e. large effect size), suggesting a “state” condition of higher intracortical inhibition in left motor cortex networks. Differences in motor thresholds (different excitatory/inhibitory ratios in DS) were evident, as well as significant differences in SPT. In fluent speakers, the left hemisphere may be marginally more excitable than the right one in motor thresholds at lower muscular activation, while active motor thresholds and SPT were higher in the left hemisphere of DS with respect to the right one, resulting also in a positive correlation with stuttering severity. Pre-TMS electromyography data gave overlapping evidence. Findings suggest the existence of a complex intracortical balance in DS tongue primary motor cortex, with a particular interplay between excitatory and inhibitory mechanisms, also in neural substrates related to silent periods. Findings are discussed with respect to functional and structural impairments in stuttering, and are also proposed as novel neural markers of a stuttering “state” in persistent DS, helping to define more focused treatments (e.g. neuro-modulation). PMID:27711148

  17. Task-dependent engagements of the primary visual cortex during kinesthetic and visual motor imagery.

    PubMed

    Mizuguchi, Nobuaki; Nakamura, Maiko; Kanosue, Kazuyuki

    2017-01-01

    Motor imagery can be divided into kinesthetic and visual aspects. In the present study, we investigated excitability in the corticospinal tract and primary visual cortex (V1) during kinesthetic and visual motor imagery. To accomplish this, we measured motor evoked potentials (MEPs) and probability of phosphene occurrence during the two types of motor imageries of finger tapping. The MEPs and phosphenes were induced by transcranial magnetic stimulation to the primary motor cortex and V1, respectively. The amplitudes of MEPs and probability of phosphene occurrence during motor imagery were normalized based on the values obtained at rest. Corticospinal excitability increased during both kinesthetic and visual motor imagery, while excitability in V1 was increased only during visual motor imagery. These results imply that modulation of cortical excitability during kinesthetic and visual motor imagery is task dependent. The present finding aids in the understanding of the neural mechanisms underlying motor imagery and provides useful information for the use of motor imagery in rehabilitation or motor imagery training. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Neural substrates of visuomotor learning based on improved feedback control and prediction

    PubMed Central

    Grafton, Scott T.; Schmitt, Paul; Horn, John Van; Diedrichsen, Jörn

    2008-01-01

    Motor skills emerge from learning feedforward commands as well as improvements in feedback control. These two components of learning were investigated in a compensatory visuomotor tracking task on a trial-by-trial basis. Between trial learning was characterized with a state-space model to provide smoothed estimates of feedforward and feedback learning, separable from random fluctuations in motor performance and error. The resultant parameters were correlated with brain activity using magnetic resonance imaging. Learning related to the generation of a feedforward command correlated with activity in dorsal premotor cortex, inferior parietal lobule, supplementary motor area and cingulate motor area, supporting a role of these areas in retrieving and executing a predictive motor command. Modulation of feedback control was associated with activity in bilateral posterior superior parietal lobule as well as right ventral premotor cortex. Performance error correlated with activity in a widespread cortical and subcortical network including bilateral parietal, premotor and rostral anterior cingulate cortex as well as the cerebellar cortex. Finally, trial-by-trial changes of kinematics, as measured by mean absolute hand acceleration, correlated with activity in motor cortex and anterior cerebellum. The results demonstrate that incremental, learning dependent changes can be modeled on a trial-by-trial basis and neural substrates for feedforward control of novel motor programs are localized to secondary motor areas. PMID:18032069

  19. Sexual motivation is reflected by stimulus-dependent motor cortex excitability.

    PubMed

    Schecklmann, Martin; Engelhardt, Kristina; Konzok, Julian; Rupprecht, Rainer; Greenlee, Mark W; Mokros, Andreas; Langguth, Berthold; Poeppl, Timm B

    2015-08-01

    Sexual behavior involves motivational processes. Findings from both animal models and neuroimaging in humans suggest that the recruitment of neural motor networks is an integral part of the sexual response. However, no study so far has directly linked sexual motivation to physiologically measurable changes in cerebral motor systems in humans. Using transcranial magnetic stimulation in hetero- and homosexual men, we here show that sexual motivation modulates cortical excitability. More specifically, our results demonstrate that visual sexual stimuli corresponding with one's sexual orientation, compared with non-corresponding visual sexual stimuli, increase the excitability of the motor cortex. The reflection of sexual motivation in motor cortex excitability provides evidence for motor preparation processes in sexual behavior in humans. Moreover, such interrelationship links theoretical models and previous neuroimaging findings of sexual behavior. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  20. The differential role of motor cortex in the stretch reflex modulation induced by changes in environmental mechanics and verbal instruction

    PubMed Central

    Shemmell, Jonathan; An, Je Hi; Perreault, Eric J.

    2009-01-01

    The motor cortex assumes an increasingly important role in higher mammals relative to that in lower mammals. This is true to such an extent that the human motor cortex is deeply involved in reflex regulation and it is common to speak of “transcortical reflex loops”. Such loops appear to add flexibility to the human stretch reflex, once considered to be immutable, allowing it to adapt across a range of functional tasks. However, the purpose of this adaptation remains unclear. A common proposal is that stretch reflexes contribute to the regulation of limb stability; increased reflex sensitivity during tasks performed in unstable environments supports this hypothesis. Alternatively, prior to movement onset, stretch reflexes can assist an imposed stretch, opposite to what would be expected from a stabilizing response. Here we show that stretch reflex modulation in tasks that require changes in limb stability is mediated by motor cortical pathways, and that these differ from pathways contributing to reflex modulation that depends on how the subject is instructed to react to an imposed perturbation. By timing muscle stretches such that the modulated portion of the reflex occurred within a cortical silent period induced by transcranial magnetic stimulation, we abolished the increase in reflex sensitivity observed when individuals stabilized arm posture within a compliant environment. Conversely, reflex modulation caused by altered task instruction was unaffected by cortical silence. These results demonstrate that task-dependent changes in reflex function can be mediated through multiple neural pathways and that these pathways have task specific roles. PMID:19846713

  1. The differential role of motor cortex in stretch reflex modulation induced by changes in environmental mechanics and verbal instruction.

    PubMed

    Shemmell, Jonathan; An, Je Hi; Perreault, Eric J

    2009-10-21

    The motor cortex assumes an increasingly important role in higher mammals relative to that in lower mammals. This is true to such an extent that the human motor cortex is deeply involved in reflex regulation and it is common to speak of "transcortical reflex loops." Such loops appear to add flexibility to the human stretch reflex, once considered to be immutable, allowing it to adapt across a range of functional tasks. However, the purpose of this adaptation remains unclear. A common proposal is that stretch reflexes contribute to the regulation of limb stability; increased reflex sensitivity during tasks performed in unstable environments supports this hypothesis. Alternatively, before movement onset, stretch reflexes can assist an imposed stretch, opposite to what would be expected from a stabilizing response. Here we show that stretch reflex modulation in tasks that require changes in limb stability is mediated by motor cortical pathways, and that these differ from pathways contributing to reflex modulation that depend on how the subject is instructed to react to an imposed perturbation. By timing muscle stretches such that the modulated portion of the reflex occurred within a cortical silent period induced by transcranial magnetic stimulation, we abolished the increase in reflex sensitivity observed when individuals stabilized arm posture within a compliant environment. Conversely, reflex modulation caused by altered task instruction was unaffected by cortical silence. These results demonstrate that task-dependent changes in reflex function can be mediated through multiple neural pathways and that these pathways have task-specific roles.

  2. Network interactions underlying mirror feedback in stroke: A dynamic causal modeling study.

    PubMed

    Saleh, Soha; Yarossi, Mathew; Manuweera, Thushini; Adamovich, Sergei; Tunik, Eugene

    2017-01-01

    Mirror visual feedback (MVF) is potentially a powerful tool to facilitate recovery of disordered movement and stimulate activation of under-active brain areas due to stroke. The neural mechanisms underlying MVF have therefore been a focus of recent inquiry. Although it is known that sensorimotor areas can be activated via mirror feedback, the network interactions driving this effect remain unknown. The aim of the current study was to fill this gap by using dynamic causal modeling to test the interactions between regions in the frontal and parietal lobes that may be important for modulating the activation of the ipsilesional motor cortex during mirror visual feedback of unaffected hand movement in stroke patients. Our intent was to distinguish between two theoretical neural mechanisms that might mediate ipsilateral activation in response to mirror-feedback: transfer of information between bilateral motor cortices versus recruitment of regions comprising an action observation network which in turn modulate the motor cortex. In an event-related fMRI design, fourteen chronic stroke subjects performed goal-directed finger flexion movements with their unaffected hand while observing real-time visual feedback of the corresponding (veridical) or opposite (mirror) hand in virtual reality. Among 30 plausible network models that were tested, the winning model revealed significant mirror feedback-based modulation of the ipsilesional motor cortex arising from the contralesional parietal cortex, in a region along the rostral extent of the intraparietal sulcus. No winning model was identified for the veridical feedback condition. We discuss our findings in the context of supporting the latter hypothesis, that mirror feedback-based activation of motor cortex may be attributed to engagement of a contralateral (contralesional) action observation network. These findings may have important implications for identifying putative cortical areas, which may be targeted with non-invasive brain stimulation as a means of potentiating the effects of mirror training.

  3. Effects of transcranial direct current stimulation of the motor cortex on prefrontal cortex activation during a neuromuscular fatigue task: an fNIRS study.

    PubMed

    Muthalib, Makii; Kan, Benjamin; Nosaka, Kazunori; Perrey, Stephane

    2013-01-01

    This study investigated whether manipulation of motor cortex excitability by transcranial direct current stimulation (tDCS) modulates neuromuscular fatigue and functional near-infrared spectroscopy (fNIRS)-derived prefrontal cortex (PFC) activation. Fifteen healthy men (27.7 ± 8.4 years) underwent anodal (2 mA, 10 min) and sham (2 mA, first 30 s only) tDCS delivered to the scalp over the right motor cortex. Subjects initially performed a baseline sustained submaximal (30 % maximal voluntary isometric contraction, MVC) isometric contraction task (SSIT) of the left elbow flexors until task failure, which was followed 50 min later by either an anodal or sham treatment condition, then a subsequent posttreatment SSIT. Endurance time (ET), torque integral (TI), and fNIRS-derived contralateral PFC oxygenated (O2Hb) and deoxygenated (HHb) hemoglobin concentration changes were determined at task failure. Results indicated that during the baseline and posttreatment SSIT, there were no significant differences in TI and ET, and increases in fNIRS-derived PFC activation at task failure were observed similarly regardless of the tDCS conditions. This suggests that the PFC neuronal activation to maintain muscle force production was not modulated by anodal tDCS.

  4. Tagging motor memories with transcranial direct current stimulation allows later artificially-controlled retrieval

    PubMed Central

    Nozaki, Daichi; Yokoi, Atsushi; Kimura, Takahiro; Hirashima, Masaya; Orban de Xivry, Jean-Jacques

    2016-01-01

    We demonstrate that human motor memories can be artificially tagged and later retrieved by noninvasive transcranial direct current stimulation (tDCS). Participants learned to adapt reaching movements to two conflicting dynamical environments that were each associated with a different tDCS polarity (anodal or cathodal tDCS) on the sensorimotor cortex. That is, we sought to determine whether divergent background activity levels within the sensorimotor cortex (anodal: higher activity; cathodal: lower activity) give rise to distinct motor memories. After a training session, application of each tDCS polarity automatically resulted in the retrieval of the motor memory corresponding to that polarity. These results reveal that artificial modulation of neural activity in the sensorimotor cortex through tDCS can act as a context for the formation and recollection of motor memories. DOI: http://dx.doi.org/10.7554/eLife.15378.001 PMID:27472899

  5. Neurofeedback-based functional near-infrared spectroscopy upregulates motor cortex activity in imagined motor tasks

    PubMed Central

    Lapborisuth, Pawan; Zhang, Xian; Noah, Adam; Hirsch, Joy

    2017-01-01

    Abstract. Neurofeedback is a method for using neural activity displayed on a computer to regulate one’s own brain function and has been shown to be a promising technique for training individuals to interact with brain–machine interface applications such as neuroprosthetic limbs. The goal of this study was to develop a user-friendly functional near-infrared spectroscopy (fNIRS)-based neurofeedback system to upregulate neural activity associated with motor imagery, which is frequently used in neuroprosthetic applications. We hypothesized that fNIRS neurofeedback would enhance activity in motor cortex during a motor imagery task. Twenty-two participants performed active and imaginary right-handed squeezing movements using an elastic ball while wearing a 98-channel fNIRS device. Neurofeedback traces representing localized cortical hemodynamic responses were graphically presented to participants in real time. Participants were instructed to observe this graphical representation and use the information to increase signal amplitude. Neural activity was compared during active and imaginary squeezing with and without neurofeedback. Active squeezing resulted in activity localized to the left premotor and supplementary motor cortex, and activity in the motor cortex was found to be modulated by neurofeedback. Activity in the motor cortex was also shown in the imaginary squeezing condition only in the presence of neurofeedback. These findings demonstrate that real-time fNIRS neurofeedback is a viable platform for brain–machine interface applications. PMID:28680906

  6. Neurofeedback-based functional near-infrared spectroscopy upregulates motor cortex activity in imagined motor tasks.

    PubMed

    Lapborisuth, Pawan; Zhang, Xian; Noah, Adam; Hirsch, Joy

    2017-04-01

    Neurofeedback is a method for using neural activity displayed on a computer to regulate one's own brain function and has been shown to be a promising technique for training individuals to interact with brain-machine interface applications such as neuroprosthetic limbs. The goal of this study was to develop a user-friendly functional near-infrared spectroscopy (fNIRS)-based neurofeedback system to upregulate neural activity associated with motor imagery, which is frequently used in neuroprosthetic applications. We hypothesized that fNIRS neurofeedback would enhance activity in motor cortex during a motor imagery task. Twenty-two participants performed active and imaginary right-handed squeezing movements using an elastic ball while wearing a 98-channel fNIRS device. Neurofeedback traces representing localized cortical hemodynamic responses were graphically presented to participants in real time. Participants were instructed to observe this graphical representation and use the information to increase signal amplitude. Neural activity was compared during active and imaginary squeezing with and without neurofeedback. Active squeezing resulted in activity localized to the left premotor and supplementary motor cortex, and activity in the motor cortex was found to be modulated by neurofeedback. Activity in the motor cortex was also shown in the imaginary squeezing condition only in the presence of neurofeedback. These findings demonstrate that real-time fNIRS neurofeedback is a viable platform for brain-machine interface applications.

  7. Bilateral primary motor cortex circuitry is modulated due to theta burst stimulation to left dorsal premotor cortex and bimanual training.

    PubMed

    Neva, Jason L; Vesia, Michael; Singh, Amaya M; Staines, W Richard

    2015-08-27

    Motor preparatory and execution activity is enhanced after a single session of bimanual visuomotor training (BMT). Recently, we have shown that increased primary motor cortex (M1) excitability occurs when BMT involves simultaneous activation of homologous muscles and these effects are enhanced when BMT is preceded by intermittent theta burst stimulation (iTBS) to the left dorsal premotor cortex (lPMd). The neural mechanisms underlying these modulations are unclear, but may include interhemispheric interactions between homologous M1s and connectivity with premotor regions. The purpose of this study was to investigate the possible intracortical and interhemispheric modulations of the extensor carpi radials (ECR) representation in M1 bilaterally due to: (1) BMT, (2) iTBS to lPMd, and (3) iTBS to lPMd followed by BMT. This study tests three related hypotheses: (1) BMT will enhance excitability within and between M1 bilaterally, (2) iTBS to lPMd will primarily enhance left M1 (lM1) excitability, and (3) the combination of these interventions will cause a greater enhancement of bilateral M1 excitability. We used single and paired-pulse transcranial magnetic stimulation (TMS) to quantify M1 circuitry bilaterally. The results demonstrate the neural mechanisms underlying the early markers of rapid functional plasticity associated with BMT and iTBS to lPMd primarily relate to modulations of long-interval inhibitory (i.e. GABAB-mediated) circuitry within and between M1s. This work provides novel insight into the underlying neural mechanisms involved in M1 excitability changes associated with BMT and iTBS to lPMd. Critically, this work may inform rehabilitation training and stimulation techniques that modulate cortical plasticity after brain injury. Copyright © 2015. Published by Elsevier B.V.

  8. A periodic network of neurochemical modules in the inferior colliculus.

    PubMed

    Chernock, Michelle L; Larue, David T; Winer, Jeffery A

    2004-02-01

    A new organization has been found in shell nuclei of rat inferior colliculus. Chemically specific modules with a periodic distribution fill about half of layer 2 of external cortex and dorsal cortex. Modules contain clusters of small glutamic acid decarboxylase-positive neurons and large boutons at higher density than in other inferior colliculus subdivisions. The modules are also present in tissue stained for parvalbumin, cytochrome oxidase, nicotinamide adenine dinucleotide phosphate-diaphorase, and acetylcholinesterase. Six to seven bilaterally symmetrical modules extend from the caudal extremity of the external cortex of the inferior colliculus to its rostral pole. Modules are from approximately 800 to 2200 microm long and have areas between 5000 and 40,000 microm2. Modules alternate with immunonegative regions. Similar modules are found in inbred and outbred strains of rat, and in both males and females. They are absent in mouse, squirrel, cat, bat, macaque monkey, and barn owl. Modules are immunonegative for glycine, calbindin, serotonin, and choline acetyltransferase. The auditory cortex and ipsi- and contralateral inferior colliculi project to the external cortex. Somatic sensory influences from the dorsal column nuclei and spinal trigeminal nucleus are the primary ascending sensory input to the external cortex; ascending auditory input to layer 2 is sparse. If the immunopositive modular neurons receive this input, the external cortex could participate in spatial orientation and somatic motor control through its intrinsic and extrinsic projections.

  9. Speech dynamics are coded in the left motor cortex in fluent speakers but not in adults who stutter

    PubMed Central

    Hoang, T. N. Linh; Neef, Andreas; Paulus, Walter; Sommer, Martin

    2015-01-01

    The precise excitability regulation of neuronal circuits in the primary motor cortex is central to the successful and fluent production of speech. Our question was whether the involuntary execution of undesirable movements, e.g. stuttering, is linked to an insufficient excitability tuning of neural populations in the orofacial region of the primary motor cortex. We determined the speech-related time course of excitability modulation in the left and right primary motor tongue representation. Thirteen fluent speakers (four females, nine males; aged 23–44) and 13 adults who stutter (four females, nine males, aged 21–55) were asked to build verbs with the verbal prefix ‘auf’. Single-pulse transcranial magnetic stimulation was applied over the primary motor cortex during the transition phase between a fixed labiodental articulatory configuration and immediately following articulatory configurations, at different latencies after transition onset. Bilateral electromyography was recorded from self-adhesive electrodes placed on the surface of the tongue. Off-line, we extracted the motor evoked potential amplitudes and normalized these amplitudes to the individual baseline excitability during the fixed configuration. Fluent speakers demonstrated a prominent left hemisphere increase of motor cortex excitability in the transition phase (P = 0.009). In contrast, the excitability of the right primary motor tongue representation was unchanged. Interestingly, adults afflicted with stuttering revealed a lack of left-hemisphere facilitation. Moreover, the magnitude of facilitation was negatively correlated with stuttering frequency. Although orofacial midline muscles are bilaterally innervated from corticobulbar projections of both hemispheres, our results indicate that speech motor plans are controlled primarily in the left primary speech motor cortex. This speech motor planning-related asymmetry towards the left orofacial motor cortex is missing in stuttering. Moreover, a negative correlation between the amount of facilitation and stuttering severity suggests that we discovered a main physiological principle of fluent speech production and its role in stuttering. PMID:25595146

  10. Toward an autonomous brain machine interface: integrating sensorimotor reward modulation and reinforcement learning.

    PubMed

    Marsh, Brandi T; Tarigoppula, Venkata S Aditya; Chen, Chen; Francis, Joseph T

    2015-05-13

    For decades, neurophysiologists have worked on elucidating the function of the cortical sensorimotor control system from the standpoint of kinematics or dynamics. Recently, computational neuroscientists have developed models that can emulate changes seen in the primary motor cortex during learning. However, these simulations rely on the existence of a reward-like signal in the primary sensorimotor cortex. Reward modulation of the primary sensorimotor cortex has yet to be characterized at the level of neural units. Here we demonstrate that single units/multiunits and local field potentials in the primary motor (M1) cortex of nonhuman primates (Macaca radiata) are modulated by reward expectation during reaching movements and that this modulation is present even while subjects passively view cursor motions that are predictive of either reward or nonreward. After establishing this reward modulation, we set out to determine whether we could correctly classify rewarding versus nonrewarding trials, on a moment-to-moment basis. This reward information could then be used in collaboration with reinforcement learning principles toward an autonomous brain-machine interface. The autonomous brain-machine interface would use M1 for both decoding movement intention and extraction of reward expectation information as evaluative feedback, which would then update the decoding algorithm as necessary. In the work presented here, we show that this, in theory, is possible. Copyright © 2015 the authors 0270-6474/15/357374-14$15.00/0.

  11. Paired motor cortex and cervical epidural electrical stimulation timed to converge in the spinal cord promotes lasting increases in motor responses

    PubMed Central

    Mishra, Asht M.; Pal, Ajay; Gupta, Disha

    2017-01-01

    Key points Pairing motor cortex stimulation and spinal cord epidural stimulation produced large augmentation in motor cortex evoked potentials if they were timed to converge in the spinal cord.The modulation of cortical evoked potentials by spinal cord stimulation was largest when the spinal electrodes were placed over the dorsal root entry zone.Repeated pairing of motor cortex and spinal cord stimulation caused lasting increases in evoked potentials from both sites, but only if the time between the stimuli was optimal.Both immediate and lasting effects of paired stimulation are likely mediated by convergence of descending motor circuits and large diameter afferents onto common interneurons in the cervical spinal cord. Abstract Convergent activity in neural circuits can generate changes at their intersection. The rules of paired electrical stimulation are best understood for protocols that stimulate input circuits and their targets. We took a different approach by targeting the interaction of descending motor pathways and large diameter afferents in the spinal cord. We hypothesized that pairing stimulation of motor cortex and cervical spinal cord would strengthen motor responses through their convergence. We placed epidural electrodes over motor cortex and the dorsal cervical spinal cord in rats; motor evoked potentials (MEPs) were measured from biceps. MEPs evoked from motor cortex were robustly augmented with spinal epidural stimulation delivered at an intensity below the threshold for provoking an MEP. Augmentation was critically dependent on the timing and position of spinal stimulation. When the spinal stimulation was timed to coincide with the descending volley from motor cortex stimulation, MEPs were more than doubled. We then tested the effect of repeated pairing of motor cortex and spinal stimulation. Repetitive pairing caused strong augmentation of cortical MEPs and spinal excitability that lasted up to an hour after just 5 min of pairing. Additional physiology experiments support the hypothesis that paired stimulation is mediated by convergence of descending motor circuits and large diameter afferents in the spinal cord. The large effect size of this protocol and the conservation of the circuits being manipulated between rats and humans makes it worth pursuing for recovery of sensorimotor function after injury to the central nervous system. PMID:28752624

  12. Paired motor cortex and cervical epidural electrical stimulation timed to converge in the spinal cord promotes lasting increases in motor responses.

    PubMed

    Mishra, Asht M; Pal, Ajay; Gupta, Disha; Carmel, Jason B

    2017-11-15

    Pairing motor cortex stimulation and spinal cord epidural stimulation produced large augmentation in motor cortex evoked potentials if they were timed to converge in the spinal cord. The modulation of cortical evoked potentials by spinal cord stimulation was largest when the spinal electrodes were placed over the dorsal root entry zone. Repeated pairing of motor cortex and spinal cord stimulation caused lasting increases in evoked potentials from both sites, but only if the time between the stimuli was optimal. Both immediate and lasting effects of paired stimulation are likely mediated by convergence of descending motor circuits and large diameter afferents onto common interneurons in the cervical spinal cord. Convergent activity in neural circuits can generate changes at their intersection. The rules of paired electrical stimulation are best understood for protocols that stimulate input circuits and their targets. We took a different approach by targeting the interaction of descending motor pathways and large diameter afferents in the spinal cord. We hypothesized that pairing stimulation of motor cortex and cervical spinal cord would strengthen motor responses through their convergence. We placed epidural electrodes over motor cortex and the dorsal cervical spinal cord in rats; motor evoked potentials (MEPs) were measured from biceps. MEPs evoked from motor cortex were robustly augmented with spinal epidural stimulation delivered at an intensity below the threshold for provoking an MEP. Augmentation was critically dependent on the timing and position of spinal stimulation. When the spinal stimulation was timed to coincide with the descending volley from motor cortex stimulation, MEPs were more than doubled. We then tested the effect of repeated pairing of motor cortex and spinal stimulation. Repetitive pairing caused strong augmentation of cortical MEPs and spinal excitability that lasted up to an hour after just 5 min of pairing. Additional physiology experiments support the hypothesis that paired stimulation is mediated by convergence of descending motor circuits and large diameter afferents in the spinal cord. The large effect size of this protocol and the conservation of the circuits being manipulated between rats and humans makes it worth pursuing for recovery of sensorimotor function after injury to the central nervous system. © 2017 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

  13. Reliability of directional information in unsorted spikes and local field potentials recorded in human motor cortex.

    PubMed

    Perge, János A; Zhang, Shaomin; Malik, Wasim Q; Homer, Mark L; Cash, Sydney; Friehs, Gerhard; Eskandar, Emad N; Donoghue, John P; Hochberg, Leigh R

    2014-08-01

    Action potentials and local field potentials (LFPs) recorded in primary motor cortex contain information about the direction of movement. LFPs are assumed to be more robust to signal instabilities than action potentials, which makes LFPs, along with action potentials, a promising signal source for brain-computer interface applications. Still, relatively little research has directly compared the utility of LFPs to action potentials in decoding movement direction in human motor cortex. We conducted intracortical multi-electrode recordings in motor cortex of two persons (T2 and [S3]) as they performed a motor imagery task. We then compared the offline decoding performance of LFPs and spiking extracted from the same data recorded across a one-year period in each participant. We obtained offline prediction accuracy of movement direction and endpoint velocity in multiple LFP bands, with the best performance in the highest (200-400 Hz) LFP frequency band, presumably also containing low-pass filtered action potentials. Cross-frequency correlations of preferred directions and directional modulation index showed high similarity of directional information between action potential firing rates (spiking) and high frequency LFPs (70-400 Hz), and increasing disparity with lower frequency bands (0-7, 10-40 and 50-65 Hz). Spikes predicted the direction of intended movement more accurately than any individual LFP band, however combined decoding of all LFPs was statistically indistinguishable from spike-based performance. As the quality of spiking signals (i.e. signal amplitude) and the number of significantly modulated spiking units decreased, the offline decoding performance decreased 3.6[5.65]%/month (for T2 and [S3] respectively). The decrease in the number of significantly modulated LFP signals and their decoding accuracy followed a similar trend (2.4[2.85]%/month, ANCOVA, p = 0.27[0.03]). Field potentials provided comparable offline decoding performance to unsorted spikes. Thus, LFPs may provide useful external device control using current human intracortical recording technology. ( NCT00912041.).

  14. Induction of motor associative plasticity in the posterior parietal cortex-primary motor network.

    PubMed

    Chao, Chi-Chao; Karabanov, Anke Ninija; Paine, Rainer; Carolina de Campos, Ana; Kukke, Sahana N; Wu, Tianxia; Wang, Han; Hallett, Mark

    2015-02-01

    There is anatomical and functional connectivity between the primary motor cortex (M1) and posterior parietal cortex (PPC) that plays a role in sensorimotor integration. In this study, we applied corticocortical paired-associative stimuli to ipsilateral PPC and M1 (parietal ccPAS) in healthy right-handed subjects to test if this procedure could modulate M1 excitability and PPC-M1 connectivity. One hundred and eighty paired transcranial magnetic stimuli to the PPC and M1 at an interstimulus interval (ISI) of 8 ms were delivered at 0.2 Hz. We found that parietal ccPAS in the left hemisphere increased the excitability of conditioned left M1 assessed by motor evoked potentials (MEPs) and the input-output curve. Motor behavior assessed by the Purdue pegboard task was unchanged compared with controls. At baseline, conditioning stimuli over the left PPC potentiated MEPs from left M1 when ISI was 8 ms. This interaction significantly attenuated at 60 min after left parietal ccPAS. Additional experiments showed that parietal ccPAS induced plasticity was timing-dependent, was absent if ISI was 100 ms, and could also be seen in the right hemisphere. Our results suggest that parietal ccPAS can modulate M1 excitability and PPC-M1 connectivity and is a new approach to modify motor excitability and sensorimotor interaction. Published by Oxford University Press 2013. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  15. The Neural Mechanism Exploration of Adaptive Motor Control: Dynamical Economic Cell Allocation in the Primary Motor Cortex.

    PubMed

    Li, Wei; Guo, Yangyang; Fan, Jing; Ma, Chaolin; Ma, Xuan; Chen, Xi; He, Jiping

    2017-05-01

    Adaptive flexibility is of significance for the smooth and efficient movements in goal attainment. However, the underlying work mechanism of the cerebral cortex in adaptive motor control still remains unclear. How does the cerebral cortex organize and coordinate the activity of a large population of cells in the implementation of various motor strategies? To explore this issue, single-unit activities from the M1 region and kinematic data were recorded simultaneously in monkeys performing 3D reach-to-grasp tasks with different perturbations. Varying motor control strategies were employed and achieved in different perturbed tasks, via the dynamic allocation of cells to modulate specific movement parameters. An economic principle was proposed for the first time to describe a basic rule for cell allocation in the primary motor cortex. This principle, defined as the Dynamic Economic Cell Allocation Mechanism (DECAM), guarantees benefit maximization in cell allocation under limited neuronal resources, and avoids committing resources to uneconomic investments for unreliable factors with no or little revenue. That is to say, the cells recruited are always preferentially allocated to those factors with reliable return; otherwise, the cells are dispatched to respond to other factors about task. The findings of this study might partially reveal the working mechanisms underlying the role of the cerebral cortex in adaptive motor control, wherein is also of significance for the design of future intelligent brain-machine interfaces and rehabilitation device.

  16. Generation of novel motor sequences: the neural correlates of musical improvisation.

    PubMed

    Berkowitz, Aaron L; Ansari, Daniel

    2008-06-01

    While some motor behavior is instinctive and stereotyped or learned and re-executed, much action is a spontaneous response to a novel set of environmental conditions. The neural correlates of both pre-learned and cued motor sequences have been previously studied, but novel motor behavior has thus far not been examined through brain imaging. In this paper, we report a study of musical improvisation in trained pianists with functional magnetic resonance imaging (fMRI), using improvisation as a case study of novel action generation. We demonstrate that both rhythmic (temporal) and melodic (ordinal) motor sequence creation modulate activity in a network of brain regions comprised of the dorsal premotor cortex, the rostral cingulate zone of the anterior cingulate cortex, and the inferior frontal gyrus. These findings are consistent with a role for the dorsal premotor cortex in movement coordination, the rostral cingulate zone in voluntary selection, and the inferior frontal gyrus in sequence generation. Thus, the invention of novel motor sequences in musical improvisation recruits a network of brain regions coordinated to generate possible sequences, select among them, and execute the decided-upon sequence.

  17. Poststimulation time interval-dependent effects of motor cortex anodal tDCS on reaction-time task performance.

    PubMed

    Molero-Chamizo, Andrés; Alameda Bailén, José R; Garrido Béjar, Tamara; García López, Macarena; Jaén Rodríguez, Inmaculada; Gutiérrez Lérida, Carolina; Pérez Panal, Silvia; González Ángel, Gloria; Lemus Corchero, Laura; Ruiz Vega, María J; Nitsche, Michael A; Rivera-Urbina, Guadalupe N

    2018-02-01

    Anodal transcranial direct current stimulation (tDCS) induces long-term potentiation-like plasticity, which is associated with long-lasting effects on different cognitive, emotional, and motor performances. Specifically, tDCS applied over the motor cortex is considered to improve reaction time in simple and complex tasks. The timing of tDCS relative to task performance could determine the efficacy of tDCS to modulate performance. The aim of this study was to compare the effects of a single session of anodal tDCS (1.5 mA, for 15 min) applied over the left primary motor cortex (M1) versus sham stimulation on performance of a go/no-go simple reaction-time task carried out at three different time points after tDCS-namely, 0, 30, or 60 min after stimulation. Performance zero min after anodal tDCS was improved during the whole course of the task. Performance 30 min after anodal tDCS was improved only in the last block of the reaction-time task. Performance 60 min after anodal tDCS was not significantly different throughout the entire task. These findings suggest that the motor cortex excitability changes induced by tDCS can improve motor responses, and these effects critically depend on the time interval between stimulation and task performance.

  18. Distinct Functional Modules for Discrete and Rhythmic Forelimb Movements in the Mouse Motor Cortex.

    PubMed

    Hira, Riichiro; Terada, Shin-Ichiro; Kondo, Masashi; Matsuzaki, Masanori

    2015-09-30

    Movements of animals are composed of two fundamental dynamics: discrete and rhythmic movements. Although the movements with distinct dynamics are thought to be differently processed in the CNS, it is unclear how they are represented in the cerebral cortex. Here, we investigated the cortical representation of movement dynamics by developing prolonged transcranial optogenetic stimulation (pTOS) using awake, channelrhodopsin-2 transgenic mice. We found two domains that induced discrete forelimb movements in the forward and backward directions, and these sandwiched a domain that generated rhythmic forelimb movements. The forward discrete movement had an intrinsic velocity profile and the rhythmic movement had an intrinsic oscillation frequency. Each of the forward discrete and rhythmic domains possessed intracortical synaptic connections within its own domain, independently projected to the spinal cord, and weakened the neuronal activity and movement induction of the other domain. pTOS-induced movements were also classified as ethologically relevant movements. Forepaw-to-mouth movement was mapped in a part of the forward discrete domain, while locomotion-like movement was in a part of the rhythmic domain. Interestingly, photostimulation of the rhythmic domain resulted in a nonrhythmic, continuous lever-pull movement when a lever was present. The motor cortex possesses functional modules for distinct movement dynamics, and these can adapt to environmental constraints for purposeful movements. Significance statement: Animal behavior has discrete and rhythmic components, such as reaching and locomotion. It is unclear how these movements with distinct dynamics are represented in the cerebral cortex. We investigated the dynamics of movements induced by long-duration transcranial photostimulation on the dorsal cortex of awake channelrhodopsin-2 transgenic mice. We found two domains causing forward and backward discrete forelimb movements and a domain for rhythmic forelimb movements. A domain for forward discrete movement and a domain for rhythmic movement mutually weakened neuronal activity and movement size. The photostimulation of the rhythmic domain also induced nonrhythmic, lever-pull movement, when the lever was present. Thus, the motor cortex has functional modules with distinct dynamics, and each module retains flexibility for adaptation to different environments. Copyright © 2015 the authors 0270-6474/15/3513311-12$15.00/0.

  19. Acute Modulation of Brain Connectivity in Parkinson Disease after Automatic Mechanical Peripheral Stimulation: A Pilot Study

    PubMed Central

    Piervincenzi, Claudia; Galli, Manuela; Melgari, Jean Marc; Salomone, Gaetano; Sale, Patrizio; Mallio, Carlo Augusto; Carducci, Filippo; Stocchi, Fabrizio

    2015-01-01

    Objective The present study shows the results of a double-blind sham-controlled pilot trial to test whether measurable stimulus-specific functional connectivity changes exist after Automatic Mechanical Peripheral Stimulation (AMPS) in patients with idiopathic Parkinson Disease. Methods Eleven patients (6 women and 5 men) with idiopathic Parkinson Disease underwent brain fMRI immediately before and after sham or effective AMPS. Resting state Functional Connectivity (RSFC) was assessed using the seed-ROI based analysis. Seed ROIs were positioned on basal ganglia, on primary sensory-motor cortices, on the supplementary motor areas and on the cerebellum. Individual differences for pre- and post-effective AMPS and pre- and post-sham condition were obtained and first entered in respective one-sample t-test analyses, to evaluate the mean effect of condition. Results Effective AMPS, but not sham stimulation, induced increase of RSFC of the sensory motor cortex, nucleus striatum and cerebellum. Secondly, individual differences for both conditions were entered into paired group t-test analysis to rule out sub-threshold effects of sham stimulation, which showed stronger connectivity of the striatum nucleus with the right lateral occipital cortex and the cuneal cortex (max Z score 3.12) and with the right anterior temporal lobe (max Z score 3.42) and of the cerebellum with the right lateral occipital cortex and the right cerebellar cortex (max Z score 3.79). Conclusions Our results suggest that effective AMPS acutely increases RSFC of brain regions involved in visuo-spatial and sensory-motor integration. Classification of Evidence This study provides Class II evidence that automatic mechanical peripheral stimulation is effective in modulating brain functional connectivity of patients with Parkinson Disease at rest. Trial Registration Clinical Trials.gov NCT01815281 PMID:26469868

  20. Acute Modulation of Brain Connectivity in Parkinson Disease after Automatic Mechanical Peripheral Stimulation: A Pilot Study.

    PubMed

    Quattrocchi, Carlo Cosimo; de Pandis, Maria Francesca; Piervincenzi, Claudia; Galli, Manuela; Melgari, Jean Marc; Salomone, Gaetano; Sale, Patrizio; Mallio, Carlo Augusto; Carducci, Filippo; Stocchi, Fabrizio

    2015-01-01

    The present study shows the results of a double-blind sham-controlled pilot trial to test whether measurable stimulus-specific functional connectivity changes exist after Automatic Mechanical Peripheral Stimulation (AMPS) in patients with idiopathic Parkinson Disease. Eleven patients (6 women and 5 men) with idiopathic Parkinson Disease underwent brain fMRI immediately before and after sham or effective AMPS. Resting state Functional Connectivity (RSFC) was assessed using the seed-ROI based analysis. Seed ROIs were positioned on basal ganglia, on primary sensory-motor cortices, on the supplementary motor areas and on the cerebellum. Individual differences for pre- and post-effective AMPS and pre- and post-sham condition were obtained and first entered in respective one-sample t-test analyses, to evaluate the mean effect of condition. Effective AMPS, but not sham stimulation, induced increase of RSFC of the sensory motor cortex, nucleus striatum and cerebellum. Secondly, individual differences for both conditions were entered into paired group t-test analysis to rule out sub-threshold effects of sham stimulation, which showed stronger connectivity of the striatum nucleus with the right lateral occipital cortex and the cuneal cortex (max Z score 3.12) and with the right anterior temporal lobe (max Z score 3.42) and of the cerebellum with the right lateral occipital cortex and the right cerebellar cortex (max Z score 3.79). Our results suggest that effective AMPS acutely increases RSFC of brain regions involved in visuo-spatial and sensory-motor integration. This study provides Class II evidence that automatic mechanical peripheral stimulation is effective in modulating brain functional connectivity of patients with Parkinson Disease at rest. Clinical Trials.gov NCT01815281.

  1. Convergence of flexor reflex and corticospinal inputs on tibialis anterior network in humans.

    PubMed

    Mackey, Ann S; Uttaro, Denise; McDonough, Maureen P; Krivis, Lisa I; Knikou, Maria

    2016-01-01

    Integration between descending and ascending inputs at supraspinal and spinal levels is a key characteristic of neural control of movement. In this study, we characterized convergence of the flexor reflex and corticospinal inputs on the tibialis anterior (TA) network in healthy human subjects. Specifically, we characterized the modulation profiles of the spinal TA flexor reflex following subthreshold and suprathreshold transcranial magnetic stimulation (TMS). We also characterized the modulation profiles of the TA motor evoked potentials (MEPs) following medial arch foot stimulation at sensory and above reflex threshold. TA flexor reflexes were evoked following stimulation of the medial arch of the foot with a 30 ms pulse train at innocuous intensities. TA MEPs were evoked following TMS of the leg motor cortex area. TMS at 0.7 and at 1.2 MEP resting threshold increased the TA flexor reflex when TMS was delivered 40-100 ms after foot stimulation, and decreased the TA flexor reflex when TMS was delivered 25-110 ms before foot stimulation. Foot stimulation at sensory and above flexor reflex threshold induced a similar time-dependent modulation in resting TA MEPs, that were facilitated when foot stimulation was delivered 40-100 ms before TMS. The flexor reflex and MEPs recorded from the medial hamstring muscle were modulated in a similar manner to that observed for the TA flexor reflex and MEP. Cutaneomuscular afferents from the distal foot can increase the output of the leg motor cortex area. Descending motor volleys that directly or indirectly depolarize flexor motoneurons increase the output of the spinal FRA interneuronal network. The parallel facilitation of flexor MEPs and flexor reflexes is likely cortical in origin. Afferent mediated facilitation of corticospinal excitability can be utilized to strengthen motor cortex output in neurological disorders. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  2. Gene Expression Changes in the Motor Cortex Mediating Motor Skill Learning

    PubMed Central

    Cheung, Vincent C. K.; DeBoer, Caroline; Hanson, Elizabeth; Tunesi, Marta; D'Onofrio, Mara; Arisi, Ivan; Brandi, Rossella; Cattaneo, Antonino; Goosens, Ki A.

    2013-01-01

    The primary motor cortex (M1) supports motor skill learning, yet little is known about the genes that contribute to motor cortical plasticity. Such knowledge could identify candidate molecules whose targeting might enable a new understanding of motor cortical functions, and provide new drug targets for the treatment of diseases which impair motor function, such as ischemic stroke. Here, we assess changes in the motor-cortical transcriptome across different stages of motor skill acquisition. Adult rats were trained on a gradually acquired appetitive reach and grasp task that required different strategies for successful pellet retrieval, or a sham version of the task in which the rats received pellet reward without needing to develop the reach and grasp skill. Tissue was harvested from the forelimb motor-cortical area either before training commenced, prior to the initial rise in task performance, or at peak performance. Differential classes of gene expression were observed at the time point immediately preceding motor task improvement. Functional clustering revealed that gene expression changes were related to the synapse, development, intracellular signaling, and the fibroblast growth factor (FGF) family, with many modulated genes known to regulate synaptic plasticity, synaptogenesis, and cytoskeletal dynamics. The modulated expression of synaptic genes likely reflects ongoing network reorganization from commencement of training till the point of task improvement, suggesting that motor performance improves only after sufficient modifications in the cortical circuitry have accumulated. The regulated FGF-related genes may together contribute to M1 remodeling through their roles in synaptic growth and maturation. PMID:23637843

  3. Enhanced alpha-oscillations in visual cortex during anticipation of self-generated visual stimulation.

    PubMed

    Stenner, Max-Philipp; Bauer, Markus; Haggard, Patrick; Heinze, Hans-Jochen; Dolan, Ray

    2014-11-01

    The perceived intensity of sensory stimuli is reduced when these stimuli are caused by the observer's actions. This phenomenon is traditionally explained by forward models of sensory action-outcome, which arise from motor processing. Although these forward models critically predict anticipatory modulation of sensory neural processing, neurophysiological evidence for anticipatory modulation is sparse and has not been linked to perceptual data showing sensory attenuation. By combining a psychophysical task involving contrast discrimination with source-level time-frequency analysis of MEG data, we demonstrate that the amplitude of alpha-oscillations in visual cortex is enhanced before the onset of a visual stimulus when the identity and onset of the stimulus are controlled by participants' motor actions. Critically, this prestimulus enhancement of alpha-amplitude is paralleled by psychophysical judgments of a reduced contrast for this stimulus. We suggest that alpha-oscillations in visual cortex preceding self-generated visual stimulation are a likely neurophysiological signature of motor-induced sensory anticipation and mediate sensory attenuation. We discuss our results in relation to proposals that attribute generic inhibitory functions to alpha-oscillations in prioritizing and gating sensory information via top-down control.

  4. Common medial frontal mechanisms of adaptive control in humans and rodents

    PubMed Central

    Frank, Michael J.; Laubach, Mark

    2013-01-01

    In this report, we describe how common brain networks within the medial frontal cortex facilitate adaptive behavioral control in rodents and humans. We demonstrate that low frequency oscillations below 12 Hz are dramatically modulated after errors in humans over mid-frontal cortex and in rats within prelimbic and anterior cingulate regions of medial frontal cortex. These oscillations were phase-locked between medial frontal cortex and motor areas in both rats and humans. In rats, single neurons that encoded prior behavioral outcomes were phase-coherent with low-frequency field oscillations particularly after errors. Inactivating medial frontal regions in rats led to impaired behavioral adjustments after errors, eliminated the differential expression of low frequency oscillations after errors, and increased low-frequency spike-field coupling within motor cortex. Our results describe a novel mechanism for behavioral adaptation via low-frequency oscillations and elucidate how medial frontal networks synchronize brain activity to guide performance. PMID:24141310

  5. Presence and Absence of Muscle Contraction Elicited by Peripheral Nerve Electrical Stimulation Differentially Modulate Primary Motor Cortex Excitability.

    PubMed

    Sasaki, Ryoki; Kotan, Shinichi; Nakagawa, Masaki; Miyaguchi, Shota; Kojima, Sho; Saito, Kei; Inukai, Yasuto; Onishi, Hideaki

    2017-01-01

    Modulation of cortical excitability by sensory inputs is a critical component of sensorimotor integration. Sensory afferents, including muscle and joint afferents, to somatosensory cortex (S1) modulate primary motor cortex (M1) excitability, but the effects of muscle and joint afferents specifically activated by muscle contraction are unknown. We compared motor evoked potentials (MEPs) following median nerve stimulation (MNS) above and below the contraction threshold based on the persistence of M-waves. Peripheral nerve electrical stimulation (PES) conditions, including right MNS at the wrist at 110% motor threshold (MT; 110% MNS condition), right MNS at the index finger (sensory digit nerve stimulation [DNS]) with stimulus intensity approximately 110% MNS (DNS condition), and right MNS at the wrist at 90% MT (90% MNS condition) were applied. PES was administered in a 4 s ON and 6 s OFF cycle for 20 min at 30 Hz. In Experiment 1 ( n = 15), MEPs were recorded from the right abductor pollicis brevis (APB) before (baseline) and after PES. In Experiment 2 ( n = 15), M- and F-waves were recorded from the right APB. Stimulation at 110% MNS at the wrist evoking muscle contraction increased MEP amplitudes after PES compared with those at baseline, whereas DNS at the index finger and 90% MNS at the wrist not evoking muscle contraction decreased MEP amplitudes after PES. M- and F-waves, which reflect spinal cord or muscular and neuromuscular junctions, did not change following PES. These results suggest that muscle contraction and concomitant muscle/joint afferent inputs specifically enhance M1 excitability.

  6. Presence and Absence of Muscle Contraction Elicited by Peripheral Nerve Electrical Stimulation Differentially Modulate Primary Motor Cortex Excitability

    PubMed Central

    Sasaki, Ryoki; Kotan, Shinichi; Nakagawa, Masaki; Miyaguchi, Shota; Kojima, Sho; Saito, Kei; Inukai, Yasuto; Onishi, Hideaki

    2017-01-01

    Modulation of cortical excitability by sensory inputs is a critical component of sensorimotor integration. Sensory afferents, including muscle and joint afferents, to somatosensory cortex (S1) modulate primary motor cortex (M1) excitability, but the effects of muscle and joint afferents specifically activated by muscle contraction are unknown. We compared motor evoked potentials (MEPs) following median nerve stimulation (MNS) above and below the contraction threshold based on the persistence of M-waves. Peripheral nerve electrical stimulation (PES) conditions, including right MNS at the wrist at 110% motor threshold (MT; 110% MNS condition), right MNS at the index finger (sensory digit nerve stimulation [DNS]) with stimulus intensity approximately 110% MNS (DNS condition), and right MNS at the wrist at 90% MT (90% MNS condition) were applied. PES was administered in a 4 s ON and 6 s OFF cycle for 20 min at 30 Hz. In Experiment 1 (n = 15), MEPs were recorded from the right abductor pollicis brevis (APB) before (baseline) and after PES. In Experiment 2 (n = 15), M- and F-waves were recorded from the right APB. Stimulation at 110% MNS at the wrist evoking muscle contraction increased MEP amplitudes after PES compared with those at baseline, whereas DNS at the index finger and 90% MNS at the wrist not evoking muscle contraction decreased MEP amplitudes after PES. M- and F-waves, which reflect spinal cord or muscular and neuromuscular junctions, did not change following PES. These results suggest that muscle contraction and concomitant muscle/joint afferent inputs specifically enhance M1 excitability. PMID:28392766

  7. Combining robotic training and inactivation of the healthy hemisphere restores pre-stroke motor patterns in mice

    PubMed Central

    Spalletti, Cristina; Alia, Claudia; Lai, Stefano; Panarese, Alessandro; Conti, Sara

    2017-01-01

    Focal cortical stroke often leads to persistent motor deficits, prompting the need for more effective interventions. The efficacy of rehabilitation can be increased by ‘plasticity-stimulating’ treatments that enhance experience-dependent modifications in spared areas. Transcallosal pathways represent a promising therapeutic target, but their role in post-stroke recovery remains controversial. Here, we demonstrate that the contralesional cortex exerts an enhanced interhemispheric inhibition over the perilesional tissue after focal cortical stroke in mouse forelimb motor cortex. Accordingly, we designed a rehabilitation protocol combining intensive, repeatable exercises on a robotic platform with reversible inactivation of the contralesional cortex. This treatment promoted recovery in general motor tests and in manual dexterity with remarkable restoration of pre-lesion movement patterns, evaluated by kinematic analysis. Recovery was accompanied by a reduction of transcallosal inhibition and ‘plasticity brakes’ over the perilesional tissue. Our data support the use of combinatorial clinical therapies exploiting robotic devices and modulation of interhemispheric connectivity. PMID:29280732

  8. A Circuit for Motor Cortical Modulation of Auditory Cortical Activity

    PubMed Central

    Nelson, Anders; Schneider, David M.; Takatoh, Jun; Sakurai, Katsuyasu; Wang, Fan

    2013-01-01

    Normal hearing depends on the ability to distinguish self-generated sounds from other sounds, and this ability is thought to involve neural circuits that convey copies of motor command signals to various levels of the auditory system. Although such interactions at the cortical level are believed to facilitate auditory comprehension during movements and drive auditory hallucinations in pathological states, the synaptic organization and function of circuitry linking the motor and auditory cortices remain unclear. Here we describe experiments in the mouse that characterize circuitry well suited to transmit motor-related signals to the auditory cortex. Using retrograde viral tracing, we established that neurons in superficial and deep layers of the medial agranular motor cortex (M2) project directly to the auditory cortex and that the axons of some of these deep-layer cells also target brainstem motor regions. Using in vitro whole-cell physiology, optogenetics, and pharmacology, we determined that M2 axons make excitatory synapses in the auditory cortex but exert a primarily suppressive effect on auditory cortical neuron activity mediated in part by feedforward inhibition involving parvalbumin-positive interneurons. Using in vivo intracellular physiology, optogenetics, and sound playback, we also found that directly activating M2 axon terminals in the auditory cortex suppresses spontaneous and stimulus-evoked synaptic activity in auditory cortical neurons and that this effect depends on the relative timing of motor cortical activity and auditory stimulation. These experiments delineate the structural and functional properties of a corticocortical circuit that could enable movement-related suppression of auditory cortical activity. PMID:24005287

  9. An unavoidable modulation? Sensory attention and human primary motor cortex excitability.

    PubMed

    Ruge, Diane; Muggleton, Neil; Hoad, Damon; Caronni, Antonio; Rothwell, John C

    2014-09-01

    The link between basic physiology and its modulation by cognitive states, such as attention, is poorly understood. A significant association becomes apparent when patients with movement disorders describe experiences with changing their attention focus and the fundamental effect that this has on their motor symptoms. Moreover, frequently used mental strategies for treating such patients, e.g. with task-specific dystonia, widely lack laboratory-based knowledge about physiological mechanisms. In this largely unexplored field, we looked at how the locus of attention, when it changed between internal (locus hand) and external (visual target), influenced excitability in the primary motor cortex (M1) in healthy humans. Intriguingly, both internal and external attention had the capacity to change M1 excitability. Both led to a reduced stimulation-induced GABA-related inhibition and a change in motor evoked potential size, i.e. an overall increased M1 excitability. These previously unreported findings indicated: (i) that cognitive state differentially interacted with M1 physiology, (ii) that our view of distraction (attention locus shifted towards external or distant location), which is used as a prevention or management strategy for use-dependent motor disorders, is too simple and currently unsupported for clinical application, and (iii) the physiological state reached through attention modulation represents an alternative explanation for frequently reported electrophysiology findings in neuropsychiatric disorders, such as an aberrant inhibition. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  10. Lateralization in motor facilitation during action observation: a TMS study.

    PubMed

    Aziz-Zadeh, Lisa; Maeda, Fumiko; Zaidel, Eran; Mazziotta, John; Iacoboni, Marco

    2002-05-01

    Action observation facilitates corticospinal excitability. This is presumably due to a premotor neural system that is active when we perform actions and when we observe actions performed by others. It has been speculated that this neural system is a precursor of neural systems subserving language. If this theory is true, we may expect hemispheric differences in the motor facilitation produced by action observation, with the language-dominant left hemisphere showing stronger facilitation than the right hemisphere. Furthermore, it has been suggested that body parts are recognized via cortical regions controlling sensory and motor processing associated with that body part. If this is true, then corticospinal facilitation during action observation should be modulated by the laterality of the observed body part. The present study addressed these two issues using TMS for each motor cortex separately as participants observed actions being performed by a left hand, a right hand, or a control stimulus on the computer screen. We found no overall difference between the right and left hemisphere for motor-evoked potential (MEP) size during action observation. However, when TMS was applied to the left motor cortex, MEPs were larger while observing right hand actions. Likewise, when TMS was applied to the right motor cortex, MEPs were larger while observing left hand actions. Our data do not suggest left hemisphere superiority in the facilitating effects of action observation on the motor system. However, they do support the notion of a sensory-motor loop according to which sensory stimulus properties (for example, the image of a left hand or a right hand) directly affect motor cortex activity, even when no motor output is required. The pattern of this effect is congruent with the pattern of motor representation in each hemisphere.

  11. Motor facilitation during observation of implied motion: Evidence for a role of the left dorsolateral prefrontal cortex.

    PubMed

    Mineo, Ludovico; Fetterman, Alexander; Concerto, Carmen; Warren, Michael; Infortuna, Carmenrita; Freedberg, David; Chusid, Eileen; Aguglia, Eugenio; Battaglia, Fortunato

    2018-06-01

    The phenomenon of motor resonance (the increase in motor cortex excitability during observation of actions) has been previously described. Transcranial magnetic stimulation (TMS) studies have demonstrated a similar effect during perception of implied motion (IM). The left dorsolateral prefrontal cortex (DLPFC) seems to be activated during action observation. Furthermore, the role of this brain area in motor resonance to IM is yet to be investigated. Fourteen healthy volunteers were enrolled into the study. We used transcranial direct current stimulation (tDCS) to stimulate DLPFC aiming to investigate whether stimulation with different polarities would affect the amplitude of motor evoked potential collected during observation of images with and without IM. The results of our experiment indicated that Cathodal tDCS over the left DLPFC prevented motor resonance during observation of IM. On the contrary, anodal and sham tDCS did not significantly modulate motor resonance to IM. The current study expands the understanding of the neural circuits engaged during observation of IM. Our results are consistent with the hypothesis that action understanding requires the interaction of large networks and that the left DLPFC plays a crucial role in generating motor resonance to IM. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Effect of light on the activity of motor cortex neurons during locomotion

    PubMed Central

    Armer, Madison C.; Nilaweera, Wijitha U.; Rivers, Trevor J.; Dasgupta, Namrata M.; Beloozerova, Irina N.

    2013-01-01

    The motor cortex plays a critical role in accurate visually guided movements such as reaching and target stepping. However, the manner in which vision influences the movement-related activity of neurons in the motor cortex is not well understood. In this study we have investigated how the locomotion-related activity of neurons in the motor cortex is modified when subjects switch between walking in the darkness and in light. Three adult cats were trained to walk through corridors of an experimental chamber for a food reward. On randomly selected trials, lights were extinguished for approximately four seconds when the cat was in a straight portion of the chamber's corridor. Discharges of 146 neurons from layer V of the motor cortex, including 51 pyramidal tract cells (PTNs), were recorded and compared between light and dark conditions. It was found that while cats’ movements during locomotion in light and darkness were similar (as judged from the analysis of three-dimensional limb kinematics and the activity of limb muscles), the firing behavior of 49% (71/146) of neurons was different between the two walking conditions. This included differences in the mean discharge rate (19%, 28/146 of neurons), depth of stride-related frequency modulation (24%, 32/131), duration of the period of elevated firing ([PEF], 19%, 25/131), and number of PEFs among stride-related neurons (26%, 34/131). 20% of responding neurons exhibited more than one type of change. We conclude that visual input plays a very significant role in determining neuronal activity in the motor cortex during locomotion by altering one, or occasionally multiple, parameters of locomotion-related discharges of its neurons. PMID:23680161

  13. Effect of light on the activity of motor cortex neurons during locomotion.

    PubMed

    Armer, Madison C; Nilaweera, Wijitha U; Rivers, Trevor J; Dasgupta, Namrata M; Beloozerova, Irina N

    2013-08-01

    The motor cortex plays a critical role in accurate visually guided movements such as reaching and target stepping. However, the manner in which vision influences the movement-related activity of neurons in the motor cortex is not well understood. In this study we have investigated how the locomotion-related activity of neurons in the motor cortex is modified when subjects switch between walking in the darkness and in light. Three adult cats were trained to walk through corridors of an experimental chamber for a food reward. On randomly selected trials, lights were extinguished for approximately 4s when the cat was in a straight portion of the chamber's corridor. Discharges of 146 neurons from layer V of the motor cortex, including 51 pyramidal tract cells (PTNs), were recorded and compared between light and dark conditions. It was found that while cats' movements during locomotion in light and darkness were similar (as judged from the analysis of three-dimensional limb kinematics and the activity of limb muscles), the firing behavior of 49% (71/146) of neurons was different between the two walking conditions. This included differences in the mean discharge rate (19%, 28/146 of neurons), depth of stride-related frequency modulation (24%, 32/131), duration of the period of elevated firing ([PEF], 19%, 25/131), and number of PEFs among stride-related neurons (26%, 34/131). 20% of responding neurons exhibited more than one type of change. We conclude that visual input plays a very significant role in determining neuronal activity in the motor cortex during locomotion by altering one, or occasionally multiple, parameters of locomotion-related discharges of its neurons. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

  14. Opposing effects of dopamine antagonism in a motor sequence task—tiapride increases cortical excitability and impairs motor learning

    PubMed Central

    Lissek, Silke; Vallana, Guido S.; Schlaffke, Lara; Lenz, Melanie; Dinse, Hubert R.; Tegenthoff, Martin

    2014-01-01

    The dopaminergic system is involved in learning and participates in the modulation of cortical excitability (CE). CE has been suggested as a marker of learning and use-dependent plasticity. However, results from separate studies on either motor CE or motor learning challenge this notion, suggesting opposing effects of dopaminergic modulation upon these parameters: while agonists decrease and antagonists increase CE, motor learning is enhanced by agonists and disturbed by antagonists. To examine whether this discrepancy persists when complex motor learning and motor CE are measured in the same experimental setup, we investigated the effects of dopaminergic (DA) antagonism upon both parameters and upon task-associated brain activation. Our results demonstrate that DA-antagonism has opposing effects upon motor CE and motor sequence learning. Tiapride did not alter baseline CE, but increased CE post training of a complex motor sequence while simultaneously impairing motor learning. Moreover, tiapride reduced activation in several brain regions associated with motor sequence performance, i.e., dorsolateral PFC (dlPFC), supplementary motor area (SMA), Broca's area, cingulate and caudate body. Blood-oxygenation-level-dependent (BOLD) intensity in anterior cingulate and caudate body, but not CE, correlated with performance across groups. In summary, our results do not support a concept of CE as a general marker of motor learning, since they demonstrate that a straightforward relation of increased CE and higher learning success does not apply to all instances of motor learning. At least for complex motor tasks that recruit a network of brain regions outside motor cortex, CE in primary motor cortex is probably no central determinant for learning success. PMID:24994972

  15. Seeing fearful body language rapidly freezes the observer's motor cortex.

    PubMed

    Borgomaneri, Sara; Vitale, Francesca; Gazzola, Valeria; Avenanti, Alessio

    2015-04-01

    Fearful body language is a salient signal alerting the observer to the presence of a potential threat in the surrounding environment. Although detecting potential threats may trigger an immediate reduction of motor output in animals (i.e., freezing behavior), it is unclear at what point in time similar reductions occur in the human motor cortex and whether they originate from excitatory or inhibitory processes. Using single-pulse and paired-pulse transcranial magnetic stimulation (TMS), here we tested the hypothesis that the observer's motor cortex implements extremely fast suppression of motor readiness when seeing emotional bodies - and fearful body expressions in particular. Participants observed pictures of body postures and categorized them as happy, fearful or neutral while receiving TMS over the right or left motor cortex at 100-125 msec after picture onset. In three different sessions, we assessed corticospinal excitability, short intracortical inhibition (SICI) and intracortical facilitation (ICF). Independently of the stimulated hemisphere and the time of the stimulation, watching fearful bodies suppressed ICF relative to happy and neutral body expressions. Moreover, happy expressions reduced ICF relative to neutral actions. No changes in corticospinal excitability or SICI were found during the task. These findings show extremely rapid bilateral modulation of the motor cortices when seeing emotional bodies, with stronger suppression of motor readiness when seeing fearful bodies. Our results provide neurophysiological support for the evolutionary notions that emotion perception is inherently linked to action systems and that fear-related cues induce an urgent mobilization of motor reactions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Reliability of directional information in unsorted spikes and local field potentials recorded in human motor cortex

    PubMed Central

    Perge, János A.; Zhang, Shaomin; Malik, Wasim Q.; Homer, Mark L.; Cash, Sydney; Friehs, Gerhard; Eskandar, Emad N.; Donoghue, John P.; Hochberg, Leigh R.

    2014-01-01

    Objective Action potentials and local field potentials (LFPs) recorded in primary motor cortex contain information about the direction of movement. LFPs are assumed to be more robust to signal instabilities than action potentials, which makes LFPs along with action potentials a promising signal source for brain-computer interface applications. Still, relatively little research has directly compared the utility of LFPs to action potentials in decoding movement direction in human motor cortex. Approach We conducted intracortical multielectrode recordings in motor cortex of two persons (T2 and [S3]) as they performed a motor imagery task. We then compared the offline decoding performance of LFPs and spiking extracted from the same data recorded across a one-year period in each participant. Main results We obtained offline prediction accuracy of movement direction and endpoint velocity in multiple LFP bands, with the best performance in the highest (200–400Hz) LFP frequency band, presumably also containing low-pass filtered action potentials. Cross-frequency correlations of preferred directions and directional modulation index showed high similarity of directional information between action potential firing rates (spiking) and high frequency LFPs (70–400Hz), and increasing disparity with lower frequency bands (0–7, 10–40 and 50–65Hz). Spikes predicted the direction of intended movement more accurately than any individual LFP band, however combined decoding of all LFPs was statistically indistinguishable from spike based performance. As the quality of spiking signals (i.e. signal amplitude) and the number of significantly modulated spiking units decreased, the offline decoding performance decreased 3.6[5.65]%/month (for T2 and [S3] respectively). The decrease in the number of significantly modulated LFP signals and their decoding accuracy followed a similar trend (2.4[2.85]%/month, ANCOVA, p=0.27[0.03]). Significance Field potentials provided comparable offline decoding performance to unsorted spikes. Thus, LFPs may provide useful external device control using current human intracortical recording technology. (Clinical trial registration number: NCT00912041) PMID:24921388

  17. The effect of the anodal transcranial direct current stimulation over the cerebellum on the motor cortex excitability.

    PubMed

    Ates, Mehlika Panpalli; Alaydin, Halil Can; Cengiz, Bulent

    2018-04-25

    This study was designed to investigate whether the cerebellum has an inhibitory effect on motor cortical excitability. Sixteen healthy adults (age range, 25-50 years, five female) participated in the study. Anodal cerebellar transcranial direct current stimulation (a-cTDCS) was used to modulate cerebellar excitability. A-cTDCS was given for 20 min at 1 mA intensity. The automatic threshold tracking method was used to investigate cortical excitability. Resting motor threshold (RMT), short interval intracortical inhibition (SICI), short interval intracortical facilitation (SICF), intracortical facilitation (ICF), and the input output curve (I-O curve) were motor cortical excitability parameters. a-cTDCS caused a reduction in overall SICI and the reduced SICF for interstimulus intervals (ISIs) to 2.4-4.4 ms. a-cTDCS has no effect on ICF, RMT, and the I-O curve. There were no significant changes in any of these cortical excitability parameters after sham cTDCS. Results of the study indicate that a-cTDCS has a dual (both inhibitory and excitatory) effect on motor cortical excitability, rather than a simple inhibitory effect. The cerebellum modulates both the inhibitory and facilitatory activities of motor cortex (M1) and suggest that cerebello-cerebral motor connectivity is more complex than solely inhibitory or facilitatory connections. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Antinociception induced by epidural motor cortex stimulation in naive conscious rats is mediated by the opioid system.

    PubMed

    Fonoff, Erich Talamoni; Dale, Camila Squarzoni; Pagano, Rosana Lima; Paccola, Carina Cicconi; Ballester, Gerson; Teixeira, Manoel Jacobsen; Giorgi, Renata

    2009-01-03

    Epidural motor cortex stimulation (MCS) has been used for treating patients with neuropathic pain resistant to other therapeutic approaches. Experimental evidence suggests that the motor cortex is also involved in the modulation of normal nociceptive response, but the underlying mechanisms of pain control have not been clarified yet. The aim of this study was to investigate the effects of epidural electrical MCS on the nociceptive threshold of naive rats. Electrodes were placed on epidural motor cortex, over the hind paw area, according to the functional mapping accomplished in this study. Nociceptive threshold and general activity were evaluated under 15-min electrical stimulating sessions. When rats were evaluated by the paw pressure test, MCS induced selective antinociception in the paw contralateral to the stimulated cortex, but no changes were noticed in the ipsilateral paw. When the nociceptive test was repeated 15 min after cessation of electrical stimulation, the nociceptive threshold returned to basal levels. On the other hand, no changes in the nociceptive threshold were observed in rats evaluated by the tail-flick test. Additionally, no behavioral or motor impairment were noticed in the course of stimulation session at the open-field test. Stimulation of posterior parietal or somatosensory cortices did not elicit any changes in the general activity or nociceptive response. Opioid receptors blockade by naloxone abolished the increase in nociceptive threshold induced by MCS. Data shown herein demonstrate that epidural electrical MCS elicits a substantial and selective antinociceptive effect, which is mediated by opioids.

  19. Contributions of Subsurface Cortical Modulations to Discrimination of Executed and Imagined Grasp Forces through Stereoelectroencephalography

    PubMed Central

    Murphy, Brian A.; Miller, Jonathan P.; Gunalan, Kabilar; Ajiboye, A. Bolu

    2016-01-01

    Stereoelectroencephalographic (SEEG) depth electrodes have the potential to record neural activity from deep brain structures not easily reached with other intracranial recording technologies. SEEG electrodes were placed through deep cortical structures including central sulcus and insular cortex. In order to observe changes in frequency band modulation, participants performed force matching trials at three distinct force levels using two different grasp configurations: a power grasp and a lateral pinch. Signals from these deeper structures were found to contain information useful for distinguishing force from rest trials as well as different force levels in some participants. High frequency components along with alpha and beta bands recorded from electrodes located near the primary motor cortex wall of central sulcus and electrodes passing through sensory cortex were found to be the most useful for classification of force versus rest although one participant did have significant modulation in the insular cortex. This study electrophysiologically corroborates with previous imaging studies that show force-related modulation occurs inside of central sulcus and insular cortex. The results of this work suggest that depth electrodes could be useful tools for investigating the functions of deeper brain structures as well as showing that central sulcus and insular cortex may contain neural signals that could be used for control of a grasp force BMI. PMID:26963246

  20. The evolution of neocortex in primates

    PubMed Central

    Kaas, Jon H.

    2013-01-01

    We can learn about the evolution of neocortex in primates through comparative studies of cortical organization in primates and those mammals that are the closest living relatives of primates, in conjunction with brain features revealed by the skull endocasts of fossil archaic primates. Such studies suggest that early primates had acquired a number of features of neocortex that now distinguish modern primates. Most notably, early primates had an array of new visual areas, and those visual areas widely shared with other mammals had been modified. Posterior parietal cortex was greatly expanded with sensorimotor modules for reaching, grasping, and personal defense. Motor cortex had become more specialized for hand use, and the functions of primary motor cortex were enhanced by the addition and development of premotor and cingulate motor areas. Cortical architecture became more varied, and cortical neuron populations became denser overall than in nonprimate ancestors. Primary visual cortex had the densest population of neurons, and this became more pronounced in the anthropoid radiation. Within the primate clade, considerable variability in cortical size, numbers of areas, and architecture evolved. PMID:22230624

  1. The evolution of neocortex in primates.

    PubMed

    Kaas, Jon H

    2012-01-01

    We can learn about the evolution of neocortex in primates through comparative studies of cortical organization in primates and those mammals that are the closest living relatives of primates, in conjunction with brain features revealed by the skull endocasts of fossil archaic primates. Such studies suggest that early primates had acquired a number of features of neocortex that now distinguish modern primates. Most notably, early primates had an array of new visual areas, and those visual areas widely shared with other mammals had been modified. Posterior parietal cortex was greatly expanded with sensorimotor modules for reaching, grasping, and personal defense. Motor cortex had become more specialized for hand use, and the functions of primary motor cortex were enhanced by the addition and development of premotor and cingulate motor areas. Cortical architecture became more varied, and cortical neuron populations became denser overall than in nonprimate ancestors. Primary visual cortex had the densest population of neurons, and this became more pronounced in the anthropoid radiation. Within the primate clade, considerable variability in cortical size, numbers of areas, and architecture evolved. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Brain-robot interface driven plasticity: Distributed modulation of corticospinal excitability.

    PubMed

    Kraus, Dominic; Naros, Georgios; Bauer, Robert; Leão, Maria Teresa; Ziemann, Ulf; Gharabaghi, Alireza

    2016-01-15

    Brain-robot interfaces (BRI) are studied as novel interventions to facilitate functional restoration in patients with severe and persistent motor deficits following stroke. They bridge the impaired connection in the sensorimotor loop by providing brain-state dependent proprioceptive feedback with orthotic devices attached to the hand or arm of the patients. The underlying neurophysiology of this BRI neuromodulation is still largely unknown. We investigated changes of corticospinal excitability with transcranial magnetic stimulation in thirteen right-handed healthy subjects who performed 40min of kinesthetic motor imagery receiving proprioceptive feedback with a robotic orthosis attached to the left hand contingent to event-related desynchronization of the right sensorimotor cortex in the β-band (16-22Hz). Neural correlates of this BRI intervention were probed by acquiring the stimulus-response curve (SRC) of both motor evoked potential (MEP) peak-to-peak amplitudes and areas under the curve. In addition, a motor mapping was obtained. The specificity of the effects was studied by comparing two neighboring hand muscles, one BRI-trained and one control muscle. Robust changes of MEP amplitude but not MEP area occurred following the BRI intervention, but only in the BRI-trained muscle. The steep part of the SRC showed an MEP increase, while the plateau of the SRC showed an MEP decrease. MEP mapping revealed a distributed pattern with a decrease of excitability in the hand area of the primary motor cortex, which controlled the BRI, but an increase of excitability in the surrounding somatosensory and premotor cortex. In conclusion, the BRI intervention induced a complex pattern of modulated corticospinal excitability, which may boost subsequent motor learning during physiotherapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. A nutrigenomics approach for the study of anti-aging interventions: olive oil phenols and the modulation of gene and microRNA expression profiles in mouse brain.

    PubMed

    Luceri, Cristina; Bigagli, Elisabetta; Pitozzi, Vanessa; Giovannelli, Lisa

    2017-03-01

    Middle-aged C57Bl/6J mice fed for 6 months with extra-virgin olive oil rich in phenols (H-EVOO, phenol dose/day: 6 mg/kg) showed cognitive and motor improvement compared to controls fed the same olive oil deprived of phenolics (L-EVOO). The aim of the present study was to evaluate whether these behavioral modifications were associated with changes in gene and miRNA expression in the brain. Two brain areas involved in cognitive and motor processes were chosen: cortex and cerebellum. Gene and miRNA profiling were analyzed by microarray and correlated with performance in behavioral tests. After 6 months, most of the gene expression changes were restricted to the cerebral cortex. The genes modulated by aging were mainly down-regulated, and the treatment with H-EVOO was associated with a significant up-regulation of genes compared to L-EVOO. Among those, we found genes previously associated with synaptic plasticity and with motor and cognitive behavior, such as Notch1, BMPs, NGFR, GLP1R and CRTC3. The agrin pathway was also significantly modulated. miRNAs were mostly up-regulated in old L-EVOO animals compared to young. However, H-EVOO-fed mice cortex displayed miRNA expression profiles similar to those observed in young mice. Sixty-three miRNAs, out of 1203 analyzed, were significantly down-regulated compared to the L-EVOO group; among them, we found miRNAs whose predicted target genes were up-regulated by the treatment, such as mir-484, mir-27, mir-137, mir-30, mir-34 and mir-124. We are among the first to report that a dietary intervention starting from middle age with food rich in phenols can modulate at the central level the expression of genes and miRNAs involved in neuronal function and synaptic plasticity, along with cognitive, motor and emotional behavior.

  4. TMS of supplementary motor area (SMA) facilitates mental rotation performance: Evidence for sequence processing in SMA.

    PubMed

    Cona, G; Marino, G; Semenza, C

    2017-02-01

    In the present study we applied online transcranial magnetic stimulation (TMS) bursts at 10Hz to the supplementary motor area (SMA) and primary motor cortex to test whether these regions are causally involved in mental rotation. Furthermore, in order to investigate what is the specific role played by SMA and primary motor cortex, two mental rotation tasks were used, which included pictures of hands and abstract objects, respectively. While primary motor cortex stimulation did not affect mental rotation performance, SMA stimulation improved the performance in the task with object stimuli, and only for the pairs of stimuli that had higher angular disparity between each other (i.e., 100° and 150°). The finding that the effect of SMA stimulation was modulated by the amount of spatial orientation information indicates that SMA is causally involved in the very act of mental rotation. More specifically, we propose that SMA mediates domain-general sequence processes, likely required to accumulate and integrate information that are, in this context, spatial. The possible physiological mechanisms underlying the facilitation of performance due to SMA stimulation are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Enhancing Motor Network Activity Using Real-Time Functional MRI Neurofeedback of Left Premotor Cortex

    PubMed Central

    Marins, Theo F.; Rodrigues, Erika C.; Engel, Annerose; Hoefle, Sebastian; Basílio, Rodrigo; Lent, Roberto; Moll, Jorge; Tovar-Moll, Fernanda

    2015-01-01

    Neurofeedback by functional magnetic resonance imaging (fMRI) is a technique of potential therapeutic relevance that allows individuals to be aware of their own neurophysiological responses and to voluntarily modulate the activity of specific brain regions, such as the premotor cortex (PMC), important for motor recovery after brain injury. We investigated (i) whether healthy human volunteers are able to up-regulate the activity of the left PMC during a right hand finger tapping motor imagery (MI) task while receiving continuous fMRI-neurofeedback, and (ii) whether successful modulation of brain activity influenced non-targeted motor control regions. During the MI task, participants of the neurofeedback group (NFB) received ongoing visual feedback representing the level of fMRI responses within their left PMC. Control (CTL) group participants were shown similar visual stimuli, but these were non-contingent on brain activity. Both groups showed equivalent levels of behavioral ratings on arousal and MI, before and during the fMRI protocol. In the NFB, but not in CLT group, brain activation during the last run compared to the first run revealed increased activation in the left PMC. In addition, the NFB group showed increased activation in motor control regions extending beyond the left PMC target area, including the supplementary motor area, basal ganglia and cerebellum. Moreover, in the last run, the NFB group showed stronger activation in the left PMC/inferior frontal gyrus when compared to the CTL group. Our results indicate that modulation of PMC and associated motor control areas can be achieved during a single neurofeedback-fMRI session. These results contribute to a better understanding of the underlying mechanisms of MI-based neurofeedback training, with direct implications for rehabilitation strategies in severe brain disorders, such as stroke. PMID:26733832

  6. Figure-ground activity in primary visual cortex (V1) of the monkey matches the speed of behavioral response.

    PubMed

    Supèr, Hans; Spekreijse, Henk; Lamme, Victor A F

    2003-06-26

    To look at an object its position in the visual scene has to be localized and subsequently appropriate oculo-motor behavior needs to be initiated. This kind of behavior is largely controlled by the cortical executive system, such as the frontal eye field. In this report, we analyzed neural activity in the visual cortex in relation to oculo-motor behavior. We show that in a figure-ground detection task, the strength of late modulated activity in the primary visual cortex correlates with the saccade latency. We propose that this may indicate that the variability of reaction times in the detection of a visual stimulus is reflected in low-level visual areas as well as in high-level areas.

  7. Visually cued motor synchronization: modulation of fMRI activation patterns by baseline condition.

    PubMed

    Cerasa, Antonio; Hagberg, Gisela E; Bianciardi, Marta; Sabatini, Umberto

    2005-01-03

    A well-known issue in functional neuroimaging studies, regarding motor synchronization, is to design suitable control tasks able to discriminate between the brain structures involved in primary time-keeper functions and those related to other processes such as attentional effort. The aim of this work was to investigate how the predictability of stimulus onsets in the baseline condition modulates the activity in brain structures related to processes involved in time-keeper functions during the performance of a visually cued motor synchronization task (VM). The rational behind this choice derives from the notion that using different stimulus predictability can vary the subject's attention and the consequently neural activity. For this purpose, baseline levels of BOLD activity were obtained from 12 subjects during a conventional-baseline condition: maintained fixation of the visual rhythmic stimuli presented in the VM task, and a random-baseline condition: maintained fixation of visual stimuli occurring randomly. fMRI analysis demonstrated that while brain areas with a documented role in basic time processing are detected independent of the baseline condition (right cerebellum, bilateral putamen, left thalamus, left superior temporal gyrus, left sensorimotor cortex, left dorsal premotor cortex and supplementary motor area), the ventral premotor cortex, caudate nucleus, insula and inferior frontal gyrus exhibited a baseline-dependent activation. We conclude that maintained fixation of unpredictable visual stimuli can be employed in order to reduce or eliminate neural activity related to attentional components present in the synchronization task.

  8. Differential Contribution of Bilateral Supplementary Motor Area to the Effective Connectivity Networks Induced by Task Conditions Using Dynamic Causal Modeling

    PubMed Central

    Tao, Zhongping; Zhang, Mu

    2014-01-01

    Abstract Functional imaging studies have indicated hemispheric asymmetry of activation in bilateral supplementary motor area (SMA) during unimanual motor tasks. However, the hemispherically special roles of bilateral SMAs on primary motor cortex (M1) in the effective connectivity networks (ECN) during lateralized tasks remain unclear. Aiming to study the differential contribution of bilateral SMAs during the motor execution and motor imagery tasks, and the hemispherically asymmetric patterns of ECN among regions involved, the present study used dynamic causal modeling to analyze the functional magnetic resonance imaging data of the unimanual motor execution/imagery tasks in 12 right-handed subjects. Our results demonstrated that distributions of network parameters underlying motor execution and motor imagery were significantly different. The variation was mainly induced by task condition modulations of intrinsic coupling. Particularly, regardless of the performing hand, the task input modulations of intrinsic coupling from the contralateral SMA to contralateral M1 were positive during motor execution, while varied to be negative during motor imagery. The results suggested that the inhibitive modulation suppressed the overt movement during motor imagery. In addition, the left SMA also helped accomplishing left hand tasks through task input modulation of left SMA→right SMA connection, implying that hemispheric recruitment occurred when performing nondominant hand tasks. The results specified differential and altered contributions of bilateral SMAs to the ECN during unimanual motor execution and motor imagery, and highlighted the contributions induced by the task input of motor execution/imagery. PMID:24606178

  9. Neuroplasticity Changes on Human Motor Cortex Induced by Acupuncture Therapy: A Preliminary Study.

    PubMed

    Yang, Yi; Eisner, Ines; Chen, Siqi; Wang, Shaosong; Zhang, Fan; Wang, Linpeng

    2017-01-01

    While neuroplasticity changes measured by transcranial magnetic stimulation have been proved to be highly correlated to motor recovery and have been tested in various forms of interventions, it has not been applied to investigate the neurophysiologic mechanism of acupuncture therapy. The aim of this study is to investigate neuroplasticity changes induced by a single session of acupuncture therapy in healthy adults, regarding the excitability change on bilateral primary motor cortex and interhemispheric inhibition. Ten subjects took a 30-minute acupuncture therapy and the same length relaxing phase in separate days. Transcranial magnetic stimulation measures, including resting motor threshold, amplitudes of motor-evoked potential, and interhemispheric inhibition, were assessed before and 10 minutes after intervention. Acupuncture treatment showed significant changes on potential amplitude from both ipsilateral and contralateral hemispheres to acupuncture compared to baseline. Also, interhemispheric inhibition from the contralateral motor cortex to the opposite showed a significant decline. The results indicated that corticomotoneuronal excitability and interhemispheric competition could be modulated by acupuncture therapy on healthy subjects. The following question about whether these changes will be observed in the same way on stroke patients and whether they correlate with the therapeutic effect on movement need to be answered by following studies. This trial is registered with ISRCTN13074245.

  10. Neuroplasticity Changes on Human Motor Cortex Induced by Acupuncture Therapy: A Preliminary Study

    PubMed Central

    Eisner, Ines; Chen, Siqi; Wang, Shaosong; Zhang, Fan

    2017-01-01

    While neuroplasticity changes measured by transcranial magnetic stimulation have been proved to be highly correlated to motor recovery and have been tested in various forms of interventions, it has not been applied to investigate the neurophysiologic mechanism of acupuncture therapy. The aim of this study is to investigate neuroplasticity changes induced by a single session of acupuncture therapy in healthy adults, regarding the excitability change on bilateral primary motor cortex and interhemispheric inhibition. Ten subjects took a 30-minute acupuncture therapy and the same length relaxing phase in separate days. Transcranial magnetic stimulation measures, including resting motor threshold, amplitudes of motor-evoked potential, and interhemispheric inhibition, were assessed before and 10 minutes after intervention. Acupuncture treatment showed significant changes on potential amplitude from both ipsilateral and contralateral hemispheres to acupuncture compared to baseline. Also, interhemispheric inhibition from the contralateral motor cortex to the opposite showed a significant decline. The results indicated that corticomotoneuronal excitability and interhemispheric competition could be modulated by acupuncture therapy on healthy subjects. The following question about whether these changes will be observed in the same way on stroke patients and whether they correlate with the therapeutic effect on movement need to be answered by following studies. This trial is registered with ISRCTN13074245. PMID:28293438

  11. The effects of combined repetitive transcranial magnetic stimulation and transcranial direct current stimulation on motor function in patients with stroke.

    PubMed

    Kwon, Tae Gun; Park, Eunhee; Kang, Chung; Chang, Won Hyuk; Kim, Yun-Hee

    2016-11-22

    Both transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), when provided to stroke patients in combination with motor training, enhance therapeutic efficacy and motor function. However, the majority of previous studies have only examined a single treatment modality. The authors investigated the modulating influence of combination dual-mode brain stimulation upon bihemispheric stimulation with motor training in stroke patients. Twenty stroke patients with hemiparesis underwent five randomly arranged sessions of diverse combinations of rTMS and tDCS. We applied cathodal or anodal tDCS over the contralesional primary motor cortex (cM1) and 10 Hz rTMS over the ipsilesional primary motor cortex (iM1) in a simultaneous or preconditioning method including sham stimulation. Immediately after dual-mode stimulation, sequential hand motor training was performed for 5 minutes. The total pulses of rTMS and the duration of tDCS and motor training were the same for all sessions. Cortical excitability and sequential motor performance were evaluated before and after each session. Motor function and corticomotor excitability following simultaneous stimulation via cathodal tDCS over the cM1 combined with 10 Hz rTMS over the iM1 were significantly increased after the intervention, with significantly greater motor improvement than seen with other treatment conditions (P < 0.05). For the combination of bihemispheric rTMS and tDCS, simultaneous stimulation of cathodal tDCS and 10 Hz rTMS results in better motor performance in stroke patients than other combination methods. This result seemed to be related to effective modulation of interhemispheric imbalance of cortical excitability by dual-mode stimulation.

  12. Age-related Differences in Pre- and Post-synaptic Motor Cortex Inhibition are Task Dependent.

    PubMed

    Opie, George M; Ridding, Michael C; Semmler, John G

    2015-01-01

    Previous research has shown age-related differences in short- (SICI) and long-interval intracortical inhibition (LICI) in both resting and active hand muscles, suggesting that healthy ageing influences post-synaptic motor cortex inhibition. However, it is not known how the ageing process effects the pre-synaptic interaction of SICI by LICI, and how these pre- and post-synaptic intracortical inhibitory circuits are modulated by the performance of different motor tasks in older adults. To examine age-related differences in pre- and post-synaptic motor cortex inhibition at rest, and during index finger abduction and precision grip. In 13 young (22.3 ± 3.8 years) and 15 old (73.7 ± 4.0 years) adults, paired-pulse transcranial magnetic stimulation (TMS) was used to measure SICI (2 ms inter-stimulus interval; ISI) and LICI (100 and 150 ms ISI), whereas triple-pulse TMS was used to investigate SICI when primed by LICI. We found no age-related difference in SICI at rest or during index finger abduction, but significantly greater SICI in older subjects during precision grip. Older adults showed reduced LICI in resting muscle (at an ISI of 150 ms), with no age-related differences in LICI during either task. When SICI was primed by LICI, disinhibition of motor cortex was reduced in older adults at rest (100 ms ISI) and during index finger abduction (150 ms ISI), but not during precision grip. Our results support age-related differences in pre- and post-synaptic motor cortex inhibition, which may contribute to impaired hand function during task performance in older adults. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Optogenetic fMRI and electrophysiological identification of region-specific connectivity between the cerebellar cortex and forebrain.

    PubMed

    Choe, Katrina Y; Sanchez, Carlos F; Harris, Neil G; Otis, Thomas S; Mathews, Paul J

    2018-06-01

    Complex animal behavior is produced by dynamic interactions between discrete regions of the brain. As such, defining functional connections between brain regions is critical in gaining a full understanding of how the brain generates behavior. Evidence suggests that discrete regions of the cerebellar cortex functionally project to the forebrain, mediating long-range communication potentially important in motor and non-motor behaviors. However, the connectivity map remains largely incomplete owing to the challenge of driving both reliable and selective output from the cerebellar cortex, as well as the need for methods to detect region specific activation across the entire forebrain. Here we utilize a paired optogenetic and fMRI (ofMRI) approach to elucidate the downstream forebrain regions modulated by activating a region of the cerebellum that induces stereotypical, ipsilateral forelimb movements. We demonstrate with ofMRI, that activating this forelimb motor region of the cerebellar cortex results in functional activation of a variety of forebrain and midbrain areas of the brain, including the hippocampus and primary motor, retrosplenial and anterior cingulate cortices. We further validate these findings using optogenetic stimulation paired with multi-electrode array recordings and post-hoc staining for molecular markers of activated neurons (i.e. c-Fos). Together, these findings demonstrate that a single discrete region of the cerebellar cortex is capable of influencing motor output and the activity of a number of downstream forebrain as well as midbrain regions thought to be involved in different aspects of behavior. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Striatal dysfunction increases basal ganglia output during motor cortex activation in parkinsonian rats.

    PubMed

    Belluscio, Mariano A; Riquelme, Luis A; Murer, M Gustavo

    2007-05-01

    During movement, inhibitory neurons in the basal ganglia output nuclei show complex modulations of firing, which are presumptively driven by corticostriatal and corticosubthalamic input. Reductions in discharge should facilitate movement by disinhibiting thalamic and brain stem nuclei while increases would do the opposite. A proposal that nigrostriatal dopamine pathway degeneration disrupts trans-striatal pathways' balance resulting in sustained overactivity of basal ganglia output nuclei neurons and Parkinson's disease clinical signs is not fully supported by experimental evidence, which instead shows abnormal synchronous oscillatory activity in animal models and patients. Yet, the possibility that variation in motor cortex activity drives transient overactivity in output nuclei neurons in parkinsonism has not been explored. In Sprague-Dawley rats with 6-hydroxydopamine (6-OHDA)-induced nigrostriatal lesions, approximately 50% substantia nigra pars reticulata (SNpr) units show abnormal cortically driven slow oscillations of discharge. Moreover, these units selectively show abnormal responses to motor cortex stimulation consisting in augmented excitations of an odd latency, which overlapped that of inhibitory responses presumptively mediated by the trans-striatal direct pathway in control rats. Delivering D1 or D2 dopamine agonists into the striatum of parkinsonian rats by reverse microdialysis reduced these abnormal excitations but had no effect on pathological oscillations. The present study establishes that dopamine-deficiency related changes of striatal function contribute to producing abnormally augmented excitatory responses to motor cortex stimulation in the SNpr. If a similar transient overactivity of basal ganglia output were driven by motor cortex input during movement, it could contribute to impeding movement initiation or execution in Parkinson's disease.

  15. The cerebellum for jocks and nerds alike.

    PubMed

    Popa, Laurentiu S; Hewitt, Angela L; Ebner, Timothy J

    2014-01-01

    Historically the cerebellum has been implicated in the control of movement. However, the cerebellum's role in non-motor functions, including cognitive and emotional processes, has also received increasing attention. Starting from the premise that the uniform architecture of the cerebellum underlies a common mode of information processing, this review examines recent electrophysiological findings on the motor signals encoded in the cerebellar cortex and then relates these signals to observations in the non-motor domain. Simple spike firing of individual Purkinje cells encodes performance errors, both predicting upcoming errors as well as providing feedback about those errors. Further, this dual temporal encoding of prediction and feedback involves a change in the sign of the simple spike modulation. Therefore, Purkinje cell simple spike firing both predicts and responds to feedback about a specific parameter, consistent with computing sensory prediction errors in which the predictions about the consequences of a motor command are compared with the feedback resulting from the motor command execution. These new findings are in contrast with the historical view that complex spikes encode errors. Evaluation of the kinematic coding in the simple spike discharge shows the same dual temporal encoding, suggesting this is a common mode of signal processing in the cerebellar cortex. Decoding analyses show the considerable accuracy of the predictions provided by Purkinje cells across a range of times. Further, individual Purkinje cells encode linearly and independently a multitude of signals, both kinematic and performance errors. Therefore, the cerebellar cortex's capacity to make associations across different sensory, motor and non-motor signals is large. The results from studying how Purkinje cells encode movement signals suggest that the cerebellar cortex circuitry can support associative learning, sequencing, working memory, and forward internal models in non-motor domains.

  16. Effect of neuromuscular electrical stimulation on motor cortex excitability upon release of tonic muscle contraction.

    PubMed

    Sugawara, Kenichi; Tanabe, Shigeo; Suzuki, Tomotaka; Higashi, Toshio

    The aim of the present study was to investigate the neurophysiological triggers underlying muscle relaxation from the contracted state, and to examine the mechanisms involved in this process and their subsequent modification by neuromuscular electrical stimulation (NMES). Single-pulse transcranial magnetic stimulation (TMS) was used to produce motor-evoked potentials (MEPs) and short-interval intracortical inhibition (SICI) in 23 healthy participants, wherein motor cortex excitability was examined at the onset of voluntary muscle relaxation following a period of voluntary tonic muscle contraction. In addition, the effects of afferent input on motor cortex excitability, as produced by NMES during muscle contraction, were examined. In particular, two NMES intensities were used for analysis: 1.2 times the sensory threshold and 1.2 times the motor threshold (MT). Participants were directed to execute constant wrist extensions and to release muscle contraction in response to an auditory "GO" signal. MEPs were recorded from the flexor carpi radialis (FCR) and extensor carpi radialis (ECR) muscles, and TMS was applied at three different time intervals (30, 60, and 90 ms) after the "GO" signal. Motor cortex excitability was greater during voluntary ECR and FCR relaxation using high-intensity NMES, and relaxation time was decreased. Each parameter differed significantly between 30 and 60 ms. Moreover, in both muscles, SICI was larger in the presence than in the absence of NMES. Therefore, the present findings suggest that terminating a muscle contraction triggers transient neurophysiological mechanisms that facilitate the NMES-induced modulation of cortical motor excitability in the period prior to muscle relaxation. High-intensity NMES might facilitate motor cortical excitability as a function of increased inhibitory intracortical activity, and therefore serve as a transient trigger for the relaxation of prime mover muscles in a therapeutic context.

  17. The cerebellum for jocks and nerds alike

    PubMed Central

    Popa, Laurentiu S.; Hewitt, Angela L.; Ebner, Timothy J.

    2014-01-01

    Historically the cerebellum has been implicated in the control of movement. However, the cerebellum's role in non-motor functions, including cognitive and emotional processes, has also received increasing attention. Starting from the premise that the uniform architecture of the cerebellum underlies a common mode of information processing, this review examines recent electrophysiological findings on the motor signals encoded in the cerebellar cortex and then relates these signals to observations in the non-motor domain. Simple spike firing of individual Purkinje cells encodes performance errors, both predicting upcoming errors as well as providing feedback about those errors. Further, this dual temporal encoding of prediction and feedback involves a change in the sign of the simple spike modulation. Therefore, Purkinje cell simple spike firing both predicts and responds to feedback about a specific parameter, consistent with computing sensory prediction errors in which the predictions about the consequences of a motor command are compared with the feedback resulting from the motor command execution. These new findings are in contrast with the historical view that complex spikes encode errors. Evaluation of the kinematic coding in the simple spike discharge shows the same dual temporal encoding, suggesting this is a common mode of signal processing in the cerebellar cortex. Decoding analyses show the considerable accuracy of the predictions provided by Purkinje cells across a range of times. Further, individual Purkinje cells encode linearly and independently a multitude of signals, both kinematic and performance errors. Therefore, the cerebellar cortex's capacity to make associations across different sensory, motor and non-motor signals is large. The results from studying how Purkinje cells encode movement signals suggest that the cerebellar cortex circuitry can support associative learning, sequencing, working memory, and forward internal models in non-motor domains. PMID:24987338

  18. Anodal Transcranial Direct Current Stimulation Reduces Psychophysically Measured Surround Suppression in the Human Visual Cortex

    PubMed Central

    Spiegel, Daniel P.; Hansen, Bruce C.; Byblow, Winston D.; Thompson, Benjamin

    2012-01-01

    Transcranial direct current stimulation (tDCS) is a safe, non-invasive technique for transiently modulating the balance of excitation and inhibition within the human brain. It has been reported that anodal tDCS can reduce both GABA mediated inhibition and GABA concentration within the human motor cortex. As GABA mediated inhibition is thought to be a key modulator of plasticity within the adult brain, these findings have broad implications for the future use of tDCS. It is important, therefore, to establish whether tDCS can exert similar effects within non-motor brain areas. The aim of this study was to assess whether anodal tDCS could reduce inhibitory interactions within the human visual cortex. Psychophysical measures of surround suppression were used as an index of inhibition within V1. Overlay suppression, which is thought to originate within the lateral geniculate nucleus (LGN), was also measured as a control. Anodal stimulation of the occipital poles significantly reduced psychophysical surround suppression, but had no effect on overlay suppression. This effect was specific to anodal stimulation as cathodal stimulation had no effect on either measure. These psychophysical results provide the first evidence for tDCS-induced reductions of intracortical inhibition within the human visual cortex. PMID:22563485

  19. Motor Cortex Excitability and BDNF Levels in Chronic Musculoskeletal Pain According to Structural Pathology

    PubMed Central

    Caumo, Wolnei; Deitos, Alícia; Carvalho, Sandra; Leite, Jorge; Carvalho, Fabiana; Dussán-Sarria, Jairo Alberto; Lopes Tarragó, Maria da Graça; Souza, Andressa; Torres, Iraci Lucena da Silva; Fregni, Felipe

    2016-01-01

    The central sensitization syndrome (CSS) encompasses disorders with overlapping symptoms in a structural pathology spectrum ranging from persistent nociception [e.g., osteoarthritis (OA)] to an absence of tissue injuries such as the one presented in fibromyalgia (FM) and myofascial pain syndrome (MPS). First, we hypothesized that these syndromes present differences in their cortical excitability parameters assessed by transcranial magnetic stimulation (TMS), namely motor evoked potential (MEP), cortical silent period (CSP), short intracortical inhibition (SICI) and short intracortical facilitation (SICF). Second, considering that the presence of tissue injury could be detected by serum neurotrophins, we hypothesized that the spectrum of structural pathology (i.e., from persistent nociception like in OA, to the absence of tissue injury like in FM and MPS), could be detected by differential efficiency of their descending pain inhibitory system, as assessed by the conditioned pain modulation (CPM) paradigm. Third, we explored whether brain-derived neurotrophic factor (BDNF) had an influence on the relationship between motor cortex excitability and structural pathology. This cross-sectional study pooled baseline data from three randomized clinical trials. We included females (n = 114), aged 19–65 years old with disability by chronic pain syndromes (CPS): FM (n = 19), MPS (n = 54), OA (n = 27) and healthy subjects (n = 14). We assessed the serum BDNF, the motor cortex excitability by parameters the TMS measures and the change on numerical pain scale [NPS (0–10)] during CPM-task. The adjusted mean (SD) on the SICI observed in the absence of tissue injury was 56.36% lower than with persistent nociceptive input [0.31(0.18) vs. 0.55 (0.32)], respectively. The BDNF was inversely correlated with the SICI and with the change on NPS (0–10)during CPM-task. These findings suggest greater disinhibition in the motor cortex and the descending pain inhibitory system in FM and MPS than in OA and healthy subjects. Likewise, the inter-hemispheric disinhibition as well as the dysfunction in the descending pain modulatory system is higher in chronic pain without tissue injury compared to a structural lesion. In addition, they suggest that a greater level of serum BDNF may be involved in the processes that mediate the disinhibition of motor cortex excitability, as well as the function of descending inhibitory pain modulation system, independently of the physiopathology mechanism of musculoskeletal pain syndromes. PMID:27471458

  20. Contribution of TMS and rTMS in the Understanding of the Pathophysiology and in the Treatment of Dystonia.

    PubMed

    Lozeron, Pierre; Poujois, Aurélia; Richard, Alexandra; Masmoudi, Sana; Meppiel, Elodie; Woimant, France; Kubis, Nathalie

    2016-01-01

    Dystonias represent a heterogeneous group of movement disorders responsible for sustained muscle contraction, abnormal postures, and muscle twists. It can affect focal or segmental body parts or be generalized. Primary dystonia is the most common form of dystonia but it can also be secondary to metabolic or structural dysfunction, the consequence of a drug's side-effect or of genetic origin. The pathophysiology is still not elucidated. Based on lesion studies, dystonia has been regarded as a pure motor dysfunction of the basal ganglia loop. However, basal ganglia lesions do not consistently produce dystonia and lesions outside basal ganglia can lead to dystonia; mild sensory abnormalities have been reported in the dystonic limb and imaging studies have shown involvement of multiple other brain regions including the cerebellum and the cerebral motor, premotor and sensorimotor cortices. Transcranial magnetic stimulation (TMS) is a non-invasive technique of brain stimulation with a magnetic field applied over the cortex allowing investigation of cortical excitability. Hyperexcitability of contralateral motor cortex has been suggested to be the trigger of focal dystonia. High or low frequency repetitive TMS (rTMS) can induce excitatory or inhibitory lasting effects beyond the time of stimulation and protocols have been developed having either a positive or a negative effect on cortical excitability and associated with prevention of cell death, γ-aminobutyric acid (GABA) interneurons mediated inhibition and brain-derived neurotrophic factor modulation. rTMS studies as a therapeutic strategy of dystonia have been conducted to modulate the cerebral areas involved in the disease. Especially, when applied on the contralateral (pre)-motor cortex or supplementary motor area of brains of small cohorts of dystonic patients, rTMS has shown a beneficial transient clinical effect in association with restrained motor cortex excitability. TMS is currently a valuable tool to improve our understanding of the pathophysiology of dystonia but large controlled studies using sham stimulation are still necessary to delineate the place of rTMS in the therapeutic strategy of dystonia. In this review, we will focus successively on the use of TMS as a tool to better understand pathophysiology, and the use of rTMS as a therapeutic strategy.

  1. Drivers from the deep: the contribution of collicular input to thalamocortical processing.

    PubMed

    Wurtz, Robert H; Sommer, Marc A; Cavanaugh, James

    2005-01-01

    A traditional view of the thalamus is that it is a relay station which receives sensory input and conveys this information to cortex. This sensory input determines most of the properties of first order thalamic neurons, and so is said to drive, rather than modulate, these neurons. This holds as a rule for first order thalamic nuclei, but in contrast, higher order thalamic nuclei receive much of their driver input back from cerebral cortex. In addition, higher order thalamic neurons receive inputs from subcortical movement-related centers. In the terminology popularized from studies of the sensory system, can we consider these ascending motor inputs to thalamus from subcortical structures to be modulators, subtly influencing the activity of their target neurons, or drivers, dictating the activity of their target neurons? This chapter summarizes relevant evidence from neuronal recording, inactivation, and stimulation of pathways projecting from the superior colliculus through thalamus to cerebral cortex. The study concludes that many inputs to the higher order nuclei of the thalamus from subcortical oculomotor areas - from the superior colliculus and probably other midbrain and pontine regions - should be regarded as motor drivers analogous to the sensory drivers at the first order thalamic nuclei. These motor drivers at the thalamus are viewed as being at the top of a series of feedback loops that provide information on impending actions, just as sensory drivers provide information about the external environment.

  2. Modulation of motor cortex excitability by paired peripheral and transcranial magnetic stimulation.

    PubMed

    Kumru, Hatice; Albu, Sergiu; Rothwell, John; Leon, Daniel; Flores, Cecilia; Opisso, Eloy; Tormos, Josep Maria; Valls-Sole, Josep

    2017-10-01

    Repetitive application of peripheral electrical stimuli paired with transcranial magnetic stimulation (rTMS) of M1 cortex at low frequency, known as paired associative stimulation (PAS), is an effective method to induce motor cortex plasticity in humans. Here we investigated the effects of repetitive peripheral magnetic stimulation (rPMS) combined with low frequency rTMS ('magnetic-PAS') on intracortical and corticospinal excitability and whether those changes were widespread or circumscribed to the cortical area controlling the stimulated muscle. Eleven healthy subjects underwent three 10min stimulation sessions: 10HzrPMS alone, applied in trains of 5 stimuli every 10s (60 trains) on the extensor carpi radialis (ECR) muscle; rTMS alone at an intensity 120% of ECR threshold, applied over motor cortex of ECR and at a frequency of 0.1Hz (60 stimuli) and magnetic PAS, i.e., paired rPMS and rTMS. We recorded motor evoked potentials (MEPs) from ECR and first dorsal interosseous (FDI) muscles. We measured resting motor threshold, motor evoked potentials (MEP) amplitude at 120% of RMT, short intracortical inhibition (SICI) at interstimulus interval (ISI) of 2ms and intracortical facilitation (ICF) at an ISI of 15ms before and immediately after each intervention. Magnetic-PAS , but not rTMS or rPMS applied separately, increased MEP amplitude and reduced short intracortical inhibition in ECR but not in FDI muscle. Magnetic-PAS can increase corticospinal excitability and reduce intracortical inhibition. The effects may be specific for the area of cortical representation of the stimulated muscle. Application of magnetic-PAS might be relevant for motor rehabilitation. Copyright © 2017 International Federation of Clinical Neurophysiology. All rights reserved.

  3. Motor Learning Enhances Use-Dependent Plasticity

    PubMed Central

    2017-01-01

    Motor behaviors are shaped not only by current sensory signals but also by the history of recent experiences. For instance, repeated movements toward a particular target bias the subsequent movements toward that target direction. This process, called use-dependent plasticity (UDP), is considered a basic and goal-independent way of forming motor memories. Most studies consider movement history as the critical component that leads to UDP (Classen et al., 1998; Verstynen and Sabes, 2011). However, the effects of learning (i.e., improved performance) on UDP during movement repetition have not been investigated. Here, we used transcranial magnetic stimulation in two experiments to assess plasticity changes occurring in the primary motor cortex after individuals repeated reinforced and nonreinforced actions. The first experiment assessed whether learning a skill task modulates UDP. We found that a group that successfully learned the skill task showed greater UDP than a group that did not accumulate learning, but made comparable repeated actions. The second experiment aimed to understand the role of reinforcement learning in UDP while controlling for reward magnitude and action kinematics. We found that providing subjects with a binary reward without visual feedback of the cursor led to increased UDP effects. Subjects in the group that received comparable reward not associated with their actions maintained the previously induced UDP. Our findings illustrate how reinforcing consistent actions strengthens use-dependent memories and provide insight into operant mechanisms that modulate plastic changes in the motor cortex. SIGNIFICANCE STATEMENT Performing consistent motor actions induces use-dependent plastic changes in the motor cortex. This plasticity reflects one of the basic forms of human motor learning. Past studies assumed that this form of learning is exclusively affected by repetition of actions. However, here we showed that success-based reinforcement signals could affect the human use-dependent plasticity (UDP) process. Our results indicate that learning augments and interacts with UDP. This effect is important to the understanding of the interplay between the different forms of motor learning and suggests that reinforcement is not only important to learning new behaviors, but can shape our subsequent behavior via its interaction with UDP. PMID:28143961

  4. Vibrissa motor cortex activity suppresses contralateral whisking behavior.

    PubMed

    Ebbesen, Christian Laut; Doron, Guy; Lenschow, Constanze; Brecht, Michael

    2017-01-01

    Anatomical, stimulation and lesion data implicate vibrissa motor cortex in whisker motor control. Work on motor cortex has focused on movement generation, but correlations between vibrissa motor cortex activity and whisking are weak. The exact role of vibrissa motor cortex remains unknown. We recorded vibrissa motor cortex neurons during various forms of vibrissal touch, which were invariably associated with whisker protraction and movement. Free whisking, object palpation and social touch all resulted in decreased cortical activity. To understand this activity decrease, we performed juxtacellular recordings, nanostimulation and in vivo whole-cell recordings. Social touch resulted in decreased spiking activity, decreased cell excitability and membrane hyperpolarization. Activation of vibrissa motor cortex by intracortical microstimulation elicited whisker retraction, as if to abort vibrissal touch. Various vibrissa motor cortex inactivation protocols resulted in contralateral protraction and increased whisker movements. These data collectively point to movement suppression as a prime function of vibrissa motor cortex activity.

  5. Neutralization of Nogo-A Enhances Synaptic Plasticity in the Rodent Motor Cortex and Improves Motor Learning in Vivo

    PubMed Central

    Weinmann, Oliver; Kellner, Yves; Yu, Xinzhu; Vicente, Raul; Gullo, Miriam; Kasper, Hansjörg; Lussi, Karin; Ristic, Zorica; Luft, Andreas R.; Rioult-Pedotti, Mengia; Zuo, Yi; Zagrebelsky, Marta; Schwab, Martin E.

    2014-01-01

    The membrane protein Nogo-A is known as an inhibitor of axonal outgrowth and regeneration in the CNS. However, its physiological functions in the normal adult CNS remain incompletely understood. Here, we investigated the role of Nogo-A in cortical synaptic plasticity and motor learning in the uninjured adult rodent motor cortex. Nogo-A and its receptor NgR1 are present at cortical synapses. Acute treatment of slices with function-blocking antibodies (Abs) against Nogo-A or against NgR1 increased long-term potentiation (LTP) induced by stimulation of layer 2/3 horizontal fibers. Furthermore, anti-Nogo-A Ab treatment increased LTP saturation levels, whereas long-term depression remained unchanged, thus leading to an enlarged synaptic modification range. In vivo, intrathecal application of Nogo-A-blocking Abs resulted in a higher dendritic spine density at cortical pyramidal neurons due to an increase in spine formation as revealed by in vivo two-photon microscopy. To investigate whether these changes in synaptic plasticity correlate with motor learning, we trained rats to learn a skilled forelimb-reaching task while receiving anti-Nogo-A Abs. Learning of this cortically controlled precision movement was improved upon anti-Nogo-A Ab treatment. Our results identify Nogo-A as an influential molecular modulator of synaptic plasticity and as a regulator for learning of skilled movements in the motor cortex. PMID:24966370

  6. Botulinum Toxin Injections Reduce Associative Plasticity in Patients with Primary Dystonia

    PubMed Central

    Kojovic, Maja; Caronni, Antonio; Bologna, Matteo; Rothwell, John C.; Bhatia, Kailash P.; Edwards, Mark J.

    2014-01-01

    Botulinum toxin injections ameliorate dystonic symptoms by blocking the neuromuscular junction and weakening dystonic contractions. We asked if botulinum toxin injections in dystonia patients might also affect the integrity of sensorimotor cortical plasticity, one of the key pathophysiological features of dystonia. We applied a paired associative stimulation protocol, known to induce long-term potentiation–like changes in the primary motor cortex hand area to 12 patients with cervical dystonia before and 1 and 3 months after botulinum toxin injections to the neck muscles. Primary motor cortex excitability was probed by measuring transcranial magnetic stimulation-evoked motor evoked potentials before and after paired associative stimulation. We also measured the input–output curve, short-interval intracortical inhibition, intracortical facilitation, short afferent inhibition, and long afferent inhibition in hand muscles and the clinical severity of dystonia. Before botulinum toxin injections, paired associative stimulation significantly facilitated motor evoked potentials in hand muscles. One month after injections, this effect was abolished, with partial recovery after 3 months. There were significant positive correlations between the facilitation produced by paired associative stimulation and (1) the time elapsed since botulinum toxin injections and (2) the clinical dystonia score. One effect of botulinum toxin injection treatment is to modulate afferent input from the neck. We propose that subsequent reorganization of the motor cortex representation of hand muscles may explain the effect of botulinum toxin on motor cortical plasticity. PMID:21469207

  7. An Activation Likelihood Estimation Meta-Analysis Study of Simple Motor Movements in Older and Young Adults

    PubMed Central

    Turesky, Ted K.; Turkeltaub, Peter E.; Eden, Guinevere F.

    2016-01-01

    The functional neuroanatomy of finger movements has been characterized with neuroimaging in young adults. However, less is known about the aging motor system. Several studies have contrasted movement-related activity in older versus young adults, but there is inconsistency among their findings. To address this, we conducted an activation likelihood estimation (ALE) meta-analysis on within-group data from older adults and young adults performing regularly paced right-hand finger movement tasks in response to external stimuli. We hypothesized that older adults would show a greater likelihood of activation in right cortical motor areas (i.e., ipsilateral to the side of movement) compared to young adults. ALE maps were examined for conjunction and between-group differences. Older adults showed overlapping likelihoods of activation with young adults in left primary sensorimotor cortex (SM1), bilateral supplementary motor area, bilateral insula, left thalamus, and right anterior cerebellum. Their ALE map differed from that of the young adults in right SM1 (extending into dorsal premotor cortex), right supramarginal gyrus, medial premotor cortex, and right posterior cerebellum. The finding that older adults uniquely use ipsilateral regions for right-hand finger movements and show age-dependent modulations in regions recruited by both age groups provides a foundation by which to understand age-related motor decline and motor disorders. PMID:27799910

  8. [Neuroanatomy of Frontal Association Cortex].

    PubMed

    Takada, Masahiko

    2016-11-01

    The frontal association cortex is composed of the prefrontal cortex and the motor-related areas except the primary motor cortex (i.e., the so-called higher motor areas), and is well-developed in primates, including humans. The prefrontal cortex receives and integrates large bits of diverse information from the parietal, temporal, and occipital association cortical areas (termed the posterior association cortex), and paralimbic association cortical areas. This information is then transmitted to the primary motor cortex via multiple motor-related areas. Given these facts, it is likely that the prefrontal cortex exerts executive functions for behavioral control. The functional input pathways from the posterior and paralimbic association cortical areas to the prefrontal cortex are classified primarily into six groups. Cognitive signals derived from the prefrontal cortex are conveyed to the rostral motor-related areas to transform them into motor signals, which finally enter the primary motor cortex via the caudal motor-related areas. Furthermore, it has been shown that, similar to the primary motor cortex, areas of the frontal association cortex form individual networks (known as "loop circuits") with the basal ganglia and cerebellum via the thalamus, and hence are extensively involved in the expression and control of behavioral actions.

  9. Structural neuroplasticity in the sensorimotor network of professional female ballet dancers.

    PubMed

    Hänggi, Jürgen; Koeneke, Susan; Bezzola, Ladina; Jäncke, Lutz

    2010-08-01

    Evidence suggests that motor, sensory, and cognitive training modulates brain structures involved in a specific practice. Functional neuroimaging revealed key brain structures involved in dancing such as the putamen and the premotor cortex. Intensive ballet dance training was expected to modulate the structures of the sensorimotor network, for example, the putamen, premotor cortex, supplementary motor area (SMA), and the corticospinal tracts. We investigated gray (GM) and white matter (WM) volumes, fractional anisotropy (FA), and mean diffusivity (MD) using magnetic resonance-based morphometry and diffusion tensor imaging in 10 professional female ballet dancers compared with 10 nondancers. In dancers compared with nondancers, decreased GM volumes were observed in the left premotor cortex, SMA, putamen, and superior frontal gyrus, and decreased WM volumes in both corticospinal tracts, both internal capsules, corpus callosum, and left anterior cingulum. FA was lower in the WM underlying the dancers' left and right premotor cortex. There were no significant differences in MD between the groups. Age of dance commencement was negatively correlated with GM and WM volume in the right premotor cortex and internal capsule, respectively, and positively correlated with WM volume in the left precentral gyrus and corpus callosum. Results were not influenced by the significantly lower body mass index of the dancers. The present findings complement the results of functional imaging studies in experts that revealed reduced neural activity in skilled compared with nonskilled subjects. Reductions in brain activity are accompanied by local decreases in GM and WM volumes and decreased FA. 2009 Wiley-Liss, Inc.

  10. BDNF Val66Met polymorphism is associated with abnormal interhemispheric transfer of a newly acquired motor skill.

    PubMed

    Morin-Moncet, Olivier; Beaumont, Vincent; de Beaumont, Louis; Lepage, Jean-Francois; Théoret, Hugo

    2014-05-01

    Recent data suggest that the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene can alter cortical plasticity within the motor cortex of carriers, which exhibits abnormally low rates of cortical reorganization after repetitive motor tasks. To verify whether long-term retention of a motor skill is also modulated by the presence of the polymorphism, 20 participants (10 Val66Val, 10 Val66Met) were tested twice at a 1-wk interval. During each visit, excitability of the motor cortex was measured by transcranial magnetic stimulations (TMS) before and after performance of a procedural motor learning task (serial reaction time task) designed to study sequence-specific learning of the right hand and sequence-specific transfer from the right to the left hand. Behavioral results showed a motor learning effect that persisted for at least a week and task-related increases in corticospinal excitability identical for both sessions and without distinction for genetic group. Sequence-specific transfer of the motor skill from the right hand to the left hand was greater in session 2 than in session 1 only in the Val66Met genetic group. Further analysis revealed that the sequence-specific transfer occurred equally at both sessions in the Val66Val genotype group. In the Val66Met genotype group, sequence-specific transfer did not occur at session 1 but did at session 2. These data suggest a limited impact of Val66Met polymorphism on the learning and retention of a complex motor skill and its associated changes in corticospinal excitability over time, and a possible modulation of the interhemispheric transfer of procedural learning. Copyright © 2014 the American Physiological Society.

  11. Anatomical Parameters of tDCS to Modulate the Motor System after Stroke: A Review

    PubMed Central

    Lefebvre, Stephanie; Liew, Sook-Lei

    2017-01-01

    Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation method to modulate the local field potential in neural tissue and consequently, cortical excitability. As tDCS is relatively portable, affordable, and accessible, the applications of tDCS to probe brain–behavior connections have rapidly increased in the last 10 years. One of the most promising applications is the use of tDCS to modulate excitability in the motor cortex after stroke and promote motor recovery. However, the results of clinical studies implementing tDCS to modulate motor excitability have been highly variable, with some studies demonstrating that as many as 50% or more of patients fail to show a response to stimulation. Much effort has therefore been dedicated to understand the sources of variability affecting tDCS efficacy. Possible suspects include the placement of the electrodes, task parameters during stimulation, dosing (current amplitude, duration of stimulation, frequency of stimulation), individual states (e.g., anxiety, motivation, attention), and more. In this review, we first briefly review potential sources of variability specific to stroke motor recovery following tDCS. We then examine how the anatomical variability in tDCS placement [e.g., neural target(s) and montages employed] may alter the neuromodulatory effects that tDCS exerts on the post-stroke motor system. PMID:28232816

  12. The role of the premotor cortex and the primary motor cortex in action verb comprehension: evidence from Granger causality analysis.

    PubMed

    Yang, Jie; Shu, Hua

    2012-08-01

    Although numerous studies find the premotor cortex and the primary motor cortex are involved in action language comprehension, so far the nature of these motor effects is still in controversy. Some researchers suggest that the motor effects reflect that the premotor cortex and the primary motor cortex make functional contributions to the semantic access of action verbs, while other authors argue that the motor effects are caused by comprehension. In the current study, we used Granger causality analysis to investigate the roles of the premotor cortex and the primary motor cortex in processing of manual-action verbs. Regions of interest were selected in the primary motor cortex (M1) and the premotor cortex based on a hand motion task, and in the left posterior middle temporal gyrus (lexical semantic area) based on the reading task effect. We found that (1) the left posterior middle temporal gyrus had a causal influence on the left M1; and (2) the left posterior middle temporal gyrus and the left premotor cortex had bidirectional causal relations. These results suggest that the premotor cortex and the primary motor cortex play different roles in manual verb comprehension. The premotor cortex may be involved in motor simulation that contributes to action language processing, while the primary motor cortex may be engaged in a processing stage influenced by the meaning access of manual-action verbs. Further investigation combining effective connectivity analysis and technique with high temporal resolution is necessary for better clarification of the roles of the premotor cortex and the primary motor cortex in action language comprehension. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Aversive stimuli exacerbate defensive motor behaviour in motor conversion disorder.

    PubMed

    Blakemore, Rebekah L; Sinanaj, Indrit; Galli, Silvio; Aybek, Selma; Vuilleumier, Patrik

    2016-12-01

    Conversion disorder or functional neurological symptom disorder (FND) can affect the voluntary motor system, without an organic cause. Functional symptoms are thought to be generated unconsciously, arising from underlying psychological stressors. However, attempts to demonstrate a direct relationship between the limbic system and disrupted motor function in FND are lacking. We tested whether negative affect would exacerbate alterations of motor control and corresponding brain activations in individuals with FND. Ten patients and ten healthy controls produced an isometric precision-grip contraction at 10% of maximum force while either viewing visual feedback of their force output, or unpleasant or pleasant emotional images (without feedback). Force magnitude was continuously recorded together with change in brain activity using fMRI. For controls, force output decayed from the target level while viewing pleasant and unpleasant images. Patients however, maintained force at the target level without decay while viewing unpleasant images, indicating a pronounced effect of negative affect on force output in FND. This emotional modulation of force control was associated with different brain activation patterns between groups. Contrasting the unpleasant with the pleasant condition, controls showed increased activity in the inferior frontal cortex and pre-supplementary motor area, whereas patients had greater activity in the cerebellum (vermis), posterior cingulate cortex, and hippocampus. Engagement of a cerebellar-limbic network in patients is consistent with heightened processing of emotional salience, and supports the role of the cerebellum in freezing responses in the presence of aversive events. These data highlight a possible neural circuit through which psychological stressors elicit defensive behaviour and modulate motor function in FND. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Focal Stroke in the Developing Rat Motor Cortex Induces Age- and Experience-Dependent Maladaptive Plasticity of Corticospinal System

    PubMed Central

    Gennaro, Mariangela; Mattiello, Alessandro; Mazziotti, Raffaele; Antonelli, Camilla; Gherardini, Lisa; Guzzetta, Andrea; Berardi, Nicoletta; Cioni, Giovanni; Pizzorusso, Tommaso

    2017-01-01

    Motor system development is characterized by an activity-dependent competition between ipsilateral and contralateral corticospinal tracts (CST). Clinical evidence suggests that age is crucial for developmental stroke outcome, with early lesions inducing a “maladaptive” strengthening of ipsilateral projections from the healthy hemisphere and worse motor impairment. Here, we investigated in developing rats the relation between lesion timing, motor outcome and CST remodeling pattern. We induced a focal ischemia into forelimb motor cortex (fM1) at two distinct pre-weaning ages: P14 and P21. We compared long-term motor outcome with changes in axonal sprouting of contralesional CST at red nucleus and spinal cord level using anterograde tracing. We found that P14 stroke caused a more severe long-term motor impairment than at P21, and induced a strong and aberrant contralesional CST sprouting onto denervated spinal cord and red nucleus. The mistargeted sprouting of CST, and the worse motor outcome of the P14 stroke rats were reversed by an early skilled motor training, underscoring the potential of early activity-dependent plasticity in modulating lesion outcome. Thus, changes in the mechanisms controlling CST plasticity occurring during the third postnatal week are associated with age-dependent regulation of the motor outcome after stroke. PMID:28706475

  15. Focal Stroke in the Developing Rat Motor Cortex Induces Age- and Experience-Dependent Maladaptive Plasticity of Corticospinal System.

    PubMed

    Gennaro, Mariangela; Mattiello, Alessandro; Mazziotti, Raffaele; Antonelli, Camilla; Gherardini, Lisa; Guzzetta, Andrea; Berardi, Nicoletta; Cioni, Giovanni; Pizzorusso, Tommaso

    2017-01-01

    Motor system development is characterized by an activity-dependent competition between ipsilateral and contralateral corticospinal tracts (CST). Clinical evidence suggests that age is crucial for developmental stroke outcome, with early lesions inducing a "maladaptive" strengthening of ipsilateral projections from the healthy hemisphere and worse motor impairment. Here, we investigated in developing rats the relation between lesion timing, motor outcome and CST remodeling pattern. We induced a focal ischemia into forelimb motor cortex (fM1) at two distinct pre-weaning ages: P14 and P21. We compared long-term motor outcome with changes in axonal sprouting of contralesional CST at red nucleus and spinal cord level using anterograde tracing. We found that P14 stroke caused a more severe long-term motor impairment than at P21, and induced a strong and aberrant contralesional CST sprouting onto denervated spinal cord and red nucleus. The mistargeted sprouting of CST, and the worse motor outcome of the P14 stroke rats were reversed by an early skilled motor training, underscoring the potential of early activity-dependent plasticity in modulating lesion outcome. Thus, changes in the mechanisms controlling CST plasticity occurring during the third postnatal week are associated with age-dependent regulation of the motor outcome after stroke.

  16. A direct GABAergic output from the basal ganglia to frontal cortex

    PubMed Central

    Saunders, Arpiar; Oldenburg, Ian A.; Berezovskii, Vladimir K.; Johnson, Caroline A.; Kingery, Nathan D.; Elliott, Hunter L.; Xie, Tiao; Gerfen, Charles R.; Sabatini, Bernardo L.

    2014-01-01

    The basal ganglia (BG) are phylogenetically conserved subcortical nuclei necessary for coordinated motor action and reward learning1. Current models postulate that the BG modulate cerebral cortex indirectly via an inhibitory output to thalamus, bidirectionally controlled by the BG via direct (dSPNs) and indirect (iSPNs) pathway striatal projection neurons2–4. The BG thalamic output sculpts cortical activity by interacting with signals from sensory and motor systems5. Here we describe a direct projection from the globus pallidus externus (GP), a central nucleus of the BG, to frontal regions of the cerebral cortex (FC). Two cell types make up the GP-FC projection, distinguished by their electrophysiological properties, cortical projections and expression of choline acetyltransferase (ChAT), a synthetic enzyme for the neurotransmitter acetylcholine (ACh). Despite these differences, ChAT+ cells, which have been historically identified as an extension of the nucleus basalis (NB), as well as ChAT− cells, release the inhibitory neurotransmitter GABA (γ-aminobutyric acid) and are inhibited by iSPNs and dSPNs of dorsal striatum. Thus GP-FC cells comprise a direct GABAergic/cholinergic projection under the control of striatum that activates frontal cortex in vivo. Furthermore, iSPN inhibition of GP-FC cells is sensitive to dopamine 2 receptor signaling, revealing a pathway by which drugs that target dopamine receptors for the treatment of neuropsychiatric disorders can act in the BG to modulate frontal cortices. PMID:25739505

  17. Modulatory Effects of the Ipsi and Contralateral Ventral Premotor Cortex (PMv) on the Primary Motor Cortex (M1) Outputs to Intrinsic Hand and Forearm Muscles in Cebus apella

    PubMed Central

    Quessy, Stephan; Côté, Sandrine L.; Hamadjida, Adjia; Deffeyes, Joan; Dancause, Numa

    2016-01-01

    The ventral premotor cortex (PMv) is a key node in the neural network involved in grasping. One way PMv can carry out this function is by modulating the outputs of the primary motor cortex (M1) to intrinsic hand and forearm muscles. As many PMv neurons discharge when grasping with either arm, both PMv within the same hemisphere (ipsilateral; iPMv) and in the opposite hemisphere (contralateral; cPMv) could modulate M1 outputs. Our objective was to compare modulatory effects of iPMv and cPMv on M1 outputs to intrinsic hand and forearm muscles. We used paired-pulse protocols with intracortical microstimulations in capuchin monkeys. A conditioning stimulus was applied in either iPMv or cPMv simultaneously or prior to a test stimulus in M1 and the effects quantified in electromyographic signals. Modulatory effects from iPMv were predominantly facilitatory, and facilitation was much more common and powerful on intrinsic hand than forearm muscles. In contrast, while the conditioning of cPMv could elicit facilitatory effects, in particular to intrinsic hand muscles, it was much more likely to inhibit M1 outputs. These data show that iPMv and cPMv have very different modulatory effects on the outputs of M1 to intrinsic hand and forearm muscles. PMID:27473318

  18. Nouns referring to tools and natural objects differentially modulate the motor system.

    PubMed

    Gough, Patricia M; Riggio, Lucia; Chersi, Fabian; Sato, Marc; Fogassi, Leonardo; Buccino, Giovanni

    2012-01-01

    While increasing evidence points to a critical role for the motor system in language processing, the focus of previous work has been on the linguistic category of verbs. Here we tested whether nouns are effective in modulating the motor system and further whether different kinds of nouns - those referring to artifacts or natural items, and items that are graspable or ungraspable - would differentially modulate the system. A Transcranial Magnetic Stimulation (TMS) study was carried out to compare modulation of the motor system when subjects read nouns referring to objects which are Artificial or Natural and which are Graspable or Ungraspable. TMS was applied to the primary motor cortex representation of the first dorsal interosseous (FDI) muscle of the right hand at 150 ms after noun presentation. Analyses of Motor Evoked Potentials (MEPs) revealed that across the duration of the task, nouns referring to graspable artifacts (tools) were associated with significantly greater MEP areas. Analyses of the initial presentation of items revealed a main effect of graspability. The findings are in line with an embodied view of nouns, with MEP measures modulated according to whether nouns referred to natural objects or artifacts (tools), confirming tools as a special class of items in motor terms. Additionally our data support a difference for graspable versus non graspable objects, an effect which for natural objects is restricted to initial presentation of items. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Parallel processing streams for motor output and sensory prediction during action preparation

    PubMed Central

    Bauer, Markus; Heinze, Hans-Jochen; Haggard, Patrick; Dolan, Raymond J.

    2014-01-01

    Sensory consequences of one's own actions are perceived as less intense than identical, externally generated stimuli. This is generally taken as evidence for sensory prediction of action consequences. Accordingly, recent theoretical models explain this attenuation by an anticipatory modulation of sensory processing prior to stimulus onset (Roussel et al. 2013) or even action execution (Brown et al. 2013). Experimentally, prestimulus changes that occur in anticipation of self-generated sensations are difficult to disentangle from more general effects of stimulus expectation, attention and task load (performing an action). Here, we show that an established manipulation of subjective agency over a stimulus leads to a predictive modulation in sensory cortex that is independent of these factors. We recorded magnetoencephalography while subjects performed a simple action with either hand and judged the loudness of a tone caused by the action. Effector selection was manipulated by subliminal motor priming. Compatible priming is known to enhance a subjective experience of agency over a consequent stimulus (Chambon and Haggard 2012). In line with this effect on subjective agency, we found stronger sensory attenuation when the action that caused the tone was compatibly primed. This perceptual effect was reflected in a transient phase-locked signal in auditory cortex before stimulus onset and motor execution. Interestingly, this sensory signal emerged at a time when the hemispheric lateralization of motor signals in M1 indicated ongoing effector selection. Our findings confirm theoretical predictions of a sensory modulation prior to self-generated sensations and support the idea that a sensory prediction is generated in parallel to motor output (Walsh and Haggard 2010), before an efference copy becomes available. PMID:25540223

  20. Parallel processing streams for motor output and sensory prediction during action preparation.

    PubMed

    Stenner, Max-Philipp; Bauer, Markus; Heinze, Hans-Jochen; Haggard, Patrick; Dolan, Raymond J

    2015-03-15

    Sensory consequences of one's own actions are perceived as less intense than identical, externally generated stimuli. This is generally taken as evidence for sensory prediction of action consequences. Accordingly, recent theoretical models explain this attenuation by an anticipatory modulation of sensory processing prior to stimulus onset (Roussel et al. 2013) or even action execution (Brown et al. 2013). Experimentally, prestimulus changes that occur in anticipation of self-generated sensations are difficult to disentangle from more general effects of stimulus expectation, attention and task load (performing an action). Here, we show that an established manipulation of subjective agency over a stimulus leads to a predictive modulation in sensory cortex that is independent of these factors. We recorded magnetoencephalography while subjects performed a simple action with either hand and judged the loudness of a tone caused by the action. Effector selection was manipulated by subliminal motor priming. Compatible priming is known to enhance a subjective experience of agency over a consequent stimulus (Chambon and Haggard 2012). In line with this effect on subjective agency, we found stronger sensory attenuation when the action that caused the tone was compatibly primed. This perceptual effect was reflected in a transient phase-locked signal in auditory cortex before stimulus onset and motor execution. Interestingly, this sensory signal emerged at a time when the hemispheric lateralization of motor signals in M1 indicated ongoing effector selection. Our findings confirm theoretical predictions of a sensory modulation prior to self-generated sensations and support the idea that a sensory prediction is generated in parallel to motor output (Walsh and Haggard 2010), before an efference copy becomes available. Copyright © 2015 the American Physiological Society.

  1. Dissociable effects of local inhibitory and excitatory theta-burst stimulation on large-scale brain dynamics

    PubMed Central

    Sale, Martin V.; Lord, Anton; Zalesky, Andrew; Breakspear, Michael; Mattingley, Jason B.

    2015-01-01

    Normal brain function depends on a dynamic balance between local specialization and large-scale integration. It remains unclear, however, how local changes in functionally specialized areas can influence integrated activity across larger brain networks. By combining transcranial magnetic stimulation with resting-state functional magnetic resonance imaging, we tested for changes in large-scale integration following the application of excitatory or inhibitory stimulation on the human motor cortex. After local inhibitory stimulation, regions encompassing the sensorimotor module concurrently increased their internal integration and decreased their communication with other modules of the brain. There were no such changes in modular dynamics following excitatory stimulation of the same area of motor cortex nor were there changes in the configuration and interactions between core brain hubs after excitatory or inhibitory stimulation of the same area. These results suggest the existence of selective mechanisms that integrate local changes in neural activity, while preserving ongoing communication between brain hubs. PMID:25717162

  2. Reversible deactivation of higher-order posterior parietal areas. II. Alterations in response properties of neurons in areas 1 and 2

    PubMed Central

    Goldring, Adam B.; Cooke, Dylan F.; Baldwin, Mary K. L.; Recanzone, Gregg H.; Gordon, Adam G.; Pan, Tingrui; Simon, Scott I.

    2014-01-01

    The role that posterior parietal (PPC) and motor cortices play in modulating neural responses in somatosensory areas 1 and 2 was examined with reversible deactivation by transient cooling. Multiunit recordings from neurons in areas 1 and 2 were collected from six anesthetized adult monkeys (Macaca mulatta) before, during, and after reversible deactivation of areas 5L or 7b or motor cortex (M1/PM), while select locations on the hand and forelimb were stimulated. Response changes were quantified as increases and decreases to stimulus-driven activity relative to baseline and analyzed during three recording epochs: during deactivation (“cool”) and at two time points after deactivation (“rewarm 1,” “rewarm 2”). Although the type of response change observed was variable, for neurons at the recording sites tested >90% exhibited a significant change in response during cooling of 7b while cooling area 5L or M1/PM produced a change in 75% and 64% of sites, respectively. These results suggest that regions in the PPC, and to a lesser extent motor cortex, shape the response characteristics of neurons in areas 1 and 2 and that this kind of feedback modulation is necessary for normal somatosensory processing. Furthermore, this modulation appears to happen on a minute-by-minute basis and may serve as the substrate for phenomena such as somatosensory attention. PMID:25143537

  3. Physiological and modeling evidence for focal transcranial electrical brain stimulation in humans: A basis for high-definition tDCS

    PubMed Central

    Edwards, Dylan; Cortes, Mar; Datta, Abhishek; Minhas, Preet; Wassermann, Eric M.; Bikson, Marom

    2015-01-01

    Transcranial Direct Current Stimulation (tDCS) is a non-invasive, low-cost, well-tolerated technique producing lasting modulation of cortical excitability. Behavioral and therapeutic outcomes of tDCS are linked to the targeted brain regions, but there is little evidence that current reaches the brain as intended. We aimed to: (1) validate a computational model for estimating cortical electric fields in human transcranial stimulation, and (2) assess the magnitude and spread of cortical electric field with a novel High-Definition tDCS (HD-tDCS) scalp montage using a 4×1-Ring electrode configuration. In three healthy adults, Transcranial Electrical Stimulation (TES) over primary motor cortex (M1) was delivered using the 4×1 montage (4× cathode, surrounding a single central anode; montage radius ~3 cm) with sufficient intensity to elicit a discrete muscle twitch in the hand. The estimated current distribution in M1 was calculated using the individualized MRI-based model, and compared with the observed motor response across subjects. The response magnitude was quantified with stimulation over motor cortex as well as anterior and posterior to motor cortex. In each case the model data were consistent with the motor response across subjects. The estimated cortical electric fields with the 4×1 montage were compared (area, magnitude, direction) for TES and tDCS in each subject. We provide direct evidence in humans that TES with a 4×1-Ring configuration can activate motor cortex and that current does not substantially spread outside the stimulation area. Computational models predict that both TES and tDCS waveforms using the 4×1-Ring configuration generate electric fields in cortex with comparable gross current distribution, and preferentially directed normal (inward) currents. The agreement of modeling and experimental data for both current delivery and focality support the use of the HD-tDCS 4×1-Ring montage for cortically targeted neuromodulation. PMID:23370061

  4. Rapid acquisition of novel interface control by small ensembles of arbitrarily selected primary motor cortex neurons

    PubMed Central

    Law, Andrew J.; Rivlis, Gil

    2014-01-01

    Pioneering studies demonstrated that novel degrees of freedom could be controlled individually by directly encoding the firing rate of single motor cortex neurons, without regard to each neuron's role in controlling movement of the native limb. In contrast, recent brain-computer interface work has emphasized decoding outputs from large ensembles that include substantially more neurons than the number of degrees of freedom being controlled. To bridge the gap between direct encoding by single neurons and decoding output from large ensembles, we studied monkeys controlling one degree of freedom by comodulating up to four arbitrarily selected motor cortex neurons. Performance typically exceeded random quite early in single sessions and then continued to improve to different degrees in different sessions. We therefore examined factors that might affect performance. Performance improved with larger ensembles. In contrast, other factors that might have reflected preexisting synaptic architecture—such as the similarity of preferred directions—had little if any effect on performance. Patterns of comodulation among ensemble neurons became more consistent across trials as performance improved over single sessions. Compared with the ensemble neurons, other simultaneously recorded neurons showed less modulation. Patterns of voluntarily comodulated firing among small numbers of arbitrarily selected primary motor cortex (M1) neurons thus can be found and improved rapidly, with little constraint based on the normal relationships of the individual neurons to native limb movement. This rapid flexibility in relationships among M1 neurons may in part underlie our ability to learn new movements and improve motor skill. PMID:24920030

  5. Motor cortex stimulation and neuropathic pain: how does motor cortex stimulation affect pain-signaling pathways?

    PubMed

    Kim, Jinhyung; Ryu, Sang Baek; Lee, Sung Eun; Shin, Jaewoo; Jung, Hyun Ho; Kim, Sung June; Kim, Kyung Hwan; Chang, Jin Woo

    2016-03-01

    Neuropathic pain is often severe. Motor cortex stimulation (MCS) is used for alleviating neuropathic pain, but the mechanism of action is still unclear. This study aimed to understand the mechanism of action of MCS by investigating pain-signaling pathways, with the expectation that MCS would regulate both descending and ascending pathways. Neuropathic pain was induced in Sprague-Dawley rats. Surface electrodes for MCS were implanted in the rats. Tactile allodynia was measured by behavioral testing to determine the effect of MCS. For the pathway study, immunohistochemistry was performed to investigate changes in c-fos and serotonin expression; micro-positron emission tomography (mPET) scanning was performed to investigate changes of glucose uptake; and extracellular electrophysiological recordings were performed to demonstrate brain activity. MCS was found to modulate c-fos and serotonin expression. In the mPET study, altered brain activity was observed in the striatum, thalamic area, and cerebellum. In the electrophysiological study, neuronal activity was increased by mechanical stimulation and suppressed by MCS. After elimination of artifacts, neuronal activity was demonstrated in the ventral posterolateral nucleus (VPL) during electrical stimulation. This neuronal activity was effectively suppressed by MCS. This study demonstrated that MCS effectively attenuated neuropathic pain. MCS modulated ascending and descending pain pathways. It regulated neuropathic pain by affecting the striatum, periaqueductal gray, cerebellum, and thalamic area, which are thought to regulate the descending pathway. MCS also appeared to suppress activation of the VPL, which is part of the ascending pathway.

  6. A cortical motor nucleus drives the basal ganglia-recipient thalamus in singing birds

    PubMed Central

    Goldberg, Jesse H.

    2012-01-01

    The pallido-recipient thalamus transmits information from the basal ganglia (BG) to the cortex and plays a critical role motor initiation and learning. Thalamic activity is strongly inhibited by pallidal inputs from the BG, but the role of non-pallidal inputs, such as excitatory inputs from cortex, is unclear. We have recorded simultaneously from presynaptic pallidal axon terminals and postsynaptic thalamocortical neurons in a BG-recipient thalamic nucleus necessary for vocal variability and learning in zebra finches. We found that song-locked rate modulations in the thalamus could not be explained by pallidal inputs alone, and persisted following pallidal lesion. Instead, thalamic activity was likely driven by inputs from a motor ‘cortical’ nucleus also necessary for singing. These findings suggest a role for cortical inputs to the pallido-recipient thalamus in driving premotor signals important for exploratory behavior and learning. PMID:22327474

  7. AMPA receptor-induced local brain-derived neurotrophic factor signaling mediates motor recovery after stroke.

    PubMed

    Clarkson, Andrew N; Overman, Justine J; Zhong, Sheng; Mueller, Rudolf; Lynch, Gary; Carmichael, S Thomas

    2011-03-09

    Stroke is the leading cause of adult disability. Recovery after stroke shares similar molecular and cellular properties with learning and memory. A main component of learning-induced plasticity involves signaling through AMPA receptors (AMPARs). We systematically tested the role of AMPAR function in motor recovery in a mouse model of focal stroke. AMPAR function controls functional recovery beginning 5 d after the stroke. Positive allosteric modulators of AMPARs enhance recovery of limb control when administered after a delay from the stroke. Conversely, AMPAR antagonists impair motor recovery. The contributions of AMPARs to recovery are mediated by release of brain-derived neurotrophic factor (BDNF) in periinfarct cortex, as blocking local BDNF function in periinfarct cortex blocks AMPAR-mediated recovery and prevents the normal pattern of motor recovery. In contrast to a delayed AMPAR role in motor recovery, early administration of AMPAR agonists after stroke increases stroke damage. These findings indicate that the role of glutamate signaling through the AMPAR changes over time in stroke: early potentiation of AMPAR signaling worsens stroke damage, whereas later potentiation of the same signaling system improves functional recovery.

  8. “Cerebellar contribution to visuo-attentional alpha rhythm: insights from weightlessness”

    PubMed Central

    Cebolla, A. M.; Petieau, M.; Dan, B.; Balazs, L.; McIntyre, J.; Cheron, G.

    2016-01-01

    Human brain adaptation in weightlessness follows the necessity to reshape the dynamic integration of the neural information acquired in the new environment. This basic aspect was here studied by the electroencephalogram (EEG) dynamics where oscillatory modulations were measured during a visuo-attentional state preceding a visuo-motor docking task. Astronauts in microgravity conducted the experiment in free-floating aboard the International Space Station, before the space flight and afterwards. We observed stronger power decrease (~ERD: event related desynchronization) of the ~10 Hz oscillation from the occipital-parietal (alpha ERD) to the central areas (mu ERD). Inverse source modelling of the stronger alpha ERD revealed a shift from the posterior cingulate cortex (BA31, from the default mode network) on Earth to the precentral cortex (BA4, primary motor cortex) in weightlessness. We also observed significant contribution of the vestibular network (BA40, BA32, and BA39) and cerebellum (lobule V, VI). We suggest that due to the high demands for the continuous readjustment of an appropriate body posture in free-floating, this visuo-attentional state required more contribution from the motor cortex. The cerebellum and the vestibular network involvement in weightlessness might support the correction signals processing necessary for postural stabilization, and the increased demand to integrate incongruent vestibular information. PMID:27883068

  9. Structural Organization of the Laryngeal Motor Cortical Network and Its Implication for Evolution of Speech Production.

    PubMed

    Kumar, Veena; Croxson, Paula L; Simonyan, Kristina

    2016-04-13

    The laryngeal motor cortex (LMC) is essential for the production of learned vocal behaviors because bilateral damage to this area renders humans unable to speak but has no apparent effect on innate vocalizations such as human laughing and crying or monkey calls. Several hypotheses have been put forward attempting to explain the evolutionary changes from monkeys to humans that potentially led to enhanced LMC functionality for finer motor control of speech production. These views, however, remain limited to the position of the larynx area within the motor cortex, as well as its connections with the phonatory brainstem regions responsible for the direct control of laryngeal muscles. Using probabilistic diffusion tractography in healthy humans and rhesus monkeys, we show that, whereas the LMC structural network is largely comparable in both species, the LMC establishes nearly 7-fold stronger connectivity with the somatosensory and inferior parietal cortices in humans than in macaques. These findings suggest that important "hard-wired" components of the human LMC network controlling the laryngeal component of speech motor output evolved from an already existing, similar network in nonhuman primates. However, the evolution of enhanced LMC-parietal connections likely allowed for more complex synchrony of higher-order sensorimotor coordination, proprioceptive and tactile feedback, and modulation of learned voice for speech production. The role of the primary motor cortex in the formation of a comprehensive network controlling speech and language has been long underestimated and poorly studied. Here, we provide comparative and quantitative evidence for the significance of this region in the control of a highly learned and uniquely human behavior: speech production. From the viewpoint of structural network organization, we discuss potential evolutionary advances of enhanced temporoparietal cortical connections with the laryngeal motor cortex in humans compared with nonhuman primates that may have contributed to the development of finer vocal motor control necessary for speech production. Copyright © 2016 the authors 0270-6474/16/364170-12$15.00/0.

  10. Timing-dependent modulation of the posterior parietal cortex–primary motor cortex pathway by sensorimotor training

    PubMed Central

    Jin, Seung-Hyun; Joutsen, Atte; Poston, Brach; Aizen, Joshua; Ellenstein, Aviva; Hallett, Mark

    2012-01-01

    Interplay between posterior parietal cortex (PPC) and ipsilateral primary motor cortex (M1) is crucial during execution of movements. The purpose of the study was to determine whether functional PPC–M1 connectivity in humans can be modulated by sensorimotor training. Seventeen participants performed a sensorimotor training task that involved tapping the index finger in synchrony to a rhythmic sequence. To explore differences in training modality, one group (n = 8) learned by visual and the other (n = 9) by auditory stimuli. Transcranial magnetic stimulation (TMS) was used to assess PPC–M1 connectivity before and after training, whereas electroencephalography (EEG) was used to assess PPC–M1 connectivity during training. Facilitation from PPC to M1 was quantified using paired-pulse TMS at conditioning-test intervals of 2, 4, 6, and 8 ms by measuring motor-evoked potentials (MEPs). TMS was applied at baseline and at four time points (0, 30, 60, and 180 min) after training. For EEG, task-related power and coherence were calculated for early and late training phases. The conditioned MEP was facilitated at a 2-ms conditioning-test interval before training. However, facilitation was abolished immediately following training, but returned to baseline at subsequent time points. Regional EEG activity and interregional connectivity between PPC and M1 showed an initial increase during early training followed by a significant decrease in the late phases. The findings indicate that parietal–motor interactions are activated during early sensorimotor training when sensory information has to be integrated into a coherent movement plan. Once the sequence is encoded and movements become automatized, PPC–M1 connectivity returns to baseline. PMID:22442568

  11. Valeriana officinalis Root Extract Modulates Cortical Excitatory Circuits in Humans.

    PubMed

    Mineo, Ludovico; Concerto, Carmen; Patel, Dhaval; Mayorga, Tyrone; Paula, Michael; Chusid, Eileen; Aguglia, Eugenio; Battaglia, Fortunato

    2017-01-01

    Valeriana officinalis extract (VE) is a popular herbal medicine used for the treatment of anxiety and sleep disorders. Although the anxiolytic and sedative effects are mainly attributed to the modulation of GABA-ergic transmission, the mechanism of action has not been fully investigated in humans. Noninvasive brain stimulation protocols can be used to elucidate the mechanisms of action of psychoactive substances at the cortical level in humans. In this study, we investigated the effects of a single dose of VE on cortical excitability as assessed with transcranial magnetic stimulation (TMS). Fifteen healthy volunteers participated in a double-blind, randomized, cross-over, placebo-controlled study. Subjects were required to take either 900 mg of VE (valerenic acid 0.8%) or placebo (an equal dose of vitamin E). Motor cortex excitability was studied by single and paired TMS before and at 1 h and 6 h after the oral administration. Cortical excitability was assessed using different TMS parameters: resting motor threshold, motor-evoked potential amplitude, cortical silent period, short-interval intracortical inhibition, and intracortical facilitation. Furthermore, we assessed sensorimotor integration by short-latency and long-latency afferent inhibition. We found a significant reduction in ICF, without any significant changes in other TMS measures of motor cortex excitability. The amount of ICF returned to baseline value 6 h after the intake of the VE. A single oral dose of VE modulates intracortical facilitatory circuits. Our results in healthy subjects could be predictive markers of treatment response in patients and further support the use of pharmaco-TMS to investigate the neuropsychiatric effects of herbal therapies in humans. © 2017 S. Karger AG, Basel.

  12. Interhemispheric gene expression differences in the cerebral cortex of humans and macaque monkeys.

    PubMed

    Muntané, Gerard; Santpere, Gabriel; Verendeev, Andrey; Seeley, William W; Jacobs, Bob; Hopkins, William D; Navarro, Arcadi; Sherwood, Chet C

    2017-09-01

    Handedness and language are two well-studied examples of asymmetrical brain function in humans. Approximately 90% of humans exhibit a right-hand preference, and the vast majority shows left-hemisphere dominance for language function. Although genetic models of human handedness and language have been proposed, the actual gene expression differences between cerebral hemispheres in humans remain to be fully defined. In the present study, gene expression profiles were examined in both hemispheres of three cortical regions involved in handedness and language in humans and their homologues in rhesus macaques: ventrolateral prefrontal cortex, posterior superior temporal cortex (STC), and primary motor cortex. Although the overall pattern of gene expression was very similar between hemispheres in both humans and macaques, weighted gene correlation network analysis revealed gene co-expression modules associated with hemisphere, which are different among the three cortical regions examined. Notably, a receptor-enriched gene module in STC was particularly associated with hemisphere and showed different expression levels between hemispheres only in humans.

  13. Improvement of spasticity following intermittent theta burst stimulation in multiple sclerosis is associated with modulation of resting-state functional connectivity of the primary motor cortices.

    PubMed

    Boutière, Clémence; Rey, Caroline; Zaaraoui, Wafaa; Le Troter, Arnaud; Rico, Audrey; Crespy, Lydie; Achard, Sophie; Reuter, Françoise; Pariollaud, Fanelly; Wirsich, Jonathan; Asquinazi, Patrick; Confort-Gouny, Sylviane; Soulier, Elisabeth; Guye, Maxime; Pelletier, Jean; Ranjeva, Jean-Philippe; Audoin, Bertrand

    2017-05-01

    Intermittent theta burst stimulation (iTBS) of the primary motor cortex improves transiently lower limbs spasticity in multiple sclerosis (MS). However, the cerebral mechanisms underlying this effect have never been investigated. To assess whether modulation of spasticity induced by iTBS is underlined by functional reorganization of the primary motor cortices. A total of 17 patients with MS suffering from lower limbs spasticity were randomized to receive real iTBS or sham iTBS during the first half of a 5-week indoor rehabilitation programme. Spasticity was assessed using the Modified Ashworth Scale and the Visual Analogue Scale at baseline, after the stimulation session and at the end of the rehabilitation programme. Resting-state functional magnetic resonance imaging (fMRI) was performed at the three time points, and brain functional networks topology was analysed using graph-theoretical approach. At the end of stimulation, improvement of spasticity was greater in real iTBS group than in sham iTBS group ( p = 0.026). iTBS had a significant effect on the balance of the connectivity degree between the stimulated and the homologous primary motor cortex ( p = 0.005). Changes in inter-hemispheric balance were correlated with improvement of spasticity (rho = 0.56, p = 0.015). This longitudinal resting-state fMRI study evidences that functional reorganization of the primary motor cortices may underlie the effect of iTBS on spasticity in MS.

  14. Occlusion of LTP-Like Plasticity in Human Primary Motor Cortex by Action Observation

    PubMed Central

    Lepage, Jean-François; Morin-Moncet, Olivier; Beaulé, Vincent; de Beaumont, Louis; Champoux, Francois; Théoret, Hugo

    2012-01-01

    Passive observation of motor actions induces cortical activity in the primary motor cortex (M1) of the onlooker, which could potentially contribute to motor learning. While recent studies report modulation of motor performance following action observation, the neurophysiological mechanism supporting these behavioral changes remains to be specifically defined. Here, we assessed whether the observation of a repetitive thumb movement – similarly to active motor practice – would inhibit subsequent long-term potentiation-like (LTP) plasticity induced by paired-associative stimulation (PAS). Before undergoing PAS, participants were asked to either 1) perform abductions of the right thumb as fast as possible; 2) passively observe someone else perform thumb abductions; or 3) passively observe a moving dot mimicking thumb movements. Motor evoked potentials (MEP) were used to assess cortical excitability before and after motor practice (or observation) and at two time points following PAS. Results show that, similarly to participants in the motor practice group, individuals observing repeated motor actions showed marked inhibition of PAS-induced LTP, while the “moving dot” group displayed the expected increase in MEP amplitude, despite differences in baseline excitability. Interestingly, LTP occlusion in the action-observation group was present even if no increase in cortical excitability or movement speed was observed following observation. These results suggest that mere observation of repeated hand actions is sufficient to induce LTP, despite the absence of motor learning. PMID:22701704

  15. A little more conversation, a little less action - candidate roles for motor cortex in speech perception

    PubMed Central

    Scott, Sophie K; McGettigan, Carolyn; Eisner, Frank

    2014-01-01

    The motor theory of speech perception assumes that activation of the motor system is essential in the perception of speech. However, deficits in speech perception and comprehension do not arise from damage that is restricted to the motor cortex, few functional imaging studies reveal activity in motor cortex during speech perception, and the motor cortex is strongly activated by many different sound categories. Here, we evaluate alternative roles for the motor cortex in spoken communication and suggest a specific role in sensorimotor processing in conversation. We argue that motor-cortex activation it is essential in joint speech, particularly for the timing of turn-taking. PMID:19277052

  16. Dissociable Frontostriatal White Matter Connectivity Underlies Reward and Motor Impulsivity

    PubMed Central

    Hampton, William H.; Alm, Kylie H.; Venkatraman, Vinod; Nugiel, Tehila; Olson, Ingrid R.

    2017-01-01

    Dysfunction of cognitive control often leads to impulsive decision-making in clinical and healthy populations. Some research suggests that a generalized cognitive control mechanism underlies the ability to modulate various types of impulsive behavior, while other evidence suggests different forms of impulsivity are dissociable, and rely on distinct neural circuitry. Past research consistently implicates several brain regions, such as the striatum and portions of the prefrontal cortex, in impulsive behavior. However the ventral and dorsal striatum are distinct in regards to function and connectivity. Nascent evidence points to the importance of frontostriatal white matter connectivity in impulsivity, yet it remains unclear whether particular tracts relate to different control behaviors. Here we used probabilistic tractography of diffusion imaging data to relate ventral and dorsal frontostriatal connectivity to reward and motor impulsivity measures. We found a double dissociation such that individual differences in white matter connectivity between the ventral striatum and the ventromedial prefrontal cortex and dorsolateral prefrontal cortex was associated with reward impulsivity, as measured by delay discounting, whereas connectivity between dorsal striatum and supplementary motor area was associated with motor impulsivity, but not vice versa. Our findings suggest that (a) structural connectivity can is associated with a large amount of behavioral variation; (b) different types of impulsivity are driven by dissociable frontostriatal neural circuitry. PMID:28189592

  17. Contribution of TMS and rTMS in the Understanding of the Pathophysiology and in the Treatment of Dystonia

    PubMed Central

    Lozeron, Pierre; Poujois, Aurélia; Richard, Alexandra; Masmoudi, Sana; Meppiel, Elodie; Woimant, France; Kubis, Nathalie

    2016-01-01

    Dystonias represent a heterogeneous group of movement disorders responsible for sustained muscle contraction, abnormal postures, and muscle twists. It can affect focal or segmental body parts or be generalized. Primary dystonia is the most common form of dystonia but it can also be secondary to metabolic or structural dysfunction, the consequence of a drug’s side-effect or of genetic origin. The pathophysiology is still not elucidated. Based on lesion studies, dystonia has been regarded as a pure motor dysfunction of the basal ganglia loop. However, basal ganglia lesions do not consistently produce dystonia and lesions outside basal ganglia can lead to dystonia; mild sensory abnormalities have been reported in the dystonic limb and imaging studies have shown involvement of multiple other brain regions including the cerebellum and the cerebral motor, premotor and sensorimotor cortices. Transcranial magnetic stimulation (TMS) is a non-invasive technique of brain stimulation with a magnetic field applied over the cortex allowing investigation of cortical excitability. Hyperexcitability of contralateral motor cortex has been suggested to be the trigger of focal dystonia. High or low frequency repetitive TMS (rTMS) can induce excitatory or inhibitory lasting effects beyond the time of stimulation and protocols have been developed having either a positive or a negative effect on cortical excitability and associated with prevention of cell death, γ-aminobutyric acid (GABA) interneurons mediated inhibition and brain-derived neurotrophic factor modulation. rTMS studies as a therapeutic strategy of dystonia have been conducted to modulate the cerebral areas involved in the disease. Especially, when applied on the contralateral (pre)-motor cortex or supplementary motor area of brains of small cohorts of dystonic patients, rTMS has shown a beneficial transient clinical effect in association with restrained motor cortex excitability. TMS is currently a valuable tool to improve our understanding of the pathophysiology of dystonia but large controlled studies using sham stimulation are still necessary to delineate the place of rTMS in the therapeutic strategy of dystonia. In this review, we will focus successively on the use of TMS as a tool to better understand pathophysiology, and the use of rTMS as a therapeutic strategy. PMID:27891079

  18. Electrical stimulation of the insular cortex as a novel target for the relief of refractory pain: An experimental approach in rodents.

    PubMed

    Dimov, Luiz Fabio; Toniolo, Elaine Flamia; Alonso-Matielo, Heloísa; de Andrade, Daniel Ciampi; Garcia-Larrea, Luis; Ballester, Gerson; Teixeira, Manoel Jacobsen; Dale, Camila Squarzoni

    2018-07-02

    Cortical electrical stimulation (CES) has shown to be an effective therapeutic alternative for neuropathic pain refractory to pharmacological treatment. The primary motor cortex(M1) was the main cortical target used in the vast majority of both invasive and non-invasive studies. Despite positive results M1-based approaches still fail to relieve pain in a significant proportion of individuals. It has been advocated that the direct stimulation of cortical areas directly implicated in the central integration of pain could increase the efficacy of analgesic brain stimulation. Here, we evaluated the behavioral effects of electrical stimulation of the insular cortex (ESI) on pain sensitivity in an experimental rat model of peripheral neuropathy, and have described the pathways involved. Animals underwent chronic constriction of the sciatic nerve in the right hind limb and had concentric electrodes implanted in the posterior dysranular insular cortex. Mechanical nociception responses were evaluated before and at the end of a 15-min session of ESI (60Hz, 210μs, 1V). ESI reversed mechanical hypersensitivity in the paw contralateral to the brain hemisphere stimulated, without inducing motor impairment in the open-field test. Pharmacological blockade of μ-opioid (MOR) or type 1-cannabinoid receptors (CB1R) abolished ESI-induced antinociceptive effects. Evaluation of CB1R and MOR spatial expression demonstrated differential modulation of CB1R and MOR in the periaqueductal gray matter (PAG) of ESI-treated rats in sub-areas involved in pain processing/modulation. These results indicate that ESI induces antinociception by functionally modulating opioid and cannabinoid systems in the PAG pain circuitry in rats with experimentally induced neuropathic pain. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. L-Dopa Modulates Functional Connectivity in Striatal Cognitive and Motor Networks: A Double-Blind Placebo-Controlled Study

    PubMed Central

    Kelly, Clare; de Zubicaray, Greig; Di Martino, Adriana; Copland, David A.; Reiss, Philip T.; Klein, Donald F.; Castellanos, F. Xavier; Milham, Michael P.; McMahon, Katie

    2010-01-01

    Functional connectivity (FC) analyses of resting-state fMRI data allow for the mapping of large-scale functional networks, and provide a novel means of examining the impact of dopaminergic challenge. Here, using a double-blind, placebo-controlled design, we examined the effect of L-dopa, a dopamine precursor, on striatal resting-state FC in 19 healthy young adults. We examined the FC of 6 striatal regions-of-interest previously shown to elicit networks known to be associated with motivational, cognitive and motor subdivisions of the caudate and putamen (Di Martino et al., Cerebral Cortex, 2008). In addition to replicating the previously demonstrated patterns of striatal FC, we observed robust effects of L-dopa. Specifically, L-dopa increased FC in motor pathways connecting the putamen ROIs with the cerebellum and brainstem. While L-dopa also increased FC between the inferior ventral striatum and ventrolateral prefrontal cortex, it disrupted ventral striatal and dorsal caudate FC with the default mode network. These alterations in FC are consistent with studies that have demonstrated dopaminergic modulation of cognitive and motor striatal networks in healthy participants. Recent studies have demonstrated altered resting state FC in several conditions believed to be characterized by abnormal dopaminergic neurotransmission. Our findings suggest that the application of similar experimental pharmacological manipulations in such populations may further our understanding of the role of dopaminergic neurotransmission in those conditions. PMID:19494158

  20. Information-Processing Modules and Their Relative Modality Specificity

    ERIC Educational Resources Information Center

    Anderson, John R.; Qin, Yulin; Jung, Kwan-Jin; Carter, Cameron S.

    2007-01-01

    This research uses fMRI to understand the role of eight cortical regions in a relatively complex information-processing task. Modality of input (visual versus auditory) and modality of output (manual versus vocal) are manipulated. Two perceptual regions (auditory cortex and fusiform gyrus) only reflected perceptual encoding. Two motor regions were…

  1. Emotional facilitation of sensory processing in the visual cortex.

    PubMed

    Schupp, Harald T; Junghöfer, Markus; Weike, Almut I; Hamm, Alfons O

    2003-01-01

    A key function of emotion is the preparation for action. However, organization of successful behavioral strategies depends on efficient stimulus encoding. The present study tested the hypothesis that perceptual encoding in the visual cortex is modulated by the emotional significance of visual stimuli. Event-related brain potentials were measured while subjects viewed pleasant, neutral, and unpleasant pictures. Early selective encoding of pleasant and unpleasant images was associated with a posterior negativity, indicating primary sources of activation in the visual cortex. The study also replicated previous findings in that affective cues also elicited enlarged late positive potentials, indexing increased stimulus relevance at higher-order stages of stimulus processing. These results support the hypothesis that sensory encoding of affective stimuli is facilitated implicitly by natural selective attention. Thus, the affect system not only modulates motor output (i.e., favoring approach or avoidance dispositions), but already operates at an early level of sensory encoding.

  2. Cortical Regulation of Striatal Medium Spiny Neuron Dendritic Remodeling in Parkinsonism: Modulation of Glutamate Release Reverses Dopamine Depletion–Induced Dendritic Spine Loss

    PubMed Central

    Garcia, Bonnie G.; Neely, M. Diana

    2010-01-01

    Striatal medium spiny neurons (MSNs) receive glutamatergic afferents from the cerebral cortex and dopaminergic inputs from the substantia nigra (SN). Striatal dopamine loss decreases the number of MSN dendritic spines. This loss of spines has been suggested to reflect the removal of tonic dopamine inhibitory control over corticostriatal glutamatergic drive, with increased glutamate release culminating in MSN spine loss. We tested this hypothesis in two ways. We first determined in vivo if decortication reverses or prevents dopamine depletion–induced spine loss by placing motor cortex lesions 4 weeks after, or at the time of, 6-hydroxydopamine lesions of the SN. Animals were sacrificed 4 weeks after cortical lesions. Motor cortex lesions significantly reversed the loss of MSN spines elicited by dopamine denervation; a similar effect was observed in the prevention experiment. We then determined if modulating glutamate release in organotypic cocultures prevented spine loss. Treatment of the cultures with the mGluR2/3 agonist LY379268 to suppress corticostriatal glutamate release completely blocked spine loss in dopamine-denervated cultures. These studies provide the first evidence to show that MSN spine loss associated with parkinsonism can be reversed and point to suppression of corticostriatal glutamate release as a means of slowing progression in Parkinson's disease. PMID:20118184

  3. Motor cortex is required for learning but not for executing a motor skill.

    PubMed

    Kawai, Risa; Markman, Timothy; Poddar, Rajesh; Ko, Raymond; Fantana, Antoniu L; Dhawale, Ashesh K; Kampff, Adam R; Ölveczky, Bence P

    2015-05-06

    Motor cortex is widely believed to underlie the acquisition and execution of motor skills, but its contributions to these processes are not fully understood. One reason is that studies on motor skills often conflate motor cortex's established role in dexterous control with roles in learning and producing task-specific motor sequences. To dissociate these aspects, we developed a motor task for rats that trains spatiotemporally precise movement patterns without requirements for dexterity. Remarkably, motor cortex lesions had no discernible effect on the acquired skills, which were expressed in their distinct pre-lesion forms on the very first day of post-lesion training. Motor cortex lesions prior to training, however, rendered rats unable to acquire the stereotyped motor sequences required for the task. These results suggest a remarkable capacity of subcortical motor circuits to execute learned skills and a previously unappreciated role for motor cortex in "tutoring" these circuits during learning. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Memory-guided drawing training increases Granger causal influences from the perirhinal cortex to V1 in the blind

    PubMed Central

    Cacciamani, Laura; Likova, Lora T.

    2017-01-01

    The perirhinal cortex (PRC) is a medial temporal lobe structure that has been implicated in not only visual memory in the sighted, but also tactile memory in the blind (Cacciamani & Likova, 2016). It has been proposed that, in the blind, the PRC may contribute to modulation of tactile memory responses that emerge in low-level “visual” area V1 as a result of training-induced cortical reorganization (Likova, 2012; 2015). While some studies in the sighted have indicated that the PRC is indeed structurally and functionally connected to the visual cortex (Clavagnier et al., 2004; Peterson et al., 2012), the PRC’s direct modulation of V1 is unknown—particularly in those who lack the visual input that typically stimulates this region. In the present study, we tested Likova’s PRC modulation hypothesis; specifically, we used fMRI to assess the PRC’s Granger causal influence on V1 activation in the blind during a tactile memory task. To do so, we trained congenital and acquired blind participants on a unique memory-guided drawing technique previously shown to result in V1 reorganization towards tactile memory representations (Likova, 2012). The tasks (20s each) included: tactile exploration of raised line drawings of faces and objects, tactile memory retrieval via drawing, and a scribble motor/memory control. FMRI before and after a week of the Cognitive-Kinesthetic training on these tasks revealed a significant increase in PRC-to-V1 Granger causality from pre- to post-training during the memory drawing task, but not during the motor/memory control. This increase in causal connectivity indicates that the training strengthened the top-down modulation of visual cortex from the PRC. This is the first study to demonstrate enhanced directed functional connectivity from the PRC to the visual cortex in the blind, implicating the PRC as a potential source of the reorganization towards tactile representations that occurs in V1 in the blind brain (Likova, 2012). PMID:28347878

  5. Memory-guided drawing training increases Granger causal influences from the perirhinal cortex to V1 in the blind.

    PubMed

    Cacciamani, Laura; Likova, Lora T

    2017-05-01

    The perirhinal cortex (PRC) is a medial temporal lobe structure that has been implicated in not only visual memory in the sighted, but also tactile memory in the blind (Cacciamani & Likova, 2016). It has been proposed that, in the blind, the PRC may contribute to modulation of tactile memory responses that emerge in low-level "visual" area V1 as a result of training-induced cortical reorganization (Likova, 2012, 2015). While some studies in the sighted have indicated that the PRC is indeed structurally and functionally connected to the visual cortex (Clavagnier, Falchier, & Kennedy, 2004; Peterson, Cacciamani, Barense, & Scalf, 2012), the PRC's direct modulation of V1 is unknown-particularly in those who lack the visual input that typically stimulates this region. In the present study, we tested Likova's PRC modulation hypothesis; specifically, we used fMRI to assess the PRC's Granger causal influence on V1 activation in the blind during a tactile memory task. To do so, we trained congenital and acquired blind participants on a unique memory-guided drawing technique previously shown to result in V1 reorganization towards tactile memory representations (Likova, 2012). The tasks (20s each) included: tactile exploration of raised line drawings of faces and objects, tactile memory retrieval via drawing, and a scribble motor/memory control. FMRI before and after a week of the Cognitive-Kinesthetic training on these tasks revealed a significant increase in PRC-to-V1 Granger causality from pre- to post-training during the memory drawing task, but not during the motor/memory control. This increase in causal connectivity indicates that the training strengthened the top-down modulation of visual cortex from the PRC. This is the first study to demonstrate enhanced directed functional connectivity from the PRC to the visual cortex in the blind, implicating the PRC as a potential source of the reorganization towards tactile representations that occurs in V1 in the blind brain (Likova, 2012). Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Excitability of the motor system: A transcranial magnetic stimulation study on singing and speaking.

    PubMed

    Royal, Isabelle; Lidji, Pascale; Théoret, Hugo; Russo, Frank A; Peretz, Isabelle

    2015-08-01

    The perception of movements is associated with increased activity in the human motor cortex, which in turn may underlie our ability to understand actions, as it may be implicated in the recognition, understanding and imitation of actions. Here, we investigated the involvement and lateralization of the primary motor cortex (M1) in the perception of singing and speech. Transcranial magnetic stimulation (TMS) was applied independently for both hemispheres over the mouth representation of the motor cortex in healthy participants while they watched 4-s audiovisual excerpts of singers producing a 2-note ascending interval (singing condition) or 4-s audiovisual excerpts of a person explaining a proverb (speech condition). Subjects were instructed to determine whether a sung interval/written proverb, matched a written interval/proverb. During both tasks, motor evoked potentials (MEPs) were recorded from the contralateral mouth muscle (orbicularis oris) of the stimulated motor cortex compared to a control task. Moreover, to investigate the time course of motor activation, TMS pulses were randomly delivered at 7 different time points (ranging from 500 to 3500 ms after stimulus onset). Results show that stimulation of the right hemisphere had a similar effect on the MEPs for both the singing and speech perception tasks, whereas stimulation of the left hemisphere significantly differed in the speech perception task compared to the singing perception task. Furthermore, analysis of the MEPs in the singing task revealed that they decreased for small musical intervals, but increased for large musical intervals, regardless of which hemisphere was stimulated. Overall, these results suggest a dissociation between the lateralization of M1 activity for speech perception and for singing perception, and that in the latter case its activity can be modulated by musical parameters such as the size of a musical interval. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. A Map of Anticipatory Activity in Mouse Motor Cortex.

    PubMed

    Chen, Tsai-Wen; Li, Nuo; Daie, Kayvon; Svoboda, Karel

    2017-05-17

    Activity in the mouse anterior lateral motor cortex (ALM) instructs directional movements, often seconds before movement initiation. It is unknown whether this preparatory activity is localized to ALM or widely distributed within motor cortex. Here we imaged activity across motor cortex while mice performed a whisker-based object localization task with a delayed, directional licking response. During tactile sensation and the delay epoch, object location was represented in motor cortex areas that are medial and posterior relative to ALM, including vibrissal motor cortex. Preparatory activity appeared first in deep layers of ALM, seconds before the behavioral response, and remained localized to ALM until the behavioral response. Later, widely distributed neurons represented the outcome of the trial. Cortical area was more predictive of neuronal selectivity than laminar location or axonal projection target. Motor cortex therefore represents sensory, motor, and outcome information in a spatially organized manner. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Role of motor cortex NMDA receptors in learning-dependent synaptic plasticity of behaving mice

    PubMed Central

    Hasan, Mazahir T.; Hernández-González, Samuel; Dogbevia, Godwin; Treviño, Mario; Bertocchi, Ilaria; Gruart, Agnès; Delgado-García, José M.

    2013-01-01

    The primary motor cortex has an important role in the precise execution of learned motor responses. During motor learning, synaptic efficacy between sensory and primary motor cortical neurons is enhanced, possibly involving long-term potentiation and N-methyl-D-aspartate (NMDA)-specific glutamate receptor function. To investigate whether NMDA receptor in the primary motor cortex can act as a coincidence detector for activity-dependent changes in synaptic strength and associative learning, here we generate mice with deletion of the Grin1 gene, encoding the essential NMDA receptor subunit 1 (GluN1), specifically in the primary motor cortex. The loss of NMDA receptor function impairs primary motor cortex long-term potentiation in vivo. Importantly, it impairs the synaptic efficacy between the primary somatosensory and primary motor cortices and significantly reduces classically conditioned eyeblink responses. Furthermore, compared with wild-type littermates, mice lacking primary motor cortex show slower learning in Skinner-box tasks. Thus, primary motor cortex NMDA receptors are necessary for activity-dependent synaptic strengthening and associative learning. PMID:23978820

  9. Forelimb training drives transient map reorganization in ipsilateral motor cortex

    PubMed Central

    Pruitt, David T.; Schmid, Ariel N.; Danaphongse, Tanya T.; Flanagan, Kate E.; Morrison, Robert A.; Kilgard, Michael P.; Rennaker, Robert L.; Hays, Seth A.

    2016-01-01

    Skilled motor training results in reorganization of contralateral motor cortex movement representations. The ipsilateral motor cortex is believed to play a role in skilled motor control, but little is known about how training influences reorganization of ipsilateral motor representations of the trained limb. To determine whether training results in reorganization of ipsilateral motor cortex maps, rats were trained to perform the isometric pull task, an automated motor task that requires skilled forelimb use. After either 3 or 6 months of training, intracortical microstimulation (ICMS) mapping was performed to document motor representations of the trained forelimb in the hemisphere ipsilateral to that limb. Motor training for 3 months resulted in a robust expansion of right forelimb representation in the right motor cortex, demonstrating that skilled motor training drives map plasticity ipsilateral to the trained limb. After 6 months of training, the right forelimb representation in the right motor cortex was significantly smaller than the representation observed in rats trained for 3 months and similar to untrained controls, consistent with a normalization of motor cortex maps. Forelimb map area was not correlated with performance on the trained task, suggesting that task performance is maintained despite normalization of cortical maps. This study provides new insights into how the ipsilateral cortex changes in response to skilled learning and may inform rehabilitative strategies to enhance cortical plasticity to support recovery after brain injury. PMID:27392641

  10. Forelimb training drives transient map reorganization in ipsilateral motor cortex.

    PubMed

    Pruitt, David T; Schmid, Ariel N; Danaphongse, Tanya T; Flanagan, Kate E; Morrison, Robert A; Kilgard, Michael P; Rennaker, Robert L; Hays, Seth A

    2016-10-15

    Skilled motor training results in reorganization of contralateral motor cortex movement representations. The ipsilateral motor cortex is believed to play a role in skilled motor control, but little is known about how training influences reorganization of ipsilateral motor representations of the trained limb. To determine whether training results in reorganization of ipsilateral motor cortex maps, rats were trained to perform the isometric pull task, an automated motor task that requires skilled forelimb use. After either 3 or 6 months of training, intracortical microstimulation (ICMS) mapping was performed to document motor representations of the trained forelimb in the hemisphere ipsilateral to that limb. Motor training for 3 months resulted in a robust expansion of right forelimb representation in the right motor cortex, demonstrating that skilled motor training drives map plasticity ipsilateral to the trained limb. After 6 months of training, the right forelimb representation in the right motor cortex was significantly smaller than the representation observed in rats trained for 3 months and similar to untrained controls, consistent with a normalization of motor cortex maps. Forelimb map area was not correlated with performance on the trained task, suggesting that task performance is maintained despite normalization of cortical maps. This study provides new insights into how the ipsilateral cortex changes in response to skilled learning and may inform rehabilitative strategies to enhance cortical plasticity to support recovery after brain injury. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Critical Involvement of the Motor Cortex in the Pathophysiology and Treatment of Parkinson’s Disease

    PubMed Central

    Lindenbach, David; Bishop, Christopher

    2013-01-01

    This review examines the involvement of the motor cortex in Parkinson’s disease (PD), a debilitating movement disorder typified by degeneration of dopamine cells of the substantia nigra. While much of PD research has focused on the caudate/putamen, many aspects of motor cortex function are abnormal in PD patients and in animal models of PD, implicating motor cortex involvement in disease symptoms and their treatment. Herein, we discuss several lines of evidence to support this hypothesis. Dopamine depletion alters regional metabolism in the motor cortex and also reduces interneuron activity, causing a breakdown in intracortical inhibition. This leads to functional reorganization of motor maps and excessive corticostriatal synchrony when movement is initiated. Recent work suggests that electrical stimulation of the motor cortex provides a clinical benefit for PD patients. Based on extant research, we identify a number of unanswered questions regarding the motor cortex in PD and argue that a better understanding of the contribution of the motor cortex to PD symptoms will facilitate the development of novel therapeutic approaches. PMID:24113323

  12. Functional connectivity and information flow of the respiratory neural network in chronic obstructive pulmonary disease.

    PubMed

    Yu, Lianchun; De Mazancourt, Marine; Hess, Agathe; Ashadi, Fakhrul R; Klein, Isabelle; Mal, Hervé; Courbage, Maurice; Mangin, Laurence

    2016-08-01

    Breathing involves a complex interplay between the brainstem automatic network and cortical voluntary command. How these brain regions communicate at rest or during inspiratory loading is unknown. This issue is crucial for several reasons: (i) increased respiratory loading is a major feature of several respiratory diseases, (ii) failure of the voluntary motor and cortical sensory processing drives is among the mechanisms that precede acute respiratory failure, (iii) several cerebral structures involved in responding to inspiratory loading participate in the perception of dyspnea, a distressing symptom in many disease. We studied functional connectivity and Granger causality of the respiratory network in controls and patients with chronic obstructive pulmonary disease (COPD), at rest and during inspiratory loading. Compared with those of controls, the motor cortex area of patients exhibited decreased connectivity with their contralateral counterparts and no connectivity with the brainstem. In the patients, the information flow was reversed at rest with the source of the network shifted from the medulla towards the motor cortex. During inspiratory loading, the system was overwhelmed and the motor cortex became the sink of the network. This major finding may help to understand why some patients with COPD are prone to acute respiratory failure. Network connectivity and causality were related to lung function and illness severity. We validated our connectivity and causality results with a mathematical model of neural network. Our findings suggest a new therapeutic strategy involving the modulation of brain activity to increase motor cortex functional connectivity and improve respiratory muscles performance in patients. Hum Brain Mapp 37:2736-2754, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

  13. Voronoi-based spatial analysis reveals selective interneuron changes in the cortex of FALS mice.

    PubMed

    Minciacchi, Diego; Kassa, Roman M; Del Tongo, Claudia; Mariotti, Raffaella; Bentivoglio, Marina

    2009-01-01

    The neurodegenerative disease amyotrophic lateral sclerosis affects lower motoneurons and corticospinal cells. Mice expressing human mutant superoxide dismutase (SOD)1 provide widely investigated models of the familial form of disease, but information on cortical changes in these mice is still limited. We here analyzed the spatial organization of interneurons characterized by parvalbumin immunoreactivity in the motor, somatosensory, and visual cortical areas of SOD1(G93A) mice. Cell number and sociological spatial behavior were assessed by digital charts of cell location in cortical samples, cell counts, and generation of two-dimensional Voronoi diagrams. In end-stage SOD1-mutant mice, an increase of parvalbumin-containing cortical interneurons was found in the motor and somatosensory areas (about 35% and 20%, respectively) with respect to wild-type littermates. Changes in cell spatial distribution, as documented by Voronoi-derived coefficients of variation, indicated increased tendency of parvalbumin cells to aggregate into clusters in the same areas of the SOD1-mutant cortex. Counts and coefficients of variation of parvalbumin cells in the visual cortex gave instead similar results in SOD1-mutant and wild-type mice. Analyses of motor and somatosensory areas in presymptomatic SOD1-mutant mice provided findings very similar to those obtained at end-stage, indicating early changes of interneurons in these cortical areas during the pathology. Altogether the data reveal in the SOD1-mutant mouse cortex an altered architectonic pattern of interneurons, which selectively affects areas involved in motor control. The findings, which can be interpreted as pathogenic factors or early disease-related adaptations, point to changes in the cortical regulation and modulation of the motor circuit during motoneuron disease.

  14. Interplay between glutamatergic and GABAergic neurotransmission alterations in cognitive and motor impairment in minimal hepatic encephalopathy.

    PubMed

    Llansola, Marta; Montoliu, Carmina; Agusti, Ana; Hernandez-Rabaza, Vicente; Cabrera-Pastor, Andrea; Gomez-Gimenez, Belen; Malaguarnera, Michele; Dadsetan, Sherry; Belghiti, Majedeline; Garcia-Garcia, Raquel; Balzano, Tiziano; Taoro, Lucas; Felipo, Vicente

    2015-09-01

    The cognitive and motor alterations in hepatic encephalopathy (HE) are the final result of altered neurotransmission and communication between neurons in neuronal networks and circuits. Different neurotransmitter systems cooperate to modulate cognitive and motor function, with a main role for glutamatergic and GABAergic neurotransmission in different brain areas and neuronal circuits. There is an interplay between glutamatergic and GABAergic neurotransmission alterations in cognitive and motor impairment in HE. This interplay may occur: (a) in different brain areas involved in specific neuronal circuits; (b) in the same brain area through cross-modulation of glutamatergic and GABAergic neurotransmission. We will summarize some examples of the (1) interplay between glutamatergic and GABAergic neurotransmission alterations in different areas in the basal ganglia-thalamus-cortex circuit in the motor alterations in minimal hepatic encephalopathy (MHE); (2) interplay between glutamatergic and GABAergic neurotransmission alterations in cerebellum in the impairment of cognitive function in MHE through altered function of the glutamate-nitric oxide-cGMP pathway. We will also comment the therapeutic implications of the above studies and the utility of modulators of glutamate and GABA receptors to restore cognitive and motor function in rats with hyperammonemia and hepatic encephalopathy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Motor cortex is required for learning but not executing a motor skill

    PubMed Central

    Kawai, Risa; Markman, Timothy; Poddar, Rajesh; Ko, Raymond; Fantana, Antoniu; Dhawale, Ashesh; Kampff, Adam R.; Ölveczky, Bence P.

    2018-01-01

    Motor cortex is widely believed to underlie the acquisition and execution of motor skills, yet its contributions to these processes are not fully understood. One reason is that studies on motor skills often conflate motor cortex’s established role in dexterous control with roles in learning and producing task-specific motor sequences. To dissociate these aspects, we developed a motor task for rats that trains spatiotemporally precise movement patterns without requirements for dexterity. Remarkably, motor cortex lesions had no discernible effect on the acquired skills, which were expressed in their distinct pre-lesion forms on the very first day of post-lesion training. Motor cortex lesions prior to training, however, rendered rats unable to acquire the stereotyped motor sequences required for the task. These results suggest a remarkable capacity of subcortical motor circuits to execute learned skills and a previously unappreciated role for motor cortex in ‘tutoring’ these circuits during learning. PMID:25892304

  16. The neurochemical basis of the contextual interference effect.

    PubMed

    Chalavi, Sima; Pauwels, Lisa; Heise, Kirstin-Friederike; Zivari Adab, Hamed; Maes, Celine; Puts, Nicolaas A J; Edden, Richard A E; Swinnen, Stephan P

    2018-06-01

    Efficient practice organization maximizes learning outcome. Although randomization of practice as compared to blocked practice damages training performance, it boosts retention performance, an effect called contextual interference. Motor learning modulates the GABAergic (gamma-aminobutyric acid) system within the sensorimotor cortex (SM); however, it is unclear whether different practice regimes differentially modulate this system and whether this is impacted by aging. Young and older participants were trained on 3 variations of a visuomotor task over 3 days, following either blocked or random practice schedule and retested 6 days later. Using magnetic resonance spectroscopy, SM and occipital cortex GABA+ levels were measured before and after training during the first and last training days. We found that (1) behavioral data confirmed the contextual interference effects, (2) within-day occipital cortex GABA+ levels decreased in random and increased in blocked group. This effect was more pronounced in older adults; and (3) baseline SM GABA+ levels predicted initial performance. These findings indicate a differential modulation of GABA levels across practice groups that is amplified by aging. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Viewing speech modulates activity in the left SI mouth cortex.

    PubMed

    Möttönen, Riikka; Järveläinen, Juha; Sams, Mikko; Hari, Riitta

    2005-02-01

    The ability to internally simulate other persons' actions is important for social interaction. In monkeys, neurons in the premotor cortex are activated both when the monkey performs mouth or hand actions and when it views or listens to actions made by others. Neuronal circuits with similar "mirror-neuron" properties probably exist in the human Broca's area and primary motor cortex. Viewing other person's hand actions also modulates activity in the primary somatosensory cortex SI, suggesting that the SI cortex is related to the human mirror-neuron system. To study the selectivity of the SI activation during action viewing, we stimulated the lower lip (with tactile pulses) and the median nerves (with electric pulses) in eight subjects to activate their SI mouth and hand cortices while the subjects either rested, listened to other person's speech, viewed her articulatory gestures, or executed mouth movements. The 55-ms SI responses to lip stimuli were enhanced by 16% (P<0.01) in the left hemisphere during speech viewing whereas listening to speech did not modulate these responses. The 35-ms responses to median-nerve stimulation remained stable during speech viewing and listening. Own mouth movements suppressed responses to lip stimuli bilaterally by 74% (P<0.001), without any effect on responses to median-nerve stimuli. Our findings show that viewing another person's articulatory gestures activates the left SI cortex in a somatotopic manner. The results provide further evidence for the view that SI is involved in "mirroring" of other persons' actions.

  18. You can count on the motor cortex: Finger counting habits modulate motor cortex activation evoked by numbers

    PubMed Central

    Tschentscher, Nadja; Hauk, Olaf; Fischer, Martin H.; Pulvermüller, Friedemann

    2012-01-01

    The embodied cognition framework suggests that neural systems for perception and action are engaged during higher cognitive processes. In an event-related fMRI study, we tested this claim for the abstract domain of numerical symbol processing: is the human cortical motor system part of the representation of numbers, and is organization of numerical knowledge influenced by individual finger counting habits? Developmental studies suggest a link between numerals and finger counting habits due to the acquisition of numerical skills through finger counting in childhood. In the present study, digits 1 to 9 and the corresponding number words were presented visually to adults with different finger counting habits, i.e. left- and right-starters who reported that they usually start counting small numbers with their left and right hand, respectively. Despite the absence of overt hand movements, the hemisphere contralateral to the hand used for counting small numbers was activated when small numbers were presented. The correspondence between finger counting habits and hemispheric motor activation is consistent with an intrinsic functional link between finger counting and number processing. PMID:22133748

  19. The auditory representation of speech sounds in human motor cortex

    PubMed Central

    Cheung, Connie; Hamilton, Liberty S; Johnson, Keith; Chang, Edward F

    2016-01-01

    In humans, listening to speech evokes neural responses in the motor cortex. This has been controversially interpreted as evidence that speech sounds are processed as articulatory gestures. However, it is unclear what information is actually encoded by such neural activity. We used high-density direct human cortical recordings while participants spoke and listened to speech sounds. Motor cortex neural patterns during listening were substantially different than during articulation of the same sounds. During listening, we observed neural activity in the superior and inferior regions of ventral motor cortex. During speaking, responses were distributed throughout somatotopic representations of speech articulators in motor cortex. The structure of responses in motor cortex during listening was organized along acoustic features similar to auditory cortex, rather than along articulatory features as during speaking. Motor cortex does not contain articulatory representations of perceived actions in speech, but rather, represents auditory vocal information. DOI: http://dx.doi.org/10.7554/eLife.12577.001 PMID:26943778

  20. Peripheral Nerve Injury in Developing Rats Reorganizes Representation Pattern in Motor Cortex

    NASA Astrophysics Data System (ADS)

    Donoghue, John P.; Sanes, Jerome N.

    1987-02-01

    We investigated the effect of neonatal nerve lesions on cerebral motor cortex organization by comparing the cortical motor representation of normal adult rats with adult rats that had one forelimb removed on the day of birth. Mapping of cerebral neocortex with electrical stimulation revealed an altered relationship between the motor cortex and the remaining muscles. Whereas distal forelimb movements are normally elicited at the lowest threshold in the motor cortex forelimb area, the same stimuli activated shoulder and trunk muscles in experimental animals. In addition, an expanded cortical representation of intact body parts was present and there was an absence of a distinct portion of motor cortex. These data demonstrate that representation patterns in motor cortex can be altered by peripheral nerve injury during development.

  1. Modulating Intrinsic Connectivity: Adjacent Subregions within Supplementary Motor Cortex, Dorsolateral Prefrontal Cortex, and Parietal Cortex Connect to Separate Functional Networks during Task and Also Connect during Rest

    PubMed Central

    Roth, Jennifer K.; Johnson, Marcia K.; Tokoglu, Fuyuze; Murphy, Isabella; Constable, R. Todd

    2014-01-01

    Supplementary motor area (SMA), the inferior frontal junction (IFJ), superior frontal junction (SFJ) and parietal cortex are active in many cognitive tasks. In a previous study, we found that subregions of each of these major areas were differentially active in component processes of executive function during working memory tasks. In the present study, each of these subregions was used as a seed in a whole brain functional connectivity analysis of working memory and resting state data. These regions show functional connectivity to different networks, thus supporting the parcellation of these major regions into functional subregions. Many regions showing significant connectivity during the working memory residual data (with task events regressed from the data) were also significantly connected during rest suggesting that these network connections to subregions within major regions of cortex are intrinsic. For some of these connections, task demands modulate activity in these intrinsic networks. Approximately half of the connections significant during task were significant during rest, indicating that some of the connections are intrinsic while others are recruited only in the service of the task. Furthermore, the network connections to traditional ‘task positive’ and ‘task negative’ (a.k.a ‘default mode’) regions shift from positive connectivity to negative connectivity depending on task demands. These findings demonstrate that such task-identified subregions are part of distinct networks, and that these networks have different patterns of connectivity for task as they do during rest, engaging connections both to task positive and task negative regions. These results have implications for understanding the parcellation of commonly active regions into more specific functional networks. PMID:24637793

  2. Motor Cortex Stimulation for Pain Relief: Do Corollary Discharges Play a Role?

    PubMed

    Brasil-Neto, Joaquim P

    2016-01-01

    Both invasive and non-invasive motor cortex stimulation techniques have been successfully employed in the treatment of chronic pain, but the precise mechanism of action of such treatments is not fully understood. It has been hypothesized that a mismatch of normal interaction between motor intention and sensory feedback may result in central pain. Sensory feedback may come from peripheral nerves, vision and also from corollary discharges originating from the motor cortex itself. Therefore, a possible mechanism of action of motor cortex stimulation might be corollary discharge reinforcement, which could counterbalance sensory feedback deficiency. In other instances, primary deficiency in the production of corollary discharges by the motor cortex might be the culprit and stimulation of cortical motor areas might then be beneficial by enhancing production of such discharges. Here we review evidence for a possible role of motor cortex corollary discharges upon both the pathophysiology and the response to motor cortex stimulation of different types of chronic pain. We further suggest that the right dorsolateral prefrontal cortex (DLPC), thought to constantly monitor incongruity between corollary discharges, vision and proprioception, might be an interesting target for non-invasive neuromodulation in cases of chronic neuropathic pain.

  3. Body stability and muscle and motor cortex activity during walking with wide stance

    PubMed Central

    Farrell, Brad J.; Bulgakova, Margarita A.; Beloozerova, Irina N.; Sirota, Mikhail G.

    2014-01-01

    Biomechanical and neural mechanisms of balance control during walking are still poorly understood. In this study, we examined the body dynamic stability, activity of limb muscles, and activity of motor cortex neurons [primarily pyramidal tract neurons (PTNs)] in the cat during unconstrained walking and walking with a wide base of support (wide-stance walking). By recording three-dimensional full-body kinematics we found for the first time that during unconstrained walking the cat is dynamically unstable in the forward direction during stride phases when only two diagonal limbs support the body. In contrast to standing, an increased lateral between-paw distance during walking dramatically decreased the cat's body dynamic stability in double-support phases and prompted the cat to spend more time in three-legged support phases. Muscles contributing to abduction-adduction actions had higher activity during stance, while flexor muscles had higher activity during swing of wide-stance walking. The overwhelming majority of neurons in layer V of the motor cortex, 82% and 83% in the forelimb and hindlimb representation areas, respectively, were active differently during wide-stance walking compared with unconstrained condition, most often by having a different depth of stride-related frequency modulation along with a different mean discharge rate and/or preferred activity phase. Upon transition from unconstrained to wide-stance walking, proximal limb-related neuronal groups subtly but statistically significantly shifted their activity toward the swing phase, the stride phase where most of body instability occurs during this task. The data suggest that the motor cortex participates in maintenance of body dynamic stability during locomotion. PMID:24790167

  4. Stimulation of the basolateral amygdala improves the acquisition of a motor skill.

    PubMed

    Bergado, Jorge A; Rojas, Yeneissy; Capdevila, Vladimir; González, Odalys; Almaguer-Melian, William

    2006-01-01

    We have previously shown that the stimulation of limbic structures related to affective life such as the amygdale can improve and reinforce neural plastic processes related to hippocampus-dependent forms of explicit memory, as spatial memory and LTP. We now assessed whether this effect is restricted to the mentioned structure and memory type, or represents a more general form of modulatory influence. Young, male Sprague Dawley rats were implanted stereotactically with one electrode in the basolateral amygdala (BLA) and trained to acquire a motor skill using their right anterior limb. A group of animals received 3 trains of 15 impulses at the BLA 15 minutes after each daily training session. A second group of implanted animals was handled in the same way, but not stimulated, while a third group was not implanted. After reaching the training criterion the left motor cortex was mapped by the observation of the movements induced by stimuli applied in discrete points of the cortex. Cortical representation of the anterior limb was increased in all trained animals, showing that the motor cortex is involved in the acquisition of the new skill. Animals receiving stimulation of the BLA showed similar cortical changes, but learned faster than non-stimulated controls. Reinforcement of neural plasticity by the activation of the amygdala is not restricted to hippocampus-dependent explicit memory, but it might represent a universal mechanism to modulate plasticity.

  5. Dissociable frontostriatal white matter connectivity underlies reward and motor impulsivity.

    PubMed

    Hampton, William H; Alm, Kylie H; Venkatraman, Vinod; Nugiel, Tehila; Olson, Ingrid R

    2017-04-15

    Dysfunction of cognitive control often leads to impulsive decision-making in clinical and healthy populations. Some research suggests that a generalized cognitive control mechanism underlies the ability to modulate various types of impulsive behavior, while other evidence suggests different forms of impulsivity are dissociable, and rely on distinct neural circuitry. Past research consistently implicates several brain regions, such as the striatum and portions of the prefrontal cortex, in impulsive behavior. However the ventral and dorsal striatum are distinct in regards to function and connectivity. Nascent evidence points to the importance of frontostriatal white matter connectivity in impulsivity, yet it remains unclear whether particular tracts relate to different control behaviors. Here we used probabilistic tractography of diffusion imaging data to relate ventral and dorsal frontostriatal connectivity to reward and motor impulsivity measures. We found a double dissociation such that individual differences in white matter connectivity between the ventral striatum and the ventromedial prefrontal cortex and dorsolateral prefrontal cortex was associated with reward impulsivity, as measured by delay discounting, whereas connectivity between dorsal striatum and supplementary motor area was associated with motor impulsivity, but not vice versa. Our findings suggest that (a) structural connectivity can is associated with a large amount of behavioral variation; (b) different types of impulsivity are driven by dissociable frontostriatal neural circuitry. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Sensory tricks and brain excitability in cervical dystonia: a transcranial magnetic stimulation study.

    PubMed

    Amadio, Stefano; Houdayer, Elise; Bianchi, Francesca; Tesfaghebriel Tekle, Habtom; Urban, Ivan Pietro; Butera, Calogera; Guerriero, Roberta; Cursi, Marco; Leocani, Letizia; Comi, Giancarlo; Del Carro, Ubaldo

    2014-08-01

    Sensory tricks such as touching the face with fingertips often improve cervical dystonia [CD]. This study is to determine whether sensory tricks modulate motor cortex excitability, assessed by paired-pulse transcranial magnetic stimulation [p-pTMS]. Eight patients with rotational CD underwent p-pTMS, at rest and when the sensory trick was applied. To test intracortical inhibition [ICI] and facilitation [ICF], the amplitude ratio between conditioned and unconditioned cortical motor evoked potentials was measured at several interstimulus intervals (ISI 1, 3, 15, and 20 ms) and compared with controls mimicking patients' sensory tricks. At rest, a significant ICF enhancement was found at ISIs 15 through 20 in patients compared with controls, whereas no significant ICI changes were observed. Sensory tricks significantly reduced the abnormal ICF in patients and did not induce any change in controls. In our CD patients, sensory tricks seem to improve dystonia through an inhibitory effect on motor cortex excitability. © 2014 International Parkinson and Movement Disorder Society.

  7. Cortical inhibition and excitation by bilateral transcranial alternating current stimulation.

    PubMed

    Cancelli, Andrea; Cottone, Carlo; Zito, Giancarlo; Di Giorgio, Marina; Pasqualetti, Patrizio; Tecchio, Franca

    2015-01-01

    Transcranial electric stimulations (tES) with amplitude-modulated currents are promising tools to enhance neuromodulation effects. It is essential to select the correct cortical targets and inhibitory/excitatory protocols to reverse changes in specific networks. We aimed at assessing the dependence of cortical excitability changes on the current amplitude of 20 Hz transcranial alternating current stimulation (tACS) over the bilateral primary motor cortex. We chose two amplitude ranges of the stimulations, around 25 μA/cm2 and 63 μA/cm2 from peak to peak, with three values (at steps of about 2.5%) around each, to generate, respectively, inhibitory and excitatory effects of the primary motor cortex. We checked such changes online through transcranial magnetic stimulation (TMS)-induced motor evoked potentials (MEPs). Cortical excitability changes depended upon current density (p = 0.001). Low current densities decreased MEP amplitudes (inhibition) while high current densities increased them (excitation). tACS targeting bilateral homologous cortical areas can induce online inhibition or excitation as a function of the current density.

  8. Trunk Robot Rehabilitation Training with Active Stepping Reorganizes and Enriches Trunk Motor Cortex Representations in Spinal Transected Rats

    PubMed Central

    Oza, Chintan S.

    2015-01-01

    Trunk motor control is crucial for postural stability and propulsion after low thoracic spinal cord injury (SCI) in animals and humans. Robotic rehabilitation aimed at trunk shows promise in SCI animal models and patients. However, little is known about the effect of SCI and robot rehabilitation of trunk on cortical motor representations. We previously showed reorganization of trunk motor cortex after adult SCI. Non-stepping training also exacerbated some SCI-driven plastic changes. Here we examine effects of robot rehabilitation that promotes recovery of hindlimb weight support functions on trunk motor cortex representations. Adult rats spinal transected as neonates (NTX rats) at the T9/10 level significantly improve function with our robot rehabilitation paradigm, whereas treadmill-only trained do not. We used intracortical microstimulation to map motor cortex in two NTX groups: (1) treadmill trained (control group); and (2) robot-assisted treadmill trained (improved function group). We found significant robot rehabilitation-driven changes in motor cortex: (1) caudal trunk motor areas expanded; (2) trunk coactivation at cortex sites increased; (3) richness of trunk cortex motor representations, as examined by cumulative entropy and mutual information for different trunk representations, increased; (4) trunk motor representations in the cortex moved toward more normal topography; and (5) trunk and forelimb motor representations that SCI-driven plasticity and compensations had caused to overlap were segregated. We conclude that effective robot rehabilitation training induces significant reorganization of trunk motor cortex and partially reverses some plastic changes that may be adaptive in non-stepping paraplegia after SCI. PMID:25948267

  9. How emotion context modulates unconscious goal activation during motor force exertion.

    PubMed

    Blakemore, Rebekah L; Neveu, Rémi; Vuilleumier, Patrik

    2017-02-01

    Priming participants with emotional or action-related concepts influences goal formation and motor force output during effort exertion tasks, even without awareness of priming information. However, little is known about neural processes underpinning how emotional cues interact with action (or inaction) goals to motivate (or demotivate) motor behaviour. In a novel functional neuroimaging paradigm, visible emotional images followed by subliminal action or inaction word primes were presented before participants performed a maximal force exertion. In neutral emotional contexts, maximum force was lower following inaction than action primes. However, arousing emotional images had interactive motivational effects on the motor system: Unpleasant images prior to inaction primes increased force output (enhanced effort exertion) relative to control primes, and engaged a motivation-related network involving ventral striatum, extended amygdala, as well as right inferior frontal cortex. Conversely, pleasant images presented before action (versus control) primes decreased force and activated regions of the default-mode network, including inferior parietal lobule and medial prefrontal cortex. These findings show that emotional context can determine how unconscious goal representations influence motivational processes and are transformed into actual motor output, without direct rewarding contingencies. Furthermore, they provide insight into altered motor behaviour in psychopathological disorders with dysfunctional motivational processes. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Dynamics of human subthalamic neuron phase-locking to motor and sensory cortical oscillations during movement.

    PubMed

    Lipski, Witold J; Wozny, Thomas A; Alhourani, Ahmad; Kondylis, Efstathios D; Turner, Robert S; Crammond, Donald J; Richardson, Robert Mark

    2017-09-01

    Coupled oscillatory activity recorded between sensorimotor regions of the basal ganglia-thalamocortical loop is thought to reflect information transfer relevant to movement. A neuronal firing-rate model of basal ganglia-thalamocortical circuitry, however, has dominated thinking about basal ganglia function for the past three decades, without knowledge of the relationship between basal ganglia single neuron firing and cortical population activity during movement itself. We recorded activity from 34 subthalamic nucleus (STN) neurons, simultaneously with cortical local field potentials and motor output, in 11 subjects with Parkinson's disease (PD) undergoing awake deep brain stimulator lead placement. STN firing demonstrated phase synchronization to both low- and high-beta-frequency cortical oscillations, and to the amplitude envelope of gamma oscillations, in motor cortex. We found that during movement, the magnitude of this synchronization was dynamically modulated in a phase-frequency-specific manner. Importantly, we found that phase synchronization was not correlated with changes in neuronal firing rate. Furthermore, we found that these relationships were not exclusive to motor cortex, because STN firing also demonstrated phase synchronization to both premotor and sensory cortex. The data indicate that models of basal ganglia function ultimately will need to account for the activity of populations of STN neurons that are bound in distinct functional networks with both motor and sensory cortices and code for movement parameters independent of changes in firing rate. NEW & NOTEWORTHY Current models of basal ganglia-thalamocortical networks do not adequately explain simple motor functions, let alone dysfunction in movement disorders. Our findings provide data that inform models of human basal ganglia function by demonstrating how movement is encoded by networks of subthalamic nucleus (STN) neurons via dynamic phase synchronization with cortex. The data also demonstrate, for the first time in humans, a mechanism through which the premotor and sensory cortices are functionally connected to the STN. Copyright © 2017 the American Physiological Society.

  11. High-Resolution 7T MR Imaging of the Motor Cortex in Amyotrophic Lateral Sclerosis.

    PubMed

    Cosottini, M; Donatelli, G; Costagli, M; Caldarazzo Ienco, E; Frosini, D; Pesaresi, I; Biagi, L; Siciliano, G; Tosetti, M

    2016-03-01

    Amyotrophic lateral sclerosis is a progressive motor neuron disorder that involves degeneration of both upper and lower motor neurons. In patients with amyotrophic lateral sclerosis, pathologic studies and ex vivo high-resolution MR imaging at ultra-high field strength revealed the co-localization of iron and activated microglia distributed in the deep layers of the primary motor cortex. The aims of the study were to measure the cortical thickness and evaluate the distribution of iron-related signal changes in the primary motor cortex of patients with amyotrophic lateral sclerosis as possible in vivo biomarkers of upper motor neuron impairment. Twenty-two patients with definite amyotrophic lateral sclerosis and 14 healthy subjects underwent a high-resolution 2D multiecho gradient-recalled sequence targeted on the primary motor cortex by using a 7T scanner. Image analysis consisted of the visual evaluation and quantitative measurement of signal intensity and cortical thickness of the primary motor cortex in patients and controls. Qualitative and quantitative MR imaging parameters were correlated with electrophysiologic and laboratory data and with clinical scores. Ultra-high field MR imaging revealed atrophy and signal hypointensity in the deep layers of the primary motor cortex of patients with amyotrophic lateral sclerosis with a diagnostic accuracy of 71%. Signal hypointensity of the deep layers of the primary motor cortex correlated with upper motor neuron impairment (r = -0.47; P < .001) and with disease progression rate (r = -0.60; P = .009). The combined high spatial resolution and sensitivity to paramagnetic substances of 7T MR imaging demonstrate in vivo signal changes of the cerebral motor cortex that resemble the distribution of activated microglia within the cortex of patients with amyotrophic lateral sclerosis. Cortical thinning and signal hypointensity of the deep layers of the primary motor cortex could constitute a marker of upper motor neuron impairment in patients with amyotrophic lateral sclerosis. © 2016 by American Journal of Neuroradiology.

  12. Modulation of the Intracortical LFP during Action Execution and Observation

    PubMed Central

    Vigneswaran, Ganesh; Philipp, Roland; Lemon, Roger N.; Kraskov, Alexander

    2015-01-01

    The activity of mirror neurons in macaque ventral premotor cortex (PMv) and primary motor cortex (M1) is modulated by the observation of another's movements. This modulation could underpin well documented changes in EEG/MEG activity indicating the existence of a mirror neuron system in humans. Because the local field potential (LFP) represents an important link between macaque single neuron and human noninvasive studies, we focused on mirror properties of intracortical LFPs recorded in the PMv and M1 hand regions in two macaques while they reached, grasped and held different objects, or observed the same actions performed by an experimenter. Upper limb EMGs were recorded to control for covert muscle activity during observation. The movement-related potential (MRP), investigated as intracortical low-frequency LFP activity (<9 Hz), was modulated in both M1 and PMv, not only during action execution but also during action observation. Moreover, the temporal LFP modulations during execution and observation were highly correlated in both cortical areas. Beta power in both PMv and M1 was clearly modulated in both conditions. Although the MRP was detected only during dynamic periods of the task (reach/grasp/release), beta decreased during dynamic and increased during static periods (hold). Comparison of LFPs for different grasps provided evidence for partially nonoverlapping networks being active during execution and observation, which might be related to different inputs to motor areas during these conditions. We found substantial information about grasp in the MRP corroborating its suitability for brain–machine interfaces, although information about grasp was generally low during action observation. PMID:26041914

  13. Sensory modality of smoking cues modulates neural cue reactivity.

    PubMed

    Yalachkov, Yavor; Kaiser, Jochen; Görres, Andreas; Seehaus, Arne; Naumer, Marcus J

    2013-01-01

    Behavioral experiments have demonstrated that the sensory modality of presentation modulates drug cue reactivity. The present study on nicotine addiction tested whether neural responses to smoking cues are modulated by the sensory modality of stimulus presentation. We measured brain activation using functional magnetic resonance imaging (fMRI) in 15 smokers and 15 nonsmokers while they viewed images of smoking paraphernalia and control objects and while they touched the same objects without seeing them. Haptically presented, smoking-related stimuli induced more pronounced neural cue reactivity than visual cues in the left dorsal striatum in smokers compared to nonsmokers. The severity of nicotine dependence correlated positively with the preference for haptically explored smoking cues in the left inferior parietal lobule/somatosensory cortex, right fusiform gyrus/inferior temporal cortex/cerebellum, hippocampus/parahippocampal gyrus, posterior cingulate cortex, and supplementary motor area. These observations are in line with the hypothesized role of the dorsal striatum for the expression of drug habits and the well-established concept of drug-related automatized schemata, since haptic perception is more closely linked to the corresponding object-specific action pattern than visual perception. Moreover, our findings demonstrate that with the growing severity of nicotine dependence, brain regions involved in object perception, memory, self-processing, and motor control exhibit an increasing preference for haptic over visual smoking cues. This difference was not found for control stimuli. Considering the sensory modality of the presented cues could serve to develop more reliable fMRI-specific biomarkers, more ecologically valid experimental designs, and more effective cue-exposure therapies of addiction.

  14. Characterization of Hand Clenching in Human Sensorimotor Cortex Using High-, and Ultra-High Frequency Band Modulations of Electrocorticogram

    PubMed Central

    Jiang, Tianxiao; Liu, Su; Pellizzer, Giuseppe; Aydoseli, Aydin; Karamursel, Sacit; Sabanci, Pulat A.; Sencer, Altay; Gurses, Candan; Ince, Nuri F.

    2018-01-01

    Functional mapping of eloquent cortex before the resection of a tumor is a critical procedure for optimizing survival and quality of life. In order to locate the hand area of the motor cortex in two patients with low-grade gliomas (LGG), we recorded electrocorticogram (ECoG) from a 113 channel hybrid high-density grid (64 large contacts with diameter of 2.7 mm and 49 small contacts with diameter of 1 mm) while they executed hand clenching movements. We investigated the spatio-spectral characteristics of the neural oscillatory activity and observed that, in both patients, the hand movements were consistently associated with a wide spread power decrease in the low frequency band (LFB: 8–32 Hz) and a more localized power increase in the high frequency band (HFB: 60–280 Hz) within the sensorimotor region. Importantly, we observed significant power increase in the ultra-high frequency band (UFB: 300–800 Hz) during hand movements of both patients within a restricted cortical region close to the central sulcus, and the motor cortical “hand knob.” Among all frequency bands we studied, the UFB modulations were closest to the central sulcus and direct cortical stimulation (DCS) positive site. Both HFB and UFB modulations exhibited different timing characteristics at different locations. Power increase in HFB and UFB starting before movement onset was observed mostly at the anterior part of the activated cortical region. In addition, the spatial patterns in HFB and UFB indicated a probable postcentral shift of the hand motor function in one of the patients. We also compared the task related subband modulations captured by the small and large contacts in our hybrid grid. We did not find any significant difference in terms of band power changes. This study shows initial evidence that event-driven neural oscillatory activity recorded from ECoG can reach up to 800 Hz. The spatial distribution of UFB oscillations was found to be more focalized and closer to the central sulcus compared to LFB and HFB. More studies are needed to characterize further the functional significance of UFB relative to LFB and HFB. PMID:29535603

  15. Characterization of Hand Clenching in Human Sensorimotor Cortex Using High-, and Ultra-High Frequency Band Modulations of Electrocorticogram.

    PubMed

    Jiang, Tianxiao; Liu, Su; Pellizzer, Giuseppe; Aydoseli, Aydin; Karamursel, Sacit; Sabanci, Pulat A; Sencer, Altay; Gurses, Candan; Ince, Nuri F

    2018-01-01

    Functional mapping of eloquent cortex before the resection of a tumor is a critical procedure for optimizing survival and quality of life. In order to locate the hand area of the motor cortex in two patients with low-grade gliomas (LGG), we recorded electrocorticogram (ECoG) from a 113 channel hybrid high-density grid (64 large contacts with diameter of 2.7 mm and 49 small contacts with diameter of 1 mm) while they executed hand clenching movements. We investigated the spatio-spectral characteristics of the neural oscillatory activity and observed that, in both patients, the hand movements were consistently associated with a wide spread power decrease in the low frequency band (LFB: 8-32 Hz) and a more localized power increase in the high frequency band (HFB: 60-280 Hz) within the sensorimotor region. Importantly, we observed significant power increase in the ultra-high frequency band (UFB: 300-800 Hz) during hand movements of both patients within a restricted cortical region close to the central sulcus, and the motor cortical "hand knob." Among all frequency bands we studied, the UFB modulations were closest to the central sulcus and direct cortical stimulation (DCS) positive site. Both HFB and UFB modulations exhibited different timing characteristics at different locations. Power increase in HFB and UFB starting before movement onset was observed mostly at the anterior part of the activated cortical region. In addition, the spatial patterns in HFB and UFB indicated a probable postcentral shift of the hand motor function in one of the patients. We also compared the task related subband modulations captured by the small and large contacts in our hybrid grid. We did not find any significant difference in terms of band power changes. This study shows initial evidence that event-driven neural oscillatory activity recorded from ECoG can reach up to 800 Hz. The spatial distribution of UFB oscillations was found to be more focalized and closer to the central sulcus compared to LFB and HFB. More studies are needed to characterize further the functional significance of UFB relative to LFB and HFB.

  16. Modulation of amplitude and latency of motor evoked potential by direction of transcranial magnetic stimulation

    NASA Astrophysics Data System (ADS)

    Sato, Aya; Torii, Tetsuya; Iwahashi, Masakuni; Itoh, Yuji; Iramina, Keiji

    2014-05-01

    The present study analyzed the effects of monophasic magnetic stimulation to the motor cortex. The effects of magnetic stimulation were evaluated by analyzing the motor evoked potentials (MEPs). The amplitude and latency of MEPs on the abductor pollicis brevis muscle were used to evaluate the effects of repetitive magnetic stimulation. A figure eight-shaped flat coil was used to stimulate the region over the primary motor cortex. The intensity of magnetic stimulation was 120% of the resting motor threshold, and the frequency of magnetic stimulation was 0.1 Hz. In addition, the direction of the current in the brain was posterior-anterior (PA) or anterior-posterior (AP). The latency of MEP was compared with PA and AP on initial magnetic stimulation. The results demonstrated that a stimulus in the AP direction increased the latency of the MEP by approximately 2.5 ms. MEP amplitude was also compared with PA and AP during 60 magnetic stimulations. The results showed that a stimulus in the PA direction gradually increased the amplitude of the MEP. However, a stimulus in the AP direction did not modulate the MEP amplitude. The average MEP amplitude induced from every 10 magnetic pulses was normalized by the average amplitude of the first 10 stimuli. These results demonstrated that the normalized MEP amplitude increased up to approximately 150%. In terms of pyramidal neuron indirect waves (I waves), magnetic stimulation inducing current flowing backward to the anterior preferentially elicited an I1 wave, and current flowing forward to the posterior elicited an I3 wave. It has been reported that the latency of the I3 wave is approximately 2.5 ms longer than the I1 wave elicitation, so the resulting difference in latency may be caused by this phenomenon. It has also been reported that there is no alteration of MEP amplitude at a frequency of 0.1 Hz. However, this study suggested that the modulation of MEP amplitude depends on stimulation strength and stimulation direction.

  17. Differential sensory cortical involvement in auditory and visual sensorimotor temporal recalibration: Evidence from transcranial direct current stimulation (tDCS).

    PubMed

    Aytemür, Ali; Almeida, Nathalia; Lee, Kwang-Hyuk

    2017-02-01

    Adaptation to delayed sensory feedback following an action produces a subjective time compression between the action and the feedback (temporal recalibration effect, TRE). TRE is important for sensory delay compensation to maintain a relationship between causally related events. It is unclear whether TRE is a sensory modality-specific phenomenon. In 3 experiments employing a sensorimotor synchronization task, we investigated this question using cathodal transcranial direct-current stimulation (tDCS). We found that cathodal tDCS over the visual cortex, and to a lesser extent over the auditory cortex, produced decreased visual TRE. However, both auditory and visual cortex tDCS did not produce any measurable effects on auditory TRE. Our study revealed different nature of TRE in auditory and visual domains. Visual-motor TRE, which is more variable than auditory TRE, is a sensory modality-specific phenomenon, modulated by the auditory cortex. The robustness of auditory-motor TRE, unaffected by tDCS, suggests the dominance of the auditory system in temporal processing, by providing a frame of reference in the realignment of sensorimotor timing signals. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Sensitivity to perception level differentiates two subnetworks within the mirror neuron system.

    PubMed

    Simon, Shiri; Mukamel, Roy

    2017-05-01

    Mirror neurons are a subset of brain cells that discharge during action execution and passive observation of similar actions. An open question concerns the functional role of their ability to match observed and executed actions. Since understanding of goals requires conscious perception of actions, we expect that mirror neurons potentially involved in action goal coding, will be modulated by changes in action perception level. Here, we manipulated perception level of action videos depicting short hand movements and measured the corresponding fMRI BOLD responses in mirror regions. Our results show that activity levels within a network of regions, including the sensorimotor cortex, primary motor cortex, dorsal premotor cortex and posterior superior temporal sulcus, are sensitive to changes in action perception level, whereas activity levels in the inferior frontal gyrus, ventral premotor cortex, supplementary motor area and superior parietal lobule are invariant to such changes. In addition, this parcellation to two sub-networks manifest as smaller functional distances within each group of regions during task and resting state. Our results point to functional differences between regions within the mirror neurons system which may have implications with respect to their possible role in action understanding. © The Author (2017). Published by Oxford University Press.

  19. Interaction of Motor Training and Intermittent Theta Burst Stimulation in Modulating Motor Cortical Plasticity: Influence of BDNF Val66Met Polymorphism

    PubMed Central

    Lee, Mina; Kim, Song E.; Kim, Won Sup; Lee, Jungyeun; Yoo, Hye Kyung; Park, Kee-Duk; Choi, Kyoung-Gyu; Jeong, Seon-Yong; Kim, Byung Gon; Lee, Hyang Woon

    2013-01-01

    Cortical physiology in human motor cortex is influenced by behavioral motor training (MT) as well as repetitive transcranial magnetic stimulation protocol such as intermittent theta burst stimulation (iTBS). This study aimed to test whether MT and iTBS can interact with each other to produce additive changes in motor cortical physiology. We hypothesized that potential interaction between MT and iTBS would be dependent on BDNF Val66Met polymorphism, which is known to affect neuroplasticity in the human motor cortex. Eighty two healthy volunteers were genotyped for BDNF polymorphism. Thirty subjects were assigned for MT alone, 23 for iTBS alone, and 29 for MT + iTBS paradigms. TMS indices for cortical excitability and motor map areas were measured prior to and after each paradigm. MT alone significantly increased the motor cortical excitability and expanded the motor map areas. The iTBS alone paradigm also enhanced excitability and increased the motor map areas to a slightly greater extent than MT alone. A combination of MT and iTBS resulted in the largest increases in the cortical excitability, and the representational motor map expansion of MT + iTBS was significantly greater than MT or iTBS alone only in Val/Val genotype. As a result, the additive interaction between MT and iTBS was highly dependent on BDNF Val66Met polymorphism. Our results may have clinical relevance in designing rehabilitative strategies that combine therapeutic cortical stimulation and physical exercise for patients with motor disabilities. PMID:23451258

  20. Interaction of motor training and intermittent theta burst stimulation in modulating motor cortical plasticity: influence of BDNF Val66Met polymorphism.

    PubMed

    Lee, Mina; Kim, Song E; Kim, Won Sup; Lee, Jungyeun; Yoo, Hye Kyung; Park, Kee-Duk; Choi, Kyoung-Gyu; Jeong, Seon-Yong; Kim, Byung Gon; Lee, Hyang Woon

    2013-01-01

    Cortical physiology in human motor cortex is influenced by behavioral motor training (MT) as well as repetitive transcranial magnetic stimulation protocol such as intermittent theta burst stimulation (iTBS). This study aimed to test whether MT and iTBS can interact with each other to produce additive changes in motor cortical physiology. We hypothesized that potential interaction between MT and iTBS would be dependent on BDNF Val66Met polymorphism, which is known to affect neuroplasticity in the human motor cortex. Eighty two healthy volunteers were genotyped for BDNF polymorphism. Thirty subjects were assigned for MT alone, 23 for iTBS alone, and 29 for MT + iTBS paradigms. TMS indices for cortical excitability and motor map areas were measured prior to and after each paradigm. MT alone significantly increased the motor cortical excitability and expanded the motor map areas. The iTBS alone paradigm also enhanced excitability and increased the motor map areas to a slightly greater extent than MT alone. A combination of MT and iTBS resulted in the largest increases in the cortical excitability, and the representational motor map expansion of MT + iTBS was significantly greater than MT or iTBS alone only in Val/Val genotype. As a result, the additive interaction between MT and iTBS was highly dependent on BDNF Val66Met polymorphism. Our results may have clinical relevance in designing rehabilitative strategies that combine therapeutic cortical stimulation and physical exercise for patients with motor disabilities.

  1. Trunk robot rehabilitation training with active stepping reorganizes and enriches trunk motor cortex representations in spinal transected rats.

    PubMed

    Oza, Chintan S; Giszter, Simon F

    2015-05-06

    Trunk motor control is crucial for postural stability and propulsion after low thoracic spinal cord injury (SCI) in animals and humans. Robotic rehabilitation aimed at trunk shows promise in SCI animal models and patients. However, little is known about the effect of SCI and robot rehabilitation of trunk on cortical motor representations. We previously showed reorganization of trunk motor cortex after adult SCI. Non-stepping training also exacerbated some SCI-driven plastic changes. Here we examine effects of robot rehabilitation that promotes recovery of hindlimb weight support functions on trunk motor cortex representations. Adult rats spinal transected as neonates (NTX rats) at the T9/10 level significantly improve function with our robot rehabilitation paradigm, whereas treadmill-only trained do not. We used intracortical microstimulation to map motor cortex in two NTX groups: (1) treadmill trained (control group); and (2) robot-assisted treadmill trained (improved function group). We found significant robot rehabilitation-driven changes in motor cortex: (1) caudal trunk motor areas expanded; (2) trunk coactivation at cortex sites increased; (3) richness of trunk cortex motor representations, as examined by cumulative entropy and mutual information for different trunk representations, increased; (4) trunk motor representations in the cortex moved toward more normal topography; and (5) trunk and forelimb motor representations that SCI-driven plasticity and compensations had caused to overlap were segregated. We conclude that effective robot rehabilitation training induces significant reorganization of trunk motor cortex and partially reverses some plastic changes that may be adaptive in non-stepping paraplegia after SCI. Copyright © 2015 the authors 0270-6474/15/357174-16$15.00/0.

  2. The effect of electroacupuncture on proteomic changes in the motor cortex of 6-OHDA Parkinsonian rats.

    PubMed

    Li, Min; Li, Lijuan; Wang, Ke; Su, Wenting; Jia, Jun; Wang, Xiaomin

    2017-10-15

    Electroacupuncture (EA) has been reported to alleviate motor deficits in Parkinson's disease (PD) patients, and PD animal models. However, the mechanisms by which EA improves motor function have not been investigated. We have employed a 6-hydroxydopamine (6-OHDA) unilateral injection induced PD model to investigate whether EA alters protein expression in the motor cortex. We found that 4weeks of EA treatment significantly improved spontaneous floor plane locomotion and rotarod performance. High-throughput proteomic analysis in the motor cortex was employed. The expression of 54 proteins were altered in the unlesioned motor cortex, and 102 protein expressions were altered in the lesioned motor cortex of 6-OHDA rats compared to sham rats. Compared to non-treatment PD control, EA treatment reversed 6 proteins in unlesioned and 19 proteins in lesioned motor cortex. The present study demonstrated that PD induces proteomic changes in the motor cortex, some of which are rescued by EA treatment. These targeted proteins were mainly involved in increasing autophagy, mRNA processing and ATP binding and maintaining the balance of neurotransmitters. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Electrical stimulation and motor recovery.

    PubMed

    Young, Wise

    2015-01-01

    In recent years, several investigators have successfully regenerated axons in animal spinal cords without locomotor recovery. One explanation is that the animals were not trained to use the regenerated connections. Intensive locomotor training improves walking recovery after spinal cord injury (SCI) in people, and >90% of people with incomplete SCI recover walking with training. Although the optimal timing, duration, intensity, and type of locomotor training are still controversial, many investigators have reported beneficial effects of training on locomotor function. The mechanisms by which training improves recovery are not clear, but an attractive theory is available. In 1949, Donald Hebb proposed a famous rule that has been paraphrased as "neurons that fire together, wire together." This rule provided a theoretical basis for a widely accepted theory that homosynaptic and heterosynaptic activity facilitate synaptic formation and consolidation. In addition, the lumbar spinal cord has a locomotor center, called the central pattern generator (CPG), which can be activated nonspecifically with electrical stimulation or neurotransmitters to produce walking. The CPG is an obvious target to reconnect after SCI. Stimulating motor cortex, spinal cord, or peripheral nerves can modulate lumbar spinal cord excitability. Motor cortex stimulation causes long-term changes in spinal reflexes and synapses, increases sprouting of the corticospinal tract, and restores skilled forelimb function in rats. Long used to treat chronic pain, motor cortex stimuli modify lumbar spinal network excitability and improve lower extremity motor scores in humans. Similarly, epidural spinal cord stimulation has long been used to treat pain and spasticity. Subthreshold epidural stimulation reduces the threshold for locomotor activity. In 2011, Harkema et al. reported lumbosacral epidural stimulation restores motor control in chronic motor complete patients. Peripheral nerve or functional electrical stimulation (FES) has long been used to activate sacral nerves to treat bladder and pelvic dysfunction and to augment motor function. In theory, FES should facilitate synaptic formation and motor recovery after regenerative therapies. Upcoming clinical trials provide unique opportunities to test the theory.

  4. Impairment of Auditory-Motor Timing and Compensatory Reorganization after Ventral Premotor Cortex Stimulation

    PubMed Central

    Kornysheva, Katja; Schubotz, Ricarda I.

    2011-01-01

    Integrating auditory and motor information often requires precise timing as in speech and music. In humans, the position of the ventral premotor cortex (PMv) in the dorsal auditory stream renders this area a node for auditory-motor integration. Yet, it remains unknown whether the PMv is critical for auditory-motor timing and which activity increases help to preserve task performance following its disruption. 16 healthy volunteers participated in two sessions with fMRI measured at baseline and following rTMS (rTMS) of either the left PMv or a control region. Subjects synchronized left or right finger tapping to sub-second beat rates of auditory rhythms in the experimental task, and produced self-paced tapping during spectrally matched auditory stimuli in the control task. Left PMv rTMS impaired auditory-motor synchronization accuracy in the first sub-block following stimulation (p<0.01, Bonferroni corrected), but spared motor timing and attention to task. Task-related activity increased in the homologue right PMv, but did not predict the behavioral effect of rTMS. In contrast, anterior midline cerebellum revealed most pronounced activity increase in less impaired subjects. The present findings suggest a critical role of the left PMv in feed-forward computations enabling accurate auditory-motor timing, which can be compensated by activity modulations in the cerebellum, but not in the homologue region contralateral to stimulation. PMID:21738657

  5. Anticipatory activity in primary motor cortex codes memorized movement sequences.

    PubMed

    Lu, Xiaofeng; Ashe, James

    2005-03-24

    Movement sequences, defined both by the component movements and by the serial order in which they are produced, are fundamental building blocks of motor behavior. The serial order of sequence production is strongly encoded in medial motor areas. It is not known to what extent sequences are further elaborated or encoded in primary motor cortex. Here, we describe cells in the primary motor cortex of the monkey that show anticipatory activity exclusively related to a specific memorized sequence of upcoming movements. In addition, the injection of muscimol, a GABA agonist, into motor cortex resulted in an increase in the error rate during sequence production, without concomitant effects on nonsequenced motor performance. Our results challenge the role of medial motor areas in the control of well-practiced movement sequences and suggest that motor cortex contains a complete apparatus for the planning and production of this complex behavior.

  6. Real-time measurement of cerebral blood flow during and after repetitive transcranial magnetic stimulation: A near-infrared spectroscopy study.

    PubMed

    Park, Eunhee; Kang, Min Jae; Lee, Ahee; Chang, Won Hyuk; Shin, Yong-Il; Kim, Yun-Hee

    2017-07-13

    To confirm the interhemispheric modulation induced by low-frequency repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex, real-time regional cerebral blood flow (rCBF) was assessed using functional near-infrared spectroscopy (fNIRS) in the contralateral primary motor cortex (M1) and premotor cortex (PM). Ten right-handed healthy subjects completed two experimental sessions that were randomly arranged for real or sham rTMS session. In the real rTMS session, fNIRS data were acquired from the right M1 and PM area, while the motor hot spot of the left M1 was stimulated with 1Hz rTMS for 1200 pulses with two boosters. In the sham stimulation session, stimulation was delivered with a disconnected coil. During the real rTMS session, the concentration of oxyhemoglobin ([oxy-Hb]) in the right M1 increased continuously until the end of the stimulation. These changes lasted for 20min, while the right PM did not show a change in [oxy-Hb] concentration. On the other hand, the concentration of deoxy-hemoglobin ([deoxy-Hb]) decreased continuously in the right M1 and PM during the real rTMS stimulation, and this change lasted for 20min after the stimulation. The sham stimulation did not exhibit any significant change in both [oxy-Hb] and [deoxy-Hb] concentration during or after the stimulation. Application of 1Hz rTMS over M1 resulted in changes of rCBF in contralateral M1 and PM, which seemed to constitute a function of interhemispheric modulation of rTMS. The fNIRS data was able to detect this physiological change of neuromodulatory action of rTMS in real-time. Copyright © 2017. Published by Elsevier B.V.

  7. Modulation of neural circuits underlying temporal production by facial expressions of pain.

    PubMed

    Ballotta, Daniela; Lui, Fausta; Porro, Carlo Adolfo; Nichelli, Paolo Frigio; Benuzzi, Francesca

    2018-01-01

    According to the Scalar Expectancy Theory, humans are equipped with a biological internal clock, possibly modulated by attention and arousal. Both emotions and pain are arousing and can absorb attentional resources, thus causing distortions of temporal perception. The aims of the present single-event fMRI study were to investigate: a) whether observation of facial expressions of pain interferes with time production; and b) the neural network subserving this kind of temporal distortions. Thirty healthy volunteers took part in the study. Subjects were asked to perform a temporal production task and a concurrent gender discrimination task, while viewing faces of unknown people with either pain-related or neutral expressions. Behavioural data showed temporal underestimation (i.e., longer produced intervals) during implicit pain expression processing; this was accompanied by increased activity of right middle temporal gyrus, a region known to be active during the perception of emotional and painful faces. Psycho-Physiological Interaction analyses showed that: 1) the activity of middle temporal gyrus was positively related to that of areas previously reported to play a role in timing: left primary motor cortex, middle cingulate cortex, supplementary motor area, right anterior insula, inferior frontal gyrus, bilateral cerebellum and basal ganglia; 2) the functional connectivity of supplementary motor area with several frontal regions, anterior cingulate cortex and right angular gyrus was correlated to the produced interval during painful expression processing. Our data support the hypothesis that observing emotional expressions distorts subjective time perception through the interaction of the neural network subserving processing of facial expressions with the brain network involved in timing. Within this frame, middle temporal gyrus appears to be the key region of the interplay between the two neural systems.

  8. Patient-conducted anodal transcranial direct current stimulation of the motor cortex alleviates pain in trigeminal neuralgia

    PubMed Central

    2014-01-01

    Background Transcranial direct current stimulation (tDCS) of the primary motor cortex has been shown to modulate pain and trigeminal nociceptive processing. Methods Ten patients with classical trigeminal neuralgia (TN) were stimulated daily for 20 minutes over two weeks using anodal (1 mA) or sham tDCS over the primary motor cortex (M1) in a randomized double-blind cross-over design. Primary outcome variable was pain intensity on a verbal rating scale (VRS 0–10). VRS and attack frequency were assessed for one month before, during and after tDCS. The impact on trigeminal pain processing was assessed with pain-related evoked potentials (PREP) and the nociceptive blink reflex (nBR) following electrical stimulation on both sides of the forehead before and after tDCS. Results Anodal tDCS reduced pain intensity significantly after two weeks of treatment. The attack frequency reduction was not significant. PREP showed an increased N2 latency and decreased peak-to-peak amplitude after anodal tDCS. No severe adverse events were reported. Conclusion Anodal tDCS over two weeks ameliorates intensity of pain in TN. It may become a valuable treatment option for patients unresponsive to conventional treatment. PMID:25424567

  9. Effect of early and late rehabilitation onset in a chronic rat model of ischemic stroke- assessment of motor cortex signaling and gait functionality over time.

    PubMed

    Nielsen, Rasmus K; Samson, Katrine L; Simonsen, Daniel; Jensen, Winnie

    2013-11-01

    The aim of the present study was to investigate the effects of ischemic stroke and onset of subsequent rehabilitation of gait function in rats. Nine male Sprague-Dawley rats were instrumented with a 16-channel intracortical (IC) electrode array. An ischemic stroke was induced within the hindlimb area of the left motor cortex. The rehabilitation consisted of a repetitive training paradigm over 28 days, initiated on day one ("Early-onset", 5 rats) and on day seven, ("Late-onset", 4 rats). Data were obtained from IC microstimulation tests, treadmill walking tests, and beam walking tests. Results revealed an expansion of the hindlimb representation within the motor cortex area and an increased amount of cortical firing rate modulation for the "Early-onset" group but not for the "Late-onset" group. Kinematic data revealed a significant change for both intervention groups. However, this difference was larger for the "Early-onset" group. Results from the beam walking test showed functional performance deficits following stroke which returned to pre-stroke level after the rehabilitative training. The results from the present study indicate the existence of a critical time period following stroke where onset of rehabilitative training may be more effective and related to a higher degree of true recovery.

  10. Intracortical circuits, sensorimotor integration and plasticity in human motor cortical projections to muscles of the lower face

    PubMed Central

    Pilurzi, G; Hasan, A; Saifee, T A; Tolu, E; Rothwell, J C; Deriu, F

    2013-01-01

    Previous studies of the cortical control of human facial muscles documented the distribution of corticobulbar projections and the presence of intracortical inhibitory and facilitatory mechanisms. Yet surprisingly, given the importance and precision in control of facial expression, there have been no studies of the afferent modulation of corticobulbar excitability or of the plasticity of synaptic connections in the facial primary motor cortex (face M1). In 25 healthy volunteers, we used standard single- and paired-pulse transcranial magnetic stimulation (TMS) methods to probe motor-evoked potentials (MEPs), short-intracortical inhibition, intracortical facilitation, short-afferent and long-afferent inhibition and paired associative stimulation in relaxed and active depressor anguli oris muscles. Single-pulse TMS evoked bilateral MEPs at rest and during activity that were larger in contralateral muscles, confirming that corticobulbar projection to lower facial muscles is bilateral and asymmetric, with contralateral predominance. Both short-intracortical inhibition and intracortical facilitation were present bilaterally in resting and active conditions. Electrical stimulation of the facial nerve paired with a TMS pulse 5–200 ms later showed no short-afferent inhibition, but long-afferent inhibition was present. Paired associative stimulation tested with an electrical stimulation–TMS interval of 20 ms significantly facilitated MEPs for up to 30 min. The long-term potentiation, evoked for the first time in face M1, demonstrates that excitability of the facial motor cortex is prone to plastic changes after paired associative stimulation. Evaluation of intracortical circuits in both relaxed and active lower facial muscles as well as of plasticity in the facial motor cortex may provide further physiological insight into pathologies affecting the facial motor system. PMID:23297305

  11. The Effects of rTMS Combined with Motor Training on Functional Connectivity in Alpha Frequency Band.

    PubMed

    Jin, Jing-Na; Wang, Xin; Li, Ying; Jin, Fang; Liu, Zhi-Peng; Yin, Tao

    2017-01-01

    It has recently been reported that repetitive transcranial magnetic stimulation combined with motor training (rTMS-MT) could improve motor function in post-stroke patients. However, the effects of rTMS-MT on cortical function using functional connectivity and graph theoretical analysis remain unclear. Ten healthy subjects were recruited to receive rTMS immediately before application of MT. Low frequency rTMS was delivered to the dominant hemisphere and non-dominant hand performed MT over 14 days. The reaction time of Nine-Hole Peg Test and electroencephalography (EEG) in resting condition with eyes closed were recorded before and after rTMS-MT. Functional connectivity was assessed by phase synchronization index (PSI), and subsequently thresholded to construct undirected graphs in alpha frequency band (8-13 Hz). We found a significant decrease in reaction time after rTMS-MT. The functional connectivity between the parietal and frontal cortex, and the graph theory statistics of node degree and efficiency in the parietal cortex increased. Besides the functional connectivity between premotor and frontal cortex, the degree and efficiency of premotor cortex showed opposite results. In addition, the number of connections significantly increased within inter-hemispheres and inter-regions. In conclusion, this study could be helpful in our understanding of how rTMS-MT modulates brain activity. The methods and results in this study could be taken as reference in future studies of the effects of rTMS-MT in stroke patients.

  12. Modeling task-specific neuronal ensembles improves decoding of grasp

    NASA Astrophysics Data System (ADS)

    Smith, Ryan J.; Soares, Alcimar B.; Rouse, Adam G.; Schieber, Marc H.; Thakor, Nitish V.

    2018-06-01

    Objective. Dexterous movement involves the activation and coordination of networks of neuronal populations across multiple cortical regions. Attempts to model firing of individual neurons commonly treat the firing rate as directly modulating with motor behavior. However, motor behavior may additionally be associated with modulations in the activity and functional connectivity of neurons in a broader ensemble. Accounting for variations in neural ensemble connectivity may provide additional information about the behavior being performed. Approach. In this study, we examined neural ensemble activity in primary motor cortex (M1) and premotor cortex (PM) of two male rhesus monkeys during performance of a center-out reach, grasp and manipulate task. We constructed point process encoding models of neuronal firing that incorporated task-specific variations in the baseline firing rate as well as variations in functional connectivity with the neural ensemble. Models were evaluated both in terms of their encoding capabilities and their ability to properly classify the grasp being performed. Main results. Task-specific ensemble models correctly predicted the performed grasp with over 95% accuracy and were shown to outperform models of neuronal activity that assume only a variable baseline firing rate. Task-specific ensemble models exhibited superior decoding performance in 82% of units in both monkeys (p  <  0.01). Inclusion of ensemble activity also broadly improved the ability of models to describe observed spiking. Encoding performance of task-specific ensemble models, measured by spike timing predictability, improved upon baseline models in 62% of units. Significance. These results suggest that additional discriminative information about motor behavior found in the variations in functional connectivity of neuronal ensembles located in motor-related cortical regions is relevant to decode complex tasks such as grasping objects, and may serve the basis for more reliable and accurate neural prosthesis.

  13. The functional role of dorso-lateral premotor cortex during mental rotation: an event-related fMRI study separating cognitive processing steps using a novel task paradigm.

    PubMed

    Lamm, Claus; Windischberger, Christian; Moser, Ewald; Bauer, Herbert

    2007-07-15

    Subjects deciding whether two objects presented at angular disparity are identical or mirror versions of each other usually show response times that linearly increase with the angle between objects. This phenomenon has been termed mental rotation. While there is widespread agreement that parietal cortex plays a dominant role in mental rotation, reports concerning the involvement of motor areas are less consistent. From a theoretical point of view, activation in motor areas suggests that mental rotation relies upon visuo-motor rather than visuo-spatial processing alone. However, the type of information that is processed by motor areas during mental rotation remains unclear. In this study we used event-related fMRI to assess whether activation in parietal and dorsolateral premotor areas (dPM) during mental rotation is distinctively related to processing spatial orientation information. Using a newly developed task paradigm we explicitly separated the processing steps (encoding, mental rotation proper and object matching) required by mental rotation tasks and additionally modulated the amount of spatial orientation information that had to be processed. Our results show that activation in dPM during mental rotation is not strongly modulated by the processing of spatial orientation information, and that activation in dPM areas is strongest during mental rotation proper. The latter finding suggests that dPM is involved in more generalized processes such as visuo-spatial attention and movement anticipation. We propose that solving mental rotation tasks is heavily dependent upon visuo-motor processes and evokes neural processing that may be considered as an implicit simulation of actual object rotation.

  14. The influence of rTMS over prefrontal and motor areas in a morphological task: grammatical vs. semantic effects.

    PubMed

    Gerfo, Emanuele Lo; Oliveri, Massimiliano; Torriero, Sara; Salerno, Silvia; Koch, Giacomo; Caltagirone, Carlo

    2008-01-31

    We investigated the differential role of two frontal regions in the processing of grammatical and semantic knowledge. Given the documented specificity of the prefrontal cortex for the grammatical class of verbs, and of the primary motor cortex for the semantic class of action words, we sought to investigate whether the prefrontal cortex is also sensitive to semantic effects, and whether the motor cortex is also sensitive to grammatical class effects. We used repetitive transcranial magnetic stimulation (rTMS) to suppress the excitability of a portion of left prefontal cortex (first experiment) and of the motor area (second experiment). In the first experiment we found that rTMS applied to the left prefrontal cortex delays the processing of action verbs' retrieval, but is not critical for retrieval of state verbs and state nouns. In the second experiment we found that rTMS applied to the left motor cortex delays the processing of action words, both name and verbs, while it is not critical for the processing of state words. These results support the notion that left prefrontal and motor cortex are involved in the process of action word retrieval. Left prefrontal cortex subserves processing of both grammatical and semantic information, whereas motor cortex contributes to the processing of semantic representation of action words without any involvement in the representation of grammatical categories.

  15. Induction of plasticity in the human motor cortex by pairing an auditory stimulus with TMS.

    PubMed

    Sowman, Paul F; Dueholm, Søren S; Rasmussen, Jesper H; Mrachacz-Kersting, Natalie

    2014-01-01

    Acoustic stimuli can cause a transient increase in the excitability of the motor cortex. The current study leverages this phenomenon to develop a method for testing the integrity of auditorimotor integration and the capacity for auditorimotor plasticity. We demonstrate that appropriately timed transcranial magnetic stimulation (TMS) of the hand area, paired with auditorily mediated excitation of the motor cortex, induces an enhancement of motor cortex excitability that lasts beyond the time of stimulation. This result demonstrates for the first time that paired associative stimulation (PAS)-induced plasticity within the motor cortex is applicable with auditory stimuli. We propose that the method developed here might provide a useful tool for future studies that measure auditory-motor connectivity in communication disorders.

  16. Rubrocerebellar Feedback Loop Isolates the Interposed Nucleus as an Independent Processor of Corollary Discharge Information in Mice

    PubMed Central

    Beitzel, Christy S.; Houck, Brenda D.; Lewis, Samantha M.

    2017-01-01

    Understanding cerebellar contributions to motor coordination requires deeper insight into how the output structures of the cerebellum, the cerebellar nuclei, integrate their inputs and influence downstream motor pathways. The magnocellular red nucleus (RNm), a brainstem premotor structure, is a major target of the interposed nucleus (IN), and has also been described in previous studies to send feedback collaterals to the cerebellum. Because such a pathway is in a key position to provide motor efferent information to the cerebellum, satisfying predictions about the use of corollary discharge in cerebellar computations, we studied it in mice of both sexes. Using anterograde viral tracing, we show that innervation of cerebellum by rubrospinal neuron collaterals is remarkably selective for the IN compared with the cerebellar cortex. Optogenetic activation of the pathway in acute mouse brain slices drove IN activity despite small amplitude synaptic currents, suggesting an active role in IN information processing. Monosynaptic transsynaptic rabies tracing indicated the pathway contacts multiple cell types within the IN. By contrast, IN inputs to the RNm targeted a region that lacked inhibitory neurons. Optogenetic drive of IN inputs to the RNm revealed strong, direct excitation but no inhibition of RNm neurons. Together, these data indicate that the cerebellar nuclei are under afferent control independent of the cerebellar cortex, potentially diversifying its roles in motor control. SIGNIFICANCE STATEMENT The common assumption that all cerebellar mossy fibers uniformly collateralize to the cerebellar nuclei and cortex underlies classic models of convergent Purkinje influence on cerebellar output. Specifically, mossy fibers are thought to both directly excite nuclear neurons and drive polysynaptic feedforward inhibition via Purkinje neurons, setting up a fundamental computational unit. Here we present data that challenge this rule. A dedicated cerebellar nuclear afferent comprised of feedback collaterals from premotor rubrospinal neurons can directly modulate IN output independent of Purkinje cell modulation. In contrast to the IN-RNm pathway, the RNm-IN feedback pathway targets multiple cell types, potentially influencing both motor output pathways and nucleo-olivary feedback. PMID:28916520

  17. Rubrocerebellar Feedback Loop Isolates the Interposed Nucleus as an Independent Processor of Corollary Discharge Information in Mice.

    PubMed

    Beitzel, Christy S; Houck, Brenda D; Lewis, Samantha M; Person, Abigail L

    2017-10-18

    Understanding cerebellar contributions to motor coordination requires deeper insight into how the output structures of the cerebellum, the cerebellar nuclei, integrate their inputs and influence downstream motor pathways. The magnocellular red nucleus (RNm), a brainstem premotor structure, is a major target of the interposed nucleus (IN), and has also been described in previous studies to send feedback collaterals to the cerebellum. Because such a pathway is in a key position to provide motor efferent information to the cerebellum, satisfying predictions about the use of corollary discharge in cerebellar computations, we studied it in mice of both sexes. Using anterograde viral tracing, we show that innervation of cerebellum by rubrospinal neuron collaterals is remarkably selective for the IN compared with the cerebellar cortex. Optogenetic activation of the pathway in acute mouse brain slices drove IN activity despite small amplitude synaptic currents, suggesting an active role in IN information processing. Monosynaptic transsynaptic rabies tracing indicated the pathway contacts multiple cell types within the IN. By contrast, IN inputs to the RNm targeted a region that lacked inhibitory neurons. Optogenetic drive of IN inputs to the RNm revealed strong, direct excitation but no inhibition of RNm neurons. Together, these data indicate that the cerebellar nuclei are under afferent control independent of the cerebellar cortex, potentially diversifying its roles in motor control. SIGNIFICANCE STATEMENT The common assumption that all cerebellar mossy fibers uniformly collateralize to the cerebellar nuclei and cortex underlies classic models of convergent Purkinje influence on cerebellar output. Specifically, mossy fibers are thought to both directly excite nuclear neurons and drive polysynaptic feedforward inhibition via Purkinje neurons, setting up a fundamental computational unit. Here we present data that challenge this rule. A dedicated cerebellar nuclear afferent comprised of feedback collaterals from premotor rubrospinal neurons can directly modulate IN output independent of Purkinje cell modulation. In contrast to the IN-RNm pathway, the RNm-IN feedback pathway targets multiple cell types, potentially influencing both motor output pathways and nucleo-olivary feedback. Copyright © 2017 the authors 0270-6474/17/3710085-12$15.00/0.

  18. Reduced NAA in motor and non-motor brain regions in amyotrophic lateral sclerosis: a cross-sectional and longitudinal study.

    PubMed

    Rule, R R; Suhy, J; Schuff, N; Gelinas, D F; Miller, R G; Weiner, M W

    2004-09-01

    After replication of previous findings we aimed to: 1) determine if previously reported (1)H MRSI differences between ALS patients and control subjects are limited to the motor cortex; and 2) determine the longitudinal metabolic changes corresponding to varying levels of diagnostic certainty. Twenty-one patients with possible/suspected ALS, 24 patients with probable/definite ALS and 17 control subjects underwent multislice (1)H MRSI co-registered with tissue-segmented MRI to obtain concentrations of the brain metabolites N-acetylaspartate (NAA), creatine, and choline in the left and right motor cortex and in gray matter and white matter of non-motor regions in the brain. In the more affected hemisphere, reductions in the ratios, NAA/Cho and NAA/Cre+Cho were observed both within (12.6% and 9.5% respectively) and outside (9.2% and 7.3% respectively) the motor cortex in probable/definite ALS. However, these reductions were significantly greater within the motor cortex (P<0.05 for NAA/Cho and P<0.005 for NAA/Cre+Cho). Longitudinal changes in NAA were observed at three months within the motor cortex of both possible/suspected ALS patients (P<0.005) and at nine months outside the motor cortex of probable/definite patients (P<0.005). However, there was no clear pattern of progressive change over time. NAA ratios are reduced in the motor cortex and outside the motor cortex in ALS, suggesting widespread neuronal injury. Longitudinal changes of NAA are not reliable, suggesting that NAA may not be a useful surrogate marker for treatment trials.

  19. Passive Transport Disrupts Grid Signals in the Parahippocampal Cortex

    PubMed Central

    Winter, Shawn S.; Mehlman, Max L.; Clark, Benjamin J.; Taube, Jeffrey S.

    2015-01-01

    Summary Navigation is usually thought of relative to landmarks, but neural signals representing space also use information generated by an animal’s movements. These signals include grid cells, which fire at multiple locations forming a repeating grid pattern. Grid cell generation depends upon theta rhythm, a 6-10 Hz EEG oscillation that is modulated by the animals’ movement velocity. We passively moved rats in a clear cart to eliminate motor related self-movement cues that drive moment-to-moment changes in theta rhythmicity. We found that passive movement maintained theta power and frequency at levels equivalent to low active movement velocity, spared overall HD cell characteristics, and abolished velocity modulation of theta rhythmicity and grid cell firing patterns. These results indicate that self-movement motor cues are necessary for generating grid-specific firing patterns, possibly by driving velocity modulation of theta rhythmicity. Velocity modulation of theta may be used as a speed signal to generate the repeating pattern of grid cells. PMID:26387719

  20. Neural Substrates for the Effects of Rehabilitative Training on Motor Recovery After Ischemic Infarct

    NASA Astrophysics Data System (ADS)

    Nudo, Randolph J.; Wise, Birute M.; Sifuentes, Frank; Milliken, Garrett W.

    1996-06-01

    Substantial functional reorganization takes place in the motor cortex of adult primates after a focal ischemic infarct, as might occur in stroke. A subtotal lesion confined to a small portion of the representation of one hand was previously shown to result in a further loss of hand territory in the adjacent, undamaged cortex of adult squirrel monkeys. In the present study, retraining of skilled hand use after similar infarcts resulted in prevention of the loss of hand territory adjacent to the infarct. In some instances, the hand representations expanded into regions formerly occupied by representations of the elbow and shoulder. Functional reorganization in the undamaged motor cortex was accompanied by behavioral recovery of skilled hand function. These results suggest that, after local damage to the motor cortex, rehabilitative training can shape subsequent reorganization in the adjacent intact cortex, and that the undamaged motor cortex may play an important role in motor recovery.

  1. Task-Relevant Information Modulates Primary Motor Cortex Activity Before Movement Onset.

    PubMed

    Calderon, Cristian B; Van Opstal, Filip; Peigneux, Philippe; Verguts, Tom; Gevers, Wim

    2018-01-01

    Monkey neurophysiology research supports the affordance competition hypothesis (ACH) proposing that cognitive information useful for action selection is integrated in sensorimotor areas. In this view, action selection would emerge from the simultaneous representation of competing action plans, in parallel biased by relevant task factors. This biased competition would take place up to primary motor cortex (M1). Although ACH is plausible in environments affording choices between actions, its relevance for human decision making is less clear. To address this issue, we designed an functional magnetic resonance imaging (fMRI) experiment modeled after monkey neurophysiology studies in which human participants processed cues conveying predictive information about upcoming button presses. Our results demonstrate that, as predicted by the ACH, predictive information (i.e., the relevant task factor) biases activity of primary motor regions. Specifically, first, activity before movement onset in contralateral M1 increases as the competition is biased in favor of a specific button press relative to activity in ipsilateral M1. Second, motor regions were more tightly coupled with fronto-parietal regions when competition between potential actions was high, again suggesting that motor regions are also part of the biased competition network. Our findings support the idea that action planning dynamics as proposed in the ACH are valid both in human and non-human primates.

  2. You can count on the motor cortex: finger counting habits modulate motor cortex activation evoked by numbers.

    PubMed

    Tschentscher, Nadja; Hauk, Olaf; Fischer, Martin H; Pulvermüller, Friedemann

    2012-02-15

    The embodied cognition framework suggests that neural systems for perception and action are engaged during higher cognitive processes. In an event-related fMRI study, we tested this claim for the abstract domain of numerical symbol processing: is the human cortical motor system part of the representation of numbers, and is organization of numerical knowledge influenced by individual finger counting habits? Developmental studies suggest a link between numerals and finger counting habits due to the acquisition of numerical skills through finger counting in childhood. In the present study, digits 1 to 9 and the corresponding number words were presented visually to adults with different finger counting habits, i.e. left- and right-starters who reported that they usually start counting small numbers with their left and right hand, respectively. Despite the absence of overt hand movements, the hemisphere contralateral to the hand used for counting small numbers was activated when small numbers were presented. The correspondence between finger counting habits and hemispheric motor activation is consistent with an intrinsic functional link between finger counting and number processing. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Investigating Synchronous Oscillation and Deep Brain Stimulation Treatment in A Model of Cortico-Basal Ganglia Network.

    PubMed

    Lu, Meili; Wei, Xile; Loparo, Kenneth A

    2017-11-01

    Altered firing properties and increased pathological oscillations in the basal ganglia have been proven to be hallmarks of Parkinson's disease (PD). Increasing evidence suggests that abnormal synchronous oscillations and suppression in the cortex may also play a critical role in the pathogenic process and treatment of PD. In this paper, a new closed-loop network including the cortex and basal ganglia using the Izhikevich models is proposed to investigate the synchrony and pathological oscillations in motor circuits and their modulation by deep brain stimulation (DBS). Results show that more coherent dynamics in the cortex may cause stronger effects on the synchrony and pathological oscillations of the subthalamic nucleus (STN). The pathological beta oscillations of the STN can both be efficiently suppressed with DBS applied directly to the STN or to cortical neurons, respectively, but the underlying mechanisms by which DBS suppresses the beta oscillations are different. This research helps to understand the dynamics of pathological oscillations in PD-related motor regions and supports the therapeutic potential of stimulation of cortical neurons.

  4. Altered neuronal activities in the motor cortex with impaired motor performance in adult rats observed after infusion of cerebrospinal fluid from amyotrophic lateral sclerosis patients.

    PubMed

    Sankaranarayani, R; Nalini, A; Rao Laxmi, T; Raju, T R

    2010-01-05

    Although definite evidences are available to state that, neuronal activity is a prime determinant of animal behavior, the specific relationship between local field potentials of the motor cortex after intervention with CSF from human patients and animal behavior have remained opaque. The present study has investigated whether cerebrospinal fluid from sporadic amyotrophic lateral sclerosis (sALS) patients could disrupt neuronal activity of the motor cortex, which could be associated with disturbances in the motor performance of adult rats. CSF from ALS patients (ALS-CSF) was infused into the lateral ventricle of Wistar rats. After 24h, the impact of ALS-CSF on the local field potentials (LFPs) of the motor cortex and on the motor behavior of animals were examined. The results indicate that ALS-CSF produced a bivariate distribution on the relative power values of the LFPs of the motor cortex 24h following infusion. However, the behavioral results did not show bimodality, instead showed consistent decrease in motor performance: on rotarod and grip strength meter. The neuronal activity of the motor cortex negatively correlated with the duration of ALS symptoms at the time of lumbar puncture. Although the effect of ALS-CSF was more pronounced at 24h following infusion, the changes observed in LFPs and motor performance appeared to revert to baseline values at later time points of testing. In the current study, we have shown that, ALS-CSF has the potential to perturb neuronal activity of the rat motor cortex which was associated with poor performance on motor function tests.

  5. Dynamic Re-wiring of Neural Circuits in the Motor Cortex in Mouse Models of Parkinson's Disease

    PubMed Central

    Lalchandani, Rupa R.; Cui, Yuting; Shu, Yu; Xu, Tonghui; Ding, Jun B.

    2015-01-01

    SUMMARY Dynamic adaptations in synaptic plasticity are critical for learning new motor skills and maintaining memory throughout life, which rapidly decline with Parkinson's disease (PD). Plasticity in the motor cortex is important for acquisition and maintenance of novel motor skills, but how the loss of dopamine in PD leads to disrupted structural and functional plasticity in the motor cortex is not well understood. Here, we utilized mouse models of PD and 2-photon imaging to show that dopamine depletion resulted in structural changes in the motor cortex. We further discovered that dopamine D1 and D2 receptor signaling were linked to selectively and distinctly regulating these aberrant changes in structural and functional plasticity. Our findings suggest that both D1 and D2 receptor signaling regulate motor cortex plasticity, and loss of dopamine results in atypical synaptic adaptations that may contribute to the impairment of motor performance and motor memory observed in PD. PMID:26237365

  6. Attention modulates specific motor cortical circuits recruited by transcranial magnetic stimulation.

    PubMed

    Mirdamadi, J L; Suzuki, L Y; Meehan, S K

    2017-09-17

    Skilled performance and acquisition is dependent upon afferent input to motor cortex. The present study used short-latency afferent inhibition (SAI) to probe how manipulation of sensory afference by attention affects different circuits projecting to pyramidal tract neurons in motor cortex. SAI was assessed in the first dorsal interosseous muscle while participants performed a low or high attention-demanding visual detection task. SAI was evoked by preceding a suprathreshold transcranial magnetic stimulus with electrical stimulation of the median nerve at the wrist. To isolate different afferent intracortical circuits in motor cortex SAI was evoked using either posterior-anterior (PA) or anterior-posterior (PA) monophasic current. In an independent sample, somatosensory processing during the same attention-demanding visual detection tasks was assessed using somatosensory-evoked potentials (SEP) elicited by median nerve stimulation. SAI elicited by AP TMS was reduced under high compared to low visual attention demands. SAI elicited by PA TMS was not affected by visual attention demands. SEPs revealed that the high visual attention load reduced the fronto-central P20-N30 but not the contralateral parietal N20-P25 SEP component. P20-N30 reduction confirmed that the visual attention task altered sensory afference. The current results offer further support that PA and AP TMS recruit different neuronal circuits. AP circuits may be one substrate by which cognitive strategies shape sensorimotor processing during skilled movement by altering sensory processing in premotor areas. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Brain dynamic neurochemical changes in dystonic patients: a magnetic resonance spectroscopy study.

    PubMed

    Marjańska, Malgorzata; Lehéricy, Stéphane; Valabrègue, Romain; Popa, Traian; Worbe, Yulia; Russo, Margherita; Auerbach, Edward J; Grabli, David; Bonnet, Cecilia; Gallea, Cécile; Coudert, Mathieu; Yahia-Cherif, Lydia; Vidailhet, Marie; Meunier, Sabine

    2013-02-01

    Measurements of the concentrations of γ-aminobutyric acid (GABA) and glutamate in the motor cortices and lentiform nuclei of dystonic patients using single-voxel (1)H magnetic resonance spectroscopy (MRS) have yielded conflicting results so far. This study aimed to investigate dynamic changes in metabolite concentrations after stimulation of the motor cortices in patients with upper limb dystonia. Using single-voxel MRS at 3 T, the concentrations of GABA, glutamate plus glutamine, and N-acetylaspartate were measured bilaterally in the primary sensorimotor cortex, lentiform nucleus, and occipital region before and after 5-Hz transcranial magnetic stimulation (TMS) over the dominant motor cortex. Data obtained from 15 patients with upper limb primary dystonia were compared with data obtained from 14 healthy volunteers. At baseline, there was no group difference in concentration of metabolites in any region. rTMS induced a local (in the stimulated motor cortex) decrease of N-acetylaspartate (P < .006) to the same extent in healthy volunteers and patients. GABA concentrations were modulated differently, however, decreasing mildly in patients and increasing mildly in healthy volunteers (P = .05). There were no remote effects in the lentiform nucleus in either group. The stimulation-induced changes in metabolite concentrations have been interpreted in view of the increased energy demand induced by rTMS. The dynamics of the GABA concentration were specifically impaired in dystonic patients. Whether these changes reflect changes in the extrasynaptic or synaptic GABA component is discussed. Copyright © 2012 Movement Disorders Society.

  8. A graph-theoretical analysis algorithm for quantifying the transition from sensory input to motor output by an emotional stimulus.

    PubMed

    Karmonik, Christof; Fung, Steve H; Dulay, M; Verma, A; Grossman, Robert G

    2013-01-01

    Graph-theoretical analysis algorithms have been used for identifying subnetworks in the human brain during the Default Mode State. Here, these methods are expanded to determine the interaction of the sensory and the motor subnetworks during the performance of an approach-avoidance paradigm utilizing the correlation strength between the signal intensity time courses as measure of synchrony. From functional magnetic resonance imaging (fMRI) data of 9 healthy volunteers, two signal time courses, one from the primary visual cortex (sensory input) and one from the motor cortex (motor output) were identified and a correlation difference map was calculated. Graph networks were created from this map and visualized with spring-embedded layouts and 3D layouts in the original anatomical space. Functional clusters in these networks were identified with the MCODE clustering algorithm. Interactions between the sensory sub-network and the motor sub-network were quantified through the interaction strengths of these clusters. The percentages of interactions involving the visual cortex ranged from 85 % to 18 % and the motor cortex ranged from 40 % to 9 %. Other regions with high interactions were: frontal cortex (19 ± 18 %), insula (17 ± 22 %), cuneus (16 ± 15 %), supplementary motor area (SMA, 11 ± 18 %) and subcortical regions (11 ± 10 %). Interactions between motor cortex, SMA and visual cortex accounted for 12 %, between visual cortex and cuneus for 8 % and between motor cortex, SMA and cuneus for 6 % of all interactions. These quantitative findings are supported by the visual impressions from the 2D and 3D network layouts.

  9. Multitarget transcranial direct current stimulation for freezing of gait in Parkinson's disease.

    PubMed

    Dagan, Moria; Herman, Talia; Harrison, Rachel; Zhou, Junhong; Giladi, Nir; Ruffini, Giulio; Manor, Brad; Hausdorff, Jeffrey M

    2018-04-01

    Recent findings suggest that transcranial direct current stimulation of the primary motor cortex may ameliorate freezing of gait. However, the effects of multitarget simultaneous stimulation of motor and cognitive networks are mostly unknown. The objective of this study was to evaluate the effects of multitarget transcranial direct current stimulation of the primary motor cortex and left dorsolateral prefrontal cortex on freezing of gait and related outcomes. Twenty patients with Parkinson's disease and freezing of gait received 20 minutes of transcranial direct current stimulation on 3 separate visits. Transcranial direct current stimulation targeted the primary motor cortex and left dorsolateral prefrontal cortex simultaneously, primary motor cortex only, or sham stimulation (order randomized and double-blinded assessments). Participants completed a freezing of gait-provoking test, the Timed Up and Go, and the Stroop test before and after each transcranial direct current stimulation session. Performance on the freezing of gait-provoking test (P = 0.010), Timed Up and Go (P = 0.006), and the Stroop test (P = 0.016) improved after simultaneous stimulation of the primary motor cortex and left dorsolateral prefrontal cortex, but not after primary motor cortex only or sham stimulation. Transcranial direct current stimulation designed to simultaneously target motor and cognitive regions apparently induces immediate aftereffects in the brain that translate into reduced freezing of gait and improvements in executive function and mobility. © 2018 International Parkinson and Movement Disorder Society. © 2018 International Parkinson and Movement Disorder Society.

  10. Lifetime Stress Cumulatively Programs Brain Transcriptome and Impedes Stroke Recovery: Benefit of Sensory Stimulation

    PubMed Central

    Zucchi, Fabíola C. R.; Yao, Youli; Ilnytskyy, Yaroslav; Robbins, Jerrah C.; Soltanpour, Nasrin; Kovalchuk, Igor; Kovalchuk, Olga; Metz, Gerlinde A. S.

    2014-01-01

    Prenatal stress (PS) represents a critical variable affecting lifetime health trajectories, metabolic and vascular functions. Beneficial experiences may attenuate the effects of PS and its programming of health outcomes in later life. Here we investigated in a rat model (1) if PS modulates recovery following cortical ischemia in adulthood; (2) if a second hit by adult stress (AS) exaggerates stress responses and ischemic damage; and (3) if tactile stimulation (TS) attenuates the cumulative effects of PS and AS. Prenatally stressed and non-stressed adult male rats underwent focal ischemic motor cortex lesion and were tested in skilled reaching and skilled walking tasks. Two groups of rats experienced recurrent restraint stress in adulthood and one of these groups also underwent daily TS therapy. Animals that experienced both PS and AS displayed the most severe motor disabilities after lesion. By contrast, TS promoted recovery from ischemic lesion and reduced hypothalamic-pituitary-adrenal axis activity. The data also showed that cumulative effects of adverse and beneficial lifespan experiences interact with disease outcomes and brain plasticity through the modulation of gene expression. Microarray analysis of the lesion motor cortex revealed that cumulative PS and AS interact with genes related to growth factors and transcription factors, which were not affected by PS or lesion alone. TS in PS+AS animals reverted these changes, suggesting a critical role for these factors in activity-dependent motor cortical reorganization after ischemic lesion. These findings suggest that beneficial experience later in life can moderate adverse consequences of early programming to improve cerebrovascular health. PMID:24651125

  11. Transcranial Direct Current Stimulation Modulates Neuronal Activity and Learning in Pilot Training

    PubMed Central

    Choe, Jaehoon; Coffman, Brian A.; Bergstedt, Dylan T.; Ziegler, Matthias D.; Phillips, Matthew E.

    2016-01-01

    Skill acquisition requires distributed learning both within (online) and across (offline) days to consolidate experiences into newly learned abilities. In particular, piloting an aircraft requires skills developed from extensive training and practice. Here, we tested the hypothesis that transcranial direct current stimulation (tDCS) can modulate neuronal function to improve skill learning and performance during flight simulator training of aircraft landing procedures. Thirty-two right-handed participants consented to participate in four consecutive daily sessions of flight simulation training and received sham or anodal high-definition-tDCS to the right dorsolateral prefrontal cortex (DLPFC) or left motor cortex (M1) in a randomized, double-blind experiment. Continuous electroencephalography (EEG) and functional near infrared spectroscopy (fNIRS) were collected during flight simulation, n-back working memory, and resting-state assessments. tDCS of the right DLPFC increased midline-frontal theta-band activity in flight and n-back working memory training, confirming tDCS-related modulation of brain processes involved in executive function. This modulation corresponded to a significantly different online and offline learning rates for working memory accuracy and decreased inter-subject behavioral variability in flight and n-back tasks in the DLPFC stimulation group. Additionally, tDCS of left M1 increased parietal alpha power during flight tasks and tDCS to the right DLPFC increased midline frontal theta-band power during n-back and flight tasks. These results demonstrate a modulation of group variance in skill acquisition through an increasing in learned skill consistency in cognitive and real-world tasks with tDCS. Further, tDCS performance improvements corresponded to changes in electrophysiological and blood-oxygenation activity of the DLPFC and motor cortices, providing a stronger link between modulated neuronal function and behavior. PMID:26903841

  12. Resting-state Functional Connectivity is an Age-dependent Predictor of Motor Learning Abilities.

    PubMed

    Mary, Alison; Wens, Vincent; Op de Beeck, Marc; Leproult, Rachel; De Tiège, Xavier; Peigneux, Philippe

    2017-10-01

    This magnetoencephalography study investigates how ageing modulates the relationship between pre-learning resting-state functional connectivity (rsFC) and subsequent learning. Neuromagnetic resting-state activity was recorded 5 min before motor sequence learning in 14 young (19-30 years) and 14 old (66-70 years) participants. We used a seed-based beta-band power envelope correlation approach to estimate rsFC maps, with the seed located in the right primary sensorimotor cortex. In each age group, the relation between individual rsFC and learning performance was investigated using Pearson's correlation analyses. Our results show that rsFC is predictive of subsequent motor sequence learning but involves different cross-network interactions in the two age groups. In young adults, decreased coupling between the sensorimotor network and the cortico-striato-cerebellar network is associated with better motor learning, whereas a similar relation is found in old adults between the sensorimotor, the dorsal-attentional and the DMNs. Additionally, age-related correlational differences were found in the dorsolateral prefrontal cortex, known to subtend attentional and controlled processes. These findings suggest that motor skill learning depends-in an age-dependent manner-on subtle interactions between resting-state networks subtending motor activity on the one hand, and controlled and attentional processes on the other hand. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. fMRI and MRS measures of neuroplasticity in the pharyngeal motor cortex

    PubMed Central

    Michou, Emilia; Williams, Steve; Vidyasagar, Rishma; Downey, Darragh; Mistry, Satish; Edden, Richard A.E.; Hamdy, Shaheen

    2016-01-01

    Introduction Paired associative stimulation (PAS), is a novel non-invasive technique where two neural substrates are employed in a temporally coordinated manner in order to modulate cortico-motor excitability within the motor cortex (M1). In swallowing, combined pharyngeal electrical and transcranial-magnetic-stimulation induced beneficial neurophysiological and behavioural effects in healthy subjects and dysphagic stroke patients. Here, we aimed to investigate the whole-brain changes in neural activation during swallowing using functional magnetic resonance imaging (fMRI) following PAS application and in parallel assess associated GABA changes with magnetic resonance spectroscopy (MRS). Methods Healthy adults (n = 11, 38 ± 9 years old) were randomised to receive real and sham PAS to the ‘stronger’ motor cortex pharyngeal representation, on 2 separate visits. Following PAS, event-related fMRI was performed to assess changes in brain activation in response to water and saliva swallowing and during rest. Data were analysed (SPM8) at P < .001. MRS data were acquired using MEGA-PRESS before and after the fMRI acquisitions on both visits and GABA concentrations were measured (AMARES, jMRUI). Results Following real PAS, BOLD signal changes (group analyses) increased at the site of stimulation during water and saliva swallowing, compared to sham PAS. It is also evident that PAS induced significant increases in BOLD signal to contralateral (to stimulation) hemispheric areas that are of importance to the swallowing neural network. Following real PAS, GABA: creatine ratio showed a trend to increase contralateral to PAS. Conclusion Targeted PAS applied to the human pharyngeal motor cortex induces local and remote changes in both primary and non-primary areas for water and saliva tasks. There is a possibility that changes of the inhibitory neurotransmitter, GABA, may play a role in the changes in BOLD signal. These findings provide evidence for the mechanisms underlying the beneficial effects of PAS on the brain swallowing network. PMID:25976926

  14. Sensory-motor interactions for vocal pitch monitoring in non-primary human auditory cortex.

    PubMed

    Greenlee, Jeremy D W; Behroozmand, Roozbeh; Larson, Charles R; Jackson, Adam W; Chen, Fangxiang; Hansen, Daniel R; Oya, Hiroyuki; Kawasaki, Hiroto; Howard, Matthew A

    2013-01-01

    The neural mechanisms underlying processing of auditory feedback during self-vocalization are poorly understood. One technique used to study the role of auditory feedback involves shifting the pitch of the feedback that a speaker receives, known as pitch-shifted feedback. We utilized a pitch shift self-vocalization and playback paradigm to investigate the underlying neural mechanisms of audio-vocal interaction. High-resolution electrocorticography (ECoG) signals were recorded directly from auditory cortex of 10 human subjects while they vocalized and received brief downward (-100 cents) pitch perturbations in their voice auditory feedback (speaking task). ECoG was also recorded when subjects passively listened to playback of their own pitch-shifted vocalizations. Feedback pitch perturbations elicited average evoked potential (AEP) and event-related band power (ERBP) responses, primarily in the high gamma (70-150 Hz) range, in focal areas of non-primary auditory cortex on superior temporal gyrus (STG). The AEPs and high gamma responses were both modulated by speaking compared with playback in a subset of STG contacts. From these contacts, a majority showed significant enhancement of high gamma power and AEP responses during speaking while the remaining contacts showed attenuated response amplitudes. The speaking-induced enhancement effect suggests that engaging the vocal motor system can modulate auditory cortical processing of self-produced sounds in such a way as to increase neural sensitivity for feedback pitch error detection. It is likely that mechanisms such as efference copies may be involved in this process, and modulation of AEP and high gamma responses imply that such modulatory effects may affect different cortical generators within distinctive functional networks that drive voice production and control.

  15. Sensory-Motor Interactions for Vocal Pitch Monitoring in Non-Primary Human Auditory Cortex

    PubMed Central

    Larson, Charles R.; Jackson, Adam W.; Chen, Fangxiang; Hansen, Daniel R.; Oya, Hiroyuki; Kawasaki, Hiroto; Howard, Matthew A.

    2013-01-01

    The neural mechanisms underlying processing of auditory feedback during self-vocalization are poorly understood. One technique used to study the role of auditory feedback involves shifting the pitch of the feedback that a speaker receives, known as pitch-shifted feedback. We utilized a pitch shift self-vocalization and playback paradigm to investigate the underlying neural mechanisms of audio-vocal interaction. High-resolution electrocorticography (ECoG) signals were recorded directly from auditory cortex of 10 human subjects while they vocalized and received brief downward (−100 cents) pitch perturbations in their voice auditory feedback (speaking task). ECoG was also recorded when subjects passively listened to playback of their own pitch-shifted vocalizations. Feedback pitch perturbations elicited average evoked potential (AEP) and event-related band power (ERBP) responses, primarily in the high gamma (70–150 Hz) range, in focal areas of non-primary auditory cortex on superior temporal gyrus (STG). The AEPs and high gamma responses were both modulated by speaking compared with playback in a subset of STG contacts. From these contacts, a majority showed significant enhancement of high gamma power and AEP responses during speaking while the remaining contacts showed attenuated response amplitudes. The speaking-induced enhancement effect suggests that engaging the vocal motor system can modulate auditory cortical processing of self-produced sounds in such a way as to increase neural sensitivity for feedback pitch error detection. It is likely that mechanisms such as efference copies may be involved in this process, and modulation of AEP and high gamma responses imply that such modulatory effects may affect different cortical generators within distinctive functional networks that drive voice production and control. PMID:23577157

  16. Role of testosterone and Y chromosome genes for the masculinization of the human brain.

    PubMed

    Savic, Ivanka; Frisen, Louise; Manzouri, Amirhossein; Nordenstrom, Anna; Lindén Hirschberg, Angelica

    2017-04-01

    Women with complete androgen insensitivity syndrome (CAIS) have a male (46,XY) karyotype but no functional androgen receptors. Their condition, therefore, offers a unique model for studying testosterone effects on cerebral sex dimorphism. We present MRI data from 16 women with CAIS and 32 male (46,XY) and 32 female (46,XX) controls. FreeSurfer software was employed to measure cortical thickness and subcortical structural volumes. Axonal connections, indexed by fractional anisotropy, (FA) were measured with diffusion tensor imaging, and functional connectivity with resting state fMRI. Compared to men, CAIS women displayed a "female" pattern by having thicker parietal and occipital cortices, lower FA values in the right corticospinal, superior and inferior longitudinal tracts, and corpus callosum. Their functional connectivity from the amygdala to the medial prefrontal cortex, was stronger and amygdala-connections to the motor cortex weaker than in control men. CAIS and control women also showed stronger posterior cingulate and precuneus connections in the default mode network. Thickness of the motor cortex, the caudate volume, and the FA in the callosal body followed, however, a "male" pattern. Altogether, these data suggest that testosterone modulates the microstructure of somatosensory and visual cortices and their axonal connections to the frontal cortex. Testosterone also influenced functional connections from the amygdala, whereas the motor cortex could, in agreement with our previous reports, be moderated by processes linked to X-chromosome gene dosage. These data raise the question about other genetic factors masculinizing the human brain than the SRY gene and testosterone. Hum Brain Mapp 38:1801-1814, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  17. Non-Invasive Brain Stimulation to Enhance Post-Stroke Recovery.

    PubMed

    Kubis, Nathalie

    2016-01-01

    Brain plasticity after stroke remains poorly understood. Patients may improve spontaneously within the first 3 months and then more slowly in the coming year. The first day, decreased edema and reperfusion of the ischemic penumbra may possibly account for these phenomena, but the improvement during the next weeks suggests plasticity phenomena and cortical reorganization of the brain ischemic areas and of more remote areas. Indeed, the injured ischemic motor cortex has a reduced cortical excitability at the acute phase and a suspension of the topographic representation of affected muscles, whereas the contralateral motor cortex has an increased excitability and an enlarged somatomotor representation; furthermore, contralateral cortex exerts a transcallosal interhemispheric inhibition on the ischemic cortex. This results from the imbalance of the physiological reciprocal interhemispheric inhibition of each hemisphere on the other, contributing to worsening of neurological deficit. Cortical excitability is measurable through transcranial magnetic stimulation (TMS) and prognosis has been established according to the presence of motor evoked potentials (MEP) at the acute phase of stroke, which is predictive of better recovery. Conversely, the lack of response to early stimulation is associated with a poor functional outcome. Non-invasive stimulation techniques such as repetitive TMS (rTMS) or transcranial direct current stimulation (tDCS) have the potential to modulate brain cortical excitability with long lasting effects. In the setting of cerebrovascular disease, around 1000 stroke subjects have been included in placebo-controlled trials so far, most often with an objective of promoting motor recovery of the upper limb. High frequency repetitive stimulation (>3 Hz) rTMS, aiming to increase excitability of the ischemic cortex, or low frequency repetitive stimulation (≤1 Hz), aiming to reduce excitability of the contralateral homonymous cortex, or combined therapies, have shown various effects on the functional disability score and neurological scales of treated patients and on the duration of the treatment. We review here the patients' characteristics and parameters of stimulation that could predict a good response, as well as safety issues. At last, we review what we have learnt from experimental studies and discuss potential directions to conduct future studies.

  18. Non-Invasive Brain Stimulation to Enhance Post-Stroke Recovery

    PubMed Central

    Kubis, Nathalie

    2016-01-01

    Brain plasticity after stroke remains poorly understood. Patients may improve spontaneously within the first 3 months and then more slowly in the coming year. The first day, decreased edema and reperfusion of the ischemic penumbra may possibly account for these phenomena, but the improvement during the next weeks suggests plasticity phenomena and cortical reorganization of the brain ischemic areas and of more remote areas. Indeed, the injured ischemic motor cortex has a reduced cortical excitability at the acute phase and a suspension of the topographic representation of affected muscles, whereas the contralateral motor cortex has an increased excitability and an enlarged somatomotor representation; furthermore, contralateral cortex exerts a transcallosal interhemispheric inhibition on the ischemic cortex. This results from the imbalance of the physiological reciprocal interhemispheric inhibition of each hemisphere on the other, contributing to worsening of neurological deficit. Cortical excitability is measurable through transcranial magnetic stimulation (TMS) and prognosis has been established according to the presence of motor evoked potentials (MEP) at the acute phase of stroke, which is predictive of better recovery. Conversely, the lack of response to early stimulation is associated with a poor functional outcome. Non-invasive stimulation techniques such as repetitive TMS (rTMS) or transcranial direct current stimulation (tDCS) have the potential to modulate brain cortical excitability with long lasting effects. In the setting of cerebrovascular disease, around 1000 stroke subjects have been included in placebo-controlled trials so far, most often with an objective of promoting motor recovery of the upper limb. High frequency repetitive stimulation (>3 Hz) rTMS, aiming to increase excitability of the ischemic cortex, or low frequency repetitive stimulation (≤1 Hz), aiming to reduce excitability of the contralateral homonymous cortex, or combined therapies, have shown various effects on the functional disability score and neurological scales of treated patients and on the duration of the treatment. We review here the patients’ characteristics and parameters of stimulation that could predict a good response, as well as safety issues. At last, we review what we have learnt from experimental studies and discuss potential directions to conduct future studies. PMID:27512367

  19. The facilitatory effects of intermittent theta burst stimulation on corticospinal excitability are enhanced by nicotine.

    PubMed

    Swayne, Orlando B C; Teo, James T H; Greenwood, Richard J; Rothwell, John C

    2009-08-01

    Intermittent theta burst stimulation (iTBS) is increasingly widely used as a means of facilitating corticospinal excitability in the human primary motor cortex. This form of facilitatory plasticity within the stimulated cortex may occur by induction of long term potentiation (LTP). In animal models, agonists of nicotinic acetylcholine receptors have been shown to modulate or induce LTP; we thus sought to test whether nicotine may modulate the effects of iTBS on corticospinal excitability in humans. A double-blind placebo-controlled cross-over design study was conducted with 10 healthy subjects. iTBS was delivered 60min after subjects took either 4mg nicotine or placebo lozenges, and motor-evoked potentials (MEPs) were then recorded for 40min after the end of stimulation. In the placebo arm, iTBS produced an increase in the amplitudes of MEPs which lasted for 5min. In the nicotine arm, iTBS produced a more pronounced facilitation of MEPs that was still present at 40min. In a control experiment, nicotine alone had no effect on MEP amplitudes when given in the absence of iTBS. These data indicate that the effects of iTBS can be enhanced and prolonged by nicotine. These results are consistent with animal models demonstrating nicotinic modulation of facilitatory plasticity, and will be of interest to investigators seeking to enhance artificially induced changes in cortical excitability.

  20. Dissociating Contributions of the Motor Cortex to Speech Perception and Response Bias by Using Transcranial Magnetic Stimulation

    PubMed Central

    Smalle, Eleonore H. M.; Rogers, Jack; Möttönen, Riikka

    2015-01-01

    Recent studies using repetitive transcranial magnetic stimulation (TMS) have demonstrated that disruptions of the articulatory motor cortex impair performance in demanding speech perception tasks. These findings have been interpreted as support for the idea that the motor cortex is critically involved in speech perception. However, the validity of this interpretation has been called into question, because it is unknown whether the TMS-induced disruptions in the motor cortex affect speech perception or rather response bias. In the present TMS study, we addressed this question by using signal detection theory to calculate sensitivity (i.e., d′) and response bias (i.e., criterion c). We used repetitive TMS to temporarily disrupt the lip or hand representation in the left motor cortex. Participants discriminated pairs of sounds from a “ba”–“da” continuum before TMS, immediately after TMS (i.e., during the period of motor disruption), and after a 30-min break. We found that the sensitivity for between-category pairs was reduced during the disruption of the lip representation. In contrast, disruption of the hand representation temporarily reduced response bias. This double dissociation indicates that the hand motor cortex contributes to response bias during demanding discrimination tasks, whereas the articulatory motor cortex contributes to perception of speech sounds. PMID:25274987

  1. Optogenetic Modulation and Multi-Electrode Analysis of Cerebellar Networks In Vivo

    PubMed Central

    Kruse, Wolfgang; Krause, Martin; Aarse, Janna; Mark, Melanie D.; Manahan-Vaughan, Denise; Herlitze, Stefan

    2014-01-01

    The firing patterns of cerebellar Purkinje cells (PCs), as the sole output of the cerebellar cortex, determine and tune motor behavior. PC firing is modulated by various inputs from different brain regions and by cell-types including granule cells (GCs), climbing fibers and inhibitory interneurons. To understand how signal integration in PCs occurs and how subtle changes in the modulation of PC firing lead to adjustment of motor behaviors, it is important to precisely record PC firing in vivo and to control modulatory pathways in a spatio-temporal manner. Combining optogenetic and multi-electrode approaches, we established a new method to integrate light-guides into a multi-electrode system. With this method we are able to variably position the light-guide in defined regions relative to the recording electrode with micrometer precision. We show that PC firing can be precisely monitored and modulated by light-activation of channelrhodopsin-2 (ChR2) expressed in PCs, GCs and interneurons. Thus, this method is ideally suited to investigate the spatio/temporal modulation of PCs in anesthetized and in behaving mice. PMID:25144735

  2. Articulatory movements modulate auditory responses to speech

    PubMed Central

    Agnew, Z.K.; McGettigan, C.; Banks, B.; Scott, S.K.

    2013-01-01

    Production of actions is highly dependent on concurrent sensory information. In speech production, for example, movement of the articulators is guided by both auditory and somatosensory input. It has been demonstrated in non-human primates that self-produced vocalizations and those of others are differentially processed in the temporal cortex. The aim of the current study was to investigate how auditory and motor responses differ for self-produced and externally produced speech. Using functional neuroimaging, subjects were asked to produce sentences aloud, to silently mouth while listening to a different speaker producing the same sentence, to passively listen to sentences being read aloud, or to read sentences silently. We show that that separate regions of the superior temporal cortex display distinct response profiles to speaking aloud, mouthing while listening, and passive listening. Responses in anterior superior temporal cortices in both hemispheres are greater for passive listening compared with both mouthing while listening, and speaking aloud. This is the first demonstration that articulation, whether or not it has auditory consequences, modulates responses of the dorsolateral temporal cortex. In contrast posterior regions of the superior temporal cortex are recruited during both articulation conditions. In dorsal regions of the posterior superior temporal gyrus, responses to mouthing and reading aloud were equivalent, and in more ventral posterior superior temporal sulcus, responses were greater for reading aloud compared with mouthing while listening. These data demonstrate an anterior–posterior division of superior temporal regions where anterior fields are suppressed during motor output, potentially for the purpose of enhanced detection of the speech of others. We suggest posterior fields are engaged in auditory processing for the guidance of articulation by auditory information. PMID:22982103

  3. Restoring Cognitive Functions Using Non-Invasive Brain Stimulation Techniques in Patients with Cerebellar Disorders

    PubMed Central

    Pope, Paul A.; Miall, R. Chris

    2014-01-01

    Numerous studies have highlighted the possibility of modulating the excitability of cerebro–cerebellar circuits bi-directionally using transcranial electrical brain stimulation, in a manner akin to that observed using magnetic stimulation protocols. It has been proposed that cerebellar stimulation activates Purkinje cells in the cerebellar cortex, leading to inhibition of the dentate nucleus, which exerts a tonic facilitatory drive onto motor and cognitive regions of cortex through a synaptic relay in the ventral–lateral thalamus. Some cerebellar deficits present with cognitive impairments if damage to non-motor regions of the cerebellum disrupts the coupling with cerebral cortical areas for thinking and reasoning. Indeed, white matter changes in the dentato–rubral tract correlate with cognitive assessments in patients with Friedreich ataxia, suggesting that this pathway is one component of the anatomical substrate supporting a cerebellar contribution to cognition. An understanding of the physiology of the cerebro–cerebellar pathway previously helped us to constrain our interpretation of results from two recent studies in which we showed cognitive enhancements in healthy participants during tests of arithmetic after electrical stimulation of the cerebellum, but only when task demands were high. Others studies have also shown how excitation of the prefrontal cortex can enhance performance in a variety of working memory tasks. Thus, future efforts might be guided toward neuro-enhancement in certain patient populations, using what is commonly termed “non-invasive brain stimulation” as a cognitive rehabilitation tool to modulate cerebro–cerebellar circuits, or for stimulation over the cerebral cortex to compensate for decreased cerebellar drive to this region. This article will address these possibilities with a review of the relevant literature covering ataxias and cerebellar cognitive affective disorders, which are characterized by thalamo–cortical disturbances. PMID:24765079

  4. Space coding for sensorimotor transformations can emerge through unsupervised learning.

    PubMed

    De Filippo De Grazia, Michele; Cutini, Simone; Lisi, Matteo; Zorzi, Marco

    2012-08-01

    The posterior parietal cortex (PPC) is fundamental for sensorimotor transformations because it combines multiple sensory inputs and posture signals into different spatial reference frames that drive motor programming. Here, we present a computational model mimicking the sensorimotor transformations occurring in the PPC. A recurrent neural network with one layer of hidden neurons (restricted Boltzmann machine) learned a stochastic generative model of the sensory data without supervision. After the unsupervised learning phase, the activity of the hidden neurons was used to compute a motor program (a population code on a bidimensional map) through a simple linear projection and delta rule learning. The average motor error, calculated as the difference between the expected and the computed output, was less than 3°. Importantly, analyses of the hidden neurons revealed gain-modulated visual receptive fields, thereby showing that space coding for sensorimotor transformations similar to that observed in the PPC can emerge through unsupervised learning. These results suggest that gain modulation is an efficient coding strategy to integrate visual and postural information toward the generation of motor commands.

  5. Motor demand-dependent activation of ipsilateral motor cortex.

    PubMed

    Buetefisch, Cathrin M; Revill, Kate Pirog; Shuster, Linda; Hines, Benjamin; Parsons, Michael

    2014-08-15

    The role of ipsilateral primary motor cortex (M1) in hand motor control during complex task performance remains controversial. Bilateral M1 activation is inconsistently observed in functional (f)MRI studies of unilateral hand performance. Two factors limit the interpretation of these data. As the motor tasks differ qualitatively in these studies, it is conceivable that M1 contributions differ with the demand on skillfulness. Second, most studies lack the verification of a strictly unilateral execution of the motor task during the acquisition of imaging data. Here, we use fMRI to determine whether ipsilateral M1 activity depends on the demand for precision in a pointing task where precision varied quantitatively while movement trajectories remained equal. Thirteen healthy participants used an MRI-compatible joystick to point to targets of four different sizes in a block design. A clustered acquisition technique allowed simultaneous fMRI/EMG data collection and confirmed that movements were strictly unilateral. Accuracy of performance increased with target size. Overall, the pointing task revealed activation in contralateral and ipsilateral M1, extending into contralateral somatosensory and parietal areas. Target size-dependent activation differences were found in ipsilateral M1 extending into the temporal/parietal junction, where activation increased with increasing demand on accuracy. The results suggest that ipsilateral M1 is active during the execution of a unilateral motor task and that its activity is modulated by the demand on precision. Copyright © 2014 the American Physiological Society.

  6. Feeling the beat: premotor and striatal interactions in musicians and non-musicians during beat perception

    PubMed Central

    Grahn, Jessica A.; Rowe, James B.

    2009-01-01

    Little is known about the underlying neurobiology of rhythm and beat perception, despite its universal cultural importance. Here we used functional magnetic resonance imaging to study rhythm perception in musicians and non-musicians. Three conditions varied in the degree to which external reinforcement versus internal generation of the beat was required. The ‘Volume’ condition strongly externally marked the beat with volume changes, the ‘Duration’ condition marked the beat with weaker accents arising from duration changes, and the ‘Unaccented’ condition required the beat to be entirely internally generated. In all conditions, beat rhythms compared to nonbeat control rhythms revealed putamen activity. The presence of a beat was also associated with greater connectivity between the putamen and the supplementary motor area (SMA), the premotor cortex (PMC) and auditory cortex. In contrast, the type of accent within the beat conditions modulated the coupling between premotor and auditory cortex, with greater modulation for musicians than non-musicians. Importantly, the putamen's response to beat conditions was not due to differences in temporal complexity between the three rhythm conditions. We propose that a cortico-subcortical network including the putamen, SMA, and PMC is engaged for the analysis of temporal sequences and prediction or generation of putative beats, especially under conditions that may require internal generation of the beat. The importance of this system for auditory-motor interaction and development of precisely timed movement is suggested here by its facilitation in musicians. PMID:19515922

  7. Feeling the beat: premotor and striatal interactions in musicians and nonmusicians during beat perception.

    PubMed

    Grahn, Jessica A; Rowe, James B

    2009-06-10

    Little is known about the underlying neurobiology of rhythm and beat perception, despite its universal cultural importance. Here we used functional magnetic resonance imaging to study rhythm perception in musicians and nonmusicians. Three conditions varied in the degree to which external reinforcement versus internal generation of the beat was required. The "volume" condition strongly externally marked the beat with volume changes, the "duration" condition marked the beat with weaker accents arising from duration changes, and the "unaccented" condition required the beat to be entirely internally generated. In all conditions, beat rhythms compared with nonbeat control rhythms revealed putamen activity. The presence of a beat was also associated with greater connectivity between the putamen and the supplementary motor area (SMA), the premotor cortex (PMC), and auditory cortex. In contrast, the type of accent within the beat conditions modulated the coupling between premotor and auditory cortex, with greater modulation for musicians than nonmusicians. Importantly, the response of the putamen to beat conditions was not attributable to differences in temporal complexity between the three rhythm conditions. We propose that a cortico-subcortical network including the putamen, SMA, and PMC is engaged for the analysis of temporal sequences and prediction or generation of putative beats, especially under conditions that may require internal generation of the beat. The importance of this system for auditory-motor interaction and development of precisely timed movement is suggested here by its facilitation in musicians.

  8. Beta-band activity and connectivity in sensorimotor and parietal cortex are important for accurate motor performance.

    PubMed

    Chung, Jae W; Ofori, Edward; Misra, Gaurav; Hess, Christopher W; Vaillancourt, David E

    2017-01-01

    Accurate motor performance may depend on the scaling of distinct oscillatory activity within the motor cortex and effective neural communication between the motor cortex and other brain areas. Oscillatory activity within the beta-band (13-30Hz) has been suggested to provide distinct functional roles for attention and sensorimotor control, yet it remains unclear how beta-band and other oscillatory activity within and between cortical regions is coordinated to enhance motor performance. We explore this open issue by simultaneously measuring high-density cortical activity and elbow flexor and extensor neuromuscular activity during ballistic movements, and manipulating error using high and low visual gain across three target distances. Compared with low visual gain, high visual gain decreased movement errors at each distance. Group analyses in 3D source-space revealed increased theta-, alpha-, and beta-band desynchronization of the contralateral motor cortex and medial parietal cortex in high visual gain conditions and this corresponded to reduced movement error. Dynamic causal modeling was used to compute connectivity between motor cortex and parietal cortex. Analyses revealed that gain affected the directionally-specific connectivity across broadband frequencies from parietal to sensorimotor cortex but not from sensorimotor cortex to parietal cortex. These new findings provide support for the interpretation that broad-band oscillations in theta, alpha, and beta frequency bands within sensorimotor and parietal cortex coordinate to facilitate accurate upper limb movement. Our findings establish a link between sensorimotor oscillations in the context of online motor performance in common source space across subjects. Specifically, the extent and distinct role of medial parietal cortex to sensorimotor beta connectivity and local domain broadband activity combine in a time and frequency manner to assist ballistic movements. These findings can serve as a model to examine whether similar source space EEG dynamics exhibit different time-frequency changes in individuals with neurological disorders that cause movement errors. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Motor learning in animal models of Parkinson’s Disease: Aberrant synaptic plasticity in the motor cortex

    PubMed Central

    Xu, Tonghui; Wang, Shaofang; Lalchandani, Rupa R.; Ding, Jun B

    2017-01-01

    In Parkinson’s disease (PD), dopamine depletion causes dramatic changes in the brain resulting in debilitating cognitive and motor deficits. PD neuropathology has been restricted to postmortem examinations, which are limited to only a single time point of PD progression. Models of PD where dopamine tone in the brain are chemically or physically disrupted are valuable tools in understanding the mechanisms of the disease. The basal ganglia have been well studied in the context of PD, and circuit changes in response to dopamine loss have been linked to the motor dysfunctions in PD. However, the etiology of the cognitive dysfunctions that are comorbid in PD patients has remained unclear until now. In this paper, we review recent studies exploring how dopamine depletion affects the motor cortex at the synaptic level. In particular, we highlight our recent findings on abnormal spine dynamics in the motor cortex of PD mouse models through in vivo, time-lapse imaging and motor-skill behavior assays. In combination with previous studies, a role of the motor cortex in skill-learning, and the impairment of this ability with the loss of dopamine, is becoming more apparent. Taken together, we conclude with a discussion on the potential role for the motor cortex in the motor-skill learning and cognitive impairments of PD, with the possibility of targeting the motor cortex for future PD therapeutics. PMID:28343366

  10. Effect of hindlimb unloading on stereological parameters of the motor cortex and hippocampus in male rats.

    PubMed

    Salehi, Mohammad Saied; Mirzaii-Dizgah, Iraj; Vasaghi-Gharamaleki, Behnoosh; Zamiri, Mohammad Javad

    2016-11-09

    Hindlimb unloading (HU) can cause motion and cognition dysfunction, although its cellular and molecular mechanisms are not well understood. The aim of the present study was to determine the stereological parameters of the brain areas involved in motion (motor cortex) and spatial learning - memory (hippocampus) under an HU condition. Sixteen adult male rats, kept under a 12 : 12 h light-dark cycle, were divided into two groups of freely moving (n=8) and HU (n=8) rats. The volume of motor cortex and hippocampus, the numerical cell density of neurons in layers I, II-III, V, and VI of the motor cortex, the entire motor cortex as well as the primary motor cortex, and the numerical density of the CA1, CA3, and dentate gyrus subregions of the hippocampus were estimated. No significant differences were observed in the evaluated parameters. Our results thus indicated that motor cortical and hippocampal atrophy and cell loss may not necessarily be involved in the motion and spatial learning memory impairment in the rat.

  11. Ongoing slow oscillatory phase modulates speech intelligibility in cooperation with motor cortical activity.

    PubMed

    Onojima, Takayuki; Kitajo, Keiichi; Mizuhara, Hiroaki

    2017-01-01

    Neural oscillation is attracting attention as an underlying mechanism for speech recognition. Speech intelligibility is enhanced by the synchronization of speech rhythms and slow neural oscillation, which is typically observed as human scalp electroencephalography (EEG). In addition to the effect of neural oscillation, it has been proposed that speech recognition is enhanced by the identification of a speaker's motor signals, which are used for speech production. To verify the relationship between the effect of neural oscillation and motor cortical activity, we measured scalp EEG, and simultaneous EEG and functional magnetic resonance imaging (fMRI) during a speech recognition task in which participants were required to recognize spoken words embedded in noise sound. We proposed an index to quantitatively evaluate the EEG phase effect on behavioral performance. The results showed that the delta and theta EEG phase before speech inputs modulated the participant's response time when conducting speech recognition tasks. The simultaneous EEG-fMRI experiment showed that slow EEG activity was correlated with motor cortical activity. These results suggested that the effect of the slow oscillatory phase was associated with the activity of the motor cortex during speech recognition.

  12. Learning-Dependent Potentiation in the Vibrissal Motor Cortex Is Closely Related to the Acquisition of Conditioned Whisker Responses in Behaving Mice

    ERIC Educational Resources Information Center

    Delgado-Garcia, Jose Maria; Troncoso, Julieta; Munera, Alejandro

    2007-01-01

    The role of the primary motor cortex in the acquisition of new motor skills was evaluated during classical conditioning of vibrissal protraction responses in behaving mice, using a trace paradigm. Conditioned stimulus (CS) presentation elicited a characteristic field potential in the vibrissal motor cortex, which was dependent on the synchronized…

  13. Sex-Specific Automatic Responses to Infant Cries: TMS Reveals Greater Excitability in Females than Males in Motor Evoked Potentials

    PubMed Central

    Messina, Irene; Cattaneo, Luigi; Venuti, Paola; de Pisapia, Nicola; Serra, Mauro; Esposito, Gianluca; Rigo, Paola; Farneti, Alessandra; Bornstein, Marc H.

    2016-01-01

    Neuroimaging reveals that infant cries activate parts of the premotor cortical system. To validate this effect in a more direct way, we used event-related transcranial magnetic stimulation (TMS). Here, we investigated the presence and the time course of modulation of motor cortex excitability in young adults who listened to infant cries. Specifically, we recorded motor evoked potentials (MEPs) from the biceps brachii (BB) and interosseus dorsalis primus (ID1) muscles as produced by TMS delivered from 0 to 250 ms after sound onset in six steps of 50 ms in 10 females and 10 males. We observed an excitatory modulation of MEPs at 100 ms from the onset of infant cry specific to females and to the ID1 muscle. We regard this modulation as a response to natural cry sounds because it was attenuated to stimuli increasingly different from natural cry and absent in a separate group of females who listened to non-cry stimuli physically matched to natural infant cries. Furthermore, the 100-ms latency of this response is not compatible with a voluntary reaction to the stimulus but suggests an automatic, bottom-up audiomotor association. The brains of adult females appear to be tuned to respond to infant cries with automatic motor excitation. PMID:26779061

  14. Plasticity in One Hemisphere, Control From Two: Adaptation in Descending Motor Pathways After Unilateral Corticospinal Injury in Neonatal Rats

    PubMed Central

    Wen, Tong-Chun; Lall, Sophia; Pagnotta, Corey; Markward, James; Gupta, Disha; Ratnadurai-Giridharan, Shivakeshavan; Bucci, Jacqueline; Greenwald, Lucy; Klugman, Madelyne; Hill, N. Jeremy; Carmel, Jason B.

    2018-01-01

    After injury to the corticospinal tract (CST) in early development there is large-scale adaptation of descending motor pathways. Some studies suggest the uninjured hemisphere controls the impaired forelimb, while others suggest that the injured hemisphere does; these pathways have never been compared directly. We tested the contribution of each motor cortex to the recovery forelimb function after neonatal injury of the CST. We cut the left pyramid (pyramidotomy) of postnatal day 7 rats, which caused a measurable impairment of the right forelimb. We used pharmacological inactivation of each motor cortex to test its contribution to a skilled reach and supination task. Rats with neonatal pyramidotomy were further impaired by inactivation of motor cortex in both the injured and the uninjured hemispheres, while the forelimb of uninjured rats was impaired only from the contralateral motor cortex. Thus, inactivation demonstrated motor control from each motor cortex. In contrast, physiological and anatomical interrogation of these pathways support adaptations only in the uninjured hemisphere. Intracortical microstimulation of motor cortex in the uninjured hemisphere of rats with neonatal pyramidotomy produced responses from both forelimbs, while stimulation of the injured hemisphere did not elicit responses from either forelimb. Both anterograde and retrograde tracers were used to label corticofugal pathways. There was no increased plasticity from the injured hemisphere, either from cortex to the red nucleus or the red nucleus to the spinal cord. In contrast, there were very strong CST connections to both halves of the spinal cord from the uninjured motor cortex. Retrograde tracing produced maps of each forelimb within the uninjured hemisphere, and these were partly segregated. This suggests that the uninjured hemisphere may encode separate control of the unimpaired and the impaired forelimbs of rats with neonatal pyramidotomy. PMID:29706871

  15. Plasticity in One Hemisphere, Control From Two: Adaptation in Descending Motor Pathways After Unilateral Corticospinal Injury in Neonatal Rats.

    PubMed

    Wen, Tong-Chun; Lall, Sophia; Pagnotta, Corey; Markward, James; Gupta, Disha; Ratnadurai-Giridharan, Shivakeshavan; Bucci, Jacqueline; Greenwald, Lucy; Klugman, Madelyne; Hill, N Jeremy; Carmel, Jason B

    2018-01-01

    After injury to the corticospinal tract (CST) in early development there is large-scale adaptation of descending motor pathways. Some studies suggest the uninjured hemisphere controls the impaired forelimb, while others suggest that the injured hemisphere does; these pathways have never been compared directly. We tested the contribution of each motor cortex to the recovery forelimb function after neonatal injury of the CST. We cut the left pyramid (pyramidotomy) of postnatal day 7 rats, which caused a measurable impairment of the right forelimb. We used pharmacological inactivation of each motor cortex to test its contribution to a skilled reach and supination task. Rats with neonatal pyramidotomy were further impaired by inactivation of motor cortex in both the injured and the uninjured hemispheres, while the forelimb of uninjured rats was impaired only from the contralateral motor cortex. Thus, inactivation demonstrated motor control from each motor cortex. In contrast, physiological and anatomical interrogation of these pathways support adaptations only in the uninjured hemisphere. Intracortical microstimulation of motor cortex in the uninjured hemisphere of rats with neonatal pyramidotomy produced responses from both forelimbs, while stimulation of the injured hemisphere did not elicit responses from either forelimb. Both anterograde and retrograde tracers were used to label corticofugal pathways. There was no increased plasticity from the injured hemisphere, either from cortex to the red nucleus or the red nucleus to the spinal cord. In contrast, there were very strong CST connections to both halves of the spinal cord from the uninjured motor cortex. Retrograde tracing produced maps of each forelimb within the uninjured hemisphere, and these were partly segregated. This suggests that the uninjured hemisphere may encode separate control of the unimpaired and the impaired forelimbs of rats with neonatal pyramidotomy.

  16. Activations in gray and white matter are modulated by uni-manual responses during within and inter-hemispheric transfer: effects of response hand and right-handedness.

    PubMed

    Diwadkar, Vaibhav A; Bellani, Marcella; Chowdury, Asadur; Savazzi, Silvia; Perlini, Cinzia; Marinelli, Veronica; Zoccatelli, Giada; Alessandrini, Franco; Ciceri, Elisa; Rambaldelli, Gianluca; Ruggieri, Mirella; Carlo Altamura, A; Marzi, Carlo A; Brambilla, Paolo

    2017-08-14

    Because the visual cortices are contra-laterally organized, inter-hemispheric transfer tasks have been used to behaviorally probe how information briefly presented to one hemisphere of the visual cortex is integrated with responses resulting from the ipsi- or contra-lateral motor cortex. By forcing rapid information exchange across diverse regions, these tasks robustly activate not only gray matter regions, but also white matter tracts. It is likely that the response hand itself (dominant or non-dominant) modulates gray and white matter activations during within and inter-hemispheric transfer. Yet the role of uni-manual responses and/or right hand dominance in modulating brain activations during such basic tasks is unclear. Here we investigated how uni-manual responses with either hand modulated activations during a basic visuo-motor task (the established Poffenberger paradigm) alternating between inter- and within-hemispheric transfer conditions. In a large sample of strongly right-handed adults (n = 49), we used a factorial combination of transfer condition [Inter vs. Within] and response hand [Dominant(Right) vs. Non-Dominant (Left)] to discover fMRI-based activations in gray matter, and in narrowly defined white matter tracts. These tracts were identified using a priori probabilistic white matter atlases. Uni-manual responses with the right hand strongly modulated activations in gray matter, and notably in white matter. Furthermore, when responding with the left hand, activations during inter-hemispheric transfer were strongly predicted by the degree of right-hand dominance, with increased right-handedness predicting decreased fMRI activation. Finally, increasing age within the middle-aged sample was associated with a decrease in activations. These results provide novel evidence of complex relationships between uni-manual responses in right-handed subjects, and activations during within- and inter-hemispheric transfer suggest that the organization of the motor system exerts sophisticated functional effects. Moreover, our evidence of activation in white matter tracts is consistent with prior studies, confirming fMRI-detectable white matter activations which are systematically modulated by experimental condition.

  17. Protein Synthesis Inhibition in the Peri-Infarct Cortex Slows Motor Recovery in Rats.

    PubMed

    Schubring-Giese, Maximilian; Leemburg, Susan; Luft, Andreas Rüdiger; Hosp, Jonas Aurel

    2016-01-01

    Neuroplasticity and reorganization of brain motor networks are thought to enable recovery of motor function after ischemic stroke. Especially in the cortex surrounding the ischemic scar (i.e., peri-infarct cortex), evidence for lasting reorganization has been found at the level of neurons and networks. This reorganization depends on expression of specific genes and subsequent protein synthesis. To test the functional relevance of the peri-infarct cortex for recovery we assessed the effect of protein synthesis inhibition within this region after experimental stroke. Long-Evans rats were trained to perform a skilled-reaching task (SRT) until they reached plateau performance. A photothrombotic stroke was induced in the forelimb representation of the primary motor cortex (M1) contralateral to the trained paw. The SRT was re-trained after stroke while the protein synthesis inhibitor anisomycin (ANI) or saline were injected into the peri-infarct cortex through implanted cannulas. ANI injections reduced protein synthesis within the peri-infarct cortex by 69% and significantly impaired recovery of reaching performance through re-training. Improvement of motor performance within a single training session remained intact, while improvement between training sessions was impaired. ANI injections did not affect infarct size. Thus, protein synthesis inhibition within the peri-infarct cortex impairs recovery of motor deficits after ischemic stroke by interfering with consolidation of motor memory between training sessions but not short-term improvements within one session.

  18. Distinct Neural Activities in Premotor Cortex during Natural Vocal Behaviors in a New World Primate, the Common Marmoset (Callithrix jacchus).

    PubMed

    Roy, Sabyasachi; Zhao, Lingyun; Wang, Xiaoqin

    2016-11-30

    Although evidence from human studies has long indicated the crucial role of the frontal cortex in speech production, it has remained uncertain whether the frontal cortex in nonhuman primates plays a similar role in vocal communication. Previous studies of prefrontal and premotor cortices of macaque monkeys have found neural signals associated with cue- and reward-conditioned vocal production, but not with self-initiated or spontaneous vocalizations (Coudé et al., 2011; Hage and Nieder, 2013), which casts doubt on the role of the frontal cortex of the Old World monkeys in vocal communication. A recent study of marmoset frontal cortex observed modulated neural activities associated with self-initiated vocal production (Miller et al., 2015), but it did not delineate whether these neural activities were specifically attributed to vocal production or if they may result from other nonvocal motor activity such as orofacial motor movement. In the present study, we attempted to resolve these issues and examined single neuron activities in premotor cortex during natural vocal exchanges in the common marmoset (Callithrix jacchus), a highly vocal New World primate. Neural activation and suppression were observed both before and during self-initiated vocal production. Furthermore, by comparing neural activities between self-initiated vocal production and nonvocal orofacial motor movement, we identified a subpopulation of neurons in marmoset premotor cortex that was activated or suppressed by vocal production, but not by orofacial movement. These findings provide clear evidence of the premotor cortex's involvement in self-initiated vocal production in natural vocal behaviors of a New World primate. Human frontal cortex plays a crucial role in speech production. However, it has remained unclear whether the frontal cortex of nonhuman primates is involved in the production of self-initiated vocalizations during natural vocal communication. Using a wireless multichannel neural recording technique, we observed in the premotor cortex neural activation and suppression both before and during self-initiated vocalizations when marmosets, a highly vocal New World primate species, engaged in vocal exchanges with conspecifics. A novel finding of the present study is the discovery of a subpopulation of premotor cortex neurons that was activated by vocal production, but not by orofacial movement. These observations provide clear evidence of the premotor cortex's involvement in vocal production in a New World primate species. Copyright © 2016 the authors 0270-6474/16/3612168-12$15.00/0.

  19. Somatosensory responses in a human motor cortex

    PubMed Central

    Donoghue, John P.; Hochberg, Leigh R.

    2013-01-01

    Somatic sensory signals provide a major source of feedback to motor cortex. Changes in somatosensory systems after stroke or injury could profoundly influence brain computer interfaces (BCI) being developed to create new output signals from motor cortex activity patterns. We had the unique opportunity to study the responses of hand/arm area neurons in primary motor cortex to passive joint manipulation in a person with a long-standing brain stem stroke but intact sensory pathways. Neurons responded to passive manipulation of the contralateral shoulder, elbow, or wrist as predicted from prior studies of intact primates. Thus fundamental properties and organization were preserved despite arm/hand paralysis and damage to cortical outputs. The same neurons were engaged by attempted arm actions. These results indicate that intact sensory pathways retain the potential to influence primary motor cortex firing rates years after cortical outputs are interrupted and may contribute to online decoding of motor intentions for BCI applications. PMID:23343902

  20. Human primary motor cortex is both activated and stabilized during observation of other person's phasic motor actions.

    PubMed

    Hari, Riitta; Bourguignon, Mathieu; Piitulainen, Harri; Smeds, Eero; De Tiège, Xavier; Jousmäki, Veikko

    2014-01-01

    When your favourite athlete flops over the high-jump bar, you may twist your body in front of the TV screen. Such automatic motor facilitation, 'mirroring' or even overt imitation is not always appropriate. Here, we show, by monitoring motor-cortex brain rhythms with magnetoencephalography (MEG) in healthy adults, that viewing intermittent hand actions of another person, in addition to activation, phasically stabilizes the viewer's primary motor cortex, with the maximum of half a second after the onset of the seen movement. Such a stabilization was evident as enhanced cortex-muscle coherence at 16-20 Hz, despite signs of almost simultaneous suppression of rolandic rhythms of approximately 7 and 15 Hz as a sign of activation of the sensorimotor cortex. These findings suggest that inhibition suppresses motor output during viewing another person's actions, thereby withholding unintentional imitation.

  1. Repeatedly pairing vagus nerve stimulation with a movement reorganizes primary motor cortex.

    PubMed

    Porter, Benjamin A; Khodaparast, Navid; Fayyaz, Tabbassum; Cheung, Ryan J; Ahmed, Syed S; Vrana, William A; Rennaker, Robert L; Kilgard, Michael P

    2012-10-01

    Although sensory and motor systems support different functions, both systems exhibit experience-dependent cortical plasticity under similar conditions. If mechanisms regulating cortical plasticity are common to sensory and motor cortices, then methods generating plasticity in sensory cortex should be effective in motor cortex. Repeatedly pairing a tone with a brief period of vagus nerve stimulation (VNS) increases the proportion of primary auditory cortex responding to the paired tone (Engineer ND, Riley JR, Seale JD, Vrana WA, Shetake J, Sudanagunta SP, Borland MS, Kilgard MP. 2011. Reversing pathological neural activity using targeted plasticity. Nature. 470:101-104). In this study, we predicted that repeatedly pairing VNS with a specific movement would result in an increased representation of that movement in primary motor cortex. To test this hypothesis, we paired VNS with movements of the distal or proximal forelimb in 2 groups of rats. After 5 days of VNS movement pairing, intracranial microstimulation was used to quantify the organization of primary motor cortex. Larger cortical areas were associated with movements paired with VNS. Rats receiving identical motor training without VNS pairing did not exhibit motor cortex map plasticity. These results suggest that pairing VNS with specific events may act as a general method for increasing cortical representations of those events. VNS movement pairing could provide a new approach for treating disorders associated with abnormal movement representations.

  2. The nexus between decision making and emotion regulation: a review of convergent neurocognitive substrates.

    PubMed

    Mitchell, Derek G V

    2011-02-02

    Emotional information, such as reward or punishment, gains rapid and often preferential access to neurocognitive resources. This ability to quickly evaluate and integrate emotion-related information is thought to benefit a range of behaviours critical for survival. Conversely, the improper use of, or preoccupation with, emotional information is associated with disruptions in functioning and psychiatric disorders. Optimally, an organism utilizes emotional information when it is significant, and minimizes its influence when it is not. Recently, similar regions of prefrontal cortex have been identified that are associated with regulating both behavioural conflict (motor response selection or inhibition) and affective conflict (emotional representation and awareness). In this review, data will be examined that concerns this convergence between decision making (modulating what we do) and emotion regulation (modulating how we feel) and an informal model will be proposed linking these processes at a neurocognitive level. The studies reviewed collectively support the conclusion that overlapping areas of prefrontal cortex perform similar computations whether the functional objective is to modulate an operant response, or an emotional one. Specifically, the idea is raised that key aspects of decision making and emotion regulation are bound by a common functional objective in which internal representations of conditioned stimuli and reinforcers are modulated to facilitate optimal behaviour or states. Emphasis is placed on dorsomedial, dorsolateral, ventrolateral, and ventromedial regions of prefrontal cortex. Copyright © 2010 Elsevier B.V. All rights reserved.

  3. Temporal Dynamics of Proactive and Reactive Motor Inhibition

    PubMed Central

    Liebrand, Matthias; Pein, Inga; Tzvi, Elinor; Krämer, Ulrike M.

    2017-01-01

    Proactive motor inhibition refers to endogenous preparatory mechanisms facilitating action inhibition, whereas reactive motor inhibition is considered to be a sudden stopping process triggered by external signals. Previous studies were inconclusive about the temporal dynamics of involved neurocognitive processes during proactive and reactive motor control. Using electroencephalography (EEG), we investigated the time-course of proactive and reactive inhibition, measuring event-related oscillations and event-related potentials (ERPs). Participants performed in a cued go/nogo paradigm with cues indicating whether the motor response might or might not have to be inhibited. Based on the dual mechanisms of control (DMC) framework by Braver, we investigated the role of attentional effects, motor preparation in the sensorimotor cortex and prefrontal cognitive control mechanisms, separating effects before and after target onset. In the cue-target interval, proactive motor inhibition was associated with increased attention, reflected in reduced visual alpha power and an increased contingent negative variation (CNV). At the same time, motor inhibition was modulated by reduced sensorimotor beta power. After target onset, proactive inhibition resulted in an increased N1, indicating allocation of attention towards relevant stimuli, increased prefrontal beta power and a modulation of sensorimotor mu activity. As in previous studies, reactive stopping of motor actions was associated with increased prefrontal beta power and increased sensorimotor beta activity. The results stress the relevance of attentional mechanisms for proactive inhibition and speak for different neurocognitive mechanisms being involved in the early preparation for and in later implementation of motor inhibition. PMID:28496405

  4. Electrical stimulation of motor cortex in the uninjured hemisphere after chronic unilateral injury promotes recovery of skilled locomotion through ipsilateral control.

    PubMed

    Carmel, Jason B; Kimura, Hiroki; Martin, John H

    2014-01-08

    Partial injury to the corticospinal tract (CST) causes sprouting of intact axons at their targets, and this sprouting correlates with functional improvement. Electrical stimulation of motor cortex augments sprouting of intact CST axons and promotes functional recovery when applied soon after injury. We hypothesized that electrical stimulation of motor cortex in the intact hemisphere after chronic lesion of the CST in the other hemisphere would restore function through ipsilateral control. To test motor skill, rats were trained and tested to walk on a horizontal ladder with irregularly spaced rungs. Eight weeks after injury, produced by pyramidal tract transection, half of the rats received forelimb motor cortex stimulation of the intact hemisphere. Rats with injury and stimulation had significantly improved forelimb control compared with rats with injury alone and achieved a level of proficiency similar to uninjured rats. To test whether recovery of forelimb function was attributable to ipsilateral control, we selectively inactivated the stimulated motor cortex using the GABA agonist muscimol. The dose of muscimol we used produces strong contralateral but no ipsilateral impairments in naive rats. In rats with injury and stimulation, but not those with injury alone, inactivation caused worsening of forelimb function; the initial deficit was reinstated. These results demonstrate that electrical stimulation can promote recovery of motor function when applied late after injury and that motor control can be exerted from the ipsilateral motor cortex. These results suggest that the uninjured motor cortex could be targeted for brain stimulation in people with large unilateral CST lesions.

  5. Subclinical recurrent neck pain and its treatment impacts motor training-induced plasticity of the cerebellum and motor cortex

    PubMed Central

    Baarbé, Julianne K.; Yielder, Paul; Haavik, Heidi; Holmes, Michael W. R.

    2018-01-01

    The cerebellum processes pain inputs and is important for motor learning. Yet, how the cerebellum interacts with the motor cortex in individuals with recurrent pain is not clear. Functional connectivity between the cerebellum and motor cortex can be measured by a twin coil transcranial magnetic stimulation technique in which stimulation is applied to the cerebellum prior to stimulation over the motor cortex, which inhibits motor evoked potentials (MEPs) produced by motor cortex stimulation alone, called cerebellar inhibition (CBI). Healthy individuals without pain have been shown to demonstrate reduced CBI following motor acquisition. We hypothesized that CBI would not reduce to the same extent in those with mild-recurrent neck pain following the same motor acquisition task. We further hypothesized that a common treatment for neck pain (spinal manipulation) would restore reduced CBI following motor acquisition. Motor acquisition involved typing an eight-letter sequence of the letters Z,P,D,F with the right index finger. Twenty-seven neck pain participants received spinal manipulation (14 participants, 18–27 years) or sham control (13 participants, 19–24 years). Twelve healthy controls (20–27 years) also participated. Participants had CBI measured; they completed manipulation or sham control followed by motor acquisition; and then had CBI re-measured. Following motor acquisition, neck pain sham controls remained inhibited (58 ± 33% of test MEP) vs. healthy controls who disinhibited (98 ± 49% of test MEP, P<0.001), while the spinal manipulation group facilitated (146 ± 95% of test MEP, P<0.001). Greater inhibition in neck pain sham vs. healthy control groups suggests that neck pain may change cerebellar-motor cortex interaction. The change to facilitation suggests that spinal manipulation may reverse inhibitory effects of neck pain. PMID:29489878

  6. Laterality of brain activity during motor imagery is modulated by the provision of source level neurofeedback.

    PubMed

    Boe, Shaun; Gionfriddo, Alicia; Kraeutner, Sarah; Tremblay, Antoine; Little, Graham; Bardouille, Timothy

    2014-11-01

    Motor imagery (MI) may be effective as an adjunct to physical practice for motor skill acquisition. For example, MI is emerging as an effective treatment in stroke neurorehabilitation. As in physical practice, the repetitive activation of neural pathways during MI can drive short- and long-term brain changes that underlie functional recovery. However, the lack of feedback about MI performance may be a factor limiting its effectiveness. The provision of feedback about MI-related brain activity may overcome this limitation by providing the opportunity for individuals to monitor their own performance of this endogenous process. We completed a controlled study to isolate neurofeedback as the factor driving changes in MI-related brain activity across repeated sessions. Eighteen healthy participants took part in 3 sessions comprised of both actual and imagined performance of a button press task. During MI, participants in the neurofeedback group received source level feedback based on activity from the left and right sensorimotor cortex obtained using magnetoencephalography. Participants in the control group received no neurofeedback. MI-related brain activity increased in the sensorimotor cortex contralateral to the imagined movement across sessions in the neurofeedback group, but not in controls. Task performance improved across sessions but did not differ between groups. Our results indicate that the provision of neurofeedback during MI allows healthy individuals to modulate regional brain activity. This finding has the potential to improve the effectiveness of MI as a tool in neurorehabilitation. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Adaptive threshold hunting for the effects of transcranial direct current stimulation on primary motor cortex inhibition.

    PubMed

    Mooney, Ronan A; Cirillo, John; Byblow, Winston D

    2018-06-01

    Primary motor cortex excitability can be modulated by anodal and cathodal transcranial direct current stimulation (tDCS). These neuromodulatory effects may, in part, be dependent on modulation within gamma-aminobutyric acid (GABA)-mediated inhibitory networks. GABAergic function can be quantified non-invasively using adaptive threshold hunting paired-pulse transcranial magnetic stimulation (TMS). The previous studies have used TMS with posterior-anterior (PA) induced current to assess tDCS effects on inhibition. However, TMS with anterior-posterior (AP) induced current in the brain provides a more robust measure of GABA-mediated inhibition. The aim of the present study was to assess the modulation of corticomotor excitability and inhibition after anodal and cathodal tDCS using TMS with PA- and AP-induced current. In 16 young adults (26 ± 1 years), we investigated the response to anodal, cathodal, and sham tDCS in a repeated-measures double-blinded crossover design. Adaptive threshold hunting paired-pulse TMS with PA- and AP-induced current was used to examine separate interneuronal populations within M1 and their influence on corticomotor excitability and short- and long-interval inhibition (SICI and LICI) for up to 60 min after tDCS. Unexpectedly, cathodal tDCS increased corticomotor excitability assessed with AP (P = 0.047) but not PA stimulation (P = 0.74). SICI AP was reduced after anodal tDCS compared with sham (P = 0.040). Pearson's correlations indicated that SICI AP and LICI AP modulation was associated with corticomotor excitability after anodal (P = 0.027) and cathodal tDCS (P = 0.042). The after-effects of tDCS on corticomotor excitability may depend on the direction of the TMS-induced current used to make assessments, and on modulation within GABA-mediated inhibitory circuits.

  8. Evolution of the cerebellar cortex: the selective expansion of prefrontal-projecting cerebellar lobules.

    PubMed

    Balsters, J H; Cussans, E; Diedrichsen, J; Phillips, K A; Preuss, T M; Rilling, J K; Ramnani, N

    2010-02-01

    It has been suggested that interconnected brain areas evolve in tandem because evolutionary pressures act on complete functional systems rather than on individual brain areas. The cerebellar cortex has reciprocal connections with both the prefrontal cortex and motor cortex, forming independent loops with each. Specifically, in capuchin monkeys cerebellar cortical lobules Crus I and Crus II connect with prefrontal cortex, whereas the primary motor cortex connects with cerebellar lobules V, VI, VIIb, and VIIIa. Comparisons of extant primate species suggest that the prefrontal cortex has expanded more than cortical motor areas in human evolution. Given the enlargement of the prefrontal cortex relative to motor cortex in humans, our hypothesis would predict corresponding volumetric increases in the parts of the cerebellum connected to the prefrontal cortex, relative to cerebellar lobules connected to the motor cortex. We tested the hypothesis by comparing the volumes of cerebellar lobules in structural MRI scans in capuchins, chimpanzees and humans. The fractions of cerebellar volume occupied by Crus I and Crus II were significantly larger in humans compared to chimpanzees and capuchins. Our results therefore support the hypothesis that in the cortico-cerebellar system, functionally related structures evolve in concert with each other. The evolutionary expansion of these prefrontal-projecting cerebellar territories might contribute to the evolution of the higher cognitive functions of humans. Copyright (c) 2009 Elsevier Inc. All rights reserved.

  9. Secondary damage in the spinal cord after motor cortex injury in rats.

    PubMed

    Weishaupt, Nina; Silasi, Gergely; Colbourne, Frederick; Fouad, Karim

    2010-08-01

    When neurons within the motor cortex are fatally injured, their axons, many of which project into the spinal cord, undergo wallerian degeneration. Pathological processes occurring downstream of the cortical damage have not been extensively studied. We created a focal forelimb motor cortex injury in rats and found that axons from cell bodies located in the hindlimb motor cortex (spared by the cortical injury) become secondarily damaged in the spinal cord. To assess axonal degeneration in the spinal cord, we quantified silver staining in the corticospinal tract (CST) at 1 week and 4 weeks after the injury. We found a significant increase in silver deposition at the thoracic spinal cord level at 4 weeks compared to 1 week post-injury. At both time points, no degenerating neurons could be found in the hindlimb motor cortex. In a separate experiment, we showed that direct injury of neurons within the hindlimb motor cortex caused marked silver deposition in the thoracic CST at 1 week post-injury, and declined thereafter. Therefore, delayed axonal degeneration in the thoracic spinal cord after a focal forelimb motor cortex injury is indicative of secondary damage at the spinal cord level. Furthermore, immunolabeling of spinal cord sections showed that a local inflammatory response dominated by partially activated Iba-1-positive microglia is mounted in the CST, a viable mechanism to cause the observed secondary degeneration of fibers. In conclusion, we demonstrate that following motor cortex injury, wallerian degeneration of axons in the spinal cord leads to secondary damage, which is likely mediated by inflammatory processes.

  10. A Visual Cortical Network for Deriving Phonological Information from Intelligible Lip Movements.

    PubMed

    Hauswald, Anne; Lithari, Chrysa; Collignon, Olivier; Leonardelli, Elisa; Weisz, Nathan

    2018-05-07

    Successful lip-reading requires a mapping from visual to phonological information [1]. Recently, visual and motor cortices have been implicated in tracking lip movements (e.g., [2]). It remains unclear, however, whether visuo-phonological mapping occurs already at the level of the visual cortex-that is, whether this structure tracks the acoustic signal in a functionally relevant manner. To elucidate this, we investigated how the cortex tracks (i.e., entrains to) absent acoustic speech signals carried by silent lip movements. Crucially, we contrasted the entrainment to unheard forward (intelligible) and backward (unintelligible) acoustic speech. We observed that the visual cortex exhibited stronger entrainment to the unheard forward acoustic speech envelope compared to the unheard backward acoustic speech envelope. Supporting the notion of a visuo-phonological mapping process, this forward-backward difference of occipital entrainment was not present for actually observed lip movements. Importantly, the respective occipital region received more top-down input, especially from left premotor, primary motor, and somatosensory regions and, to a lesser extent, also from posterior temporal cortex. Strikingly, across participants, the extent of top-down modulation of the visual cortex stemming from these regions partially correlated with the strength of entrainment to absent acoustic forward speech envelope, but not to present forward lip movements. Our findings demonstrate that a distributed cortical network, including key dorsal stream auditory regions [3-5], influences how the visual cortex shows sensitivity to the intelligibility of speech while tracking silent lip movements. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Ethanol modulates cortical activity: direct evidence with combined TMS and EEG.

    PubMed

    Kähkönen, S; Kesäniemi, M; Nikouline, V V; Karhu, J; Ollikainen, M; Holi, M; Ilmoniemi, R J

    2001-08-01

    The motor cortex of 10 healthy subjects was stimulated by transcranial magnetic stimulation (TMS) before and after ethanol challenge (0.8 g/kg resulting in blood concentration of 0.77 +/- 0.14 ml/liter). The electrical brain activity resulting from the brief electromagnetic pulse was recorded with high-resolution electroencephalography (EEG) and located using inversion algorithms. Focal magnetic pulses to the left motor cortex were delivered with a figure-of-eight coil at the random interstimulus interval of 1.5-2.5 s. The stimulation intensity was adjusted to the motor threshold of abductor digiti minimi. Two conditions before and after ethanol ingestion (30 min) were applied: (1) real TMS, with the coil pressed against the scalp; and (2) control condition, with the coil separated from the scalp by a 2-cm-thick piece of plastic. A separate EMG control recording of one subject during TMS was made with two bipolar platinum needle electrodes inserted to the left temporal muscle. In each condition, 120 pulses were delivered. The EEG was recorded from 60 scalp electrodes. A peak in the EEG signals was observed at 43 ms after the TMS pulse in the real-TMS condition but not in the control condition or in the control scalp EMG. Potential maps before and after ethanol ingestion were significantly different from each other (P = 0.01), but no differences were found in the control condition. Ethanol changed the TMS-evoked potentials over right frontal and left parietal areas, the underlying effect appearing to be largest in the right prefrontal area. Our findings suggest that ethanol may have changed the functional connectivity between prefrontal and motor cortices. This new noninvasive method provides direct evidence about the modulation of cortical connectivity after ethanol challenge. Copyright 2001 Academic Press.

  12. High Working Memory Load Increases Intracortical Inhibition in Primary Motor Cortex and Diminishes the Motor Affordance Effect.

    PubMed

    Freeman, Scott M; Itthipuripat, Sirawaj; Aron, Adam R

    2016-05-18

    Motor affordances occur when the visual properties of an object elicit behaviorally relevant motor representations. Typically, motor affordances only produce subtle effects on response time or on motor activity indexed by neuroimaging/neuroelectrophysiology, but sometimes they can trigger action itself. This is apparent in "utilization behavior," where individuals with frontal cortex damage inappropriately grasp affording objects. This raises the possibility that, in healthy-functioning individuals, frontal cortex helps ensure that irrelevant affordance provocations remain below the threshold for actual movement. In Experiment 1, we tested this "frontal control" hypothesis by "loading" the frontal cortex with an effortful working memory (WM) task (which ostensibly consumes frontal resources) and examined whether this increased EEG measures of motor affordances to irrelevant affording objects. Under low WM load, there were typical motor affordance signatures: an event-related desynchronization in the mu frequency and an increased P300 amplitude for affording (vs nonaffording) objects over centroparietal electrodes. Contrary to our prediction, however, these affordance measures were diminished under high WM load. In Experiment 2, we tested competing mechanisms responsible for the diminished affordance in Experiment 1. We used paired-pulse transcranial magnetic stimulation over primary motor cortex to measure long-interval cortical inhibition. We found greater long-interval cortical inhibition for high versus low load both before and after the affording object, suggesting that a tonic inhibition state in primary motor cortex could prevent the affordance from provoking the motor system. Overall, our results suggest that a high WM load "sets" the motor system into a suppressed state that mitigates motor affordances. Is an irrelevant motor affordance more likely to be triggered when you are under low or high cognitive load? We examined this using physiological measures of the motor affordance while working memory load was varied. We observed a typical motor affordance signature when working memory load was low; however, it was abolished when load was high. Further, there was increased intracortical inhibition in primary motor cortex under high working memory load. This suggests that being in a state of high cognitive load "sets" the motor system to be imperturbable to distracting motor influences. This makes a novel link between working memory load and the balance of excitatory/inhibitory activity in the motor cortex and potentially has implications for disorders of impulsivity. Copyright © 2016 the authors 0270-6474/16/365544-12$15.00/0.

  13. Causal Influence of Articulatory Motor Cortex on Comprehending Single Spoken Words: TMS Evidence.

    PubMed

    Schomers, Malte R; Kirilina, Evgeniya; Weigand, Anne; Bajbouj, Malek; Pulvermüller, Friedemann

    2015-10-01

    Classic wisdom had been that motor and premotor cortex contribute to motor execution but not to higher cognition and language comprehension. In contrast, mounting evidence from neuroimaging, patient research, and transcranial magnetic stimulation (TMS) suggest sensorimotor interaction and, specifically, that the articulatory motor cortex is important for classifying meaningless speech sounds into phonemic categories. However, whether these findings speak to the comprehension issue is unclear, because language comprehension does not require explicit phonemic classification and previous results may therefore relate to factors alien to semantic understanding. We here used the standard psycholinguistic test of spoken word comprehension, the word-to-picture-matching task, and concordant TMS to articulatory motor cortex. TMS pulses were applied to primary motor cortex controlling either the lips or the tongue as subjects heard critical word stimuli starting with bilabial lip-related or alveolar tongue-related stop consonants (e.g., "pool" or "tool"). A significant cross-over interaction showed that articulatory motor cortex stimulation delayed comprehension responses for phonologically incongruent words relative to congruous ones (i.e., lip area TMS delayed "tool" relative to "pool" responses). As local TMS to articulatory motor areas differentially delays the comprehension of phonologically incongruous spoken words, we conclude that motor systems can take a causal role in semantic comprehension and, hence, higher cognition. © The Author 2014. Published by Oxford University Press.

  14. Causal Influence of Articulatory Motor Cortex on Comprehending Single Spoken Words: TMS Evidence

    PubMed Central

    Schomers, Malte R.; Kirilina, Evgeniya; Weigand, Anne; Bajbouj, Malek; Pulvermüller, Friedemann

    2015-01-01

    Classic wisdom had been that motor and premotor cortex contribute to motor execution but not to higher cognition and language comprehension. In contrast, mounting evidence from neuroimaging, patient research, and transcranial magnetic stimulation (TMS) suggest sensorimotor interaction and, specifically, that the articulatory motor cortex is important for classifying meaningless speech sounds into phonemic categories. However, whether these findings speak to the comprehension issue is unclear, because language comprehension does not require explicit phonemic classification and previous results may therefore relate to factors alien to semantic understanding. We here used the standard psycholinguistic test of spoken word comprehension, the word-to-picture-matching task, and concordant TMS to articulatory motor cortex. TMS pulses were applied to primary motor cortex controlling either the lips or the tongue as subjects heard critical word stimuli starting with bilabial lip-related or alveolar tongue-related stop consonants (e.g., “pool” or “tool”). A significant cross-over interaction showed that articulatory motor cortex stimulation delayed comprehension responses for phonologically incongruent words relative to congruous ones (i.e., lip area TMS delayed “tool” relative to “pool” responses). As local TMS to articulatory motor areas differentially delays the comprehension of phonologically incongruous spoken words, we conclude that motor systems can take a causal role in semantic comprehension and, hence, higher cognition. PMID:25452575

  15. Cerebellar Modulation of Cortically Evoked Complex Movements in Rats.

    PubMed

    Viaro, Riccardo; Bonazzi, Laura; Maggiolini, Emma; Franchi, Gianfranco

    2017-07-01

    Intracortical microstimulation (ICMS) delivered to the motor cortex (M1) via long- or short-train duration (long- or short-duration ICMS) can evoke coordinated complex movements or muscle twitches, respectively. The role of subcortical cerebellar input in M1 output, in terms of long- and short-duration ICMS-evoked movement and motor skill performance, was evaluated in rats with bilateral lesion of the deep cerebellar nuclei. After the lesion, distal forelimb movements were seldom observed, and almost 30% of proximal forelimb movements failed to match criteria defining the movement class observed under control conditions. The classifiable movements could be evoked in different cortical regions with respect to control and many kinematic variables were strongly affected. Furthermore, movement endpoints within the rat's workspace shrunk closer to the body, while performance in the reaching/grasping task worsened. Surprisingly, neither the threshold current values for evoking movements nor the overall size of forelimb movement representation changed with respect to controls in either long- or short-duration ICMS. We therefore conclude that cerebellar input via the motor thalamus is crucial for expressing the basic functional features of the motor cortex. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. The rat corticospinal system is functionally and anatomically segregated.

    PubMed

    Olivares-Moreno, Rafael; Moreno-Lopez, Yunuen; Concha, Luis; Martínez-Lorenzana, Guadalupe; Condés-Lara, Miguel; Cordero-Erausquin, Matilde; Rojas-Piloni, Gerardo

    2017-12-01

    The descending corticospinal (CS) projection has been considered a key element for motor control, which results from direct and indirect modulation of spinal cord pre-motor interneurons in the intermediate gray matter of the spinal cord, which, in turn, influences motoneurons in the ventral horn. The CS tract (CST) is also involved in a selective and complex modulation of sensory information in the dorsal horn. However, little is known about the spinal network engaged by the CST and the organization of CS projections that may encode different cortical outputs to the spinal cord. This study addresses the issue of whether the CS system exerts parallel control on different spinal networks, which together participate in sensorimotor integration. Here, we show that in the adult rat, two different and partially intermingled CS neurons in the sensorimotor cortex activate, with different time latencies, distinct spinal cord neurons located in the dorsal horn and intermediate zone of the same segment. The fact that different populations of CS neurons project in a segregated manner suggests that CST is composed of subsystems controlling different spinal cord circuits that modulate motor outputs and sensory inputs in a coordinated manner.

  17. Memory Accumulation Mechanisms in Human Cortex Are Independent of Motor Intentions

    PubMed Central

    Tosoni, Annalisa; Mignogna, Valeria; McAvoy, Mark P.; Shulman, Gordon L.; Corbetta, Maurizio; Romani, Gian Luca

    2014-01-01

    Previous studies on perceptual decision-making have often emphasized a tight link between decisions and motor intentions. Human decisions, however, also depend on memories or experiences that are not closely tied to specific motor responses. Recent neuroimaging findings have suggested that, during episodic retrieval, parietal activity reflects the accumulation of evidence for memory decisions. It is currently unknown, however, whether these evidence accumulation signals are functionally linked to signals for motor intentions coded in frontoparietal regions and whether activity in the putative memory accumulator tracks the amount of evidence for only previous experience, as reflected in “old” reports, or for both old and new decisions, as reflected in the accuracy of memory judgments. Here, human participants used saccadic-eye and hand-pointing movements to report recognition judgments on pictures defined by different degrees of evidence for old or new decisions. A set of cortical regions, including the middle intraparietal sulcus, showed a monotonic variation of the fMRI BOLD signal that scaled with perceived memory strength (older > newer), compatible with an asymmetrical memory accumulator. Another set, including the hippocampus and the angular gyrus, showed a nonmonotonic response profile tracking memory accuracy (higher > lower evidence), compatible with a symmetrical accumulator. In contrast, eye and hand effector-specific regions in frontoparietal cortex tracked motor intentions but were not modulated by the amount of evidence for the effector outcome. We conclude that item recognition decisions are supported by a combination of symmetrical and asymmetrical accumulation signals largely segregated from motor intentions. PMID:24828652

  18. Preferential coding of eye/hand motor actions in the human ventral occipito-temporal cortex.

    PubMed

    Tosoni, Annalisa; Guidotti, Roberto; Del Gratta, Cosimo; Committeri, Giorgia; Sestieri, Carlo

    2016-12-01

    The human ventral occipito-temporal cortex (OTC) contains areas specialized for particular perceptual/semantic categories, such as faces (fusiform face area, FFA) and places (parahippocampal place area, PPA). This organization has been interpreted as reflecting the visual structure of the world, i.e. perceptual similarity and/or eccentricity biases. However, recent functional magnetic resonance imaging (fMRI) studies have shown not only that regions of the OTC are modulated by non-visual, action-related object properties but also by motor planning and execution, although the functional role and specificity of this motor-related activity are still unclear. Here, through a reanalysis of previously published data, we tested whether the selectivity for perceptual/semantic categories in the OTC corresponds to a preference for particular motor actions. The results demonstrate for the first time that face- and place-selective regions of the OTC exhibit preferential BOLD response to the execution of hand pointing and saccadic eye movements, respectively. Moreover, multivariate analyses provide novel evidence for the consistency across neural representations of stimulus category and movement effector in OTC. According to a 'spatial hypothesis', this pattern of results originates from the match between the region eccentricity bias and the typical action space of the motor effectors. Alternatively, the double dissociation may be caused by the different effect produced by hand vs. eye movements on regions coding for body representation. Overall, the present findings offer novel insights on the coupling between visual and motor cortical representations. Copyright © 2016. Published by Elsevier Ltd.

  19. Dopamine D1 receptor activation maintains motor coordination and balance in rats.

    PubMed

    Avila-Luna, Alberto; Gálvez-Rosas, Arturo; Durand-Rivera, Alfredo; Ramos-Languren, Laura-Elisa; Ríos, Camilo; Arias-Montaño, José-Antonio; Bueno-Nava, Antonio

    2018-02-01

    Dopamine (DA) modulates motor coordination, and its depletion, as in Parkinson's disease, produces motor impairment. The basal ganglia, cerebellum and cerebral cortex are interconnected, have functional roles in motor coordination, and possess dopamine D 1 receptors (D 1 Rs), which are expressed at a particularly high density in the basal ganglia. In this study, we examined whether the activation of D 1 Rs modulates motor coordination and balance in the rat using a beam-walking test that has previously been used to detect motor coordination deficits. The systemic administration of the D 1 R agonist SKF-38393 at 2, 3, or 4 mg/kg did not alter the beam-walking scores, but the subsequent administration of the D 1 R antagonist SCH-23390 at 1 mg/kg did produce deficits in motor coordination, which were reversed by the full agonist SKF-82958. The co-administration of SKF-38393 and SCH-23390 did not alter the beam-walking scores compared with the control group, but significantly prevented the increase in beam-walking scores induced by SCH-23390. The effect of the D 1 R agonist to prevent and reverse the effect of the D 1 R antagonist in beam-walking scores is an indicator that the function of D 1 Rs is necessary to maintain motor coordination and balance in rats. Our results support that D 1 Rs mediate the SCH-23390-induced deficit in motor coordination.

  20. Passive Transport Disrupts Grid Signals in the Parahippocampal Cortex.

    PubMed

    Winter, Shawn S; Mehlman, Max L; Clark, Benjamin J; Taube, Jeffrey S

    2015-10-05

    Navigation is usually thought of relative to landmarks, but neural signals representing space also use information generated by an animal's movements. These signals include grid cells, which fire at multiple locations, forming a repeating grid pattern. Grid cell generation depends upon theta rhythm, a 6-10 Hz electroencephalogram (EEG) oscillation that is modulated by the animals' movement velocity. We passively moved rats in a clear cart to eliminate motor related self-movement cues that drive moment-to-moment changes in theta rhythmicity. We found that passive movement maintained theta power and frequency at levels equivalent to low active movement velocity, spared overall head-direction (HD) cell characteristics, but abolished both velocity modulation of theta rhythmicity and grid cell firing patterns. These results indicate that self-movement motor cues are necessary for generating grid-specific firing patterns, possibly by driving velocity modulation of theta rhythmicity, which may be used as a speed signal to generate the repeating pattern of grid cells. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Similarities between GCS and human motor cortex: complex movement coordination

    NASA Astrophysics Data System (ADS)

    Rodríguez, Jose A.; Macias, Rosa; Molgo, Jordi; Guerra, Dailos

    2014-07-01

    The "Gran Telescopio de Canarias" (GTC1) is an optical-infrared 10-meter segmented mirror telescope at the ORM observatory in Canary Islands (Spain). The GTC control system (GCS), the brain of the telescope, is is a distributed object & component oriented system based on RT-CORBA and it is responsible for the management and operation of the telescope, including its instrumentation. On the other hand, the Human motor cortex (HMC) is a region of the cerebrum responsible for the coordination of planning, control, and executing voluntary movements. If we analyze both systems, as far as the movement control of their mechanisms and body parts is concerned, we can find extraordinary similarities in their architectures. Both are structured in layers, and their functionalities are comparable from the movement conception until the movement action itself: In the GCS we can enumerate the Sequencer high level components, the Coordination libraries, the Control Kit library and the Device Driver library as the subsystems involved in the telescope movement control. If we look at the motor cortex, we can also enumerate the primary motor cortex, the secondary motor cortices, which include the posterior parietal cortex, the premotor cortex, and the supplementary motor area (SMA), the motor units, the sensory organs and the basal ganglia. From all these components/areas we will analyze in depth the several subcortical regions, of the the motor cortex, that are involved in organizing motor programs for complex movements and the GCS coordination framework, which is composed by a set of classes that allow to the high level components to transparently control a group of mechanisms simultaneously.

  2. TMS-induced modulation of action sentence priming in the ventral premotor cortex.

    PubMed

    Tremblay, Pascale; Sato, Marc; Small, Steven L

    2012-01-01

    Despite accumulating evidence that cortical motor areas, particularly the lateral premotor cortex, are activated during language comprehension, the question of whether motor processes help mediate the semantic encoding of language remains controversial. To address this issue, we examined whether low frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) of the left ventral premotor cortex (PMv) can interfere with the comprehension of sentences describing manual actions, visual properties of manipulable and non-manipulable objects, and actions of the lips and mouth. Using a primed semantic decision task, sixteen participants were asked to determine for a given sentence whether or not an auditorily presented target word was congruent with the sentence. We hypothesized that if the left PMv is contributing semantic information that is used to comprehend action and object related sentences, then TMS applied over PMv should result in a disruption of semantic priming. Our results show that TMS reduces semantic priming, induces a shift in response bias, and increases response sensitivity, but does so only during the processing of manual action sentences. This suggests a preferential contribution of PMv to the processing of sentences describing manual actions compared to other types of sentences. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Intracortical Microstimulation Maps of Motor, Somatosensory, and Posterior Parietal Cortex in Tree Shrews (Tupaia belangeri) Reveal Complex Movement Representations.

    PubMed

    Baldwin, Mary K L; Cooke, Dylan F; Krubitzer, Leah

    2017-02-01

    Long-train intracortical microstimulation (LT-ICMS) is a popular method for studying the organization of motor and posterior parietal cortex (PPC) in mammals. In primates, LT-ICMS evokes both multijoint and multiple-body-part movements in primary motor, premotor, and PPC. In rodents, LT-ICMS evokes complex movements of a single limb in motor cortex. Unfortunately, very little is known about motor/PPC organization in other mammals. Tree shrews are closely related to both primates and rodents and could provide insights into the evolution of complex movement domains in primates. The present study investigated the extent of cortex in which movements could be evoked with ICMS and the characteristics of movements elicited using both short train (ST) and LT-ICMS in tree shrews. We demonstrate that LT-ICMS and ST-ICMS maps are similar, with the movements elicited with ST-ICMS being truncated versions of those elicited with LT-ICMS. In addition, LT-ICMS-evoked complex movements within motor cortex similar to those in rodents. More complex movements involving multiple body parts such as the hand and mouth were also elicited in motor cortex and PPC, as in primates. Our results suggest that complex movement networks present in PPC and motor cortex were present in mammals prior to the emergence of primates. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  4. Dynamic Increase in Corticomuscular Coherence during Bilateral, Cyclical Ankle Movements

    PubMed Central

    Yoshida, Takashi; Masani, Kei; Zabjek, Karl; Chen, Robert; Popovic, Milos R.

    2017-01-01

    In humans, the midline primary motor cortex is active during walking. However, the exact role of such cortical participation is unknown. To delineate the role of the primary motor cortex in walking, we examined whether the primary motor cortex would activate leg muscles during movements that retained specific requirements of walking (i.e., locomotive actions). We recorded electroencephalographic and electromyographic signals from 15 healthy, young men while they sat and performed bilateral, cyclical ankle movements. During dorsiflexion, near-20-Hz coherence increased cyclically between the midline primary motor cortex and the co-contracting antagonistic pair (i.e., tibialis anterior and medial gastrocnemius muscles) in both legs. Thus, we have shown that dynamic increase in corticomuscular coherence, which has been observed during walking, also occurs during simple bilateral cyclical movements of the feet. A possible mechanism for such coherence is corticomuscular communication, in which the primary motor cortex participates in the control of movement. Furthermore, because our experimental task isolated certain locomotive actions, the observed coherence suggests that the human primary motor cortex may participate in these actions (i.e., maintaining a specified movement frequency, bilaterally coordinating the feet, and stabilizing the posture of the feet). Additional studies are needed to identify the exact cortical and subcortical interactions that cause corticomuscular coherence and to further delineate the functional role of the primary motor cortex during bilateral cyclical movements such as walking. PMID:28420971

  5. Motor cortex embeds muscle-like commands in an untangled population response

    PubMed Central

    Russo, Abigail A.; Bittner, Sean R.; Perkins, Sean M.; Seely, Jeffrey S.; London, Brian M.; Lara, Antonio H.; Miri, Andrew; Marshall, Najja J.; Kohn, Adam; Jessell, Thomas M.; Abbott, Laurence F.; Cunningham, John P.; Churchland, Mark M.

    2018-01-01

    Summary Primate motor cortex projects to spinal interneurons and motor neurons, suggesting that motor cortex activity may be dominated by muscle-like commands. Extensive observations during reaching lend support to this view, but evidence remains ambiguous and much-debated. To provide a different perspective, we employed a novel behavioral paradigm that affords extensive comparison between time-evolving neural and muscle activity. We found that single motor cortex neurons displayed many muscle-like properties, but the structure of population activity was not muscle-like. Unlike muscle activity, neural activity was structured to avoid ‘tangling’: moments where similar activity patterns led to dissimilar future patterns. Avoidance of tangling was present across tasks and species. Network models revealed a potential reason for this consistent feature: low tangling confers noise robustness. Finally, we were able to predict motor cortex activity from muscle activity alone, by leveraging the hypothesis that muscle-like commands are embedded in additional structure that yields low tangling. PMID:29398358

  6. Perspectives on classical controversies about the motor cortex.

    PubMed

    Omrani, Mohsen; Kaufman, Matthew T; Hatsopoulos, Nicholas G; Cheney, Paul D

    2017-09-01

    Primary motor cortex has been studied for more than a century, yet a consensus on its functional contribution to movement control is still out of reach. In particular, there remains controversy as to the level of control produced by motor cortex ("low-level" movement dynamics vs. "high-level" movement kinematics) and the role of sensory feedback. In this review, we present different perspectives on the two following questions: What does activity in motor cortex reflect? and How do planned motor commands interact with incoming sensory feedback during movement? The four authors each present their independent views on how they think the primary motor cortex (M1) controls movement. At the end, we present a dialogue in which the authors synthesize their views and suggest possibilities for moving the field forward. While there is not yet a consensus on the role of M1 or sensory feedback in the control of upper limb movements, such dialogues are essential to take us closer to one. Copyright © 2017 the American Physiological Society.

  7. Is the ipsilateral cortex surrounding the lesion or the non-injured contralateral cortex important for motor recovery in rats with photochemically induced cortical lesions?

    PubMed

    Takata, Kotaro; Yamauchi, Hideki; Tatsuno, Hisashi; Hashimoto, Keiji; Abo, Masahiro

    2006-01-01

    To determine whether the ipsilateral cortex surrounding the lesion or the non-injured contralateral cortex is important for motor recovery after brain damage in the photochemically initiated thrombosis (PIT) model. We induced PIT in the sensorimotor cortex in rats and examined the recovery of motor function using the beam-walking test. In 24 rats, the right sensorimotor cortex was lesioned after 2 days of training for the beam-walking test (group 1). After 10 days, PIT was induced in the left sensorimotor cortex. Eight additional rats (group 2) received 2 days training in beam walking, then underwent the beam-walking test to evaluate function. After 10 days of testing, the left sensorimotor cortex was lesioned and recovery was monitored by the beam-walking test for 8 days. In group 1 animals, left hindlimb function caused by a right sensorimotor cortex lesion recovered within 10 days after the operation. Right hindlimb function caused by the left-side lesion recovered within 6 days. In group 2, right hindlimb function caused by induction of the left-side lesion after a total of 12 days of beam-walking training and testing recovered within 6 days as with the double PIT model. The training effect may be relevant to reorganization and neuromodulation. Motor recovery patterns did not indicate whether motor recovery was dependent on the ipsilateral cortex surrounding the lesion or the cortex of the contralateral side. The results emphasize the need for selection of appropriate programs tailored to the area of cortical damage in order to enhance motor functional recovery in this model. Copyright 2006 S. Karger AG, Basel.

  8. Interhemispheric modulation of dual-mode, noninvasive brain stimulation on motor function.

    PubMed

    Park, Eunhee; Kim, Yun-Hee; Chang, Won Hyuk; Kwon, Tae Gun; Shin, Yong-Il

    2014-06-01

    To investigate the effects of simultaneous, bihemispheric, dual-mode stimulation using repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) on motor functions and cortical excitability in healthy individuals. Twenty-five healthy, right-handed volunteers (10 men, 15 women; mean age, 25.5 years) were enrolled. All participants received four randomly arranged, dual-mode, simultaneous stimulations under the following conditions: condition 1, high-frequency rTMS over the right primary motor cortex (M1) and sham tDCS over the left M1; condition 2, high-frequency rTMS over the right M1 and anodal tDCS over the left M1; condition 3, high-frequency rTMS over the right M1 and cathodal tDCS over the left M1; and condition 4, sham rTMS and sham tDCS. The cortical excitability of the right M1 and motor functions of the left hand were assessed before and after each simulation. Motor evoked potential (MEP) amplitudes after stimulation were significantly higher than before stimulation, under the conditions 1 and 2. The MEP amplitude in condition 2 was higher than both conditions 3 and 4, while the MEP amplitude in condition 1 was higher than condition 4. The results of the Purdue Pegboard test and the box and block test showed significant improvement in conditions 1 and 2 after stimulation. Simultaneous stimulation by anodal tDCS over the left M1 with high-frequency rTMS over the right M1 could produce interhemispheric modulation and homeostatic plasticity, which resulted in modulation of cortical excitability and motor functions.

  9. [Change of character of intersystemic interactions in newborn rat pups under conditions of a decrease of central influences (urethane anesthesia)].

    PubMed

    Kuznetsov, S V; Sizonov, V A; Dmitrieva, L E

    2014-01-01

    On newborn rat pups, for the first day after birth, there was studied the character of mutual influences between the slow-wave rhythmical components of the cardiac, respiratory, and motor activities reflecting interactions between the main functional systems of the developing organism. The study was carried out in norm and after pharmacological depression of the spontaneous periodical motor activity (SPMA) performed by narcotization of rat pups with urethane at low (0.5 g/kg, i/p) and maximal (1 g/kg, i/p) doses. Based on the complex of our obtained data, it is possible to conclude that after birth in rat pups the intersystemic interactions are realized mainly by the slow-wave oscillations of the near- and manyminute diapason. The correlational interactions mediated by rhythms of the decasecond diapason do not play essential role in integrative processes. Injection to the animals of urethane producing selective suppression of reaction of consciousness, but not affecting activating influences of reticular formation on cerebral cortex does not cause marked changes of autonomous parameters, but modulates structure and expression of spontaneous periodical motor activity. There occurs an essential decrease of mutual influences between motor and cardiovascular systems. In the case of preservation of motor activity bursts, a tendency for enhancement of correlational relations between the modulating rhythms of motor and somatomotor systems is observed. The cardiorespiratory interactions, more pronounced in intact rat pups in the near- and many-minute modulation diapason, under conditions of urethane, somewhat decrease, whereas the rhythmical components of the decasecond diapason--are weakly enhanced.

  10. tDCS-induced alterations in GABA concentration within primary motor cortex predict motor learning and motor memory: a 7 T magnetic resonance spectroscopy study.

    PubMed

    Kim, Soyoung; Stephenson, Mary C; Morris, Peter G; Jackson, Stephen R

    2014-10-01

    Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that alters cortical excitability in a polarity specific manner and has been shown to influence learning and memory. tDCS may have both on-line and after-effects on learning and memory, and the latter are thought to be based upon tDCS-induced alterations in neurochemistry and synaptic function. We used ultra-high-field (7 T) magnetic resonance spectroscopy (MRS), together with a robotic force adaptation and de-adaptation task, to investigate whether tDCS-induced alterations in GABA and Glutamate within motor cortex predict motor learning and memory. Note that adaptation to a robot-induced force field has long been considered to be a form of model-based learning that is closely associated with the computation and 'supervised' learning of internal 'forward' models within the cerebellum. Importantly, previous studies have shown that on-line tDCS to the cerebellum, but not to motor cortex, enhances model-based motor learning. Here we demonstrate that anodal tDCS delivered to the hand area of the left primary motor cortex induces a significant reduction in GABA concentration. This effect was specific to GABA, localised to the left motor cortex, and was polarity specific insofar as it was not observed following either cathodal or sham stimulation. Importantly, we show that the magnitude of tDCS-induced alterations in GABA concentration within motor cortex predicts individual differences in both motor learning and motor memory on the robotic force adaptation and de-adaptation task. Copyright © 2014. Published by Elsevier Inc.

  11. Analysis on bilateral hindlimb mapping in motor cortex of the rat by an intracortical microstimulation method.

    PubMed

    Seong, Han Yu; Cho, Ji Young; Choi, Byeong Sam; Min, Joong Kee; Kim, Yong Hwan; Roh, Sung Woo; Kim, Jeong Hoon; Jeon, Sang Ryong

    2014-04-01

    Intracortical microstimulation (ICMS) is a technique that was developed to derive movement representation of the motor cortex. Although rats are now commonly used in motor mapping studies, the precise characteristics of rat motor map, including symmetry and consistency across animals, and the possibility of repeated stimulation have not yet been established. We performed bilateral hindlimb mapping of motor cortex in six Sprague-Dawley rats using ICMS. ICMS was applied to the left and the right cerebral hemisphere at 0.3 mm intervals vertically and horizontally from the bregma, and any movement of the hindlimbs was noted. The majority (80%± 11%) of responses were not restricted to a single joint, which occurred simultaneously at two or three hindlimb joints. The size and shape of hindlimb motor cortex was variable among rats, but existed on the convex side of the cerebral hemisphere in all rats. The results did not show symmetry according to specific joints in each rats. Conclusively, the hindlimb representation in the rat motor cortex was conveniently mapped using ICMS, but the characteristics and inter-individual variability suggest that precise individual mapping is needed to clarify motor distribution in rats.

  12. Relationship between physiological excitatory and inhibitory measures of excitability in the left vs. right human motor cortex and peripheral electrodermal activity.

    PubMed

    Bracco, Martina; Turriziani, Patrizia; Smirni, Daniela; Mangano, Renata Giuseppa; Oliveri, Massimiliano

    2017-02-22

    The current study was aimed at investigating the relationships of excitatory and inhibitory circuits of the left vs. right primary motor cortex with peripheral electrodermal activity (EDA). Ten healthy subjects participated in two experimental sessions. In each session, EDA was recorded for 10min from the palmar surface of the left hand. Immediately after EDA recording, Transcranial Magnetic Stimulation (TMS) was used to probe excitatory and inhibitory circuits of the left or right primary motor cortex using two protocols of stimulation: the input-output curve for recording of motor evoked potentials, for testing excitatory circuits; the long-interval cortical inhibition (LICI) protocol, for testing inhibitory circuits. In both cases, motor evoked potentials were recorded with surface electrodes from a contralateral hand muscle. The main results showed that in the right motor cortex, excitatory circuits directly correlate and inhibitory circuits inversely correlate with sympathetic activation. In the left motor cortex, both excitatory and inhibitory circuits are inversely correlated with sympathetic activation. These findings may suggest a bi-hemispheric mode of control of vegetative system by motor cortices, with the right hemisphere mainly involved in sympathetic control. Copyright © 2017. Published by Elsevier B.V.

  13. Intrinsic signature of essential tremor in the cerebello-frontal network

    PubMed Central

    Popa, Traian; García-Lorenzo, Daniel; Valabregue, Romain; Legrand, André-Pierre; Marais, Lea; Degos, Bertrand; Hubsch, Cecile; Fernández-Vidal, Sara; Bardinet, Eric; Roze, Emmanuel; Lehéricy, Stéphane; Vidailhet, Marie; Meunier, Sabine

    2015-01-01

    See Raethjen and Muthuraman (doi:10.1093/brain/awv238) for a scientific commentary on this article. Essential tremor is a movement disorder characterized by tremor during voluntary movements, mainly affecting the upper limbs. The cerebellum and its connections to the cortex are known to be involved in essential tremor, but no task-free intrinsic signatures of tremor related to structural cerebellar defects have so far been found in the cortical motor network. Here we used voxel-based morphometry, tractography and resting-state functional MRI at 3 T to compare structural and functional features in 19 patients with essential tremor and homogeneous symptoms in the upper limbs, and 19 age- and gender-matched healthy volunteers. Both structural and functional abnormalities were found in the patients' cerebellum and supplementary motor area. Relative to the healthy controls, the essential tremor patients' cerebellum exhibited less grey matter in lobule VIII and less effective connectivity between each cerebellar cortex and the ipsilateral dentate nucleus. The patient's supplementary motor area exhibited (i) more grey matter; (ii) a lower amplitude of low-frequency fluctuation of the blood oxygenation level-dependent signal; (iii) less effective connectivity between each supplementary motor area and the ipsilateral primary motor hand area, and (iv) a higher probability of connection between supplementary motor area fibres and the spinal cord. Structural and functional changes in the supplementary motor area, but not in the cerebellum, correlated with clinical severity. In addition, changes in the cerebellum and supplementary motor area were interrelated, as shown by a correlation between the lower amplitude of low-frequency fluctuation in the supplementary motor area and grey matter loss in the cerebellum. The structural and functional changes observed in the supplementary motor area might thus be a direct consequence of cerebellar defects: the supplementary motor area would attempt to reduce tremor in the motor output by reducing its communication with M1 hand areas and by directly modulating motor output via its corticospinal projections. PMID:26115677

  14. A quantitative meta-analysis and review of motor learning in the human brain

    PubMed Central

    Hardwick, Robert M.; Rottschy, Claudia; Miall, R. Chris; Eickhoff, Simon B.

    2013-01-01

    Neuroimaging studies have improved our understanding of which brain structures are involved in motor learning. Despite this, questions remain regarding the areas that contribute consistently across paradigms with different task demands. For instance, sensorimotor tasks focus on learning novel movement kinematics and dynamics, while serial response time task (SRTT) variants focus on sequence learning. These differing task demands are likely to elicit quantifiably different patterns of neural activity on top of a potentially consistent core network. The current study identified consistent activations across 70 motor learning experiments using activation likelihood estimation (ALE) meta-analysis. A global analysis of all tasks revealed a bilateral cortical–subcortical network consistently underlying motor learning across tasks. Converging activations were revealed in the dorsal premotor cortex, supplementary motor cortex, primary motor cortex, primary somatosensory cortex, superior parietal lobule, thalamus, putamen and cerebellum. These activations were broadly consistent across task specific analyses that separated sensorimotor tasks and SRTT variants. Contrast analysis indicated that activity in the basal ganglia and cerebellum was significantly stronger for sensorimotor tasks, while activity in cortical structures and the thalamus was significantly stronger for SRTT variants. Additional conjunction analyses then indicated that the left dorsal premotor cortex was activated across all analyses considered, even when controlling for potential motor confounds. The highly consistent activation of the left dorsal premotor cortex suggests it is a critical node in the motor learning network. PMID:23194819

  15. Transcranial Direct Current Stimulation over the Medial Prefrontal Cortex and Left Primary Motor Cortex (mPFC-lPMC) Affects Subjective Beauty but Not Ugliness

    PubMed Central

    Nakamura, Koyo; Kawabata, Hideaki

    2015-01-01

    Neuroaesthetics has been searching for the neural bases of the subjective experience of beauty. It has been demonstrated that neural activities in the medial prefrontal cortex (mPFC) and the left primary motor cortex (lPMC) correlate with the subjective experience of beauty. Although beauty and ugliness seem to be semantically and conceptually opposite, it is still unknown whether these two evaluations represent extreme opposites in unitary or bivariate dimensions. In this study, we applied transcranial direct current stimulation (tDCS) to examine whether non-invasive brain stimulation modulates two types of esthetic evaluation; evaluating beauty and ugliness. Participants rated the subjective beauty and ugliness of abstract paintings before and after the application of tDCS. Application of cathodal tDCS over the mPFC with anode electrode over the lPMC, which induced temporal inhibition of neural excitability of the mPFC, led to a decrease in beauty ratings but not ugliness ratings. There were no changes in ratings of both beauty and ugliness when applying anodal tDCS or sham stimulation over the mPFC. Results from our experiment indicate that the mPFC and the lPMC have a causal role in generating the subjective experience of beauty, with beauty and ugliness evaluations constituting two distinct dimensions. PMID:26696865

  16. High-order motor cortex in rats receives somatosensory inputs from the primary motor cortex via cortico-cortical pathways.

    PubMed

    Kunori, Nobuo; Takashima, Ichiro

    2016-12-01

    The motor cortex of rats contains two forelimb motor areas; the caudal forelimb area (CFA) and the rostral forelimb area (RFA). Although the RFA is thought to correspond to the premotor and/or supplementary motor cortices of primates, which are higher-order motor areas that receive somatosensory inputs, it is unknown whether the RFA of rats receives somatosensory inputs in the same manner. To investigate this issue, voltage-sensitive dye (VSD) imaging was used to assess the motor cortex in rats following a brief electrical stimulation of the forelimb. This procedure was followed by intracortical microstimulation (ICMS) mapping to identify the motor representations in the imaged cortex. The combined use of VSD imaging and ICMS revealed that both the CFA and RFA received excitatory synaptic inputs after forelimb stimulation. Further evaluation of the sensory input pathway to the RFA revealed that the forelimb-evoked RFA response was abolished either by the pharmacological inactivation of the CFA or a cortical transection between the CFA and RFA. These results suggest that forelimb-related sensory inputs would be transmitted to the RFA from the CFA via the cortico-cortical pathway. Thus, the present findings imply that sensory information processed in the RFA may be used for the generation of coordinated forelimb movements, which would be similar to the function of the higher-order motor cortex in primates. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  17. Priming theta burst stimulation enhances motor cortex plasticity in young but not old adults.

    PubMed

    Opie, George M; Vosnakis, Eleni; Ridding, Michael C; Ziemann, Ulf; Semmler, John G

    Primary motor cortex neuroplasticity is reduced in old adults, which may contribute to the motor deficits commonly observed in the elderly. Previous research in young subjects suggests that the neuroplastic response can be enhanced using non-invasive brain stimulation (NIBS), with a larger plastic response observed following priming with both long-term potentiation (LTP) and depression (LTD)-like protocols. However, it is not known if priming stimulation can also modulate plasticity in older adults. To investigate if priming NIBS can be used to modulate motor cortical plasticity in old subjects. In 16 young (22.3 ± 1.0 years) and 16 old (70.2 ± 1.7 years) subjects, we investigated the response to intermittent theta burst stimulation (iTBS; LTP-like) when applied 10 min after sham stimulation, continuous TBS (cTBS; LTD-like) or an identical block of iTBS. Corticospinal plasticity was assessed by recording changes in motor evoked potential (MEP) amplitude. In young subjects, priming with cTBS (cTBS + iTBS) resulted in larger MEPs than priming with either iTBS (iTBS + iTBS; P = 0.001) or sham (sham + iTBS; P < 0.0001), while larger MEPs were seen following iTBS + iTBS than sham + iTBS (P < 0.0001). In old subjects, the response to iTBS + iTBS was not different to sham + iTBS (P > 0.9), whereas the response to cTBS + iTBS was reduced relative to iTBS + iTBS (P = 0.02) and sham + iTBS (P = 0.04). Priming TBS is ineffective for modifying M1 plasticity in older adults, which may limit the therapeutic use of priming stimulation in neurological conditions common in the elderly. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Non-stationary discharge patterns in motor cortex under subthalamic nucleus deep brain stimulation.

    PubMed

    Santaniello, Sabato; Montgomery, Erwin B; Gale, John T; Sarma, Sridevi V

    2012-01-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) directly modulates the basal ganglia (BG), but how such stimulation impacts the cortex upstream is largely unknown. There is evidence of cortical activation in 6-hydroxydopamine (OHDA)-lesioned rodents and facilitation of motor evoked potentials in Parkinson's disease (PD) patients, but the impact of the DBS settings on the cortical activity in normal vs. Parkinsonian conditions is still debated. We use point process models to analyze non-stationary activation patterns and inter-neuronal dependencies in the motor and sensory cortices of two non-human primates during STN DBS. These features are enhanced after treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which causes a consistent PD-like motor impairment, while high-frequency (HF) DBS (i.e., ≥100 Hz) strongly reduces the short-term patterns (period: 3-7 ms) both before and after MPTP treatment, and elicits a short-latency post-stimulus activation. Low-frequency DBS (i.e., ≤50 Hz), instead, has negligible effects on the non-stationary features. Finally, by using tools from the information theory [i.e., receiver operating characteristic (ROC) curve and information rate (IR)], we show that the predictive power of these models is dependent on the DBS settings, i.e., the probability of spiking of the cortical neurons (which is captured by the point process models) is significantly conditioned on the timely delivery of the DBS input. This dependency increases with the DBS frequency and is significantly larger for high- vs. low-frequency DBS. Overall, the selective suppression of non-stationary features and the increased modulation of the spike probability suggest that HF STN DBS enhances the neuronal activation in motor and sensory cortices, presumably because of reinforcement mechanisms, which perhaps involve the overlap between feedback antidromic and feed-forward orthodromic responses along the BG-thalamo-cortical loop.

  19. Dissociating movement from movement timing in the rat primary motor cortex.

    PubMed

    Knudsen, Eric B; Powers, Marissa E; Moxon, Karen A

    2014-11-19

    Neural encoding of the passage of time to produce temporally precise movements remains an open question. Neurons in several brain regions across different experimental contexts encode estimates of temporal intervals by scaling their activity in proportion to the interval duration. In motor cortex the degree to which this scaled activity relies upon afferent feedback and is guided by motor output remains unclear. Using a neural reward paradigm to dissociate neural activity from motor output before and after complete spinal transection, we show that temporally scaled activity occurs in the rat hindlimb motor cortex in the absence of motor output and after transection. Context-dependent changes in the encoding are plastic, reversible, and re-established following injury. Therefore, in the absence of motor output and despite a loss of afferent feedback, thought necessary for timed movements, the rat motor cortex displays scaled activity during a broad range of temporally demanding tasks similar to that identified in other brain regions. Copyright © 2014 the authors 0270-6474/14/3415576-11$15.00/0.

  20. The influence of moving with music on motor cortical activity.

    PubMed

    Stegemöller, Elizabeth L; Izbicki, Patricia; Hibbing, Paul

    2018-06-19

    Although there is a growing interest in using music to improve movement performance in various populations, there remains a need to better understand how music influences motor cortical activity. Listening to music is tightly linked to neural processes within the motor cortex and can modulate motor cortical activity in healthy young adult (HYAs). There is limited evidence regarding how moving to music modulates motor cortical activity. Thus, the purpose of this study was to explore the influence of moving to music on motor cortical activity in HYAs. Electroencephalography was collected while 32 HYAs tapped their index finger in time with a tone and with two contrasting music styles. Two movement rates were presented for each condition. Power spectra were obtained from data collected over the primary sensorimotor region and supplemental motor area and were compared between conditions. Results revealed a significant difference between both music conditions and the tone only condition for both the regions. For both music styles, power was increased in the beta band for low movement rates and increased in the alpha band for high movement rates. A secondary analysis determining the effect of music experience on motor cortical activity revealed a significant difference between musicians and non-musicians. Power in the beta band was increased across all conditions. The results of this study provide the initial step towards a more complete understanding of the neurophysiological underpinnings of music on movement performance which may inform future studies and therapeutic strategies. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Decoding complete reach and grasp actions from local primary motor cortex populations.

    PubMed

    Vargas-Irwin, Carlos E; Shakhnarovich, Gregory; Yadollahpour, Payman; Mislow, John M K; Black, Michael J; Donoghue, John P

    2010-07-21

    How the activity of populations of cortical neurons generates coordinated multijoint actions of the arm, wrist, and hand is poorly understood. This study combined multielectrode recording techniques with full arm motion capture to relate neural activity in primary motor cortex (M1) of macaques (Macaca mulatta) to arm, wrist, and hand postures during movement. We find that the firing rate of individual M1 neurons is typically modulated by the kinematics of multiple joints and that small, local ensembles of M1 neurons contain sufficient information to reconstruct 25 measured joint angles (representing an estimated 10 functionally independent degrees of freedom). Beyond showing that the spiking patterns of local M1 ensembles represent a rich set of naturalistic movements involving the entire upper limb, the results also suggest that achieving high-dimensional reach and grasp actions with neuroprosthetic devices may be possible using small intracortical arrays like those already being tested in human pilot clinical trials.

  2. Parallel, but Dissociable, Processing in Discrete Corticostriatal Inputs Encodes Skill Learning.

    PubMed

    Kupferschmidt, David A; Juczewski, Konrad; Cui, Guohong; Johnson, Kari A; Lovinger, David M

    2017-10-11

    Changes in cortical and striatal function underlie the transition from novel actions to refined motor skills. How discrete, anatomically defined corticostriatal projections function in vivo to encode skill learning remains unclear. Using novel fiber photometry approaches to assess real-time activity of associative inputs from medial prefrontal cortex to dorsomedial striatum and sensorimotor inputs from motor cortex to dorsolateral striatum, we show that associative and sensorimotor inputs co-engage early in action learning and disengage in a dissociable manner as actions are refined. Disengagement of associative, but not sensorimotor, inputs predicts individual differences in subsequent skill learning. Divergent somatic and presynaptic engagement in both projections during early action learning suggests potential learning-related in vivo modulation of presynaptic corticostriatal function. These findings reveal parallel processing within associative and sensorimotor circuits that challenges and refines existing views of corticostriatal function and expose neuronal projection- and compartment-specific activity dynamics that encode and predict action learning. Published by Elsevier Inc.

  3. Top-down modulation of visual processing and knowledge after 250 ms supports object constancy of category decisions

    PubMed Central

    Schendan, Haline E.; Ganis, Giorgio

    2015-01-01

    People categorize objects more slowly when visual input is highly impoverished instead of optimal. While bottom-up models may explain a decision with optimal input, perceptual hypothesis testing (PHT) theories implicate top-down processes with impoverished input. Brain mechanisms and the time course of PHT are largely unknown. This event-related potential study used a neuroimaging paradigm that implicated prefrontal cortex in top-down modulation of occipitotemporal cortex. Subjects categorized more impoverished and less impoverished real and pseudo objects. PHT theories predict larger impoverishment effects for real than pseudo objects because top-down processes modulate knowledge only for real objects, but different PHT variants predict different timing. Consistent with parietal-prefrontal PHT variants, around 250 ms, the earliest impoverished real object interaction started on an N3 complex, which reflects interactive cortical activity for object cognition. N3 impoverishment effects localized to both prefrontal and occipitotemporal cortex for real objects only. The N3 also showed knowledge effects by 230 ms that localized to occipitotemporal cortex. Later effects reflected (a) word meaning in temporal cortex during the N400, (b) internal evaluation of prior decision and memory processes and secondary higher-order memory involving anterotemporal parts of a default mode network during posterior positivity (P600), and (c) response related activity in posterior cingulate during an anterior slow wave (SW) after 700 ms. Finally, response activity in supplementary motor area during a posterior SW after 900 ms showed impoverishment effects that correlated with RTs. Convergent evidence from studies of vision, memory, and mental imagery which reflects purely top-down inputs, indicates that the N3 reflects the critical top-down processes of PHT. A hybrid multiple-state interactive, PHT and decision theory best explains the visual constancy of object cognition. PMID:26441701

  4. Lateralization of motor excitability during observation of bimanual signs.

    PubMed

    Möttönen, Riikka; Farmer, Harry; Watkins, Kate E

    2010-08-01

    Viewing another person's hand actions enhances excitability in an observer's left and right primary motor (M1) cortex. We aimed to determine whether viewing communicative hand actions alters this bilateral sensorimotor resonance. Using single-pulse transcranial magnetic stimulation (TMS), we measured excitability in the left and right M1 while right-handed non-signing participants observed bimanual communicative hand actions, i.e., meaningful signs in British Sign Language. TMS-induced motor evoked potentials were recorded from hand muscles during sign observation before and after teaching the participants to associate meanings with half of the signs. Before this teaching, when participants did not know that the presented hand actions were signs, excitability of left and right M1 was modulated equally. After learning the meanings of half the signs, excitability of the left, but not right, M1 was significantly enhanced. This left-lateralized enhancement of M1 excitability occurred during observation of signs with known and unknown meanings. The findings suggest that awareness of the communicative nature of another person's hand actions strengthens sensorimotor resonance in the left M1 cortex and alters hemispheric balance during action observation. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  5. Audio-vocal interaction in single neurons of the monkey ventrolateral prefrontal cortex.

    PubMed

    Hage, Steffen R; Nieder, Andreas

    2015-05-06

    Complex audio-vocal integration systems depend on a strong interconnection between the auditory and the vocal motor system. To gain cognitive control over audio-vocal interaction during vocal motor control, the PFC needs to be involved. Neurons in the ventrolateral PFC (VLPFC) have been shown to separately encode the sensory perceptions and motor production of vocalizations. It is unknown, however, whether single neurons in the PFC reflect audio-vocal interactions. We therefore recorded single-unit activity in the VLPFC of rhesus monkeys (Macaca mulatta) while they produced vocalizations on command or passively listened to monkey calls. We found that 12% of randomly selected neurons in VLPFC modulated their discharge rate in response to acoustic stimulation with species-specific calls. Almost three-fourths of these auditory neurons showed an additional modulation of their discharge rates either before and/or during the monkeys' motor production of vocalization. Based on these audio-vocal interactions, the VLPFC might be well positioned to combine higher order auditory processing with cognitive control of the vocal motor output. Such audio-vocal integration processes in the VLPFC might constitute a precursor for the evolution of complex learned audio-vocal integration systems, ultimately giving rise to human speech. Copyright © 2015 the authors 0270-6474/15/357030-11$15.00/0.

  6. Effects of motion speed in action representations

    PubMed Central

    van Dam, Wessel O.; Speed, Laura J.; Lai, Vicky T.; Vigliocco, Gabriella; Desai, Rutvik H.

    2017-01-01

    Grounded cognition accounts of semantic representation posit that brain regions traditionally linked to perception and action play a role in grounding the semantic content of words and sentences. Sensory-motor systems are thought to support partially abstract simulations through which conceptual content is grounded. However, which details of sensory-motor experience are included in, or excluded from these simulations, is not well understood. We investigated whether sensory-motor brain regions are differentially involved depending on the speed of actions described in a sentence. We addressed this issue by examining the neural signature of relatively fast (The old lady scurried across the road) and slow (The old lady strolled across the road) action sentences. The results showed that sentences that implied fast motion modulated activity within the right posterior superior temporal sulcus and the angular and middle occipital gyri, areas associated with biological motion and action perception. Sentences that implied slow motion resulted in greater signal within the right primary motor cortex and anterior inferior parietal lobule, areas associated with action execution and planning. These results suggest that the speed of described motion influences representational content and modulates the nature of conceptual grounding. Fast motion events are represented more visually whereas motor regions play a greater role in representing conceptual content associated with slow motion. PMID:28160739

  7. The effects of paired associative stimulation on knee extensor motor excitability of individuals post-stroke: A pilot study

    PubMed Central

    Rogers, Lynn M.; Brown, David A.; Stinear, James W.

    2012-01-01

    Objective Paired associative stimulation (PAS) modulates bilateral distal lower limb motor pathways during walking. We assessed the effects of inhibitory PAS applied to the vastus medialis (VM) motor pathways of chronic stroke patients. Methods PAS consisted of 120 electrical stimuli applied to the femoral nerve paired with transcranial magnetic stimulation (TMS) of the lower limb primary motor cortex so that the estimated arrival of the afferent volley occurred 8 ms after delivery of the magnetic stimulus. Stimulus pairs were delivered to the non-paretic VM motor system of 11 chronic stroke patients and the right limb motor system of 11 non-impaired subjects at 0.19 Hz. The effects of PAS on VM motor pathway excitability and muscle activity were assessed during pedaling. TMS-induced motor evoked potential (MEP) amplitudes and the percent of VM activity in the flexion phase of active pedaling (%FLEXVM) was examined before and after PAS. Results Inhibitory PAS reduced VM MEP amplitudes in the target limb (p < 0.05) of both groups, while post-PAS paretic VM MEP amplitudes increased for some patients and decreased for others. Group mean paretic limb %FLEXVM was not altered by inhibitory PAS. Conclusions These results indicate PAS can be used to manipulate motor cortical excitability in proximal lower limb representations, however the sign of induced modulation was unpredictable and cyclic muscle activity was not modified. Significance The study has important implications for the development of therapies involving non-invasive brain stimulation to modify abnormal motor behavior following stroke. PMID:21130032

  8. The effects of paired associative stimulation on knee extensor motor excitability of individuals post-stroke: a pilot study.

    PubMed

    Rogers, Lynn M; Brown, David A; Stinear, James W

    2011-06-01

    Paired associative stimulation (PAS) modulates bilateral distal lower limb motor pathways during walking. We assessed the effects of inhibitory PAS applied to the vastus medialis (VM) motor pathways of chronic stroke patients. PAS consisted of 120 electrical stimuli applied to the femoral nerve paired with transcranial magnetic stimulation (TMS) of the lower limb primary motor cortex so that the estimated arrival of the afferent volley occurred 8 ms after delivery of the magnetic stimulus. Stimulus pairs were delivered to the non-paretic VM motor system of 11 chronic stroke patients and the right limb motor system of 11 non-impaired subjects at 0.19 Hz. The effects of PAS on VM motor pathway excitability and muscle activity were assessed during pedaling. TMS-induced motor evoked potential (MEP) amplitudes and the percent of VM activity in the flexion phase of active pedaling (% FLEXVM) was examined before and after PAS. Inhibitory PAS reduced VM MEP amplitudes in the target limb (p<0.05) of both groups, while post-PAS paretic VM MEP amplitudes increased for some patients and decreased for others. Group mean paretic limb % FLEXVM was not altered by inhibitory PAS. These results indicate PAS can be used to manipulate motor cortical excitability in proximal lower limb representations, however the sign of induced modulation was unpredictable and cyclic muscle activity was not modified. The study has important implications for the development of therapies involving non-invasive brain stimulation to modify abnormal motor behavior following stroke. Copyright © 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  9. Driving Human Motor Cortical Oscillations Leads to Behaviorally Relevant Changes in Local GABAA Inhibition: A tACS-TMS Study

    PubMed Central

    van Ede, Freek

    2017-01-01

    Beta and gamma oscillations are the dominant oscillatory activity in the human motor cortex (M1). However, their physiological basis and precise functional significance remain poorly understood. Here, we used transcranial magnetic stimulation (TMS) to examine the physiological basis and behavioral relevance of driving beta and gamma oscillatory activity in the human M1 using transcranial alternating current stimulation (tACS). tACS was applied using a sham-controlled crossover design at individualized intensity for 20 min and TMS was performed at rest (before, during, and after tACS) and during movement preparation (before and after tACS). We demonstrated that driving gamma frequency oscillations using tACS led to a significant, duration-dependent decrease in local resting-state GABAA inhibition, as quantified by short interval intracortical inhibition. The magnitude of this effect was positively correlated with the magnitude of GABAA decrease during movement preparation, when gamma activity in motor circuitry is known to increase. In addition, gamma tACS-induced change in GABAA inhibition was closely related to performance in a motor learning task such that subjects who demonstrated a greater increase in GABAA inhibition also showed faster short-term learning. The findings presented here contribute to our understanding of the neurophysiological basis of motor rhythms and suggest that tACS may have similar physiological effects to endogenously driven local oscillatory activity. Moreover, the ability to modulate local interneuronal circuits by tACS in a behaviorally relevant manner provides a basis for tACS as a putative therapeutic intervention. SIGNIFICANCE STATEMENT Gamma oscillations have a vital role in motor control. Using a combined tACS-TMS approach, we demonstrate that driving gamma frequency oscillations modulates GABAA inhibition in the human motor cortex. Moreover, there is a clear relationship between the change in magnitude of GABAA inhibition induced by tACS and the magnitude of GABAA inhibition observed during task-related synchronization of oscillations in inhibitory interneuronal circuits, supporting the hypothesis that tACS engages endogenous oscillatory circuits. We also show that an individual's physiological response to tACS is closely related to their ability to learn a motor task. These findings contribute to our understanding of the neurophysiological basis of motor rhythms and their behavioral relevance and offer the possibility of developing tACS as a therapeutic tool. PMID:28348136

  10. Motor cortex inhibition

    PubMed Central

    Isaacs, K.M.; Augusta, M.; MacNeil, L.K.; Mostofsky, S.H.

    2011-01-01

    Objective: Attention-deficit/hyperactivity disorder (ADHD) is a childhood-onset behavioral diagnosis in which children often fail to meet age norms in development of motor control, particularly timed repetitive and sequential movements, motor overflow, and balance. The neural substrate of this motor delay may include mechanisms of synaptic inhibition in or adjacent to the motor cortex. The primary objective of this study was to determine whether transcranial magnetic stimulation (TMS)–evoked measures, particularly short interval cortical inhibition (SICI), in motor cortex correlate with the presence and severity of ADHD in childhood as well as with commonly observed delays in motor control. Methods: In this case-control study, behavioral ratings, motor skills, and motor cortex physiology were evaluated in 49 children with ADHD (mean age 10.6 years, 30 boys) and 49 typically developing children (mean age 10.5 years, 30 boys), all right-handed, aged 8–12 years. Motor skills were evaluated with the Physical and Neurological Examination for Subtle Signs (PANESS) and the Motor Assessment Battery for Children version 2. SICI and other physiologic measures were obtained using TMS in the left motor cortex. Results: In children with ADHD, mean SICI was reduced by 40% (p < 0.0001) and less SICI correlated with higher ADHD severity (r = −0.52; p = 0.002). Mean PANESS motor development scores were 59% worse in children with ADHD (p < 0.0001). Worse PANESS scores correlated modestly with less SICI (r = −.30; p = 0.01). Conclusion: Reduced TMS-evoked SICI correlates with ADHD diagnosis and symptom severity and also reflects motor skill development in children. PMID:21321335

  11. Expectations Do Not Alter Early Sensory Processing during Perceptual Decision-Making.

    PubMed

    Rungratsameetaweemana, Nuttida; Itthipuripat, Sirawaj; Salazar, Annalisa; Serences, John T

    2018-06-13

    Two factors play important roles in shaping perception: the allocation of selective attention to behaviorally relevant sensory features, and prior expectations about regularities in the environment. Signal detection theory proposes distinct roles of attention and expectation on decision-making such that attention modulates early sensory processing, whereas expectation influences the selection and execution of motor responses. Challenging this classic framework, recent studies suggest that expectations about sensory regularities enhance the encoding and accumulation of sensory evidence during decision-making. However, it is possible, that these findings reflect well documented attentional modulations in visual cortex. Here, we tested this framework in a group of male and female human participants by examining how expectations about stimulus features (orientation and color) and expectations about motor responses impacted electroencephalography (EEG) markers of early sensory processing and the accumulation of sensory evidence during decision-making (the early visual negative potential and the centro-parietal positive potential, respectively). We first demonstrate that these markers are sensitive to changes in the amount of sensory evidence in the display. Then we show, counter to recent findings, that neither marker is modulated by either feature or motor expectations, despite a robust effect of expectations on behavior. Instead, violating expectations about likely sensory features and motor responses impacts posterior alpha and frontal theta oscillations, signals thought to index overall processing time and cognitive conflict. These findings are inconsistent with recent theoretical accounts and suggest instead that expectations primarily influence decisions by modulating post-perceptual stages of information processing. SIGNIFICANCE STATEMENT Expectations about likely features or motor responses play an important role in shaping behavior. Classic theoretical frameworks posit that expectations modulate decision-making by biasing late stages of decision-making including the selection and execution of motor responses. In contrast, recent accounts suggest that expectations also modulate decisions by improving the quality of early sensory processing. However, these effects could instead reflect the influence of selective attention. Here we examine the effect of expectations about sensory features and motor responses on a set of electroencephalography (EEG) markers that index early sensory processing and later post-perceptual processing. Counter to recent empirical results, expectations have little effect on early sensory processing but instead modulate EEG markers of time-on-task and cognitive conflict. Copyright © 2018 the authors 0270-6474/18/385632-17$15.00/0.

  12. Intact intracortical microstimulation (ICMS) representations of rostral and caudal forelimb areas in rats with quinolinic acid lesions of the medial or lateral caudate-putamen in an animal model of Huntington's disease.

    PubMed

    Karl, Jenni M; Sacrey, Lori-Ann R; McDonald, Robert J; Whishaw, Ian Q

    2008-09-05

    Neurotoxic, cell-specific lesions of the rat caudate-putamen (CPu) have been proposed as a model of human Huntington's disease and as such impair performance on many motor tasks, including skilled forelimbs tasks such as reaching for food. Because the CPu and motor cortex share reciprocal connections, it has been proposed that the motor deficits are due in part to a secondary disruption of motor cortex. The purpose of the present study was to examine the functionality of the motor cortex using intracortical microstimulation (ICMS) following neurotoxic lesions of the CPu. ICMS maps have been shown to be sensitive indicators of motor skill, cortical injury, learning, and experience. Long-evans hooded rats received a sham, a medial, or a lateral CPu lesion using the neurotoxin, quinolinic acid (2,3-pyridinedicarboxylic acid). Two weeks later the motor cortex was stimulated under light ketamine anesthesia. Neither lateral nor medial lesions of the CPu altered the stimulation threshold for eliciting forelimb movements, the type of movements elicited, or the size of the rostral forelimb (RFA) and caudal forelimb areas (CFA) from which movements were elicited. The preservation of ICMS forelimb movement representations (the forelimb map) in rats with cell-specific CPu lesions suggests motor impairments following lesions of the lateral striatum are not due to the disruption of the motor map. Therefore, the impairments that follow striatal cell loss are due either to alterations in circuitry that is independent of motor cortex or to alterations in circuitry afferent to the motor cortex projections.

  13. Atlas of optimal coil orientation and position for TMS: A computational study.

    PubMed

    Gomez-Tames, Jose; Hamasaka, Atsushi; Laakso, Ilkka; Hirata, Akimasa; Ugawa, Yoshikazu

    2018-04-17

    Transcranial magnetic stimulation (TMS) activates target brain structures in a non-invasive manner. The optimal orientation of the TMS coil for the motor cortex is well known and can be estimated using motor evoked potentials. However, there are no easily measurable responses for activation of other cortical areas and the optimal orientation for these areas is currently unknown. This study investigated the electric field strength, optimal coil orientation, and relative locations to optimally stimulate the target cortex based on computed electric field distributions. A total of 518,616 stimulation scenarios were studied using realistic head models (2401 coil locations × 12 coil angles × 18 head models). Inter-subject registration methods were used to generate an atlas of optimized TMS coil orientations on locations on the standard brain. We found that the maximum electric field strength is greater in primary somatosensory cortex and primary motor cortex than in other cortical areas. Additionally, a universal optimal coil orientation applicable to most subjects is more feasible at the primary somatosensory cortex and primary motor cortex. We confirmed that optimal coil angle follows the anatomical shape of the hand motor area to realize personalized optimization of TMS. Finally, on average, the optimal coil positions for TMS on the scalp deviated 5.5 mm from the scalp points with minimum cortex-scalp distance. This deviation was minimal at the premotor cortex and primary motor cortex. Personalized optimal coil orientation is preferable for obtaining the most effective stimulation. Copyright © 2018. Published by Elsevier Inc.

  14. The interaction between embodiment and empathy in facial expression recognition

    PubMed Central

    Jospe, Karine; Flöel, Agnes; Lavidor, Michal

    2018-01-01

    Abstract Previous research has demonstrated that the Action-Observation Network (AON) is involved in both emotional-embodiment (empathy) and action-embodiment mechanisms. In this study, we hypothesized that interfering with the AON will impair action recognition and that this impairment will be modulated by empathy levels. In Experiment 1 (n = 90), participants were asked to recognize facial expressions while their facial motion was restricted. In Experiment 2 (n = 50), we interfered with the AON by applying transcranial Direct Current Stimulation to the motor cortex. In both experiments, we found that interfering with the AON impaired the performance of participants with high empathy levels; however, for the first time, we demonstrated that the interference enhanced the performance of participants with low empathy. This novel finding suggests that the embodiment module may be flexible, and that it can be enhanced in individuals with low empathy by simple manipulation of motor activation. PMID:29378022

  15. The aging motor system as a model for plastic changes of GABA-mediated intracortical inhibition and their behavioral relevance.

    PubMed

    Heise, Kirstin-F; Zimerman, Maximo; Hoppe, Julia; Gerloff, Christian; Wegscheider, Karl; Hummel, Friedhelm C

    2013-05-22

    Since GABAA-mediated intracortical inhibition has been shown to underlie plastic changes throughout the lifespan from development to aging, here, the aging motor system was used as a model to analyze the interdependence of plastic alterations within the inhibitory motorcortical network and level of behavioral performance. Double-pulse transcranial magnetic stimulation (dpTMS) was used to examine inhibition by means of short-interval intracortical inhibition (SICI) of the contralateral primary motor cortex in a sample of 64 healthy right-handed human subjects covering a wide range of the adult lifespan (age range 20-88 years, mean 47.6 ± 20.7, 34 female). SICI was evaluated during resting state and in an event-related condition during movement preparation in a visually triggered simple reaction time task. In a subgroup (N = 23), manual motor performance was tested with tasks of graded dexterous demand. Weak resting-state inhibition was associated with an overall lower manual motor performance. Better event-related modulation of inhibition correlated with better performance in more demanding tasks, in which fast alternating activation of cortical representations are necessary. Declining resting-state inhibition was associated with weakened event-related modulation of inhibition. Therefore, reduced resting-state inhibition might lead to a subsequent loss of modulatory capacity, possibly reflecting malfunctioning precision in GABAAergic neurotransmission; the consequence is an inevitable decline in motor function.

  16. Paired associative stimulation modulates corticomotor excitability in chronic stroke: A preliminary investigation.

    PubMed

    Palmer, Jacqueline A; Wolf, Steven L; Borich, Michael R

    2018-01-01

    Paired associative stimulation (PAS) combining repeated pairing of electrical stimulation of a peripheral nerve with transcranial magnetic stimulation (TMS) over the primary motor cortex (M1) can induce neuroplastic adaptations in the human brain and enhance motor learning in neurologically-intact individuals. However, the extent to which PAS is an effective technique for inducing associative plasticity and improving motor function in individuals post-stroke is unclear. The objective of this pilot study was to investigate the effects of a single session of PAS to modulate corticomotor excitability and motor skill performance in individuals post-stroke. Seven individuals with chronic stroke completed two separate visits separated by at least one week. We assessed general corticomotor excitability, intracortical network activity and behavioral outcomes prior to and at three time points following PAS and compared these outcomes to those following a sham PAS condition (PASSHAM). Following PAS, we found increased general corticomotor excitability but no significant difference in behavioral measures between PAS conditions. There was a relationship between PAS-induced corticomotor excitability increase and enhanced motor skill performance across post-PAS testing time points. These results provide preliminary evidence for the potential of PAS to increase corticomotor excitability that could favorably impact motor skill performance in chronic individuals post-stroke and are an important first step for future studies investigating the clinical application and behavioral relevance of PAS interventions in post stroke patient populations.

  17. The role of the medial prefrontal cortex in the play fighting of rats.

    PubMed

    Bell, Heather C; McCaffrey, David R; Forgie, Margaret L; Kolb, Bryan; Pellis, Sergio M

    2009-12-01

    Although decorticated rats are able to engage in play, their play is abnormal in three ways. First, decorticates do not display the normal, age-related shifts in defensive strategies during development. Second, decorticates do not modify their defensive tactics in response to the social identity of their partners. Third, decorticates display a global shift in defensive tactics from more complex to less complex strategies. It has been shown that lesions of the motor cortex (MC) selectively produce the abnormal developmental effects on play, and that lesions of the orbitofrontal cortex (OFC) selectively produce the deficits in behavioral discrimination between social partners. In the current set of experiments, we demonstrate that lesions of the medial prefrontal cortex (mPFC) produce the shift from more complex to less complex defensive tactics, while leaving intact the age-related and partner-related modulation of defensive strategies. Thus, we have evidence for a triple dissociation of function between the MC, the OFC, and the mPFC with respect to social play behavior.

  18. Direct sensorimotor corticospinal modulation of dorsal horn neuronal C-fiber responses in the rat.

    PubMed

    Rojas-Piloni, Gerardo; Martínez-Lorenzana, Guadalupe; Condés-Lara, Miguel; Rodríguez-Jiménez, Javier

    2010-09-10

    Clinically, the stimulation of motor cortical areas has been used to alleviate certain pain conditions. However, the attempts to understand the mechanisms of cortical nociceptive modulation at the spinal cord level have yielded controversial results. The objectives of the present work were to: 1) determine the effects of activating and suppressing the activity of sensorimotor cortical neurons on the nociceptive electrophysiological responses of the segmental C-fibers, and 2) evaluate the contribution of direct and indirect corticospinal projections in segmental nociceptive modulation. By means of a bipolar matrix of stimulation electrodes we mapped the stimulation of cortical areas that modulate C-fiber evoked field potentials in the dorsal horn. In addition, suppressing the cortical activity by means of cortical spreading depression, we observed that the C-fiber evoked field potentials in the dorsal horn are facilitated when cortical activity is suppressed specifically in sensorimotor cortex. Moreover, the C-fiber evoked field potentials were inhibited during spontaneous activation of cortical projecting neurons. Furthermore, after a lesion of the pyramidal tract contralateral to the spinal cord recording sites, the cortical action was suppressed. Our results show that corticospinal tract fibers arising from the sensorimotor cortex modulate directly the nociceptive C-fiber evoked responses of the dorsal horn. 2010. Published by Elsevier B.V.

  19. Function of basal ganglia in bridging cognitive and motor modules to perform an action

    PubMed Central

    Nagano-Saito, Atsuko; Martinu, Kristina; Monchi, Oury

    2014-01-01

    The basal ganglia (BG) are thought to be involved in the integration of multiple sources of information, and their dysfunction can lead to disorders such as Parkinson's disease (PD). PD patients show motor and cognitive dysfunction with specific impairments in the internal generation of motor actions and executive deficits, respectively. The role of the BG, then, would be to integrate information from several sources in order to make a decision on a resulting action adequate for the required task. Reanalyzing the data set from our previous study (Martinu et al., 2012), we investigated this hypothesis by applying a graph theory method to a series of fMRI data during the performance of self-initiated (SI) finger movement tasks obtained in healthy volunteers (HV) and early stage PD patients. Dorsally, connectivity strength between the medial prefrontal areas (mPFC) and cortical regions including the primary motor area (M1), the extrastriate visual cortex, and the associative cortex, was reduced in the PD patients. The connectivity strengths were positively correlated to activity in the striatum in both groups. Ventrally, all connectivity between the striatum, the thalamus, and the extrastriate visual cortex decreased in strength in the PD, as did the connectivity between the striatum and the ventrolateral PFC (VLPFC). Individual response time (RT) was negatively correlated to connectivity strength between the dorsolateral PFC (DLPFC) and the striatum and positively correlated to connectivity between the VLPFC and the striatum in the HV. These results indicate that the BG, with the mPFC and thalamus, are involved in integrating multiple sources of information from areas such as DLPFC, and VLPFC, connecting to M1, thereby determining a network that leads to the adequate decision and performance of the resulting action. PMID:25071432

  20. Modulation of Effects of Intermittent Theta Burst Stimulation Applied Over Primary Motor Cortex (M1) by Conditioning Stimulation of the Opposite M1

    PubMed Central

    Ragert, Patrick; Camus, Mickael; Vandermeeren, Yves; Dimyan, Michael A.; Cohen, Leonardo G.

    2009-01-01

    The excitability of the human primary motor cortex (M1) as tested with transcranial magnetic stimulation (TMS) depends on its previous history of neural activity. Homeostatic plasticity might be one important physiological mechanism for the regulation of corticospinal excitability and synaptic plasticity. Although homeostatic plasticity has been demonstrated locally within M1, it is not known whether priming M1 could result in similar homeostatic effects in the homologous M1 of the opposite hemisphere. Here, we sought to determine whether down-regulating excitability (priming) in the right (R) M1 with 1-Hz repetitive transcranial magnetic stimulation (rTMS) changes the excitability-enhancing effect of intermittent theta burst stimulation (iTBS) applied over the homologous left (L) M1. Subjects were randomly allocated to one of four experimental groups in a sham-controlled parallel design with real or sham R M1 1-Hz TMS stimulation always preceding L M1 iTBS or sham by about 10 min. The primary outcome measure was corticospinal excitability in the L M1, as measured by recruitment curves (RCs). Secondary outcome measures included pinch force, simple reaction time, and tapping speed assessed in the right hand. The main finding of this study was that preconditioning R M1 with 1-Hz rTMS significantly decreased the excitability-enhancing effects of subsequent L M1 iTBS on RCs. Application of 1-Hz rTMS over R M1 alone and iTBS over L M1 alone resulted in increased RC in L M1 relative to sham interventions. The present findings are consistent with the hypothesis that homeostatic mechanisms operating across hemispheric boundaries contribute to regulate motor cortical function in the primary motor cortex. PMID:19474173

  1. Surround Inhibition in the Primary Motor Cortex is Task-specifically Modulated in Non-professional Musicians but not in Healthy Controls During Real Piano Playing.

    PubMed

    Márquez, Gonzalo; Keller, Martin; Lundbye-Jensen, Jesper; Taube, Wolfgang

    2018-03-01

    Research has indicated that at the onset of a finger movement, unwanted contractions of adjacent muscles are prevented by inhibiting the cortical areas representing these muscles. This so-called surround inhibition (SI) seems relevant for the performance of selective finger movements but may not be necessary for tasks involving functional coupling between different finger muscles. Therefore, the present study compared SI between isolated finger movement and complex selective finger movements while playing a three-finger sequence on the piano in nine non-professional musicians and 10 untrained control participants. Transcranial magnetic stimulation (TMS) was applied to the contralateral motor cortex to assess SI in the first dorsal interosseous (FDI), abductor pollicis brevis (APB) and abductor digiti minimi (ADM) during the movement preparation and the late phasic phases. The results reveal stronger SI during the preparation phase than during the phasic phase (30.6% vs. 10.7%; P < 0.05) in the isolated-finger condition in both musicians and controls. Results also show higher SI in musicians during the preparation phase of the isolated finger condition compared to the preparation phase of the three-finger sequence (40% vs. 15%; P < 0.05). However, the control group did not show this task-specific modulation of SI (isolated: 25% vs. sequence: 25%; P > 0.05). Thus, musicians were able to modulate SI between conditions whereas control participants revealed constant levels of SI. Therefore, it may be assumed that long-term training as observed in skilled musicians is accompanied by task-specific effects on SI modulation potentially relating to the ability to perform selective and complex finger movements. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. The effect of rTMS over the inferior parietal lobule on EEG sensorimotor reactivity differs according to self-reported traits of autism in typically developing individuals.

    PubMed

    Puzzo, Ignazio; Cooper, Nicholas R; Cantarella, Simona; Fitzgerald, Paul B; Russo, Riccardo

    2013-12-06

    Previous research suggested that EEG markers of mirror neuron system activation may differ, in the normal population as a function of different levels of the autistic spectrum quotient; (AQ). The present study aimed at modulating the EEG sensorimotor reactivity induced by hand movement observation by means of repetitive transcranial magnetic stimulation (rTMS) applied to the inferior parietal lobule. We examined how the resulting rTMS modulation differed in relation to the self-reported autistic traits in the typically developing population. Results showed that during sham stimulation, all participants had significantly greater sensorimotor alpha reactivity (motor cortex-C electrodes) when observing hand movements compared to static hands. This sensorimotor alpha reactivity difference was reduced during active rTMS stimulation. Results also revealed that in the average AQ group at sham there was a significant increase in low beta during hand movement than static hand observation (pre-motor areas-FC electrodes) and that (like alpha over the C electrodes) this difference is abolished when active rTMS is delivered. Participants with high AQ scores showed no significant difference in low beta sensorimotor reactivity between active and sham rTMS during static hand or hand movement observation. These findings suggest that unlike sham, active rTMS over the IPL modulates the oscillatory activity of the low beta frequency of a distal area, namely the anterior sector of the sensorimotor cortex, when participants observe videos of static hand. Importantly, this modulation differs according to the degree of self-reported traits of autism in a typically developing population. © 2013 Elsevier B.V. All rights reserved.

  3. Complete reorganization of the motor cortex of adult rats following long-term spinal cord injuries.

    PubMed

    Tandon, Shashank; Kambi, Niranjan; Mohammed, Hisham; Jain, Neeraj

    2013-07-01

    Understanding brain reorganization following long-term spinal cord injuries is important for optimizing recoveries based on residual function as well as developing brain-controlled assistive devices. Although it has been shown that the motor cortex undergoes partial reorganization within a few weeks after peripheral and spinal cord injuries, it is not known if the motor cortex of rats is capable of large-scale reorganization after longer recovery periods. Here we determined the organization of the rat (Rattus norvegicus) motor cortex at 5 or more months after chronic lesions of the spinal cord at cervical levels using intracortical microstimulation. The results show that, in the rats with the lesions, stimulation of neurons in the de-efferented forelimb motor cortex no longer evokes movements of the forelimb. Instead, movements of the body parts in the adjacent representations, namely the whiskers and neck were evoked. In addition, at many sites, movements of the ipsilateral forelimb were observed at threshold currents. The extent of representations of the eye, jaw and tongue movements was unaltered by the lesion. Thus, large-scale reorganization of the motor cortex leads to complete filling-in of the de-efferented cortex by neighboring representations following long-term partial spinal cord injuries at cervical levels in adult rats. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  4. [Effects of intermittent hypoxia on the responses of genioglossus motor cortex to transcranial magnetic stimulation in rats].

    PubMed

    Li, Ting; Wang, Wei; Kong, De-lei; Su, Jiao; Kang, Jian

    2012-04-01

    To explore the influence of intermittent hypoxia on the responses of genioglossus motor cortex to transcranial magnetic stimulation. Male Sprague-Dawley rats were randomly divided into a control group and a chronic intermittent hypoxia group. Transcranial magnetic stimulation was applied in genioglossus motor cortex of the 2 groups. The responses of transcranial magnetic stimulation were recorded and analyzed by single factor analysis of variance. The anterolateral area provided an optimal motor evoked potential response to transcranial magnetic stimulation in the genioglossus motor cortex of the rats. Genioglossus motor evoked potential latency and amplitude were significantly modified by intermittent hypoxic exposure, with a significant decrease in latency (F = 3.294, P < 0.01) at the 1st day [(4.90 ± 0.54) ms] and the 14th day [(4.64 ± 1.71) ms], and an increase in amplitude (F = 1.905, P < 0.05) at the 1st day [(2.28 ± 0.57) mV] and the 7th day [(1.89 ± 0.20) mV]. Intermittent hypoxia could increase the transcranial magnetic stimulation response of genioglossus motor cortex in rats.

  5. Interacting Brain Modules for Memory: An Adaptive Representations Architecture

    DTIC Science & Technology

    2008-06-01

    term intention goal is to satisfy hunger . This decision will be passed back to the prefrontal cortex and forwarded to more motor planning areas...continues until the first action of the sequence is decided upon, perhaps rising from a chair. The medium term goal of hunger satiation remains. The... Neuropsychology , 20, 451-486. Smith, L., & Gasser, M. (2005). The development of embodied cognition: Six lessons from babies. Artificial Life, 11, 13

  6. Frontal top-down signals increase coupling of auditory low-frequency oscillations to continuous speech in human listeners.

    PubMed

    Park, Hyojin; Ince, Robin A A; Schyns, Philippe G; Thut, Gregor; Gross, Joachim

    2015-06-15

    Humans show a remarkable ability to understand continuous speech even under adverse listening conditions. This ability critically relies on dynamically updated predictions of incoming sensory information, but exactly how top-down predictions improve speech processing is still unclear. Brain oscillations are a likely mechanism for these top-down predictions [1, 2]. Quasi-rhythmic components in speech are known to entrain low-frequency oscillations in auditory areas [3, 4], and this entrainment increases with intelligibility [5]. We hypothesize that top-down signals from frontal brain areas causally modulate the phase of brain oscillations in auditory cortex. We use magnetoencephalography (MEG) to monitor brain oscillations in 22 participants during continuous speech perception. We characterize prominent spectral components of speech-brain coupling in auditory cortex and use causal connectivity analysis (transfer entropy) to identify the top-down signals driving this coupling more strongly during intelligible speech than during unintelligible speech. We report three main findings. First, frontal and motor cortices significantly modulate the phase of speech-coupled low-frequency oscillations in auditory cortex, and this effect depends on intelligibility of speech. Second, top-down signals are significantly stronger for left auditory cortex than for right auditory cortex. Third, speech-auditory cortex coupling is enhanced as a function of stronger top-down signals. Together, our results suggest that low-frequency brain oscillations play a role in implementing predictive top-down control during continuous speech perception and that top-down control is largely directed at left auditory cortex. This suggests a close relationship between (left-lateralized) speech production areas and the implementation of top-down control in continuous speech perception. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Frontal Top-Down Signals Increase Coupling of Auditory Low-Frequency Oscillations to Continuous Speech in Human Listeners

    PubMed Central

    Park, Hyojin; Ince, Robin A.A.; Schyns, Philippe G.; Thut, Gregor; Gross, Joachim

    2015-01-01

    Summary Humans show a remarkable ability to understand continuous speech even under adverse listening conditions. This ability critically relies on dynamically updated predictions of incoming sensory information, but exactly how top-down predictions improve speech processing is still unclear. Brain oscillations are a likely mechanism for these top-down predictions [1, 2]. Quasi-rhythmic components in speech are known to entrain low-frequency oscillations in auditory areas [3, 4], and this entrainment increases with intelligibility [5]. We hypothesize that top-down signals from frontal brain areas causally modulate the phase of brain oscillations in auditory cortex. We use magnetoencephalography (MEG) to monitor brain oscillations in 22 participants during continuous speech perception. We characterize prominent spectral components of speech-brain coupling in auditory cortex and use causal connectivity analysis (transfer entropy) to identify the top-down signals driving this coupling more strongly during intelligible speech than during unintelligible speech. We report three main findings. First, frontal and motor cortices significantly modulate the phase of speech-coupled low-frequency oscillations in auditory cortex, and this effect depends on intelligibility of speech. Second, top-down signals are significantly stronger for left auditory cortex than for right auditory cortex. Third, speech-auditory cortex coupling is enhanced as a function of stronger top-down signals. Together, our results suggest that low-frequency brain oscillations play a role in implementing predictive top-down control during continuous speech perception and that top-down control is largely directed at left auditory cortex. This suggests a close relationship between (left-lateralized) speech production areas and the implementation of top-down control in continuous speech perception. PMID:26028433

  8. A theory about a role of the hyper direct pathway in pattern expression by the basal ganglia.

    PubMed

    Jourdan, Ivan; Barttfeld, Pablo; Zanutto, B Silvano

    2010-01-01

    The Basal Ganglia (BG) are a group of nuclei, in the brain of mammalians and other vertebrates, strongly connected with the cerebral cortex, thalamus and other brain areas. The BG are associated with several brain functions including learning and motor control. When there is cortical activation, there is a strong synchronization between BG and cortex, i.e. when a given task is being executed or in the case of Parkinson disease[1], [2]. If we consider the internal segment of the Globus Pallidus (GPi) there is synchronism between GPi-cortex at frequencies as low as 3Hz to as high as 85Hz [1], [3]. In the other hand, in a delta sleep or in an anesthetized case, a very low frequency correlation is observed (1-10 Hz), but no high frequency correlation between GPi-cortex [1], [2], [3]. It is unknown why this decorrelation happens. But It is agreement that when there is no pattern to select, like in delta sleep or with an anesthetized model, the BG network would maintain the GPi and cortex decorrelated at high frequencies. Many thalamus-BG and thalamus-BG-cortex loops are modulators of the BG activity. Particularly there exists an anatomic thalamus-BG loop, formed by GPi, intralaminar thalamic nuclei (IL) and Subthalamic Nucleus (STN) [4]. Using a computational model, based on an "Integrate and Fire" neural network, we analyzed the IL nucleus as a modulator of the so-called hyper direct pathway. Our results show that, in an anesthetic case, this thalamic path could be relevant to allow a high frequency decorrelated state between the GPi and cortex.

  9. Information processing in the hemisphere of the cerebellar cortex for control of wrist movement

    PubMed Central

    Tomatsu, Saeka; Ishikawa, Takahiro; Tsunoda, Yoshiaki; Lee, Jongho; Hoffman, Donna S.

    2015-01-01

    A region of cerebellar lobules V and VI makes strong loop connections with the primary motor (M1) and premotor (PM) cortical areas and is assumed to play essential roles in limb motor control. To examine its functional role, we compared the activities of its input, intermediate, and output elements, i.e., mossy fibers (MFs), Golgi cells (GoCs), and Purkinje cells (PCs), in three monkeys performing wrist movements in two different forearm postures. The results revealed distinct steps of information processing. First, MF activities displayed temporal and directional properties that were remarkably similar to those of M1/PM neurons, suggesting that MFs relay near copies of outputs from these motor areas. Second, all GoCs had a stereotyped pattern of activity independent of movement direction or forearm posture. Instead, GoC activity resembled an average of all MF activities. Therefore, inhibitory GoCs appear to provide a filtering function that passes only prominently modulated MF inputs to granule cells. Third, PCs displayed highly complex spatiotemporal patterns of activity, with coordinate frames distinct from those of MF inputs and directional tuning that changed abruptly before movement onset. The complexity of PC activities may reflect rapidly changing properties of the peripheral motor apparatus during movement. Overall, the cerebellar cortex appears to transform a representation of outputs from M1/PM into different movement representations in a posture-dependent manner and could work as part of a forward model that predicts the state of the peripheral motor apparatus. PMID:26467515

  10. A Preliminary Comparison of Motor Learning Across Different Non-invasive Brain Stimulation Paradigms Shows No Consistent Modulations.

    PubMed

    Lopez-Alonso, Virginia; Liew, Sook-Lei; Fernández Del Olmo, Miguel; Cheeran, Binith; Sandrini, Marco; Abe, Mitsunari; Cohen, Leonardo G

    2018-01-01

    Non-invasive brain stimulation (NIBS) has been widely explored as a way to safely modulate brain activity and alter human performance for nearly three decades. Research using NIBS has grown exponentially within the last decade with promising results across a variety of clinical and healthy populations. However, recent work has shown high inter-individual variability and a lack of reproducibility of previous results. Here, we conducted a small preliminary study to explore the effects of three of the most commonly used excitatory NIBS paradigms over the primary motor cortex (M1) on motor learning (Sequential Visuomotor Isometric Pinch Force Tracking Task) and secondarily relate changes in motor learning to changes in cortical excitability (MEP amplitude and SICI). We compared anodal transcranial direct current stimulation (tDCS), paired associative stimulation (PAS 25 ), and intermittent theta burst stimulation (iTBS), along with a sham tDCS control condition. Stimulation was applied prior to motor learning. Participants ( n = 28) were randomized into one of the four groups and were trained on a skilled motor task. Motor learning was measured immediately after training (online), 1 day after training (consolidation), and 1 week after training (retention). We did not find consistent differential effects on motor learning or cortical excitability across groups. Within the boundaries of our small sample sizes, we then assessed effect sizes across the NIBS groups that could help power future studies. These results, which require replication with larger samples, are consistent with previous reports of small and variable effect sizes of these interventions on motor learning.

  11. Effect of transcranial direct current stimulation (tDCS) during complex whole body motor skill learning.

    PubMed

    Kaminski, Elisabeth; Hoff, Maike; Sehm, Bernhard; Taubert, Marco; Conde, Virginia; Steele, Christopher J; Villringer, Arno; Ragert, Patrick

    2013-09-27

    The aim of the study was to investigate tDCS effects on motor skill learning in a complex whole body dynamic balance task (DBT). We hypothesized that tDCS over the supplementary motor area (SMA), a region that is known to be involved in the control of multi-joint whole body movements, will result in polarity specific changes in DBT learning. In a randomized sham-controlled, double-blinded parallel design, we applied 20 min of tDCS over the supplementary motor area (SMA) and prefrontal cortex (PFC) while subjects performed a DBT. Anodal tDCS over SMA with the cathode placed over contralateral PFC impaired motor skill learning of the DBT compared to sham. This effect was still present on the second day of training. Reversing the polarity (cathode over SMA, anode over PFC) did not affect motor skill learning neither on the first nor on the second day of training. To better disentangle whether the impaired motor skill learning was due to a modulation of SMA or PFC, we performed an additional control experiment. Here, we applied anodal tDCS over SMA together with a larger and presumably more ineffective electrode (cathode) over PFC. Interestingly this alternative tDCS electrode setup did not affect the outcome of DBT learning. Our results provide novel evidence that a modulation of the (right) PFC seems to impair complex multi-joint motor skill learning. Hence, future studies should take the positioning of both tDCS electrodes into account when investigating complex motor skill learning. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  12. A Preliminary Comparison of Motor Learning Across Different Non-invasive Brain Stimulation Paradigms Shows No Consistent Modulations

    PubMed Central

    Lopez-Alonso, Virginia; Liew, Sook-Lei; Fernández del Olmo, Miguel; Cheeran, Binith; Sandrini, Marco; Abe, Mitsunari; Cohen, Leonardo G.

    2018-01-01

    Non-invasive brain stimulation (NIBS) has been widely explored as a way to safely modulate brain activity and alter human performance for nearly three decades. Research using NIBS has grown exponentially within the last decade with promising results across a variety of clinical and healthy populations. However, recent work has shown high inter-individual variability and a lack of reproducibility of previous results. Here, we conducted a small preliminary study to explore the effects of three of the most commonly used excitatory NIBS paradigms over the primary motor cortex (M1) on motor learning (Sequential Visuomotor Isometric Pinch Force Tracking Task) and secondarily relate changes in motor learning to changes in cortical excitability (MEP amplitude and SICI). We compared anodal transcranial direct current stimulation (tDCS), paired associative stimulation (PAS25), and intermittent theta burst stimulation (iTBS), along with a sham tDCS control condition. Stimulation was applied prior to motor learning. Participants (n = 28) were randomized into one of the four groups and were trained on a skilled motor task. Motor learning was measured immediately after training (online), 1 day after training (consolidation), and 1 week after training (retention). We did not find consistent differential effects on motor learning or cortical excitability across groups. Within the boundaries of our small sample sizes, we then assessed effect sizes across the NIBS groups that could help power future studies. These results, which require replication with larger samples, are consistent with previous reports of small and variable effect sizes of these interventions on motor learning. PMID:29740271

  13. Plasticity of cortical inhibition in dystonia is impaired after motor learning and Paired-Associative Stimulation

    PubMed Central

    Meunier, Sabine; Russmann, Heike; Shamim, Ejaz; Lamy, Jean-Charles; Hallett, Mark

    2012-01-01

    Summary Artificial induction of plasticity by paired associative stimulation (PAS) in healthy subjects (HV) demonstrates Hebbian-like plasticity in selected inhibitory networks as well as excitatory ones. In a group of 17 patients with focal hand dystonia and a group of 19 HV, we evaluated how PAS and the learning of a simple motor task influence the circuits supporting long interval intracortical inhibition (LICI, reflecting activity of GABAB interneurons) and long latency afferent inhibition (LAI, reflecting activity of somatosensory inputs to the motor cortex). In HV, PAS and motor learning induced LTP-like plasticity of excitatory networks and a lasting decrease of LAI and LICI in the motor representation of the targeted or trained muscle. The better the motor performance, the larger was the decrease of LAI. Although motor performance in the patient group was similar to that of the control group, LAI did not decrease during the motor learning as it did in the control group. In contrast, LICI was normally modulated. In patients the results after PAS did not match those obtained after motor learning: LAI was paradoxically increased and LICI did not exhibit any change. In the normal situation, decreased excitability in inhibitory circuits after induction of LTP-like plasticity may help to shape the cortical maps according to the new sensorimotor task. In patients, the abnormal or absent modulation of afferent and intracortical long-interval inhibition might indicate maladaptive plasticity that possibly contributes to the difficulty that they have to learn a new sensorimotor task.“ PMID:22429246

  14. HCN channels segregate stimulation‐evoked movement responses in neocortex and allow for coordinated forelimb movements in rodents

    PubMed Central

    Farrell, Jordan S.; Palmer, Laura A.; Singleton, Anna C.; Pittman, Quentin J.; Teskey, G. Campbell

    2016-01-01

    Key points The present study tested whether HCN channels contribute to the organization of motor cortex and to skilled motor behaviour during a forelimb reaching task.Experimental reductions in HCN channel signalling increase the representation of complex multiple forelimb movements in motor cortex as assessed by intracortical microstimulation.Global HCN1KO mice exhibit reduced reaching accuracy and atypical movements during a single‐pellet reaching task relative to wild‐type controls.Acute pharmacological inhibition of HCN channels in forelimb motor cortex decreases reaching accuracy and increases atypical movements during forelimb reaching. Abstract The mechanisms by which distinct movements of a forelimb are generated from the same area of motor cortex have remained elusive. Here we examined a role for HCN channels, given their ability to alter synaptic integration, in the expression of forelimb movement responses during intracortical microstimulation (ICMS) and movements of the forelimb on a skilled reaching task. We used short‐duration high‐resolution ICMS to evoke forelimb movements following pharmacological (ZD7288), experimental (electrically induced cortical seizures) or genetic approaches that we confirmed with whole‐cell patch clamp to substantially reduce I h current. We observed significant increases in the number of multiple movement responses evoked at single sites in motor maps to all three experimental manipulations in rats or mice. Global HCN1 knockout mice were less successful and exhibited atypical movements on a skilled‐motor learning task relative to wild‐type controls. Furthermore, in reaching‐proficient rats, reaching accuracy was reduced and forelimb movements were altered during infusion of ZD7288 within motor cortex. Thus, HCN channels play a critical role in the separation of overlapping movement responses and allow for successful reaching behaviours. These data provide a novel mechanism for the encoding of multiple movement responses within shared networks of motor cortex. This mechanism supports a viewpoint of primary motor cortex as a site of dynamic integration for behavioural output. PMID:27568501

  15. Repetitive Transcranial Magnetic Stimulation to the Primary Motor Cortex Interferes with Motor Learning by Observing

    ERIC Educational Resources Information Center

    Brown, Liana E.; Wilson, Elizabeth T.; Gribble, Paul L.

    2009-01-01

    Neural representations of novel motor skills can be acquired through visual observation. We used repetitive transcranial magnetic stimulation (rTMS) to test the idea that this "motor learning by observing" is based on engagement of neural processes for learning in the primary motor cortex (M1). Human subjects who observed another person learning…

  16. Neuromuscular changes and the rapid adaptation following a bout of damaging eccentric exercise.

    PubMed

    Goodall, S; Thomas, K; Barwood, M; Keane, K; Gonzalez, J T; St Clair Gibson, A; Howatson, G

    2017-08-01

    An initial bout of eccentric exercise is known to protect against muscle damage following a repeated bout of the same exercise; however, the neuromuscular adaptations owing to this phenomenon are unknown. To determine whether neuromuscular disturbances are modulated following a repeated bout of eccentric exercise. Following eccentric exercise performed with the elbow flexors, we measured maximal voluntary force, resting twitch force, muscle soreness, creatine kinase (CK) and voluntary activation (VA) using motor point and motor cortex stimulation at baseline, immediately post-exercise and at 1, 2, 3, 4 and 7 days post-exercise on two occasions, separated by 3 weeks. Significant muscle damage and fatigue were evident following the first exercise bout; maximal voluntary contraction (MVC) was reduced immediately by 35% and remained depressed at 7 days post-exercise. Soreness and CK release peaked at 3 and 4 days post-exercise respectively. Resting twitch force remained significantly reduced at 7 days (-48%), whilst VA measured with motor point and motor cortex stimulation was reduced until 2 and 3 days respectively. A repeated bout effect (RBE) was observed with attenuated soreness and CK release and a quicker recovery of MVC and resting twitch force. A similar decrement in VA was observed following both bouts; however, following the repeated bout there was a significantly smaller reduction in, and a faster recovery of, VA measured using motor cortical stimulation. Our data suggest that the RBE may be explained, partly, by a modification in motor corticospinal drive. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  17. Exposure to Inorganic Mercury Causes Oxidative Stress, Cell Death, and Functional Deficits in the Motor Cortex.

    PubMed

    Teixeira, Francisco B; de Oliveira, Ana C A; Leão, Luana K R; Fagundes, Nathália C F; Fernandes, Rafael M; Fernandes, Luanna M P; da Silva, Márcia C F; Amado, Lilian L; Sagica, Fernanda E S; de Oliveira, Edivaldo H C; Crespo-Lopez, Maria E; Maia, Cristiane S F; Lima, Rafael R

    2018-01-01

    Mercury is a toxic metal that can be found in the environment in three different forms - elemental, organic and inorganic. Inorganic mercury has a lower liposolubility, which results in a lower organism absorption and reduced passage through the blood-brain barrier. For this reason, exposure models that use inorganic mercury in rats in order to evaluate its effects on the central nervous system are rare, especially in adult subjects. This study investigated if a chronic exposure to low doses of mercury chloride (HgCl2), an inorganic form of mercury, is capable of promoting motor alterations and neurodegenerative in the motor cortex of adult rats. Forty animals were exposed to a dose of 0.375 mg/kg/day, for 45 days. They were then submitted to motor evaluation and euthanized to collect the motor cortex. Measurement of mercury deposited in the brain parenchyma, evaluation of oxidative balance, quantification of cellular cytotoxicity and apoptosis and density of mature neurons and astrocytes of the motor cortex were performed. It was observed that chronic exposure to inorganic mercury caused a decrease in balance and fine motor coordination, formation of mercury deposits and oxidative stress verified by the increase of lipoperoxidation and nitrite concentration and a decrease of the total antioxidant capacity. In addition, we found that this model of exposure to inorganic mercury caused cell death by cytotoxicity and induction of apoptosis with a decreased number of neurons and astrocytes in the motor cortex. Our results provide evidence that exposure to inorganic mercury in low doses, even in spite of its poor ability to cross biological barriers, is still capable of inducing motor deficits, cell death by cytotoxicity and apoptosis, and oxidative stress in the motor cortex of adult rats.

  18. Exposure to Inorganic Mercury Causes Oxidative Stress, Cell Death, and Functional Deficits in the Motor Cortex

    PubMed Central

    Teixeira, Francisco B.; de Oliveira, Ana C. A.; Leão, Luana K. R.; Fagundes, Nathália C. F.; Fernandes, Rafael M.; Fernandes, Luanna M. P.; da Silva, Márcia C. F.; Amado, Lilian L.; Sagica, Fernanda E. S.; de Oliveira, Edivaldo H. C.; Crespo-Lopez, Maria E.; Maia, Cristiane S. F.; Lima, Rafael R.

    2018-01-01

    Mercury is a toxic metal that can be found in the environment in three different forms – elemental, organic and inorganic. Inorganic mercury has a lower liposolubility, which results in a lower organism absorption and reduced passage through the blood–brain barrier. For this reason, exposure models that use inorganic mercury in rats in order to evaluate its effects on the central nervous system are rare, especially in adult subjects. This study investigated if a chronic exposure to low doses of mercury chloride (HgCl2), an inorganic form of mercury, is capable of promoting motor alterations and neurodegenerative in the motor cortex of adult rats. Forty animals were exposed to a dose of 0.375 mg/kg/day, for 45 days. They were then submitted to motor evaluation and euthanized to collect the motor cortex. Measurement of mercury deposited in the brain parenchyma, evaluation of oxidative balance, quantification of cellular cytotoxicity and apoptosis and density of mature neurons and astrocytes of the motor cortex were performed. It was observed that chronic exposure to inorganic mercury caused a decrease in balance and fine motor coordination, formation of mercury deposits and oxidative stress verified by the increase of lipoperoxidation and nitrite concentration and a decrease of the total antioxidant capacity. In addition, we found that this model of exposure to inorganic mercury caused cell death by cytotoxicity and induction of apoptosis with a decreased number of neurons and astrocytes in the motor cortex. Our results provide evidence that exposure to inorganic mercury in low doses, even in spite of its poor ability to cross biological barriers, is still capable of inducing motor deficits, cell death by cytotoxicity and apoptosis, and oxidative stress in the motor cortex of adult rats. PMID:29867340

  19. Transcranial Direct Current Stimulation Modulates Neuronal Networks in Attention Deficit Hyperactivity Disorder.

    PubMed

    Sotnikova, Anna; Soff, Cornelia; Tagliazucchi, Enzo; Becker, Katja; Siniatchkin, Michael

    2017-09-01

    Anodal transcranial direct current stimulation (tDCS) of the prefrontal cortex has been repeatedly shown to improve working memory (WM). Since patients with attention deficit hyperactivity disorder (ADHD) are characterized by both underactivation of the prefrontal cortex and deficits in WM, the modulation of prefrontal activity with tDCS in ADHD patients may increase their WM performance as well as improve the activation and connectivity of the WM network. In the present study, this hypothesis was tested using a double-blind sham-controlled experimental design. After randomization, sixteen adolescents with ADHD underwent either anodal tDCS over the left dorsolateral prefrontal cortex (DLPFC, 1 mA, 20 min) or sham stimulation with simultaneous fMRI during n-back WM task. Both in one-back and two-back conditions, tDCS led to a greater activation (compared with sham stimulation) of the left DLPFC (under the electrode), left premotor cortex, left supplementary motor cortex, and precuneus. The effects of tDCS were long-lasting and influenced resting state functional connectivity even 20 min after the stimulation, with patterns of strengthened DLPFC connectivity after tDCS outlining the WM network. In summary, anodal tDCS caused increased neuronal activation and connectivity, not only in the brain area under the stimulating electrode (i.e. left DLPFC) but also in other, more remote brain regions. Because of moderate behavioral effects of tDCS, the significance of this technique for ADHD treatment has to be investigated in further studies.

  20. Increased GABA-A receptor binding and reduced connectivity at the motor cortex in children with hemiplegic cerebral palsy: a multimodal investigation using 18F-fluoroflumazenil PET, immunohistochemistry, and MR imaging.

    PubMed

    Park, Hae-Jeong; Kim, Chul Hoon; Park, Eun Sook; Park, Bumhee; Oh, So Ra; Oh, Maeng-Keun; Park, Chang Il; Lee, Jong Doo

    2013-08-01

    γ-aminobutyric acid (GABA)-A receptor-mediated neural transmission is important to promote practice-dependent plasticity after brain injury. This study investigated alterations in GABA-A receptor binding and functional and anatomic connectivity within the motor cortex in children with cerebral palsy (CP). We conducted (18)F-fluoroflumazenil PET on children with hemiplegic CP to investigate whether in vivo GABA-A receptor binding is altered in the ipsilateral or contralateral hemisphere of the lesion site. To evaluate changes in the GABA-A receptor subunit after prenatal brain injury, we performed GABA-A receptor immunohistochemistry using rat pups with a diffuse hypoxic ischemic insult. We also performed diffusion tensor MR imaging and resting-state functional MR imaging on the same children with hemiplegic CP to investigate alterations in anatomic and functional connectivity at the motor cortex with increased GABA-A receptor binding. In children with hemiplegic CP, the (18)F-fluoroflumazenil binding potential was increased within the ipsilateral motor cortex. GABA-A receptors with the α1 subunit were highly expressed exclusively within cortical layers III, IV, and VI of the motor cortex in rat pups. The motor cortex with increased GABA-A receptor binding in children with hemiplegic CP had reduced thalamocortical and corticocortical connectivity, which might be linked to increased GABA-A receptor distribution in cortical layers in rats. Increased expression of the GABA-A receptor α1 subunit within the ipsilateral motor cortex may be an important adaptive mechanism after prenatal brain injury in children with CP but may be associated with improper functional connectivity after birth and have adverse effects on the development of motor plasticity.

  1. Comparison of functional recovery of manual dexterity after unilateral spinal cord lesion or motor cortex lesion in adult macaque monkeys.

    PubMed

    Hoogewoud, Florence; Hamadjida, Adjia; Wyss, Alexander F; Mir, Anis; Schwab, Martin E; Belhaj-Saif, Abderraouf; Rouiller, Eric M

    2013-01-01

    In relation to mechanisms involved in functional recovery of manual dexterity from cervical cord injury or from motor cortical injury, our goal was to determine whether the movements that characterize post-lesion functional recovery are comparable to original movement patterns or do monkeys adopt distinct strategies to compensate the deficits depending on the type of lesion? To this aim, data derived from earlier studies, using a skilled finger task (the modified Brinkman board from which pellets are retrieved from vertical or horizontal slots), in spinal cord and motor cortex injured monkeys were analyzed and compared. Twelve adult macaque monkeys were subjected to a hemi-section of the cervical cord (n = 6) or to a unilateral excitotoxic lesion of the hand representation in the primary motor cortex (n = 6). In addition, in each subgroup, one half of monkeys (n = 3) were treated for 30 days with a function blocking antibody against the neurite growth inhibitory protein Nogo-A, while the other half (n = 3) represented control animals. The motor deficits, and the extent and time course of functional recovery were assessed. For some of the parameters investigated (wrist angle for horizontal slots and movement types distribution for vertical slots after cervical injury; movement types distribution for horizontal slots after motor cortex lesion), post-lesion restoration of the original movement patterns ("true" recovery) led to a quantitatively better functional recovery. In the motor cortex lesion groups, pharmacological reversible inactivation experiments showed that the peri-lesion territory of the primary motor cortex or re-arranged, spared domain of the lesion zone, played a major role in the functional recovery, together with the ipsilesional intact premotor cortex.

  2. Comparison of Functional Recovery of Manual Dexterity after Unilateral Spinal Cord Lesion or Motor Cortex Lesion in Adult Macaque Monkeys

    PubMed Central

    Hoogewoud, Florence; Hamadjida, Adjia; Wyss, Alexander F.; Mir, Anis; Schwab, Martin E.; Belhaj-Saif, Abderraouf; Rouiller, Eric M.

    2013-01-01

    In relation to mechanisms involved in functional recovery of manual dexterity from cervical cord injury or from motor cortical injury, our goal was to determine whether the movements that characterize post-lesion functional recovery are comparable to original movement patterns or do monkeys adopt distinct strategies to compensate the deficits depending on the type of lesion? To this aim, data derived from earlier studies, using a skilled finger task (the modified Brinkman board from which pellets are retrieved from vertical or horizontal slots), in spinal cord and motor cortex injured monkeys were analyzed and compared. Twelve adult macaque monkeys were subjected to a hemi-section of the cervical cord (n = 6) or to a unilateral excitotoxic lesion of the hand representation in the primary motor cortex (n = 6). In addition, in each subgroup, one half of monkeys (n = 3) were treated for 30 days with a function blocking antibody against the neurite growth inhibitory protein Nogo-A, while the other half (n = 3) represented control animals. The motor deficits, and the extent and time course of functional recovery were assessed. For some of the parameters investigated (wrist angle for horizontal slots and movement types distribution for vertical slots after cervical injury; movement types distribution for horizontal slots after motor cortex lesion), post-lesion restoration of the original movement patterns (“true” recovery) led to a quantitatively better functional recovery. In the motor cortex lesion groups, pharmacological reversible inactivation experiments showed that the peri-lesion territory of the primary motor cortex or re-arranged, spared domain of the lesion zone, played a major role in the functional recovery, together with the ipsilesional intact premotor cortex. PMID:23885254

  3. Impact of Prefrontal Theta Burst Stimulation on Clinical Neuropsychological Tasks.

    PubMed

    Viejo-Sobera, Raquel; Redolar-Ripoll, Diego; Boixadós, Mercè; Palaus, Marc; Valero-Cabré, Antoni; Marron, Elena M

    2017-01-01

    Theta burst stimulation (TBS) protocols hold high promise in neuropsychological rehabilitation. Nevertheless, their ability to either decrease (continuous, cTBS) or increase (intermittent, iTBS) cortical excitability in areas other than the primary motor cortex, and their consistency modulating human behaviors with clinically relevant tasks remain to be fully established. The behavioral effects of TBS over the dorsolateral prefrontal cortex (dlPFC) are particularly interesting given its involvement in working memory (WM) and executive functions (EF), often impaired following frontal brain damage. We aimed to explore the ability of cTBS and iTBS to modulate WM and EF in healthy individuals, assessed with clinical neuropsychological tests (Digits Backward, 3-back task, Stroop Test, and Tower of Hanoi). To this end, 36 participants were assessed using the four tests 1 week prior to stimulation and immediately following a single session of either cTBS, iTBS, or sham TBS, delivered to the left dlPFC. No significant differences were found across stimulation conditions in any of the clinical tasks. Nonetheless, in some of them, active stimulation induced significant pre/post performance modulations, which were not found for the sham condition. More specifically, sham stimulation yielded improvements in the 3-back task and the Color, Color-Word, and Interference Score of the Stroop Test, an effect likely caused by task practice. Both, iTBS and cTBS, produced improvements in Digits Backward and impairments in 3-back task accuracy. Moreover, iTBS increased Interference Score in the Stroop Test in spite of the improved word reading and impaired color naming, whereas cTBS decreased the time required to complete the Tower of Hanoi. Differing from TBS outcomes reported for cortico-spinal measures on the primary motor cortex, our analyses did not reveal any of the expected performance differences across stimulation protocols. However, if one considers independently pre/post differences for each individual outcome measure and task, either one or both of the active protocols appeared to modulate WM and EF. We critically discuss the value, potential explanations, and some plausible interpretations for this set of subtle impacts of left dlPFC TBS in humans.

  4. Impact of Prefrontal Theta Burst Stimulation on Clinical Neuropsychological Tasks

    PubMed Central

    Viejo-Sobera, Raquel; Redolar-Ripoll, Diego; Boixadós, Mercè; Palaus, Marc; Valero-Cabré, Antoni; Marron, Elena M.

    2017-01-01

    Theta burst stimulation (TBS) protocols hold high promise in neuropsychological rehabilitation. Nevertheless, their ability to either decrease (continuous, cTBS) or increase (intermittent, iTBS) cortical excitability in areas other than the primary motor cortex, and their consistency modulating human behaviors with clinically relevant tasks remain to be fully established. The behavioral effects of TBS over the dorsolateral prefrontal cortex (dlPFC) are particularly interesting given its involvement in working memory (WM) and executive functions (EF), often impaired following frontal brain damage. We aimed to explore the ability of cTBS and iTBS to modulate WM and EF in healthy individuals, assessed with clinical neuropsychological tests (Digits Backward, 3-back task, Stroop Test, and Tower of Hanoi). To this end, 36 participants were assessed using the four tests 1 week prior to stimulation and immediately following a single session of either cTBS, iTBS, or sham TBS, delivered to the left dlPFC. No significant differences were found across stimulation conditions in any of the clinical tasks. Nonetheless, in some of them, active stimulation induced significant pre/post performance modulations, which were not found for the sham condition. More specifically, sham stimulation yielded improvements in the 3-back task and the Color, Color-Word, and Interference Score of the Stroop Test, an effect likely caused by task practice. Both, iTBS and cTBS, produced improvements in Digits Backward and impairments in 3-back task accuracy. Moreover, iTBS increased Interference Score in the Stroop Test in spite of the improved word reading and impaired color naming, whereas cTBS decreased the time required to complete the Tower of Hanoi. Differing from TBS outcomes reported for cortico-spinal measures on the primary motor cortex, our analyses did not reveal any of the expected performance differences across stimulation protocols. However, if one considers independently pre/post differences for each individual outcome measure and task, either one or both of the active protocols appeared to modulate WM and EF. We critically discuss the value, potential explanations, and some plausible interpretations for this set of subtle impacts of left dlPFC TBS in humans. PMID:28867993

  5. Type-2 diabetes mellitus reduces cortical thickness and decreases oxidative metabolism in sensorimotor regions after stroke.

    PubMed

    Ferris, Jennifer K; Peters, Sue; Brown, Katlyn E; Tourigny, Katherine; Boyd, Lara A

    2018-05-01

    Individuals with type-2 diabetes mellitus experience poor motor outcomes after ischemic stroke. Recent research suggests that type-2 diabetes adversely impacts neuronal integrity and function, yet little work has considered how these neuronal changes affect sensorimotor outcomes after stroke. Here, we considered how type-2 diabetes impacted the structural and metabolic function of the sensorimotor cortex after stroke using volumetric magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). We hypothesized that the combination of chronic stroke and type-2 diabetes would negatively impact the integrity of sensorimotor cortex as compared to individuals with chronic stroke alone. Compared to stroke alone, individuals with stroke and diabetes had lower cortical thickness bilaterally in the primary somatosensory cortex, and primary and secondary motor cortices. Individuals with stroke and diabetes also showed reduced creatine levels bilaterally in the sensorimotor cortex. Contralesional primary and secondary motor cortex thicknesses were negatively related to sensorimotor outcomes in the paretic upper-limb in the stroke and diabetes group such that those with thinner primary and secondary motor cortices had better motor function. These data suggest that type-2 diabetes alters cerebral energy metabolism, and is associated with thinning of sensorimotor cortex after stroke. These factors may influence motor outcomes after stroke.

  6. State-dependent spike and local field synchronization between motor cortex and substantia nigra in hemiparkinsonian rats.

    PubMed

    Brazhnik, Elena; Cruz, Ana V; Avila, Irene; Wahba, Marian I; Novikov, Nikolay; Ilieva, Neda M; McCoy, Alex J; Gerber, Colin; Walters, Judith R

    2012-06-06

    Excessive beta frequency oscillatory and synchronized activity has been reported in the basal ganglia of parkinsonian patients and animal models of the disease. To gain insight into processes underlying this activity, this study explores relationships between oscillatory activity in motor cortex and basal ganglia output in behaving rats after dopamine cell lesion. During inattentive rest, 7 d after lesion, increases in motor cortex-substantia nigra pars reticulata (SNpr) coherence emerged in the 8-25 Hz range, with significant increases in local field potential (LFP) power in SNpr but not motor cortex. In contrast, during treadmill walking, marked increases in both motor cortex and SNpr LFP power, as well as coherence, emerged in the 25-40 Hz band with a peak frequency at 30-35 Hz. Spike-triggered waveform averages showed that 77% of SNpr neurons, 77% of putative cortical interneurons, and 44% of putative pyramidal neurons were significantly phase-locked to the increased cortical LFP activity in the 25-40 Hz range. Although the mean lag between cortical and SNpr LFPs fluctuated around zero, SNpr neurons phase-locked to cortical LFP oscillations fired, on average, 17 ms after synchronized spiking in motor cortex. High coherence between LFP oscillations in cortex and SNpr supports the view that cortical activity facilitates entrainment and synchronization of activity in basal ganglia after loss of dopamine. However, the dramatic increases in cortical power and relative timing of phase-locked spiking in these areas suggest that additional processes help shape the frequency-specific tuning of the basal ganglia-thalamocortical network during ongoing motor activity.

  7. The cerebellum mediates conflict resolution.

    PubMed

    Schweizer, Tom A; Oriet, Chris; Meiran, Nachshon; Alexander, Michael P; Cusimano, Michael; Stuss, Donald T

    2007-12-01

    Regions within the frontal and parietal cortex have been implicated as important neural correlates for cognitive control during conflict resolution. Despite the extensive reciprocal connectivity between the cerebellum and these putatively critical cortical areas, a role for the cerebellum in conflict resolution has never been identified. We used a task-switching paradigm that separates processes related to task-set switching and the management of response conflict independent of motor processing. Eleven patients with chronic, focal lesions to the cerebellum and 11 healthy controls were compared. Patients were slower and less accurate in conditions involving conflict resolution. In the absence of response conflict, however, tasks-witching abilities were not impaired in our patients. The cerebellum may play an important role in coordinating with other areas of cortex to modulate active response states. These results are the first demonstration of impaired conflict resolution following cerebellar lesions in the presence of an intact prefrontal cortex.

  8. Speech target modulates speaking induced suppression in auditory cortex

    PubMed Central

    Ventura, Maria I; Nagarajan, Srikantan S; Houde, John F

    2009-01-01

    Background Previous magnetoencephalography (MEG) studies have demonstrated speaking-induced suppression (SIS) in the auditory cortex during vocalization tasks wherein the M100 response to a subject's own speaking is reduced compared to the response when they hear playback of their speech. Results The present MEG study investigated the effects of utterance rapidity and complexity on SIS: The greatest difference between speak and listen M100 amplitudes (i.e., most SIS) was found in the simple speech task. As the utterances became more rapid and complex, SIS was significantly reduced (p = 0.0003). Conclusion These findings are highly consistent with our model of how auditory feedback is processed during speaking, where incoming feedback is compared with an efference-copy derived prediction of expected feedback. Thus, the results provide further insights about how speech motor output is controlled, as well as the computational role of auditory cortex in transforming auditory feedback. PMID:19523234

  9. Choice reaching with a LEGO arm robot (CoRLEGO): The motor system guides visual attention to movement-relevant information

    PubMed Central

    Strauss, Soeren; Woodgate, Philip J.W.; Sami, Saber A.; Heinke, Dietmar

    2015-01-01

    We present an extension of a neurobiologically inspired robotics model, termed CoRLEGO (Choice reaching with a LEGO arm robot). CoRLEGO models experimental evidence from choice reaching tasks (CRT). In a CRT participants are asked to rapidly reach and touch an item presented on the screen. These experiments show that non-target items can divert the reaching movement away from the ideal trajectory to the target item. This is seen as evidence attentional selection of reaching targets can leak into the motor system. Using competitive target selection and topological representations of motor parameters (dynamic neural fields) CoRLEGO is able to mimic this leakage effect. Furthermore if the reaching target is determined by its colour oddity (i.e. a green square among red squares or vice versa), the reaching trajectories become straighter with repetitions of the target colour (colour streaks). This colour priming effect can also be modelled with CoRLEGO. The paper also presents an extension of CoRLEGO. This extension mimics findings that transcranial direct current stimulation (tDCS) over the motor cortex modulates the colour priming effect (Woodgate et al., 2015). The results with the new CoRLEGO suggest that feedback connections from the motor system to the brain’s attentional system (parietal cortex) guide visual attention to extract movement-relevant information (i.e. colour) from visual stimuli. This paper adds to growing evidence that there is a close interaction between the motor system and the attention system. This evidence contradicts the traditional conceptualization of the motor system as the endpoint of a serial chain of processing stages. At the end of the paper we discuss CoRLEGO’s predictions and also lessons for neurobiologically inspired robotics emerging from this work. PMID:26667353

  10. The role of hearing ability and speech distortion in the facilitation of articulatory motor cortex.

    PubMed

    Nuttall, Helen E; Kennedy-Higgins, Daniel; Devlin, Joseph T; Adank, Patti

    2017-01-08

    Excitability of articulatory motor cortex is facilitated when listening to speech in challenging conditions. Beyond this, however, we have little knowledge of what listener-specific and speech-specific factors engage articulatory facilitation during speech perception. For example, it is unknown whether speech motor activity is independent or dependent on the form of distortion in the speech signal. It is also unknown if speech motor facilitation is moderated by hearing ability. We investigated these questions in two experiments. We applied transcranial magnetic stimulation (TMS) to the lip area of primary motor cortex (M1) in young, normally hearing participants to test if lip M1 is sensitive to the quality (Experiment 1) or quantity (Experiment 2) of distortion in the speech signal, and if lip M1 facilitation relates to the hearing ability of the listener. Experiment 1 found that lip motor evoked potentials (MEPs) were larger during perception of motor-distorted speech that had been produced using a tongue depressor, and during perception of speech presented in background noise, relative to natural speech in quiet. Experiment 2 did not find evidence of motor system facilitation when speech was presented in noise at signal-to-noise ratios where speech intelligibility was at 50% or 75%, which were significantly less severe noise levels than used in Experiment 1. However, there was a significant interaction between noise condition and hearing ability, which indicated that when speech stimuli were correctly classified at 50%, speech motor facilitation was observed in individuals with better hearing, whereas individuals with relatively worse but still normal hearing showed more activation during perception of clear speech. These findings indicate that the motor system may be sensitive to the quantity, but not quality, of degradation in the speech signal. Data support the notion that motor cortex complements auditory cortex during speech perception, and point to a role for the motor cortex in compensating for differences in hearing ability. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Cooperation Not Competition: Bihemispheric tDCS and fMRI Show Role for Ipsilateral Hemisphere in Motor Learning.

    PubMed

    Waters, Sheena; Wiestler, Tobias; Diedrichsen, Jörn

    2017-08-02

    What is the role of ipsilateral motor and premotor areas in motor learning? One view is that ipsilateral activity suppresses contralateral motor cortex and, accordingly, that inhibiting ipsilateral regions can improve motor learning. Alternatively, the ipsilateral motor cortex may play an active role in the control and/or learning of unilateral hand movements. We approached this question by applying double-blind bihemispheric transcranial direct current stimulation (tDCS) over both contralateral and ipsilateral motor cortex in a between-group design during 4 d of unimanual explicit sequence training in human participants. Independently of whether the anode was placed over contralateral or ipsilateral motor cortex, bihemispheric stimulation yielded substantial performance gains relative to unihemispheric or sham stimulation. This performance advantage appeared to be supported by plastic changes in both hemispheres. First, we found that behavioral advantages generalized strongly to the untrained hand, suggesting that tDCS strengthened effector-independent representations. Second, functional imaging during speed-matched execution of trained sequences conducted 48 h after training revealed sustained, polarity-independent increases in activity in both motor cortices relative to the sham group. These results suggest a cooperative rather than competitive interaction of the two motor cortices during skill learning and suggest that bihemispheric brain stimulation during unimanual skill learning may be beneficial because it harnesses plasticity in the ipsilateral hemisphere. SIGNIFICANCE STATEMENT Many neurorehabilitation approaches are based on the idea that is beneficial to boost excitability in the contralateral hemisphere while attenuating that of the ipsilateral cortex to reduce interhemispheric inhibition. We observed that bihemispheric transcranial direct current stimulation (tDCS) with the excitatory anode either over contralateral or ipsilateral motor cortex facilitated motor learning nearly twice as strongly as unihemispheric tDCS. These increases in motor learning were accompanied by increases in fMRI activation in both motor cortices that outlasted the stimulation period, as well as increased generalization to the untrained hand. Collectively, our findings suggest a cooperative rather than a competitive role of the hemispheres and imply that it is most beneficial to harness plasticity in both hemispheres in neurorehabilitation of motor deficits. Copyright © 2017 Waters et al.

  12. Interindividual differences in motor network connectivity and behavioral response to iTBS in stroke patients.

    PubMed

    Diekhoff-Krebs, Svenja; Pool, Eva-Maria; Sarfeld, Anna-Sophia; Rehme, Anne K; Eickhoff, Simon B; Fink, Gereon R; Grefkes, Christian

    2017-01-01

    Cerebral plasticity-inducing approaches like repetitive transcranial magnetic stimulation (rTMS) are of high interest in situations where reorganization of neural networks can be observed, e.g., after stroke. However, an increasing number of studies suggest that improvements in motor performance of the stroke-affected hand following modulation of primary motor cortex (M1) excitability by rTMS shows a high interindividual variability. We here tested the hypothesis that in stroke patients the interindividual variability of behavioral response to excitatory rTMS is related to interindividual differences in network connectivity of the stimulated region. Chronic stroke patients ( n  = 14) and healthy controls ( n  = 12) were scanned with functional magnetic resonance imaging (fMRI) while performing a simple hand motor task. Dynamic causal modeling (DCM) was used to investigate effective connectivity of key motor regions. On two different days after the fMRI experiment, patients received either intermittent theta-burst stimulation (iTBS) over ipsilesional M1 or control stimulation over the parieto-occipital cortex. Motor performance and TMS parameters of cortical excitability were measured before and after iTBS. Our results revealed that patients with better motor performance of the affected hand showed stronger endogenous coupling between supplemental motor area (SMA) and M1 before starting the iTBS intervention. Applying iTBS to ipsilesional M1 significantly increased ipsilesional M1 excitability and decreased contralesional M1 excitability as compared to control stimulation. Individual behavioral improvements following iTBS specifically correlated with neural coupling strengths in the stimulated hemisphere prior to stimulation, especially for connections targeting the stimulated M1. Combining endogenous connectivity and behavioral parameters explained 82% of the variance in hand motor performance observed after iTBS. In conclusion, the data suggest that the individual susceptibility to iTBS after stroke is influenced by interindividual differences in motor network connectivity of the lesioned hemisphere.

  13. Auditory perception modulated by word reading.

    PubMed

    Cao, Liyu; Klepp, Anne; Schnitzler, Alfons; Gross, Joachim; Biermann-Ruben, Katja

    2016-10-01

    Theories of embodied cognition positing that sensorimotor areas are indispensable during language comprehension are supported by neuroimaging and behavioural studies. Among others, the auditory system has been suggested to be important for understanding sound-related words (visually presented) and the motor system for action-related words. In this behavioural study, using a sound detection task embedded in a lexical decision task, we show that in participants with high lexical decision performance sound verbs improve auditory perception. The amount of modulation was correlated with lexical decision performance. Our study provides convergent behavioural evidence of auditory cortex involvement in word processing, supporting the view of embodied language comprehension concerning the auditory domain.

  14. Analysis of Time-Dependent Brain Network on Active and MI Tasks for Chronic Stroke Patients

    PubMed Central

    Chang, Won Hyuk; Kim, Yun-Hee; Lee, Seong-Whan; Kwon, Gyu Hyun

    2015-01-01

    Several researchers have analyzed brain activities by investigating brain networks. However, there is a lack of the research on the temporal characteristics of the brain network during a stroke by EEG and the comparative studies between motor execution and imagery, which became known to have similar motor functions and pathways. In this study, we proposed the possibility of temporal characteristics on the brain networks of a stroke. We analyzed the temporal properties of the brain networks for nine chronic stroke patients by the active and motor imagery tasks by EEG. High beta band has a specific role in the brain network during motor tasks. In the high beta band, for the active task, there were significant characteristics of centrality and small-worldness on bilateral primary motor cortices at the initial motor execution. The degree centrality significantly increased on the contralateral primary motor cortex, and local efficiency increased on the ipsilateral primary motor cortex. These results indicate that the ipsilateral primary motor cortex constructed a powerful subnetwork by influencing the linked channels as compensatory effect, although the contralateral primary motor cortex organized an inefficient network by using the connected channels due to lesions. For the MI task, degree centrality and local efficiency significantly decreased on the somatosensory area at the initial motor imagery. Then, there were significant correlations between the properties of brain networks and motor function on the contralateral primary motor cortex and somatosensory area for each motor execution/imagery task. Our results represented that the active and MI tasks have different mechanisms of motor acts. Based on these results, we indicated the possibility of customized rehabilitation according to different motor tasks. We expect these results to help in the construction of the customized rehabilitation system depending on motor tasks by understanding temporal functional characteristics on brain network for a stroke. PMID:26656269

  15. Dopamine acting at D1-like, D2-like and α1-adrenergic receptors differentially modulates theta and gamma oscillatory activity in primary motor cortex.

    PubMed

    Özkan, Mazhar; Johnson, Nicholas W; Sehirli, Umit S; Woodhall, Gavin L; Stanford, Ian M

    2017-01-01

    The loss of dopamine (DA) in Parkinson's is accompanied by the emergence of exaggerated theta and beta frequency neuronal oscillatory activity in the primary motor cortex (M1) and basal ganglia. DA replacement therapy or deep brain stimulation reduces the power of these oscillations and this is coincident with an improvement in motor performance implying a causal relationship. Here we provide in vitro evidence for the differential modulation of theta and gamma activity in M1 by DA acting at receptors exhibiting conventional and non-conventional DA pharmacology. Recording local field potentials in deep layer V of rat M1, co-application of carbachol (CCh, 5 μM) and kainic acid (KA, 150 nM) elicited simultaneous oscillations at a frequency of 6.49 ± 0.18 Hz (theta, n = 84) and 34.97 ± 0.39 Hz (gamma, n = 84). Bath application of DA resulted in a decrease in gamma power with no change in theta power. However, application of either the D1-like receptor agonist SKF38393 or the D2-like agonist quinpirole increased the power of both theta and gamma suggesting that the DA-mediated inhibition of oscillatory power is by action at other sites other than classical DA receptors. Application of amphetamine, which promotes endogenous amine neurotransmitter release, or the adrenergic α1-selective agonist phenylephrine mimicked the action of DA and reduced gamma power, a result unaffected by prior co-application of D1 and D2 receptor antagonists SCH23390 and sulpiride. Finally, application of the α1-adrenergic receptor antagonist prazosin blocked the action of DA on gamma power suggestive of interaction between α1 and DA receptors. These results show that DA mediates complex actions acting at dopamine D1-like and D2-like receptors, α1 adrenergic receptors and possibly DA/α1 heteromultimeric receptors to differentially modulate theta and gamma activity in M1.

  16. Modulation of left primary motor cortex excitability after bimanual training and intermittent theta burst stimulation to left dorsal premotor cortex.

    PubMed

    Neva, Jason L; Vesia, Michael; Singh, Amaya M; Staines, W Richard

    2014-03-15

    Bimanual visuomotor movement training (BMT) enhances the excitability of human preparatory premotor and primary motor (M1) cortices compared to unimanual movement. This occurs when BMT involves mirror symmetrical movements of both upper-limbs (in-phase) but not with non-symmetrical movements (anti-phase). The neural mechanisms mediating the effect of BMT is unclear, but may involve interhemispheric connections between homologous M1 representations as well as the dorsal premotor cortices (PMd). The purpose of this study is to assess how intermittent theta burst stimulation (iTBS) of the left PMd affects left M1 excitability, and the possible combined effects of iTBS to left PMd applied before a single session of BMT. Left M1 excitability was quantified using transcranial magnetic stimulation (TMS) in terms of both the amplitudes and spatial extent of motor evoked potentials (MEPs) for the extensor carpi radialis (ECR) before and multiple time points following (1) BMT, (2) iTBS to left PMd or (3) iTBS to left PMd and BMT. Although there was not a greater increase in either specific measure of M1 excitability due to the combination of the interventions, iTBS applied before BMT showed that both the spatial extent and global MEP amplitude for the ECR became larger in parallel, whereas the spatial extent was enhanced with BMT alone and global MEP amplitude was enhanced with iTBS to left PMd alone. These results suggest that the modulation of rapid functional M1 excitability associated with BMT and iTBS of the left PMd could operate under related early markers of neuro-plastic mechanisms, which may be expressed in concurrent and distinct patterns of M1 excitability. Critically, this work may guide rehabilitation training and stimulation techniques that modulate cortical excitability after brain injury. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Cerebral somatic pain modulation during autogenic training in fMRI.

    PubMed

    Naglatzki, R P; Schlamann, M; Gasser, T; Ladd, M E; Sure, U; Forsting, M; Gizewski, E R

    2012-10-01

    Functional magnetic resonance imaging (fMRI) studies are increasingly employed in different conscious states. Autogenic training (AT) is a common clinically used relaxation method. The purpose of this study was to investigate the cerebral modulation of pain activity patterns due to AT and to correlate the effects to the degree of experience with AT and strength of stimuli. Thirteen volunteers familiar with AT were studied with fMRI during painful electrical stimulation in a block design alternating between resting state and electrical stimulation, both without AT and while employing the same paradigm when utilizing their AT abilities. The subjective rating of painful stimulation and success in modulation during AT was assessed. During painful electrical stimulation without AT, fMRI revealed activation of midcingulate, right secondary sensory, right supplementary motor, and insular cortices, the right thalamus and left caudate nucleus. In contrast, utilizing AT only activation of left insular and supplementary motor cortices was revealed. The paired t-test revealed pain-related activation in the midcingulate, posterior cingulate and left anterior insular cortices for the condition without AT, and activation in the left ventrolateral prefrontal cortex under AT. Activation of the posterior cingulate cortex and thalamus correlated with the amplitude of electrical stimulation. This study revealed an effect on cerebral pain processing while performing AT. This might represent the cerebral correlate of different painful stimulus processing by subjects who are trained in performing relaxation techniques. However, due to the absence of a control group, further studies are needed to confirm this theory. © 2012 European Federation of International Association for the Study of Pain Chapters.

  18. Experience-dependent modulation of feedback integration during singing: role of the right anterior insula.

    PubMed

    Kleber, Boris; Zeitouni, Anthony G; Friberg, Anders; Zatorre, Robert J

    2013-04-03

    Somatosensation plays an important role in the motor control of vocal functions, yet its neural correlate and relation to vocal learning is not well understood. We used fMRI in 17 trained singers and 12 nonsingers to study the effects of vocal-fold anesthesia on the vocal-motor singing network as a function of singing expertise. Tasks required participants to sing musical target intervals under normal conditions and after anesthesia. At the behavioral level, anesthesia altered pitch accuracy in both groups, but singers were less affected than nonsingers, indicating an experience-dependent effect of the intervention. At the neural level, this difference was accompanied by distinct patterns of decreased activation in singers (cortical and subcortical sensory and motor areas) and nonsingers (subcortical motor areas only) respectively, suggesting that anesthesia affected the higher-level voluntary (explicit) motor and sensorimotor integration network more in experienced singers, and the lower-level (implicit) subcortical motor loops in nonsingers. The right anterior insular cortex (AIC) was identified as the principal area dissociating the effect of expertise as a function of anesthesia by three separate sources of evidence. First, it responded differently to anesthesia in singers (decreased activation) and nonsingers (increased activation). Second, functional connectivity between AIC and bilateral A1, M1, and S1 was reduced in singers but augmented in nonsingers. Third, increased BOLD activity in right AIC in singers was correlated with larger pitch deviation under anesthesia. We conclude that the right AIC and sensory-motor areas play a role in experience-dependent modulation of feedback integration for vocal motor control during singing.

  19. Dopamine D1 receptor activation maintains motor coordination in injured rats but does not accelerate the recovery of the motor coordination deficit.

    PubMed

    Avila-Luna, Alberto; Gálvez-Rosas, Arturo; Alfaro-Rodríguez, Alfonso; Reyes-Legorreta, Celia; Garza-Montaño, Paloma; González-Piña, Rigoberto; Bueno-Nava, Antonio

    2018-01-15

    The sensorimotor cortex and the striatum are interconnected by the corticostriatal pathway, suggesting that cortical injury alters the striatal function that is associated with skilled movements and motor learning, which are functions that may be modulated by dopamine (DA). In this study, we explored motor coordination and balance in order to investigate whether the activation of D 1 receptors (D 1 Rs) modulates functional recovery after cortical injury. The results of the beam-walking test showed motor deficit in the injured group at 24, 48 and 96h post-injury, and the recovery time was observed at 192h after cortical injury. In the sham and injured rats, systemic administration of the D 1 R antagonist SCH-23390 (1mg/kg) alone at 24, 48, 96 and 192h significantly (P<0.01) increased the motor deficit, while administration of the D 1 R agonist SKF-38393 alone (2, 3 and 4mg/kg) at 24, 48, 96 and 192h post-injury did not produce a significant difference; however, the co-administration of SKF-38393 and SCH-23390 prevented the antagonist-induced increase in the motor deficit. The cortical+striatal injury showed significantly increased the motor deficit at 24, 48, 96 and 192h post-injury (P<0.01) but did not show recovery at 192h. In conclusion, the administration of the D 1 R agonist did not accelerate the motor recovery, but the activation of D 1 Rs maintained motor coordination, confirming that an intact striatum may be necessary for achieving recovery. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Induction of cortical plasticity and improved motor performance following unilateral and bilateral transcranial direct current stimulation of the primary motor cortex.

    PubMed

    Kidgell, Dawson J; Goodwill, Alicia M; Frazer, Ashlyn K; Daly, Robin M

    2013-07-01

    Transcranial direct current stimulation (tDCS) is a non-invasive technique that modulates the excitability of neurons within the primary motor cortex (M1). Research shows that anodal-tDCS applied over the non-dominant M1 (i.e. unilateral stimulation) improves motor function of the non-dominant hand. Similarly, previous studies also show that applying cathodal tDCS over the dominant M1 improves motor function of the non-dominant hand, presumably by reducing interhemispheric inhibition. In the present study, one condition involved anodal-tDCS over the non-dominant M1 (unilateral stimulation) whilst a second condition involved applying cathodal-tDCS over the dominant M1 and anodal-tDCS over non-dominant M1 (bilateral stimulation) to determine if unilateral or bilateral stimulation differentially modulates motor function of the non-dominant hand. Using a randomized, cross-over design, 11 right-handed participants underwent three stimulation conditions: 1) unilateral stimulation, that involved anodal-tDCS applied over the non-dominant M1, 2) bilateral stimulation, whereby anodal-tDCS was applied over the non-dominant M1, and cathodal-tDCS over the dominant M1, and 3) sham stimulation. Transcranial magnetic stimulation (TMS) was performed before, immediately after, 30 and 60 minutes after stimulation to elucidate the neural mechanisms underlying any potential after-effects on motor performance. Motor function was evaluated by the Purdue pegboard test. There were significant improvements in motor function following unilateral and bilateral stimulation when compared to sham stimulation at all-time points (all P < 0.05); however there was no difference across time points between unilateral and bilateral stimulation. There was also a similar significant increase in corticomotor excitability with both unilateral and bilateral stimulation immediately post, 30 minutes and 60 minutes compared to sham stimulation (all P < 0.05). Unilateral and bilateral stimulation reduced short-interval intracortical inhibition (SICI) immediately post and at 30 minutes (all P < 0.05), but returned to baseline in both conditions at 60 minutes. There was no difference between unilateral and bilateral stimulation for SICI (P > 0.05). Furthermore, changes in corticomotor plasticity were not related to changes in motor performance. These results indicate that tDCS induced behavioural changes in the non-dominant hand as a consequence of mechanisms associated with use-dependant cortical plasticity that is independent of the electrode arrangement.

  1. Role of the primary motor cortex in the maintenance and treatment of pain in fibromyalgia.

    PubMed

    Castillo Saavedra, Laura; Mendonca, Mariana; Fregni, Felipe

    2014-09-01

    Fibromyalgia is a highly prevalent, debilitating disease, characterized by chronic widespread pain. The mechanisms underlying pain are not completely understood, but it is believed to be associated with important neuroplastic changes in pain-related neural circuits. Although the involvement of the pain matrix in fibromyalgia is well established, another area that has been found to play a role in the maintenance and treatment of chronic pain is the primary motor cortex (M1). Maladaptive plasticity of M1 is a common finding in patients with chronic pain and many studies in animal models and in human subjects have shown that modulation of the activity of this cortical area induces significant analgesic effects. Furthermore, studies in other chronic pain syndromes have found alterations in baseline characteristics of M1, including an increase in cortical excitability and an abnormally enhanced response to incoming sensory stimuli. Given these findings, we hypothesize that M1 is a major modulator of pain in fibromyalgia and therefore its baseline activity reflects this strong feedback between M1 and pain-related neural areas. However, the feedback loop between M1 and the pain matrix is not enough to decrease pain in fibromyalgia per se, thus increasing its modulatory effect by engaging this network through different behavioral and modulatory techniques is a potentially beneficial treatment for pain in fibromyalgia. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. [Neurology of laughter and humour: pathological laughing and crying].

    PubMed

    Arias, Manuel

    2011-10-01

    Laughter, which is usually a healthy biological phenomenon, may be also a symptom of several severe brain pathologies. To review the neurobiological bases of laughter and humour, as well as those of pathological laughing and crying syndrome. At the mesencephalic-pontine junction there is a central coordinator of the nuclei that innervate the muscles involved in laughter (facial expression, respiratory and phonatory). This centre receives connections from three systems: inhibitory (pre-motor and motor cortex), excitatory (temporal cortex, amygdala, hypothalamus) and modulator (cerebellum). Humour is a complex phenomenon with a range of components: the perception of the unexpected incongruence (occipitotemporal area, prefrontal cortex), emotional (reward circuit) and volitional (temporal and frontal cortex). Functional magnetic resonance imaging studies do not reveal a markedly prominent role of the right frontal lobe in processing humour, as had been suggested in the classical studies. The causes of pathological laughing and crying syndrome can be classified in two groups: altered behaviour with unmotivated happiness (Angelman syndrome, schizophrenia, manias, dementia) and interference with the inhibitory/excitatory mechanisms (gelastic epilepsy, fou rire prodromique in strokes, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease and Parkinson-plus, traumatic injuries, tumours). Serotonin and noradrenalin reuptake inhibitors, levodopa, lamotrigine and the association of dextromethorphan/quinidine can be effective in certain cases of pathological laughing and crying. As human neurobiological phenomena, laughter and humour also belong to the field of clinical neurology; their processing is affected in a number of different diseases and, in certain cases, effective treatment can be established.

  3. The somatotopy of speech: Phonation and articulation in the human motor cortex

    PubMed Central

    Brown, Steven; Laird, Angela R.; Pfordresher, Peter Q.; Thelen, Sarah M.; Turkeltaub, Peter; Liotti, Mario

    2010-01-01

    A sizable literature on the neuroimaging of speech production has reliably shown activations in the orofacial region of the primary motor cortex. These activations have invariably been interpreted as reflecting “mouth” functioning and thus articulation. We used functional magnetic resonance imaging to compare an overt speech task with tongue movement, lip movement, and vowel phonation. The results showed that the strongest motor activation for speech was the somatotopic larynx area of the motor cortex, thus reflecting the significant contribution of phonation to speech production. In order to analyze further the phonatory component of speech, we performed a voxel-based meta-analysis of neuroimaging studies of syllable-singing (11 studies) and compared the results with a previously-published meta-analysis of oral reading (11 studies), showing again a strong overlap in the larynx motor area. Overall, these findings highlight the under-recognized presence of phonation in imaging studies of speech production, and support the role of the larynx motor cortex in mediating the “melodicity” of speech. PMID:19162389

  4. Magnetothermal genetic deep brain stimulation of motor behaviors in awake, freely moving mice

    PubMed Central

    Zhang, Qian; Castellanos Rubio, Idoia; del Pino, Pablo

    2017-01-01

    Establishing how neurocircuit activation causes particular behaviors requires modulating the activity of specific neurons. Here, we demonstrate that magnetothermal genetic stimulation provides tetherless deep brain activation sufficient to evoke motor behavior in awake mice. The approach uses alternating magnetic fields to heat superparamagnetic nanoparticles on the neuronal membrane. Neurons, heat-sensitized by expressing TRPV1 are activated with magnetic field application. Magnetothermal genetic stimulation in the motor cortex evoked ambulation, deep brain stimulation in the striatum caused rotation around the body-axis, and stimulation near the ridge between ventral and dorsal striatum caused freezing-of-gait. The duration of the behavior correlated tightly with field application. This approach provides genetically and spatially targetable, repeatable and temporarily precise activation of deep-brain circuits without the need for surgical implantation of any device. PMID:28826470

  5. Laryngeal Motor Cortex and Control of Speech in Humans

    PubMed Central

    Simonyan, Kristina; Horwitz, Barry

    2011-01-01

    Speech production is one of the most complex and rapid motor behaviors and involves a precise coordination of over 100 laryngeal, orofacial and respiratory muscles. Yet, we lack a complete understanding of laryngeal motor cortical control during production of speech and other voluntary laryngeal behaviors. In recent years, a number of studies have confirmed the laryngeal motor cortical representation in humans and provided some information about its interactions with other cortical and subcortical regions that are principally involved in vocal motor control of speech production. In this review, we discuss the organization of the peripheral and central laryngeal control based on neuroimaging and electrical stimulation studies in humans and neuroanatomical tracing studies in non-human primates. We hypothesize that the location of the laryngeal motor cortex in the primary motor cortex and its direct connections with the brainstem laryngeal motoneurons in humans, as oppose to its location in the premotor cortex with only indirect connections to the laryngeal motoneurons in non-human primates, may represent one of the major evolutionary developments in humans towards the ability to speak and vocalize voluntarily. PMID:21362688

  6. Advancing functional dysconnectivity and atrophy in progressive supranuclear palsy.

    PubMed

    Brown, Jesse A; Hua, Alice Y; Trujllo, Andrew; Attygalle, Suneth; Binney, Richard J; Spina, Salvatore; Lee, Suzee E; Kramer, Joel H; Miller, Bruce L; Rosen, Howard J; Boxer, Adam L; Seeley, William W

    2017-01-01

    Progressive supranuclear palsy syndrome (PSP-S) results from neurodegeneration within a network of brainstem, subcortical, frontal and parietal cortical brain regions. It is unclear how network dysfunction progresses and relates to longitudinal atrophy and clinical decline. In this study, we evaluated patients with PSP-S (n = 12) and healthy control subjects (n = 20) at baseline and 6 months later. Subjects underwent structural MRI and task-free functional MRI (tf-fMRI) scans and clinical evaluations at both time points. At baseline, voxel based morphometry (VBM) revealed that patients with mild-to-moderate clinical symptoms showed structural atrophy in subcortex and brainstem, prefrontal cortex (PFC; supplementary motor area, paracingulate, dorsal and ventral medial PFC), and parietal cortex (precuneus). Tf-fMRI functional connectivity (FC) was examined in a rostral midbrain tegmentum (rMT)-anchored intrinsic connectivity network that is compromised in PSP-S. In healthy controls, this network contained a medial parietal module, a prefrontal-paralimbic module, and a subcortical-brainstem module. Baseline FC deficits in PSP-S were most severe in rMT network integrative hubs in the prefrontal-paralimbic and subcortical-brainstem modules. Longitudinally, patients with PSP-S had declining intermodular FC between the subcortical-brainstem and parietal modules, while progressive atrophy was observed in subcortical-brainstem regions (midbrain, pallidum) and posterior frontal (perirolandic) cortex. This suggested that later-stage subcortical-posterior cortical change may follow an earlier-stage subcortical-anterior cortical disease process. Clinically, patients with more severe baseline impairment showed greater subsequent prefrontal-parietal cortical FC declines and posterior frontal atrophy rates, while patients with more rapid longitudinal clinical decline showed coupled prefrontal-paralimbic FC decline. VBM and FC can augment disease monitoring in PSP-S by tracking the disease through stages while detecting changes that accompany heterogeneous clinical progression.

  7. State-Dependent Spike and Local Field Synchronization between Motor Cortex and Substantia Nigra in Hemiparkinsonian Rats

    PubMed Central

    Brazhnik, Elena; Cruz, Ana V.; Avila, Irene; Wahba, Marian I.; Novikov, Nikolay; Ilieva, Neda M.; McCoy, Alex J.; Gerber, Colin; Walters, Judith. R.

    2012-01-01

    Excessive beta frequency oscillatory and synchronized activity has been reported in the basal ganglia of Parkinsonian patients and animal models of the disease. To gain insight into processes underlying this activity, this study explores relationships between oscillatory activity in motor cortex and basal ganglia output in behaving rats after dopamine cell lesion. During inattentive rest, seven days after lesion, increases in motor cortex-substantia nigra pars reticulata (SNpr) coherence emerged in the 8–25 Hz range, with significant increases in local field potential (LFP) power in SNpr but not motor cortex. In contrast, during treadmill walking, marked increases in both motor cortex and SNpr LFP power, as well as coherence, emerged in the 25–40 Hz band with a peak frequency at 30–35 Hz. Spike-triggered waveform averages showed that 77% of SNpr neurons, 77% of putative cortical interneurons and 44% of putative pyramidal neurons were significantly phase-locked to the increased cortical LFP activity in the 25–40 Hz range. Although the mean lag between cortical and SNpr LFPs fluctuated around zero, SNpr neurons phase-locked to cortical LFP oscillations fired, on average, 17 ms after synchronized spiking in motor cortex. High coherence between LFP oscillations in cortex and SNpr supports the view that cortical activity facilitates entrainment and synchronization of activity in basal ganglia after loss of dopamine. However, the dramatic increases in cortical power and relative timing of phase-locked spiking in these areas suggest that additional processes help shape the frequency-specific tuning of the basal ganglia-thalamocortical network during ongoing motor activity. PMID:22674263

  8. Reduced cortico-motor facilitation in a normal sample with high traits of autism.

    PubMed

    Puzzo, Ignazio; Cooper, Nicholas R; Vetter, Petra; Russo, Riccardo; Fitzgerald, Paul B

    2009-12-25

    Recent research in social neuroscience proposes a link between mirror neuron system (MNS) and social cognition. The MNS has been proposed to be the neural mechanism underlying action recognition and intention understanding and more broadly social cognition. Pre-motor MNS has been suggested to modulate the motor cortex during action observation. This modulation results in an enhanced cortico-motor excitability reflected in increased motor evoked potentials (MEPs) at the muscle of interest during action observation. Anomalous MNS activity has been reported in the autistic population whose social skills are notably impaired. It is still an open question whether traits of autism in the normal population are linked to the MNS functioning. We measured TMS-induced MEPs in normal individuals with high and low traits of autism as measured by the autistic quotient (AQ), while observing videos of hand or mouth actions, static images of a hand or mouth or a blank screen. No differences were observed between the two while they observed a blank screen. However participants with low traits of autism showed significantly greater MEP amplitudes during observation of hand/mouth actions relative to static hand/mouth stimuli. In contrast, participants with high traits of autism did not show such a MEP amplitude difference between observation of actions and static stimuli. These results are discussed with reference to MNS functioning.

  9. Influence of mirror therapy on human motor cortex.

    PubMed

    Fukumura, Kenji; Sugawara, Kenichi; Tanabe, Shigeo; Ushiba, Junichi; Tomita, Yutaka

    2007-07-01

    This article investigates whether or not mirror therapy alters the neural mechanisms in human motor cortex. Six healthy volunteers participated. The study investigated the effects of three main factors of mirror therapy (observation of hand movements in a mirror, motor imagery of an assumed affected hand, and assistance in exercising the assumed affected hand) on excitability changes in the human motor cortex to clarify the contribution of each factor. The increase in motor-evoked potential (MEP) amplitudes during motor imagery tended to be larger with a mirror than without one. Moreover, MEP amplitudes increased greatly when movements were assisted. Watching the movement of one hand in a mirror makes it easier to move the other hand in the same way. Moreover, the increase in MEP amplitudes is related to the synergic effects of afferent information and motor imagery.

  10. Effects of 10 Hz and 20 Hz Transcranial Alternating Current Stimulation on Automatic Motor Control.

    PubMed

    Cappon, Davide; D'Ostilio, Kevin; Garraux, Gaëtan; Rothwell, John; Bisiacchi, Patrizia

    2016-01-01

    In a masked prime choice reaction task, presentation of a compatible prime increases the reaction time to the following imperative stimulus if the interval between mask and prime is around 80-250 ms. This is thought to be due to automatic suppression of the motor plan evoked by the prime, which delays reaction to the imperative stimulus. Oscillatory activity in motor networks around the beta frequency range of 20 Hz is important in suppression of movement. Transcranial alternating current at 20 Hz may be able to drive oscillations in the beta range. To investigate whether transcranial alternating current stimulation (tACS) at 20 Hz would increase automatic inhibition in a masked prime task. As a control we used 10 Hz tACS. Stimulation was delivered at alpha (10 Hz) and beta (20 Hz) frequency over the supplementary motor area and the primary motor cortex (simultaneous tACS of SMA-M1), which are part of the BG-cortical motor loop, during the execution of the subliminal masked prime left/right choice reaction task. We measured the effects on reaction times. Corticospinal excitability was assessed by measuring the amplitude of motor evoked potentials (MEPs) evoked in the first dorsal interosseous muscle by transcranial magnetic stimulation (TMS) over M1. The 10 and 20-Hz tACS over SMA-M1 had different effects on automatic inhibition. The 20 Hz tACS increased the duration of automatic inhibition whereas it was decreased by 10 Hz tACS. Neurophysiologically, 20 Hz tACS reduced the amplitude of MEPs evoked from M1, whereas there was no change after 10 Hz tACS. Automatic mechanisms of motor inhibition can be modulated by tACS over motor areas of cortex. tACS may be a useful additional tool to investigate the causal links between endogenous brain oscillations and specific cognitive processes. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Noninvasive EEG correlates of overground and stair walking.

    PubMed

    Brantley, Justin A; Luu, Trieu Phat; Ozdemir, Recep; Zhu, Fangshi; Winslow, Anna T; Huang, Helen; Contreras-Vidal, Jose L

    2016-08-01

    Automated walking intention detection remains a challenge in lower-limb neuroprosthetic systems. Here, we assess the feasibility of extracting motor intent from scalp electroencephalography (EEG). First, we evaluated the corticomuscular coherence between central EEG electrodes (C1, Cz, C2) and muscles of the shank and thigh during walking on level ground and stairs. Second, we trained decoders to predict the linear envelope of the surface electromyogram (EMG). We observed significant EEG-led corticomuscular coupling between electrodes and sEMG (tibialis anterior) in the high delta (3-4 Hz) and low theta (4-5 Hz) frequency bands during level walking, indicating efferent signaling from the cortex to peripheral motor neurons. The coherence was increased between EEG and vastus lateralis and tibialis anterior in the delta band (<; 2 Hz) during stair ascent, indicating a task specific modulation in corticomuscular coupling. However, EMG was the leading signal for biceps femoris and gastrocnemius coherence during stair ascent, possibly representing afferent feedback loops from periphery to the motor cortex. Decoder validation showed that EEG signals contained information about the sEMG patterns during over ground walking, however, the accuracy of the predicted sEMG patterns decreased during the stair condition. Overall, these initial findings support the feasibility of integrating sEMG and EEG into a hybrid decoder for volitional control of lower limb neuroprostheses.

  12. Laminar-specific distribution of zinc: evidence for presence of layer IV in forelimb motor cortex in the rat.

    PubMed

    Alaverdashvili, Mariam; Hackett, Mark J; Pickering, Ingrid J; Paterson, Phyllis G

    2014-12-01

    The rat is the most widely studied pre-clinical model system of various neurological and neurodegenerative disorders affecting hand function. Although brain injury to the forelimb region of the motor cortex in rats mostly induces behavioral abnormalities in motor control of hand movements, behavioral deficits in the sensory-motor domain are also observed. This questions the prevailing view that cortical layer IV, a recipient of sensory information from the thalamus, is absent in rat motor cortex. Because zinc-containing neurons are generally not found in pathways that run from the thalamus, an absence of zinc (Zn) in a cortical layer would be suggestive of sensory input from the thalamus. To test this hypothesis, we used synchrotron micro X-ray fluorescence imaging to measure Zn distribution across cortical layers. Zn maps revealed a heterogeneous layered Zn distribution in primary and secondary motor cortices of the forelimb region in the adult rat. Two wider bands with elevated Zn content were separated by a narrow band having reduced Zn content, and this was evident in two rat strains. The Zn distribution pattern was comparable to that in sensorimotor cortex, which is known to contain a well demarcated layer IV. Juxtaposition of Zn maps and the images of brain stained for Nissl bodies revealed a "Zn valley" in primary motor cortex, apparently starting at the ventral border of pyramidal layer III and ending at the close vicinity of layer V. This finding indicates the presence of a conspicuous cortical layer between layers III and V, i.e. layer IV, the presence of which previously has been disputed. The results have implications for the use of rat models to investigate human brain function and neuropathology, such as after stroke. The presence of layer IV in the forelimb region of the motor cortex suggests that therapeutic interventions used in rat models of motor cortex injury should target functional abnormalities in both motor and sensory domains. The finding is also critical for future investigation of the biochemical mechanisms through which therapeutic interventions can enhance neural plasticity, particularly through Zn dependent pathways. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Laminar-specific distribution of zinc: Evidence for presence of layer IV in forelimb motor cortex in the rat

    PubMed Central

    Alaverdashvili, Mariam; Hackett, Mark J.; Pickering, Ingrid J.; Paterson, Phyllis G.

    2015-01-01

    The rat is the most widely studied pre-clinical model system of various neurological and neurodegenerative disorders affecting hand function. Although brain injury to the forelimb region of the motor cortex in rats mostly induces behavioral abnormalities in motor control of hand movements, behavioral deficits in the sensory-motor domain are also observed. This questions the prevailing view that cortical layer IV, a recipient of sensory information from the thalamus, is absent in rat motor cortex. Because zinc-containing neurons are generally not found in pathways that run from the thalamus, an absence of zinc (Zn) in a cortical layer would be suggestive of sensory input from the thalamus. To test this hypothesis, we used synchrotron micro X-ray fluorescence imaging to measure Zn distribution across cortical layers. Zn maps revealed a heterogeneous layered Zn distribution in primary and secondary motor cortices of the forelimb region in the adult rat. Two wider bands with elevated Zn content were separated by a narrow band having reduced Zn content, and this was evident in two rat strains. The Zn distribution pattern was comparable to that in sensorimotor cortex, which is known to contain a well demarcated layer IV. Juxtaposition of Zn maps and the images of brain stained for Nissl bodies revealed a “Zn valley” in primary motor cortex, apparently starting at the ventral border of pyramidal layer III and ending at the close vicinity of layer V. This finding indicates the presence of a conspicuous cortical layer between layers III and V, i.e. layer IV, the presence of which previously has been disputed. The results have implications for the use of rat models to investigate human brain function and neuropathology, such as after stroke. The presence of layer IV in the forelimb region of the motor cortex suggests that therapeutic interventions used in rat models of motor cortex injury should target functional abnormalities in both motor and sensory domains. The finding is also critical for future investigation of the biochemical mechanisms through which therapeutic interventions can enhance neural plasticity, particularly through Zn dependent pathways. PMID:25192655

  14. Neuropsychological Investigation of Motor Impairments in Autism

    PubMed Central

    Duffield, Tyler; Trontel, Haley; Bigler, Erin D.; Froehlich, Alyson; Prigge, Molly B.; Travers, Brittany; Green, Ryan R.; Cariello, Annahir N.; Cooperrider, Jason; Nielsen, Jared; Alexander, Andrew; Anderson, Jeffrey; Fletcher, P. Thomas; Lange, Nicholas; Zielinski, Brandon; Lainhart, Janet

    2013-01-01

    It is unclear how standardized neuropsychological measures of motor function relate to brain volumes of motor regions in autism spectrum disorder (ASD). An all male sample composed of 59 ASD and 30 controls (ages 5–33 years) completed three measures of motor function: strength of grip (SOG), finger tapping test (FTT), and grooved peg-board test (GPT). Likewise, all participants underwent magnetic resonance imaging with region of interest (ROI) volumes obtained to include the following regions: motor cortex (pre-central gyrus), somatosensory cortex (post-central gyrus), thalamus, basal ganglia, cerebellum and caudal middle frontal gyrus. These traditional neuropsychological measures of motor function are assumed to differ in motor complexity with GPT requiring the most followed by FTT and SOG. Performance by ASD participants on the GPT and FTT differed significantly from controls, with the largest effect size differences observed on the more complex GPT task. Differences on the SOG task between the two groups were non-significant. Since more complex motor tasks tap more complex networks, poorer GPT performance by those with ASD may reflect less efficient motor networks. There was no gross pathology observed in classic motor areas of the brain in ASD, as region of interest (ROI) volumes did not differ, but FTT was negatively related to motor cortex volume in ASD. The results suggest a hierarchical motor disruption in ASD, with difficulties evident only in more complex tasks as well as a potential anomalous size-function relation in motor cortex in ASD. PMID:23985036

  15. Transcranial magnetic stimulation potentiates glutamatergic neurotransmission in depressed adolescents.

    PubMed

    Croarkin, Paul E; Nakonezny, Paul A; Wall, Christopher A; Murphy, Lauren L; Sampson, Shirlene M; Frye, Mark A; Port, John D

    2016-01-30

    Abnormalities in glutamate neurotransmission may have a role in the pathophysiology of adolescent depression. The present pilot study examined changes in cortical glutamine/glutamate ratios in depressed adolescents receiving high-frequency repetitive transcranial magnetic stimulation. Ten adolescents with treatment-refractory major depressive disorder received up to 30 sessions of 10-Hz repetitive transcranial magnetic stimulation at 120% motor threshold with 3000 pulses per session applied to the left dorsolateral prefrontal cortex. Baseline, posttreatment, and 6-month follow-up proton magnetic resonance spectroscopy scans of the anterior cingulate cortex and left dorsolateral prefrontal cortex were collected at 3T with 8-cm(3) voxels. Glutamate metabolites were quantified with 2 distinct proton magnetic resonance spectroscopy sequences in each brain region. After repetitive transcranial magnetic stimulation and at 6 months of follow-up, glutamine/glutamate ratios increased in the anterior cingulate cortex and left dorsolateral prefrontal cortex with both measurements. The increase in the glutamine/glutamate ratio reached statistical significance with the TE-optimized PRESS sequence in the anterior cingulate cortex. Glutamine/glutamate ratios increased in conjunction with depressive symptom improvement. This reached statistical significance with the TE-optimized PRESS sequence in the left dorsolateral prefrontal cortex. High-frequency repetitive transcranial magnetic stimulation applied to the left dorsolateral prefrontal cortex may modulate glutamate neurochemistry in depressed adolescents. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Changes in cortical, cerebellar and basal ganglia representation after comprehensive long term unilateral hand motor training.

    PubMed

    Walz, A D; Doppl, K; Kaza, E; Roschka, S; Platz, T; Lotze, M

    2015-02-01

    We were interested in motor performance gain after unilateral hand motor training and associated changes of cerebral and cerebellar movement representation tested with functional magnetic resonance imaging (fMRI) before and after training. Therefore, we trained the left hand of strongly right-handed healthy participants with a comprehensive training (arm ability training, AAT) over two weeks. Motor performance was tested for the trained and non-trained hand before and after the training period. Functional imaging was performed for the trained and the non-trained hand separately and comprised force modulation with the fist, sequential finger movements and a fast writing task. After the training period the performance gain of tapping movements was comparable for both hand sides, whereas the motor performance for writing showed a higher training effect for the trained hand. fMRI showed a reduction of activation in supplementary motor, dorsolateral prefrontal cortex, parietal cortical areas and lateral cerebellar areas during sequential finger movements over time. During left hand writing lateral cerebellar hemisphere also showed reduced activation, while activation of the anterior cerebellar hemisphere was increased. An initially high anterior cerebellar activation magnitude was a predictive value for high training outcome of finger tapping and visual guided movements. During the force modulation task we found increased activation in the striate. Overall, a comprehensive long-term training of the less skillful hand in healthy participants resulted in relevant motor performance improvements, as well as an intermanual learning transfer differently pronounced for the type of movement tested. Whereas cortical motor area activation decreased over time, cerebellar anterior hemisphere and striatum activity seem to represent increasing resources after long-term motor training. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Plasticity of cortical inhibition in dystonia is impaired after motor learning and paired-associative stimulation.

    PubMed

    Meunier, Sabine; Russmann, Heike; Shamim, Ejaz; Lamy, Jean-Charles; Hallett, Mark

    2012-03-01

    Artificial induction of plasticity by paired associative stimulation (PAS) in healthy volunteers (HV) demonstrates Hebbian-like plasticity in selected inhibitory networks as well as excitatory networks. In a group of 17 patients with focal hand dystonia and a group of 19 HV, we evaluated how PAS and the learning of a simple motor task influence the circuits supporting long-interval intracortical inhibition (LICI, reflecting activity of GABA(B) interneurons) and long-latency afferent inhibition (LAI, reflecting activity of somatosensory inputs to the motor cortex). In HV, PAS and motor learning induced long-term potentiation (LTP)-like plasticity of excitatory networks and a lasting decrease of LAI and LICI in the motor representation of the targeted or trained muscle. The better the motor performance, the larger was the decrease of LAI. Although motor performance in the patient group was similar to that of the control group, LAI did not decrease during the motor learning as it did in the control group. In contrast, LICI was normally modulated. In patients the results after PAS did not match those obtained after motor learning: LAI was paradoxically increased and LICI did not exhibit any change. In the normal situation, decreased excitability in inhibitory circuits after induction of LTP-like plasticity may help to shape the cortical maps according to the new sensorimotor task. In patients, the abnormal or absent modulation of afferent and intracortical long-interval inhibition might indicate maladaptive plasticity that possibly contributes to the difficulty that they have to learn a new sensorimotor task. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  18. Motor Cortex Reorganization across the Lifespan

    ERIC Educational Resources Information Center

    Plowman, Emily K.; Kleim, Jeffrey A.

    2010-01-01

    The brain is a highly dynamic structure with the capacity for profound structural and functional change. Such neural plasticity has been well characterized within motor cortex and is believed to represent one of the neural mechanisms for acquiring and modifying motor behaviors. A number of behavioral and neural signals have been identified that…

  19. Systematic assessment of duration and intensity of anodal transcranial direct current stimulation on primary motor cortex excitability.

    PubMed

    Tremblay, Sara; Larochelle-Brunet, Félix; Lafleur, Louis-Philippe; El Mouderrib, Sofia; Lepage, Jean-François; Théoret, Hugo

    2016-09-01

    Since the initial demonstration of linear effects of stimulation duration and intensity on the strength of after-effects associated with transcranial direct current stimulation (tDCS), few studies have systematically assessed how varying these parameters modulates corticospinal excitability. Therefore, the objective of this study was to systematically evaluate the effects of anodal tDCS on corticospinal excitability at two stimulation intensities (1 mA, 2 mA) and durations (10 min, 20 min), and determine the value of several variables in predicting response. Two groups of 20 individuals received, in two separate sessions, 1 and 2 mA anodal tDCS (left primary motor cortex (M1)-right supra-orbital montage) for either 10- or 20-min. Transcranial magnetic stimulation was delivered over left M1 and motor evoked potentials (MEPs) of the contralateral hand were recorded prior to tDCS and every 5 min for 20-min post-tDCS. The following predictive variables were evaluated: I-wave recruitment, stimulation intensity, baseline M1 excitability and inter-trial MEP variability. Results show that anodal tDCS failed to significantly modulate corticospinal excitability in all conditions. Furthermore, low response rates were identified across all parameter combinations. No baseline measure was significantly correlated with increases in MEP amplitude. However, a decrease in inter-trial MEP variability was linked to response to anodal tDCS. In conclusion, the present findings are consistent with recent reports showing high levels of inter-subject variability in the neurophysiological response to tDCS, which may partly explain inconsistent group results. Furthermore, the level of variability in the neurophysiological outcome measure, i.e. MEPs, appears to be related to response. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  20. Neurofeedback training of alpha-band coherence enhances motor performance.

    PubMed

    Mottaz, Anais; Solcà, Marco; Magnin, Cécile; Corbet, Tiffany; Schnider, Armin; Guggisberg, Adrian G

    2015-09-01

    Neurofeedback training of motor cortex activations with brain-computer interface systems can enhance recovery in stroke patients. Here we propose a new approach which trains resting-state functional connectivity associated with motor performance instead of activations related to movements. Ten healthy subjects and one stroke patient trained alpha-band coherence between their hand motor area and the rest of the brain using neurofeedback with source functional connectivity analysis and visual feedback. Seven out of ten healthy subjects were able to increase alpha-band coherence between the hand motor cortex and the rest of the brain in a single session. The patient with chronic stroke learned to enhance alpha-band coherence of his affected primary motor cortex in 7 neurofeedback sessions applied over one month. Coherence increased specifically in the targeted motor cortex and in alpha frequencies. This increase was associated with clinically meaningful and lasting improvement of motor function after stroke. These results provide proof of concept that neurofeedback training of alpha-band coherence is feasible and behaviorally useful. The study presents evidence for a role of alpha-band coherence in motor learning and may lead to new strategies for rehabilitation. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  1. Plasticity and alterations of trunk motor cortex following spinal cord injury and non-stepping robot and treadmill training.

    PubMed

    Oza, Chintan S; Giszter, Simon F

    2014-06-01

    Spinal cord injury (SCI) induces significant reorganization in the sensorimotor cortex. Trunk motor control is crucial for postural stability and propulsion after low thoracic SCI and several rehabilitative strategies are aimed at trunk stability and control. However little is known about the effect of SCI and rehabilitation training on trunk motor representations and their plasticity in the cortex. Here, we used intracortical microstimulation to examine the motor cortex representations of the trunk in relation to other representations in three groups of chronic adult complete low thoracic SCI rats: chronic untrained, treadmill trained (but 'non-stepping') and robot assisted treadmill trained (but 'non-stepping') and compared with a group of normal rats. Our results demonstrate extensive and significant reorganization of the trunk motor cortex after chronic adult SCI which includes (1) expansion and rostral displacement of trunk motor representations in the cortex, with the greatest significant increase observed for rostral (to injury) trunk, and slight but significant increase of motor representation for caudal (to injury) trunk at low thoracic levels in all spinalized rats; (2) significant changes in coactivation and the synergy representation (or map overlap) between different trunk muscles and between trunk and forelimb. No significant differences were observed between the groups of transected rats for the majority of the comparisons. However, (3) the treadmill and robot-treadmill trained groups of rats showed a further small but significant rostral migration of the trunk representations, beyond the shift caused by transection alone. We conclude that SCI induces a significant reorganization of the trunk motor cortex, which is not qualitatively altered by non-stepping treadmill training or non-stepping robot assisted treadmill training, but is shifted further from normal topography by the training. This shift may potentially make subsequent rehabilitation with stepping longer or less successful. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Motor learning and modulation of prefrontal cortex: an fNIRS assessment

    NASA Astrophysics Data System (ADS)

    Ono, Yumie; Noah, Jack Adam; Zhang, Xian; Nomoto, Yasunori; Suzuki, Tatsuya; Shimada, Sotaro; Tachibana, Atsumichi; Bronner, Shaw; Hirsch, Joy

    2015-12-01

    Objective. Prefrontal hemodynamic responses are observed during performance of motor tasks. Using a dance video game (DVG), a complex motor task that requires temporally accurate footsteps with given visual and auditory cues, we investigated whether 20 h of DVG training modified hemodynamic responses of the prefrontal cortex in six healthy young adults. Approach. Fronto-temporal activity during actual DVG play was measured using functional near-infrared spectroscopy (fNIRS) pre- and post-training. To evaluate the training-induced changes in the time-courses of fNIRS signals, we employed a regression analysis using the task-specific template fNIRS signals that were generated from alternate well-trained and/or novice DVG players. The HRF was also separately incorporated as a template to construct an alternate regression model. Change in coefficients for template functions at pre- and post- training were determined and compared among different models. Main results. Training significantly increased the motor performance using the number of temporally accurate steps in the DVG as criteria. The mean oxygenated hemoglobin (ΔoxyHb) waveform changed from an activation above baseline pattern to that of a below baseline pattern. Participants showed significantly decreased coefficients for regressors of the ΔoxyHb response of novice players and HRF. The model using ΔoxyHb responses from both well-trained and novice players of DVG as templates showed the best fit for the ΔoxyHb responses of the participants at both pre- and post-training when analyzed with Akaike information criteria. Significance. These results suggest that the coefficients for the template ΔoxyHb responses of the novice players are sensitive indicators of motor learning during the initial stage of training and thus clinically useful to determine the improvement in motor performance when patients are engaged in a specific rehabilitation program.

  3. Motor Cortical Visuomotor Feedback Activity Is Initially Isolated from Downstream Targets in Output-Null Neural State Space Dimensions.

    PubMed

    Stavisky, Sergey D; Kao, Jonathan C; Ryu, Stephen I; Shenoy, Krishna V

    2017-07-05

    Neural circuits must transform new inputs into outputs without prematurely affecting downstream circuits while still maintaining other ongoing communication with these targets. We investigated how this isolation is achieved in the motor cortex when macaques received visual feedback signaling a movement perturbation. To overcome limitations in estimating the mapping from cortex to arm movements, we also conducted brain-machine interface (BMI) experiments where we could definitively identify neural firing patterns as output-null or output-potent. This revealed that perturbation-evoked responses were initially restricted to output-null patterns that cancelled out at the neural population code readout and only later entered output-potent neural dimensions. This mechanism was facilitated by the circuit's large null space and its ability to strongly modulate output-potent dimensions when generating corrective movements. These results show that the nervous system can temporarily isolate portions of a circuit's activity from its downstream targets by restricting this activity to the circuit's output-null neural dimensions. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Driving Human Motor Cortical Oscillations Leads to Behaviorally Relevant Changes in Local GABAA Inhibition: A tACS-TMS Study.

    PubMed

    Nowak, Magdalena; Hinson, Emily; van Ede, Freek; Pogosyan, Alek; Guerra, Andrea; Quinn, Andrew; Brown, Peter; Stagg, Charlotte J

    2017-04-26

    Beta and gamma oscillations are the dominant oscillatory activity in the human motor cortex (M1). However, their physiological basis and precise functional significance remain poorly understood. Here, we used transcranial magnetic stimulation (TMS) to examine the physiological basis and behavioral relevance of driving beta and gamma oscillatory activity in the human M1 using transcranial alternating current stimulation (tACS). tACS was applied using a sham-controlled crossover design at individualized intensity for 20 min and TMS was performed at rest (before, during, and after tACS) and during movement preparation (before and after tACS). We demonstrated that driving gamma frequency oscillations using tACS led to a significant, duration-dependent decrease in local resting-state GABA A inhibition, as quantified by short interval intracortical inhibition. The magnitude of this effect was positively correlated with the magnitude of GABA A decrease during movement preparation, when gamma activity in motor circuitry is known to increase. In addition, gamma tACS-induced change in GABA A inhibition was closely related to performance in a motor learning task such that subjects who demonstrated a greater increase in GABA A inhibition also showed faster short-term learning. The findings presented here contribute to our understanding of the neurophysiological basis of motor rhythms and suggest that tACS may have similar physiological effects to endogenously driven local oscillatory activity. Moreover, the ability to modulate local interneuronal circuits by tACS in a behaviorally relevant manner provides a basis for tACS as a putative therapeutic intervention. SIGNIFICANCE STATEMENT Gamma oscillations have a vital role in motor control. Using a combined tACS-TMS approach, we demonstrate that driving gamma frequency oscillations modulates GABA A inhibition in the human motor cortex. Moreover, there is a clear relationship between the change in magnitude of GABA A inhibition induced by tACS and the magnitude of GABA A inhibition observed during task-related synchronization of oscillations in inhibitory interneuronal circuits, supporting the hypothesis that tACS engages endogenous oscillatory circuits. We also show that an individual's physiological response to tACS is closely related to their ability to learn a motor task. These findings contribute to our understanding of the neurophysiological basis of motor rhythms and their behavioral relevance and offer the possibility of developing tACS as a therapeutic tool. Copyright © 2017 Nowak et al.

  5. Cerebellum in Levodopa-Induced Dyskinesias: The Unusual Suspect in the Motor Network

    PubMed Central

    Kishore, Asha; Popa, Traian

    2014-01-01

    The exact mechanisms that generate levodopa-induced dyskinesias (LID) during chronic levodopa therapy for Parkinson’s disease (PD) are not yet fully established. The most widely accepted theories incriminate the non-physiological synthesis, release and reuptake of dopamine generated by exogenously administered levodopa in the striatum, and the aberrant plasticity in the cortico-striatal loops. However, normal motor performance requires the correct recruitment of motor maps. This depends on a high level of synergy within the primary motor cortex (M1) as well as between M1 and other cortical and subcortical areas, for which dopamine is necessary. The plastic mechanisms within M1, which are crucial for the maintenance of this synergy, are disrupted both during “OFF” and dyskinetic states in PD. When tested without levodopa, dyskinetic patients show loss of treatment benefits on long-term potentiation and long-term depression-like plasticity of the intracortical circuits. When tested with the regular pulsatile levodopa doses, they show further impairment of the M1 plasticity, such as inability to depotentiate an already facilitated synapse and paradoxical facilitation in response to afferent input aimed at synaptic inhibition. Dyskinetic patients have also severe impairment of the associative, sensorimotor plasticity of M1 attributed to deficient cerebellar modulation of sensory afferents to M1. Here, we review the anatomical and functional studies, including the recently described bidirectional connections between the cerebellum and the basal ganglia that support a key role of the cerebellum in the generation of LID. This model stipulates that aberrant neuronal synchrony in PD with LID may propagate from the subthalamic nucleus to the cerebellum and “lock” the cerebellar cortex in a hyperactive state. This could affect critical cerebellar functions such as the dynamic and discrete modulation of M1 plasticity and the matching of motor commands with sensory information from the environment during motor performance. We propose that in dyskinesias, M1 neurons have lost the ability to depotentiate an activated synapse when exposed to acute pulsatile, non-physiological, dopaminergic surges and become abnormally receptive to unfiltered, aberrant, and non-salient afferent inputs from the environment. The motor program selection in response to such non-salient and behaviorally irrelevant afferent inputs would be abnormal and involuntary. The motor responses are worsened by the lack of normal subcortico–cortical inputs from cerebellum and basal ganglia, because of the aberrant plasticity at their own synapses. Artificial cerebellar stimulation might help re-establish the cerebellar and basal ganglia control over the non-salient inputs to the motor areas during synaptic dopaminergic surges. PMID:25183959

  6. Prediction of movement intention using connectivity within motor-related network: An electrocorticography study.

    PubMed

    Kang, Byeong Keun; Kim, June Sic; Ryun, Seokyun; Chung, Chun Kee

    2018-01-01

    Most brain-machine interface (BMI) studies have focused only on the active state of which a BMI user performs specific movement tasks. Therefore, models developed for predicting movements were optimized only for the active state. The models may not be suitable in the idle state during resting. This potential maladaptation could lead to a sudden accident or unintended movement resulting from prediction error. Prediction of movement intention is important to develop a more efficient and reasonable BMI system which could be selectively operated depending on the user's intention. Physical movement is performed through the serial change of brain states: idle, planning, execution, and recovery. The motor networks in the primary motor cortex and the dorsolateral prefrontal cortex are involved in these movement states. Neuronal communication differs between the states. Therefore, connectivity may change depending on the states. In this study, we investigated the temporal dynamics of connectivity in dorsolateral prefrontal cortex and primary motor cortex to predict movement intention. Movement intention was successfully predicted by connectivity dynamics which may reflect changes in movement states. Furthermore, dorsolateral prefrontal cortex is crucial in predicting movement intention to which primary motor cortex contributes. These results suggest that brain connectivity is an excellent approach in predicting movement intention.

  7. Intracortical Microstimulation (ICMS) Activates Motor Cortex Layer 5 Pyramidal Neurons Mainly Transsynaptically.

    PubMed

    Hussin, Ahmed T; Boychuk, Jeffery A; Brown, Andrew R; Pittman, Quentin J; Teskey, G Campbell

    2015-01-01

    Intracortical microstimulation (ICMS) is a technique used for a number of purposes including the derivation of cortical movement representations (motor maps). Its application can activate the output layer 5 of motor cortex and can result in the elicitation of body movements depending upon the stimulus parameters used. The extent to which pyramidal tract projection neurons of the motor cortex are activated transsynaptically or directly by ICMS remains an open question. Given this uncertainty in the mode of activation, we used a preparation that combined patch clamp whole-cell recordings from single layer 5 pyramidal neurons and extracellular ICMS in slices of motor cortex as well as a standard in vivo mapping technique to ask how ICMS activated motor cortex pyramidal neurons. We measured changes in synaptic spike threshold and spiking rate to ICMS in vitro and movement threshold in vivo in the presence or absence of specific pharmacological blockers of glutamatergic (AMPA, NMDA and Kainate) receptors and GABAA receptors. With major excitatory and inhibitory synaptic transmission blocked (with DNQX, APV and bicuculline methiodide), we observed a significant increase in the ICMS current intensity required to elicit a movement in vivo as well as to the first spike and an 85% reduction in spiking responses in vitro. Subsets of neurons were still responsive after the synaptic block, especially at higher current intensities, suggesting a modest direct activation. Taken together our data indicate a mainly synaptic mode of activation to ICMS in layer 5 of rat motor cortex. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Therapy induces widespread reorganization of motor cortex after complete spinal transection that supports motor recovery.

    PubMed

    Ganzer, Patrick D; Manohar, Anitha; Shumsky, Jed S; Moxon, Karen A

    2016-05-01

    Reorganization of the somatosensory system and its relationship to functional recovery after spinal cord injury (SCI) has been well studied. However, little is known about the impact of SCI on organization of the motor system. Recent studies suggest that step-training paradigms in combination with spinal stimulation, either electrically or through pharmacology, are more effective than step training alone at inducing recovery and that reorganization of descending corticospinal circuits is necessary. However, simpler, passive exercise combined with pharmacotherapy has also shown functional improvement after SCI and reorganization of, at least, the sensory cortex. In this study we assessed the effect of passive exercise and serotonergic (5-HT) pharmacological therapies on behavioral recovery and organization of the motor cortex. We compared the effects of passive hindlimb bike exercise to bike exercise combined with daily injections of 5-HT agonists in a rat model of complete mid-thoracic transection. 5-HT pharmacotherapy combined with bike exercise allowed the animals to achieve unassisted weight support in the open field. This combination of therapies also produced extensive expansion of the axial trunk motor cortex into the deafferented hindlimb motor cortex and, surprisingly, reorganization within the caudal and even the rostral forelimb motor cortex areas. The extent of the axial trunk expansion was correlated to improvement in behavioral recovery of hindlimbs during open field locomotion, including weight support. From a translational perspective, these data suggest a rationale for developing and optimizing cost-effective, non-invasive, pharmacological and passive exercise regimes to promote plasticity that supports restoration of movement after spinal cord injury. Copyright © 2016. Published by Elsevier Inc.

  9. Studies of sensory and motor cortex physiology: with observations on akinesia in Parkinson's disease.

    PubMed

    Hallett, M; Cohen, L G; Bierner, S M

    1991-01-01

    Magnetic stimulation of the brain can be used to investigate sensory and motor physiology and pathophysiology in intact humans. Although uncommon, it is possible for magnetic stimulation over sensorimotor cortex to produce paresthesis. With magnetic stimulation, it is also possible to block the conscious sensation of an electrical shock delivered to the index finger. The magnetic stimulus must be delivered in the interval from 300 msec before to 200 msec after the cutaneous shock and must be delivered over the contralateral hand region of the sensorimotor cortex. In a reaction time situation, the expected voluntary response may be delayed by a magnetic stimulus delivered over the sensorimotor cortex just before the movement. With the use of a relatively weak magnetic stimulus that does not produce a motor evoked potential (MEP) when the body part is at rest, but that will produce a response when the body part is activated, the reaction time can be divided into two periods. In the first period, there is no MEP and the motor cortex remains 'inexcitable'. In the second period, there is a gradual increase in MEP amplitude even though the voluntary electromyographic activity has not yet appeared. This 'excitable' period indicates the activation of motor cortex before the motor command is delivered. Application of this technique to the analysis of prolonged reaction time (akinesia) in patients with Parkinson's disease shows that the excitable period is prolonged. This describes the mechanism underlying the difficulty in the generation of a motor command in these patients.

  10. EEG activation differences in the pre-motor cortex and supplementary motor area between normal individuals with high and low traits of autism.

    PubMed

    Puzzo, Ignazio; Cooper, Nicholas R; Vetter, Petra; Russo, Riccardo

    2010-06-25

    The human mirror neuron system (hMNS) is believed to provide a basic mechanism for social cognition. Event-related desynchronization (ERD) in alpha (8-12Hz) and low beta band (12-20Hz) over sensori-motor cortex has been suggested to index mirror neurons' activity. We tested whether autistic traits revealed by high and low scores on the Autistic Quotient (AQ) in the normal population are linked to variations in the electroencephalogram (EEG) over motor, pre-motor cortex and supplementary motor area (SMA) during action observation. Results revealed that in the low AQ group, the pre-motor cortex and SMA were more active during hand action than static hand observation whereas in the high AQ group the same areas were active both during static and hand action observation. In fact participants with high traits of autism showed greater low beta ERD while observing the static hand than those with low traits and this low beta ERD was not significantly different when they watched hand actions. Over primary motor cortex, the classical alpha and low beta ERD during hand actions relative to static hand observation was found across all participants. These findings suggest that the observation-execution matching system works differently according to the degree of autism traits in the normal population and that this is differentiated in terms of the EEG according to scalp site and bandwidth. Copyright 2010 Elsevier B.V. All rights reserved.

  11. Sensorimotor Rhythm BCI with Simultaneous High Definition-Transcranial Direct Current Stimulation Alters Task Performance.

    PubMed

    Baxter, Bryan S; Edelman, Bradley J; Nesbitt, Nicholas; He, Bin

    Transcranial direct current stimulation (tDCS) has been used to alter the excitability of neurons within the cerebral cortex. Improvements in motor learning have been found in multiple studies when tDCS was applied to the motor cortex before or during task learning. The motor cortex is also active during the performance of motor imagination, a cognitive task during which a person imagines, but does not execute, a movement. Motor imagery can be used with noninvasive brain computer interfaces (BCIs) to control virtual objects in up to three dimensions, but to master control of such devices requires long training times. To evaluate the effect of high-definition tDCS on the performance and underlying electrophysiology of motor imagery based BCI. We utilize high-definition tDCS to investigate the effect of stimulation on motor imagery-based BCI performance across and within sessions over multiple training days. We report a decreased time-to-hit with anodal stimulation both within and across sessions. We also found differing electrophysiological changes of the stimulated sensorimotor cortex during online BCI task performance for left vs. right trials. Cathodal stimulation led to a decrease in alpha and beta band power during task performance compared to sham stimulation for right hand imagination trials. These results suggest that unilateral tDCS over the sensorimotor motor cortex differentially affects cortical areas based on task specific neural activation. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. tDCS over the motor cortex improves lexical retrieval of action words in poststroke aphasia.

    PubMed

    Branscheidt, Meret; Hoppe, Julia; Zwitserlood, Pienie; Liuzzi, Gianpiero

    2018-02-01

    One-third of stroke survivors worldwide suffer from aphasia. Speech and language therapy (SLT) is considered effective in treating aphasia, but because of time constraints, improvements are often limited. Noninvasive brain stimulation is a promising adjuvant strategy to facilitate SLT. However, stroke might render "classical" language regions ineffective as stimulation sites. Recent work showed the effectiveness of motor cortex stimulation together with intensive naming therapy to improve outcomes in aphasia (Meinzer et al. 2016). Although that study highlights the involvement of the motor cortex, the functional aspects by which it influences language remain unclear. In the present study, we focus on the role of motor cortex in language, investigating its functional involvement in access to specific lexico-semantic (object vs. action relatedness) information in poststroke aphasia. To this end, we tested effects of anodal transcranial direct current stimulation (tDCS) to the left motor cortex on lexical retrieval in 16 patients with poststroke aphasia in a sham-controlled, double-blind study design. Critical stimuli were action and object words, and pseudowords. Participants performed a lexical decision task, deciding whether stimuli were words or pseudowords. Anodal tDCS improved accuracy in lexical decision, especially for words with action-related content and for pseudowords with an "action-like" ending ( t 15  = 2.65, P = 0.036), but not for words with object-related content and pseudowords with "object-like" characteristics. We show as a proof-of-principle that the motor cortex may play a specific role in access to lexico-semantic content. Thus motor-cortex stimulation may strengthen content-specific word-to-semantic concept associations during language treatment in poststroke aphasia. NEW & NOTEWORTHY The role of motor cortex (MC) in language processing has been debated in both health and disease. Recent work has suggested that MC stimulation together with speech and language therapy enhances outcomes in aphasia. We show that MC stimulation has a differential effect on object- and action-word processing in poststroke aphasia. We propose that MC stimulation may specifically strengthen word-to-semantic concept association in aphasia. Our results potentially provide a way to tailor therapies for language rehabilitation.

  13. The mechanism of neurofeedback training for treatment of central neuropathic pain in paraplegia: a pilot study.

    PubMed

    Hassan, Muhammad Abul; Fraser, Matthew; Conway, Bernard A; Allan, David B; Vuckovic, Aleksandra

    2015-10-13

    Central neuropathic pain has a prevalence of 40% in patients with spinal cord injury. Electroencephalography (EEG) studies showed that this type of pain has identifiable signatures, that could potentially be targeted by a neuromodulation therapy. The aim of the study was to investigate the putative mechanism of neurofeedback training on central neuropathic pain and its underlying brain signatures in patients with chronic paraplegia. Patients' EEG activity was modulated from the sensory-motor cortex, electrode location C3/Cz/C4/P4 in up to 40 training sessions Results. Six out of seven patients reported immediate reduction of pain during neurofeedback training. Best results were achieved with suppressing Ɵ and higher β (20-30 Hz) power and reinforcing α power at C4. Four patients reported clinically significant long-term reduction of pain (>30%) which lasted at least a month beyond the therapy. EEG during neurofeedback revealed a wide spread modulation of power in all three frequency bands accompanied with changes in the coherence most notable in the beta band. The standardized low resolution electromagnetic tomography analysis of EEG before and after neurofeedback therapy showed the statistically significant reduction of power in beta frequency band in all tested patients. Areas with reduced power included the Dorsolateral Prefrontal Cortex, the Anterior Cingulate Cortex and the Insular Cortex. Neurofeedback training produces both immediate and longer term reduction of central neuropathic pain that is accompanied with a measurable short and long term modulation of cortical activity. Controlled trials are required to confirm the efficacy of this neurofeedback protocol on treatment of pain. The study is a registered UKCRN clinical trial Nr 9824.

  14. Physiology of the motor cortex in polio survivors.

    PubMed

    Lupu, Vitalie D; Danielian, Laura; Johnsen, Jacqueline A; Vasconcelos, Olavo M; Prokhorenko, Olga A; Jabbari, Bahman; Campbell, William W; Floeter, Mary Kay

    2008-02-01

    We hypothesized that the corticospinal system undergoes functional changes in long-term polio survivors. Central motor conduction times (CMCTs) to the four limbs were measured in 24 polio survivors using transcranial magnetic stimulation (TMS). Resting motor thresholds and CMCTs were normal. In 17 subjects whose legs were affected by polio and 13 healthy controls, single- and paired-pulse TMS was used to assess motor cortex excitability while recording from tibialis anterior (TA) muscles at rest and following maximal contraction until fatigue. In polio survivors the slope of the recruitment curve was normal, but maximal motor evoked potentials (MEPs) were larger than in controls. MEPs were depressed after fatiguing exercise. Three patients with central fatigue by twitch interpolation had a trend toward slower recovery. There was no association with symptoms of post-polio syndrome. These changes occurring after polio may allow the motor cortex to activate a greater proportion of the motor neurons innervating affected muscles.

  15. Refinement of learned skilled movement representation in motor cortex deep output layer

    PubMed Central

    Li, Qian; Ko, Ho; Qian, Zhong-Ming; Yan, Leo Y. C.; Chan, Danny C. W.; Arbuthnott, Gordon; Ke, Ya; Yung, Wing-Ho

    2017-01-01

    The mechanisms underlying the emergence of learned motor skill representation in primary motor cortex (M1) are not well understood. Specifically, how motor representation in the deep output layer 5b (L5b) is shaped by motor learning remains virtually unknown. In rats undergoing motor skill training, we detect a subpopulation of task-recruited L5b neurons that not only become more movement-encoding, but their activities are also more structured and temporally aligned to motor execution with a timescale of refinement in tens-of-milliseconds. Field potentials evoked at L5b in vivo exhibit persistent long-term potentiation (LTP) that parallels motor performance. Intracortical dopamine denervation impairs motor learning, and disrupts the LTP profile as well as the emergent neurodynamical properties of task-recruited L5b neurons. Thus, dopamine-dependent recruitment of L5b neuronal ensembles via synaptic reorganization may allow the motor cortex to generate more temporally structured, movement-encoding output signal from M1 to downstream circuitry that drives increased uniformity and precision of movement during motor learning. PMID:28598433

  16. Dynamic Reconfiguration of the Supplementary Motor Area Network during Imagined Music Performance

    PubMed Central

    Tanaka, Shoji; Kirino, Eiji

    2017-01-01

    The supplementary motor area (SMA) has been shown to be the center for motor planning and is active during music listening and performance. However, limited data exist on the role of the SMA in music. Music performance requires complex information processing in auditory, visual, spatial, emotional, and motor domains, and this information is integrated for the performance. We hypothesized that the SMA is engaged in multimodal integration of information, distributed across several regions of the brain to prepare for ongoing music performance. To test this hypothesis, functional networks involving the SMA were extracted from functional magnetic resonance imaging (fMRI) data that were acquired from musicians during imagined music performance and during the resting state. Compared with the resting condition, imagined music performance increased connectivity of the SMA with widespread regions in the brain including the sensorimotor cortices, parietal cortex, posterior temporal cortex, occipital cortex, and inferior and dorsolateral prefrontal cortex. Increased connectivity of the SMA with the dorsolateral prefrontal cortex suggests that the SMA is under cognitive control, while increased connectivity with the inferior prefrontal cortex suggests the involvement of syntax processing. Increased connectivity with the parietal cortex, posterior temporal cortex, and occipital cortex is likely for the integration of spatial, emotional, and visual information. Finally, increased connectivity with the sensorimotor cortices was potentially involved with the translation of thought planning into motor programs. Therefore, the reconfiguration of the SMA network observed in this study is considered to reflect the multimodal integration required for imagined and actual music performance. We propose that the SMA network construct “the internal representation of music performance” by integrating multimodal information required for the performance. PMID:29311870

  17. Altered cerebral hemodyamics and cortical thinning in asymptomatic carotid artery stenosis.

    PubMed

    Marshall, Randolph S; Asllani, Iris; Pavol, Marykay A; Cheung, Ying-Kuen; Lazar, Ronald M

    2017-01-01

    Cortical thinning is a potentially important biomarker, but the pathophysiology in cerebrovascular disease is unknown. We investigated the association between regional cortical blood flow and regional cortical thickness in patients with asymptomatic unilateral high-grade internal carotid artery disease without stroke. Twenty-nine patients underwent high resolution anatomical and single-delay, pseudocontinuous arterial spin labeling magnetic resonance imaging with partial volume correction to assess gray matter baseline flow. Cortical thickness was estimated using Freesurfer software, followed by co-registration onto each patient's cerebral blood flow image space. Paired t-tests assessed regional cerebral blood flow in motor cortex (supplied by the carotid artery) and visual cortex (indirectly supplied by the carotid) on the occluded and unoccluded side. Pearson correlations were calculated between cortical thickness and regional cerebral blood flow, along with age, hypertension, diabetes and white matter hyperintensity volume. Multiple regression and generalized estimating equation were used to predict cortical thickness bilaterally and in each hemisphere separately. Cortical blood flow correlated with thickness in motor cortex bilaterally (p = 0.0002), and in the occluded and unoccluded sides individually; age (p = 0.002) was also a predictor of cortical thickness in the motor cortex. None of the variables predicted cortical thickness in visual cortex. Blood flow was significantly lower on the occluded versus unoccluded side in the motor cortex (p<0.0001) and in the visual cortex (p = 0.018). On average, cortex was thinner on the side of occlusion in motor but not in visual cortex. The association between cortical blood flow and cortical thickness in carotid arterial territory with greater thinning on the side of the carotid occlusion suggests that altered cerebral hemodynamics is a factor in cortical thinning.

  18. Structural brain correlates of unconstrained motor activity in people with schizophrenia.

    PubMed

    Farrow, Tom F D; Hunter, Michael D; Wilkinson, Iain D; Green, Russell D J; Spence, Sean A

    2005-11-01

    Avolition affects quality of life in chronic schizophrenia. We investigated the relationship between unconstrained motor activity and the volume of key executive brain regions in 16 male patients with schizophrenia. Wristworn actigraphy monitors were used to record motor activity over a 20 h period. Structural magnetic resonance imaging brain scans were parcellated and individual volumes for anterior cingulate cortex and dorsolateral prefrontal cortex extracted. Patients'total activity was positively correlated with volume of left anterior cingulate cortex. These data suggest that the volume of specific executive structures may affect (quantifiable) motor behaviours, having further implications for models of the 'will' and avolition.

  19. [CHANGES IN THE NUMBER OF NEURONS IN THE MOTOR CORTEX OF RATS AND THEIR LOCOMOTOR ACTIVITY IN THE AGE ASPECT].

    PubMed

    Piavchenko, G A; Shmarkova, L I; Nozdrin, V I

    2015-01-01

    Using Laboras hardware-software complex, which is a system of automatic registration of behavioral reactions, the locomotor activity 1-, 8- and 16-month-old male rats (12 animals in each group) was recorded followed by counting the number of neuron cell bodies of in the layer V of the motor cortex in Nissl stained slides. It was found that the number of neurons in the motor cortex varied in different age groups. Maximal number of neurons was observed in 8-month-old animals. Motor activity was found to correlate with the number of neurons.

  20. Impairments in prehension produced by early postnatal sensory motor cortex activity blockade.

    PubMed

    Martin, J H; Donarummo, L; Hacking, A

    2000-02-01

    This study examined the effects of blocking neural activity in sensory motor cortex during early postnatal development on prehension. We infused muscimol, either unilaterally or bilaterally, into the sensory motor cortex of cats to block activity continuously between postnatal weeks 3-7. After stopping infusion, we trained animals to reach and grasp a cube of meat and tested behavior thereafter. Animals that had not received muscimol infusion (unilateral saline infusion; age-matched) reached for the meat accurately with small end-point errors. They grasped the meat using coordinated digit flexion followed by forearm supination on 82.7% of trials. Performance using either limb did not differ significantly. In animals receiving unilateral muscimol infusion, reaching and grasping using the limb ipsilateral to the infusion were similar to controls. The limb contralateral to infusion showed significant increases in systematic and variable reaching end-point errors, often requiring subsequent corrective movements to contact the meat. Grasping occurred on only 14.8% of trials, replaced on most trials by raking without distal movements. Compensatory adjustments in reach length and angle, to maintain end-point accuracy as movements were started from a more lateral position, were less effective using the contralateral limb than ipsilateral limb. With bilateral inactivations, the form of reaching and grasping impairments was identical to that produced by unilateral inactivation, but the magnitude of the reaching impairments was less. We discuss these results in terms of the differential effects of unilateral and bilateral inactivation on corticospinal tract development. We also investigated the degree to which these prehension impairments after unilateral blockade reflect control by each hemisphere. In animals that had received unilateral blockade between postnatal weeks (PWs) 3 and 7, we silenced on-going activity (after PW 11) during task performance using continuous muscimol infusion. We inactivated the right (previously active) and then the left (previously silenced) sensory motor cortex. Inactivation of the ipsilateral (right) sensory motor cortex produced a further increase in systematic error and less frequent normal grasping. Reinactivation of the contralateral (left) cortex produced larger increases in reaching and grasping impairments than those produced by ipsilateral inactivation. This suggests that the impaired limb receives bilateral sensory motor cortex control but that control by the contralateral (initially silenced) cortex predominates. Our data are consistent with the hypothesis that the normal development of skilled motor behavior requires activity in sensory motor cortex during early postnatal life.

  1. Aging, self-referencing, and medial prefrontal cortex.

    PubMed

    Gutchess, Angela H; Kensinger, Elizabeth A; Schacter, Daniel L

    2007-01-01

    The lateral prefrontal cortex undergoes both structural and functional changes with healthy aging. In contrast, there is little structural change in the medial prefrontal cortex, but relatively little is known about the functional changes to this region with age. Using an event-related fMRI design, we investigated the response of medial prefrontal cortex during self-referencing in order to compare age groups on a task that young and elderly perform similarly and that is known to actively engage the region in young adults. Nineteen young (M age = 23) and seventeen elderly (M age = 72) judged whether adjectives described themselves, another person, or were presented in upper case. We assessed the overlap in activations between young and elderly for the self-reference effect (self vs. other person), and found that both groups engage medial prefrontal cortex and mid-cingulate during self-referencing. The only cerebral differences between the groups in self versus other personality assessment were found in somatosensory and motor-related areas. In contrast, age-related modulations were found in the cerebral network recruited for emotional valence processing. Elderly (but not young) showed increased activity in the dorsal prefrontal cortex for positive relative to negative items, which could reflect an increase in controlled processing of positive information for elderly adults.

  2. The Evolution of Human Handedness

    PubMed Central

    Smaers, Jeroen B; Steele, James; Case, Charleen R; Amunts, Katrin

    2013-01-01

    There is extensive evidence for an early vertebrate origin of lateralized motor behavior and of related asymmetries in underlying brain systems. We investigate human lateralized motor functioning in a broad comparative context of evolutionary neural reorganization. We quantify evolutionary trends in the fronto-cerebellar system (involved in motor learning) across 46 million years of divergent primate evolution by comparing rates of evolution of prefrontal cortex, frontal motor cortex, and posterior cerebellar hemispheres along individual branches of the primate tree of life. We provide a detailed evolutionary model of the neuroanatomical changes leading to modern human lateralized motor functioning, demonstrating an increased role for the fronto-cerebellar system in the apes dating to their evolutionary divergence from the monkeys (∼30 million years ago (Mya)), and a subsequent shift toward an increased role for prefrontal cortex over frontal motor cortex in the fronto-cerebellar system in the Homo-Pan ancestral lineage (∼10 Mya) and in the human ancestral lineage (∼6 Mya). We discuss these results in the context of cortico-cerebellar functions and their likely role in the evolution of human tool use and speech. PMID:23647442

  3. Neuron activity in rat hippocampus and motor cortex during discrimination reversal.

    PubMed

    Disterhoft, J F; Segal, M

    1978-01-01

    Chronic unit activity and gross movement were recorded from rats during two discrimination reversals in a classical appetitive conditioning situation. The anticipatory movement decreased in response to the former CS+ tone and increased to the previous CS- tone after each reversal. Hippocampus and motor cortex were differently related to these two kinds of behavioral change. Response rates of hippocampal neurons were more closely related to the increased movement response to the former CS- which now signaled food. Motor cortex neuron responses were more closely correlated with the decrease in movement responses to the former CS+ which became neutral after the reversal. It appeared that hippocampal neurons could have been involved in one cognitive aspect of the situation, motor cortex neurons in another. The data were related to current functional concepts of these brain regions.

  4. Manipulating motor performance and memory through real-time fMRI neurofeedback.

    PubMed

    Scharnowski, Frank; Veit, Ralf; Zopf, Regine; Studer, Petra; Bock, Simon; Diedrichsen, Jörn; Goebel, Rainer; Mathiak, Klaus; Birbaumer, Niels; Weiskopf, Nikolaus

    2015-05-01

    Task performance depends on ongoing brain activity which can be influenced by attention, arousal, or motivation. However, such modulating factors of cognitive efficiency are unspecific, can be difficult to control, and are not suitable to facilitate neural processing in a regionally specific manner. Here, we non-pharmacologically manipulated regionally specific brain activity using technically sophisticated real-time fMRI neurofeedback. This was accomplished by training participants to simultaneously control ongoing brain activity in circumscribed motor and memory-related brain areas, namely the supplementary motor area and the parahippocampal cortex. We found that learned voluntary control over these functionally distinct brain areas caused functionally specific behavioral effects, i.e. shortening of motor reaction times and specific interference with memory encoding. The neurofeedback approach goes beyond improving cognitive efficiency by unspecific psychological factors such as attention, arousal, or motivation. It allows for directly manipulating sustained activity of task-relevant brain regions in order to yield specific behavioral or cognitive effects. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  5. Sensorimotor Integration by Corticospinal System

    PubMed Central

    Moreno-López, Yunuen; Olivares-Moreno, Rafael; Cordero-Erausquin, Matilde; Rojas-Piloni, Gerardo

    2016-01-01

    The corticospinal (CS) tract is a complex system which targets several areas of the spinal cord. In particular, the CS descending projection plays a major role in motor command, which results from direct and indirect control of spinal cord pre-motor interneurons as well as motoneurons. But in addition, this system is also involved in a selective and complex modulation of sensory feedback. Despite recent evidence confirms that CS projections drive distinct segmental neural circuits that are part of the sensory and pre-motor pathways, little is known about the spinal networks engaged by the corticospinal tract (CST), the organization of CS projections, the intracortical microcircuitry, and the synaptic interactions in the sensorimotor cortex (SMC) that may encode different cortical outputs to the spinal cord. Here is stressed the importance of integrated approaches for the study of sensorimotor function of CS system, in order to understand the functional compartmentalization and hierarchical organization of layer 5 output neurons, who are key elements for motor control and hence, of behavior. PMID:27013985

  6. Sensorimotor Integration by Corticospinal System.

    PubMed

    Moreno-López, Yunuen; Olivares-Moreno, Rafael; Cordero-Erausquin, Matilde; Rojas-Piloni, Gerardo

    2016-01-01

    The corticospinal (CS) tract is a complex system which targets several areas of the spinal cord. In particular, the CS descending projection plays a major role in motor command, which results from direct and indirect control of spinal cord pre-motor interneurons as well as motoneurons. But in addition, this system is also involved in a selective and complex modulation of sensory feedback. Despite recent evidence confirms that CS projections drive distinct segmental neural circuits that are part of the sensory and pre-motor pathways, little is known about the spinal networks engaged by the corticospinal tract (CST), the organization of CS projections, the intracortical microcircuitry, and the synaptic interactions in the sensorimotor cortex (SMC) that may encode different cortical outputs to the spinal cord. Here is stressed the importance of integrated approaches for the study of sensorimotor function of CS system, in order to understand the functional compartmentalization and hierarchical organization of layer 5 output neurons, who are key elements for motor control and hence, of behavior.

  7. Manipulating motor performance and memory through real-time fMRI neurofeedback

    PubMed Central

    Scharnowski, Frank; Veit, Ralf; Zopf, Regine; Studer, Petra; Bock, Simon; Diedrichsen, Jörn; Goebel, Rainer; Mathiak, Klaus; Birbaumer, Niels; Weiskopf, Nikolaus

    2015-01-01

    Task performance depends on ongoing brain activity which can be influenced by attention, arousal, or motivation. However, such modulating factors of cognitive efficiency are unspecific, can be difficult to control, and are not suitable to facilitate neural processing in a regionally specific manner. Here, we non-pharmacologically manipulated regionally specific brain activity using technically sophisticated real-time fMRI neurofeedback. This was accomplished by training participants to simultaneously control ongoing brain activity in circumscribed motor and memory-related brain areas, namely the supplementary motor area and the parahippocampal cortex. We found that learned voluntary control over these functionally distinct brain areas caused functionally specific behavioral effects, i.e. shortening of motor reaction times and specific interference with memory encoding. The neurofeedback approach goes beyond improving cognitive efficiency by unspecific psychological factors such as attention, arousal, or motivation. It allows for directly manipulating sustained activity of task-relevant brain regions in order to yield specific behavioral or cognitive effects. PMID:25796342

  8. New modules are added to vibrissal premotor circuitry with the emergence of exploratory whisking

    PubMed Central

    Takatoh, Jun; Nelson, Anders; Zhou, Xiang; Bolton, M. McLean; Ehlers, Michael D.; Arenkiel, Benjamin R.; Mooney, Richard; Wang, Fan

    2012-01-01

    SUMMARY Rodents begin to use bilaterally coordinated, rhythmic sweeping of their vibrissae (“whisking”) for environmental exploration around two weeks after birth. Whether and how vibrissal control circuitry changes after birth is unknown, and relevant premotor circuitry remains poorly characterized. Using a modified rabies virus transsynaptic tracing strategy, we labeled neurons synapsing directly onto vibrissa facial motor neurons (vFMNs). Sources of potential excitatory, inhibitory, and modulatory vFMN premotor neurons, and differences between the premotor circuitry for vFMNs innervating intrinsic versus extrinsic vibrissal muscles, were systematically characterized. The emergence of whisking is accompanied by the addition of “new” sets of bilateral excitatory inputs to vFMNs from neurons in the lateral paragigantocellularis (LPGi). Furthermore, descending axons from the motor cortex directly innervate LPGi premotor neurons. Thus, neural modules well suited to facilitate the bilateral coordination and cortical control of whisking are added to premotor circuitry in parallel with the emergence of this exploratory behavior. PMID:23352170

  9. Mirror Neurons of Ventral Premotor Cortex Are Modulated by Social Cues Provided by Others' Gaze.

    PubMed

    Coudé, Gino; Festante, Fabrizia; Cilia, Adriana; Loiacono, Veronica; Bimbi, Marco; Fogassi, Leonardo; Ferrari, Pier Francesco

    2016-03-16

    Mirror neurons (MNs) in the inferior parietal lobule and ventral premotor cortex (PMv) can code the intentions of other individuals using contextual cues. Gaze direction is an important social cue that can be used for understanding the meaning of actions made by other individuals. Here we addressed the issue of whether PMv MNs are influenced by the gaze direction of another individual. We recorded single-unit activity in macaque PMv while the monkey was observing an experimenter performing a grasping action and orienting his gaze either toward (congruent gaze condition) or away (incongruent gaze condition) from a target object. The results showed that one-half of the recorded MNs were modulated by the gaze direction of the human agent. These gaze-modulated neurons were evenly distributed between those preferring a gaze direction congruent with the direction where the grasping action was performed and the others that preferred an incongruent gaze. Whereas the presence of congruent responses is in line with the usual coupling of hand and gaze in both executed and observed actions, the incongruent responses can be explained by the long exposure of the monkeys to this condition. Our results reveal that the representation of observed actions in PMv is influenced by contextual information not only extracted from physical cues, but also from cues endowed with biological or social value. In this study, we present the first evidence showing that social cues modulate MNs in the monkey ventral premotor cortex. These data suggest that there is an integrated representation of other's hand actions and gaze direction at the single neuron level in the ventral premotor cortex, and support the hypothesis of a functional role of MNs in decoding actions and understanding motor intentions. Copyright © 2016 the authors 0270-6474/16/363145-12$15.00/0.

  10. Population Response Profiles in Early Visual Cortex Are Biased in Favor of More Valuable Stimuli

    PubMed Central

    Saproo, Sameer

    2010-01-01

    Voluntary and stimulus-driven shifts of attention can modulate the representation of behaviorally relevant stimuli in early areas of visual cortex. In turn, attended items are processed faster and more accurately, facilitating the selection of appropriate behavioral responses. Information processing is also strongly influenced by past experience and recent studies indicate that the learned value of a stimulus can influence relatively late stages of decision making such as the process of selecting a motor response. However, the learned value of a stimulus can also influence the magnitude of cortical responses in early sensory areas such as V1 and S1. These early effects of stimulus value are presumed to improve the quality of sensory representations; however, the nature of these modulations is not clear. They could reflect nonspecific changes in response amplitude associated with changes in general arousal or they could reflect a bias in population responses so that high-value features are represented more robustly. To examine this issue, subjects performed a two-alternative forced choice paradigm with a variable-interval payoff schedule to dynamically manipulate the relative value of two stimuli defined by their orientation (one was rotated clockwise from vertical, the other counterclockwise). Activation levels in visual cortex were monitored using functional MRI and feature-selective voxel tuning functions while subjects performed the behavioral task. The results suggest that value not only modulates the relative amplitude of responses in early areas of human visual cortex, but also sharpens the response profile across the populations of feature-selective neurons that encode the critical stimulus feature (orientation). Moreover, changes in space- or feature-based attention cannot easily explain the results because representations of both the selected and the unselected stimuli underwent a similar feature-selective modulation. This sharpening in the population response profile could theoretically improve the probability of correctly discriminating high-value stimuli from low-value alternatives. PMID:20410360

  11. Saccade Modulation by Optical and Electrical Stimulation in the Macaque Frontal Eye Field

    PubMed Central

    Grimaldi, Piercesare; Schweers, Nicole

    2013-01-01

    Recent studies have demonstrated that strong neural modulations can be evoked with optogenetic stimulation in macaque motor cortex without observing any evoked movements (Han et al., 2009, 2011; Diester et al., 2011). It remains unclear why such perturbations do not generate movements and if conditions exist under which they may evoke movements. In this study, we examine the effects of five optogenetic constructs in the macaque frontal eye field and use electrical microstimulation to assess whether optical perturbation of the local network leads to observable motor changes during optical, electrical, and combined stimulation. We report a significant increase in the probability of evoking saccadic eye movements when low current electrical stimulation is coupled to optical stimulation compared with when electrical stimulation is used alone. Experiments combining channelrhodopsin 2 (ChR2) and electrical stimulation with simultaneous fMRI revealed no discernible fMRI activity at the electrode tip with optical stimulation but strong activity with electrical stimulation. Our findings suggest that stimulation with current ChR2 optogenetic constructs generates subthreshold activity that contributes to the initiation of movements but, in most cases, is not sufficient to evoke a motor response. PMID:24133271

  12. Motor deficits correlate with resting state motor network connectivity in patients with brain tumours

    PubMed Central

    Mikell, Charles B.; Youngerman, Brett E.; Liston, Conor; Sisti, Michael B.; Bruce, Jeffrey N.; Small, Scott A.; McKhann, Guy M.

    2012-01-01

    While a tumour in or abutting primary motor cortex leads to motor weakness, how tumours elsewhere in the frontal or parietal lobes affect functional connectivity in a weak patient is less clear. We hypothesized that diminished functional connectivity in a distributed network of motor centres would correlate with motor weakness in subjects with brain masses. Furthermore, we hypothesized that interhemispheric connections would be most vulnerable to subtle disruptions in functional connectivity. We used task-free functional magnetic resonance imaging connectivity to probe motor networks in control subjects and patients with brain tumours (n = 22). Using a control dataset, we developed a method for automated detection of key nodes in the motor network, including the primary motor cortex, supplementary motor area, premotor area and superior parietal lobule, based on the anatomic location of the hand-motor knob in the primary motor cortex. We then calculated functional connectivity between motor network nodes in control subjects, as well as patients with and without brain masses. We used this information to construct weighted, undirected graphs, which were then compared to variables of interest, including performance on a motor task, the grooved pegboard. Strong connectivity was observed within the identified motor networks between all nodes bilaterally, and especially between the primary motor cortex and supplementary motor area. Reduced connectivity was observed in subjects with motor weakness versus subjects with normal strength (P < 0.001). This difference was driven mostly by decreases in interhemispheric connectivity between the primary motor cortices (P < 0.05) and between the left primary motor cortex and the right premotor area (P < 0.05), as well as other premotor area connections. In the subjects without motor weakness, however, performance on the grooved pegboard did not relate to interhemispheric connectivity, but rather was inversely correlated with connectivity between the left premotor area and left supplementary motor area, for both the left and the right hands (P < 0.01). Finally, two subjects who experienced severe weakness following surgery for their brain tumours were followed longitudinally, and the subject who recovered showed reconstitution of her motor network at follow-up. The subject who was persistently weak did not reconstitute his motor network. Motor weakness in subjects with brain tumours that do not involve primary motor structures is associated with decreased connectivity within motor functional networks, particularly interhemispheric connections. Motor networks become weaker as the subjects become weaker, and may become strong again during motor recovery. PMID:22408270

  13. Cortical Modulation of Motor Control Biofeedback among the Elderly with High Fall Risk during a Posture Perturbation Task with Augmented Reality

    PubMed Central

    Chang, Chun-Ju; Yang, Tsui-Fen; Yang, Sai-Wei; Chern, Jen-Suh

    2016-01-01

    The cerebral cortex provides sensorimotor integration and coordination during motor control of daily functional activities. Power spectrum density based on electroencephalography (EEG) has been employed as an approach that allows an investigation of the spatial–temporal characteristics of neuromuscular modulation; however, the biofeedback mechanism associated with cortical activation during motor control remains unclear among elderly individuals. Thirty one community-dwelling elderly participants were divided into low fall-risk potential (LF) and high fall-risk potential (HF) groups based upon the results obtained from a receiver operating characteristic analysis of the ellipse area of the center of pressure. Electroencephalography (EEG) was performed while the participants stood on a 6-degree-of-freedom Stewart platform, which generated continuous perturbations and done either with or without the virtual reality scene. The present study showed that when there was visual stimulation and poor somatosensory coordination, a higher level of cortical response was activated in order to keep postural balance. The elderly participants in the LF group demonstrated a significant and strong correlation between postural-related cortical regions; however, the elderly individuals in the HF group did not show such a relationship. Moreover, we were able to clarify the roles of various brainwave bands functioning in motor control. Specifically, the gamma and beta bands in the parietal–occipital region facilitate the high-level cortical modulation and sensorimotor integration, whereas the theta band in the frontal–central region is responsible for mediating error detection during perceptual motor tasks. Finally, the alpha band is associated with processing visual challenges in the occipital lobe.With a variety of motor control demands, increment in brainwave band coordination is required to maintain postural stability. These investigations shed light on the cortical modulation of motor control among elderly participants with varying fall-risk potentials. The results suggest that, although elderly adults may be without neurological deficits, inefficient central modulation during challenging postural conditions could be an internal factor that contributes to the risk of fall. Furthermore, training that helps to improve coordinated sensorimotor integration may be a useful approach to reduce the risk of fall among elderly populations or when patients suffer from neurological deficits. PMID:27199732

  14. The motilin agonist erythromycin increases hunger by modulating homeostatic and hedonic brain circuits in healthy women: a randomized, placebo-controlled study.

    PubMed

    Zhao, Dongxing; Meyer-Gerspach, Anne Christin; Deloose, Eveline; Iven, Julie; Weltens, Nathalie; Depoortere, Inge; O'daly, Owen; Tack, Jan; Van Oudenhove, Lukas

    2018-01-29

    The motilin agonist, erythromycin, induces gastric phase III of the migrating motor complex, which in turn generates hunger peaks. To identify the brain mechanisms underlying these orexigenic effects, 14 healthy women participated in a randomized, placebo-controlled crossover study. Functional magnetic resonance brain images were acquired for 50 minutes interprandially. Intravenous infusion of erythromycin (40 mg) or saline started 10 minutes after the start of scanning. Blood samples (for glucose and hormone levels) and hunger ratings were collected at fixed timepoints. Thirteen volunteers completed the study, without any adverse events. Brain regions involved in homeostatic and hedonic control of appetite and food intake responded to erythromycin, including pregenual anterior cingulate cortex, anterior insula cortex, orbitofrontal cortex, amygdala, caudate, pallidum and putamen bilaterally, right accumbens, hypothalamus, and midbrain. Octanoylated ghrelin levels decreased, whereas both glucose and insulin increased after erythromycin. Hunger were higher after erythromycin, and these differences covaried with the brain response in most of the abovementioned regions. The motilin agonist erythromycin increases hunger by modulating neurocircuitry related to homeostatic and hedonic control of appetite and feeding. These results confirm recent behavioural findings identifying motilin as a key orexigenic hormone in humans, and identify the brain mechanisms underlying its effect.

  15. Somatotopic Semantic Priming and Prediction in the Motor System

    PubMed Central

    Grisoni, Luigi; Dreyer, Felix R.; Pulvermüller, Friedemann

    2016-01-01

    The recognition of action-related sounds and words activates motor regions, reflecting the semantic grounding of these symbols in action information; in addition, motor cortex exerts causal influences on sound perception and language comprehension. However, proponents of classic symbolic theories still dispute the role of modality-preferential systems such as the motor cortex in the semantic processing of meaningful stimuli. To clarify whether the motor system carries semantic processes, we investigated neurophysiological indexes of semantic relationships between action-related sounds and words. Event-related potentials revealed that action-related words produced significantly larger stimulus-evoked (Mismatch Negativity-like) and predictive brain responses (Readiness Potentials) when presented in body-part-incongruent sound contexts (e.g., “kiss” in footstep sound context; “kick” in whistle context) than in body-part-congruent contexts, a pattern reminiscent of neurophysiological correlates of semantic priming. Cortical generators of the semantic relatedness effect were localized in areas traditionally associated with semantic memory, including left inferior frontal cortex and temporal pole, and, crucially, in motor areas, where body-part congruency of action sound–word relationships was indexed by a somatotopic pattern of activation. As our results show neurophysiological manifestations of action-semantic priming in the motor cortex, they prove semantic processing in the motor system and thus in a modality-preferential system of the human brain. PMID:26908635

  16. Reorganization of corticospinal output during motor learning

    PubMed Central

    Peters, Andrew J.; Lee, Jun; Hedrick, Nathan G.; O’Neil, Keelin; Komiyama, Takaki

    2017-01-01

    Motor learning is accompanied by widespread changes within the motor cortex, but it is unknown whether these changes are ultimately funneled through a stable corticospinal output channel or if the corticospinal output itself is plastic. We investigated the consistency of the relationship between corticospinal neuron activity and movement through in vivo two-photon calcium imaging in mice learning a lever-press task. Corticospinal neurons exhibited heterogeneous correlations with movement, with the majority of movement-modulated neurons decreasing activity during movement. Individual cells changed their activity across days which led to novel associations between corticospinal activity and movement. Unlike previous observations in layer 2/3, activity accompanying learned movements did not become more consistent with learning, and instead the activity of dissimilar movements became more decorrelated. These results indicate that the relationship between corticospinal activity and movement is dynamic, and the types of activity and plasticity are different from and possibly complementary to layer 2/3. PMID:28671694

  17. Walking the talk--speech activates the leg motor cortex.

    PubMed

    Liuzzi, Gianpiero; Ellger, Tanja; Flöel, Agnes; Breitenstein, Caterina; Jansen, Andreas; Knecht, Stefan

    2008-09-01

    Speech may have evolved from earlier modes of communication based on gestures. Consistent with such a motor theory of speech, cortical orofacial and hand motor areas are activated by both speech production and speech perception. However, the extent of speech-related activation of the motor cortex remains unclear. Therefore, we examined if reading and listening to continuous prose also activates non-brachiofacial motor representations like the leg motor cortex. We found corticospinal excitability of bilateral leg muscle representations to be enhanced by speech production and silent reading. Control experiments showed that speech production yielded stronger facilitation of the leg motor system than non-verbal tongue-mouth mobilization and silent reading more than a visuo-attentional task thus indicating speech-specificity of the effect. In the frame of the motor theory of speech this finding suggests that the system of gestural communication, from which speech may have evolved, is not confined to the hand but includes gestural movements of other body parts as well.

  18. Motor skills training promotes motor functional recovery and induces synaptogenesis in the motor cortex and striatum after intracerebral hemorrhage in rats.

    PubMed

    Tamakoshi, Keigo; Ishida, Akimasa; Takamatsu, Yasuyuki; Hamakawa, Michiru; Nakashima, Hiroki; Shimada, Haruka; Ishida, Kazuto

    2014-03-01

    We investigated the effects of motor skills training on several types of motor function and synaptic plasticity following intracerebral hemorrhage (ICH) in rats. Male Wistar rats were injected with collagenase into the left striatum to induce ICH, and they were randomly assigned to the ICH or sham groups. Each group was divided into the motor skills training (acrobatic training) and control (no exercise) groups. The acrobatic group performed acrobatic training from 4 to 28 days after surgery. Motor functions were assessed by motor deficit score, the horizontal ladder test and the wide or narrow beam walking test at several time points after ICH. The number of ΔFosB-positive cells was counted using immunohistochemistry to examine neuronal activation, and the PSD95 protein levels were analyzed by Western blotting to examine synaptic plasticity in the bilateral sensorimotor cortices and striata at 14 and 29 days after ICH. Motor skills training following ICH significantly improved gross motor function in the early phase after ICH and skilled motor coordinated function in the late phase. The number of ΔFosB-positive cells in the contralateral sensorimotor cortex in the acrobatic group significantly increased compared to the control group. PSD95 protein expression in the motor cortex significantly increased in the late phase, and in the striatum, the protein level significantly increased in the early phase by motor skills training after ICH compared to no training after ICH. We demonstrated that motor skills training improved motor function after ICH in rats and enhanced the neural activity and synaptic plasticity in the striatum and sensorimotor cortex. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Functional connectivity between somatosensory and motor brain areas predicts individual differences in motor learning by observing.

    PubMed

    McGregor, Heather R; Gribble, Paul L

    2017-08-01

    Action observation can facilitate the acquisition of novel motor skills; however, there is considerable individual variability in the extent to which observation promotes motor learning. Here we tested the hypothesis that individual differences in brain function or structure can predict subsequent observation-related gains in motor learning. Subjects underwent an anatomical MRI scan and resting-state fMRI scans to assess preobservation gray matter volume and preobservation resting-state functional connectivity (FC), respectively. On the following day, subjects observed a video of a tutor adapting her reaches to a novel force field. After observation, subjects performed reaches in a force field as a behavioral assessment of gains in motor learning resulting from observation. We found that individual differences in resting-state FC, but not gray matter volume, predicted postobservation gains in motor learning. Preobservation resting-state FC between left primary somatosensory cortex and bilateral dorsal premotor cortex, primary motor cortex, and primary somatosensory cortex and left superior parietal lobule was positively correlated with behavioral measures of postobservation motor learning. Sensory-motor resting-state FC can thus predict the extent to which observation will promote subsequent motor learning. NEW & NOTEWORTHY We show that individual differences in preobservation brain function can predict subsequent observation-related gains in motor learning. Preobservation resting-state functional connectivity within a sensory-motor network may be used as a biomarker for the extent to which observation promotes motor learning. This kind of information may be useful if observation is to be used as a way to boost neuroplasticity and sensory-motor recovery for patients undergoing rehabilitation for diseases that impair movement such as stroke. Copyright © 2017 the American Physiological Society.

  20. FUNCTIONAL RECOVERY FOLLOWING MOTOR CORTEX LESIONS IN NON-HUMAN PRIMATES: EXPERIMENTAL IMPLICATIONS FOR HUMAN STROKE PATIENTS

    PubMed Central

    Darling, Warren G.; Pizzimenti, Marc A.; Morecraft, Robert J.

    2013-01-01

    This review discusses selected classical works and contemporary research on recovery of contralesional fine hand motor function following lesions to motor areas of the cerebral cortex in non-human primates. Findings from both the classical literature and contemporary studies show that lesions of cortical motor areas induce paresis initially, but are followed by remarkable recovery of fine hand/digit motor function that depends on lesion size and post-lesion training. Indeed, in recent work where considerable quantification of fine digit function associated with grasping and manipulating small objects has been observed, very favorable recovery is possible with minimal forced use of the contralesional limb. Studies of the mechanisms underlying recovery have shown that following small lesions of the digit areas of primary motor cortex (M1), there is expansion of the digit motor representations into areas of M1 that did not produce digit movements prior to the lesion. However, after larger lesions involving the elbow, wrist and digit areas of M1, no such expansion of the motor representation was observed, suggesting that recovery was due to other cortical or subcortical areas taking over control of hand/digit movements. Recently, we showed that one possible mechanism of recovery after lesion to the arm areas of M1 and lateral premotor cortex is enhancement of corticospinal projections from the medially located supplementary motor area (M2) to spinal cord laminae containing neurons which have lost substantial input from the lateral motor areas and play a critical role in reaching and digit movements. Because human stroke and brain injury patients show variable, and usually poorer, recovery of hand motor function than that of nonhuman primates after motor cortex damage, we conclude with a discussion of implications of this work for further experimentation to improve recovery of hand function in human stroke patients. PMID:21960307

  1. Fusimotor control of spindle sensitivity regulates central and peripheral coding of joint angles.

    PubMed

    Lan, Ning; He, Xin

    2012-01-01

    Proprioceptive afferents from muscle spindles encode information about peripheral joint movements for the central nervous system (CNS). The sensitivity of muscle spindle is nonlinearly dependent on the activation of gamma (γ) motoneurons in the spinal cord that receives inputs from the motor cortex. How fusimotor control of spindle sensitivity affects proprioceptive coding of joint position is not clear. Furthermore, what information is carried in the fusimotor signal from the motor cortex to the muscle spindle is largely unknown. In this study, we addressed the issue of communication between the central and peripheral sensorimotor systems using a computational approach based on the virtual arm (VA) model. In simulation experiments within the operational range of joint movements, the gamma static commands (γ(s)) to the spindles of both mono-articular and bi-articular muscles were hypothesized (1) to remain constant, (2) to be modulated with joint angles linearly, and (3) to be modulated with joint angles nonlinearly. Simulation results revealed a nonlinear landscape of Ia afferent with respect to both γ(s) activation and joint angle. Among the three hypotheses, the constant and linear strategies did not yield Ia responses that matched the experimental data, and therefore, were rejected as plausible strategies of spindle sensitivity control. However, if γ(s) commands were quadratically modulated with joint angles, a robust linear relation between Ia afferents and joint angles could be obtained in both mono-articular and bi-articular muscles. With the quadratic strategy of spindle sensitivity control, γ(s) commands may serve as the CNS outputs that inform the periphery of central coding of joint angles. The results suggest that the information of joint angles may be communicated between the CNS and muscles via the descending γ(s) efferent and Ia afferent signals.

  2. Visuomotor signals for reaching movements in the rostro-dorsal sector of the monkey thalamic reticular nucleus.

    PubMed

    Saga, Yosuke; Nakayama, Yoshihisa; Inoue, Ken-Ichi; Yamagata, Tomoko; Hashimoto, Masashi; Tremblay, Léon; Takada, Masahiko; Hoshi, Eiji

    2017-05-01

    The thalamic reticular nucleus (TRN) collects inputs from the cerebral cortex and thalamus and, in turn, sends inhibitory outputs to the thalamic relay nuclei. This unique connectivity suggests that the TRN plays a pivotal role in regulating information flow through the thalamus. Here, we analyzed the roles of TRN neurons in visually guided reaching movements. We first used retrograde transneuronal labeling with rabies virus, and showed that the rostro-dorsal sector of the TRN (TRNrd) projected disynaptically to the ventral premotor cortex (PMv). In other experiments, we recorded neurons from the TRNrd or PMv while monkeys performed a visuomotor task. We found that neurons in the TRNrd and PMv showed visual-, set-, and movement-related activity modulation. These results indicate that the TRNrd, as well as the PMv, is involved in the reception of visual signals and in the preparation and execution of reaching movements. The fraction of neurons that were non-selective for the location of visual signals or the direction of reaching movements was greater in the TRNrd than in the PMv. Furthermore, the fraction of neurons whose activity increased from the baseline was greater in the TRNrd than in the PMv. The timing of activity modulation of visual-related and movement-related neurons was similar in TRNrd and PMv neurons. Overall, our data suggest that TRNrd neurons provide motor thalamic nuclei with inhibitory inputs that are predominantly devoid of spatial selectivity, and that these signals modulate how these nuclei engage in both sensory processing and motor output during visually guided reaching behavior. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  3. Disassociation between primary motor cortical activity and movement kinematics during adaptation to reach perturbations.

    PubMed

    Cai, X; Shimansky, Y P; Weber, D J; He, Jiping

    2004-01-01

    The relationship between movement kinematics and motor cortical activity was studied in monkeys performing a center-out reaching task during their adaptation to force perturbations applied to the wrist. The main feature of adaptive changes in movement kinematics was anticipatory deviation of hand paths in the direction opposite to that of the upcoming perturbation. We identified a group of neurons in the dorsal lateral portion of the primary motor cortex where a gradual buildup of spike activity immediately preceding the actual (in perturbation trials) or the "would-be" (in unperturbed/catch trials) perturbation onset was observed. These neurons were actively involved in the adaptation process, which was evident from the gradual increase in the amplitude of their movement-related modulation of spike activity from virtual zero and development of certain directional tuning pattern (DTP). However, the day-to-day dynamics of the kinematics adaptation was dramatically different from that of the neuronal activity. Hence, the adaptive modification of the motor cortical activity is more likely to reflect the development of the internal model of the perturbation dynamics, rather than motor instructions determining the adaptive behavior.

  4. The Role of Dopamine in Normal Rodent Motor Cortex: Physiological Effects and Structural Correlates

    DTIC Science & Technology

    1999-04-05

    things she does on a daily basis made the lab a great place to do research. Susan’s expertise in molecular techniques was evident from day one , and I...applied OA on the spontaneous activity (SA) of PTNs. the receptors that mediate these effects, and DA’s effects on glutamate induced excitation of PTNs...numerous neurons in the motor cortex and may have profound effects on motor cortex activity, through its influence on PTNs. iv The Role of Dopamine in

  5. Disorganization of Oligodendrocyte Development in the Layer II/III of the Sensorimotor Cortex Causes Motor Coordination Dysfunction in a Model of White Matter Injury in Neonatal Rats.

    PubMed

    Ueda, Yoshitomo; Misumi, Sachiyo; Suzuki, Mina; Ogawa, Shino; Nishigaki, Ruriko; Ishida, Akimasa; Jung, Cha-Gyun; Hida, Hideki

    2018-01-01

    We previously established neonatal white matter injury (WMI) model rat that is made by right common carotid artery dissection at postnatal day 3, followed by 6% hypoxia for 60 min. This model has fewer oligodendrocyte progenitor cells and reduced myelin basic protein (MBP) positive areas in the sensorimotor cortex, but shows no apparent neuronal loss. However, how motor deficits are induced in this model is unclear. To elucidate the relationship between myelination disturbance and concomitant motor deficits, we first performed motor function tests (gait analysis, grip test, horizontal ladder test) and then analyzed myelination patterns in the sensorimotor cortex using transmission electron microscopy (TEM) and Contactin associated protein 1 (Caspr) staining in the neonatal WMI rats in adulthood. Behavioral tests revealed imbalanced motor coordination in this model. Motor deficit scores were higher in the neonatal WMI model, while hindlimb ladder stepping scores and forelimb grasping force were comparable to controls. Prolonged forelimb swing times and decreased hindlimb paw angles on the injured side were revealed by gait analysis. TEM revealed no change in myelinated axon number and the area g-ratio in the layer II/III of the cortex. Electromyographical durations and latencies in the gluteus maximus in response to electrical stimulation of the brain area were unchanged in the model. Caspr staining revealed fewer positive dots in layers II/III of the WMI cortex, indicating fewer and/or longer myelin sheath. These data suggest that disorganization of oligodendrocyte development in layers II/III of the sensorimotor cortex relates to imbalanced motor coordination in the neonatal WMI model rat.

  6. Propofol attenuates low-frequency fluctuations of resting-state fMRI BOLD signal in the anterior frontal cortex upon loss of consciousness.

    PubMed

    Liu, Xiaolin; Lauer, Kathryn K; Douglas Ward, B; Roberts, Christopher; Liu, Suyan; Gollapudy, Suneeta; Rohloff, Robert; Gross, William; Chen, Guangyu; Xu, Zhan; Binder, Jeffrey R; Li, Shi-Jiang; Hudetz, Anthony G

    2017-02-15

    Recent studies indicate that spontaneous low-frequency fluctuations (LFFs) of resting-state functional magnetic resonance imaging (rs-fMRI) blood oxygen level-dependent (BOLD) signals are driven by the slow (<0.1Hz) modulation of ongoing neuronal activity synchronized locally and across remote brain regions. How regional LFFs of the BOLD fMRI signal are altered during anesthetic-induced alteration of consciousness is not well understood. Using rs-fMRI in 15 healthy participants, we show that during administration of propofol to achieve loss of behavioral responsiveness indexing unconsciousness, the fractional amplitude of LFF (fALFF index) was reduced in comparison to wakeful baseline in the anterior frontal regions, temporal pole, hippocampus, parahippocampal gyrus, and amygdala. Such changes were absent in large areas of the motor, parietal, and sensory cortices. During light sedation characterized by the preservation of overt responsiveness and therefore consciousness, fALFF was reduced in the subcortical areas, temporal pole, medial orbital frontal cortex, cingulate cortex, and cerebellum. Between light sedation and deep sedation, fALFF was reduced primarily in the medial and dorsolateral frontal areas. The preferential reduction of LFFs in the anterior frontal regions is consistent with frontal to sensory-motor cortical disconnection and may contribute to the suppression of consciousness during general anesthesia. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Propofol attenuates low-frequency fluctuations of resting-state fMRI BOLD signal in the anterior frontal cortex upon loss of consciousness

    PubMed Central

    Liu, Xiaolin; Lauer, Kathryn K.; Ward, B. Douglas; Roberts, Christopher; Liu, Suyan; Gollapudy, Suneeta; Rohloff, Robert; Gross, William; Chen, Guangyu; Xu, Zhan; Binder, Jeffrey R.; Li, Shi-Jiang; Hudetz, Anthony G.

    2017-01-01

    Recent studies indicate that spontaneous low-frequency fluctuations (LFFs) of resting-state functional magnetic resonance imaging (rs-fMRI) blood oxygen level-dependent (BOLD) signals are driven by the slow (<0.1 Hz) modulation of ongoing neuronal activity synchronized locally and across remote brain regions. How regional LFFs of the BOLD fMRI signal are altered during anesthetic-induced alteration of consciousness is not well understood. Using rs-fMRI in 15 healthy participants, we show that during administration of propofol to achieve loss of behavioral responsiveness indexing unconsciousness, the fractional amplitude of LFF (fALFF index) was reduced in comparison to wakeful baseline in the anterior frontal regions, temporal pole, hippocampus, parahippocampal gyrus, and amygdala. Such changes were absent in large areas of the motor, parietal, and sensory cortices. During light sedation characterized by the preservation of overt responsiveness and therefore consciousness, fALFF was reduced in the subcortical areas, temporal pole, medial orbital frontal cortex, cingulate cortex, and cerebellum. Between light sedation and deep sedation, fALFF was reduced primarily in the medial and dorsolateral frontal areas. The preferential reduction of LFFs in the anterior frontal regions is consistent with frontal to sensory-motor cortical disconnection and may contribute to the suppression of consciousness during general anesthesia. PMID:27993673

  8. Transcranial direct current stimulation over the primary motor vs prefrontal cortex in refractory chronic migraine: A pilot randomized controlled trial.

    PubMed

    Andrade, Suellen Marinho; de Brito Aranha, Renata Emanuela Lyra; de Oliveira, Eliane Araújo; de Mendonça, Camila Teresa Ponce Leon; Martins, Wanessa Kallyne Nascimento; Alves, Nelson Torro; Fernández-Calvo, Bernardino

    2017-07-15

    Although transcranial direct current stimulation (tDCS) represents a therapeutic option for the prophylaxis of chronic migraine, the target area for application of the electrical current to the cortex has not yet been well established. Here we sought to determine whether a treatment protocol involving 12 sessions of 2mA, 20min anodal stimulation of the left primary motor (M1) or dorsolateral prefrontal cortex (DLPFC) could offer clinical benefits in the management of pain from migraine. Thirteen participants were assessed before and after treatment, using the Headache Impact Test-6, Visual Analogue Scale and Medical Outcomes Study 36 - Item Short - Form Health Survey. After treatment, group DLPFC exhibited a better performance compared with groups M1 and sham. On intragroup comparison, groups DLPFC and M1 exhibited a greater reduction in headache impact and pain intensity and a higher quality of life after treatment. No significant change was found in group sham. The participants in group M1 exhibited more adverse effects, especially headache, heartburn, and sleepiness, than did those in the other two groups. Transcranial direct current stimulation is a safe and efficacious technique for treating chronic migraine. However, it should be kept in mind that the site of cortical stimulation might modulate the patient's response to treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Motor cortex electrical stimulation augments sprouting of the corticospinal tract and promotes recovery of motor function

    PubMed Central

    Carmel, Jason B.; Martin, John H.

    2014-01-01

    The corticospinal system—with its direct spinal pathway, the corticospinal tract (CST) – is the primary system for controlling voluntary movement. Our approach to CST repair after injury in mature animals was informed by our finding that activity drives establishment of connections with spinal cord circuits during postnatal development. After incomplete injury in maturity, spared CST circuits sprout, and partially restore lost function. Our approach harnesses activity to augment this injury-dependent CST sprouting and to promote function. Lesion of the medullary pyramid unilaterally eliminates all CST axons from one hemisphere and allows examination of CST sprouting from the unaffected hemisphere. We discovered that 10 days of electrical stimulation of either the spared CST or motor cortex induces CST axon sprouting that partially reconstructs the lost CST. Stimulation also leads to sprouting of the cortical projection to the magnocellular red nucleus, where the rubrospinal tract originates. Coordinated outgrowth of the CST and cortical projections to the red nucleus could support partial re-establishment of motor systems connections to the denervated spinal motor circuits. Stimulation restores skilled motor function in our animal model. Lesioned animals have a persistent forelimb deficit contralateral to pyramidotomy in the horizontal ladder task. Rats that received motor cortex stimulation either after acute or chronic injury showed a significant functional improvement that brought error rate to pre-lesion control levels. Reversible inactivation of the stimulated motor cortex reinstated the impairment demonstrating the importance of the stimulated system to recovery. Motor cortex electrical stimulation is an effective approach to promote spouting of spared CST axons. By optimizing activity-dependent sprouting in animals, we could have an approach that can be translated to the human for evaluation with minimal delay. PMID:24994971

  10. Prefrontal rTMS for treating depression: location and intensity results from the OPT-TMS multi-site clinical trial.

    PubMed

    Johnson, Kevin A; Baig, Mirza; Ramsey, Dave; Lisanby, Sarah H; Avery, David; McDonald, William M; Li, Xingbao; Bernhardt, Elisabeth R; Haynor, David R; Holtzheimer, Paul E; Sackeim, Harold A; George, Mark S; Nahas, Ziad

    2013-03-01

    Motor cortex localization and motor threshold determination often guide Transcranial Magnetic Stimulation (TMS) placement and intensity settings for non-motor brain stimulation. However, anatomic variability results in variability of placement and effective intensity. Post-study analysis of the OPT-TMS Study reviewed both the final positioning and the effective intensity of stimulation (accounting for relative prefrontal scalp-cortex distances). We acquired MRI scans of 185 patients in a multi-site trial of left prefrontal TMS for depression. Scans had marked motor sites (localized with TMS) and marked prefrontal sites (5 cm anterior of motor cortex by the "5 cm rule"). Based on a visual determination made before the first treatment, TMS therapy occurred either at the 5 cm location or was adjusted 1 cm forward. Stimulation intensity was 120% of resting motor threshold. The "5 cm rule" would have placed stimulation in premotor cortex for 9% of patients, which was reduced to 4% with adjustments. We did not find a statistically significant effect of positioning on remission, but no patients with premotor stimulation achieved remission (0/7). Effective stimulation ranged from 93 to 156% of motor threshold, and no seizures were induced across this range. Patients experienced remission with effective stimulation intensity ranging from 93 to 146% of motor threshold, and we did not find a significant effect of effective intensity on remission. Our data indicates that individualized positioning methods are useful to reduce variability in placement. Stimulation at 120% of motor threshold, unadjusted for scalp-cortex distances, appears safe for a broad range of patients. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Measurements of evoked electroencephalograph by transcranial magnetic stimulation applied to motor cortex and posterior parietal cortex

    NASA Astrophysics Data System (ADS)

    Iwahashi, Masakuni; Koyama, Yohei; Hyodo, Akira; Hayami, Takehito; Ueno, Shoogo; Iramina, Keiji

    2009-04-01

    To investigate the functional connectivity, the evoked potentials by stimulating at the motor cortex, the posterior parietal cortex, and the cerebellum by transcranial magnetic stimulation (TMS) were measured. It is difficult to measure the evoked electroencephalograph (EEG) by the magnetic stimulation because of the large artifact induced by the magnetic pulse. We used an EEG measurement system with sample-and-hold circuit and an independent component analysis to eliminate the electromagnetic interaction emitted from TMS. It was possible to measure EEG signals from all electrodes over the head within 10 ms after applying the TMS. When the motor area was stimulated by TMS, the spread of evoked electrical activity to the contralateral hemisphere was observed at 20 ms after stimulation. However, when the posterior parietal cortex was stimulated, the evoked electrical activity to the contralateral hemisphere was not observed. When the cerebellum was stimulated, the cortical activity propagated from the stimulated point to the frontal area and the contralateral hemisphere at around 20 ms after stimulation. These results suggest that the motor area has a strong interhemispheric connection and the posterior parietal cortex has no interhemispheric connection.

  12. Recruitment of Additional Corticospinal Pathways in the Human Brain with State-Dependent Paired Associative Stimulation.

    PubMed

    Kraus, Dominic; Naros, Georgios; Guggenberger, Robert; Leão, Maria Teresa; Ziemann, Ulf; Gharabaghi, Alireza

    2018-02-07

    Standard brain stimulation protocols modify human motor cortex excitability by modulating the gain of the activated corticospinal pathways. However, the restoration of motor function following lesions of the corticospinal tract requires also the recruitment of additional neurons to increase the net corticospinal output. For this purpose, we investigated a novel protocol based on brain state-dependent paired associative stimulation.Motor imagery (MI)-related electroencephalography was recorded in healthy males and females for brain state-dependent control of both cortical and peripheral stimulation in a brain-machine interface environment. State-dependency was investigated with concurrent, delayed, and independent stimulation relative to the MI task. Specifically, sensorimotor event-related desynchronization (ERD) in the β-band (16-22 Hz) triggered peripheral stimulation through passive hand opening by a robotic orthosis and transcranial magnetic stimulation to the respective cortical motor representation, either synchronously or subsequently. These MI-related paradigms were compared with paired cortical and peripheral input applied independent of the brain state. Cortical stimulation resulted in a significant increase in corticospinal excitability only when applied brain state-dependently and synchronously to peripheral input. These gains were resistant to a depotentiation task, revealed a nonlinear evolution of plasticity, and were mediated via the recruitment of additional corticospinal neurons rather than via synchronization of neuronal firing. Recruitment of additional corticospinal pathways may be achieved when cortical and peripheral inputs are applied concurrently, and during β-ERD. These findings resemble a gating mechanism and are potentially important for developing closed-loop brain stimulation for the treatment of hand paralysis following lesions of the corticospinal tract. SIGNIFICANCE STATEMENT The activity state of the motor system influences the excitability of corticospinal pathways to external input. State-dependent interventions harness this property to increase the connectivity between motor cortex and muscles. These stimulation protocols modulate the gain of the activated pathways, but not the overall corticospinal recruitment. In this study, a brain-machine interface paired peripheral stimulation through passive hand opening with transcranial magnetic stimulation to the respective cortical motor representation during volitional β-band desynchronization. Cortical stimulation resulted in the recruitment of additional corticospinal pathways, but only when applied brain state-dependently and synchronously to peripheral input. These effects resemble a gating mechanism and may be important for the restoration of motor function following lesions of the corticospinal tract. Copyright © 2018 the authors 0270-6474/18/381397-12$15.00/0.

  13. Reorganization of Motor Cortex by Vagus Nerve Stimulation Requires Cholinergic Innervation.

    PubMed

    Hulsey, Daniel R; Hays, Seth A; Khodaparast, Navid; Ruiz, Andrea; Das, Priyanka; Rennaker, Robert L; Kilgard, Michael P

    2016-01-01

    Vagus nerve stimulation (VNS) paired with forelimb training drives robust, specific reorganization of movement representations in the motor cortex. The mechanisms that underlie VNS-dependent enhancement of map plasticity are largely unknown. The cholinergic nucleus basalis (NB) is a critical substrate in cortical plasticity, and several studies suggest that VNS activates cholinergic circuitry. We examined whether the NB is required for VNS-dependent enhancement of map plasticity in the motor cortex. Rats were trained to perform a lever pressing task and then received injections of the immunotoxin 192-IgG-saporin to selectively lesion cholinergic neurons of the NB. After lesion, rats underwent five days of motor training during which VNS was paired with successful trials. At the conclusion of behavioral training, intracortical microstimulation was used to document movement representations in motor cortex. VNS paired with forelimb training resulted in a substantial increase in the representation of proximal forelimb in rats with an intact NB compared to untrained controls. NB lesions prevent this VNS-dependent increase in proximal forelimb area and result in representations similar to untrained controls. Motor performance was similar between groups, suggesting that differences in forelimb function cannot account for the difference in proximal forelimb representation. Together, these findings indicate that the NB is required for VNS-dependent enhancement of plasticity in the motor cortex and may provide insight into the mechanisms that underlie the benefits of VNS therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. FGF-2 induces behavioral recovery after early adolescent injury to the motor cortex of rats.

    PubMed

    Nemati, Farshad; Kolb, Bryan

    2011-11-20

    Motor cortex injuries in adulthood lead to poor performance in behavioral tasks sensitive to limb movements in the rat. We have shown previously that motor cortex injury on day 10 or day 55 allow significant spontaneous recovery but not injury in early adolescence (postnatal day 35 "P35"). Previous studies have indicated that injection of basic fibroblast growth factor (FGF-2) enhances behavioral recovery after neonatal cortical injury but such effect has not been studied following motor cortex lesions in early adolescence. The present study undertook to investigate the possibility of such behavioral recovery. Rats with unilateral motor cortex lesions were assigned to two groups in which they received FGF-2 or bovine serum albumin (BSA) and were tested in a number of behavioral tests (postural asymmetry, skilled reaching, sunflower seed manipulation, forepaw inhibition in swimming). Golgi-Cox analysis was used to examine the dendritic structure of pyramidal cells in the animals' parietal (layer III) and forelimb (layer V) area of the cortex. The results indicated that rats injected with FGF-2 (but not BSA) showed significant behavioral recovery that was associated with increased dendritic length and spine density. The present study suggests a role for FGF-2 in the recovery of function following injury during early adolescence. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Influence of stimulant medication and response speed on lateralization of movement-related potentials in attention-deficit/hyperactivity disorder.

    PubMed

    Bender, Stephan; Resch, Franz; Klein, Christoph; Renner, Tobias; Fallgatter, Andreas J; Weisbrod, Matthias; Romanos, Marcel

    2012-01-01

    Hyperactivity is one of the core symptoms in attention deficit hyperactivity disorder (ADHD). However, it remains unclear in which way the motor system itself and its development are affected by the disorder. Movement-related potentials (MRP) can separate different stages of movement execution, from the programming of a movement to motor post-processing and memory traces. Pre-movement MRP are absent or positive during early childhood and display a developmental increase of negativity. We examined the influences of response-speed, an indicator of the level of attention, and stimulant medication on lateralized MRP in 16 children with combined type ADHD compared to 20 matched healthy controls. We detected a significantly diminished lateralisation of MRP over the pre-motor and primary motor cortex during movement execution (initial motor potential peak, iMP) in patients with ADHD. Fast reactions (indicating increased visuo-motor attention) led to increased lateralized negativity during movement execution only in healthy controls, while in children with ADHD faster reaction times were associated with more positive amplitudes. Even though stimulant medication had some effect on attenuating group differences in lateralized MRP, this effect was insufficient to normalize lateralized iMP amplitudes. A reduced focal (lateralized) motor cortex activation during the command to muscle contraction points towards an immature motor system and a maturation delay of the (pre-) motor cortex in children with ADHD. A delayed maturation of the neuronal circuitry, which involves primary motor cortex, may contribute to ADHD pathophysiology.

  16. Ipsilateral corticotectal projections from the primary, premotor and supplementary motor cortical areas in adult macaque monkeys: a quantitative anterograde tracing study

    PubMed Central

    Fregosi, Michela; Rouiller, Eric M.

    2018-01-01

    The corticotectal projection from cortical motor areas is one of several descending pathways involved in the indirect control of spinal motoneurons. In non-human primates, previous studies reported that cortical projections to the superior colliculus originated from the premotor cortex and the primary motor cortex, whereas no projection originated from the supplementary motor area. The aim of the present study was to investigate and compare the properties of corticotectal projections originating from these three cortical motor areas in intact adult macaques (n=9). The anterograde tracer BDA was injected into one of these cortical areas in each animal. Individual axonal boutons, both en passant and terminaux, were charted and counted in the different layers of the ipsilateral superior colliculus. The data confirmed the presence of strong corticotectal projections from the premotor cortex. A new observation was that strong corticotectal projections were also found to originate from the supplementary motor area (its proper division). The corticotectal projection from the primary motor cortex was quantitatively less strong than that from either the premotor or supplementary motor areas. The corticotectal projection from each motor area was directed mainly to the deep layer of the superior colliculus, although its intermediate layer was also a consistent target of fairly dense terminations. The strong corticotectal projections from non-primary motor areas are in position to influence the preparation and planning of voluntary movements. PMID:28921678

  17. Plasticity in the sensorimotor cortex induced by Music-supported therapy in stroke patients: a TMS study.

    PubMed

    Grau-Sánchez, Jennifer; Amengual, Julià L; Rojo, Nuria; Veciana de Las Heras, Misericordia; Montero, Jordi; Rubio, Francisco; Altenmüller, Eckart; Münte, Thomas F; Rodríguez-Fornells, Antoni

    2013-01-01

    Playing a musical instrument demands the engagement of different neural systems. Recent studies about the musician's brain and musical training highlight that this activity requires the close interaction between motor and somatosensory systems. Moreover, neuroplastic changes have been reported in motor-related areas after short and long-term musical training. Because of its capacity to promote neuroplastic changes, music has been used in the context of stroke neurorehabilitation. The majority of patients suffering from a stroke have motor impairments, preventing them to live independently. Thus, there is an increasing demand for effective restorative interventions for neurological deficits. Music-supported Therapy (MST) has been recently developed to restore motor deficits. We report data of a selected sample of stroke patients who have been enrolled in a MST program (1 month intense music learning). Prior to and after the therapy, patients were evaluated with different behavioral motor tests. Transcranial Magnetic Stimulation (TMS) was applied to evaluate changes in the sensorimotor representations underlying the motor gains observed. Several parameters of excitability of the motor cortex were assessed as well as the cortical somatotopic representation of a muscle in the affected hand. Our results revealed that participants obtained significant motor improvements in the paretic hand and those changes were accompanied by changes in the excitability of the motor cortex. Thus, MST leads to neuroplastic changes in the motor cortex of stroke patients which may explain its efficacy.

  18. Plasticity in the sensorimotor cortex induced by Music-supported therapy in stroke patients: a TMS study

    PubMed Central

    Grau-Sánchez, Jennifer; Amengual, Julià L.; Rojo, Nuria; Veciana de las Heras, Misericordia; Montero, Jordi; Rubio, Francisco; Altenmüller, Eckart; Münte, Thomas F.; Rodríguez-Fornells, Antoni

    2013-01-01

    Playing a musical instrument demands the engagement of different neural systems. Recent studies about the musician's brain and musical training highlight that this activity requires the close interaction between motor and somatosensory systems. Moreover, neuroplastic changes have been reported in motor-related areas after short and long-term musical training. Because of its capacity to promote neuroplastic changes, music has been used in the context of stroke neurorehabilitation. The majority of patients suffering from a stroke have motor impairments, preventing them to live independently. Thus, there is an increasing demand for effective restorative interventions for neurological deficits. Music-supported Therapy (MST) has been recently developed to restore motor deficits. We report data of a selected sample of stroke patients who have been enrolled in a MST program (1 month intense music learning). Prior to and after the therapy, patients were evaluated with different behavioral motor tests. Transcranial Magnetic Stimulation (TMS) was applied to evaluate changes in the sensorimotor representations underlying the motor gains observed. Several parameters of excitability of the motor cortex were assessed as well as the cortical somatotopic representation of a muscle in the affected hand. Our results revealed that participants obtained significant motor improvements in the paretic hand and those changes were accompanied by changes in the excitability of the motor cortex. Thus, MST leads to neuroplastic changes in the motor cortex of stroke patients which may explain its efficacy. PMID:24027507

  19. Motor and mental training in older people: Transfer, interference, and associated functional neural responses.

    PubMed

    Boraxbekk, C J; Hagkvist, Filip; Lindner, Philip

    2016-08-01

    Learning new motor skills may become more difficult with advanced age. In the present study, we randomized 56 older individuals, including 30 women (mean age 70.6 years), to 6 weeks of motor training, mental (motor imagery) training, or a combination of motor and mental training of a finger tapping sequence. Performance improvements and post-training functional magnetic resonance imaging (fMRI) were used to investigate performance gains and associated underlying neural processes. Motor-only training and a combination of motor and mental training improved performance in the trained task more than mental-only training. The fMRI data showed that motor training was associated with a representation in the premotor cortex and mental training with a representation in the secondary visual cortex. Combining motor and mental training resulted in both premotor and visual cortex representations. During fMRI scanning, reduced performance was observed in the combined motor and mental training group, possibly indicating interference between the two training methods. We concluded that motor and motor imagery training in older individuals is associated with different functional brain responses. Furthermore, adding mental training to motor training did not result in additional performance gains compared to motor-only training and combining training methods may result in interference between representations, reducing performance. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Cortical NMDA receptor expression in human chronic alcoholism: influence of the TaqIA allele of ANKK1.

    PubMed

    Ridge, Justin P; Dodd, Peter R

    2009-10-01

    Real-time RT-PCR normalized to GAPDH was used to assay N-methyl-D-aspartate (NMDA) receptor NR1, NR2A and NR2B subunit mRNA in human autopsy cortex tissue from chronic alcoholics with and without comorbid cirrhosis of the liver and matched controls. Subunit expression was influenced by the subject's genotype. The TaqIA polymorphism selectively modulated NMDA receptor mean transcript expression in cirrhotic-alcoholic superior frontal cortex, in diametrically opposite ways in male and female subjects. Genetic make-up may differentially influence vulnerability to brain damage by altering the excitation: inhibition balance, particularly in alcoholics with comorbid cirrhosis of the liver. The TaqIA polymorphism occurs within the poorly characterised ankyrin-repeat containing kinase 1 (ANKK1) gene. Using PCR, ANKK1 mRNA transcript was detected in inferior temporal, occipital, superior frontal and primary motor cortex of control human brain. ANKK1 expression may mediate the influence of the TaqIA polymorphism on phenotype.

  1. Lip movements entrain the observers’ low-frequency brain oscillations to facilitate speech intelligibility

    PubMed Central

    Park, Hyojin; Kayser, Christoph; Thut, Gregor; Gross, Joachim

    2016-01-01

    During continuous speech, lip movements provide visual temporal signals that facilitate speech processing. Here, using MEG we directly investigated how these visual signals interact with rhythmic brain activity in participants listening to and seeing the speaker. First, we investigated coherence between oscillatory brain activity and speaker’s lip movements and demonstrated significant entrainment in visual cortex. We then used partial coherence to remove contributions of the coherent auditory speech signal from the lip-brain coherence. Comparing this synchronization between different attention conditions revealed that attending visual speech enhances the coherence between activity in visual cortex and the speaker’s lips. Further, we identified a significant partial coherence between left motor cortex and lip movements and this partial coherence directly predicted comprehension accuracy. Our results emphasize the importance of visually entrained and attention-modulated rhythmic brain activity for the enhancement of audiovisual speech processing. DOI: http://dx.doi.org/10.7554/eLife.14521.001 PMID:27146891

  2. Altered brain network modules induce helplessness in major depressive disorder.

    PubMed

    Peng, Daihui; Shi, Feng; Shen, Ting; Peng, Ziwen; Zhang, Chen; Liu, Xiaohua; Qiu, Meihui; Liu, Jun; Jiang, Kaida; Fang, Yiru; Shen, Dinggang

    2014-10-01

    The abnormal brain functional connectivity (FC) has been assumed to be a pathophysiological aspect of major depressive disorder (MDD). However, it is poorly understood, regarding the underlying patterns of global FC network and their relationships with the clinical characteristics of MDD. Resting-state functional magnetic resonance imaging data were acquired from 16 first episode, medication-naïve MDD patients and 16 healthy control subjects. The global FC network was constructed using 90 brain regions. The global topological patterns, e.g., small-worldness and modularity, and their relationships with depressive characteristics were investigated. Furthermore, the participant coefficient and module degree of MDD patients were measured to reflect the regional roles in module network, and the impairment of FC was examined by network based statistic. Small-world property was not altered in MDD. However, MDD patients exhibited 5 atypically reorganized modules compared to the controls. A positive relationship was also found among MDD patients between the intra-module I and helplessness factor evaluated via the Hamilton Depression Scale. Specifically, eight regions exhibited the abnormal participant coefficient or module degree, e.g., left superior orbital frontal cortex and right amygdala. The decreased FC was identified among the sub-network of 24 brain regions, e.g., frontal cortex, supplementary motor area, amygdala, thalamus, and hippocampus. The limited size of MDD samples precluded meaningful study of distinct clinical characteristics in relation to aberrant FC. The results revealed altered patterns of brain module network at the global level in MDD patients, which might contribute to the feelings of helplessness. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Altered brain network modules induce helplessness in major depressive disorder

    PubMed Central

    Peng, Daihui; Shi, Feng; Shen, Ting; Peng, Ziwen; Zhang, Chen; Liu, Xiaohua; Qiu, Meihui; Liu, Jun; Jiang, Kaida; Shen, Dinggang

    2017-01-01

    Objective The abnormal brain functional connectivity (FC) has been assumed to be a pathophysiological aspect of major depressive disorder (MDD). However, it is poorly understood, regarding the underlying patterns of global FC network and their relationships with the clinical characteristics of MDD. Methods Resting-state functional magnetic resonance imaging data were acquired from 16 first episode, medication-naïve MDD patients and 16 healthy control subjects. The global FC network was constructed using 90 brain regions. The global topological patterns, e.g., small-worldness and modularity, and their relationships with depressive characteristics were investigated. Furthermore, the participant coefficient and module degree of MDD patients were measured to reflect the regional roles in module network, and the impairment of FC was examined by network based statistic. Results Small-world property was not altered in MDD. However, MDD patients exhibited 5 atypically reorganized modules compared to the controls. A positive relationship was also found among MDD patients between the intra-module I and helplessness factor evaluated via the Hamilton Depression Scale. Specifically, eight regions exhibited the abnormal participant coefficient or module degree, e.g., left superior orbital frontal cortex and right amygdala. The decreased FC was identified among the sub-network of 24 brain regions, e.g., frontal cortex, supplementary motor area, amygdala, thalamus, and hippocampus. Limitation The limited size of MDD samples precluded meaningful study of distinct clinical characteristics in relation to aberrant FC. Conclusions The results revealed altered patterns of brain module network at the global level in MDD patients, which might contribute to the feelings of helplessness. PMID:25033474

  4. Structural Covariance of the Prefrontal-Amygdala Pathways Associated with Heart Rate Variability.

    PubMed

    Wei, Luqing; Chen, Hong; Wu, Guo-Rong

    2018-01-01

    The neurovisceral integration model has shown a key role of the amygdala in neural circuits underlying heart rate variability (HRV) modulation, and suggested that reciprocal connections from amygdala to brain regions centered on the central autonomic network (CAN) are associated with HRV. To provide neuroanatomical evidence for these theoretical perspectives, the current study used covariance analysis of MRI-based gray matter volume (GMV) to map structural covariance network of the amygdala, and then determined whether the interregional structural correlations related to individual differences in HRV. The results showed that covariance patterns of the amygdala encompassed large portions of cortical (e.g., prefrontal, cingulate, and insula) and subcortical (e.g., striatum, hippocampus, and midbrain) regions, lending evidence from structural covariance analysis to the notion that the amygdala was a pivotal node in neural pathways for HRV modulation. Importantly, participants with higher resting HRV showed increased covariance of amygdala to dorsal medial prefrontal cortex and anterior cingulate cortex (dmPFC/dACC) extending into adjacent medial motor regions [i.e., pre-supplementary motor area (pre-SMA)/SMA], demonstrating structural covariance of the prefrontal-amygdala pathways implicated in HRV, and also implying that resting HRV may reflect the function of neural circuits underlying cognitive regulation of emotion as well as facilitation of adaptive behaviors to emotion. Our results, thus, provide anatomical substrates for the neurovisceral integration model that resting HRV may index an integrative neural network which effectively organizes emotional, cognitive, physiological and behavioral responses in the service of goal-directed behavior and adaptability.

  5. Women's Preference for a Male Acquaintance Enhances Social Reward Processing of Material Goods in the Anterior Cingulate Cortex.

    PubMed

    Nakagawa, Jun; Takahashi, Muneyoshi; Okada, Rieko; Matsushima, Eisuke; Matsuda, Tetsuya

    2015-01-01

    Men, like the male of many animal species, use gifts to build satisfactory relationships with a desired woman. From the woman's perspective, all gifts are not always equally rewarding; the reward value of a gift depends on two factors: (1) the giver and (2) the type of the gift (the gift's social meaning). In this study, we investigated how these two factors interactively determine the reward value of a gift. Specifically, we examined how the neural processing for understanding a gift's social meaning is modulated by preferences for the giver. We performed a functional magnetic resonance imaging (fMRI) study in which a female participant was asked to judge a gift from a male she was acquainted with in real life. We examined the interactive effects between (1) the female participant's attitude toward the male acquaintance (liked vs. uninteresting) and (2) the type of the gift (romantic [e.g., bouquet, earrings, and perfumes] vs. non-romantic [e.g., pencils, memo pad, and moneybox]). We found that preference for an acquaintance selectively modulated activity in the anterior cingulate cortex (ACC) in response to romantic gifts, compared to non-romantic gifts. In contrast, if the woman was indifferent toward an acquaintance, no activity modulation was observed in this area for the same gifts. In addition, the ACC showed functional connectivity with the supplementary motor area/dorsal ACC (SMA/dACC), an area within the dorsal mediofrontal cortex, suggesting that it integrates action monitoring and emotional and cognitive processing in decision-making. These results suggest that attitude toward an opposite sex member has a modulatory role in recognizing the social meaning of material goods--preference for the member is a powerful modulator of social reward processing.

  6. The mediating role of phosphodiesterase type 4 in the dopaminergic modulation of motor impulsivity.

    PubMed

    Heckman, P R A; Blokland, A; Van Goethem, N P; Van Hagen, B T J; Prickaerts, J

    2018-09-17

    The current study investigated the mediating role of phosphodiesterase type 4 (PDE4) regulated cAMP in the dopaminergic modulation of premature responding (action restraint) in rats. Response inhibition, which includes action restraint, finds its neurobiological origin in cortico-striatal-thalamic circuitry and can be modulated by dopamine. Intracellularly, the effect of dopamine is largely mediated through the cAMP/PKA signaling cascade. Areas in the prefrontal cortex are very sensitive to their neurochemical environment, including catecholamine levels. As a result, we investigated the effects of intracellular modulation of the dopamine cascade by means of PDE4 inhibition by roflumilast on premature responding in a hypo, normal and hyper dopaminergic state of the brain. As a hypo dopaminergic model we induced a 6-OHDA lesion in the (rat) prefrontal cortex, more specifically the infralimbic cortex. For the hyper dopaminergic state we also turned to a well-established model of impaired action restraint, namely the systemic administration of d-amphetamine. In line with the notion of a U-shaped relation between dopamine and impulsive responding, we found that both increasing and decreasing dopamine levels resulted in an increase in premature responding in the choice serial reaction time task (CSRTT). The PDE4 inhibitor roflumilast increased premature responses in combination with d-amphetamine, whereas a decrease in premature responding after roflumilast treatment was found in the 6-OHDA lesioned animals. As a result, it would be interesting to test the effects of PDE4 inhibition in disorders affected by disrupted impulse control related to cortico-striatal-thalamic hypodopaminergia including attention deficit hyperactivity disorder (ADHD). Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Women’s Preference for a Male Acquaintance Enhances Social Reward Processing of Material Goods in the Anterior Cingulate Cortex

    PubMed Central

    Nakagawa, Jun; Takahashi, Muneyoshi; Okada, Rieko; Matsushima, Eisuke; Matsuda, Tetsuya

    2015-01-01

    Men, like the male of many animal species, use gifts to build satisfactory relationships with a desired woman. From the woman’s perspective, all gifts are not always equally rewarding; the reward value of a gift depends on two factors: (1) the giver and (2) the type of the gift (the gift’s social meaning). In this study, we investigated how these two factors interactively determine the reward value of a gift. Specifically, we examined how the neural processing for understanding a gift’s social meaning is modulated by preferences for the giver. We performed a functional magnetic resonance imaging (fMRI) study in which a female participant was asked to judge a gift from a male she was acquainted with in real life. We examined the interactive effects between (1) the female participant’s attitude toward the male acquaintance (liked vs. uninteresting) and (2) the type of the gift (romantic [e.g., bouquet, earrings, and perfumes] vs. non-romantic [e.g., pencils, memo pad, and moneybox]). We found that preference for an acquaintance selectively modulated activity in the anterior cingulate cortex (ACC) in response to romantic gifts, compared to non-romantic gifts. In contrast, if the woman was indifferent toward an acquaintance, no activity modulation was observed in this area for the same gifts. In addition, the ACC showed functional connectivity with the supplementary motor area/dorsal ACC (SMA/dACC), an area within the dorsal mediofrontal cortex, suggesting that it integrates action monitoring and emotional and cognitive processing in decision-making. These results suggest that attitude toward an opposite sex member has a modulatory role in recognizing the social meaning of material goods—preference for the member is a powerful modulator of social reward processing. PMID:26301954

  8. Winning the game: brain processes in expert, young elite and amateur table tennis players.

    PubMed

    Wolf, Sebastian; Brölz, Ellen; Scholz, David; Ramos-Murguialday, Ander; Keune, Philipp M; Hautzinger, Martin; Birbaumer, Niels; Strehl, Ute

    2014-01-01

    (1) compared with amateurs and young elite, expert table tennis players are characterized by enhanced cortical activation in the motor and fronto-parietal cortex during motor imagery in response to table tennis videos; (2) in elite athletes, world rank points are associated with stronger cortical activation. To this aim, electroencephalographic data were recorded in 14 expert, 15 amateur and 15 young elite right-handed table tennis players. All subjects watched videos of a serve and imagined themselves responding with a specific table tennis stroke. With reference to a baseline period, power decrease/increase of the sensorimotor rhythm (SMR) during the pretask- and task period indexed the cortical activation/deactivation (event-related desynchronization/synchronization, ERD/ERS). Regarding hypothesis (1), 8-10 Hz SMR ERD was stronger in elite athletes than in amateurs with an intermediate ERD in young elite athletes in the motor cortex. Regarding hypothesis (2), there was no correlation between ERD/ERS in the motor cortex and world rank points in elite experts, but a weaker ERD in the fronto-parietal cortex was associated with higher world rank points. These results suggest that motor skill in table tennis is associated with focused excitability of the motor cortex during reaction, movement planning and execution with high attentional demands. Among elite experts, less activation of the fronto-parietal attention network may be necessary to become a world champion.

  9. Re-thinking the role of motor cortex: Context-sensitive motor outputs?

    PubMed Central

    Gandolla, Marta; Ferrante, Simona; Molteni, Franco; Guanziroli, Eleonora; Frattini, Tiziano; Martegani, Alberto; Ferrigno, Giancarlo; Friston, Karl; Pedrocchi, Alessandra; Ward, Nick S.

    2014-01-01

    The standard account of motor control considers descending outputs from primary motor cortex (M1) as motor commands and efference copy. This account has been challenged recently by an alternative formulation in terms of active inference: M1 is considered as part of a sensorimotor hierarchy providing top–down proprioceptive predictions. The key difference between these accounts is that predictions are sensitive to the current proprioceptive context, whereas efference copy is not. Using functional electric stimulation to experimentally manipulate proprioception during voluntary movement in healthy human subjects, we assessed the evidence for context sensitive output from M1. Dynamic causal modeling of functional magnetic resonance imaging responses showed that FES altered proprioception increased the influence of M1 on primary somatosensory cortex (S1). These results disambiguate competing accounts of motor control, provide some insight into the synaptic mechanisms of sensory attenuation and may speak to potential mechanisms of action of FES in promoting motor learning in neurorehabilitation. PMID:24440530

  10. Re-thinking the role of motor cortex: context-sensitive motor outputs?

    PubMed

    Gandolla, Marta; Ferrante, Simona; Molteni, Franco; Guanziroli, Eleonora; Frattini, Tiziano; Martegani, Alberto; Ferrigno, Giancarlo; Friston, Karl; Pedrocchi, Alessandra; Ward, Nick S

    2014-05-01

    The standard account of motor control considers descending outputs from primary motor cortex (M1) as motor commands and efference copy. This account has been challenged recently by an alternative formulation in terms of active inference: M1 is considered as part of a sensorimotor hierarchy providing top-down proprioceptive predictions. The key difference between these accounts is that predictions are sensitive to the current proprioceptive context, whereas efference copy is not. Using functional electric stimulation to experimentally manipulate proprioception during voluntary movement in healthy human subjects, we assessed the evidence for context sensitive output from M1. Dynamic causal modeling of functional magnetic resonance imaging responses showed that FES altered proprioception increased the influence of M1 on primary somatosensory cortex (S1). These results disambiguate competing accounts of motor control, provide some insight into the synaptic mechanisms of sensory attenuation and may speak to potential mechanisms of action of FES in promoting motor learning in neurorehabilitation. Copyright © 2014 unknown. Published by Elsevier Inc. All rights reserved.

  11. Motor cortex stimulation does not lead to functional recovery after experimental cortical injury in rats.

    PubMed

    Schönfeld, Lisa-Maria; Jahanshahi, Ali; Lemmens, Evi; Bauwens, Matthias; Hescham, Sarah-Anna; Schipper, Sandra; Lagiere, Melanie; Hendrix, Sven; Temel, Yasin

    2017-01-01

    Motor impairments are among the major complications that develop after cortical damage caused by either stroke or traumatic brain injury. Motor cortex stimulation (MCS) can improve motor functions in animal models of stroke by inducing neuroplasticity. In the current study, the therapeutic effect of chronic MCS was assessed in a rat model of severe cortical damage. A controlled cortical impact (CCI) was applied to the forelimb area of the motor cortex followed by implantation of a flat electrode covering the lesioned area. Forelimb function was assessed using the Montoya staircase test and the cylinder test before and after a period of chronic MCS. Furthermore, the effect of MCS on tissue metabolism and lesion size was measured using [18F]-fluorodesoxyglucose (FDG) μPET scanning. CCI caused a considerable lesion at the level of the motor cortex and dorsal striatum together with a long-lasting behavioral phenotype of forelimb impairment. However, MCS applied to the CCI lesion did not lead to any improvement in limb functioning when compared to non-stimulated control rats. Also, MCS neither changed lesion size nor distribution of FDG. The use of MCS as a standalone treatment did not improve motor impairments in a rat model of severe cortical damage using our specific treatment modalities.

  12. Primary Motor Cortex Involvement in Initial Learning during Visuomotor Adaptation

    ERIC Educational Resources Information Center

    Riek, Stephan; Hinder, Mark R.; Carson, Richard G.

    2012-01-01

    Human motor behaviour is continually modified on the basis of errors between desired and actual movement outcomes. It is emerging that the role played by the primary motor cortex (M1) in this process is contingent upon a variety of factors, including the nature of the task being performed, and the stage of learning. Here we used repetitive TMS to…

  13. Ventral Premotor to Primary Motor Cortical Interactions during Noxious and Naturalistic Action Observation

    ERIC Educational Resources Information Center

    Lago, Angel; Koch, Giacomo; Cheeran, Binith; Marquez, Gonzalo; Sanchez, Jose Andres; Ezquerro, Milagros; Giraldez, Manolo; Fernandez-del-Olmo, Miguel

    2010-01-01

    Within the motor system, cortical areas such as the primary motor cortex (M1) and the ventral premotor cortex (PMv), are thought to be activated during the observation of actions performed by others. However, it is not known how the connections between these areas become active during action observation or whether these connections are modulated…

  14. Activation of the Parieto-Premotor Network Is Associated with Vivid Motor Imagery—A Parametric fMRI Study

    PubMed Central

    Lorey, Britta; Pilgramm, Sebastian; Bischoff, Matthias; Stark, Rudolf; Vaitl, Dieter; Kindermann, Stefan; Munzert, Jörn; Zentgraf, Karen

    2011-01-01

    The present study examined the neural basis of vivid motor imagery with parametrical functional magnetic resonance imaging. 22 participants performed motor imagery (MI) of six different right-hand movements that differed in terms of pointing accuracy needs and object involvement, i.e., either none, two big or two small squares had to be pointed at in alternation either with or without an object grasped with the fingers. After each imagery trial, they rated the perceived vividness of motor imagery on a 7-point scale. Results showed that increased perceived imagery vividness was parametrically associated with increasing neural activation within the left putamen, the left premotor cortex (PMC), the posterior parietal cortex of the left hemisphere, the left primary motor cortex, the left somatosensory cortex, and the left cerebellum. Within the right hemisphere, activation was found within the right cerebellum, the right putamen, and the right PMC. It is concluded that the perceived vividness of MI is parametrically associated with neural activity within sensorimotor areas. The results corroborate the hypothesis that MI is an outcome of neural computations based on movement representations located within motor areas. PMID:21655298

  15. Behavioural exposure and sleep do not modify corticospinal and intracortical excitability in the human motor system.

    PubMed

    Doeltgen, Sebastian H; Ridding, Michael C

    2010-03-01

    Behavioural exposure and sleep may bidirectionally modify the excitability of cortical networks including those in the motor cortex. Here we tested whether the excitability of intracortical inhibitory and excitatory networks within the primary motor cortex exhibited changes suggestive of a time of day influence. Short-interval intracortical inhibition (SICI) and facilitation (ICF), and input-output curves (IO curves) were investigated using transcranial magnetic stimulation (TMS). Recordings were made from the resting right first dorsal interosseous (FDI) muscle in 10 healthy subjects on three occasions: 9A.M. and 4P.M. of the same day, and 9A.M. of the following day. There was no significant change in any of the measures across the three assessments. These findings provide evidence that time of day does not significantly influence corticospinal and intracortical excitability in the primary motor cortex. These results provide no support for the hypothesis that synapses within the motor cortex undergo potentiation due to daytime use and behavioural experiences. Additionally, these findings provide evidence that measurement of motor cortical excitability is not systematically biased by time-of-day dependent variability and thus does not pose a confound in studies assessing corticospinal excitability longitudinally.

  16. Laterality and the evolution of the prefronto-cerebellar system in anthropoids.

    PubMed

    Smaers, Jeroen B; Steele, James; Case, Charleen R; Amunts, Katrin

    2013-06-01

    There is extensive evidence for an early vertebrate origin of lateralized motor behavior and of related asymmetries in underlying brain systems. We investigate human lateralized motor functioning in a broad comparative context of evolutionary neural reorganization. We quantify evolutionary trends in the fronto-cerebellar system (involved in motor learning) across 46 million years of divergent primate evolution by comparing rates of evolution of prefrontal cortex, frontal motor cortex, and posterior cerebellar hemispheres along individual branches of the primate tree of life. We provide a detailed evolutionary model of the neuroanatomical changes leading to modern human lateralized motor functioning, demonstrating an increased role for the fronto-cerebellar system in the apes dating to their evolutionary divergence from the monkeys (∼30 million years ago (Mya)), and a subsequent shift toward an increased role for prefrontal cortex over frontal motor cortex in the fronto-cerebellar system in the Homo-Pan ancestral lineage (∼10 Mya) and in the human ancestral lineage (∼6 Mya). We discuss these results in the context of cortico-cerebellar functions and their likely role in the evolution of human tool use and speech. © 2013 New York Academy of Sciences.

  17. Right vs. left sensorimotor cortex suction-ablation in the rat: no difference in beam-walking recovery.

    PubMed

    Goldstein, L B

    1995-03-13

    The ability of rats to traverse a narrow elevated beam has been used to quantitate recovery of hindlimb motor function after unilateral injury to the sensorimotor cortex. We tested the hypothesis that the rate of spontaneous beam-walking recovery varies with the side of the cortex lesion. Groups of rats that were trained at the beam-walking task underwent suction-ablation of either the right or left hindlimb sensorimotor cortex. There was no difference in hindlimb motor function between the groups on the first post-operative beam-waking trial carried out the day after cortex ablation and no difference between the groups in overall recovery rates over the next two weeks. Subsequent analyses of lesion surface parameters showed no differences in lesion size or extent. Regardless of the side of the lesion, there were also no differences between the right and left hemispheres in norepinephrine content of the lesioned or contralateral cortex. We conclude that the side of sensorimotor cortex ablation injury does not differentially affect the rate of spontaneous motor recovery as measured with the beam-walking task.

  18. The Influence of rTMS over Prefrontal and Motor Areas in a Morphological Task: Grammatical vs. Semantic Effects

    ERIC Educational Resources Information Center

    LoGerfo, Emanuele; Oliveri, Massimiliano; Torriero, Sara; Salerno, Silvia; Koch, Giacomo; Caltagirone, Carlo

    2008-01-01

    We investigated the differential role of two frontal regions in the processing of grammatical and semantic knowledge. Given the documented specificity of the prefrontal cortex for the grammatical class of verbs, and of the primary motor cortex for the semantic class of action words, we sought to investigate whether the prefrontal cortex is also…

  19. Normalization of sensorimotor integration by repetitive transcranial magnetic stimulation in cervical dystonia.

    PubMed

    Zittel, S; Helmich, R C; Demiralay, C; Münchau, A; Bäumer, T

    2015-08-01

    Previous studies indicated that sensorimotor integration and plasticity of the sensorimotor system are impaired in dystonia patients. We investigated motor evoked potential amplitudes and short latency afferent inhibition to examine corticospinal excitability and cortical sensorimotor integration, before and after inhibitory 1 Hz repetitive transcranial magnetic stimulation over primary sensory and primary motor cortex in patients with cervical dystonia (n = 12). Motor evoked potentials were recorded from the right first dorsal interosseous muscle after application of unconditioned transcranial magnetic test stimuli and after previous conditioning electrical stimulation of the right index finger at short interstimulus intervals of 25, 30 and 40 ms. Results were compared to a group of healthy age-matched controls. At baseline, motor evoked potential amplitudes did not differ between groups. Short latency afferent inhibition was reduced in cervical dystonia patients compared to healthy controls. Inhibitory 1 Hz sensory cortex repetitive transcranial magnetic stimulation but not motor cortex repetitive transcranial magnetic stimulation increased motor evoked potential amplitudes in cervical dystonia patients. Additionally, both 1 Hz repetitive transcranial magnetic stimulation over primary sensory and primary motor cortex normalized short latency afferent inhibition in these patients. In healthy subjects, sensory repetitive transcranial magnetic stimulation had no influence on motor evoked potential amplitudes and short latency afferent inhibition. Plasticity of sensorimotor circuits is altered in cervical dystonia patients.

  20. Choice reaching with a LEGO arm robot (CoRLEGO): The motor system guides visual attention to movement-relevant information.

    PubMed

    Strauss, Soeren; Woodgate, Philip J W; Sami, Saber A; Heinke, Dietmar

    2015-12-01

    We present an extension of a neurobiologically inspired robotics model, termed CoRLEGO (Choice reaching with a LEGO arm robot). CoRLEGO models experimental evidence from choice reaching tasks (CRT). In a CRT participants are asked to rapidly reach and touch an item presented on the screen. These experiments show that non-target items can divert the reaching movement away from the ideal trajectory to the target item. This is seen as evidence attentional selection of reaching targets can leak into the motor system. Using competitive target selection and topological representations of motor parameters (dynamic neural fields) CoRLEGO is able to mimic this leakage effect. Furthermore if the reaching target is determined by its colour oddity (i.e. a green square among red squares or vice versa), the reaching trajectories become straighter with repetitions of the target colour (colour streaks). This colour priming effect can also be modelled with CoRLEGO. The paper also presents an extension of CoRLEGO. This extension mimics findings that transcranial direct current stimulation (tDCS) over the motor cortex modulates the colour priming effect (Woodgate et al., 2015). The results with the new CoRLEGO suggest that feedback connections from the motor system to the brain's attentional system (parietal cortex) guide visual attention to extract movement-relevant information (i.e. colour) from visual stimuli. This paper adds to growing evidence that there is a close interaction between the motor system and the attention system. This evidence contradicts the traditional conceptualization of the motor system as the endpoint of a serial chain of processing stages. At the end of the paper we discuss CoRLEGO's predictions and also lessons for neurobiologically inspired robotics emerging from this work. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  1. Intracortical inhibition in the human trigeminal motor system.

    PubMed

    Jaberzadeh, Shapour; Pearce, Sophie L; Miles, Timothy S; Türker, Kemal S; Nordstrom, Michael A

    2007-08-01

    To investigate the presence and features of short-interval intracortical inhibition (SICI) in the human trigeminal motor system. Surface electromyogram (EMG) was recorded from left and right digastric muscles in 7 subjects, along with additional experiments with intramuscular EMG in 2 subjects. Focal transcranial magnetic stimulation (TMS) was used to activate the motor cortex of one hemisphere and elicit motor evoked potentials (MEPs) in digastric muscles on each side, at rest and while subjects activated the muscles at 10% maximal EMG. Paired or single TMS pulses were delivered in blocks of trials, while conditioning TMS intensity and interstimulus interval (ISI) were varied. At rest, paired TMS (3-ms ISI) with conditioning intensities 0.8-0.9x active motor threshold (TA) reduced the digastric MEP amplitude to a similar extent bilaterally. Conditioning at 0.5-0.7TA did not significantly reduce the MEP. MEP amplitude was reduced to a similar extent in both digastric muscles by ISIs between 1 and 4 ms (0.8TA). Voluntary bilateral activation of digastric muscles reduced the effectiveness of conditioning TMS compared to the resting state, with no differences between sides. The similarity of the responses in both digastric muscles was not due to EMG cross-talk (estimated to be approximately 10% in surface records and approximately 2% in intramuscular records), as the intramuscular records showed the same pattern as the surface records. The effects of paired-pulse TMS on digastric are similar to those reported for contralateral hand muscles, and are consistent with activation of SICI circuits in M1 by conditioning TMS. Our evidence further suggests that the corticomotor representations of left and right digastric muscles in M1 of a single hemisphere receive analogous inhibitory modulation from SICI circuits. SICI has been demonstrated in the face area of motor cortex controlling the trigeminal motor system in normal subjects. This method can be used to investigate abnormalities of SICI in movement disorders affecting the masticatory muscles in humans.

  2. Transcranial direct current stimulation (tDCS) of the primary motor cortex and robot-assisted arm training in chronic incomplete cervical spinal cord injury: A proof of concept sham-randomized clinical study.

    PubMed

    Yozbatiran, Nuray; Keser, Zafer; Davis, Matthew; Stampas, Argyrios; O'Malley, Marcia K; Cooper-Hay, Catherine; Frontera, Joel; Fregni, Felipe; Francisco, Gerard E

    2016-07-15

    After cervical spinal cord injury, current options for treatment of upper extremity motor functions have been limited to traditional approaches. However, there is a substantial need to explore more rigorous alternative treatments to facilitate motor recovery. To demonstrate whether anodal-primary motor cortex (M1) excitability enhancement (with cathodal-supra orbital area) (atDCS) combined with robot-assisted arm training (R-AAT) will provide greater improvement in contralateral arm and hand motor functions compared to sham stimulation (stDCS) and R-AAT in patients with chronic, incomplete cervical spinal cord injury (iCSCI). In this parallel-group, double-blinded, randomized and sham-controlled trial, nine participants with chronic iCSCI (AIS C and D level) were randomized to receive 10 sessions of atDCS or stDSC combined with R-AAT. Feasibility and tolerability was assessed with attrition rate and occurrence of adverse events, Changes in arm and hand function were assessed with Jebson Taylor Hand Function Test (JTHFT). Amount of Use Scale of Motor Activity Log (AOU-MAL), American Spinal Injury Association Upper Extremity Motor Score and Modified Ashworth Scale (MAS) at baseline, after treatment, and at two-month follow-up. None of the participants missed a treatment session or dropped-out due to adverse events related to the treatment protocol. Participants tended to perform better in JTHFT and AOU-MAL after treatment. Active group at post-treatment and two-month follow-up demonstrated better arm and hand performance compared to sham group. These preliminary findings support that modulating excitatory input of the corticospinal tracts on spinal circuits may be a promising strategy in improving arm and hand functions in persons with incomplete tetraplegia. Further study is needed to explore the underlying mechanisms of recovery.

  3. Extent and Location of the Excitatory and Inhibitory Cortical Hand Representation Maps: A Navigated Transcranial Magnetic Stimulation Study.

    PubMed

    Pitkänen, Minna; Kallioniemi, Elisa; Julkunen, Petro

    2015-09-01

    Voluntary muscle action and control are modulated by the primary motor cortex, which is characterized by a well-defined somatotopy. Muscle action and control depend on a sensitive balance between excitatory and inhibitory mechanisms in the cortex and in the corticospinal tract. The cortical locations evoking excitatory and inhibitory responses in brain stimulation can be mapped, for example, as a pre-surgical procedure. The purpose of this study was to find the differences between excitatory and inhibitory motor representations mapped using navigated transcranial magnetic stimulation (nTMS). The representations of small hand muscles were mapped to determine the areas and the center of gravities (CoGs) in both hemispheres of healthy right-handed volunteers. The excitatory representations were obtained via resting motor evoked potential (MEP) mapping, with and without a stimulation grid. The inhibitory representations were mapped using the grid and measuring corticospinal silent periods (SPs) during voluntary muscle contraction. The excitatory representations were larger on the dominant hemisphere compared with the non-dominant (p < 0.05). The excitatory CoGs were more medial (p < 0.001) and anterior (p < 0.001) than the inhibitory CoGs. The use of the grid did not influence the areas or the CoGs. The results support the common hypothesis that the MEP and SP representations are located at adjacent sites. Furthermore, the dominant hemisphere seems to be better organized for controlling excitatory motor functions with respect to TMS. In addition, the inhibitory representations could provide further information about motor reorganization and aid in surgery planning when the functional cortical representations are located in abnormal cortical regions.

  4. The dissociation between command following and communication in disorders of consciousness: an fMRI study in healthy subjects.

    PubMed

    Osborne, Natalie R; Owen, Adrian M; Fernández-Espejo, Davinia

    2015-01-01

    Neuroimaging studies have identified a subgroup of patients with a Disorder of Consciousness (DOC) who, while being behaviorally non-responsive, are nevertheless able to follow commands by modulating their brain activity in motor imagery (MI) tasks. These techniques have even allowed for binary communication in a small number of DOC patients. However, the majority of patients who can follow commands are unable to use their responses to communicate. A similar dissociation between present command following (CF) and absent communication abilities has been reported in overt behavioral assessments. However, the neural correlates of this dissociation in both overt and covert modalities are unknown. Here, we used functional magnetic resonance imaging (fMRI) to explore the neural mechanisms underlying CF and selection of responses for binary communication using either executed or imagined movements. Fifteen healthy participants executed or imagined two different types of arm movements that were either pre-determined by the experimenters (CF) or decided by them (action selection, AS). Action selection involved greater activity in high-level associative areas in frontal and parietal regions than CF. Additionally, motor execution (ME), as compared to MI, activated contralateral motor cortex, while the opposite contrast revealed activation in the ipsilateral sensorimotor cortex and the left inferior frontal gyrus. Importantly, there was no interaction between the task (CF/AS) and modality (MI/ME). Our results suggest that the neural processes involved in following a motor command or selecting between two motor actions are not dependent on how the response is expressed (via ME/MI). They also suggest a potential neural basis for the distinction in cognitive abilities seen in DOC patients.

  5. Dual-hemisphere transcranial direct current stimulation over primary motor cortex enhances consolidation of a ballistic thumb movement.

    PubMed

    Koyama, Soichiro; Tanaka, Satoshi; Tanabe, Shigeo; Sadato, Norihiro

    2015-02-19

    Transcranial direct current stimulation (tDCS) is a noninvasive technique that modulates motor performance and learning. Previous studies have shown that tDCS over the primary motor cortex (M1) can facilitate consolidation of various motor skills. However, the effect of tDCS on consolidation of newly learned ballistic movements remains unknown. The present study tested the hypothesis that tDCS over M1 enhances consolidation of ballistic thumb movements in healthy adults. Twenty-eight healthy subjects participated in an experiment with a single-blind, sham-controlled, between-group design. Fourteen subjects practiced a ballistic movement with their left thumb during dual-hemisphere tDCS. Subjects received 1mA anodal tDCS over the contralateral M1 and 1mA cathodal tDCS over the ipsilateral M1 for 25min during the training session. The remaining 14 subjects underwent identical training sessions, except that dual-hemisphere tDCS was applied for only the first 15s (sham group). All subjects performed the task again at 1h and 24h later. Primary measurements examined improvement in peak acceleration of the ballistic thumb movement at 1h and 24h after stimulation. Improved peak acceleration was significantly greater in the tDCS group (144.2±15.1%) than in the sham group (98.7±9.1%) (P<0.05) at 24h, but not 1h, after stimulation. Thus, dual-hemisphere tDCS over M1 enhanced consolidation of ballistic thumb movement in healthy adults. Dual-hemisphere tDCS over M1 may be useful to improve elemental motor behaviors, such as ballistic movements, in patients with subcortical strokes. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  6. The dissociation between command following and communication in disorders of consciousness: an fMRI study in healthy subjects

    PubMed Central

    Osborne, Natalie R.; Owen, Adrian M.; Fernández-Espejo, Davinia

    2015-01-01

    Neuroimaging studies have identified a subgroup of patients with a Disorder of Consciousness (DOC) who, while being behaviorally non-responsive, are nevertheless able to follow commands by modulating their brain activity in motor imagery (MI) tasks. These techniques have even allowed for binary communication in a small number of DOC patients. However, the majority of patients who can follow commands are unable to use their responses to communicate. A similar dissociation between present command following (CF) and absent communication abilities has been reported in overt behavioral assessments. However, the neural correlates of this dissociation in both overt and covert modalities are unknown. Here, we used functional magnetic resonance imaging (fMRI) to explore the neural mechanisms underlying CF and selection of responses for binary communication using either executed or imagined movements. Fifteen healthy participants executed or imagined two different types of arm movements that were either pre-determined by the experimenters (CF) or decided by them (action selection, AS). Action selection involved greater activity in high-level associative areas in frontal and parietal regions than CF. Additionally, motor execution (ME), as compared to MI, activated contralateral motor cortex, while the opposite contrast revealed activation in the ipsilateral sensorimotor cortex and the left inferior frontal gyrus. Importantly, there was no interaction between the task (CF/AS) and modality (MI/ME). Our results suggest that the neural processes involved in following a motor command or selecting between two motor actions are not dependent on how the response is expressed (via ME/MI). They also suggest a potential neural basis for the distinction in cognitive abilities seen in DOC patients. PMID:26441593

  7. Paradigm Shifts in Voluntary Force Control and Motor Unit Behaviors with the Manipulated Size of Visual Error Perception

    PubMed Central

    Chen, Yi-Ching; Lin, Yen-Ting; Chang, Gwo-Ching; Hwang, Ing-Shiou

    2017-01-01

    The detection of error information is an essential prerequisite of a feedback-based movement. This study investigated the differential behavior and neurophysiological mechanisms of a cyclic force-tracking task using error-reducing and error-enhancing feedback. The discharge patterns of a relatively large number of motor units (MUs) were assessed with custom-designed multi-channel surface electromyography following mathematical decomposition of the experimentally-measured signals. Force characteristics, force-discharge relation, and phase-locking cortical activities in the contralateral motor cortex to individual MUs were contrasted among the low (LSF), normal (NSF), and high scaling factor (HSF) conditions, in which the sizes of online execution errors were displayed with various amplification ratios. Along with a spectral shift of the force output toward a lower band, force output with a more phase-lead became less irregular, and tracking accuracy was worse in the LSF condition than in the HSF condition. The coherent discharge of high phasic (HP) MUs with the target signal was greater, and inter-spike intervals were larger, in the LSF condition than in the HSF condition. Force-tracking in the LSF condition manifested with stronger phase-locked EEG activity in the contralateral motor cortex to discharge of the (HP) MUs (LSF > NSF, HSF). The coherent discharge of the (HP) MUs during the cyclic force-tracking predominated the force-discharge relation, which increased inversely to the error scaling factor. In conclusion, the size of visualized error gates motor unit discharge, force-discharge relation, and the relative influences of the feedback and feedforward processes on force control. A smaller visualized error size favors voluntary force control using a feedforward process, in relation to a selective central modulation that enhance the coherent discharge of (HP) MUs. PMID:28348530

  8. Paradigm Shifts in Voluntary Force Control and Motor Unit Behaviors with the Manipulated Size of Visual Error Perception.

    PubMed

    Chen, Yi-Ching; Lin, Yen-Ting; Chang, Gwo-Ching; Hwang, Ing-Shiou

    2017-01-01

    The detection of error information is an essential prerequisite of a feedback-based movement. This study investigated the differential behavior and neurophysiological mechanisms of a cyclic force-tracking task using error-reducing and error-enhancing feedback. The discharge patterns of a relatively large number of motor units (MUs) were assessed with custom-designed multi-channel surface electromyography following mathematical decomposition of the experimentally-measured signals. Force characteristics, force-discharge relation, and phase-locking cortical activities in the contralateral motor cortex to individual MUs were contrasted among the low (LSF), normal (NSF), and high scaling factor (HSF) conditions, in which the sizes of online execution errors were displayed with various amplification ratios. Along with a spectral shift of the force output toward a lower band, force output with a more phase-lead became less irregular, and tracking accuracy was worse in the LSF condition than in the HSF condition. The coherent discharge of high phasic (HP) MUs with the target signal was greater, and inter-spike intervals were larger, in the LSF condition than in the HSF condition. Force-tracking in the LSF condition manifested with stronger phase-locked EEG activity in the contralateral motor cortex to discharge of the (HP) MUs (LSF > NSF, HSF). The coherent discharge of the (HP) MUs during the cyclic force-tracking predominated the force-discharge relation, which increased inversely to the error scaling factor. In conclusion, the size of visualized error gates motor unit discharge, force-discharge relation, and the relative influences of the feedback and feedforward processes on force control. A smaller visualized error size favors voluntary force control using a feedforward process, in relation to a selective central modulation that enhance the coherent discharge of (HP) MUs.

  9. It's how you get there: walking down a virtual alley activates premotor and parietal areas.

    PubMed

    Wagner, Johanna; Solis-Escalante, Teodoro; Scherer, Reinhold; Neuper, Christa; Müller-Putz, Gernot

    2014-01-01

    Voluntary drive is crucial for motor learning, therefore we are interested in the role that motor planning plays in gait movements. In this study we examined the impact of an interactive Virtual Environment (VE) feedback task on the EEG patterns during robot assisted walking. We compared walking in the VE modality to two control conditions: walking with a visual attention paradigm, in which visual stimuli were unrelated to the motor task; and walking with mirror feedback, in which participants observed their own movements. Eleven healthy participants were considered. Application of independent component analysis to the EEG revealed three independent component clusters in premotor and parietal areas showing increased activity during walking with the adaptive VE training paradigm compared to the control conditions. During the interactive VE walking task spectral power in frequency ranges 8-12, 15-20, and 23-40 Hz was significantly (p ≤ 0.05) decreased. This power decrease is interpreted as a correlate of an active cortical area. Furthermore activity in the premotor cortex revealed gait cycle related modulations significantly different (p ≤ 0.05) from baseline in the frequency range 23-40 Hz during walking. These modulations were significantly (p ≤ 0.05) reduced depending on gait cycle phases in the interactive VE walking task compared to the control conditions. We demonstrate that premotor and parietal areas show increased activity during walking with the adaptive VE training paradigm, when compared to walking with mirror- and movement unrelated feedback. Previous research has related a premotor-parietal network to motor planning and motor intention. We argue that movement related interactive feedback enhances motor planning and motor intention. We hypothesize that this might improve gait recovery during rehabilitation.

  10. Brain network dysfunction in youth with obsessive-compulsive disorder induced by simple uni-manual behavior: The role of the dorsal anterior cingulate cortex

    PubMed Central

    Friedman, Amy L.; Burgess, Ashley; Ramaseshan, Karthik; Easter, Phil; Khatib, Dalal; Chowdury, Asadur; Arnold, Paul D.; Hanna, Gregory L.; Rosenberg, David R.; Diwadkar, Vaibhav A.

    2017-01-01

    In an effort to elucidate differences in functioning brain networks between youth with obsessive-compulsive disorder and controls, we used fMRI signals to analyze brain network interactions of the dorsal anterior cingulate cortex (dACC) during visually coordinated motor responses. Subjects made a uni-manual response to briefly presented probes, at periodic (allowing participants to maintain a “motor set”) or random intervals (demanding reactive responses). Network interactions were assessed using psycho-physiological interaction (PPI), a basic model of functional connectivity evaluating modulatory effects of the dACC in the context of each task condition. Across conditions, OCD were characterized by hyper-modulation by the dACC, with loci alternatively observed as both condition-general and condition-specific. Thus, dynamically driven task demands during simple uni-manual motor control induce compensatory network interactions in cortical-thalamic regions in OCD. These findings support previous research in OCD showing compensatory network interactions during complex memory tasks, but establish that these network effects are observed during basic sensorimotor processing. Thus, these patterns of network dysfunction may in fact be independent of the complexity of tasks used to induce brain network activity. Hypothesis-driven approaches coupled with sophisticated network analyses are a highly valuable approach in using fMRI to uncover mechanisms in disorders like OCD. PMID:27992792

  11. Effects of theta burst stimulation on motor cortex excitability in Parkinson's disease.

    PubMed

    Zamir, Orit; Gunraj, Carolyn; Ni, Zhen; Mazzella, Filomena; Chen, Robert

    2012-04-01

    Long-term potentiation (LTP)-like plasticity induced by paired associative stimulation (PAS) is impaired in Parkinson's disease (PD). Intermittent theta burst stimulation (iTBS) is another rTMS protocol that produces LTP-like effects and increases cortical excitability but its effects are independent of afferent input. The aim of the present study was to examine the effects of iTBS on cortical excitability in PD. iTBS was applied to the motor cortex in 10 healthy subjects and 12 PD patients ON and OFF dopaminergic medications. Motor evoked potential (MEP) before and for 60 min after iTBS were used to examine the changes in cortical excitability induced by iTBS. Paired-pulse TMS was used to test whether intracortical circuits, including short interval intracortical inhibition, intracortical facilitation, short and long latency afferent inhibition, were modulated by iTBS. After iTBS, the control, PD ON and OFF groups had similar increases in MEP amplitude compared to baseline over the course of 60 min. Changes in intracortical circuits induced by iTBS were also similar for the different groups. iTBS produced similar effects on cortical excitability for PD patients and controls. Spike-timing dependent heterosynaptic LTP-like plasticity induced by PAS may be more impaired in PD than frequency dependent homosynaptic LTP-like plasticity induced by iTBS. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  12. Optogenetic stimulation of cortex to map evoked whisker movements in awake head-restrained mice.

    PubMed

    Auffret, Matthieu; Ravano, Veronica L; Rossi, Giulia M C; Hankov, Nicolas; Petersen, Merissa F A; Petersen, Carl C H

    2018-01-01

    Whisker movements are used by rodents to touch objects in order to extract spatial and textural tactile information about their immediate surroundings. To understand the mechanisms of such active sensorimotor processing it is important to investigate whisker motor control. The activity of neurons in the neocortex affects whisker movements, but many aspects of the organization of cortical whisker motor control remain unknown. Here, we filmed whisker movements evoked by sequential optogenetic stimulation of different locations across the left dorsal sensorimotor cortex of awake head-restrained mice. Whisker movements were evoked by optogenetic stimulation of many regions in the dorsal sensorimotor cortex. Optogenetic stimulation of whisker sensory barrel cortex evoked retraction of the contralateral whisker after a short latency, and a delayed rhythmic protraction of the ipsilateral whisker. Optogenetic stimulation of frontal cortex evoked rhythmic bilateral whisker protraction with a longer latency compared to stimulation of sensory cortex. Compared to frontal cortex stimulation, larger amplitude bilateral rhythmic whisking in a less protracted position was evoked at a similar latency by stimulating a cortical region posterior to Bregma and close to the midline. These data suggest that whisker motor control might be broadly distributed across the dorsal mouse sensorimotor cortex. Future experiments must investigate the complex neuronal circuits connecting specific cell-types in various cortical regions with the whisker motor neurons located in the facial nucleus. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  13. Motor Cortex Activity During Functional Motor Skills: An fNIRS Study.

    PubMed

    Nishiyori, Ryota; Bisconti, Silvia; Ulrich, Beverly

    2016-01-01

    Assessments of brain activity during motor task performance have been limited to fine motor movements due to technological constraints presented by traditional neuroimaging techniques, such as functional magnetic resonance imaging. Functional near-infrared spectroscopy (fNIRS) offers a promising method by which to overcome these constraints and investigate motor performance of functional motor tasks. The current study used fNIRS to quantify hemodynamic responses within the primary motor cortex in twelve healthy adults as they performed unimanual right, unimanual left, and bimanual reaching, and stepping in place. Results revealed that during both unimanual reaching tasks, the contralateral hemisphere showed significant activation in channels located approximately 3 cm medial to the C3 (for right-hand reach) and C4 (for left-hand reach) landmarks. Bimanual reaching and stepping showed activation in similar channels, which were located bilaterally across the primary motor cortex. The medial channels, surrounding Cz, showed significantly higher activations during stepping when compared to bimanual reaching. Our results extend the viability of fNIRS to study motor function and build a foundation for future investigation of motor development in infants during nascent functional behaviors and monitor how they may change with age or practice.

  14. Increased sensorimotor network activity in DYT1 dystonia: a functional imaging study

    PubMed Central

    Argyelan, Miklos; Habeck, Christian; Ghilardi, M. Felice; Fitzpatrick, Toni; Dhawan, Vijay; Pourfar, Michael; Bressman, Susan B.; Eidelberg, David

    2010-01-01

    Neurophysiological studies have provided evidence of primary motor cortex hyperexcitability in primary dystonia, but several functional imaging studies suggest otherwise. To address this issue, we measured sensorimotor activation at both the regional and network levels in carriers of the DYT1 dystonia mutation and in control subjects. We used 15Oxygen-labelled water and positron emission tomography to scan nine manifesting DYT1 carriers, 10 non-manifesting DYT1 carriers and 12 age-matched controls while they performed a kinematically controlled motor task; they were also scanned in a non-motor audio-visual control condition. Within- and between-group contrasts were analysed with statistical parametric mapping. For network analysis, we first identified a normal motor-related activation pattern in a set of 39 motor and audio-visual scans acquired in an independent cohort of 18 healthy volunteer subjects. The expression of this pattern was prospectively quantified in the motor and control scans acquired in each of the gene carriers and controls. Network values for the three groups were compared with ANOVA and post hoc contrasts. Voxel-wise comparison of DYT1 carriers and controls revealed abnormally increased motor activation responses in the former group (P < 0.05, corrected; statistical parametric mapping), localized to the sensorimotor cortex, dorsal premotor cortex, supplementary motor area and the inferior parietal cortex. Network analysis of the normative derivation cohort revealed a significant normal motor-related activation pattern topography (P < 0.0001) characterized by covarying neural activity in the sensorimotor cortex, dorsal premotor cortex, supplementary motor area and cerebellum. In the study cohort, normal motor-related activation pattern expression measured during movement was abnormally elevated in the manifesting gene carriers (P < 0.001) but not in their non-manifesting counterparts. In contrast, in the non-motor control condition, abnormal increases in network activity were present in both groups of gene carriers (P < 0.001). In this condition, normal motor-related activation pattern expression in non-manifesting carriers was greater than in controls, but lower than in affected carriers. In the latter group, measures of normal motor-related activation pattern expression in the audio-visual condition correlated with independent dystonia clinical ratings (r = 0.70, P = 0.04). These findings confirm that overexcitability of the sensorimotor system is a robust feature of dystonia. The presence of elevated normal motor-related activation pattern expression in the non-motor condition suggests that abnormal integration of audio-visual input with sensorimotor network activity is an important trait feature of this disorder. Lastly, quantification of normal motor-related activation pattern expression in individual cases may have utility as an objective descriptor of therapeutic response in trials of new treatments for dystonia and related disorders. PMID:20207699

  15. [Facial nerve injuries cause changes in central nervous system microglial cells].

    PubMed

    Cerón, Jeimmy; Troncoso, Julieta

    2016-12-01

    Our research group has described both morphological and electrophysiological changes in motor cortex pyramidal neurons associated with contralateral facial nerve injury in rats. However, little is known about those neural changes, which occur together with changes in surrounding glial cells. To characterize the effect of the unilateral facial nerve injury on microglial proliferation and activation in the primary motor cortex. We performed immunohistochemical experiments in order to detect microglial cells in brain tissue of rats with unilateral facial nerve lesion sacrificed at different times after the injury. We caused two types of lesions: reversible (by crushing, which allows functional recovery), and irreversible (by section, which produces permanent paralysis). We compared the brain tissues of control animals (without surgical intervention) and sham-operated animals with animals with lesions sacrificed at 1, 3, 7, 21 or 35 days after the injury. In primary motor cortex, the microglial cells of irreversibly injured animals showed proliferation and activation between three and seven days post-lesion. The proliferation of microglial cells in reversibly injured animals was significant only three days after the lesion. Facial nerve injury causes changes in microglial cells in the primary motor cortex. These modifications could be involved in the generation of morphological and electrophysiological changes previously described in the pyramidal neurons of primary motor cortex that command facial movements.

  16. Attention to Automatic Movements in Parkinson's Disease: Modified Automatic Mode in the Striatum

    PubMed Central

    Wu, Tao; Liu, Jun; Zhang, Hejia; Hallett, Mark; Zheng, Zheng; Chan, Piu

    2015-01-01

    We investigated neural correlates when attending to a movement that could be made automatically in healthy subjects and Parkinson's disease (PD) patients. Subjects practiced a visuomotor association task until they could perform it automatically, and then directed their attention back to the automated task. Functional MRI was obtained during the early-learning, automatic stage, and when re-attending. In controls, attention to automatic movement induced more activation in the dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex, and rostral supplementary motor area. The motor cortex received more influence from the cortical motor association regions. In contrast, the pattern of the activity and connectivity of the striatum remained at the level of the automatic stage. In PD patients, attention enhanced activity in the DLPFC, premotor cortex, and cerebellum, but the connectivity from the putamen to the motor cortex decreased. Our findings demonstrate that, in controls, when a movement achieves the automatic stage, attention can influence the attentional networks and cortical motor association areas, but has no apparent effect on the striatum. In PD patients, attention induces a shift from the automatic mode back to the controlled pattern within the striatum. The shifting between controlled and automatic behaviors relies in part on striatal function. PMID:24925772

  17. Progressive motor cortex functional reorganization following 6-hydroxydopamine lesioning in rats.

    PubMed

    Viaro, Riccardo; Morari, Michele; Franchi, Gianfranco

    2011-03-23

    Many studies have attempted to correlate changes of motor cortex activity with progression of Parkinson's disease, although results have been controversial. In the present study we used intracortical microstimulation (ICMS) combined with behavioral testing in 6-hydroxydopamine hemilesioned rats to evaluate the impact of dopamine depletion on movement representations in primary motor cortex (M1) and motor behavior. ICMS allows for motor-effective stimulation of corticofugal neurons in motor areas so as to obtain topographic movements representations based on movement type, area size, and threshold currents. Rats received unilateral 6-hydroxydopamine in the nigrostriatal bundle, causing motor impairment. Changes in M1 were time dependent and bilateral, although stronger in the lesioned than the intact hemisphere. Representation size and threshold current were maximally impaired at 15 d, although inhibition was still detectable at 60-120 d after lesion. Proximal forelimb movements emerged at the expense of the distal ones. Movement lateralization was lost mainly at 30 d after lesion. Systemic L-3,4-dihydroxyphenylalanine partially attenuated motor impairment and cortical changes, particularly in the caudal forelimb area, and completely rescued distal forelimb movements. Local application of the GABA(A) antagonist bicuculline partially restored cortical changes, particularly in the rostral forelimb area. The local anesthetic lidocaine injected into the M1 of the intact hemisphere restored movement lateralization in the lesioned hemisphere. This study provides evidence for motor cortex remodeling after unilateral dopamine denervation, suggesting that cortical changes were associated with dopamine denervation, pathogenic intracortical GABA inhibition, and altered interhemispheric activity.

  18. Combined motor point associative stimulation (MPAS) and transcranial direct current stimulation (tDCS) improves plateaued manual dexterity performance.

    PubMed

    Hoseini, Najmeh; Munoz-Rubke, Felipe; Wan, Hsuan-Yu; Block, Hannah J

    2016-10-28

    Motor point associative stimulation (MPAS) in hand muscles is known to modify motor cortex excitability and improve learning rate, but not plateau of performance, in manual dexterity tasks. Central stimulation of motor cortex, such as transcranial direct current stimulation (tDCS), can have similar effects if accompanied by motor practice, which can be difficult and tiring for patients. Here we asked whether adding tDCS to MPAS could improve manual dexterity in healthy individuals who are already performing at their plateau, with no motor practice during stimulation. We hypothesized that MPAS could provide enough coordinated muscle activity to make motor practice unnecessary, and that this combination of stimulation techniques could yield improvements even in subjects at or near their peak. If so, this approach could have a substantial effect on patients with impaired dexterity, who are far from their peak. MPAS was applied for 30min to two right hand muscles important for manual dexterity. tDCS was simultaneously applied over left sensorimotor cortex. The motor cortex input/output (I/O) curve was assessed with transcranial magnetic stimulation (TMS), and manual dexterity was assessed with the Purdue Pegboard Test. Compared to sham or cathodal tDCS combined with MPAS, anodal tDCS combined with MPAS significantly increased the plateau of manual dexterity. This result suggests that MPAS has the potential to substitute for motor practice in mediating a beneficial effect of tDCS on manual dexterity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Low signal intensity in motor cortex on susceptibility-weighted MR imaging is correlated with clinical signs of amyotrophic lateral sclerosis: a pilot study.

    PubMed

    Endo, Hironobu; Sekiguchi, Kenji; Shimada, Hitoshi; Ueda, Takehiro; Kowa, Hisatomo; Kanda, Fumio; Toda, Tatsushi

    2018-03-01

    There is no reliable objective indicator for upper motor neuron dysfunction in amyotrophic lateral sclerosis (ALS). To determine the clinical significance and potential utility of magnetic resonance (MR) signals, we investigated the relationship between clinical symptoms and susceptibility changes in the motor cortex measured using susceptibility-weighted MR imaging taken by readily available 3-T MRI in clinical practice. Twenty-four ALS patients and 14 control subjects underwent 3-T MR T1-weighted imaging and susceptibility-weighted MR imaging with the principles of echo-shifting with a train of observations (PRESTO) sequence. We analysed relationships between relative susceptibility changes in the motor cortex assessed using voxel-based analysis (VBA) and clinical scores, including upper motor neuron score, ALS functional rating scale revised score, and Medical Research Council sum score on physical examination. Patients with ALS exhibited significantly lower signal intensity in the precentral gyrus on susceptibility-weighted MR imaging compared with controls. Clinical scores were significantly correlated with susceptibility changes. Importantly, the extent of the susceptibility changes in the bilateral precentral gyri was significantly correlated with upper motor neuron scores. The results of our pilot study using VBA indicated that low signal intensity in motor cortex on susceptibility-weighted MR imaging may correspond to clinical symptoms, particularly upper motor neuron dysfunction. Susceptibility-weighted MR imaging may be a useful diagnostic tool as an objective indicator of upper motor neuron dysfunction.

  20. Cortical ensemble activity increasingly predicts behaviour outcomes during learning of a motor task

    NASA Astrophysics Data System (ADS)

    Laubach, Mark; Wessberg, Johan; Nicolelis, Miguel A. L.

    2000-06-01

    When an animal learns to make movements in response to different stimuli, changes in activity in the motor cortex seem to accompany and underlie this learning. The precise nature of modifications in cortical motor areas during the initial stages of motor learning, however, is largely unknown. Here we address this issue by chronically recording from neuronal ensembles located in the rat motor cortex, throughout the period required for rats to learn a reaction-time task. Motor learning was demonstrated by a decrease in the variance of the rats' reaction times and an increase in the time the animals were able to wait for a trigger stimulus. These behavioural changes were correlated with a significant increase in our ability to predict the correct or incorrect outcome of single trials based on three measures of neuronal ensemble activity: average firing rate, temporal patterns of firing, and correlated firing. This increase in prediction indicates that an association between sensory cues and movement emerged in the motor cortex as the task was learned. Such modifications in cortical ensemble activity may be critical for the initial learning of motor tasks.

  1. Neural correlates underlying micrographia in Parkinson’s disease

    PubMed Central

    Zhang, Jiarong; Hallett, Mark; Feng, Tao; Hou, Yanan; Chan, Piu

    2016-01-01

    Micrographia is a common symptom in Parkinson’s disease, which manifests as either a consistent or progressive reduction in the size of handwriting or both. Neural correlates underlying micrographia remain unclear. We used functional magnetic resonance imaging to investigate micrographia-related neural activity and connectivity modulations. In addition, the effect of attention and dopaminergic administration on micrographia was examined. We found that consistent micrographia was associated with decreased activity and connectivity in the basal ganglia motor circuit; while progressive micrographia was related to the dysfunction of basal ganglia motor circuit together with disconnections between the rostral supplementary motor area, rostral cingulate motor area and cerebellum. Attention significantly improved both consistent and progressive micrographia, accompanied by recruitment of anterior putamen and dorsolateral prefrontal cortex. Levodopa improved consistent micrographia accompanied by increased activity and connectivity in the basal ganglia motor circuit, but had no effect on progressive micrographia. Our findings suggest that consistent micrographia is related to dysfunction of the basal ganglia motor circuit; while dysfunction of the basal ganglia motor circuit and disconnection between the rostral supplementary motor area, rostral cingulate motor area and cerebellum likely contributes to progressive micrographia. Attention improves both types of micrographia by recruiting additional brain networks. Levodopa improves consistent micrographia by restoring the function of the basal ganglia motor circuit, but does not improve progressive micrographia, probably because of failure to repair the disconnected networks. PMID:26525918

  2. Enhanced brain motor activity in patients with MS after a single dose of 3,4-diaminopyridine.

    PubMed

    Mainero, C; Inghilleri, M; Pantano, P; Conte, A; Lenzi, D; Frasca, V; Bozzao, L; Pozzilli, C

    2004-06-08

    3,4-diaminopyridine (3,4-DAP), a potassium (K+) channel blocker, improves fatigue and motor function in multiple sclerosis (MS). Although it was thought to do so by restoring conduction to demyelinated axons, recent experimental data show that aminopyridines administered at clinical doses potentiate synaptic transmission. To investigate motor cerebral activity with fMRI and transcranial magnetic stimulation (TMS) after a single oral dose of 3,4-DAP in patients with MS. Twelve right-handed women (mean +/- SD age 40.9 +/- 9.3 years) underwent fMRI on two separate occasions (under 3,4-DAP and under placebo) during a simple motor task with the right hand. FMRI data were analyzed with SPM99. After fMRI, patients underwent single-pulse TMS to test motor threshold, amplitude, and latency of motor evoked potentials, central conduction time, and the cortical silent period; paired-pulse TMS to investigate intracortical inhibition (ICI) and intracortical facilitation (ICF); and quantitative electromyography during maximal voluntary contraction. FMRI motor-evoked brain activation was greater under 3,4-DAP than under placebo in the ipsilateral sensorimotor cortex and supplementary motor area (p < 0.05). 3,4-DAP decreased ICI and increased ICF; central motor conduction time and muscular fatigability did not change. 3,4-DAP may modulate brain motor activity in patients with MS, probably by enhancing excitatory synaptic transmission.

  3. Comparative study of ipsilesional and contralesional repetitive transcranial magnetic stimulations for acute infarction.

    PubMed

    Watanabe, Kosuke; Kudo, Yosuke; Sugawara, Eriko; Nakamizo, Tomoki; Amari, Kazumitsu; Takahashi, Koji; Tanaka, Osamu; Endo, Miho; Hayakawa, Yuko; Johkura, Ken

    2018-01-15

    Repetitive transcranial magnetic stimulation (rTMS) is reported to improve chronic post-stoke hemiparesis. However, application of rTMS during the acute phase of post-stroke has not fully been investigated. We investigated the safety and the efficacy of intermittent theta-burst stimulation (iTBS) of the affected motor cortex and 1-Hz stimulation of the unaffected hemisphere during the acute phase in patients with hemiparesis due to capsular infarction. Twenty one patients who met the study criteria were randomly assigned to receive, starting within 7days after stroke onset and for a period of 10days, iTBS of the affected motor cortex hand area (n=8), 1-Hz stimulation of the unaffected motor cortex hand area (n=7), or sham stimulation (n=6). Upper limb motor function was evaluated before rTMS and 12weeks after onset of the stroke. Evaluation was based on the Fugl-Meyer Assessment (FMA), Stroke Impairment Assessment Set (SIAS), Modified Ashworth Scale (MAS), grip strength, and motor evoked potential (MEP) amplitude in the first dorsal interosseous (FDI) muscle. Both iTBS applied to the affected motor cortex hand area and 1-Hz stimulation applied to the unaffected motor cortex hand area enhanced motor recovery. In comparison to sham stimulation, iTBS increased the SIAS finger-function test score, and 1-Hz stimulation decreased the MAS wrist and finger score. Ipsilesional iTBS and contralesional 1-Hz stimulation applied during the acute phase of stroke have different effects: ipsilesional iTBS improves movement of the affected limb, whereas contralesional 1-Hz stimulation reduces spasticity of the affected limb. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Anatomical evidence for brainstem circuits mediating feeding motor programs in the leopard frog, Rana pipiens.

    PubMed

    Anderson, C W

    2001-09-01

    Using injections of small molecular weight fluorescein dextran amines, combined with activity-dependent uptake of sulforhodamine 101 (SR101), brainstem circuits presumed to be involved in feeding motor output were investigated. As has been shown previously in other studies, projections to the cerebellar nuclei were identified from the cerebellar cortex, the trigeminal motor nucleus, and the vestibular nuclei. Results presented here suggest an additional pathway from the hypoglossal motor nuclei to the cerebellar nucleus as well as an afferent projection from the peripheral hypoglossal nerve to the Purkinje cell layer of the cerebellar cortex. Injections in the cerebellar cortex combined with retrograde labeling of the peripheral hypoglossal nerve demonstrate anatomical convergence at the level of the medial reticular formation. This suggests a possible integrative region for afferent feedback from the hypoglossal nerve and information through the Purkinje cell layer of the cerebellar cortex. The activity-dependent uptake of SR101 additionally suggests a reciprocal, polysynaptic pathway between this same area of the medial reticular formation and the trigeminal motor nuclei. The trigeminal motor neurons innervate the m adductor mandibulae, the primary mouth-closing muscle. The SR101 uptake clearly labeled the ventrolateral hypoglossal nuclei, the medial reticular formation, and the Purkinje cell layer of the cerebellar cortex. Unlike retrograde labeling of the peripheral hypoglossal nerve, stimulating the hypoglossal nerve while SR101 was bath-applied labeled trigeminal motor neurons. This, combined with the dextran labeling, suggests a reciprocal connection between the trigeminal motor nuclei and the cerebellar nuclei, as well as the medulla. Taken together, these data are important for understanding the neurophysiological pathways used to coordinate the proper timing of an extremely rapid, goal-directed movement and may prove useful for elucidating some of the first principles of sensorimotor integration.

  5. Neural correlates of conversion disorder: overview and meta-analysis of neuroimaging studies on motor conversion disorder.

    PubMed

    Boeckle, Markus; Liegl, Gregor; Jank, Robert; Pieh, Christoph

    2016-06-10

    Conversion Disorders (CD) are prevalent functional disorders. Although the pathogenesis is still not completely understood, an interaction of genetic, neurobiological, and psychosocial factors is quite likely. The aim of this study is to provide a systematic overview on imaging studies on CDs and investigate neuronal areas involved in Motor Conversion Disorders (MCD). A systematic literature search was conducted on CD. Subsequently a meta-analysis of functional neuroimaging studies on MCD was implemented using an Activation Likelihood Estimation (ALE). We calculated differences between patients and healthy controls as well as between affected versus unaffected sides in addition to an overall analysis in order to identify neuronal areas related to MCD. Patients with MCD differ from healthy controls in the amygdala, superior temporal lobe, retrosplenial area, primary motor cortex, insula, red nucleus, thalamus, anterior as well as dorsolateral prefrontal and frontal cortex. When comparing affected versus unaffected sides, temporal cortex, dorsal anterior cingulate cortex, supramarginal gyrus, dorsal temporal lobe, anterior insula, primary somatosensory cortex, superior frontal gyrus and anterior prefrontal as well as frontal cortex show significant differences. Neuronal areas seem to be involved in the pathogenesis, maintenance or as a result of MCD. Areas that are important for motor-planning, motor-selection or autonomic response seem to be especially relevant. Our results support the emotional unawareness theory but also underline the need of more support by conduction imaging studies on both CD and MCD.

  6. Combinatorial Motor Training Results in Functional Reorganization of Remaining Motor Cortex after Controlled Cortical Impact in Rats

    PubMed Central

    Combs, Hannah L.; Jones, Theresa A.; Kozlowski, Dorothy A.

    2016-01-01

    Abstract Cortical reorganization subsequent to post-stroke motor rehabilitative training (RT) has been extensively examined in animal models and humans. However, similar studies focused on the effects of motor training after traumatic brain injury (TBI) are lacking. We previously reported that after a moderate/severe TBI in adult male rats, functional improvements in forelimb use were accomplished only with a combination of skilled forelimb reach training and aerobic exercise, with or without nonimpaired forelimb constraint. Thus, the current study was designed to examine the relationship between functional motor cortical map reorganization after experimental TBI and the behavioral improvements resulting from this combinatorial rehabilitative regime. Adult male rats were trained to proficiency on a skilled reaching task, received a unilateral controlled cortical impact (CCI) over the forelimb area of the caudal motor cortex (CMC). Three days post-CCI, animals began RT (n = 13) or no rehabilitative training (NoRT) control procedures (n = 13). The RT group participated in daily skilled reach training, voluntary aerobic exercise, and nonimpaired forelimb constraint. This RT regimen significantly improved impaired forelimb reaching success and normalized reaching strategies, consistent with previous findings. RT also enlarged the area of motor cortical wrist representation, derived by intracortical microstimulation, compared to NoRT. These findings indicate that sufficient RT can greatly improve motor function and improve the functional integrity of remaining motor cortex after a moderate/severe CCI. When compared with findings from stroke models, these findings also suggest that more intense RT may be needed to improve motor function and remodel the injured cortex after TBI. PMID:26421759

  7. Combinatorial Motor Training Results in Functional Reorganization of Remaining Motor Cortex after Controlled Cortical Impact in Rats.

    PubMed

    Combs, Hannah L; Jones, Theresa A; Kozlowski, Dorothy A; Adkins, DeAnna L

    2016-04-15

    Cortical reorganization subsequent to post-stroke motor rehabilitative training (RT) has been extensively examined in animal models and humans. However, similar studies focused on the effects of motor training after traumatic brain injury (TBI) are lacking. We previously reported that after a moderate/severe TBI in adult male rats, functional improvements in forelimb use were accomplished only with a combination of skilled forelimb reach training and aerobic exercise, with or without nonimpaired forelimb constraint. Thus, the current study was designed to examine the relationship between functional motor cortical map reorganization after experimental TBI and the behavioral improvements resulting from this combinatorial rehabilitative regime. Adult male rats were trained to proficiency on a skilled reaching task, received a unilateral controlled cortical impact (CCI) over the forelimb area of the caudal motor cortex (CMC). Three days post-CCI, animals began RT (n = 13) or no rehabilitative training (NoRT) control procedures (n = 13). The RT group participated in daily skilled reach training, voluntary aerobic exercise, and nonimpaired forelimb constraint. This RT regimen significantly improved impaired forelimb reaching success and normalized reaching strategies, consistent with previous findings. RT also enlarged the area of motor cortical wrist representation, derived by intracortical microstimulation, compared to NoRT. These findings indicate that sufficient RT can greatly improve motor function and improve the functional integrity of remaining motor cortex after a moderate/severe CCI. When compared with findings from stroke models, these findings also suggest that more intense RT may be needed to improve motor function and remodel the injured cortex after TBI.

  8. Action Verbs and the Primary Motor Cortex: A Comparative TMS Study of Silent Reading, Frequency Judgments, and Motor Imagery

    ERIC Educational Resources Information Center

    Tomasino, Barbara; Fink, Gereon R.; Sparing, Roland; Dafotakis, Manuel; Weiss, Peter H.

    2008-01-01

    Single pulse transcranial magnetic stimulation (TMS) was applied to the hand area of the left primary motor cortex or, as a control, to the vertex (STIMULATION: TMS[subscript M1] vs. TMS[subscript vertex]) while right-handed volunteers silently read verbs related to hand actions. We examined three different tasks and time points for stimulation…

  9. Effective Connectivity Hierarchically Links Temporoparietal and Frontal Areas of the Auditory Dorsal Stream with the Motor Cortex Lip Area during Speech Perception

    ERIC Educational Resources Information Center

    Murakami, Takenobu; Restle, Julia; Ziemann, Ulf

    2012-01-01

    A left-hemispheric cortico-cortical network involving areas of the temporoparietal junction (Tpj) and the posterior inferior frontal gyrus (pIFG) is thought to support sensorimotor integration of speech perception into articulatory motor activation, but how this network links with the lip area of the primary motor cortex (M1) during speech…

  10. Cerebellar theta burst stimulation modulates short latency afferent inhibition in Alzheimer's disease patients

    PubMed Central

    Di Lorenzo, Francesco; Martorana, Alessandro; Ponzo, Viviana; Bonnì, Sonia; D'Angelo, Egidio; Caltagirone, Carlo; Koch, Giacomo

    2013-01-01

    The dysfunction of cholinergic neurons is a typical hallmark in Alzheimer's disease (AD). Previous findings demonstrated that high density of cholinergic receptors is found in the thalamus and the cerebellum compared with the cerebral cortex and the hippocampus. We aimed at investigating whether activation of the cerebello-thalamo-cortical pathway by means of cerebellar theta burst stimulation (TBS) could modulate central cholinergic functions evaluated in vivo by using the neurophysiological determination of Short-Latency Afferent Inhibition (SLAI). We tested the SLAI circuit before and after administration of cerebellar continuous TBS (cTBS) in 12 AD patients and in 12 healthy age-matched control subjects (HS). We also investigated potential changes of intracortical circuits of the contralateral primary motor cortex (M1) by assessing short intracortical inhibition (SICI) and intracortical facilitation (ICF). SLAI was decreased in AD patients compared to HS. Cerebellar cTBS partially restored SLAI in AD patients at later inter-stimulus intervals (ISIs), but did not modify SLAI in HS. SICI and ICF did not differ in the two groups and were not modulated by cerebellar cTBS. These results demonstrate that cerebellar magnetic stimulation is likely to affect mechanisms of cortical cholinergic activity, suggesting that the cerebellum may have a direct influence on the cholinergic dysfunction in AD. PMID:23423358

  11. Modulation of working memory load distinguishes individuals with and without balance impairments following mild traumatic brain injury.

    PubMed

    Woytowicz, Elizabeth J; Sours, Chandler; Gullapalli, Rao P; Rosenberg, Joseph; Westlake, Kelly P

    2018-01-01

    Balance and gait deficits can persist after mild traumatic brain injury (TBI), yet an understanding of the underlying neural mechanism remains limited. The purpose of this study was to investigate differences in attention network modulation in patients with and without balance impairments 2-8 weeks following mild TBI. Using functional magnetic resonance imaging, we compared activity and functional connectivity of cognitive brain regions of the default mode, central-executive and salience networks during a 2-back working memory task in participants with mild TBI and balance impairments (n = 7, age 47 ± 15 years) or no balance impairments (n = 7, age 47 ± 15 years). We first identified greater activation in the lateral occipital cortex in the balance impaired group. Second, we observed stronger connectivity of left pre-supplementary motor cortex in the balance impaired group during the working memory task, which was related to decreased activation of regions within the salience and central executive networks and greater suppression of the default mode network. Results suggest a link between impaired balance and modulation of cognitive resources in patients in mTBI. Findings also highlight the potential importance of moving beyond traditional balance assessments towards an integrative assessment of cognition and balance in this population.

  12. TMS activation of interhemispheric pathways between the posterior parietal cortex and the contralateral motor cortex

    PubMed Central

    Koch, Giacomo; Ruge, Diane; Cheeran, Binith; Fernandez Del Olmo, Miguel; Pecchioli, Cristiano; Marconi, Barbara; Versace, Viviana; Lo Gerfo, Emanuele; Torriero, Sara; Oliveri, Massimiliano; Caltagirone, Carlo; Rothwell, John C

    2009-01-01

    Using a twin coil transcranial magnetic stimulation (tc-TMS) approach we have previously demonstrated that facilitation may be detected in the primary motor cortex (M1) following stimulation over the ipsilateral caudal intraparietal sulcus (cIPS). Here we tested the interhemispheric interactions between the IPS and the contralateral motor cortex (M1). We found that conditioning the right cIPS facilitated contralateral M1 when the conditioning stimulus had an intensity of 90% resting motor threshold (RMT) but not at 70% or 110% RMT. Facilitation was maximal when the interstimulus interval (ISI) between cIPS and M1 was 6 or 12 ms. These facilitatory effects were mediated by interactions with specific groups of interneurons in the contralateral M1. In fact, short intracortical inhibition (SICI) was reduced following cIPS stimulation. Moreover, additional comparison of facilitation of responses evoked by anterior–posterior versus posterior–anterior stimulation of M1 suggested that facilitation was more effective on early I1/I2 circuits than on I3 circuits. In contrast to these effects, stimulation of anterior IPS (aIPS) at 90% RMT induced inhibition, instead of facilitation, of contralateral M1 at ISIs of 10–12 ms. Finally, we found similar facilitation between left cIPS and right M1 although the conditioning stimuli had to have a higher intensity compared with stimulation of right cIPS (110% instead of 90% RMT). These findings demonstrate that different subregions of the posterior parietal cortex (PPC) in humans exert both facilitatory and inhibitory effects towards the contralateral primary motor cortex. These corticocortical projections could contribute to a variety of motor tasks such as bilateral manual coordination, movement planning in space and grasping. PMID:19622612

  13. Differential Effects of HRAS Mutation on LTP-Like Activity Induced by Different Protocols of Repetitive Transcranial Magnetic Stimulation.

    PubMed

    Dileone, Michele; Ranieri, Federico; Florio, Lucia; Capone, Fioravante; Musumeci, Gabriella; Leoni, Chiara; Mordillo-Mateos, Laura; Tartaglia, Marco; Zampino, Giuseppe; Di Lazzaro, Vincenzo

    2016-01-01

    Costello syndrome (CS) is a rare congenital disorder due to a G12S amino acid substitution in HRAS protoncogene. Previous studies have shown that Paired Associative Stimulation (PAS), a repetitive brain stimulation protocol inducing motor cortex plasticity by coupling peripheral nerve stimulation with brain stimulation, leads to an extremely pronounced motor cortex excitability increase in CS patients. Intermittent Theta Burst Stimulation (iTBS) represents a protocol able to induce motor cortex plasticity by trains of stimuli at 50 Hz. In healthy subjects PAS and iTBS produce similar after-effects in motor cortex excitability. Experimental models showed that HRAS-dependent signalling pathways differently affect LTP induced by different patterns of repetitive synaptic stimulation. We aimed to compare iTBS-induced after-effects on motor cortex excitability with those produced by PAS in CS patients and to observe whether HRAS mutation differentially affects two different forms of neuromodulation protocols. We evaluated in vivo after-effects induced by PAS and iTBS applied over the right motor cortex in 4 CS patients and in 21 healthy age-matched controls. Our findings confirmed HRAS-dependent extremely pronounced PAS-induced after-effects and showed for the first time that iTBS induces no change in MEP amplitude in CS patients whereas both protocols lead to an increase of about 50% in controls. CS patients are characterized by an impairment of iTBS-related LTP-like phenomena besides enhanced PAS-induced after-effects, suggesting that HRAS-dependent signalling pathways have a differential influence on PAS- and iTBS-induced plasticity in humans. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Neural dynamics and information representation in microcircuits of motor cortex.

    PubMed

    Tsubo, Yasuhiro; Isomura, Yoshikazu; Fukai, Tomoki

    2013-01-01

    The brain has to analyze and respond to external events that can change rapidly from time to time, suggesting that information processing by the brain may be essentially dynamic rather than static. The dynamical features of neural computation are of significant importance in motor cortex that governs the process of movement generation and learning. In this paper, we discuss these features based primarily on our recent findings on neural dynamics and information coding in the microcircuit of rat motor cortex. In fact, cortical neurons show a variety of dynamical behavior from rhythmic activity in various frequency bands to highly irregular spike firing. Of particular interest are the similarity and dissimilarity of the neuronal response properties in different layers of motor cortex. By conducting electrophysiological recordings in slice preparation, we report the phase response curves (PRCs) of neurons in different cortical layers to demonstrate their layer-dependent synchronization properties. We then study how motor cortex recruits task-related neurons in different layers for voluntary arm movements by simultaneous juxtacellular and multiunit recordings from behaving rats. The results suggest an interesting difference in the spectrum of functional activity between the superficial and deep layers. Furthermore, the task-related activities recorded from various layers exhibited power law distributions of inter-spike intervals (ISIs), in contrast to a general belief that ISIs obey Poisson or Gamma distributions in cortical neurons. We present a theoretical argument that this power law of in vivo neurons may represent the maximization of the entropy of firing rate with limited energy consumption of spike generation. Though further studies are required to fully clarify the functional implications of this coding principle, it may shed new light on information representations by neurons and circuits in motor cortex.

  15. Organizing principles for the cerebral cortex network of commissural and association connections

    PubMed Central

    Swanson, Larry W.; Hahn, Joel D.; Sporns, Olaf

    2017-01-01

    Cognition is supported by a network of axonal connections between gray matter regions within and between right and left cerebral cortex. Global organizing principles of this circuitry were examined with network analysis tools applied to monosynaptic association (within one side) and commissural (between sides) connections between all 77 cortical gray matter regions in each hemisphere of the rat brain. The analysis used 32,350 connection reports expertly collated from published pathway tracing experiments, and 5,394 connections of a possible 23,562 were identified, for a connection density of 23%—of which 20% (1,084) were commissural. Network community detection yielded a stable bihemispheric six-module solution, with an identical set in each hemisphere of three modules topographically forming a lateral core and medial shell arrangement of cortical regions. Functional correlations suggest the lateral module deals preferentially with environmental sensory-motor interactions and the ventromedial module deals preferentially with visceral control, affect, and short-term memory, whereas the dorsomedial module resembles the default mode network. Analysis of commissural connections revealed a set of unexpected rules to help generate hypotheses. Most notably, there is an order of magnitude more heterotopic than homotopic projections; all cortical regions send more association than commissural connections, and for each region, the latter are always a subset of the former; the number of association connections from each cortical region strongly correlates with the number of its commissural connections; and the module (dorsomedial) lying closest to the corpus callosum has the most complete set of commissural connections—and apparently the most complex function. PMID:29078382

  16. Organizing principles for the cerebral cortex network of commissural and association connections.

    PubMed

    Swanson, Larry W; Hahn, Joel D; Sporns, Olaf

    2017-11-07

    Cognition is supported by a network of axonal connections between gray matter regions within and between right and left cerebral cortex. Global organizing principles of this circuitry were examined with network analysis tools applied to monosynaptic association (within one side) and commissural (between sides) connections between all 77 cortical gray matter regions in each hemisphere of the rat brain. The analysis used 32,350 connection reports expertly collated from published pathway tracing experiments, and 5,394 connections of a possible 23,562 were identified, for a connection density of 23%-of which 20% (1,084) were commissural. Network community detection yielded a stable bihemispheric six-module solution, with an identical set in each hemisphere of three modules topographically forming a lateral core and medial shell arrangement of cortical regions. Functional correlations suggest the lateral module deals preferentially with environmental sensory-motor interactions and the ventromedial module deals preferentially with visceral control, affect, and short-term memory, whereas the dorsomedial module resembles the default mode network. Analysis of commissural connections revealed a set of unexpected rules to help generate hypotheses. Most notably, there is an order of magnitude more heterotopic than homotopic projections; all cortical regions send more association than commissural connections, and for each region, the latter are always a subset of the former; the number of association connections from each cortical region strongly correlates with the number of its commissural connections; and the module (dorsomedial) lying closest to the corpus callosum has the most complete set of commissural connections-and apparently the most complex function. Copyright © 2017 the Author(s). Published by PNAS.

  17. The observation of manual grasp actions affects the control of speech: a combined behavioral and Transcranial Magnetic Stimulation study.

    PubMed

    Gentilucci, Maurizio; Campione, Giovanna Cristina; Dalla Volta, Riccardo; Bernardis, Paolo

    2009-12-01

    Does the mirror system affect the control of speech? This issue was addressed in behavioral and Transcranial Magnetic Stimulation (TMS) experiments. In behavioral experiment 1, participants pronounced the syllable /da/ while observing (1) a hand grasping large and small objects with power and precision grasps, respectively, (2) a foot interacting with large and small objects and (3) differently sized objects presented alone. Voice formant 1 was higher when observing power as compared to precision grasp, whereas it remained unaffected by observation of the different types of foot interaction and objects alone. In TMS experiment 2, we stimulated hand motor cortex, while participants observed the two types of grasp. Motor Evoked Potentials (MEPs) of hand muscles active during the two types of grasp were greater when observing power than precision grasp. In experiments 3-5, TMS was applied to tongue motor cortex of participants silently pronouncing the syllable /da/ and simultaneously observing power and precision grasps, pantomimes of the two types of grasps, and differently sized objects presented alone. Tongue MEPs were greater when observing power than precision grasp either executed or pantomimed. Finally, in TMS experiment 6, the observation of foot interaction with large and small objects did not modulate tongue MEPs. We hypothesized that grasp observation activated motor commands to the mouth as well as to the hand that were congruent with the hand kinematics implemented in the observed type of grasp. The commands to the mouth selectively affected postures of phonation organs and consequently basic features of phonological units.

  18. Optogenetically induced spatiotemporal gamma oscillations and neuronal spiking activity in primate motor cortex.

    PubMed

    Lu, Yao; Truccolo, Wilson; Wagner, Fabien B; Vargas-Irwin, Carlos E; Ozden, Ilker; Zimmermann, Jonas B; May, Travis; Agha, Naubahar S; Wang, Jing; Nurmikko, Arto V

    2015-06-01

    Transient gamma-band (40-80 Hz) spatiotemporal patterns are hypothesized to play important roles in cortical function. Here we report the direct observation of gamma oscillations as spatiotemporal waves induced by targeted optogenetic stimulation, recorded by intracortical multichannel extracellular techniques in macaque monkeys during their awake resting states. Microelectrode arrays integrating an optical fiber at their center were chronically implanted in primary motor (M1) and ventral premotor (PMv) cortices of two subjects. Targeted brain tissue was transduced with the red-shifted opsin C1V1(T/T). Constant (1-s square pulses) and ramp stimulation induced narrowband gamma oscillations during awake resting states. Recordings across 95 microelectrodes (4 × 4-mm array) enabled us to track the transient gamma spatiotemporal patterns manifested, e.g., as concentric expanding and spiral waves. Gamma oscillations were induced well beyond the light stimulation volume, via network interactions at distal electrode sites, depending on optical power. Despite stimulation-related modulation in spiking rates, neuronal spiking remained highly asynchronous during induced gamma oscillations. In one subject we examined stimulation effects during preparation and execution of a motor task and observed that movement execution largely attenuated optically induced gamma oscillations. Our findings demonstrate that, beyond previously reported induced gamma activity under periodic drive, a prolonged constant stimulus above a certain threshold may carry primate motor cortex network dynamics into gamma oscillations, likely via a Hopf bifurcation. More broadly, the experimental capability in combining microelectrode array recordings and optogenetic stimulation provides an important approach for probing spatiotemporal dynamics in primate cortical networks during various physiological and behavioral conditions.

  19. Optogenetically induced spatiotemporal gamma oscillations and neuronal spiking activity in primate motor cortex

    PubMed Central

    Lu, Yao; Truccolo, Wilson; Wagner, Fabien B.; Vargas-Irwin, Carlos E.; Ozden, Ilker; Zimmermann, Jonas B.; May, Travis; Agha, Naubahar S.; Wang, Jing

    2015-01-01

    Transient gamma-band (40–80 Hz) spatiotemporal patterns are hypothesized to play important roles in cortical function. Here we report the direct observation of gamma oscillations as spatiotemporal waves induced by targeted optogenetic stimulation, recorded by intracortical multichannel extracellular techniques in macaque monkeys during their awake resting states. Microelectrode arrays integrating an optical fiber at their center were chronically implanted in primary motor (M1) and ventral premotor (PMv) cortices of two subjects. Targeted brain tissue was transduced with the red-shifted opsin C1V1(T/T). Constant (1-s square pulses) and ramp stimulation induced narrowband gamma oscillations during awake resting states. Recordings across 95 microelectrodes (4 × 4-mm array) enabled us to track the transient gamma spatiotemporal patterns manifested, e.g., as concentric expanding and spiral waves. Gamma oscillations were induced well beyond the light stimulation volume, via network interactions at distal electrode sites, depending on optical power. Despite stimulation-related modulation in spiking rates, neuronal spiking remained highly asynchronous during induced gamma oscillations. In one subject we examined stimulation effects during preparation and execution of a motor task and observed that movement execution largely attenuated optically induced gamma oscillations. Our findings demonstrate that, beyond previously reported induced gamma activity under periodic drive, a prolonged constant stimulus above a certain threshold may carry primate motor cortex network dynamics into gamma oscillations, likely via a Hopf bifurcation. More broadly, the experimental capability in combining microelectrode array recordings and optogenetic stimulation provides an important approach for probing spatiotemporal dynamics in primate cortical networks during various physiological and behavioral conditions. PMID:25761956

  20. Output Properties of the Cortical Hindlimb Motor Area in Spinal Cord-Injured Rats.

    PubMed

    Frost, Shawn B; Dunham, Caleb L; Barbay, Scott; Krizsan-Agbas, Dora; Winter, Michelle K; Guggenmos, David J; Nudo, Randolph J

    2015-11-01

    The purpose of this study was to examine neuronal activity levels in the hindlimb area of motor cortex following spinal cord injury (SCI) in rats and compare the results with measurements in normal rats. Fifteen male Fischer-344 rats received a 200 Kdyn contusion injury in the thoracic cord at level T9-T10. After a minimum of 4 weeks following SCI, intracortical microstimulation (ICMS) and single-unit recording techniques were used in both the forelimb and hindlimb motor areas (FLA, HLA) under ketamine anesthesia. Although movements could be evoked using ICMS in the forelimb area with relatively low current levels, no movements or electromyographical responses could be evoked from ICMS in the HLA in any of the injured rats. During the same procedure, electrophysiological recordings were obtained with a single-shank, 16-channel Michigan probe (Neuronexus) to monitor activity. Neural spikes were discriminated using principle component analysis. Neural activity (action potentials) was collected and digitized for a duration of 5 min. Despite the inability to evoke movement from stimulation of cortex, robust single-unit activity could be recorded reliably from hindlimb motor cortex in SCI rats. Activity in the motor cortex of SCI rats was significantly higher compared with uninjured rats, and increased in hindlimb and forelimb motor cortex by similar amounts. These results demonstrate that in a rat model of thoracic SCI, an increase in single-unit cortical activity can be reliably recorded for several weeks post-injury.

  1. Output Properties of the Cortical Hindlimb Motor Area in Spinal Cord-Injured Rats

    PubMed Central

    Dunham, Caleb L.; Barbay, Scott; Krizsan-Agbas, Dora; Winter, Michelle K.; Guggenmos, David J.; Nudo, Randolph J.

    2015-01-01

    Abstract The purpose of this study was to examine neuronal activity levels in the hindlimb area of motor cortex following spinal cord injury (SCI) in rats and compare the results with measurements in normal rats. Fifteen male Fischer-344 rats received a 200 Kdyn contusion injury in the thoracic cord at level T9–T10. After a minimum of 4 weeks following SCI, intracortical microstimulation (ICMS) and single-unit recording techniques were used in both the forelimb and hindlimb motor areas (FLA, HLA) under ketamine anesthesia. Although movements could be evoked using ICMS in the forelimb area with relatively low current levels, no movements or electromyographical responses could be evoked from ICMS in the HLA in any of the injured rats. During the same procedure, electrophysiological recordings were obtained with a single-shank, 16-channel Michigan probe (Neuronexus) to monitor activity. Neural spikes were discriminated using principle component analysis. Neural activity (action potentials) was collected and digitized for a duration of 5 min. Despite the inability to evoke movement from stimulation of cortex, robust single-unit activity could be recorded reliably from hindlimb motor cortex in SCI rats. Activity in the motor cortex of SCI rats was significantly higher compared with uninjured rats, and increased in hindlimb and forelimb motor cortex by similar amounts. These results demonstrate that in a rat model of thoracic SCI, an increase in single-unit cortical activity can be reliably recorded for several weeks post-injury. PMID:26406381

  2. Winning the game: brain processes in expert, young elite and amateur table tennis players

    PubMed Central

    Wolf, Sebastian; Brölz, Ellen; Scholz, David; Ramos-Murguialday, Ander; Keune, Philipp M.; Hautzinger, Martin; Birbaumer, Niels; Strehl, Ute

    2014-01-01

    This study tested two hypotheses: (1) compared with amateurs and young elite, expert table tennis players are characterized by enhanced cortical activation in the motor and fronto-parietal cortex during motor imagery in response to table tennis videos; (2) in elite athletes, world rank points are associated with stronger cortical activation. To this aim, electroencephalographic data were recorded in 14 expert, 15 amateur and 15 young elite right-handed table tennis players. All subjects watched videos of a serve and imagined themselves responding with a specific table tennis stroke. With reference to a baseline period, power decrease/increase of the sensorimotor rhythm (SMR) during the pretask- and task period indexed the cortical activation/deactivation (event-related desynchronization/synchronization, ERD/ERS). Regarding hypothesis (1), 8–10 Hz SMR ERD was stronger in elite athletes than in amateurs with an intermediate ERD in young elite athletes in the motor cortex. Regarding hypothesis (2), there was no correlation between ERD/ERS in the motor cortex and world rank points in elite experts, but a weaker ERD in the fronto-parietal cortex was associated with higher world rank points. These results suggest that motor skill in table tennis is associated with focused excitability of the motor cortex during reaction, movement planning and execution with high attentional demands. Among elite experts, less activation of the fronto-parietal attention network may be necessary to become a world champion. PMID:25386126

  3. The cerebellum: a neuronal learning machine?

    NASA Technical Reports Server (NTRS)

    Raymond, J. L.; Lisberger, S. G.; Mauk, M. D.

    1996-01-01

    Comparison of two seemingly quite different behaviors yields a surprisingly consistent picture of the role of the cerebellum in motor learning. Behavioral and physiological data about classical conditioning of the eyelid response and motor learning in the vestibulo-ocular reflex suggests that (i) plasticity is distributed between the cerebellar cortex and the deep cerebellar nuclei; (ii) the cerebellar cortex plays a special role in learning the timing of movement; and (iii) the cerebellar cortex guides learning in the deep nuclei, which may allow learning to be transferred from the cortex to the deep nuclei. Because many of the similarities in the data from the two systems typify general features of cerebellar organization, the cerebellar mechanisms of learning in these two systems may represent principles that apply to many motor systems.

  4. Neuronal ensemble control of prosthetic devices by a human with tetraplegia

    NASA Astrophysics Data System (ADS)

    Hochberg, Leigh R.; Serruya, Mijail D.; Friehs, Gerhard M.; Mukand, Jon A.; Saleh, Maryam; Caplan, Abraham H.; Branner, Almut; Chen, David; Penn, Richard D.; Donoghue, John P.

    2006-07-01

    Neuromotor prostheses (NMPs) aim to replace or restore lost motor functions in paralysed humans by routeing movement-related signals from the brain, around damaged parts of the nervous system, to external effectors. To translate preclinical results from intact animals to a clinically useful NMP, movement signals must persist in cortex after spinal cord injury and be engaged by movement intent when sensory inputs and limb movement are long absent. Furthermore, NMPs would require that intention-driven neuronal activity be converted into a control signal that enables useful tasks. Here we show initial results for a tetraplegic human (MN) using a pilot NMP. Neuronal ensemble activity recorded through a 96-microelectrode array implanted in primary motor cortex demonstrated that intended hand motion modulates cortical spiking patterns three years after spinal cord injury. Decoders were created, providing a `neural cursor' with which MN opened simulated e-mail and operated devices such as a television, even while conversing. Furthermore, MN used neural control to open and close a prosthetic hand, and perform rudimentary actions with a multi-jointed robotic arm. These early results suggest that NMPs based upon intracortical neuronal ensemble spiking activity could provide a valuable new neurotechnology to restore independence for humans with paralysis.

  5. [Intranasal epitalon infusion modulates neuronal activity in the rat neocortex].

    PubMed

    Sibarov, D A; Vol'nova, A B; Frolov, D S; Nosdrachev, A D

    2006-08-01

    Properties of tetrapeptide epitalon (Ala-Glu-Asp-Gly) constructed on the basis of pineal peptide extract, have been studied. The intranasal infusions: a noninvasive way to deliver this peptide to CNS hypassing the blood-brain barrier, was used. The aim of the study is to estimate epitalon action on rat motor cortex spontaneous activity. Wistar male rats were anesthetized with urethane (1 g/kg). Extracellular unit recording was made using glass microelectrodes (1-2 MOhm). After recording of spontaneous activity (10-15 min), epitalon intranasal infusion (2 ng) was followed by 30-minute recording. Within a few minutes after the infusion, significant activation of neural activity was observed (2-2.5-fold higher frequency of neuronal spikes). Complex response consisting of several phases was identified in some recordings. The spikes frequency growth during 5 to 7 min (first phase) after the infusion was followed by the second (11-12 min) and the third (17-18 min) phases. An increase of neuronal spontaneous activity was conditioned by the higher frequency of already active units and by the involvement of previously silent cells. At least the first phase of epitalon action can be explained by direct action of the peptide on the cells of the motor cortex.

  6. Frontal Theta Dynamics during Response Conflict in Long-Term Mindfulness Meditators

    PubMed Central

    Jo, Han-Gue; Malinowski, Peter; Schmidt, Stefan

    2017-01-01

    Mindfulness meditators often show greater efficiency in resolving response conflicts than non-meditators. However, the neural mechanisms underlying the improved behavioral efficiency are unclear. Here, we investigated frontal theta dynamics—a neural mechanism involved in cognitive control processes—in long-term mindfulness meditators. The dynamics of EEG theta oscillations (4–8 Hz) recorded over the medial frontal cortex (MFC) were examined in terms of their power (MFC theta power) and their functional connectivity with other brain areas (the MFC-centered theta network). Using a flanker-type paradigm, EEG data were obtained from 22 long-term mindfulness meditators and compared to those from 23 matched controls without meditation experience. Meditators showed more efficient cognitive control after conflicts, evidenced by fewer error responses irrespective of response timing. Furthermore, meditators exhibited enhanced conflict modulations of the MFC-centered theta network shortly before the response, in particular for the functional connection between the MFC and the motor cortex. In contrast, MFC theta power was comparable between groups. These results suggest that the higher behavioral efficiency after conflicts in mindfulness meditators could be a function of increased engagement to control the motor system in association with the MFC-centered theta network. PMID:28638334

  7. Corticomotor Responses to Attentionally Demanding Motor Performance: A Mini-Review

    PubMed Central

    Corp, Daniel  T.; Drury, Hannah G. K.; Young, Kayleigh; Do, Michael; Perkins, Tom; Pearce, Alan J.

    2013-01-01

    Increased attentional demand has been shown to reduce motor performance, leading to increases in accidents, particularly in elderly populations. While these deficits have been well documented behaviorally, their cortical correlates are less well known. Increased attention has been shown to affect activity in prefrontal regions of the cortex. However there have been varying results within past research investigating corticomotor regions, mediating motor performance. This mini-review initially discusses past behavioral research, before moving to studies investigating corticomotor areas in response to changes in attention. Recent dual task studies have revealed a possible decline in the ability of older, but not younger, adults to activate inhibitory processes within the motor cortex, which may be correlated with poor motor performance, and thus accidents. A reduction in cortical inhibition may be caused by neurodegeneration within prefrontal regions of the cortex with age, rendering older adults less able to allocate attention to corticomotor regions. PMID:23579267

  8. Alterations of motor performance and brain cortex mitochondrial function during ethanol hangover.

    PubMed

    Bustamante, Juanita; Karadayian, Analia G; Lores-Arnaiz, Silvia; Cutrera, Rodolfo A

    2012-08-01

    Ethanol has been known to affect various behavioral parameters in experimental animals, even several hours after ethanol (EtOH) is absent from blood circulation, in the period known as hangover. The aim of this study was to assess the effects of acute ethanol hangover on motor performance in association with the brain cortex energetic metabolism. Evaluation of motor performance and brain cortex mitochondrial function during alcohol hangover was performed in mice 6 hours after a high ethanol dose (hangover onset). Animals were injected i.p. either with saline (control group) or with ethanol (3.8 g/kg BW) (hangover group). Ethanol hangover group showed a bad motor performance compared with control animals (p < .05). Oxygen uptake in brain cortex mitochondria from hangover animals showed a 34% decrease in the respiratory control rate as compared with the control group. Mitochondrial complex activities were decreased being the complex I-III the less affected by the hangover condition; complex II-III was markedly decreased by ethanol hangover showing 50% less activity than controls. Complex IV was 42% decreased as compared with control animals. Hydrogen peroxide production was 51% increased in brain cortex mitochondria from the hangover group, as compared with the control animals. Quantification of the mitochondrial transmembrane potential indicated that ethanol injected animals presented 17% less ability to maintain the polarized condition as compared with controls. These results indicate that a clear decrease in proton motive force occurs in brain cortex mitochondria during hangover conditions. We can conclude that a decreased motor performance observed in the hangover group of animals could be associated with brain cortex mitochondrial dysfunction and the resulting impairment of its energetic metabolism. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Resting-state Functional Magnetic Resonance Imaging Analysis of Brain Functional Activity in Rats with Ischemic Stroke Treated by Electro-acupuncture.

    PubMed

    Liang, Shengxiang; Lin, Yunjiao; Lin, Bingbing; Li, Jianhong; Liu, Weilin; Chen, Lidian; Zhao, Shujun; Tao, Jing

    2017-09-01

    To evaluate whether electro-acupuncture (EA) treatment at acupoints of Zusanli (ST 36) and Quchi (LI 11) could reduce motor impairments and enhance brain functional recovery in rats with ischemic stroke. A rat model of middle cerebral artery occlusion (MCAO) was established. EA at ST 36 and LI 11was started at 24 hours (MCAO + EA group) after ischemic stroke. The nontreatment (MCAO) and sham-operated control (SC) groups were included as controls. The neurologic deficits of all groups were assessed by Zea Longa scores and the modified neurologic severity scores on 24 hours and 8 days after MCAO. To further investigate the effect of EA on infract volume and brain function, magnetic resonance imaging was used to estimate the brain lesion and brain neural activities of each group at 8 days after ischemic stroke. Within 1 week after EA treatment, the neurologic deficits were significantly alleviated, and the cerebral infarctions were improved, including visual cortex, motor cortex, striatum, dorsal thalamus, and hippocampus. Furthermore, whole brain neural activities of auditory cortex, lateral nucleus group of dorsal thalamus, hippocampus, motor cortex, orbital cortex, sensory cortex, and striatum were decreased in MCAO group, whereas that of brain neural activities were increased after EA treatment, suggesting these brain regions are in accordance with the brain structure analysis. EA at ST 36 and LI 11 could enhance the neural activity of motor function-related brain regions, including motor cortex, dorsal thalamus, and striatum in rats, which is a potential treatment for ischemia stroke. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  10. Altered resting-state effective connectivity of fronto-parietal motor control systems on the primary motor network following stroke

    PubMed Central

    Inman, Cory S.; James, G. Andrew; Hamann, Stephan; Rajendra, Justin K.; Pagnoni, Giuseppe; Butler, Andrew J.

    2011-01-01

    Previous brain imaging work suggests that stroke alters the effective connectivity (the influence neural regions exert upon each other) of motor execution networks. The present study examines the intrinsic effective connectivity of top-down motor control in stroke survivors (n=13) relative to healthy participants (n=12). Stroke survivors exhibited significant deficits in motor function, as assessed by the Fugl-Meyer Motor Assessment. We used structural equation modeling (SEM) of resting-state fMRI data to investigate the relationship between motor deficits and the intrinsic effective connectivity between brain regions involved in motor control and motor execution. An exploratory adaptation of SEM determined the optimal model of motor execution effective connectivity in healthy participants, and confirmatory SEM assessed stroke survivors’ fit to that model. We observed alterations in spontaneous resting-state effective connectivity from fronto-parietal guidance systems to the motor network in stroke survivors. More specifically, diminished connectivity was found in connections from the superior parietal cortex to primary motor cortex and supplementary motor cortex. Furthermore, the paths demonstrated large individual variance in stroke survivors but less variance in healthy participants. These findings suggest that characterizing the deficits in resting-state connectivity of top-down processes in stroke survivors may help optimize cognitive and physical rehabilitation therapies by individually targeting specific neural pathway. PMID:21839174

  11. Neural correlates of motor recovery after stroke: a longitudinal fMRI study

    PubMed Central

    Ward, N. S.; Brown, M. M.; Thompson, A. J.; Frackowiak, R. S. J.

    2013-01-01

    Summary Recovery of motor function after stroke may occur over weeks or months and is often attributed to cerebral reorganization. We have investigated the longitudinal relationship between recovery after stroke and task-related brain activation during a motor task as measured using functional MRI (fMRI). Eight first-ever stroke patients presenting with hemiparesis resulting from cerebral infarction sparing the primary motor cortex, and four control subjects were recruited. Subjects were scanned on a number of occasions whilst performing an isometric dynamic visually paced hand grip task. Recovery in the patient group was assessed using a battery of outcome measures at each time point. Task-related brain activations decreased over sessions as a function of recovery in a number of primary and non-primary motor regions in all patients, but no session effects were seen in the controls. Furthermore, consistent decreases across sessions correlating with recovery were seen across the whole patient group independent of rate of recovery or initial severity, in primary motor cortex, premotor and prefrontal cortex, supplementary motor areas, cingulate sulcus, temporal lobe, striate cortex, cerebellum, thalamus and basal ganglia. Although recovery-related increases were seen in different brain regions in four patients, there were no consistent effects across the group. These results further our understanding of the recovery process by demonstrating for the first time a clear temporal relationship between recovery and task-related activation of the motor system after stroke. PMID:12937084

  12. Simultaneous Top-down Modulation of the Primary Somatosensory Cortex and Thalamic Nuclei during Active Tactile Discrimination

    PubMed Central

    Pais-Vieira, Miguel; Lebedev, Mikhail A.; Wiest, Michael C.; Nicolelis, Miguel A.L.

    2013-01-01

    The rat somatosensory system contains multiple thalamocortical loops (TCL) that altogether process, in fundamentally different ways, tactile stimuli delivered passively or actively sampled. To elucidate potential top-down mechanisms that govern TCL processing in awake, behaving animals, we simultaneously recorded neuronal ensemble activity across multiple cortical and thalamic areas while rats performed an active aperture discrimination task. Single neurons located in the primary somatosensory cortex (S1), the ventroposterior medial (VPM) and the posterior medial (POM) thalamic nuclei of the trigeminal somatosensory pathways exhibited prominent anticipatory firing modulations prior to the whiskers touching the aperture edges. This cortical and thalamic anticipatory firing could not be explained by whisker movements or whisker stimulation, because neither trigeminal ganglion sensory-evoked responses nor EMG activity were detected during the same period. Both thalamic and S1 anticipatory activity were predictive of the animal’s discrimination accuracy. Inactivation of the primary motor cortex (M1) with muscimol affected anticipatory patterns in S1 and the thalamus, and impaired the ability to predict the animal’s performance accuracy based on thalamocortical anticipatory activity. These findings suggest that neural processing in TCLs is launched in anticipation of whisker contact with objects, depends on top-down effects generated in part by M1 activity, and cannot be explained by the classical feedforward model of the rat trigeminal system. PMID:23447616

  13. Evolution of columns, modules, and domains in the neocortex of primates.

    PubMed

    Kaas, Jon H

    2012-06-26

    The specialized regions of neocortex of mammals, called areas, have been divided into smaller functional units called minicolumns, columns, modules, and domains. Here we describe some of these functional subdivisions of areas in primates and suggest when they emerged in mammalian evolution. We distinguish several types of these smaller subdivisions. Minicolumns, vertical arrays of neurons that are more densely interconnected with each other than with laterally neighboring neurons, are present in all cortical areas. Classic columns are defined by a repeating pattern of two or more types of cortex distinguished by having different inputs and neurons with different response properties. Sensory stimuli that continuously vary along a stimulus dimension may activate groups of neurons that vary continuously in location, producing "columns" without specific boundaries. Other groups or columns of cortical neurons are separated by narrow septa of fibers that reflect discontinuities in the receptor sheet. Larger regions of posterior parietal cortex and frontal motor cortex are parts of networks devoted to producing different sequences of movements. We distinguish these larger functionally distinct regions as domains. Columns of several types have evolved independently a number of times. Some of the columns found in primates likely emerged with the first primates, whereas others likely were present in earlier ancestors. The sizes and shapes of columns seem to depend on the balance of neuron activation patterns and molecular signals during development.

  14. [Anticipatory postural adjustment in bimanual unloading: role of the motor cortex in motor learning].

    PubMed

    Kazennikov, O V; Solopova, I A; Talis, V L; Ioffe, M E

    2006-01-01

    The role of the motor cortex was investigated during learning unusual postural adjustment. Healthy subjects held their right (postural) forearm in a horizontal position while supporting a 1-kG load via an electromagnet. The postural forearm position was perturbed by the load release triggered by other elbow voluntary movement. Repetition of the imposed unloading test resulted in a progressive reduction of the maximal forearm rotation, accompanied by the anticipatory decrease in m. biceps brachii activity (learning). Control situation consisted of the voluntary forearm loading. Using the transcranial magnetic stimulation we examined changes in the motor evoked potential of the m. biceps brahii at the beginning and at the end of learning. The evoked potential amplitude did not significantly change in process of the decrease of m. biceps brachii activity. At the end of learning, motor evoked potential / baseline electromyogram ratio increased as compared to the beginning of learning and to the control situation. The results highlight the fundamental role of the motor cortex in suppression of synergies which interfere with formation of a new coordination during motor learning.

  15. Distributed neural signatures of natural audiovisual speech and music in the human auditory cortex.

    PubMed

    Salmi, Juha; Koistinen, Olli-Pekka; Glerean, Enrico; Jylänki, Pasi; Vehtari, Aki; Jääskeläinen, Iiro P; Mäkelä, Sasu; Nummenmaa, Lauri; Nummi-Kuisma, Katarina; Nummi, Ilari; Sams, Mikko

    2017-08-15

    During a conversation or when listening to music, auditory and visual information are combined automatically into audiovisual objects. However, it is still poorly understood how specific type of visual information shapes neural processing of sounds in lifelike stimulus environments. Here we applied multi-voxel pattern analysis to investigate how naturally matching visual input modulates supratemporal cortex activity during processing of naturalistic acoustic speech, singing and instrumental music. Bayesian logistic regression classifiers with sparsity-promoting priors were trained to predict whether the stimulus was audiovisual or auditory, and whether it contained piano playing, speech, or singing. The predictive performances of the classifiers were tested by leaving one participant at a time for testing and training the model using the remaining 15 participants. The signature patterns associated with unimodal auditory stimuli encompassed distributed locations mostly in the middle and superior temporal gyrus (STG/MTG). A pattern regression analysis, based on a continuous acoustic model, revealed that activity in some of these MTG and STG areas were associated with acoustic features present in speech and music stimuli. Concurrent visual stimulus modulated activity in bilateral MTG (speech), lateral aspect of right anterior STG (singing), and bilateral parietal opercular cortex (piano). Our results suggest that specific supratemporal brain areas are involved in processing complex natural speech, singing, and piano playing, and other brain areas located in anterior (facial speech) and posterior (music-related hand actions) supratemporal cortex are influenced by related visual information. Those anterior and posterior supratemporal areas have been linked to stimulus identification and sensory-motor integration, respectively. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. The Functional Organization and Cortical Connections of Motor Cortex in Squirrels

    PubMed Central

    Cooke, Dylan F.; Padberg, Jeffrey; Zahner, Tony

    2012-01-01

    Despite extraordinary diversity in the rodent order, studies of motor cortex have been limited to only 2 species, rats and mice. Here, we examine the topographic organization of motor cortex in the Eastern gray squirrel (Sciurus carolinensis) and cortical connections of motor cortex in the California ground squirrel (Spermophilus beecheyi). We distinguish a primary motor area, M1, based on intracortical microstimulation (ICMS), myeloarchitecture, and patterns of connectivity. A sensorimotor area between M1 and the primary somatosensory area, S1, was also distinguished based on connections, functional organization, and myeloarchitecture. We term this field 3a based on similarities with area 3a in nonrodent mammals. Movements are evoked with ICMS in both M1 and 3a in a roughly somatotopic pattern. Connections of 3a and M1 are distinct and suggest the presence of a third far rostral field, termed “F,” possibly involved in motor processing based on its connections. We hypothesize that 3a is homologous to the dysgranular zone (DZ) in S1 of rats and mice. Our results demonstrate that squirrels have both similar and unique features of M1 organization compared with those described in rats and mice, and that changes in 3a/DZ borders appear to have occurred in both lineages. PMID:22021916

  17. No evidence of somatotopic place of articulation feature mapping in motor cortex during passive speech perception.

    PubMed

    Arsenault, Jessica S; Buchsbaum, Bradley R

    2016-08-01

    The motor theory of speech perception has experienced a recent revival due to a number of studies implicating the motor system during speech perception. In a key study, Pulvermüller et al. (2006) showed that premotor/motor cortex differentially responds to the passive auditory perception of lip and tongue speech sounds. However, no study has yet attempted to replicate this important finding from nearly a decade ago. The objective of the current study was to replicate the principal finding of Pulvermüller et al. (2006) and generalize it to a larger set of speech tokens while applying a more powerful statistical approach using multivariate pattern analysis (MVPA). Participants performed an articulatory localizer as well as a speech perception task where they passively listened to a set of eight syllables while undergoing fMRI. Both univariate and multivariate analyses failed to find evidence for somatotopic coding in motor or premotor cortex during speech perception. Positive evidence for the null hypothesis was further confirmed by Bayesian analyses. Results consistently show that while the lip and tongue areas of the motor cortex are sensitive to movements of the articulators, they do not appear to preferentially respond to labial and alveolar speech sounds during passive speech perception.

  18. Repetitive Transcranial Direct Current Stimulation Induced Excitability Changes of Primary Visual Cortex and Visual Learning Effects-A Pilot Study.

    PubMed

    Sczesny-Kaiser, Matthias; Beckhaus, Katharina; Dinse, Hubert R; Schwenkreis, Peter; Tegenthoff, Martin; Höffken, Oliver

    2016-01-01

    Studies on noninvasive motor cortex stimulation and motor learning demonstrated cortical excitability as a marker for a learning effect. Transcranial direct current stimulation (tDCS) is a non-invasive tool to modulate cortical excitability. It is as yet unknown how tDCS-induced excitability changes and perceptual learning in visual cortex correlate. Our study aimed to examine the influence of tDCS on visual perceptual learning in healthy humans. Additionally, we measured excitability in primary visual cortex (V1). We hypothesized that anodal tDCS would improve and cathodal tDCS would have minor or no effects on visual learning. Anodal, cathodal or sham tDCS were applied over V1 in a randomized, double-blinded design over four consecutive days (n = 30). During 20 min of tDCS, subjects had to learn a visual orientation-discrimination task (ODT). Excitability parameters were measured by analyzing paired-stimulation behavior of visual-evoked potentials (ps-VEP) and by measuring phosphene thresholds (PTs) before and after the stimulation period of 4 days. Compared with sham-tDCS, anodal tDCS led to an improvement of visual discrimination learning (p < 0.003). We found reduced PTs and increased ps-VEP ratios indicating increased cortical excitability after anodal tDCS (PT: p = 0.002, ps-VEP: p = 0.003). Correlation analysis within the anodal tDCS group revealed no significant correlation between PTs and learning effect. For cathodal tDCS, no significant effects on learning or on excitability could be seen. Our results showed that anodal tDCS over V1 resulted in improved visual perceptual learning and increased cortical excitability. tDCS is a promising tool to alter V1 excitability and, hence, perceptual visual learning.

  19. Improving ideomotor limb apraxia by electrical stimulation of the left posterior parietal cortex.

    PubMed

    Bolognini, Nadia; Convento, Silvia; Banco, Elisabetta; Mattioli, Flavia; Tesio, Luigi; Vallar, Giuseppe

    2015-02-01

    Limb apraxia, a deficit of planning voluntary gestures, is most frequently caused by damage to the left hemisphere, where, according to an influential neurofunctional model, gestures are planned, before being executed through the motor cortex of the hemisphere contralateral to the acting hand. We used anodal transcranial direct current stimulation delivered to the left posterior parietal cortex (PPC), the right motor cortex (M1), and a sham stimulation condition, to modulate the ability of six left-brain-damaged patients with ideomotor apraxia, and six healthy control subjects, to imitate hand gestures, and to perform skilled hand movements using the left hand. Transcranial direct current stimulation delivered to the left PPC reduced the time required to perform skilled movements, and planning, but not execution, times in imitating gestures, in both patients and controls. In patients, the amount of decrease of planning times brought about by left PPC transcranial direct current stimulation was influenced by the size of the parietal lobe damage, with a larger parietal damage being associated with a smaller improvement. Of interest from a clinical perspective, left PPC stimulation also ameliorated accuracy in imitating hand gestures in patients. Instead, transcranial direct current stimulation to the right M1 diminished execution, but not planning, times in both patients and healthy controls. In conclusion, by using a transcranial stimulation approach, we temporarily improved ideomotor apraxia in the left hand of left-brain-damaged patients, showing a role of the left PPC in planning gestures. This evidence opens up novel perspectives for the use of transcranial direct current stimulation in the rehabilitation of limb apraxia. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Role of cerebellum in learning postural tasks.

    PubMed

    Ioffe, M E; Chernikova, L A; Ustinova, K I

    2007-01-01

    For a long time, the cerebellum has been known to be a structure related to posture and equilibrium control. According to the anatomic structure of inputs and internal structure of the cerebellum, its role in learning was theoretically reasoned and experimentally proved. The hypothesis of an inverse internal model based on feedback-error learning mechanism combines feedforward control by the cerebellum and feedback control by the cerebral motor cortex. The cerebellar cortex is suggested to acquire internal models of the body and objects in the external world. During learning of a new tool the motor cortex receives feedback from the realized movement while the cerebellum produces only feedforward command. To realize a desired movement without feedback of the realized movement, the cerebellum needs to form an inverse model of the hand/arm system. This suggestion was supported by FMRi data. The role of cerebellum in learning new postural tasks mainly concerns reorganization of natural synergies. A learned postural pattern in dogs has been shown to be disturbed after lesions of the cerebral motor cortex or cerebellar nuclei. In humans, learning voluntary control of center of pressure position is greatly disturbed after cerebellar lesions. However, motor cortex and basal ganglia are also involved in the feedback learning postural tasks.

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