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.

Evaluation of muscle hyperactivity of the grimacing muscles by unilateral tight eyelid closure and stapedius muscle tone.

PubMed

Shiba, Masato; Matsuo, Kiyoshi; Ban, Ryokuya; Nagai, Fumio

2012-10-01

Muscle hyperactivity of grimacing muscles, including the orbicularis oculi and corrugator supercilii muscles that cause crow's feet and a glabellar frown line with ageing, cannot be accurately evaluated by surface observation. In 71 subjects, this study investigated the extent to which grimacing muscles are innervated by the bilateral motor cortices, whether the corticofacial projection to the grimacing muscles affects the facially innervated stapedius muscle tone by measuring static compliance of the tympanic membrane, and whether unilateral tight eyelid closure with contraction of the grimacing muscles changes static compliance. Unilateral tight eyelid closure and its subsequent change in the contralateral vertical medial eyebrow position revealed that motor neurons of the orbicularis oculi and corrugator supercilii muscles were innervated by the bilateral motor cortices with weak-to-strong contralateral dominance. The orbicularis oculi, corrugator supercilii, and stapedius muscles innervated by the bilateral motor cortices had increased muscle hyperactivity, which lowered the vertical medial eyebrow position and decreased the static compliance of the tympanic membrane more than those innervated by the unilateral motor cortex. Unilateral enhanced tight eyelid closure with contraction of the grimacing muscles in certain subjects ipsilaterally decreased the static compliance with increased contraction of the stapedius muscle, which probably occurs to immobilise the tympanic membrane and protect the inner ear from loud sound. Evaluation of unilateral tight eyelid closure and the subsequent change in the contralateral vertical medial eyebrow position as well as a measurement of the static compliance for the stapedius muscle tone has revealed muscle hyperactivity of grimacing muscles.

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.

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.

Motor correlates of models of secondary bilateral synchrony and multiple epileptic foci.

PubMed

Jiruska, Premysl; Proks, Jan; Otáhal, Jakub; Mares, Pavel

2007-10-01

Bilateral synchronous epileptiform discharges registered in patients with partial epilepsies may be generated by different pathophysiological mechanisms. Differentiation between underlying mechanisms is often crucial for correct diagnosis and adequate treatment in clinical epileptology. The aim of this study was to model in rats two possible mechanisms--secondary bilateral sychrony and interaction between multiple epilepic foci. Furthermore, to describe in detail semiology, laterality and differences in motor phenomena. Secondary bilateral synchrony was modeled by unilateral topical application of bicuculline methiodide (BMI) over the sensorimotor cortex. Bilateral symmetric application of BMI was used as a model of multiple epileptic foci. Electrographic and behavioural phenomena were recorded for 1h following the application of BMI. Electroencephalogram in both groups was characterized by presence of bilateral synchronous discharges. Myoclonic and clonic seizures involving forelimb and head muscles represented the most common motor seizure pattern in both groups. Significant differences were found in the laterality of motor phenomena. Motor seizures in unilateral foci always started in the contralateral limbs whereas symmetrical foci exhibited bilateral independent onset of convulsions. Similar lateralization was observed in interictal motor phenomena (myoclonic jerks). An important influence of posture on epileptic motor phenomena was demonstrated. Active or passive changes in animal posture (verticalization to bipedal posture) caused conversion from unilateral myoclonic jerks or clonic seizures to bilaterally synchronous (generalized) motor phenomena in both groups.

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.

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

Effects of different electrical brain stimulation protocols on subcomponents of motor skill learning.

PubMed

Prichard, George; Weiller, Cornelius; Fritsch, Brita; Reis, Janine

2014-01-01

Noninvasive electrical brain stimulation (NEBS) with transcranial direct current (tDCS) or random noise stimulation (tRNS) applied to the primary motor cortex (M1) can augment motor learning. We tested whether different types of stimulation alter particular aspects of learning a tracing task over three consecutive days, namely skill acquisition (online/within session effects) or consolidation (offline/between session effects). Motor training on a tracing task over three consecutive days was combined with different types and montages of stimulation (tDCS, tRNS). Unilateral M1 stimulation using tRNS as well as unilateral and bilateral M1 tDCS all enhanced motor skill learning compared to sham stimulation. In all groups, this appeared to be driven by online effects without an additional offline effect. Unilateral tDCS resulted in large skill gains immediately following the onset of stimulation, while tRNS exerted more gradual effects. Control stimulation of the right temporal lobe did not enhance skill learning relative to sham. The mechanisms of action of tDCS and tRNS are likely different. Hence, the time course of skill improvement within sessions could point to specific and temporally distinct interactions with the physiological process of motor skill learning. Exploring the parameters of NEBS on different tasks and in patients with brain injury will allow us to maximize the benefits of NEBS for neurorehabilitation. Copyright © 2014 Elsevier Inc. All rights reserved.

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

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.

SKILLED BIMANUAL TRAINING DRIVES MOTOR CORTEX PLASTICITY IN CHILDREN WITH UNILATERAL CEREBRAL PALSY

PubMed Central

Friel, Kathleen M.; Kuo, Hsing-Ching; Fuller, Jason; Ferre, Claudio L.; Brandão, Marina; Carmel, Jason B.; Bleyenheuft, Yannick; Gowatsky, Jaimie L.; Stanford, Arielle D.; Rowny, Stefan B.; Luber, Bruce; Bassi, Bruce; Murphy, David LK; Lisanby, Sarah H.; Gordon, Andrew M.

2015-01-01

Background Intensive bimanual therapy can improve hand function in children with unilateral spastic cerebral palsy (USCP). We compared the effects of structured bimanual skill training vs. unstructured bimanual practice on motor outcomes and motor map plasticity in children with USCP. Objective We hypothesized that structured skill training would produce greater motor map plasticity than unstructured practice. Methods Twenty children with USCP (average age 9,5; 12 males) received therapy in a day-camp-setting, 6 h/day, 5 days/week, for 3 weeks. In structured skill training (n=10), children performed progressively more difficult movements and practiced functional goals. In unstructured practice (n=10), children engaged in bimanual activities but did not practice skillful movements or functional goals. We used the Assisting Hand Assessment (AHA), Jebsen-Taylor test of Hand Function (JTTHF) and Canadian Occupational Performance Measure (COPM) to measure hand function. We used single-pulse transcranial magnetic stimulation (TMS) to map the representation of first dorsal interosseous (FDI) and flexor carpi radialis (FCR) muscles bilaterally. Results Both groups showed significant improvements in bimanual hand use (AHA; p<0.05) and hand dexterity (JTTHF; p<0.001). However, only the structured skill group showed increases in the size of the affected hand motor map and amplitudes of motor evoked potentials (p<0.01). Most children who showed the most functional improvements (COPM) had the largest changes in map size. Conclusions These findings uncover a dichotomy of plasticity: the unstructured practice group improved hand function but did not show changes in motor maps. Skill training is important for driving motor cortex plasticity in children with USCP. PMID:26867559

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.

Enhanced motor learning with bilateral transcranial direct current stimulation: Impact of polarity or current flow direction?

PubMed

Naros, Georgios; Geyer, Marc; Koch, Susanne; Mayr, Lena; Ellinger, Tabea; Grimm, Florian; Gharabaghi, Alireza

2016-04-01

Bilateral transcranial direct current stimulation (TDCS) is superior to unilateral TDCS when targeting motor learning. This effect could be related to either the current flow direction or additive polarity-specific effects on each hemisphere. This sham-controlled randomized study included fifty right-handed healthy subjects in a parallel-group design who performed an exoskeleton-based motor task of the proximal left arm on three consecutive days. Prior to training, we applied either sham, right anodal (a-TDCS), left cathodal (c-TDCS), concurrent a-TDCS and c-TDCS with two independent current sources and return electrodes (double source (ds)-TDCS) or classical bilateral stimulation (bi-TDCS). Motor performance improved over time for both unilateral (a-TDCS, c-TDCS) and bilateral (bi-TDCS, ds-TDCS) TDCS montages. However, only the two bilateral paradigms led to an improvement of the final motor performance at the end of the training period as compared to the sham condition. There was no difference between the two bilateral stimulation conditions (bi-TDCS, ds-TDCS). Bilateral TDCS is more effective than unilateral stimulation due to its polarity-specific effects on each hemisphere rather than due to its current flow direction. This study is the first systematic evaluation of stimulation polarity and current flow direction of bi-hemispheric motor cortex TDCS on motor learning of proximal upper limb muscles. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Use-Dependent Dendritic Regrowth Is Limited after Unilateral Controlled Cortical Impact to the Forelimb Sensorimotor Cortex

PubMed Central

Jones, Theresa A.; Liput, Daniel J.; Maresh, Erin L.; Donlan, Nicole; Parikh, Toral J.; Marlowe, Dana

2012-01-01

Abstract Compensatory neural plasticity occurs in both hemispheres following unilateral cortical damage incurred by seizures, stroke, and focal lesions. Plasticity is thought to play a role in recovery of function, and is important for the utility of rehabilitation strategies. Such effects have not been well described in models of traumatic brain injury (TBI). We examined changes in immunoreactivity for neural structural and plasticity-relevant proteins in the area surrounding a controlled cortical impact (CCI) to the forelimb sensorimotor cortex (FL-SMC), and in the contralateral homotopic cortex over time (3–28 days). CCI resulted in considerable motor deficits in the forelimb contralateral to injury, and increased reliance on the ipsilateral forelimb. The density of dendritic processes, visualized with immunostaining for microtubule-associated protein-2 (MAP-2), were bilaterally decreased at all time points. Synaptophysin (SYN) immunoreactivity increased transiently in the injured hemisphere, but this reflected an atypical labeling pattern, and it was unchanged in the contralateral hemisphere compared to uninjured controls. The lack of compensatory neuronal structural plasticity in the contralateral homotopic cortex, despite behavioral asymmetries, is in contrast to previous findings in stroke models. In the cortex surrounding the injury (but not the contralateral cortex), decreases in dendrites were accompanied by neurodegeneration, as indicated by Fluoro-Jade B (FJB) staining, and increased expression of the growth-inhibitory protein Nogo-A. These studies indicate that, following unilateral CCI, the cortex undergoes neuronal structural degradation in both hemispheres out to 28 days post-injury, which may be indicative of compromised compensatory plasticity. This is likely to be an important consideration in designing therapeutic strategies aimed at enhancing plasticity following TBI. PMID:22352953

Use-dependent dendritic regrowth is limited after unilateral controlled cortical impact to the forelimb sensorimotor cortex.

PubMed

Jones, Theresa A; Liput, Daniel J; Maresh, Erin L; Donlan, Nicole; Parikh, Toral J; Marlowe, Dana; Kozlowski, Dorothy A

2012-05-01

Compensatory neural plasticity occurs in both hemispheres following unilateral cortical damage incurred by seizures, stroke, and focal lesions. Plasticity is thought to play a role in recovery of function, and is important for the utility of rehabilitation strategies. Such effects have not been well described in models of traumatic brain injury (TBI). We examined changes in immunoreactivity for neural structural and plasticity-relevant proteins in the area surrounding a controlled cortical impact (CCI) to the forelimb sensorimotor cortex (FL-SMC), and in the contralateral homotopic cortex over time (3-28 days). CCI resulted in considerable motor deficits in the forelimb contralateral to injury, and increased reliance on the ipsilateral forelimb. The density of dendritic processes, visualized with immunostaining for microtubule-associated protein-2 (MAP-2), were bilaterally decreased at all time points. Synaptophysin (SYN) immunoreactivity increased transiently in the injured hemisphere, but this reflected an atypical labeling pattern, and it was unchanged in the contralateral hemisphere compared to uninjured controls. The lack of compensatory neuronal structural plasticity in the contralateral homotopic cortex, despite behavioral asymmetries, is in contrast to previous findings in stroke models. In the cortex surrounding the injury (but not the contralateral cortex), decreases in dendrites were accompanied by neurodegeneration, as indicated by Fluoro-Jade B (FJB) staining, and increased expression of the growth-inhibitory protein Nogo-A. These studies indicate that, following unilateral CCI, the cortex undergoes neuronal structural degradation in both hemispheres out to 28 days post-injury, which may be indicative of compromised compensatory plasticity. This is likely to be an important consideration in designing therapeutic strategies aimed at enhancing plasticity following TBI.

Effects of bilateral and unilateral locus coeruleus lesions on beam-walking recovery after subsequent unilateral sensorimotor cortex suction-ablation in the rat.

PubMed

Goldstein, L B

1997-01-01

The recovery of beam-walking ability following a unilateral sensorimotor cortex lesion in the rat is hypothesized to be noradrenergically-mediated. We carried out two experiments to further test this hypothesis. In the first experiment, bilateral 6-hydroxydopamine locus coeruleus (LC) lesions or sham LC lesions were made 2 weeks prior to a right sensorimotor cortex suction-ablation lesion or sham cortex lesion. In the second experiment, unilateral left or right LC lesions or sham LC lesions were made 2 weeks prior to a right sensorimotor cortex lesion or sham cortex lesion. Beam-walking recovery was measured over the 12 days following cortex lesioning in each experiment. Bilateral, unilateral left, and unilateral right LC lesions resulted in impaired recovery. These data provide additional support for the hypothesis that beam-walking recovery after sensorimotor cortex injury is, at least in part, noradrenergically mediated.

A Primary Role for Nucleus Accumbens and Related Limbic Network in Vocal Tics.

PubMed

McCairn, Kevin W; Nagai, Yuji; Hori, Yukiko; Ninomiya, Taihei; Kikuchi, Erika; Lee, Ju-Young; Suhara, Tetsuya; Iriki, Atsushi; Minamimoto, Takafumi; Takada, Masahiko; Isoda, Masaki; Matsumoto, Masayuki

2016-01-20

Inappropriate vocal expressions, e.g., vocal tics in Tourette syndrome, severely impact quality of life. Neural mechanisms underlying vocal tics remain unexplored because no established animal model representing the condition exists. We report that unilateral disinhibition of the nucleus accumbens (NAc) generates vocal tics in monkeys. Whole-brain PET imaging identified prominent, bilateral limbic cortico-subcortical activation. Local field potentials (LFPs) developed abnormal spikes in the NAc and the anterior cingulate cortex (ACC). Vocalization could occur without obvious LFP spikes, however, when phase-phase coupling of alpha oscillations were accentuated between the NAc, ACC, and the primary motor cortex. These findings contrasted with myoclonic motor tics induced by disinhibition of the dorsolateral putamen, where PET activity was confined to the ipsilateral sensorimotor system and LFP spikes always preceded motor tics. We propose that vocal tics emerge as a consequence of dysrhythmic alpha coupling between critical nodes in the limbic and motor networks. VIDEO ABSTRACT. Copyright © 2016 Elsevier Inc. All rights reserved.

Enhanced left-finger deftness following dominant upper- and lower-limb amputation.

PubMed

Swanberg, Kelley M; Clark, Abigail M; Kline, Julia E; Yurkiewicz, Ilana R; Chan, Brenda L; Pasquina, Paul F; Heilman, Kenneth M; Tsao, Jack W

2011-09-01

After amputation, the sensorimotor cortex reorganizes, and these alterations might influence motor functions of the remaining extremities. The authors examined how amputation of the dominant or nondominant upper or lower extremity alters deftness in the intact limbs. The participants were 32 unilateral upper- or lower-extremity amputees and 6 controls. Upper-extremity deftness was tested by coin rotation (finger deftness) and pegboard (arm, hand, and finger deftness) tasks. Following right-upper- or right-lower-extremity amputation, the left hand's finger movements were defter than the left-hand fingers of controls. In contrast, with left-upper- or left-lower-extremity amputation, the right hand's finger performance was the same as that of the controls. Although this improvement might be related to increased use (practice), the finding that right-lower-extremity amputation also improved the left hand's finger deftness suggests an alternative mechanism. Perhaps in right-handed persons the left motor cortex inhibits the right side of the body more than the right motor cortex inhibits the left side, and the physiological changes induced by right-sided amputation reduced this inhibition.

Bereitschaftspotential as an indicator of movement preparation in supplementary motor area and motor cortex.

PubMed

Deecke, L

1987-01-01

Topographical studies in humans of the Bereitschaftspotential (BP, or readiness potential, as averaged from the electroencephalogram) and the Bereitschaftsmagnetfeld (BM, or readiness magnetic field, as averaged from the magnetoencephalogram) revealed a widespread distribution of motor preparation over both hemispheres even before unilateral movement. This indicates the existence of several generators responsible for the BP, including generators in the ipsilateral hemisphere, which is in agreement with measurements of regional cerebral blood flow or regional cerebral energy metabolism. Nevertheless, two principal generators seem to prevail: (1) An early generator, starting its activity 1s or more before the motor act, with its maximum at the vertex. For this and other reasons, early BP generation probably stems from cortical tissue representing or including the supplementary motor area (SMA). (2) A later generator, starting its activity about 0.5s before the onset of movement and biased towards the contralateral hemisphere (contralateral preponderance of negativity, CPN). For unilateral finger movements the CPN succeeds the BP's initial bilateral symmetry in the later preparation period. Thus, this lateralized BP component probably stems from the primary motor area, MI (area 4, hand representation). While regional cerebral blood flow or regional cerebral energy metabolism show that the SMA is active in conjunction with motor acts, these data do not permit the conclusion that SMA activity precedes motor acts. This can only be shown by the Bereitschaftspotential, which proves that SMA activity occurs before the onset of movement and, what is more, before the onset of MI activity. This important order of events (first SMA, then MI activation) has been elucidated by our BP studies. It gives the SMA an important functional role: the initiation of voluntary movement. The recording of movement-related potentials associated with manual hand-tracking and motor learning points to the SMA and frontal cortex having an important role in these functions.

Mirror illusion reduces motor cortical inhibition in the ipsilateral primary motor cortex during forceful unilateral muscle contractions.

PubMed

Zult, Tjerk; Goodall, Stuart; Thomas, Kevin; Hortobágyi, Tibor; Howatson, Glyn

2015-04-01

Forceful, unilateral contractions modulate corticomotor paths targeting the resting, contralateral hand. However, it is unknown whether mirror-viewing of a slowly moving but forcefully contracting hand would additionally affect these paths. Here we examined corticospinal excitability and short-interval intracortical inhibition (SICI) of the right-ipsilateral primary motor cortex (M1) in healthy young adults under no-mirror and mirror conditions at rest and during right wrist flexion at 60% maximal voluntary contraction (MVC). During the no-mirror conditions neither hand was visible, whereas in the mirror conditions participants looked at the right hand's reflection in the mirror. Corticospinal excitability increased during contractions in the left flexor carpi radialis (FCR) (contraction 0.41 mV vs. rest 0.21 mV) and extensor carpi radialis (ECR) (contraction 0.56 mV vs. rest 0.39 mV), but there was no mirror effect (FCR: P = 0.743, ηp (2) = 0.005; ECR: P = 0.712, ηp (2) = 0.005). However, mirror-viewing of the contracting and moving wrist attenuated SICI relative to test pulse in the left FCR by ∼9% compared with the other conditions (P < 0.05, d ≥ 0.62). Electromyographic activity in the resting left hand prior to stimulation was not affected by the mirror (FCR: P = 0.255, ηp (2) = 0.049; ECR: P = 0.343, ηp (2) = 0.035) but increased twofold during contractions. Thus viewing the moving hand in the mirror and not just the mirror image of the nonmoving hand seems to affect motor cortical inhibitory networks in the M1 associated with the mirror image. Future studies should determine whether the use of a mirror could increase interlimb transfer produced by cross-education, especially in patient groups with unilateral orthopedic and neurological conditions. Copyright © 2015 the American Physiological Society.

Mirror illusion reduces motor cortical inhibition in the ipsilateral primary motor cortex during forceful unilateral muscle contractions

PubMed Central

Goodall, Stuart; Thomas, Kevin; Hortobágyi, Tibor; Howatson, Glyn

2015-01-01

Forceful, unilateral contractions modulate corticomotor paths targeting the resting, contralateral hand. However, it is unknown whether mirror-viewing of a slowly moving but forcefully contracting hand would additionally affect these paths. Here we examined corticospinal excitability and short-interval intracortical inhibition (SICI) of the right-ipsilateral primary motor cortex (M1) in healthy young adults under no-mirror and mirror conditions at rest and during right wrist flexion at 60% maximal voluntary contraction (MVC). During the no-mirror conditions neither hand was visible, whereas in the mirror conditions participants looked at the right hand's reflection in the mirror. Corticospinal excitability increased during contractions in the left flexor carpi radialis (FCR) (contraction 0.41 mV vs. rest 0.21 mV) and extensor carpi radialis (ECR) (contraction 0.56 mV vs. rest 0.39 mV), but there was no mirror effect (FCR: P = 0.743, ηp2 = 0.005; ECR: P = 0.712, ηp2 = 0.005). However, mirror-viewing of the contracting and moving wrist attenuated SICI relative to test pulse in the left FCR by ∼9% compared with the other conditions (P < 0.05, d ≥ 0.62). Electromyographic activity in the resting left hand prior to stimulation was not affected by the mirror (FCR: P = 0.255, ηp2 = 0.049; ECR: P = 0.343, ηp2 = 0.035) but increased twofold during contractions. Thus viewing the moving hand in the mirror and not just the mirror image of the nonmoving hand seems to affect motor cortical inhibitory networks in the M1 associated with the mirror image. Future studies should determine whether the use of a mirror could increase interlimb transfer produced by cross-education, especially in patient groups with unilateral orthopedic and neurological conditions. PMID:25632077

Association between hemodynamic activity and motor performance in six-month-old full-term and preterm infants: a functional near-infrared spectroscopy study.

PubMed

de Oliveira, Suelen Rosa; de Paula Machado, Ana Carolina Cabral; de Paula, Jonas Jardim; de Moraes, Paulo Henrique Paiva; Nahin, Maria Juliana Silvério; Magalhães, Lívia de Castro; Novi, Sergio L; Mesquita, Rickson C; de Miranda, Débora Marques; Bouzada, Maria Cândida Ferrarez

2018-01-01

This study aimed to assess task-induced activation in motor cortex and its association with motor performance in full-term and preterm born infants at six months old. A cross-sectional study of 73 six-month-old infants was conducted (35 full-term and 38 preterm infants). Motor performance was assessed using the Bayley Scales of Infant Development third edition-Bayley-III. Brain hemodynamic activity during motor task was measured by functional near-infrared spectroscopy (fNIRS). Motor performance was similar in full-term and preterm infants. However, differences in hemodynamic response were identified. Full terms showed a more homogeneous unilateral and contralateral activated area, whereas in preterm-born the activation response was predominantly bilateral. The full-term group also exhibited a shorter latency for the hemodynamic response than the preterm group. Hemodynamic activity in the left sensorimotor region was positively associated with motor performance measured by Bayley-III. The results highlight the adequacy of fNIRS to assess differences in task-induced activation in sensorimotor cortex between groups. The association between motor performance and the hemodynamic activity require further investigation and suggest that fNIRS can become a suitable auxiliary tool to investigate aspects of neural basis on early development of motor abilities.

Habenula functional resting-state connectivity in pediatric CRPS.

PubMed

Erpelding, Nathalie; Sava, Simona; Simons, Laura E; Lebel, Alyssa; Serrano, Paul; Becerra, Lino; Borsook, David

2014-01-01

The habenula (Hb) is a small brain structure located in the posterior end of the medial dorsal thalamus and through medial (MHb) and lateral (LHb) Hb connections, it acts as a conduit of information between forebrain and brainstem structures. The role of the Hb in pain processing is well documented in animals and recently also in acute experimental pain in humans. However, its function remains unknown in chronic pain disorders. Here, we investigated Hb resting-state functional connectivity (rsFC) in patients with complex regional pain syndrome (CRPS) compared with healthy controls. Twelve pediatric patients with unilateral lower-extremity CRPS (9 females; 10-17 yr) and 12 age- and sex-matched healthy controls provided informed consent to participate in the study. In healthy controls, Hb functional connections largely overlapped with previously described anatomical connections in cortical, subcortical, and brainstem structures. Compared with controls, patients exhibited an overall Hb rsFC reduction with the rest of the brain and, specifically, with the anterior midcingulate cortex, dorsolateral prefrontal cortex, supplementary motor cortex, primary motor cortex, and premotor cortex. Our results suggest that Hb rsFC parallels anatomical Hb connections in the healthy state and that overall Hb rsFC is reduced in patients, particularly connections with forebrain areas. Patients' decreased Hb rsFC to brain regions implicated in motor, affective, cognitive, and pain inhibitory/modulatory processes may contribute to their symptomatology.

Layer 5 Pyramidal Neurons' Dendritic Remodeling and Increased Microglial Density in Primary Motor Cortex in a Murine Model of Facial Paralysis

PubMed Central

Urrego, Diana; Troncoso, Julieta; Múnera, Alejandro

2015-01-01

This work was aimed at characterizing structural changes in primary motor cortex layer 5 pyramidal neurons and their relationship with microglial density induced by facial nerve lesion using a murine facial paralysis model. Adult transgenic mice, expressing green fluorescent protein in microglia and yellow fluorescent protein in projecting neurons, were submitted to either unilateral section of the facial nerve or sham surgery. Injured animals were sacrificed either 1 or 3weeks after surgery. Two-photon excitation microscopy was then used for evaluating both layer 5 pyramidal neurons and microglia in vibrissal primary motor cortex (vM1). It was found that facial nerve lesion induced long-lasting changes in the dendritic morphology of vM1 layer 5 pyramidal neurons and in their surrounding microglia. Dendritic arborization of the pyramidal cells underwent overall shrinkage. Apical dendrites suffered transient shortening while basal dendrites displayed sustained shortening. Moreover, dendrites suffered transient spine pruning. Significantly higher microglial cell density was found surrounding vM1 layer 5 pyramidal neurons after facial nerve lesion with morphological bias towards the activated phenotype. These results suggest that facial nerve lesions elicit active dendrite remodeling due to pyramidal neuron and microglia interaction, which could be the pathophysiological underpinning of some neuropathic motor sequelae in humans. PMID:26064916

Vagus Nerve Stimulation Delivered During Motor Rehabilitation Improves Recovery in a Rat Model of Stroke

PubMed Central

Khodaparast, Navid; Hays, Seth A.; Sloan, Andrew M.; Fayyaz, Tabbassum; Hulsey, Daniel R.; Rennaker, Robert L.; Kilgard, Michael P.

2014-01-01

Neural plasticity is widely believed to support functional recovery following brain damage. Vagus nerve stimulation paired with different forelimb movements causes long-lasting map plasticity in rat primary motor cortex that is specific to the paired movement. We tested the hypothesis that repeatedly pairing vagus nerve stimulation with upper forelimb movements would improve recovery of motor function in a rat model of stroke. Rats were separated into three groups: vagus nerve stimulation during rehab, vagus nerve stimulation after rehab, and rehab alone. Animals underwent 4 training stages: shaping (motor skill learning), pre-lesion training, post-lesion training, and therapeutic training. Rats were given a unilateral ischemic lesion within motor cortex and implanted with a left vagus nerve cuff. Animals were allowed one week of recovery before post-lesion baseline training. During the therapeutic training stage, rats received vagus nerve stimulation paired with each successful trial. All seventeen trained rats demonstrated significant contralateral forelimb impairment when performing a bradykinesia assessment task. Forelimb function was recovered completely to pre-lesion levels when vagus nerve stimulation was delivered during rehab training. Alternatively, intensive rehab training alone (without stimulation) failed to restore function to pre-lesion levels. Delivering the same amount of stimulation after rehab training did not yield improvements compared to rehab alone. These results demonstrate that vagus nerve stimulation repeatedly paired with successful forelimb movements can improve recovery after motor cortex ischemia and may be a viable option for stroke rehabilitation. PMID:24553102

High-Frequency Stimulation of the Subthalamic Nucleus Activates Motor Cortex Pyramidal Tract Neurons by a Process Involving Local Glutamate, GABA and Dopamine Receptors in Hemi-Parkinsonian Rats.

PubMed

Chuang, Chi-Fen; Wu, Chen-Wei; Weng, Ying; Hu, Pei-San; Yeh, Shin-Rung; Chang, Yen-Chung

2018-04-30

Deep brain stimulation (DBS) is widely used to treat advanced Parkinson’s disease (PD). Here, we investigated how DBS applied on the subthalamic nucleus (STN) influenced the neural activity in the motor cortex. Rats, which had the midbrain dopaminergic neurons partially depleted unilaterally, called the hemi-Parkinsonian rats, were used as a study model. c-Fos expression in the neurons was used as an indicator of neural activity. Application of high-frequency stimulation (HFS) upon the STN was used to mimic the DBS treatment. The motor cortices in the two hemispheres of hemi-Parkinsonian rats were found to contain unequal densities of c-Fos-positive (Fos+) cells, and STN-HFS rectified this bilateral imbalance. In addition, STN-HFS led to the intense c-Fos expression in a group of motor cortical neurons which exhibited biochemical and anatomical characteristics resembling those of the pyramidal tract (PT) neurons sending efferent projections to the STN. The number of PT neurons expressing high levels of c-Fos was significantly reduced by local application of the antagonists of non-N-methyl-D-aspartate (non-NMDA) glutamate receptors, gammaaminobutyric acid A (GABAA) receptors and dopamine receptors in the upper layers of the motor cortex. The results indicate that the coincident activations of synapses and dopamine receptors in the motor cortex during STN-HFS trigger the intense expression of c-Fos of the PT neurons. The implications of the results on the cellular mechanism underlying the therapeutic effects of STN-DBS on the movement disorders of PD are also discussed.

Semantic processing in the left versus right cerebral hemispheres following unilateral hand contractions.

PubMed

Turner, Casey E; Hahn, Michael E; Kellogg, Ronald T

2017-03-01

Unilateral hand contractions increase activation in the motor cortex of the contralateral hemisphere, providing a means to alter the relative degree of activation in the right hemisphere versus the left hemisphere through spreading activation. Prior research reported enhanced verbal creativity as measured by performance on remote associate problems in Hebrew from left-hand contractions (right-hemisphere activation). We sought to extend the previous findings to English problems and to homograph interpretation. In Experiment 1, unilateral hand contractions in fact altered performance on the English remote associates, but in the direction of improved performance following right-hand contractions and left-hemisphere activation. In Experiment 2, the probability of retrieving atypical interpretations of homographs with multiple meanings was least likely for left-hemisphere dominant strong right handers, but the hand contraction manipulation had no effect.

A hand and a field effect in on-line motor control in unilateral optic ataxia.

PubMed

Blangero, Annabelle; Gaveau, Valérie; Luauté, Jacques; Rode, Gilles; Salemme, Romeo; Guinard, Marine; Boisson, Dominique; Rossetti, Yves; Pisella, Laure

2008-05-01

Patients with bilateral optic ataxia fail to show rapid perturbation-induced corrections during manual aiming movements. Based on this, it has been proposed that this pathology results from a disruption of processes of on-line motor control in the posterior parietal cortex (PPC). Here, we show that on-line motor control performance in a patient with unilateral optic ataxia is similar to that of pointing towards stationary targets in peripheral vision, showing the same combination of hand and field effects. We also show that in the patient, manual correction towards his ataxic field was possible only when a preceding saccade (100msec earlier) rapidly provides foveal information about the new target location. In control subjects, manual correction was often, but not necessarily preceded by a saccade. These results allow us to put forward a model of visuo-manual transformation, which involves updating of the reach plan based on the target-eye error, and rely upon two dissociated spatial representations (of the hand and of the target, respectively) within the PPC.

Should the injured and intact hemispheres be treated differently during the early phases of physical restorative therapy in experimental stroke or parkinsonism?

PubMed

Schallert, Tim; Fleming, Sheila M; Woodlee, Martin T

2003-02-01

Over a century ago the intact cortex was proposed to contribute to recovery from unilateral brain injury, but its possible role in functional outcome has become more appreciated in recent years as a result of anatomic, metabolic and behavioral studies. Although use of the contralesional limb is naturally impaired after sensorimotor cortex injury, neural and astrocytic events in the intact hemisphere may give rise to, and may be influenced by, an enhanced ability to compensate for lost motor function. The debate is still open as to whether the neural changes are generally compensatory in nature, with activity in the homotopic cortex leading to greater capability in the nonimpaired limb, or whether they are actually a matter of reorganization in the homotopic cortex leading to connections to denervated targets in the opposite hemisphere, thus allowing the homotopic cortex to control motor programs there. Although both phenomena may occur to some degree, there is mounting evidence in support of the former view. Careful behavioral techniques have been developed that can expose compensatory tricks, and the time course of these behaviors correlates well with anatomic data. Moreover, if the intact cortex sustains a second lesion after recovery from the first, forelimb sensorimotor function specific to the first-impaired side of the body is not worsened. Partial denervation of callosal fibers coming from the injured hemisphere, plus preferential use of the good forelimb caused by a cortical injury, may increase trophic factors in the intact hemisphere. These and related events seem to provide a growth-favorable environment there that permits motor learning in the intact forelimb at a level of skill exceeding that which a normal animal can attain in the same period of time. There are anecdotal cases in human neurologic patients that are consistent with these findings. For example, a colleague of the authors who sustained a unilateral infarction that rendered his dominant right hand severely impaired noticed that soon after the stroke he was able to use his left hand for writing and computers as well as he had ever used his right hand. Cross-midline placing tests also indicate that the structural events observed in the intact cortex may potentiate projections to the damaged hemisphere. These changes may help restore the capacity of tactile information projecting to the intact hemisphere to control limb placing in the impaired forelimb. Neural events in the injured hemisphere can be affected by behavior differently than the neural events in the intact hemisphere. Different therapeutic strategies might well be used on opposing limbs at different times after unilateral sensorimotor cortex injury to optimize recovery (and, indeed, to avoid exaggerating the insult). Finally, the details of reorganization in both hemispheres differ greatly depending on the type of brain injury sustained (eg, in stroke versus Parkinson's disease), suggesting that an approach that considers the role of both hemispheres is likely to be beneficial in research on a broad variety of brain pathologies.

Ephrin-B3 is the midline barrier that prevents corticospinal tract axons from recrossing, allowing for unilateral motor control.

PubMed

Kullander, K; Croll, S D; Zimmer, M; Pan, L; McClain, J; Hughes, V; Zabski, S; DeChiara, T M; Klein, R; Yancopoulos, G D; Gale, N W

2001-04-01

Growing axons follow highly stereotypical pathways, guided by a variety of attractive and repulsive cues, before establishing specific connections with distant targets. A particularly well-known example that illustrates the complexity of axonal migration pathways involves the axonal projections of motor neurons located in the motor cortex. These projections take a complex route during which they first cross the midline, then form the corticospinal tract, and ultimately connect with motor neurons in the contralateral side of the spinal cord. These obligatory contralateral connections account for why one side of the brain controls movement on the opposing side of the body. The netrins and slits provide well-known midline signals that regulate axonal crossings at the midline. Herein we report that a member of the ephrin family, ephrin-B3, also plays a key role at the midline to regulate axonal crossing. In particular, we show that ephrin-B3 acts as the midline barrier that prevents corticospinal tract projections from recrossing when they enter the spinal gray matter. We report that in ephrin-B3(-/-) mice, corticospinal tract projections freely recross in the spinal gray matter, such that the motor cortex on one side of the brain now provides bilateral input to the spinal cord. This neuroanatomical abnormality in ephrin-B3(-/-) mice correlates with loss of unilateral motor control, yielding mice that simultaneously move their right and left limbs and thus have a peculiar hopping gait quite unlike the alternate step gait displayed by normal mice. The corticospinal and walking defects in ephrin-B3(-/-) mice resemble those recently reported for mice lacking the EphA4 receptor, which binds ephrin-B3 as well as other ephrins, suggesting that the binding of EphA4-bearing axonal processes to ephrin-B3 at the midline provides the repulsive signal that prevents corticospinal tract projections from recrossing the midline in the developing spinal cord.

Prolyl hydroxylase regulates axonal rewiring and motor recovery after traumatic brain injury

PubMed Central

Miyake, S; Muramatsu, R; Hamaguchi, M; Yamashita, T

2015-01-01

Prolyl 4-hydroxylases (PHDs; PHD1, PHD2, and PHD3) are a component of cellular oxygen sensors that regulate the adaptive response depending on the oxygen concentration stabilized by hypoxia/stress-regulated genes transcription. In normoxic condition, PHD2 is required to stabilize hypoxia inducible factors. Silencing of PHD2 leads to the activation of intracellular signaling including RhoA and Rho-associated protein kinase (ROCK), which are key regulators of neurite growth. In this study, we determined that genetic or pharmacological inhibition of PHD2 in cultured cortical neurons prevents neurite elongation through a ROCK-dependent mechanism. We then explored the role of PHDs in axonal reorganization following a traumatic brain injury in adult mice. Unilateral destruction of motor cortex resulted in behavioral deficits due to disruption of the corticospinal tract (CST), a part of the descending motor pathway. In the spinal cord, sprouting of fibers from the intact side of the CST into the denervated side is thought to contribute to the recovery process following an injury. Intracortical infusion of PHD inhibitors into the intact side of the motor cortex abrogated spontaneous formation of CST collaterals and functional recovery after damage to the sensorimotor cortex. These findings suggest PHDs have an important role in the formation of compensatory axonal networks following an injury and may represent a new molecular target for the central nervous system disorders. PMID:25675298

Task-specificity of unilateral anodal and dual-M1 tDCS effects on motor learning.

PubMed

Karok, Sophia; Fletcher, David; Witney, Alice G

2017-01-08

Task-specific effects of transcranial direct current stimulation (tDCS) on motor learning were investigated in 30 healthy participants. In a sham-controlled, mixed design, participants trained on 3 different motor tasks (Purdue Pegboard Test, Visuomotor Grip Force Tracking Task and Visuomotor Wrist Rotation Speed Control Task) over 3 consecutive days while receiving either unilateral anodal over the right primary motor cortex (M1), dual-M1 or sham stimulation. Retention sessions were administered 7 and 28 days after the end of training. In the Purdue Pegboard Test, both anodal and dual-M1 stimulation reduced average completion time approximately equally, an improvement driven by online learning effects and maintained for about 1 week. The Visuomotor Grip Force Tracking Task and the Visuomotor Wrist Rotation Speed Control Task were associated with an advantage of dual-M1 tDCS in consolidation processes both between training sessions and when testing at long-term retention; both were maintained for at least 1 month. This study demonstrates that M1-tDCS enhances and sustains motor learning with different electrode montages. Stimulation-induced effects emerged at different learning phases across the tasks, which strongly suggests that the influence of tDCS on motor learning is dynamic with respect to the functional recruitment of the distributed motor system at the time of stimulation. Divergent findings regarding M1-tDCS effects on motor learning may partially be ascribed to task-specific consequences and the effects of offline consolidation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Microstructure of transcallosal motor fibers reflects type of cortical (re-)organization in congenital hemiparesis.

PubMed

Juenger, Hendrik; Koerte, Inga K; Muehlmann, Marc; Mayinger, Michael; Mall, Volker; Krägeloh-Mann, Ingeborg; Shenton, Martha E; Berweck, Steffen; Staudt, Martin; Heinen, Florian

2014-11-01

Early unilateral brain lesions can lead to different types of corticospinal (re-)organization of motor networks. In one group of patients, the contralesional hemisphere exerts motor control not only over the contralateral non-paretic hand but also over the (ipsilateral) paretic hand, as the primary motor cortex is (re-)organized in the contralesional hemisphere. Another group of patients with early unilateral lesions shows "normal" contralateral motor projections starting in the lesioned hemisphere. We investigated how these different patterns of cortical (re-)organization affect interhemispheric transcallosal connectivity in patients with congenital hemiparesis. Eight patients with ipsilateral motor projections (group IPSI) versus 7 patients with contralateral motor projections (group CONTRA) underwent magnetic resonance diffusion tensor imaging (DTI). The corpus callosum (CC) was subdivided in 5 areas (I-V) in the mid-sagittal slice and volumetric information. The following diffusion parameters were calculated: fractional anisotropy (FA), trace, radial diffusivity (RD), and axial diffusivity (AD). DTI revealed significantly lower FA, increased trace and RD for group IPSI compared to group CONTRA in area III of the corpus callosum, where transcallosal motor fibers cross the CC. In the directly neighboring area IV, where transcallosal somatosensory fibers cross the CC, no differences were found for these DTI parameters between IPSI and CONTRA. Volume of callosal subsections showed significant differences for area II (connecting premotor cortices) and III, where group IPSI had lower volume. The results of this study demonstrate that the callosal microstructure in patients with congenital hemiparesis reflects the type of cortical (re-)organization. Early lesions disrupting corticospinal motor projections to the paretic hand consecutively affect the development or maintenance of transcallosal motor fibers. Copyright © 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Functional neuroimaging of recovery from motor conversion disorder: A case report.

PubMed

Dogonowski, Anne-Marie; Andersen, Kasper W; Sellebjerg, Finn; Schreiber, Karen; Madsen, Kristoffer H; Siebner, Hartwig R

2018-03-27

A patient with motor conversion disorder presented with a functional paresis of the left hand. After exclusion of structural brain damage, she was repeatedly examined with whole-brain functional magnetic resonance imaging, while she performed visually paced finger-tapping tasks. The dorsal premotor cortex showed a bilateral deactivation in the acute-subacute phase. Recovery from unilateral hand paresis was associated with a gradual increase in task-based activation of the dorsal premotor cortex bilaterally. The right medial prefrontal cortex displayed the opposite pattern, showing initial task-based activation that gradually diminished with recovery. The inverse dynamics of premotor and medial prefrontal activity over time were found during unimanual finger-tapping with the affected and non-affected hand as well as during bimanual finger-tapping. These observations suggest that reduced premotor and increased medial prefrontal activity reflect an effector-independent cortical dysfunction in conversion paresis which gradually disappears in parallel with clinical remission of paresis. The results link the medial prefrontal and dorsal premotor areas to the generation of intentional actions. We hypothesise that an excessive 'veto' signal generated in medial prefrontal cortex along with decreased premotor activity might constitute the functional substrate of conversion disorder. This notion warrants further examination in a larger group of affected patients. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Comprehensive analysis of area-specific and time-dependent changes in gene expression in the motor cortex of macaque monkeys during recovery from spinal cord injury.

PubMed

Higo, Noriyuki; Sato, Akira; Yamamoto, Tatsuya; Oishi, Takao; Nishimura, Yukio; Murata, Yumi; Onoe, Hirotaka; Isa, Tadashi; Kojima, Toshio

2018-05-01

The present study aimed to assess the molecular bases of cortical compensatory mechanisms following spinal cord injury in primates. To accomplish this, comprehensive changes in gene expression were investigated in the bilateral primary motor cortex (M1), dorsal premotor cortex (PMd), and ventral premotor cortex (PMv) after a unilateral lesion of the lateral corticospinal tract (l-CST). At 2 weeks after the lesion, a large number of genes exhibited altered expression levels in the contralesional M1, which is directly linked to the lesioned l-CST. Gene ontology and network analyses indicated that these changes in gene expression are involved in the atrophy and plasticity changes observed in neurons. Orchestrated gene expression changes were present when behavioral recovery was attained 3 months after the lesion, particularly among the bilateral premotor areas, and a large number of these genes are involved in plasticity. Moreover, several genes abundantly expressed in M1 of intact monkeys were upregulated in both the PMd and PMv after the l-CST lesion. These area-specific and time-dependent changes in gene expression may underlie the molecular mechanisms of functional recovery following a lesion of the l-CST. © 2018 Wiley Periodicals, Inc.

Effects of electroacupuncture on metabolic changes in motor cortex and striatum of 6-hydroxydopamine-induced Parkinsonian rats.

PubMed

Li, Min; Wang, Ke; Su, Wen-Ting; Jia, Jun; Wang, Xiao-Min

2017-10-06

To explore the possible underlying mechanism by investigating the effect of electroacupuncture (EA) treatment on the primary motor cortex and striatum in a unilateral 6-hydroxydopamine (6-OHDA) induced rat Parkinson's disease (PD) model. Male Sprague-Dawley rats were randomly divided into sham group (n=16), model group (n=14), and EA group (n=14). EA stimulation at Dazhui (GV 14) and Baihui (GV20) was applied to PD rats in the EA group for 4 weeks. Behavioral tests were conducted to evaluate the effectiveness of EA treatment. Metabolites were detected by 7.0 T proton nuclear magnetic resonance. Following 4 weeks of EA treatment in PD model rats, the abnormal behavioral impairment induced by 6-OHDA was alleviated. In monitoring changes in metabolic activity, ratios of myoinositol/creatine (Cr) and N-acetyl aspartate (NAA)/Cr in the primary motor cortex were significantly lower at the injected side than the non-injected side in PD rats (P=0.024 and 0.020). The ratios of glutamate + glutamine (Glx)/Cr and NAA/Cr in the striatum were higher and lower, respectively, at the injected side than the non-injected side (P=0.046 and 0.008). EA treatment restored the balance of metabolic activity in the primary motor cortex and striatum. In addition, the taurine/Cr ratio and Glx/Cr ratio were elevated in the striatum of PD model rats compared to sham-lesioned rats (P=0.026 and 0.000). EA treatment alleviated the excessive glutamatergic transmission by down-regulating the striatal Glx/Cr ratio (P=0.001). The Glx/Cr ratio was negatively correlated with floor plane spontaneous locomotion in PD rats (P=0.027 and P=0.0007). EA treatment is able to normalize the metabolic balance in the primary motor cortex and striatum of PD rats, which may contribute to its therapeutic effect on motor deficits. The striatal Glx/Cr ratio may serve as a potential indicator of PD and a therapeutic target of EA treatment.

Impaired glutamatergic projection from the motor cortex to the subthalamic nucleus in 6-hydroxydopamine-lesioned hemi-parkinsonian rats.

PubMed

Wang, Yan-Yan; Wang, Yong; Jiang, Hai-Fei; Liu, Jun-Hua; Jia, Jun; Wang, Ke; Zhao, Fei; Luo, Min-Hua; Luo, Min-Min; Wang, Xiao-Min

2018-02-01

The glutamatergic projection from the motor cortex to the subthalamic nucleus (STN) constitutes the cortico-basal ganglia circuit and plays a critical role in the control of movement. Emerging evidence shows that the cortico-STN pathway is susceptible to dopamine depletion. Specifically in Parkinson's disease (PD), abnormal electrophysiological activities were observed in the motor cortex and STN, while the STN serves as a key target of deep brain stimulation for PD therapy. However, direct morphological changes in the cortico-STN connectivity in response to PD progress are poorly understood at present. In the present study, we used a trans-synaptic anterograde tracing method with herpes simplex virus-green fluorescent protein (HSV-GFP) to monitor the cortico-STN connectivity in a rat model of PD. We found that the connectivity from the primary motor cortex (M1) to the STN was impaired in parkinsonian rats as manifested by a marked decrease in trans-synaptic infection of HSV-GFP from M1 neurons to STN neurons in unilateral 6-hydroxydopamine (6-OHDA)-lesioned rats. Ultrastructural analysis with electron microscopy revealed that excitatory synapses in the STN were also impaired in parkinsonian rats. Glutamatergic terminals identified by a specific marker (vesicular glutamate transporter 1) were reduced in the STN, while glutamatergic neurons showed an insignificant change in their total number in both the M1 and STN regions. These results indicate that the M1-STN glutamatergic connectivity is downregulated in parkinsonian rats. This downregulation is mediated probably via a mechanism involving the impairments of excitatory terminals and synapses in the STN. Copyright © 2017. Published by Elsevier Inc.

Contralesional Axonal Remodeling of the Corticospinal System in Adult Rats After Stroke and Bone Marrow Stromal Cell Treatment

PubMed Central

Liu, Zhongwu; Li, Yi; Zhang, Xueguo; Savant-Bhonsale, Smita; Chopp, Michael

2008-01-01

Background and Purpose Motor recovery after stroke is associated with neuronal reorganization in bilateral hemispheres. We investigated contralesional corticospinal tract remodeling in the brain and spinal cord in rats after stroke and treatment of bone marrow stromal cells. Methods Adult male Wistar rats were subjected to permanent right middle cerebral artery occlusion. Phosphate-buffered saline or bone marrow stromal cells were injected into a tail vein 1 day postischemia. An adhesive removal test was performed weekly to monitor functional recovery. Threshold currents of intracortical microstimulation on the left motor cortex for evoking bilateral forelimb movements were measured 6 weeks after stroke. When intracortical microstimulation was completed, biotinylated dextran amine was injected into the left motor cortex to anterogradely label the corticospinal tract. At 4 days before euthanization, pseudorabies virus-152-EGFP and 614-mRFP were injected into left or right forelimb extensor muscles, respectively. All animals were euthanized 8 weeks after stroke. Results In normal rats (n=5), the corticospinal tract showed a unilateral innervation pattern. In middle cerebral artery occlusion rats (n=8), our data demonstrated that: 1) stroke reduced the stimulation threshold evoking ipsilateral forelimb movement; 2) EGFP-positive pyramidal neurons were increased in the left intact cortex, which were labeled from the left stroke-impaired forelimb; and 3) biotinylated dextran amine-labeled contralesional axons sprouted into the denervated spinal cord. Bone marrow stromal cells significantly enhanced all 3 responses (n=8, P<0.05). Conclusions Our data demonstrated that corticospinal tract fibers originating from the contralesional motor cortex sprout into the denervated spinal cord after stroke and bone marrow stromal cells treatment, which may contribute to functional recovery. PMID:18617661

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.

Motor cortex stimulation suppresses cortical responses to noxious hindpaw stimulation after spinal cord lesion in rats.

PubMed

Jiang, Li; Ji, Yadong; Voulalas, Pamela J; Keaser, Michael; Xu, Su; Gullapalli, Rao P; Greenspan, Joel; Masri, Radi

2014-01-01

Motor cortex stimulation (MCS) is a potentially effective treatment for chronic neuropathic pain. The neural mechanisms underlying the reduction of hyperalgesia and allodynia after MCS are not completely understood. To investigate the neural mechanisms responsible for analgesic effects after MCS. We test the hypothesis that MCS attenuates evoked blood oxygen-level dependent signals in cortical areas involved in nociceptive processing in an animal model of chronic neuropathic pain. We used adult female Sprague-Dawley rats (n = 10) that received unilateral electrolytic lesions of the right spinal cord at the level of C6 (SCL animals). In these animals, we performed magnetic resonance imaging (fMRI) experiments to study the analgesic effects of MCS. On the day of fMRI experiment, 14 days after spinal cord lesion, the animals were anesthetized and epidural bipolar platinum electrodes were placed above the left primary motor cortex. Two 10-min sessions of fMRI were performed before and after a session of MCS (50 μA, 50 Hz, 300 μs, for 30 min). During each fMRI session, the right hindpaw was electrically stimulated (noxious stimulation: 5 mA, 5 Hz, 3 ms) using a block design of 20 s stimulation off and 20 s stimulation on. A general linear model-based statistical parametric analysis was used to analyze whole brain activation maps. Region of interest (ROI) analysis and paired t-test were used to compare changes in activation before and after MCS in these ROI. MCS suppressed evoked blood oxygen dependent signals significantly (Family-wise error corrected P < 0.05) and bilaterally in 2 areas heavily implicated in nociceptive processing. These areas consisted of the primary somatosensory cortex and the prefrontal cortex. These findings suggest that, in animals with SCL, MCS attenuates hypersensitivity by suppressing activity in the primary somatosensory cortex and prefrontal cortex. Copyright © 2014. Published by Elsevier Inc.

Regional cerebral blood flow changes associated with focal electrically administered seizure therapy (FEAST).

PubMed

Chahine, George; Short, Baron; Spicer, Ken; Schmidt, Matthew; Burns, Carol; Atoui, Mia; George, Mark S; Sackeim, Harold A; Nahas, Ziad

2014-01-01

Use of electroconvulsive therapy (ECT) is limited by cognitive disturbance. Focal electrically-administered seizure therapy (FEAST) is designed to initiate focal seizures in the prefrontal cortex. To date, no studies have documented the effects of FEAST on regional cerebral blood flow (rCBF). A 72 year old depressed man underwent three single photon emission computed tomography (SPECT) scans to capture the onset and resolution of seizures triggered with right unilateral FEAST. We used Bioimage Suite for within-subject statistical analyses of perfusion differences ictally and post-ictally compared with the baseline scan. Early ictal increases in regional cerebral blood flow (rCBF) were limited to the right prefrontal cortex. Post-ictally, perfusion was reduced in bilateral frontal and occipital cortices and increased in left motor and precuneus cortex. FEAST appears to triggers focal onsets of seizure activity in the right prefrontal cortex with subsequent generalization. Future studies are needed on a larger sample. Copyright © 2014 Elsevier Inc. All rights reserved.

Symmetry of fMRI activation in the primary sensorimotor cortex during unilateral chewing.

PubMed

Lotze, M; Domin, M; Kordass, B

2017-05-01

Functional magnetic resonance imaging (fMRI) is one of the most advanced techniques to analyze the cerebral effects on many behavior aspects of the oral system such as chewing and mastication. Studies on imaging of the cerebral representation of chewing demonstrated differential results with respect to cortical lateralization during unilateral chewing. The aim of our study is to clarify the effects of cerebral responses during unilateral chewing. We used fMRI to compare brain activities during occlusal function in centric occlusion on natural teeth and chewing on a gum located on the right or the left teeth in 15 healthy subjects. Group data were performed by Talairach normalization and in addition by an assignment of activation maxima to individual anatomical landmarks in order to avoid possible loss of spatial preciseness of activation sites by normalization procedures. Evaluation of group data by Talairach normalization revealed representation sites for occlusal movements in bilateral primary (S1) and secondary (S2) somatosensory cortices, primary motor (M1) and premotor cortices, supplementary motor area (SMA) and medial cingulate gyrus, bilateral anterior cerebellar hemispheres and vermis, insula, orbitofrontal cortex, thalamus, and left pallidum. Right-sided chewing showed no differential activation to left-sided chewing, and both showed activation in areas also involved in bilateral occlusion. Both techniques, the one based on group normalization and the one based on an individual evaluation method, revealed remarkable low differences in activation maximum location in the primary motor, the primary and secondary somatosensory cortices, and the anterior cerebellar lobe. All chewing movements tested involved bilateral sensorimotor activation without a significant lateralization of activation intensities. Overall, a general lateralization of occlusion movements to the dominant side could not be verified in the present study. Chewing on the left or on the right side of teeth makes no difference for brain representation of chewing. The results describe the basic effects of what we can expect by evaluation of cerebral effects of chewing and mastication. Based on these results, clinical fMRI studies can be performed in different patient groups.

Magnetoencephalographic study of hand and foot sensorimotor organization in 325 consecutive patients evaluated for tumor or epilepsy surgery

PubMed Central

Willemse, Ronald B.; Hillebrand, Arjan; Ronner, Hanneke E.; Peter Vandertop, W.; Stam, Cornelis J.

2015-01-01

Objectives The presence of intracranial lesions or epilepsy may lead to functional reorganization and hemispheric lateralization. We applied a clinical magnetoencephalography (MEG) protocol for the localization of the contralateral and ipsilateral S1 and M1 of the foot and hand in patients with non-lesional epilepsy, stroke, developmental brain injury, traumatic brain injury and brain tumors. We investigated whether differences in activation patterns could be related to underlying pathology. Methods Using dipole fitting, we localized the sources underlying sensory and motor evoked magnetic fields (SEFs and MEFs) of both hands and feet following unilateral stimulation of the median nerve (MN) and posterior tibial nerve (PTN) in 325 consecutive patients. The primary motor cortex was localized using beamforming following a self-paced repetitive motor task for each hand and foot. Results The success rate for motor and sensory localization for the feet was significantly lower than for the hands (motor_hand 94.6% versus motor_feet 81.8%, p < 0.001; sensory_hand 95.3% versus sensory_feet 76.0%, p < 0.001). MN and PTN stimulation activated 86.6% in the contralateral S1, with ipsilateral activation < 0.5%. Motor cortex activation localized contralaterally in 76.1% (5.2% ipsilateral, 7.6% bilateral and 11.1% failures) of all motor MEG recordings. The ipsilateral motor responses were found in 43 (14%) out of 308 patients with motor recordings (range: 8.3–50%, depending on the underlying pathology), and had a higher occurrence in the foot than in the hand (motor_foot 44.8% versus motor_hand 29.6%, p = 0.031). Ipsilateral motor responses tended to be more frequent in patients with a history of stroke, traumatic brain injury (TBI) or developmental brain lesions (p = 0.063). Conclusions MEG localization of sensorimotor cortex activation was more successful for the hand compared to the foot. In patients with neural lesions, there were signs of brain reorganization as measured by more frequent ipsilateral motor cortical activation of the foot in addition to the traditional sensory and motor activation patterns in the contralateral hemisphere. The presence of ipsilateral neural reorganization, especially around the foot motor area, suggests that careful mapping of the hand and foot in both contralateral and ipsilateral hemispheres prior to surgery might minimize postoperative deficits. PMID:26693401

Plasticity Induced by Intermittent Theta Burst Stimulation in Bilateral Motor Cortices Is Not Altered in Older Adults

PubMed Central

Dickins, Daina S. E.; Sale, Martin V.

2015-01-01

Numerous studies have reported that plasticity induced in the motor cortex by transcranial magnetic stimulation (TMS) is attenuated in older adults. Those investigations, however, have focused solely on the stimulated hemisphere. Compared to young adults, older adults exhibit more widespread activity across bilateral motor cortices during the performance of unilateral motor tasks, suggesting that the manifestation of plasticity might also be altered. To address this question, twenty young (<35 years old) and older adults (>65 years) underwent intermittent theta burst stimulation (iTBS) whilst attending to the hand targeted by the plasticity-inducing procedure. The amplitude of motor evoked potentials (MEPs) elicited by single pulse TMS was used to quantify cortical excitability before and after iTBS. Individual responses to iTBS were highly variable, with half the participants showing an unexpected decrease in cortical excitability. Contrary to predictions, however, there were no age-related differences in the magnitude or manifestation of plasticity across bilateral motor cortices. The findings suggest that advancing age does not influence the capacity for, or manifestation of, plasticity induced by iTBS. PMID:26064691

Varieties of paw and digit movement during spontaneous food handling in rats: postures, bimanual coordination, preferences, and the effect of forelimb cortex lesions.

PubMed

Whishaw, I Q; Coles, B L

1996-05-01

This study describes how rats use their paws and digits when handling a wide range of foodstuffs, including food pellets, grapes, sunflower seeds, shelled and unshelled peanuts, and different sized pastas, etc. Analysis of videorecordings show that the rats display digit postures that include variations in the spacing of the digits, differences in the relative use of different digits, and interlimb differences in paw and digit posture. The rats also display limb preferences in that one paw is used in a supporting function while the other rotates, flips, or pushes the food as is required by the shape of the item. There is a significant correlation between the paw used for manipulation and food items of similar shape but no correlation between the limb used for manipulation and that used for skilled reaching. Small unilateral lesions to the forepaw area of somatic sensorimotor cortex produced impairments in use of the paw contralateral to the lesions. These results: (1) reveal a surprising complexity in the way in which rats use their paws and digits in manipulating food; (2) show that rats have limb preferences in spontaneous food handling; and (3) show that manipulatory dexterity is dependent upon the integrity of the forelimb area of motor cortex. The results are discussed in relation to the evolution of motor skill, the use of rats for investigating questions of motor system organization, neural plasticity, and recovery of function after brain damage.

The effect of video-guidance on passive movement in patients with cerebral palsy: fMRI study.

PubMed

Dinomais, Mickael; Chinier, Eva; Lignon, Gregoire; Richard, Isabelle; Ter Minassian, Aram; Tich, Sylvie Nguyen The

2013-10-01

In patients with cerebral palsy (CP), neuroimaging studies have demonstrated that passive movement and action-observation tasks have in common to share neuronal activation in all or part of areas involved in motor system. Action observation with simultaneous congruent passive movements may have additional effects in the recruitment of brain motor areas. The aim of this functional magnetic resonance imaging (fMRI) study was to examine brain activation in patients with unilateral CP during passive movement with and without simultaneous observation of simple hand movement. Eighteen patients with unilateral CP (fourteen male, mean age 14 years and 2 months) participated in the study. Using fMRI block design, brain activation following passive simple opening-closing hand movement of either the paretic or nonparetic hand with and without simultaneous observation of a similar movement performed by either the left or right hand of an actor was compared. Passive movement of the paretic hand performed simultaneously to the observation of congruent movement activated more "higher motor areas" including contralesional pre-supplementary motor area, superior frontal gyrus (extending to premotor cortex), and superior and inferior parietal regions than nonvideo-guided passive movement of the paretic hand. Passive movement of the paretic hand recruited more ipsilesional sensorimotor areas compared to passive movement of the nonparetic hand. Our study showed that the combination of observation of congruent hand movement simultaneously to passive movement of the paretic hand recruits more motor areas, giving neuronal substrate to propose video-guided passive movement of paretic hand in CP rehabilitation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Rehabilitation-triggered cortical plasticity after stroke: in vivo imaging at multiple scales (Conference Presentation)

NASA Astrophysics Data System (ADS)

Allegra Mascaro, Anna Letizia; Conti, Emilia; Lai, Stefano; Spalletti, Cristina; Di Giovanna, Antonino Paolo; Alia, Claudia; Panarese, Alessandro; Sacconi, Leonardo; Micera, Silvestro; Caleo, Matteo; Pavone, Francesco S.

2017-02-01

Neurorehabilitation protocols based on the use of robotic devices provide a highly repeatable therapy and have recently shown promising clinical results. Little is known about how rehabilitation molds the brain to promote motor recovery of the affected limb. We used a custom-made robotic platform that provides quantitative assessment of forelimb function in a retraction test. Complementary imaging techniques allowed us to access to the multiple facets of robotic rehabilitation-induced cortical plasticity after unilateral photothrombotic stroke in mice Primary Motor Cortex (Caudal Forelimb Area - CFA). First, we analyzed structural features of vasculature and dendritic reshaping in the peri-infarct area with two-photon fluorescence microscopy. Longitudinal analysis of dendritic branches and spines of pyramidal neurons suggests that robotic rehabilitation promotes the stabilization of peri-infarct cortical excitatory circuits, which is not accompanied by consistent vascular reorganization towards pre-stroke conditions. To investigate if this structural stabilization was linked to functional remapping, we performed mesoscale wide-field imaging on GCaMP6 mice while performing the motor task on the robotic platform. We revealed temporal and spatial features of the motor-triggered cortical activation, shining new light on rehabilitation-induced functional remapping of the ipsilesional cortex. Finally, by using an all-optical approach that combines optogenetic activation of the contralesional hemisphere and wide-field functional imaging of peri-infarct area, we dissected the effect of robotic rehabilitation on inter-hemispheric cortico-cortical connectivity.

Graded motor imagery and the impact on pain processing in a case of CRPS.

PubMed

Walz, Andrea D; Usichenko, Taras; Moseley, G Lorimer; Lotze, Martin

2013-03-01

Graded motor imagery (GMI) shows promising results for patients with complex regional pain syndrome (CRPS). In a case with chronic unilateral CRPS type I, we applied GMI for 6 weeks and recorded clinical parameters and cerebral activation using functional magnetic resonance imaging (fMRI; pre-GMI, after each GMI block, and after 6 mo). Changes in fMRI activity were mapped during movement execution in areas associated with pain processing. A healthy participant served as a control for habituation effects. Pain intensity decreased over the course of GMI, and relief was maintained at follow-up. fMRI during movement execution revealed marked changes in S1 and S2 (areas of discriminative pain processing), which seemed to be associated with pain reduction, but none in the anterior insula and the anterior cingulate cortex (areas of affective pain processing). After mental rotation training, the activation intensity of the posterior parietal cortex was reduced to one third. Our case report develops a design capable of differentiating cerebral changes associated with behavioral therapy of CRPS type I study.

Normalizing motor-related brain activity: subthalamic nucleus stimulation in Parkinson disease.

PubMed

Grafton, S T; Turner, R S; Desmurget, M; Bakay, R; Delong, M; Vitek, J; Crutcher, M

2006-04-25

To test whether therapeutic unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson disease (PD) leads to normalization in the pattern of brain activation during movement execution and control of movement extent. Six patients with PD were imaged off medication by PET during performance of a visually guided tracking task with the DBS voltage programmed for therapeutic (effective) or subtherapeutic (ineffective) stimulation. Data from patients with PD during ineffective stimulation were compared with a group of 13 age-matched control subjects to identify sites with abnormal patterns of activation. Conjunction analysis was used to identify those areas in patients with PD where activity normalized when they were treated with effective stimulation. For movement execution, effective DBS caused an increase of activation in the supplementary motor area (SMA), superior parietal cortex, and cerebellum toward a more normal pattern. At rest, effective stimulation reduced overactivity of SMA. Therapeutic stimulation also induced reductions of movement related "overactivity" compared with healthy subjects in prefrontal, temporal lobe, and basal ganglia circuits, consistent with the notion that many areas are recruited to compensate for ineffective motor initiation. Normalization of activity related to the control of movement extent was associated with reductions of activity in primary motor cortex, SMA, and basal ganglia. Effective subthalamic nucleus stimulation leads to task-specific modifications with appropriate recruitment of motor areas as well as widespread, nonspecific reductions of compensatory or competing cortical activity.

Implied functional crossed cerebello-cerebral diaschisis and interhemispheric compensation during hand grasping more than 20 years after unilateral cerebellar injury in early childhood.

PubMed

Nakahachi, Takayuki; Ishii, Ryouhei; Canuet, Leonides; Iwase, Masao

2015-01-01

Crossed cerebello-cerebral diaschisis (CCCD) conventionally refers to decreased resting cerebral activity caused by injury to the contralateral cerebellum. We investigated whether functional activation of a contralesional cerebral cortical region controlling a specific task is reduced during task performance in a patient with a unilateral cerebellar lesion. We also examined functional compensation by the corresponding ipsilesional cerebral cortex. It was hypothesized that dysfunction of the primary sensorimotor cortex (SM1) contralateral to the cerebellar lesion would be detected together with a compensatory increase in neural activity of the ipsilesional SM1. To test these possibilities, we conducted non-invasive functional neuroimaging techniques for bilateral SM1 during hand grasping, a task known to activate predominantly the SM1 contralateral to the grasping hand. Activity in SM1 during hand grasping was measured electrophysiologically by magnetoencephalography and hemodynamically by near-infrared spectroscopy in an adult with mild right hemiataxia associated with a large injury of the right cerebellum due to resection of a tumor in early childhood. During left hand grasping, increased neural activity was detected predominantly in the right SM1, the typical developmental pattern. In contrast, neural activity increased in the bilateral SM1 with slight right-side dominance during right (ataxic) hand grasping. This study reported a case that implied functional CCCD and compensatory neural activity in the SM1 during performance of a simple hand motor task in an adult with unilateral cerebellar injury and mild hemiataxia 24 years prior to the study without rehabilitative interventions. This suggests that unilateral cerebellar injuries in early childhood may result in persistent functional abnormalities in the cerebrum into adulthood. Therapeutic treatments that target functional CCCD and interhemispheric compensation might be effective for treating ataxia due to unilateral cerebellar damage.

Motor cortex and hippocampus are the two main cortical targets in LGI1-antibody encephalitis.

PubMed

Navarro, Vincent; Kas, Aurélie; Apartis, Emmanuelle; Chami, Linda; Rogemond, Véronique; Levy, Pierre; Psimaras, Dimitri; Habert, Marie-Odile; Baulac, Michel; Delattre, Jean-Yves; Honnorat, Jérome

2016-04-01

Encephalitis associated with antibodies against leucine-rich glioma-inactivated 1 (LGI1) protein is increasingly recognized as an auto-immune disorder associated with characteristic tonic-dystonic seizures. The cortical or subcortical origin of these motor events is not clear. Some patients also present with different epileptic seizures and with cognitive impairment. The frequency of these features and their timing during the natural history of this encephalitis have not been fully described. We therefore reviewed data from 34 patients harbouring antibodies against LGI1 protein (21-81 years, median age 64) referred to the French Reference Centre for Neurological Paraneoplastic Syndrome. Three types of evidence suggested tonic-dystonic seizures were of cortical origin: (i) a slow, unilateral, frontal electroencephalographic wave, of duration ∼580 ms and amplitude ∼71 µV, preceded the contralateral tonic-dystonic seizures in simultaneous electroencephalographic and myographic records from seven of seven patients tested; (ii) 18-Fluorodeoxyglucose imaging revealed a strong hypermetabolism in primary motor cortex, controlateral to the affected limb, during encephalitis for five patients tested, as compared with data from the same patients after remission or from 16 control subjects; and (iii) features of polymyographic records of tonic-dystonic seizure events pointed to a cortical origin. Myoclonic patterns with brief, rhythmic bursts were present in three of five patients tested and a premyoclonic potential was identified in the cortex of one patient. Initially during encephalitis, 11 of 34 patients exhibited tonic-dystonic seizures (32%). Distinct epileptic syndromes were evident in 13 patients (38%). They were typically simple, focal seizures from the temporal lobe, consisting of vegetative symptoms or fear. At later stages, 22 of 32 patients displayed tonic-dystonic seizures (68%) and 29 patients presented frequent seizures (91%) including status epilepticus. Cognitive impairment, either anterograde amnesia or confusion was evident in 30 of 34 patients (88%). Brain imaging was normal in patients with isolated tonic-dystonic seizures; in patients with limbic symptoms it revealed initially a hippocampal hyperintensity in 8 of 19 patients (42%) and 17 of 24 patients (70%) at later stages. Our data suggest that the major signs of LGI1-antibody encephalitis can be linked to involvement of motor cortex and hippocampus. They occur in parallel with striatum involvement. One of these cortical targets is involved, often unilaterally at disease onset. As the encephalitis progresses, in the absence of immunomodulatory treatment, the second cortical target is affected and effects become bilateral. Progression to the second cortical target occurs with a variable delay of days to several months. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Neurophysiological mechanisms and functional impact of mirror movements in children with unilateral spastic cerebral palsy.

PubMed

Kuo, Hsing-Ching; Friel, Kathleen M; Gordon, Andrew M

2018-02-01

Children with unilateral spastic cerebral palsy (CP) often have mirror movements, i.e. involuntary imitations of unilateral voluntary movements of the contralateral upper extremity. The pathophysiology of mirror movements has been investigated in small and heterogeneous cohorts in the literature. Specific pathophysiology of mirror movements and their impact on upper extremity function require systematic investigation in larger and homogeneous cohorts of children with unilateral spastic CP. Here we review two possible neurophysiological mechanisms underlying mirror movements in children with CP and those with typical development: (1) an ipsilateral corticospinal tract projecting from the contralesional motor cortex (M1) to both upper extremities; (2) insufficient interhemispheric inhibition between the two M1s. We also discuss clinical implications of mirror movements in children with unilateral CP and suggest that a thorough examination of the relationship between the pathophysiology and clinical manifestations of mirror movements is warranted. We suggest two premises: (1) the presence of mirror movements is indicative of an ipsilateral corticospinal tract reorganization; and (2) the corticospinal tract organization may affect patients' responses to certain treatment. If these premises are supported through future research, mirror movements should be clinically evaluated for patient selection to maximize benefits of therapy, hence promoting individualized medicine in this population. Mirror movements may be indicative of the underlying corticospinal tract reorganization in children with unilateral spastic cerebral palsy (CP). Future research will benefit from systematic investigations of the relationship between mirror movements and its pathophysiology. Mirror movements may be a potential biomarker for individualized medicine in children with unilateral spastic CP. © 2017 Mac Keith Press.

Optimal dose of hyperbaric bupivacaine 0.5% for unilateral spinal anesthesia during diagnostic knee arthroscopy

PubMed Central

Atef, HM; El-Kasaby, AM; Omera, MA; Badr, MD

2010-01-01

Objective To determine the dose of hyperbaric bupivacaine 0.5% required for unilateral spinal anesthesia during diagnostic knee arthroscopy. Patients and methods This prospective, randomized, clinical study was performed in 80 patients who were assigned to four groups to receive different doses of intrathecal hyperbaric bupivacaine (5 mg, 7.5 mg, 10 mg and 12.5 mg in Groups 1, 2, 3, and 4 respectively). Onset of sensory and motor block, hemodynamic changes, regression of motor block, and incidence of complications were recorded. Results Unilateral sensory block was reported in 90% and 85% of patients in Group 1 and Group 2, respectively, but not in any patient in Group 3 and Group 4. Unilateral motor block (modified Bromage scale 0) was reported in 95% of patients in Group 1, 90% in Group 2, and only 5% in Group 3, while no patient in Group 4 showed unilateral motor block. The time required for regression of motor block (Bromage scale 0) was prolonged with higher doses. The incidence of nausea, vomiting, and urine retention was similar in the study groups. Conclusion Unilateral sensory and motor block can be achieved with doses of 5 mg and 7.5 mg hyperbaric bupivacaine 0.5% with a stable hemodynamic state. However, 7.5 mg of hyperbaric bupivacaine 0.5% was the dose required for adequate unilateral spinal anesthesia. PMID:22915874

Neuronal network-based mathematical modeling of perceived verticality in acute unilateral vestibular lesions: from nerve to thalamus and cortex.

PubMed

Glasauer, S; Dieterich, M; Brandt, T

2018-05-29

Acute unilateral lesions of vestibular graviceptive pathways from the otolith organs and semicircular canals via vestibular nuclei and the thalamus to the parieto-insular vestibular cortex regularly cause deviations of perceived verticality in the frontal roll plane. These tilts are ipsilateral in peripheral and in ponto-medullary lesions and contralateral in ponto-mesencephalic lesions. Unilateral lesions of the vestibular thalamus or cortex cause smaller tilts of the perceived vertical, which may be either ipsilateral or contralateral. Using a neural network model, we previously explained why unilateral vestibular midbrain lesions rarely manifest with rotational vertigo. We here extend this approach, focussing on the direction-specific deviations of perceived verticality in the roll plane caused by acute unilateral vestibular lesions from the labyrinth to the cortex. Traditionally, the effect of unilateral peripheral lesions on perceived verticality has been attributed to a lesion-based bias of the otolith system. We here suggest, on the basis of a comparison of model simulations with patient data, that perceived visual tilt after peripheral lesions is caused by the effect of a torsional semicircular canal bias on the central gravity estimator. We further argue that the change of gravity coding from a peripheral/brainstem vectorial representation in otolith coordinates to a distributed population coding at thalamic and cortical levels can explain why unilateral thalamic and cortical lesions have a variable effect on perceived verticality. Finally, we propose how the population-coding network for gravity direction might implement the elements required for the well-known perceptual underestimation of the subjective visual vertical in tilted body positions.

Neurosteroid allopregnanolone reduces ipsilateral visual cortex potentiation following unilateral optic nerve injury.

PubMed

Sergeeva, Elena G; Espinosa-Garcia, Claudia; Atif, Fahim; Pardue, Machelle T; Stein, Donald G

2018-05-02

In adult mice with unilateral optic nerve crush injury (ONC), we studied visual response plasticity in the visual cortex following stimulation with sinusoidal grating. We examined visually evoked potentials (VEP) in the primary visual cortex ipsilateral and contralateral to the crushed nerve. We found that unilateral ONC induces enhancement of visual response on the side ipsilateral to the injury that is evoked by visual stimulation to the intact eye. This enhancement was associated with supranormal spatial frequency thresholds in the intact eye when tested using optomotor response. To probe whether injury-induced disinhibition caused the potentiation, we treated animals with the neurosteroid allopregnanolone, a potent agonist of the GABA A receptor, one hour after crush and on post-injury days 3, 8, 13, and 18. Allopregnanolone diminished enhancement of the VEP and this effect was associated with the upregulated synthesis of the δ-subunit of the GABA A receptor. Our study shows a new aspect of experience-dependent plasticity following unilateral ONC. This hyper-activity in the ipsilateral visual cortex is prevented by upregulation of GABA inhibition with allopregnanolone. Our findings suggest the therapeutic potential of allopregnanolone for modulation of plasticity in certain eye and brain disorders and a possible role for disinhibition in ipsilateral hyper-activity following unilateral ONC. Copyright © 2018. Published by Elsevier Inc.

Post-Stroke Longitudinal Alterations of Inter-Hemispheric Correlation and Hemispheric Dominance in Mouse Pre-Motor Cortex

PubMed Central

Panarese, Alessandro; Alia, Claudia; Micera, Silvestro; Caleo, Matteo; Di Garbo, Angelo

2016-01-01

Purpose Limited restoration of function is known to occur spontaneously after an ischemic injury to the primary motor cortex. Evidence suggests that Pre-Motor Areas (PMAs) may “take over” control of the disrupted functions. However, little is known about functional reorganizations in PMAs. Forelimb movements in mice can be driven by two cortical regions, Caudal and Rostral Forelimb Areas (CFA and RFA), generally accepted as primary motor and pre-motor cortex, respectively. Here, we examined longitudinal changes in functional coupling between the two RFAs following unilateral photothrombotic stroke in CFA (mm from Bregma: +0.5 anterior, +1.25 lateral). Methods Local field potentials (LFPs) were recorded from the RFAs of both hemispheres in freely moving injured and naïve mice. Neural signals were acquired at 9, 16 and 23 days after surgery (sub-acute period in stroke animals) through one bipolar electrode per hemisphere placed in the center of RFA, with a ground screw over the occipital bone. LFPs were pre-processed through an efficient method of artifact removal and analysed through: spectral,cross-correlation, mutual information and Granger causality analysis. Results Spectral analysis demonstrated an early decrease (day 9) in the alpha band power in both the RFAs. In the late sub-acute period (days 16 and 23), inter-hemispheric functional coupling was reduced in ischemic animals, as shown by a decrease in the cross-correlation and mutual information measures. Within the gamma and delta bands, correlation measures were already reduced at day 9. Granger analysis, used as a measure of the symmetry of the inter-hemispheric causal connectivity, showed a less balanced activity in the two RFAs after stroke, with more frequent oscillations of hemispheric dominance. Conclusions These results indicate robust electrophysiological changes in PMAs after stroke. Specifically, we found alterations in transcallosal connectivity, with reduced inter-hemispheric functional coupling and a fluctuating dominance pattern. These reorganizations may underlie vicariation of lost functions following stroke. PMID:26752066

Post-Stroke Longitudinal Alterations of Inter-Hemispheric Correlation and Hemispheric Dominance in Mouse Pre-Motor Cortex.

PubMed

Vallone, Fabio; Lai, Stefano; Spalletti, Cristina; Panarese, Alessandro; Alia, Claudia; Micera, Silvestro; Caleo, Matteo; Di Garbo, Angelo

2016-01-01

Limited restoration of function is known to occur spontaneously after an ischemic injury to the primary motor cortex. Evidence suggests that Pre-Motor Areas (PMAs) may "take over" control of the disrupted functions. However, little is known about functional reorganizations in PMAs. Forelimb movements in mice can be driven by two cortical regions, Caudal and Rostral Forelimb Areas (CFA and RFA), generally accepted as primary motor and pre-motor cortex, respectively. Here, we examined longitudinal changes in functional coupling between the two RFAs following unilateral photothrombotic stroke in CFA (mm from Bregma: +0.5 anterior, +1.25 lateral). Local field potentials (LFPs) were recorded from the RFAs of both hemispheres in freely moving injured and naïve mice. Neural signals were acquired at 9, 16 and 23 days after surgery (sub-acute period in stroke animals) through one bipolar electrode per hemisphere placed in the center of RFA, with a ground screw over the occipital bone. LFPs were pre-processed through an efficient method of artifact removal and analysed through: spectral,cross-correlation, mutual information and Granger causality analysis. Spectral analysis demonstrated an early decrease (day 9) in the alpha band power in both the RFAs. In the late sub-acute period (days 16 and 23), inter-hemispheric functional coupling was reduced in ischemic animals, as shown by a decrease in the cross-correlation and mutual information measures. Within the gamma and delta bands, correlation measures were already reduced at day 9. Granger analysis, used as a measure of the symmetry of the inter-hemispheric causal connectivity, showed a less balanced activity in the two RFAs after stroke, with more frequent oscillations of hemispheric dominance. These results indicate robust electrophysiological changes in PMAs after stroke. Specifically, we found alterations in transcallosal connectivity, with reduced inter-hemispheric functional coupling and a fluctuating dominance pattern. These reorganizations may underlie vicariation of lost functions following stroke.

Converging levels of analysis in the cognitive neuroscience of visual attention.

PubMed Central

Duncan, J

1998-01-01

Experiments using behavioural, lesion, functional imaging and single neuron methods are considered in the context of a neuropsychological model of visual attention. According to this model, inputs compete for representation in multiple visually responsive brain systems, sensory and motor, cortical and subcortical. Competition is biased by advance priming of neurons responsive to current behavioural targets. Across systems competition is integrated such that the same, selected object tends to become dominant throughout. The behavioural studies reviewed concern divided attention within and between modalities. They implicate within-modality competition as one main restriction on concurrent stimulus identification. In contrast to the conventional association of lateral attentional focus with parietal lobe function, the lesion studies show attentional bias to be a widespread consequence of unilateral cortical damage. Although the clinical syndrome of unilateral neglect may indeed be associated with parietal lesions, this probably reflects an assortment of further deficits accompanying a simple attentional imbalance. The functional imaging studies show joint involvement of lateral prefrontal and occipital cortex in lateral attentional focus and competition. The single unit studies suggest how competition in several regions of extrastriate cortex is biased by advance priming of neurons responsive to current behavioural targets. Together, the concepts of competition, priming and integration allow a unified theoretical approach to findings from behavioural to single neuron levels. PMID:9770224

Bilateral Activity-Dependent Interactions in the Developing Corticospinal System

PubMed Central

Friel, Kathleen M.; Martin, John H.

2009-01-01

Activity-dependent competition between the corticospinal (CS) systems in each hemisphere drives postnatal development of motor skills and stable CS tract connections with contralateral spinal motor circuits. Unilateral restriction of motor cortex (M1) activity during an early postnatal critical period impairs contralateral visually guided movements later in development and in maturity. Silenced M1 develops aberrant connections with the contralateral spinal cord whereas the initially active M1, in the other hemisphere, develops bilateral connections. In this study, we determined whether the aberrant pattern of CS tract terminations and motor impairments produced by early postnatal M1 activity restriction could be abrogated by reducing activity-dependent synaptic competition from the initially active M1 later in development. We first inactivated M1 unilaterally between postnatal weeks 5–7. We next inactivated M1 on the other side from weeks 7–11 (alternate inactivation), to reduce the competitive advantage that this side may have over the initially inactivated side. Alternate inactivation redirected aberrant contralateral CS tract terminations from the initially silenced M1 to their normal spinal territories and reduced the density of aberrant ipsilateral terminations from the initially active side. Normal movement endpoint control during visually guided locomotion was fully restored. This reorganization of CS terminals reveals an unsuspected late plasticity after the critical period for establishing the pattern of CS terminations in the spinal cord. Our findings show that robust bilateral interactions between the developing CS systems on each side are important for achieving balance between contralateral and ipsilateral CS tract connections and visuomotor control. PMID:17928450

Changes in interhemispheric motor connectivity after muscle fatigue

NASA Astrophysics Data System (ADS)

Peltier, Scott; LaConte, Stephen M.; Niyazov, Dmitriy; Liu, Jing; Sahgal, Vinod; Yue, Guang; Hu, Xiaoping

2005-04-01

Synchronized oscillations in resting state timecourses have been detected in recent fMRI studies. These oscillations are low frequency in nature (< 0.08 Hz), and seem to be a property of symmetric cortices. These fluctuations are important as a potential signal of interest, which could indicate connectivity between functionally related areas of the brain. It has also been shown that the synchronized oscillations decrease in some spontaneous pathological states. Thus, detection of these functional connectivity patterns may help to serve as a gauge of normal brain activity. The cognitive effects of muscle fatigue are not well characterized. Sustained fatigue has the potential to dynamically alter activity in brain networks. In this work, we examined the interhemispheric correlations in the left and right primary motor cortices and how they change with muscle fatigue. Resting-state functional MRI imaging was done before and after a repetitive unilateral fatigue task. We find that the number of significant correlations in the bilateral motor network decreases with fatigue. These results suggest that resting-state interhemispheric motor cortex functional connectivity is affected by muscle fatigue.

Spine Topographical Distribution of Skin α-Synuclein Deposits in Idiopathic Parkinson Disease.

PubMed

Donadio, Vincenzo; Incensi, Alex; Rizzo, Giovanni; Scaglione, Cesa; Capellari, Sabina; Fileccia, Enrico; Avoni, Patrizia; Liguori, Rocco

2017-05-01

Phosphorylated α-synuclein (p-syn) in skin nerves mainly in the proximal sites is a promising neurodegenerative biomarker for idiopathic Parkinson disease (IPD). However, the p-syn spine distribution particularly in patients with unilateral motor dysfunctions remains undefined. This study aimed to investigate in IPD p-syn differences between left and right cervical spine sites in patients with prevalent unilateral motor symptoms, and cervical and thoracic spine sites in patients with bilateral motor symptoms. We enrolled 28 IPD patients fulfilling clinical diagnostic criteria associated with abnormal nigro-striatal DatScan and cardiac MIBG: 15 with prevalently unilateral motor symptoms demonstrated by DatScan; 13 with bilateral motor symptoms and DatScan abnormalities. Patients underwent skin biopsy searching for intraneural p-syn deposits: skin samples were taken from C7 paravertebral left and right sites in unilateral patients and from cervical (C7) and thoracic (Th12) paravertebral spine regions in bilateral patients. Unilateral patients displayed 20% of abnormal p-syn deposits in the affected motor site, 60% in both sites and 20% only in the non-affected site. P-syn was found in all patients in C7 but in only 62% of patients in Th12. Our data showed that cervical p-syn deposits displayed a uniform distribution between both sides not following the motor dysfunction in unilateral patients, and skin nerve p-syn deposits demonstrated a spine gradient with the cervical site expressing the highest positivity. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

Bilateral versus ipsilesional cortico-subcortical activity patterns in stroke show hemispheric dependence.

PubMed

Vidal, Ana C; Banca, Paula; Pascoal, Augusto G; Cordeiro, Gustavo; Sargento-Freitas, João; Gouveia, Ana; Castelo-Branco, Miguel

2018-01-01

Background Understanding of interhemispheric interactions in stroke patients during motor control is an important clinical neuroscience quest that may provide important clues for neurorehabilitation. In stroke patients bilateral overactivation in both hemispheres has been interpreted as a poor prognostic indicator of functional recovery. In contrast, ipsilesional patterns have been linked with better motor outcomes. Aim We investigated the pathophysiology of hemispheric interactions during limb movement without and with contralateral restraint, to mimic the effects of constraint-induced movement therapy. We used neuroimaging to probe brain activity with such a movement-dependent interhemispheric modulation paradigm. Methods We used a functional magnetic resonance imaging block design during which the plegic/paretic upper limb was recruited/mobilized to perform unilateral arm elevation, as a function of presence versus absence of contralateral limb restriction (n = 20, with balanced left/right lesion sites). Results Analysis of 10 right hemispheric stroke participants yielded bilateral sensorimotor cortex activation in all movement phases in contrast with the unilateral dominance seen in the 10 left hemispheric stroke participants. Superimposition of contralateral restriction led to a prominent shift from activation to deactivation response patterns, in particular in cortical and basal ganglia motor areas in right hemispheric stroke. Left hemispheric stroke was, in general, characterized by reduced activation patterns, even in the absence of restriction, which induced additional cortical silencing. Conclusion The observed hemispheric-dependent activation/deactivation shifts is novel and these pathophysiological observations suggest short-term neuroplasticity that may be useful for hemisphere-tailored neurorehabilitation.

Bilateral versus ipsilesional cortico-subcortical activity patterns in stroke show hemispheric dependence.

PubMed

Vidal, A Cristina; Banca, Paula; Pascoal, Augusto G; Santo, Gustavo C; Sargento-Freitas, João; Gouveia, Ana; Castelo-Branco, Miguel

2017-01-01

Background Understanding of interhemispheric interactions in stroke patients during motor control is an important clinical neuroscience quest that may provide important clues for neurorehabilitation. In stroke patients, bilateral overactivation in both hemispheres has been interpreted as a poor prognostic indicator of functional recovery. In contrast, ipsilesional patterns have been linked with better motor outcomes. Aim We investigated the pathophysiology of hemispheric interactions during limb movement without and with contralateral restraint, to mimic the effects of constraint-induced movement therapy. We used neuroimaging to probe brain activity with such a movement-dependent interhemispheric modulation paradigm. Methods We used an fMRI block design during which the plegic/paretic upper limb was recruited/mobilized to perform unilateral arm elevation, as a function of presence versus absence of contralateral limb restriction ( n = 20, with balanced left/right lesion sites). Results Analysis of 10 right-hemispheric stroke participants yielded bilateral sensorimotor cortex activation in all movement phases in contrast with the unilateral dominance seen in the 10 left-hemispheric stroke participants. Superimposition of contralateral restriction led to a prominent shift from activation to deactivation response patterns, in particular in cortical and basal ganglia motor areas in right-hemispheric stroke. Left-hemispheric stroke was in general characterized by reduced activation patterns, even in the absence of restriction, which induced additional cortical silencing. Conclusion The observed hemispheric-dependent activation/deactivation shifts are novel and these pathophysiological observations suggest short-term neuroplasticity that may be useful for hemisphere-tailored neurorehabilitation.

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.

[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.

Acoustic input and efferent activity regulate the expression of molecules involved in cochlear micromechanics

PubMed Central

Lamas, Veronica; Arévalo, Juan C.; Juiz, José M.; Merchán, Miguel A.

2015-01-01

Electromotile activity in auditory outer hair cells (OHCs) is essential for sound amplification. It relies on the highly specialized membrane motor protein prestin, and its interactions with the cytoskeleton. It is believed that the expression of prestin and related molecules involved in OHC electromotility may be dynamically regulated by signals from the acoustic environment. However little is known about the nature of such signals and how they affect the expression of molecules involved in electromotility in OHCs. We show evidence that prestin oligomerization is regulated, both at short and relatively long term, by acoustic input and descending efferent activity originating in the cortex, likely acting in concert. Unilateral removal of the middle ear ossicular chain reduces levels of trimeric prestin, particularly in the cochlea from the side of the lesion, whereas monomeric and dimeric forms are maintained or even increased in particular in the contralateral side, as shown in Western blots. Unilateral removal of the auditory cortex (AC), which likely causes an imbalance in descending efferent activity on the cochlea, also reduces levels of trimeric and tetrameric forms of prestin in the side ipsilateral to the lesion, whereas in the contralateral side prestin remains unaffected, or even increased in the case of trimeric and tetrameric forms. As far as efferent inputs are concerned, unilateral ablation of the AC up-regulates the expression of α10 nicotinic Ach receptor (nAChR) transcripts in the cochlea, as shown by RT-Quantitative real-time PCR (qPCR). This suggests that homeostatic synaptic scaling mechanisms may be involved in dynamically regulating OHC electromotility by medial olivocochlear efferents. Limited, unbalanced efferent activity after unilateral AC removal, also affects prestin and β-actin mRNA levels. These findings support that the concerted action of acoustic and efferent inputs to the cochlea is needed to regulate the expression of major molecules involved in OHC electromotility, both at the transcriptional and posttranscriptional levels. PMID:25653600

Detection of reduced interhemispheric cortical communication during task execution in multiple sclerosis patients using functional near-infrared spectroscopy

NASA Astrophysics Data System (ADS)

Jimenez, Jon J.; Yang, Runze; Nathoo, Nabeela; Varshney, Vishal P.; Golestani, Ali-Mohammad; Goodyear, Bradley G.; Metz, Luanne M.; Dunn, Jeff F.

2014-07-01

Multiple sclerosis (MS) impairs brain activity through demyelination and loss of axons. Increased brain activity is accompanied by increases in microvascular hemoglobin oxygen saturation (oxygenation) and total hemoglobin, which can be measured using functional near-infrared spectroscopy (fNIRS). Due to the potentially reduced size and integrity of the white matter tracts within the corpus callosum, it may be expected that MS patients have reduced functional communication between the left and right sides of the brain; this could potentially be an indicator of disease progression. To assess interhemispheric communication in MS, we used fNIRS during a unilateral motor task and the resting state. The magnitude of the change in hemoglobin parameters in the motor cortex was significantly reduced in MS patients during the motor task relative to healthy control subjects. There was also a significant decrease in interhemispheric communication between the motor cortices (expressed as coherence) in MS patients compared to controls during the motor task, but not during the resting state. fNIRS assessment of interhemispheric coherence during task execution may be a useful marker in disorders with white matter damage or axonal loss, including MS.

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.

Motor Learning of a Bimanual Task in Children with Unilateral Cerebral Palsy

ERIC Educational Resources Information Center

Hung, Ya-Ching; Gordon, Andrew M.

2013-01-01

Children with unilateral cerebral palsy (CP) have been shown to improve their motor performance with sufficient practice. However, little is known about how they learn goal-oriented tasks. In the current study, 21 children with unilateral CP (age 4-10 years old) and 21 age-matched typically developed children (TDC) practiced a simple bimanual…

Explicit and implicit motor learning in children with unilateral cerebral palsy.

PubMed

van der Kamp, John; Steenbergen, Bert; Masters, Rich S W

2017-07-30

The current study aimed to investigate the capacity for explicit and implicit learning in children with unilateral cerebral palsy. Children with left and right unilateral cerebral palsy and typically developing children shuffled disks toward a target. A prism-adaptation design was implemented, consisting of pre-exposure, prism exposure, and post-exposure phases. Half of the participants were instructed about the function of the prism glasses, while the other half were not. For each trial, the distance between the target and the shuffled disk was determined. Explicit learning was indicated by the rate of adaptation during the prism exposure phase, whereas implicit learning was indicated by the magnitude of the negative after-effect at the start of the post-exposure phase. Results No significant effects were revealed between typically developing participants and participants with unilateral cerebral palsy. Comparison of participants with left and right unilateral cerebral palsy demonstrated that participants with right unilateral cerebral palsy had a significantly lower rate of adaptation than participants with left unilateral cerebral palsy, but only when no instructions were provided. The magnitude of the negative after-effects did not differ significantly between participants with right and left unilateral cerebral palsy. The capacity for explicit motor learning is reduced among individuals with right unilateral cerebral palsy when accumulation of declarative knowledge is unguided (i.e., discovery learning). In contrast, the capacity for implicit learning appears to remain intact among individuals with left as well as right unilateral cerebral palsy. Implications for rehabilitation Implicit motor learning interventions are recommended for individuals with cerebral palsy, particularly for individuals with right unilateral cerebral palsy Explicit motor learning interventions for individual with cerebral palsy - if used - best consist of singular verbal instruction.

Brain Activity and Human Unilateral Chewing

PubMed Central

Quintero, A.; Ichesco, E.; Myers, C.; Schutt, R.; Gerstner, G.E.

2012-01-01

Brain mechanisms underlying mastication have been studied in non-human mammals but less so in humans. We used functional magnetic resonance imaging (fMRI) to evaluate brain activity in humans during gum chewing. Chewing was associated with activations in the cerebellum, motor cortex and caudate, cingulate, and brainstem. We also divided the 25-second chew-blocks into 5 segments of equal 5-second durations and evaluated activations within and between each of the 5 segments. This analysis revealed activation clusters unique to the initial segment, which may indicate brain regions involved with initiating chewing. Several clusters were uniquely activated during the last segment as well, which may represent brain regions involved with anticipatory or motor events associated with the end of the chew-block. In conclusion, this study provided evidence for specific brain areas associated with chewing in humans and demonstrated that brain activation patterns may dynamically change over the course of chewing sequences. PMID:23103631

The side of chronic low back pain matters: evidence from the primary motor cortex excitability and the postural adjustments of multifidi muscles.

PubMed

Massé-Alarie, Hugo; Beaulieu, Louis-David; Preuss, Richard; Schneider, Cyril

2017-03-01

Hemispheric lateralization of pain processing was reported with overactivation of the right frontal lobe. Specifically in chronic low back pain (CLBP), functional changes in the left primary motor cortex (M1) with impaired anticipatory postural activation (APA) of trunk muscles have been observed. Given the connections between frontal and M1 areas for motor planning, it is hypothesized that the pain side could differently influence M1 function and APA of paravertebral multifidus (MF) muscles. This study aimed at testing whether people with right- versus left-sided CLBP showed different M1 excitability and APA. Thirty-five individuals with lateralized CLBP (19 right-sided and 16 left-sided) and 13 pain-free subjects (normative values) were tested for the excitability of MF M1 area (active motor threshold-AMT) with transcranial magnetic stimulation and for the latency of MF APA during bilateral shoulder flexion and during unilateral hip extension in prone lying. In the right-sided CLBP group, the AMT of both M1 areas was lower than in the left-sided group and the pain-free subjects; the latency of MF APA was shorter in bilateral shoulder flexion and in the left hip extension tasks as compared to the left-sided group. In CLBP, an earlier MF APA was correlated with lower AMT in both tasks. People with right-sided CLBP presented with increased M1 excitability in both hemispheres and earlier MF APA. These results likely rely on cortical motor adaptation related to the tasks and axial muscles tested. Future studies should investigate whether CLBP side-related differences have a clinical impact, e.g. in diagnosis and intervention.

Functional networks of motor inhibition in conversion disorder patients and feigning subjects.

PubMed

Hassa, Thomas; de Jel, Esther; Tuescher, Oliver; Schmidt, Roger; Schoenfeld, Mircea Ariel

2016-01-01

The neural correlates of motor inhibition leading to paresis in conversion disorder are not well known. The key question is whether they are different of those of normal subjects feigning the symptoms. Thirteen conversion disorder patients with hemiparesis and twelve healthy controls were investigated using functional magnetic resonance tomography under conditions of passive motor stimulation of the paretic/feigned paretic and the non-paretic hand. Healthy controls were also investigated in a non-feigning condition. During passive movement of the affected right hand conversion disorder patients exhibited activations in the bilateral triangular part of the inferior frontal gyri (IFG), with a left side dominance compared to controls in non-feigning condition. Feigning controls revealed for the same condition a weak unilateral activation in the right triangular part of IFG and an activity decrease in frontal midline areas, which couldn't be observed in patients. The results suggest that motor inhibition in conversion disorder patients is mediated by the IFG that was also involved in inhibition processes in normal subjects. The activity pattern in feigning controls resembled that of conversion disorder patients but with a clear difference in the medial prefrontal cortex. Healthy controls showed decreased activity in this region during feigning compared to non-feigning conditions suggesting a reduced sense of self-agency during feigning. Remarkably, no activity differences could be observed in medial prefrontal cortex for patients vs healthy controls in feigning or non-feigning conditions suggesting self-agency related activity in patients to be in between those of non-feigning and feigning healthy subjects.

Functional difference in short- and long-latency interhemispheric inhibitions from active to resting hemisphere during a unilateral muscle contraction.

PubMed

Uehara, Kazumasa; Morishita, Takuya; Kubota, Shinji; Hirano, Masato; Funase, Kozo

2014-01-01

The aim of the present study was to investigate whether there is a functional difference in short-latency (SIHI) and long-latency (LIHI) interhemispheric inhibition from the active to the resting primary motor cortex (M1) with paired-pulse transcranial magnetic stimulation during a unilateral muscle contraction. In nine healthy right-handed participants, IHI was tested from the dominant to the nondominant M1 and vice versa under resting conditions or during performance of a sustained unilateral muscle contraction with the right or left first dorsal interosseous muscle at 10% and 30% maximum voluntary contraction. To obtain measurements of SIHI and LIHI, a conditioning stimulus (CS) was applied over the M1 contralateral to the muscle contraction, followed by a test stimulus over the M1 ipsilateral to the muscle contraction at short (10 ms) and long (40 ms) interstimulus intervals. We used four CS intensities to investigate SIHI and LIHI from the active to the resting M1 systematically. The amount of IHI during the unilateral muscle contractions showed a significant difference between SIHI and LIHI, but the amount of IHI during the resting condition did not. In particular, SIHI during the muscle contractions, but not LIHI, significantly increased with increase in CS intensity compared with the resting condition. Laterality of IHI was not detected in any of the experimental conditions. The present study provides novel evidence that a functional difference between SIHI and LIHI from the active to the resting M1 exists during unilateral muscle contractions.

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

Fornix and retrosplenial contribution to a hippocampo-thalamic circuit underlying conditional learning.

PubMed

Dumont, Julie R; Petrides, Michael; Sziklas, Viviane

2010-05-01

Rats with combined bilateral lesions of the retrosplenial cortex and the fornix or rats with unilateral lesions to the anterior thalamus and the hippocampus, made in opposite hemispheres (disconnection preparation), and combined with unilateral damage of the retrosplenial cortex in either hemisphere, were tested on a spatial-visual conditional learning task in which they learned arbitrary associations between stimuli and the scene in which they were embedded. All experimental groups were impaired in comparison with normal animals. The more severe deficits occurred when (1) both the fornix and the retrosplenial cortex were damaged bilaterally thus depriving the hippocampus both from subcortical interactions via the fornix and retrosplenial-mediated interactions and (2) when, in the crossed lesion preparation, the unilateral retrosplenial lesion was made in the hemisphere with the intact hippocampus, again because this lesion would be maximally disconnecting the hippocampus from functional interaction with the anterior thalamic nucleus and retrosplenial-mediated input.

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.

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.

Unilateral hearing during development: hemispheric specificity in plastic reorganizations

PubMed Central

Kral, Andrej; Heid, Silvia; Hubka, Peter; Tillein, Jochen

2013-01-01

The present study investigates the hemispheric contributions of neuronal reorganization following early single-sided hearing (unilateral deafness). The experiments were performed on ten cats from our colony of deaf white cats. Two were identified in early hearing screening as unilaterally congenitally deaf. The remaining eight were bilaterally congenitally deaf, unilaterally implanted at different ages with a cochlear implant. Implanted animals were chronically stimulated using a single-channel portable signal processor for two to five months. Microelectrode recordings were performed at the primary auditory cortex under stimulation at the hearing and deaf ear with bilateral cochlear implants. Local field potentials (LFPs) were compared at the cortex ipsilateral and contralateral to the hearing ear. The focus of the study was on the morphology and the onset latency of the LFPs. With respect to morphology of LFPs, pronounced hemisphere-specific effects were observed. Morphology of amplitude-normalized LFPs for stimulation of the deaf and the hearing ear was similar for responses recorded at the same hemisphere. However, when comparisons were performed between the hemispheres, the morphology was more dissimilar even though the same ear was stimulated. This demonstrates hemispheric specificity of some cortical adaptations irrespective of the ear stimulated. The results suggest a specific adaptation process at the hemisphere ipsilateral to the hearing ear, involving specific (down-regulated inhibitory) mechanisms not found in the contralateral hemisphere. Finally, onset latencies revealed that the sensitive period for the cortex ipsilateral to the hearing ear is shorter than that for the contralateral cortex. Unilateral hearing experience leads to a functionally-asymmetric brain with different neuronal reorganizations and different sensitive periods involved. PMID:24348345

Unilateral hearing during development: hemispheric specificity in plastic reorganizations.

PubMed

Kral, Andrej; Heid, Silvia; Hubka, Peter; Tillein, Jochen

2013-01-01

The present study investigates the hemispheric contributions of neuronal reorganization following early single-sided hearing (unilateral deafness). The experiments were performed on ten cats from our colony of deaf white cats. Two were identified in early hearing screening as unilaterally congenitally deaf. The remaining eight were bilaterally congenitally deaf, unilaterally implanted at different ages with a cochlear implant. Implanted animals were chronically stimulated using a single-channel portable signal processor for two to five months. Microelectrode recordings were performed at the primary auditory cortex under stimulation at the hearing and deaf ear with bilateral cochlear implants. Local field potentials (LFPs) were compared at the cortex ipsilateral and contralateral to the hearing ear. The focus of the study was on the morphology and the onset latency of the LFPs. With respect to morphology of LFPs, pronounced hemisphere-specific effects were observed. Morphology of amplitude-normalized LFPs for stimulation of the deaf and the hearing ear was similar for responses recorded at the same hemisphere. However, when comparisons were performed between the hemispheres, the morphology was more dissimilar even though the same ear was stimulated. This demonstrates hemispheric specificity of some cortical adaptations irrespective of the ear stimulated. The results suggest a specific adaptation process at the hemisphere ipsilateral to the hearing ear, involving specific (down-regulated inhibitory) mechanisms not found in the contralateral hemisphere. Finally, onset latencies revealed that the sensitive period for the cortex ipsilateral to the hearing ear is shorter than that for the contralateral cortex. Unilateral hearing experience leads to a functionally-asymmetric brain with different neuronal reorganizations and different sensitive periods involved.

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.

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

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

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.

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

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

Callosal disconnection syndrome in a left-handed patient due to infarction of the total length of the corpus callosum.

PubMed

Lausberg, H; Göttert, R; Münssinger, U; Boegner, F; Marx, P

1999-03-01

We report on a left-handed patient with an ischemic infarction affecting exclusively the total length of the corpus callosum. This lesion clinically correlated with an almost complete callosal disconnection syndrome as described in callosotomy subjects, including unilateral verbal anosmia, hemialexia, unilateral ideomotor apraxia, unilateral agraphia, unilateral tactile anomia, unilateral constructional apraxia, lack of somesthetic transfer and dissociative phenomena. Despite the patient's left-handedness, his pattern of deficits was similar to the disconnection syndrome found in right-handers. Our report focusses on motor dominance and praxis. We followed-up the improvement in left apraxia and investigated the ability to initiate and learn a new visuo-motor skill. The results permit two tentative assumptions: (1) that the improvement in left apraxia was due to a compensatory increase in ipsilateral proximal muscle control, and (2) that motor dominance, i.e. the competence to initiate and learn a new movement pattern, was hemispherically dissociable from manual dominance in the sense of praxis control.

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

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.

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.

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

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

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.

[Changes of brain function and cognitive function after carotid artery stenting].

PubMed

Lu, Z X; Deng, G; Wei, H L; Zhao, G F; Wen, L Z; Chen, X

2017-10-24

Objective: To investigate the effect of carotid artery stenting(CAS) on cognitive function and brain function based on changes of a battery of neuropsychological tests and magnetic resonance imaging. Methods: Thirty-three patients were included with 17 in the stent-placement group and 16 in the control group (receiving medical treatment), among whom, the unilateral or bilateral severe internal carotid artery stenosis was confirmed by cerebral vascular angiography in the department of Interventional Radiology and Vascular Surgery of Zhongda Hospital Southeast University from June 2015 to September 2016.Neuropsychological tests and rest-state blood oxygenation level dependent fMRI were performed at the baseline and six months follow-up.The baseline characteristics and follow-up changes were compared in each group. Results: The overall cognitive function of the stent-placement group was statistically significantly improved ( P <0.05) compared with control group, mainly in the executive function, memory, attention and other aspects.The value of amplitude of low-frequency fluctuation(ALFF) showed statistically significant increase ( P <0.05, Alphasim correction) in left prefrontal cortex ( t =5.861 3, P <0.05), the somatosensory association cortex in left superior parietal lobe( t =5.601 2, P <0.05) and bilateral motor cortical area in posterior frontal lobe ( t =5.288 5, P <0.05). The ALFF showed statistically significant decrease ( P <0.05, Alphasim correction) in left retrosplenial cingulate cortex( t =-5.590 4, P <0.05), left insular cortex ( t =-6.340 8, P <0.05), right insular cortex ( t =-8.129 9, P <0.05) and left dorsal anterior cingulate cortex ( t =-5.584 8, P <0.05). There was no statistically significant difference ( P >0.05, Alphasim correction)between baseline and follow-up results in control group.Besides, the ALFF changes of the left insular cortex ( r =-0.591, P =0.033) and bilateral motor cortical area ( r =-0.659, P =0.014) were negatively correlated with auditory verb learning test (AVLT) score changes.The ALFF change of bilateral motor cortical area was negatively correlated with the AVLT-delay score change ( r =-0.588, P =0.034). And the ALFF change on right insular cortex and the frontal assessment battery (FAB) score change was positively correlated ( r =0.638, P =0.025). Conclusions: The overall cognitive function of patients with carotid artery stenosis significantly improve after CAS compared with medical treatment.The change of ALFF value in related brain area is also statistically significant.ALFF Change most in area of Default Mode Network may suggest a mechanism of postoperative neurological recovery in patients with carotid artery stenosis.

Alterations in primary motor cortex neurotransmission and gene expression in hemi-parkinsonian rats with drug-induced dyskinesia.

PubMed

Lindenbach, D; Conti, M M; Ostock, C Y; Dupre, K B; Bishop, C

2015-12-03

Treatment of Parkinson's disease (PD) with dopamine replacement relieves symptoms of poverty of movement, but often causes drug-induced dyskinesias. Accumulating clinical and pre-clinical evidence suggests that the primary motor cortex (M1) is involved in the pathophysiology of PD and that modulating cortical activity may be a therapeutic target in PD and dyskinesia. However, surprisingly little is known about how M1 neurotransmitter tone or gene expression is altered in PD, dyskinesia or associated animal models. The present study utilized the rat unilateral 6-hydroxydopamine (6-OHDA) model of PD/dyskinesia to characterize structural and functional changes taking place in M1 monoamine innervation and gene expression. 6-OHDA caused dopamine pathology in M1, although the lesion was less severe than in the striatum. Rats with 6-OHDA lesions showed a PD motor impairment and developed dyskinesia when given L-DOPA or the D1 receptor agonist, SKF81297. M1 expression of two immediate-early genes (c-Fos and ARC) was strongly enhanced by either L-DOPA or SKF81297. At the same time, expression of genes specifically involved in glutamate and GABA signaling were either modestly affected or unchanged by lesion and/or treatment. We conclude that M1 neurotransmission and signal transduction in the rat 6-OHDA model of PD/dyskinesia mirror features of human PD, supporting the utility of the model to study M1 dysfunction in PD and the elucidation of novel pathophysiological mechanisms and therapeutic targets. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Conditional genetic deletion of PTEN after a spinal cord injury enhances regenerative growth of CST axons and motor function recovery in mice

PubMed Central

Danilov, Camelia A.; Steward, Oswald

2015-01-01

Previous studies indicate that conditional genetic deletion of phosphatase and tensin homolog (PTEN) in neonatal mice enhances the ability of axons to regenerate following spinal cord injury (SCI) in adults. Here, we assessed whether deleting PTEN in adult neurons post-SCI is also effective, and whether enhanced regenerative growth is accompanied by enhanced recovery of voluntary motor function. PTENloxP/loxP mice received moderate contusion injuries at cervical level 5 (C5). One group received unilateral injections of adeno-associated virus expressing CRE (AAV-CRE) into the sensorimotor cortex; controls received a vector expressing green fluorescent protein (AAV-GFP) or injuries only (no vector injections). Forelimb function was tested for 14 weeks post-SCI using a grip strength meter (GSM) and a hanging task. The corticospinal tract (CST) was traced by injecting mini-ruby BDA into the sensorimotor cortex. Forelimb gripping ability was severely impaired immediately post-SCI but recovered slowly over time. The extent of recovery was significantly greater in PTEN-deleted mice in comparison to either the AAV-GFP group or the injury only group. BDA tract tracing revealed significantly higher numbers of BDA-labeled axons in caudal segments in the PTEN-deleted group compared to control groups. In addition, in the PTEN-deleted group, there were exuberant collaterals extending from the main tract rostral to the lesion, into and around the scar tissue at the injury site. These results indicate that PTEN deletion in adult mice shortly post-SCI can enhance regenerative growth of CST axons and forelimb motor function recovery. PMID:25704959

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.

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.

Using motor behavior during an early critical period to restore skilled limb movement after damage to the corticospinal motor system during development

PubMed Central

Friel, KM; Chakrabarty, S; H-C, Kuo; Martin, JH

2012-01-01

This study investigated requirements for restoring motor function after corticospinal (CS) system damage during early postnatal development. Activity-dependent competition between the CS tracts (CST) of the two hemispheres is imperative for normal development. Blocking primary motor cortex (M1) activity unilaterally during a critical period (postnatal weeks-PW-5–7) produces permanent contralateral motor skill impairments, loss of M1 motor map, aberrant CS terminations, and decreases in CST presynaptic sites and spinal cholinergic interneuron numbers. To repair these motor systems impairments and restore function, we manipulated motor experience in three groups of cats after this CST injury produced by inactivation. One group wore a jacket restraining the limb ipsilateral to inactivation, forcing use of the contralateral, impaired, limb, for the month following M1 inactivation (PW8–13; “Restraint Alone”). A second group wore the restraint during PW8–13, and was also trained for 1 h/day in a reaching task with the contralateral forelimb (“Early Training”). To test the efficacy of intervention during adolescence, a third group wore the restraint and received reach training during PW20–24 (“Delayed Training”). Early training restored CST connections and the M1 motor map; increased cholinergic spinal interneurons numbers on the contralateral, relative to ipsilateral, side; and abrogated limb control impairments. Delayed training restored CST connectivity and the M1 motor map, but not contralateral spinal cholinergic cell counts or motor performance. Restraint alone only restored CST connectivity. Our findings stress the need to reestablish the integrated functions of the CS system at multiple hierarchical levels in restoring skilled motor function after developmental injury. PMID:22764234

Comparison of two spinal needle types to achieve a unilateral spinal block.

PubMed

Kuusniemi, Kristiina; Leino, Kari; Lertola, Kaarlo; Pihlajamäki, Kalevi; Pitkänen, Mikko

2013-04-01

Unilateral spinal anesthesia is beneficial in patients undergoing unilateral leg surgery. The direction and the shape of the spinal needle are thought to influence the unilateral distribution of the local anesthetic in the intrathecal space. Therefore, to study the effects of different spinal needles we compared the effects of the Whitacre and Quincke spinal needles. This was a prospective, randomized, double-blind study of 60 consecutive outpatients scheduled for unilateral lower-limb surgery. The patients were randomized to receive spinal anesthesia with 1.2 ml of 0.5 % plain bupivacaine using either a 27-G Whitacre or a Quincke needle. One half of the local anesthetic was injected towards the nondependent side and the other half was directed cranially. The spread of spinal anesthesia, both sensory and motor blocks, was defined as the primary endpoint and was recorded at 10, 20, and 30 min after the spinal injection, at the end of the operation, 2 h after the spinal injection, and every 30 min thereafter until there was no motor block. Secondary endpoints included patient satisfaction and adverse effects. There was no difference in the spread of sensory or motor blocks between the Whitacre and the Quincke groups. However, the sensory and motor blocks on the operated and the nonoperated sides were significantly different at all testing times, as expected. There was no difference in the incidence of adverse effects or patient satisfaction scores between the Whitacre and the Quincke groups. Unilateral spinal block for outpatient surgery can be achieved with both pencil-point (Whitacre) and Quincke needles using 6.0 mg of plain bupivacaine. Neither the spread of sensory and motor blocks nor the corresponding recovery times appeared to be different between the groups. Nor was there any difference in patient satisfaction.

Traumatic injury to the immature frontal lobe: a new murine model of long-term motor impairment in the absence of psychosocial or cognitive deficits.

PubMed

Chen, Chien-Yi; Noble-Haeusslein, Linda J; Ferriero, Donna; Semple, Bridgette D

2013-01-01

Traumatic brain injury in children commonly involves the frontal lobes and is associated with distinct structural and behavioral changes. Despite the clinical significance of injuries localized to this region during brain development, the mechanisms underlying secondary damage and long-term recovery are poorly understood. Here, we have characterized the first model of unilateral focal traumatic injury to the developing frontal lobe. Male C57Bl/6J mice at postnatal day (p)21, an age approximating a toddler-aged child, received a controlled cortical impact or sham surgery to the left frontal lobe and were euthanized 1 or 7 days later. A necrotic cavity and local inflammatory response were largely confined to the unilateral frontal lobe, dorsal corpus callosum and striatum anterior to the bregma. While cell death and accumulated β-amyloid precursor protein were characteristic features of the pericontusional motor cortex, corpus callosum, cingulum and dorsal striatum, underlying structures including the hippocampus showed no overt pathology. To determine the long-term functional consequences of injury at p21, two additional cohorts were subjected to a battery of behavioral tests in adolescence (p35-45) or adulthood (p70-80). In both cohorts, brain-injured mice showed normal levels of anxiety, sociability, spatial learning and memory. The signature phenotypic features were deficits in motor function and motor learning, coincident with a reduction in ipsilateral cortical brain volumes. Together, these findings demonstrate classic morphological features of a focal traumatic injury, including early cell death and axonal injury, and long-term volumetric loss of cortical volumes. The presence of deficits in sensorimotor function and coordination in the absence of abnormal findings related to anxiety, sociability and memory likely reflects several variables, including the unique location of the injury and the emergence of favorable compensatory mechanisms during subsequent brain development. © 2013 S. Karger AG, Basel.

Traumatic injury to the immature frontal lobe: A new murine model of long-term motor impairment in the absence of psychosocial or cognitive deficits

PubMed Central

Chen, Chien-Yi; Noble-Haeusslein, Linda J; Ferriero, Donna; Semple, Bridgette D

2014-01-01

Traumatic brain injury in children commonly involves the frontal lobes, and is associated with distinct structural and behavioral changes. Despite the clinical significance of injuries localized to this region during brain development, the mechanisms underlying secondary damage and long-term recovery are poorly understood. Here we have characterized the first model of unilateral focal traumatic injury to the developing frontal lobe. Male C57Bl/6J mice at postnatal day (p) 21, an age approximating a toddler-aged child, received a controlled cortical impact or sham surgery to the left frontal lobe and were euthanized 1 and 7 d later. A necrotic cavity and local inflammatory response were largely confined to the unilateral frontal lobe, dorsal corpus callosum and striatum anterior to Bregma. While cell death and accumulated beta-amyloid precursor protein were characteristic features of the peri-contusional motor cortex, corpus callosum, cingulum and dorsal striatum, underlying structures including the hippocampus showed no overt pathology. To determine the long-term functional consequences of injury at p21, two additional cohorts were subjected to a battery of behavioral tests in adolescence (p35-45) or adulthood (p70-80). In both cohorts, brain-injured mice showed normal levels of anxiety, sociability, spatial learning and memory. The signature phenotypic features were deficits in motor function and motor learning, coincident with a reduction in ipsilateral cortical brain volumes. Together, these findings demonstrate classic morphological features of a focal traumatic injury, including early cell death and axonal injury, and long-term volumetric loss of cortical volumes. The presence of deficits in sensorimotor function and coordination in the absence of abnormal findings related to anxiety, sociability and memory, likely reflect several variables including the unique location of the injury and the emergence of favorable compensatory mechanisms during subsequent brain development. PMID:24247103

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

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.

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.

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.

Focal atrophy of the unilateral masticatory muscles caused by pure trigeminal motor neuropathy: case report.

PubMed

Kämppi, Antti; Kämppi, Leena; Kemppainen, Pentti; Kanerva, Mari; Toppila, Jussi; Auranen, Mari

2018-05-01

Patients with unknown clinical or radiological asymmetry in the face structures combined with atrophy and weakness of the masticatory muscles should be comprehensively examined clinically and with MRI, neurophysiological measurements, and serologically. Malignant lesions or benign idiopathic unilateral trigeminal motor neuropathy should be considered as an etiological explanation for the asymmetry.

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.

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.

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

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.

Asymmetrical Interhemispheric Connections Develop in Cat Visual Cortex after Early Unilateral Convergent Strabismus: Anatomy, Physiology, and Mechanisms

PubMed Central

Bui Quoc, Emmanuel; Ribot, Jérôme; Quenech’Du, Nicole; Doutremer, Suzette; Lebas, Nicolas; Grantyn, Alexej; Aushana, Yonane; Milleret, Chantal

2011-01-01

In the mammalian primary visual cortex, the corpus callosum contributes to the unification of the visual hemifields that project to the two hemispheres. Its development depends on visual experience. When this is abnormal, callosal connections must undergo dramatic anatomical and physiological changes. However, data concerning these changes are sparse and incomplete. Thus, little is known about the impact of abnormal postnatal visual experience on the development of callosal connections and their role in unifying representation of the two hemifields. Here, the effects of early unilateral convergent strabismus (a model of abnormal visual experience) were fully characterized with respect to the development of the callosal connections in cat visual cortex, an experimental model for humans. Electrophysiological responses and 3D reconstruction of single callosal axons show that abnormally asymmetrical callosal connections develop after unilateral convergent strabismus, resulting from an extension of axonal branches of specific orders in the hemisphere ipsilateral to the deviated eye and a decreased number of nodes and terminals in the other (ipsilateral to the non-deviated eye). Furthermore this asymmetrical organization prevents the establishment of a unifying representation of the two visual hemifields. As a general rule, we suggest that crossed and uncrossed retino-geniculo-cortical pathways contribute successively to the development of the callosal maps in visual cortex. PMID:22275883

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.

Assessment of the structural brain network reveals altered connectivity in children with unilateral cerebral palsy due to periventricular white matter lesions.

PubMed

Pannek, Kerstin; Boyd, Roslyn N; Fiori, Simona; Guzzetta, Andrea; Rose, Stephen E

2014-01-01

Cerebral palsy (CP) is a term to describe the spectrum of disorders of impaired motor and sensory function caused by a brain lesion occurring early during development. Diffusion MRI and tractography have been shown to be useful in the study of white matter (WM) microstructure in tracts likely to be impacted by the static brain lesion. The purpose of this study was to identify WM pathways with altered connectivity in children with unilateral CP caused by periventricular white matter lesions using a whole-brain connectivity approach. Data of 50 children with unilateral CP caused by periventricular white matter lesions (5-17 years; manual ability classification system [MACS] I = 25/II = 25) and 17 children with typical development (CTD; 7-16 years) were analysed. Structural and High Angular Resolution Diffusion weighted Images (HARDI; 64 directions, b = 3000 s/mm(2)) were acquired at 3 T. Connectomes were calculated using whole-brain probabilistic tractography in combination with structural parcellation of the cortex and subcortical structures. Connections with altered fractional anisotropy (FA) in children with unilateral CP compared to CTD were identified using network-based statistics (NBS). The relationship between FA and performance of the impaired hand in bimanual tasks (Assisting Hand Assessment-AHA) was assessed in connections that showed significant differences in FA compared to CTD. FA was reduced in children with unilateral CP compared to CTD. Seven pathways, including the corticospinal, thalamocortical, and fronto-parietal association pathways were identified simultaneously in children with left and right unilateral CP. There was a positive relationship between performance of the impaired hand in bimanual tasks and FA within the cortico-spinal and thalamo-cortical pathways (r(2) = 0.16-0.44; p < 0.05). This study shows that network-based analysis of structural connectivity can identify alterations in FA in unilateral CP, and that these alterations in FA are related to clinical function. Application of this connectome-based analysis to investigate alterations in connectivity following treatment may elucidate the neurological correlates of improved functioning due to intervention.

Effect of motor imagery in children with unilateral cerebral palsy: fMRI study.

PubMed

Chinier, Eva; N'Guyen, Sylvie; Lignon, Grégoire; Ter Minassian, Aram; Richard, Isabelle; Dinomais, Mickaël

2014-01-01

Motor imagery is considered as a promising therapeutic tool for rehabilitation of motor planning problems in patients with cerebral palsy. However motor planning problems may lead to poor motor imagery ability. The aim of this functional magnetic resonance imaging study was to examine and compare brain activation following motor imagery tasks in patients with hemiplegic cerebral palsy with left or right early brain lesions. We tested also the influence of the side of imagined hand movement. Twenty patients with clinical hemiplegic cerebral palsy (sixteen males, mean age 12 years and 10 months, aged 6 years 10 months to 20 years 10 months) participated in this study. Using block design, brain activations following motor imagery of a simple opening-closing hand movement performed by either the paretic or nonparetic hand was examined. During motor imagery tasks, patients with early right brain damages activated bilateral fronto-parietal network that comprise most of the nodes of the network well described in healthy subjects. Inversely, in patients with left early brain lesion brain activation following motor imagery tasks was reduced, compared to patients with right brain lesions. We found also a weak influence of the side of imagined hand movement. Decreased activations following motor imagery in patients with right unilateral cerebral palsy highlight the dominance of the left hemisphere during motor imagery tasks. This study gives neuronal substrate to propose motor imagery tasks in unilateral cerebral palsy rehabilitation at least for patients with right brain lesions.

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

[A case of anti-MOG antibody-positive multiphasic disseminated encephalomyelitis co-occurring with unilateral cerebral cortical encephalitis].

PubMed

Fukushima, Naoya; Suzuki, Miki; Ogawa, Ryo; Hayashi, Kitami; Takanashi, Jun-Ichi; Ohashi, Takashi

2017-11-25

A 20-year-old woman first developed acute disseminated encephalomyelitis (ADEM) at 11 years of age. At 17 years of age, she was hospitalized due to generalized seizure and diagnosed with encephalitis. Brain MRI revealed a FLAIR-hyperintense lesion in the unilateral cerebral cortex. At 18 years of age, serum anti-myelin oligodendrocyte glycoprotein (MOG) antibody was detected. At 20 years of age, she was admitted to our hospital, diagnosed with multifocal disseminated encephalomyelitis (MDEM). MDEM has been observed in patients that are seropositive for the anti-MOG antibody. More recently, unilateral cerebral cortex encephalitis with epilepsy has also been reported in such patients. The co-occurrence of MDEM and cortical encephalitis in the same patient has important implications for the pathogenesis of anti-MOG antibody-associated autoimmune diseases.

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.

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

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.

Altered neuronal activity in the primary motor cortex and globus pallidus after dopamine depletion in rats.

PubMed

Wang, Min; Li, Min; Geng, Xiwen; Song, Zhimin; Albers, H Elliott; Yang, Maoquan; Zhang, Xiao; Xie, Jinlu; Qu, Qingyang; He, Tingting

2015-01-15

The involvement of dopamine (DA) neuron loss in the etiology of Parkinson's disease has been well documented. The neural mechanisms underlying the effects of DA loss and the resultant motor dysfunction remain unknown. To gain insights into how loss of DA disrupts the electrical processes in the cortico-subcortical network, the present study explores the effects of DA neuron depletion on electrical activity in the primary motor cortex (M1), on the external and the internal segment of the globus pallidus (GPe and GPi respectively), and on their temporal relationships. Comparison of local field potentials (LFPs) in these brain regions from unilateral hemispheric DA neuron depleted rats and neurologically intact rats revealed that the spectrum power of LFPs in 12-70Hz (for M1, and GPe) and in 25-40Hz (for GPi) was significantly greater in the DA depleted rats than that in the control group. These changes were associated with a shortening of latency in LFP activities between M1 and GPe, from several hundred milliseconds in the intact animals to close to zero in the DA depleted animals. LFP oscillations in M1 were significantly more synchronized with those in GPe in the DA depleted rats compared with those in the control rats. By contrast, the synchronization of oscillation in LFP activities between M1 and GPi did not differ between the DA depleted and intact rats. Not surprisingly, rats that had DA neuron depletion spent more time along the ladder compared with the control rats. These data suggest that enhanced oscillatory activity and increased synchronization of LFPs may contribute to movement impairment in the rat model of Parkinson's disease. Copyright © 2014 Elsevier B.V. All rights reserved.

Adaptive changes in the motor cortex during and after longterm forelimb immobilization in adult rats.

PubMed

Viaro, Riccardo; Budri, Mirco; Parmiani, Pierantonio; Franchi, Gianfranco

2014-05-15

Experimental and clinical studies have attempted to evaluate the changes in cortical activity seen after immobilization-induced longterm sensorimotor restriction, although results remain controversial. We used intracortical microstimulation (ICMS), which provides topographic movement representations of the motor areas in both hemispheres with optimal spatial characterization, combined with behavioural testing to unravel the effects of limb immobilization on movement representations in the rat primary motor cortex (M1). Unilateral forelimb immobilization in rats was achieved by casting the entire limb and leaving the cast in place for 15 or 30 days. Changes in M1 were bilateral and specific for the forelimb area, but were stronger in the contralateral-to-cast hemisphere. The threshold current required to evoke forelimb movement increased progressively over the period in cast, whereas the forelimb area size decreased and the non-excitable area size increased. Casting resulted in a redistribution of proximal/distal movement representations: proximal forelimb representation increased, whereas distal representation decreased in size. ICMS after cast removal showed a reversal of changes, which remained partial at 15 days. Local application of the GABAA-antagonist bicuculline revealed the impairment of cortical synaptic connectivity in the forelimb area during the period of cast and for up to 15 days after cast removal. Six days of rehabilitation using a rotarod performance protocol after cast removal did not advance map size normalization in the contralateral-to-cast M1 and enabled the cortical output towards the distal forelimb only in sites that had maintained their excitability. These results are relevant to our understanding of adult M1 plasticity during and after sensorimotor deprivation, and to new approaches to conditions that require longterm limb immobilization. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

Conditional genetic deletion of PTEN after a spinal cord injury enhances regenerative growth of CST axons and motor function recovery in mice.

PubMed

Danilov, Camelia A; Steward, Oswald

2015-04-01

Previous studies indicate that conditional genetic deletion of phosphatase and tensin homolog (PTEN) in neonatal mice enhances the ability of axons to regenerate following spinal cord injury (SCI) in adults. Here, we assessed whether deleting PTEN in adult neurons post-SCI is also effective, and whether enhanced regenerative growth is accompanied by enhanced recovery of voluntary motor function. PTEN(loxP/loxP) mice received moderate contusion injuries at cervical level 5 (C5). One group received unilateral injections of adeno-associated virus expressing CRE (AAV-CRE) into the sensorimotor cortex; controls received a vector expressing green fluorescent protein (AAV-GFP) or injuries only (no vector injections). Forelimb function was tested for 14weeks post-SCI using a grip strength meter (GSM) and a hanging task. The corticospinal tract (CST) was traced by injecting mini-ruby BDA into the sensorimotor cortex. Forelimb gripping ability was severely impaired immediately post-SCI but recovered slowly over time. The extent of recovery was significantly greater in PTEN-deleted mice in comparison to either the AAV-GFP group or the injury only group. BDA tract tracing revealed significantly higher numbers of BDA-labeled axons in caudal segments in the PTEN-deleted group compared to control groups. In addition, in the PTEN-deleted group, there were exuberant collaterals extending from the main tract rostral to the lesion and into and around the scar tissue at the injury site. These results indicate that PTEN deletion in adult mice shortly post-SCI can enhance regenerative growth of CST axons and forelimb motor function recovery. Copyright © 2015 Elsevier Inc. All rights reserved.

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…

Functional connectivity of the rodent brain using optical imaging

NASA Astrophysics Data System (ADS)

Guevara Codina, Edgar

The aim of this thesis is to apply functional connectivity in a variety of animal models, using several optical imaging modalities. Even at rest, the brain shows high metabolic activity: the correlation in slow spontaneous fluctuations identifies remotely connected areas of the brain; hence the term "functional connectivity". Ongoing changes in spontaneous activity may provide insight into the neural processing that takes most of the brain metabolic activity, and so may provide a vast source of disease related changes. Brain hemodynamics may be modified during disease and affect resting-state activity. The thesis aims to better understand these changes in functional connectivity due to disease, using functional optical imaging. The optical imaging techniques explored in the first two contributions of this thesis are Optical Imaging of Intrinsic Signals and Laser Speckle Contrast Imaging, together they can estimate the metabolic rate of oxygen consumption, that closely parallels neural activity. They both have adequate spatial and temporal resolution and are well adapted to image the convexity of the mouse cortex. In the last article, a depth-sensitive modality called photoacoustic tomography was used in the newborn rat. Optical coherence tomography and laminar optical tomography were also part of the array of imaging techniques developed and applied in other collaborations. The first article of this work shows the changes in functional connectivity in an acute murine model of epileptiform activity. Homologous correlations are both increased and decreased with a small dependence on seizure duration. These changes suggest a potential decoupling between the hemodynamic parameters in resting-state networks, underlining the importance to investigate epileptic networks with several independent hemodynamic measures. The second study examines a novel murine model of arterial stiffness: the unilateral calcification of the right carotid. Seed-based connectivity analysis showed a decreasing trend of homologous correlation in the motor and cingulate cortices. Graph analyses showed a randomization of the cortex functional networks, suggesting a loss of connectivity, more specifically in the motor cortex ipsilateral to the treated carotid; however these changes are not reflected in differentiated metabolic estimates. Confounds remain due to the fact that carotid rigidification gives rise to neural decline in the hippocampus as well as unilateral alteration of vascular pulsatility; however the results support the need to look at several hemodynamic parameters when imaging the brain after arterial remodeling. The third article of this thesis studies a model of inflammatory injury on the newborn rat. Oxygen saturation and functional connectivity were assessed with photoacoustic tomography. Oxygen saturation was decreased in the site of the lesion and on the cortex ipsilateral to the injury; however this decrease is not fully explained by hypovascularization revealed by histology. Seed-based functional connectivity analysis showed that inter-hemispheric connectivity is not affected by inflammatory injury.

The Role of Primary Motor Cortex (M1) Glutamate and GABA Signaling in l-DOPA-Induced Dyskinesia in Parkinsonian Rats

PubMed Central

Conti, Melissa M.; Ostock, Corinne Y.; George, Jessica A.; Goldenberg, Adam A.; Melikhov-Sosin, Mitchell; Nuss, Emily E.

2016-01-01

Long-term treatment of Parkinson's disease with l-DOPA almost always leads to the development of involuntary movements termed l-DOPA-induced dyskinesia. Whereas hyperdopaminergic signaling in the basal ganglia is thought to cause dyskinesia, alterations in primary motor cortex (M1) activity are also prominent during dyskinesia, suggesting that the cortex may represent a therapeutic target. The present study used the rat unilateral 6-hydroxydopamine lesion model of Parkinson's disease to characterize in vivo changes in GABA and glutamate neurotransmission within M1 and determine their contribution to behavioral output. 6-Hydroxydopamine lesion led to parkinsonian motor impairment that was partially reversed by l-DOPA. Among sham-lesioned rats, l-DOPA did not change glutamate or GABA efflux. Likewise, 6-hydroxydopamine lesion did not impact GABA or glutamate among rats chronically treated with saline. However, we observed an interaction of lesion and treatment whereby, among lesioned rats, l-DOPA given acutely (1 d) or chronically (14–16 d) reduced glutamate efflux and enhanced GABA efflux. Site-specific microinjections into M1 demonstrated that l-DOPA-induced dyskinesia was reduced by M1 infusion of a D1 antagonist, an AMPA antagonist, or a GABAA agonist. Overall, the present study demonstrates that l-DOPA-induced dyskinesia is associated with increased M1 inhibition and that exogenously enhancing M1 inhibition may attenuate dyskinesia, findings that are in agreement with functional imaging and transcranial magnetic stimulation studies in human Parkinson's disease patients. Together, our study suggests that increasing M1 inhibitory tone is an endogenous compensatory response designed to limit dyskinesia severity and that potentiating this response is a viable therapeutic strategy. SIGNIFICANCE STATEMENT Most Parkinson's disease patients will receive l-DOPA and eventually develop hyperkinetic involuntary movements termed dyskinesia. Such symptoms can be as debilitating as the disease itself. Although dyskinesia is associated with dynamic changes in primary motor cortex physiology, to date, there are no published studies investigating in vivo neurotransmitter release in M1 during dyskinesia. In parkinsonian rats, l-DOPA administration reduced M1 glutamate efflux and enhanced GABA efflux, coincident with the emergence of dyskinetic behaviors. Dyskinesia could be reduced by local M1 modulation of D1, AMPA, and GABAA receptors, providing preclinical support for the notion that exogenously blunting M1 signaling (pharmacologically or with cortical stimulation) is a therapeutic approach to the treatment of debilitating dyskinesias. PMID:27656025

The Role of Primary Motor Cortex (M1) Glutamate and GABA Signaling in l-DOPA-Induced Dyskinesia in Parkinsonian Rats.

PubMed

Lindenbach, David; Conti, Melissa M; Ostock, Corinne Y; George, Jessica A; Goldenberg, Adam A; Melikhov-Sosin, Mitchell; Nuss, Emily E; Bishop, Christopher

2016-09-21

Long-term treatment of Parkinson's disease with l-DOPA almost always leads to the development of involuntary movements termed l-DOPA-induced dyskinesia. Whereas hyperdopaminergic signaling in the basal ganglia is thought to cause dyskinesia, alterations in primary motor cortex (M1) activity are also prominent during dyskinesia, suggesting that the cortex may represent a therapeutic target. The present study used the rat unilateral 6-hydroxydopamine lesion model of Parkinson's disease to characterize in vivo changes in GABA and glutamate neurotransmission within M1 and determine their contribution to behavioral output. 6-Hydroxydopamine lesion led to parkinsonian motor impairment that was partially reversed by l-DOPA. Among sham-lesioned rats, l-DOPA did not change glutamate or GABA efflux. Likewise, 6-hydroxydopamine lesion did not impact GABA or glutamate among rats chronically treated with saline. However, we observed an interaction of lesion and treatment whereby, among lesioned rats, l-DOPA given acutely (1 d) or chronically (14-16 d) reduced glutamate efflux and enhanced GABA efflux. Site-specific microinjections into M1 demonstrated that l-DOPA-induced dyskinesia was reduced by M1 infusion of a D1 antagonist, an AMPA antagonist, or a GABAA agonist. Overall, the present study demonstrates that l-DOPA-induced dyskinesia is associated with increased M1 inhibition and that exogenously enhancing M1 inhibition may attenuate dyskinesia, findings that are in agreement with functional imaging and transcranial magnetic stimulation studies in human Parkinson's disease patients. Together, our study suggests that increasing M1 inhibitory tone is an endogenous compensatory response designed to limit dyskinesia severity and that potentiating this response is a viable therapeutic strategy. Most Parkinson's disease patients will receive l-DOPA and eventually develop hyperkinetic involuntary movements termed dyskinesia. Such symptoms can be as debilitating as the disease itself. Although dyskinesia is associated with dynamic changes in primary motor cortex physiology, to date, there are no published studies investigating in vivo neurotransmitter release in M1 during dyskinesia. In parkinsonian rats, l-DOPA administration reduced M1 glutamate efflux and enhanced GABA efflux, coincident with the emergence of dyskinetic behaviors. Dyskinesia could be reduced by local M1 modulation of D1, AMPA, and GABAA receptors, providing preclinical support for the notion that exogenously blunting M1 signaling (pharmacologically or with cortical stimulation) is a therapeutic approach to the treatment of debilitating dyskinesias. Copyright © 2016 the authors 0270-6474/16/369873-15$15.00/0.

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.

A comparison of low dose hyperbaric levobupivacaine and hypobaric levobupivacaine in unilateral spinal anaesthesia.

PubMed

Kaya, M; Oztürk, I; Tuncel, G; Senel, G Ozalp; Eskiçirak, H; Kadioğullari, N

2010-11-01

The aim of this study was to compare the clinical effects and characteristics of hyperbaric and hypobaric levobupivacaine for unilateral spinal anaesthesia. Sixty patients were randomly allocated into two groups to receive either 7.5 mg (1.5 ml) hyperbaric levobupivacaine 0.5% or 7.5 mg (4 ml) hypobaric levobupivacaine 0.1875% for elective arthroscopic surgery of the knee under spinal anaesthesia. The level and duration of sensory block, intensity and duration of motor block were recorded. Unilateral sensory block was observed in 27 patients (90%) in the hyperbaric group and 24 patients (80%) in the hypobaric group in the lateral position. After 15 minutes, patients were turned to supine to redistribute the spinal block toward the non-operative side, but spinal anaesthesia was still unilateral in 18 patients (60%) in the hyperbaric group and 10 patients (33%) in the hypobaric group (P = 0.038). Time to readiness for home discharge and complete recovery of sensory block were similar in both groups. In the hyperbaric group, the motor block scores were higher on the operative side during first 10 minutes than they were in the hypobaric group (P < 0.002). Motor block regression was faster in the hyperbaric group (P = 0.01). Hyperbaric and hypobaric levobupivacaine both provided satisfactory unilateral spinal anaesthesia with good haemodynamic stability for arthroscopic surgery, but with more frequent unilateral spinal anaesthesia in the hyperbaric group.

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

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.

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.

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

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.

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.

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

Cognition and bimanual performance in children with unilateral cerebral palsy: protocol for a multicentre, cross-sectional study.

PubMed

Hoare, Brian; Ditchfield, Michael; Thorley, Megan; Wallen, Margaret; Bracken, Jenny; Harvey, Adrienne; Elliott, Catherine; Novak, Iona; Crichton, Ali

2018-05-08

Motor outcomes of children with unilateral cerebral palsy are clearly documented and well understood, yet few studies describe the cognitive functioning in this population, and the associations between the two is poorly understood. Using two hands together in daily life involves complex motor and cognitive processes. Impairment in either domain may contribute to difficulties with bimanual performance. Research is yet to derive whether, and how, cognition affects a child's ability to use their two hands to perform bimanual tasks. This study will use a prospective, cross-sectional multi-centre observational design. Children (aged 6-12 years) with unilateral cerebral palsy will be recruited from one of five Australian treatment centres. We will examine associations between cognition, bimanual performance and brain neuropathology (lesion type and severity) in a sample of 131 children. The primary outcomes are: Motor - the Assisting Hand Assessment; Cognitive - Executive Function; and Brain - lesion location on structural MRI. Secondary data collected will include: Motor - Box and Blocks, ABILHAND- Kids, Sword Test; Cognitive - standard neuropsychological measures of intelligence. We will use generalized linear modelling and structural equation modelling techniques to investigate relationships between bimanual performance, executive function and brain lesion location. This large multi-centre study will examine how cognition affects bimanual performance in children with unilateral cerebral palsy. First, it is anticipated that distinct relationships between bimanual performance and cognition (executive function) will be identified. Second, it is anticipated that interrelationships between bimanual performance and cognition will be associated with common underlying neuropathology. Findings have the potential to improve the specificity of existing upper limb interventions by providing more targeted treatments and influence the development of novel methods to improve both cognitive and motor outcomes in children with unilateral cerebral palsy. ACTRN12614000631606 ; Date of retrospective registration 29/05/2014.

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

Effect of neck flexion on somatosensory and motor evoked potentials in Hirayama disease.

PubMed

Abraham, A; Gotkine, M; Drory, V E; Blumen, S C

2013-11-15

Hirayama disease (HD) is a rare motor disorder mainly affecting young men, characterized by atrophy and weakness of forearm and hand muscles corresponding to a C7-T1 myotome distribution. The weakness is usually unilateral or asymmetric and progression usually stops within several years. The etiology of HD is not well understood. One hypothesis, mainly based on MRI findings, is that the weakness is a consequence of cervical flexion myelopathy. The aim of this study was to explore the function of corticospinal and ascending somatosensory pathways during neck flexion using evoked responses. 15 men with HD and 7 age-matched control male subjects underwent somatosensory evoked potentials (SSEP) and motor evoked potentials (MEP) studies with the neck in neutral position and fully flexed. SSEP studies included electrical stimulation of median and ulnar nerves at the wrist, and tibial nerve at the ankle with recording over the ipsilateral Erb's point, cervical spine, and contralateral sensory cortex. MEP recordings were obtained by magnetic stimulation of the motor cortex and the cervical lower spinal roots; the evoked responses were recorded from the contralateral thenar and abductor hallucis muscles. MEP recordings demonstrated significant lower amplitudes, and slightly prolonged latencies in HD patients on cervical stimulation, compared to control subjects. During neck flexion, MEP studies also demonstrated a statistically significant drop in mean upper limb amplitude on cervical stimulation in HD patients, as well as in control subjects, although to a lesser degree. In contrast, no significant differences were found in SSEP studies in HD patients compared to control subjects, or between neutral and flexed position in these groups. The study shows a negative effect of cervical flexion on MEP amplitudes in HD patients as well as in control subjects, requiring more studies to investigate its significance. Neck flexion did not have an influence on any SSEP parameters in patients or controls. © 2013 Elsevier B.V. All rights reserved.

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.

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.

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.

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.

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

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.

Clubfoot Does Not Impair Gross Motor Development in 5-Year-Olds.

PubMed

Zapata, Karina A; Karol, Lori A; Jeans, Kelly A; Jo, Chan-Hee

2018-04-01

To evaluate the gross motor development of 5-year-olds using the Peabody Developmental Motor Scales, 2nd Edition (PDMS-2), test after initial nonoperative management of clubfoot as infants. The PDMS-2 Stationary, Locomotion, and Object Manipulation subtests were assessed on 128 children with idiopathic clubfeet at the age of 5 years. Children were categorized by their initial clubfoot severity as greater than 13, unilateral or bilateral involvement, and required surgery. Children with treated clubfeet had average gross motor scores (99 Gross Motor Quotient) compared with age-matched normative scores. Children with more severe clubfeet required surgery significantly more than children with less severe scores (P < .01). Peabody scores were not significantly different according to initial clubfoot severity, unilateral versus bilateral involvement, and surgical versus nonsurgical outcomes. Clubfoot does not significantly impair gross motor development in 5-year-olds.

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.

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.

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

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

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.

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.

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

Loss of regional accent after damage to the speech production network.

PubMed

Berthier, Marcelo L; Dávila, Guadalupe; Moreno-Torres, Ignacio; Beltrán-Corbellini, Álvaro; Santana-Moreno, Daniel; Roé-Vellvé, Núria; Thurnhofer-Hemsi, Karl; Torres-Prioris, María José; Massone, María Ignacia; Ruiz-Cruces, Rafael

2015-01-01

Lesion-symptom mapping studies reveal that selective damage to one or more components of the speech production network can be associated with foreign accent syndrome, changes in regional accent (e.g., from Parisian accent to Alsatian accent), stronger regional accent, or re-emergence of a previously learned and dormant regional accent. Here, we report loss of regional accent after rapidly regressive Broca's aphasia in three Argentinean patients who had suffered unilateral or bilateral focal lesions in components of the speech production network. All patients were monolingual speakers with three different native Spanish accents (Cordobés or central, Guaranítico or northeast, and Bonaerense). Samples of speech production from the patient with native Córdoba accent were compared with previous recordings of his voice, whereas data from the patient with native Guaranítico accent were compared with speech samples from one healthy control matched for age, gender, and native accent. Speech samples from the patient with native Buenos Aires's accent were compared with data obtained from four healthy control subjects with the same accent. Analysis of speech production revealed discrete slowing in speech rate, inappropriate long pauses, and monotonous intonation. Phonemic production remained similar to those of healthy Spanish speakers, but phonetic variants peculiar to each accent (e.g., intervocalic aspiration of /s/ in Córdoba accent) were absent. While basic normal prosodic features of Spanish prosody were preserved, features intrinsic to melody of certain geographical areas (e.g., rising end F0 excursion in declarative sentences intoned with Córdoba accent) were absent. All patients were also unable to produce sentences with different emotional prosody. Brain imaging disclosed focal left hemisphere lesions involving the middle part of the motor cortex, the post-central cortex, the posterior inferior and/or middle frontal cortices, insula, anterior putamen and supplementary motor area. Our findings suggest that lesions affecting the middle part of the left motor cortex and other components of the speech production network disrupt neural processes involved in the production of regional accent features.

Loss of regional accent after damage to the speech production network

PubMed Central

Berthier, Marcelo L.; Dávila, Guadalupe; Moreno-Torres, Ignacio; Beltrán-Corbellini, Álvaro; Santana-Moreno, Daniel; Roé-Vellvé, Núria; Thurnhofer-Hemsi, Karl; Torres-Prioris, María José; Massone, María Ignacia; Ruiz-Cruces, Rafael

2015-01-01

Lesion-symptom mapping studies reveal that selective damage to one or more components of the speech production network can be associated with foreign accent syndrome, changes in regional accent (e.g., from Parisian accent to Alsatian accent), stronger regional accent, or re-emergence of a previously learned and dormant regional accent. Here, we report loss of regional accent after rapidly regressive Broca’s aphasia in three Argentinean patients who had suffered unilateral or bilateral focal lesions in components of the speech production network. All patients were monolingual speakers with three different native Spanish accents (Cordobés or central, Guaranítico or northeast, and Bonaerense). Samples of speech production from the patient with native Córdoba accent were compared with previous recordings of his voice, whereas data from the patient with native Guaranítico accent were compared with speech samples from one healthy control matched for age, gender, and native accent. Speech samples from the patient with native Buenos Aires’s accent were compared with data obtained from four healthy control subjects with the same accent. Analysis of speech production revealed discrete slowing in speech rate, inappropriate long pauses, and monotonous intonation. Phonemic production remained similar to those of healthy Spanish speakers, but phonetic variants peculiar to each accent (e.g., intervocalic aspiration of /s/ in Córdoba accent) were absent. While basic normal prosodic features of Spanish prosody were preserved, features intrinsic to melody of certain geographical areas (e.g., rising end F0 excursion in declarative sentences intoned with Córdoba accent) were absent. All patients were also unable to produce sentences with different emotional prosody. Brain imaging disclosed focal left hemisphere lesions involving the middle part of the motor cortex, the post-central cortex, the posterior inferior and/or middle frontal cortices, insula, anterior putamen and supplementary motor area. Our findings suggest that lesions affecting the middle part of the left motor cortex and other components of the speech production network disrupt neural processes involved in the production of regional accent features. PMID:26594161

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.

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.

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.

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

The impact of unilateral brain damage on anticipatory grip force scaling when lifting everyday objects.

PubMed

Eidenmüller, S; Randerath, J; Goldenberg, G; Li, Y; Hermsdörfer, J

2014-08-01

The scaling of our finger forces according to the properties of manipulated objects is an elementary prerequisite of skilled motor behavior. Lesions of the motor-dominant left brain may impair several aspects of motor planning. For example, limb-apraxia, a tool-use disorder after left brain damage is thought to be caused by deficient recall or integration of tool-use knowledge into an action plan. The aim of the present study was to investigate whether left brain damage affects anticipatory force scaling when lifting everyday objects. We examined 26 stroke patients with unilateral brain damage (16 with left brain damage, ten with right brain damage) and 21 healthy control subjects. Limb apraxia was assessed by testing pantomime of familiar tool-use and imitation of meaningless hand postures. Participants grasped and lifted twelve randomly presented everyday objects. Grip force was measured with help of sensors fixed on thumb, index and middle-finger. The maximum rate of grip force was determined to quantify the precision of anticipation of object properties. Regression analysis yielded clear deficits of anticipation in the group of patients with left brain damage, while the comparison of patient with right brain damage with their respective control group did not reveal comparable deficits. Lesion-analyses indicate that brain structures typically associated with a tool-use network in the left hemisphere play an essential role for anticipatory grip force scaling, especially the left inferior frontal gyrus (IFG) and the premotor cortex (PMC). Furthermore, significant correlations of impaired anticipation with limb apraxia scores suggest shared representations. However, the presence of dissociations, implicates also independent processes. Overall, our findings suggest that the left hemisphere is engaged in anticipatory grip force scaling for lifting everyday objects. The underlying neural substrate is not restricted to a single region or stream; instead it may rely on the intact functioning of a left hemisphere network that may overlap with the left hemisphere dominant tool-use network. Copyright © 2014 Elsevier Ltd. All rights reserved.

Motor learning and cross-limb transfer rely upon distinct neural adaptation processes.

PubMed

Stöckel, Tino; Carroll, Timothy J; Summers, Jeffery J; Hinder, Mark R

2016-08-01

Performance benefits conferred in the untrained limb after unilateral motor practice are termed cross-limb transfer. Although the effect is robust, the neural mechanisms remain incompletely understood. In this study we used noninvasive brain stimulation to reveal that the neural adaptations that mediate motor learning in the trained limb are distinct from those that underlie cross-limb transfer to the opposite limb. Thirty-six participants practiced a ballistic motor task with their right index finger (150 trials), followed by intermittent theta-burst stimulation (iTBS) applied to the trained (contralateral) primary motor cortex (cM1 group), the untrained (ipsilateral) M1 (iM1 group), or the vertex (sham group). After stimulation, another 150 training trials were undertaken. Motor performance and corticospinal excitability were assessed before motor training, pre- and post-iTBS, and after the second training bout. For all groups, training significantly increased performance and excitability of the trained hand, and performance, but not excitability, of the untrained hand, indicating transfer at the level of task performance. The typical facilitatory effect of iTBS on MEPs was reversed for cM1, suggesting homeostatic metaplasticity, and prior performance gains in the trained hand were degraded, suggesting that iTBS interfered with learning. In stark contrast, iM1 iTBS facilitated both performance and excitability for the untrained hand. Importantly, the effects of cM1 and iM1 iTBS on behavior were exclusive to the hand contralateral to stimulation, suggesting that adaptations within the untrained M1 contribute to cross-limb transfer. However, the neural processes that mediate learning in the trained hemisphere vs. transfer in the untrained hemisphere appear distinct. Copyright © 2016 the American Physiological Society.

Motor learning and cross-limb transfer rely upon distinct neural adaptation processes

PubMed Central

Carroll, Timothy J.; Summers, Jeffery J.; Hinder, Mark R.

2016-01-01

Performance benefits conferred in the untrained limb after unilateral motor practice are termed cross-limb transfer. Although the effect is robust, the neural mechanisms remain incompletely understood. In this study we used noninvasive brain stimulation to reveal that the neural adaptations that mediate motor learning in the trained limb are distinct from those that underlie cross-limb transfer to the opposite limb. Thirty-six participants practiced a ballistic motor task with their right index finger (150 trials), followed by intermittent theta-burst stimulation (iTBS) applied to the trained (contralateral) primary motor cortex (cM1 group), the untrained (ipsilateral) M1 (iM1 group), or the vertex (sham group). After stimulation, another 150 training trials were undertaken. Motor performance and corticospinal excitability were assessed before motor training, pre- and post-iTBS, and after the second training bout. For all groups, training significantly increased performance and excitability of the trained hand, and performance, but not excitability, of the untrained hand, indicating transfer at the level of task performance. The typical facilitatory effect of iTBS on MEPs was reversed for cM1, suggesting homeostatic metaplasticity, and prior performance gains in the trained hand were degraded, suggesting that iTBS interfered with learning. In stark contrast, iM1 iTBS facilitated both performance and excitability for the untrained hand. Importantly, the effects of cM1 and iM1 iTBS on behavior were exclusive to the hand contralateral to stimulation, suggesting that adaptations within the untrained M1 contribute to cross-limb transfer. However, the neural processes that mediate learning in the trained hemisphere vs. transfer in the untrained hemisphere appear distinct. PMID:27169508

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.

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.

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.

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

[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.

Gross Motor Skills in Children With Idiopathic Clubfoot and the Association Between Gross Motor Skills, Foot Involvement, Gait, and Foot Motion.

PubMed

Lööf, Elin; Andriesse, Hanneke; André, Marie; Böhm, Stephanie; Iversen, Maura D; Broström, Eva W

2017-02-24

Little is known regarding gross motor skills (GMS) in children with idiopathic clubfoot (IC). This study describes GMS, specifically foot involvement and asymmetries, and analyses the association between GMS, gait, and foot status in children with IC. Gross motor tasks and gait were analyzed in children with IC and typically developed (TD) children. GMS were assessed using videotapes and the Clubfoot Assessment Protocol (CAP). The Gait Deviation Index (GDI) and GDI-Kinetic were calculated from gait analyses. Children were divided into bilateral, unilateral clubfoot, or TD groups. To analyze asymmetries, feet within each group were further classified into superior or inferior foot, depending on their CAP scores. Correlations identified associations between CAP and GDI, GDI-Kinetic, passive foot motion, and Dimeglio Classification Scores at birth in the clubfeet. In total, 75 children (mean age, 5 years) were enrolled (bilateral n=22, unilateral clubfoot n=25, TD=28). Children with clubfeet demonstrated significantly lower GMS, gait, and foot motion compared with TD children. One leg standing and hopping deviated in 84% and 91%, respectively, in at least one foot in children with clubfoot. Gross motor asymmetries were evident in both children with bilateral and unilateral involvement. In children with unilateral clubfoot, contralateral feet showed few deviations in GMS compared with TD; however, differences existed in gait and foot motion. The association between GMS and gait, foot motion, and initial foot status varied between poor and moderate. Gross motor deficits and asymmetries are present in children with both bilateral and unilateral IC. Development of GMS of the contralateral foot mirrors that of TD children, but modifies to the clubfoot in gait and foot motion. The weak association with gait, foot motion, and initial clubfoot severity indicates that gross motor measurements represent a different outcome entity in clubfoot treatment. We therefore, recommend gross motor task evaluation for children with IC. Level II-prognostic studies.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/.

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

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.

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.

Assessment of the structural brain network reveals altered connectivity in children with unilateral cerebral palsy due to periventricular white matter lesions

PubMed Central

Pannek, Kerstin; Boyd, Roslyn N.; Fiori, Simona; Guzzetta, Andrea; Rose, Stephen E.

2014-01-01

Background Cerebral palsy (CP) is a term to describe the spectrum of disorders of impaired motor and sensory function caused by a brain lesion occurring early during development. Diffusion MRI and tractography have been shown to be useful in the study of white matter (WM) microstructure in tracts likely to be impacted by the static brain lesion. Aim The purpose of this study was to identify WM pathways with altered connectivity in children with unilateral CP caused by periventricular white matter lesions using a whole-brain connectivity approach. Methods Data of 50 children with unilateral CP caused by periventricular white matter lesions (5–17 years; manual ability classification system [MACS] I = 25/II = 25) and 17 children with typical development (CTD; 7–16 years) were analysed. Structural and High Angular Resolution Diffusion weighted Images (HARDI; 64 directions, b = 3000 s/mm2) were acquired at 3 T. Connectomes were calculated using whole-brain probabilistic tractography in combination with structural parcellation of the cortex and subcortical structures. Connections with altered fractional anisotropy (FA) in children with unilateral CP compared to CTD were identified using network-based statistics (NBS). The relationship between FA and performance of the impaired hand in bimanual tasks (Assisting Hand Assessment—AHA) was assessed in connections that showed significant differences in FA compared to CTD. Results FA was reduced in children with unilateral CP compared to CTD. Seven pathways, including the corticospinal, thalamocortical, and fronto-parietal association pathways were identified simultaneously in children with left and right unilateral CP. There was a positive relationship between performance of the impaired hand in bimanual tasks and FA within the cortico-spinal and thalamo-cortical pathways (r2 = 0.16–0.44; p < 0.05). Conclusion This study shows that network-based analysis of structural connectivity can identify alterations in FA in unilateral CP, and that these alterations in FA are related to clinical function. Application of this connectome-based analysis to investigate alterations in connectivity following treatment may elucidate the neurological correlates of improved functioning due to intervention. PMID:25003031

Hand Function in Relation to Brain Lesions and Corticomotor-Projection Pattern in Children with Unilateral Cerebral Palsy

ERIC Educational Resources Information Center

Holmstrom, Linda; Vollmer, Brigitte; Tedroff, Kristina; Islam, Mominul; Persson, Jonas Ke; Kits, Annika; Forssberg, Hans; Eliasson, Ann-Christin

2010-01-01

Aim: To investigate relationships between hand function, brain lesions, and corticomotor projections in children with unilateral cerebral palsy (CP). Method: The study included 17 children (nine males, eight females; mean age 11.4 [SD 2.4] range 7-16y), with unilateral CP at Gross Motor Function Classification System level I and Manual Ability…

Intracortical inhibition and facilitation with unilateral dominant, unilateral nondominant and bilateral movement tasks in left- and right-handed adults.

PubMed

McCombe Waller, Sandy; Forrester, Larry; Villagra, Federico; Whitall, Jill

2008-06-15

To investigate intracortical inhibition and facilitation in response to unilateral dominant, nondominant and bilateral biceps activation and short-term upper extremity training in right- and left-handed adults. Paired-pulse transcranial magnetic stimulation was used to measure intracortical excitability in motor dominant and nondominant cortices of 26 nondisabled adults. Neural facilitation and inhibition were measured in each hemisphere during unilateral dominant, nondominant and bilateral arm activation and after training in each condition. No differences were seen between right- and left-handed subjects. Intracortical facilitation and decreased inhibition were seen in each hemisphere with unilateral activation/training of contralateral muscles and bilateral muscle activation/training. Persistent intracortical inhibition was seen in each hemisphere with ipsilateral muscle activation/training. Inhibition was greater in the nondominant hemisphere during dominant hemisphere activation (dominant arm contraction). Strongly dominant individuals show no difference in intracortical responses given handedness. Intracortical activity with unilateral and bilateral arm activation and short-term training differs based on hemispheric dominance, with the motor dominant hemisphere exerting a larger inhibitory influence over the nondominant hemisphere. Bilateral activation and training have a disinhibitory effect in both dominant and nondominant hemispheres.

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.

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

[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.

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

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

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

Effects of Bilateral Repetitive Transcranial Magnetic Stimulation on Post-Stroke Dysphagia.

PubMed

Park, Eunhee; Kim, Min Su; Chang, Won Hyuk; Oh, Su Mi; Kim, Yun Kwan; Lee, Ahee; Kim, Yun-Hee

Optimal protocol of repetitive transcranial magnetic stimulation (rTMS) on post-stroke dysphagia remains uncertain with regard to its clinical efficacy. The aim of the present study is to investigate the effects of high-frequency rTMS at the bilateral motor cortices over the cortical representation of the mylohyoid muscles in the patients with post-stroke dysphagia. This study was a single-blind, randomized controlled study with a blinded observer. Thirty-five stroke patients were randomly divided into three intervention groups: the bilateral stimulation group, the unilateral stimulation group, and the sham stimulation group. For the bilateral stimulation group, 500 pulses of 10 Hz rTMS over the ipsilesional and 500 pulses of 10 Hz rTMS over the contralesional motor cortices over the cortical areas that project to the mylohyoid muscles were administered daily for 2 consecutive weeks. For the unilateral stimulation group, 500 pulses of 10 Hz rTMS over the ipsilesional motor cortex over the cortical representation of the mylohyoid muscle and the same amount of sham rTMS over the contralesional hemisphere were applied. For the sham stimulation group, sham rTMS was applied at the bilateral motor cortices. Clinical swallowing function and videofluoroscopic swallowing studies were assessed before the intervention (T0), immediately after the intervention (T1) and 3 weeks after the intervention (T2) using Clinical Dysphagia Scale (CDS), Dysphagia Outcome and Severity Scale (DOSS), Penetration Aspiration Scale (PAS), and Videofluoroscopic Dysphagia Scale (VDS). There were significant time and intervention interaction effects in the CDS, DOSS, PAS, and VDS scores (p < 0.05). In the direct comparison of the changes in the swallowing parameters among the three groups, the change in CDS scores at T1 and T2 showed a significantly higher improvement in the bilateral simulation group than in two other groups (p < 0.05). There was a significantly larger change in the DOSS, PAS, and VDS scores at T1 in the bilateral stimulation group than in two other groups (p < 0.05). The results of the present study provide substantial evidence that 10 Hz rTMS at the bilateral motor cortices over the cortical areas projecting to the mylohyoid muscles is effective as an additional treatment strategy to traditional dysphagia therapies. Copyright © 2016. Published by Elsevier Inc.

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…

Characterization of the resting-state brain network topology in the 6-hydroxydopamine rat model of Parkinson’s disease

PubMed Central

Simmons, Camilla; Mesquita, Michel B.; Wood, Tobias C.; Williams, Steve C. R.; Vernon, Anthony C.; Cash, Diana

2017-01-01

Resting-state functional MRI (rsfMRI) is an imaging technology that has recently gained attention for its ability to detect disruptions in functional brain networks in humans, including in patients with Parkinson’s disease (PD), revealing early and widespread brain network abnormalities. This methodology is now readily applicable to experimental animals offering new possibilities for cross-species translational imaging. In this context, we herein describe the application of rsfMRI to the unilaterally-lesioned 6-hydroxydopamine (6-OHDA) rat, a robust experimental model of the dopamine depletion implicated in PD. Using graph theory to analyse the rsfMRI data, we were able to provide meaningful and translatable measures of integrity, influence and segregation of the underlying functional brain architecture. Specifically, we confirm that rats share a similar functional brain network topology as observed in humans, characterised by small-worldness and modularity. Interestingly, we observed significantly reduced functional connectivity in the 6-OHDA rats, primarily in the ipsilateral (lesioned) hemisphere as evidenced by significantly lower node degree, local efficiency and clustering coefficient in the motor, orbital and sensorimotor cortices. In contrast, we found significantly, and bilaterally, increased thalamic functional connectivity in the lesioned rats. The unilateral deficits in the cortex are consistent with the unilateral nature of this model and further support the validity of the rsfMRI technique in rodents. We thereby provide a methodological framework for the investigation of brain networks in other rodent experimental models of PD, as well as of animal models in general, for cross-comparison with human data. PMID:28249008

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.

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

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.

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.

Motor skills of children with unilateral visual impairment in the Infant Aphakia Treatment Study.

PubMed

Celano, Marianne; Hartmann, E Eugenie; DuBois, Lindreth G; Drews-Botsch, Carolyn

2016-02-01

To assess motor functioning in children aged 4 years 6 months enrolled in the Infant Aphakia Treatment Study, and to determine contributions of visual acuity and stereopsis to measured motor skills. One hundred and four children (53% female) with unilateral aphakia randomized to intraocular lens or contact lens treatment were evaluated at 4 years 6 months (age range 4y 6mo-4y 11mo) for monocular recognition visual acuity, motor skills, and stereopsis by a traveling examiner masked to treatment condition. Motor skills were assessed with the Movement Assessment Battery for Children--Second Edition (MABC-2). Visual acuity was operationalized as log10 of the minimum angle of resolution (logMAR) value for treated eye, best logMAR value for either eye, and intraocular logMAR difference. Student's t-tests showed no significant differences in MABC-2 scores between the intraocular lens and contact lens groups. The mean total score was low (6.43; 18th centile) compared with the normative reference group. Motor functioning was not related to visual acuity in the treated eye or to intraocular logMAR difference, but was predicted in a regression model by the better visual acuity of either eye (usually the fellow eye), even after accounting for the influence of age at surgery, examiner, orthotropic ocular alignment, and stereopsis. Children with unilateral congenital cataract may have delayed motor functioning at 4 years 6 months, which may adversely affect their social and academic functioning. © 2015 Mac Keith Press.

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.

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.

Visual Field Function in School-Aged Children with Spastic Unilateral Cerebral Palsy Related to Different Patterns of Brain Damage

ERIC Educational Resources Information Center

Jacobson, Lena; Rydberg, Agneta; Eliasson, Ann-Christin; Kits, Annika; Flodmark, Olof

2010-01-01

Aim: To relate visual field function to brain morphology in children with unilateral cerebral palsy (CP). Method: Visual field function was assessed using the confrontation technique and Goldmann perimetry in 29 children (15 males, 14 females; age range 7-17y, median age 11y) with unilateral CP classified at Gross Motor Function Classification…

Magnetic resonance spectroscopy of current hand amputees reveals evidence for neuronal-level changes in former sensorimotor cortex

PubMed Central

Choi, In-Young; Lee, Phil; Peng, Huiling; Kaufman, Christina L.; Frey, Scott H.

2017-01-01

Deafferentation is accompanied by large-scale functional reorganization of maps in the primary sensory and motor areas of the hemisphere contralateral to injury. Animal models of deafferentation suggest a variety of cellular-level changes including depression of neuronal metabolism and even neuronal death. Whether similar neuronal changes contribute to patterns of reorganization within the contralateral sensorimotor cortex of chronic human amputees is uncertain. We used functional MRI-guided proton magnetic resonance spectroscopy to test the hypothesis that unilateral deafferentation is associated with lower levels of N-acetylaspartate (NAA, a putative marker of neuronal integrity) in the sensorimotor hand territory located contralateral to the missing hand in chronic amputees (n = 19) compared with the analogous hand territory of age- and sex-matched healthy controls (n = 28). We also tested whether former amputees [i.e., recipients of replanted (n = 3) or transplanted (n = 2) hands] exhibit NAA levels that are indistinguishable from controls, possible evidence for reversal of the effects of deafferentation. As predicted, relative to controls, current amputees exhibited lower levels of NAA that were negatively and significantly correlated with the time after amputation. Contrary to our prediction, NAA levels in both replanted and transplanted patients fell within the range of the current amputees. We suggest that lower levels of NAA in current amputees reflects altered neuronal integrity consequent to chronic deafferentation. Thus local changes in NAA levels may provide a means of assessing neuroplastic changes in deafferented cortex. Results from former amputees suggest that these changes may not be readily reversible through reafferentation. NEW & NOTEWORTHY This study is the first to use functional magnetic resonance-guided magnetic resonance spectroscopy to examine neurochemical mechanisms underlying functional reorganization in the primary somatosensory and motor cortices consequent to upper extremity amputation and its potential reversal through hand replantation or transplantation. We provide evidence for selective alteration of cortical neuronal integrity associated with amputation-related deafferentation that may not be reversible. PMID:28179478

Cortical lamina-dependent blood volume changes in human brain at 7 T.

PubMed

Huber, Laurentius; Goense, Jozien; Kennerley, Aneurin J; Trampel, Robert; Guidi, Maria; Reimer, Enrico; Ivanov, Dimo; Neef, Nicole; Gauthier, Claudine J; Turner, Robert; Möller, Harald E

2015-02-15

Cortical layer-dependent high (sub-millimeter) resolution functional magnetic resonance imaging (fMRI) in human or animal brain can be used to address questions regarding the functioning of cortical circuits, such as the effect of different afferent and efferent connectivities on activity in specific cortical layers. The sensitivity of gradient echo (GE) blood oxygenation level-dependent (BOLD) responses to large draining veins reduces its local specificity and can render the interpretation of the underlying laminar neural activity impossible. The application of the more spatially specific cerebral blood volume (CBV)-based fMRI in humans has been hindered by the low sensitivity of the noninvasive modalities available. Here, a vascular space occupancy (VASO) variant, adapted for use at high field, is further optimized to capture layer-dependent activity changes in human motor cortex at sub-millimeter resolution. Acquired activation maps and cortical profiles show that the VASO signal peaks in gray matter at 0.8-1.6mm depth, and deeper compared to the superficial and vein-dominated GE-BOLD responses. Validation of the VASO signal change versus well-established iron-oxide contrast agent based fMRI methods in animals showed the same cortical profiles of CBV change, after normalization for lamina-dependent baseline CBV. In order to evaluate its potential of revealing small lamina-dependent signal differences due to modulations of the input-output characteristics, layer-dependent VASO responses were investigated in the ipsilateral hemisphere during unilateral finger tapping. Positive activation in ipsilateral primary motor cortex and negative activation in ipsilateral primary sensory cortex were observed. This feature is only visible in high-resolution fMRI where opposing sides of a sulcus can be investigated independently because of a lack of partial volume effects. Based on the results presented here, we conclude that VASO offers good reproducibility, high sensitivity and lower sensitivity than GE-BOLD to changes in larger vessels, making it a valuable tool for layer-dependent fMRI studies in humans. Copyright © 2014 Elsevier Inc. All rights reserved.

Suppression of metabolic activity caused by infantile strabismus and strabismic amblyopia in striate visual cortex of macaque monkeys.

PubMed

Wong, Agnes M F; Burkhalter, Andreas; Tychsen, Lawrence

2005-02-01

Suppression is a major sensorial abnormality in humans and monkeys with infantile strabismus. We previously reported evidence of metabolic suppression in the visual cortex of strabismic macaques, using the mitochondrial enzyme cytochrome oxidase as an anatomic label. The purpose of this study was to further elucidate alterations in cortical metabolic activity, with or without amblyopia. Six macaque monkeys were used in the experiments (four strabismic and two control). Three of the strabismic monkeys had naturally occurring, infantile strabismus (two esotropic, one exotropic). The fourth strabismic monkey had infantile microesotropia induced by alternating monocular occlusion in the first months of life. Ocular motor behaviors and visual acuity were tested after infancy in each animal, and development of stereopsis was recorded during infancy in one strabismic and one control monkey. Ocular dominance columns (ODCs) of the striate visual cortex (area V1) were labeled using cytochrome oxidase (CO) histochemistry alone, or CO in conjunction with an anterograde tracer ([H 3 ]proline or WGA-HRP) injected into one eye. Each of the strabismic monkeys showed inequalities of metabolic activity in ODCs of opposite ocularity, visible as rows of lighter CO staining, corresponding to ODCs of lower metabolic activity, alternating with rows of darker CO staining, corresponding to ODCs of higher metabolic activity. In monkeys who had infantile strabismus and unilateral amblyopia, lower metabolic activity was found in (suppressed) ODCs driven by the nondominant eye in each hemisphere. In monkeys who had infantile esotropia and alternating fixation (no amblyopia), metabolic activity was lower in ODCs driven by the ipsilateral eye in each hemisphere. The suppression included a monocular core zone at the center of ODCs and binocular border zones at the boundaries of ODCs. This suppression was not evident in the monocular lamina of the LGN, indicating an intracortical rather than subcortical mechanism. Suppression of metabolic activity in ODCs of V1 differs depending upon whether infantile strabismus is alternating or occurs in conjunction with unilateral amblyopia. Our findings reinforce the principle that unrepaired strabismus promotes abnormal competition in V1, observable as interocular suppression of ODCs.

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

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…

Outcome-dependent coactivation of lip and tongue primary somatosensory representation following hypoglossal-facial transfer after peripheral facial palsy.

PubMed

Rottler, Philipp; Schroeder, Henry W S; Lotze, Martin

2014-02-01

A hypoglossal-facial transfer is a common surgical strategy for reanimating the face after persistent total hemifacial palsy. We were interested in how motor recovery is associated with cortical reorganization of lip and tongue representation in the primary sensorimotor cortex after the transfer. Therefore, we used functional magnetic resonance imaging (fMRI) in 13 patients who underwent a hypoglossal-facial transfer after unilateral peripheral facial palsy. To identify primary motor and somatosensory tongue and lip representation sites, we measured repetitive tongue and lip movements during fMRI. Electromyography (EMG) of the perioral muscles during tongue and lip movements and standardized evaluation of lip elevation served as outcome parameters. We found an association of cortical representation sites in the pre- and postcentral gyrus (decreased distance of lip and tongue representation) with symmetry of recovered lip movements (lip elevation) and coactivation of the lip during voluntary tongue movements (EMG-activity of the lip during tongue movements). Overall, our study shows that hypoglossal-facial transfer resulted in an outcome-dependent cortical reorganization with activation of the cortical tongue area for restituded movement of the lip. Copyright © 2012 Wiley Periodicals, Inc.

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

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.

Is hemiplegic cerebral palsy equivalent to amblyopia of the corticospinal system?

PubMed

Eyre, Janet A; Smith, Martin; Dabydeen, Lyvia; Clowry, Gavin J; Petacchi, Eliza; Battini, Roberta; Guzzetta, Andrea; Cioni, Giovanni

2007-11-01

Subjects with severe hemiplegic cerebral palsy have increased ipsilateral corticospinal projections from their noninfarcted cortex. We investigated whether their severe impairment might, in part, be caused by activity-dependent, competitive displacement of surviving contralateral corticospinal projections from the affected cortex by more active ipsilateral corticospinal projections from the nonaffected cortex, thereby compounding the impairment. Transcranial magnetic stimulation (TMS) characterized corticospinal tract development from each hemisphere over the first 2 years in 32 healthy children, 14 children with unilateral stroke, and 25 with bilateral lesions. Magnetic resonance imaging and anatomic studies compared corticospinal tract growth in 13 patients with perinatal stroke with 46 healthy subjects. Infants with unilateral lesions initially had responses after TMS of the affected cortex, which became progressively more abnormal, and seven were eventually lost. There was associated hypertrophy of the ipsilateral corticospinal axons projecting from the noninfarcted cortex. Magnetic resonance imaging and anatomic studies demonstrated hypertrophy of the corticospinal tract from the noninfarcted hemisphere. TMS findings soon after the stroke did not predict impairment; subsequent loss of responses and hypertrophy of ipsilateral corticospinal axons from the noninfarcted cortex predicted severe impairment at 2 years. Infants with bilateral lesions maintained responses to TMS from both hemispheres with a normal pattern of development. Rather than representing "reparative plasticity," increased ipsilateral projections from the noninfarcted cortex compound disability by competitively displacing surviving contralateral corticospinal projections from the infarcted cortex. This may provide a pathophysiological explanation for why signs of hemiplegic cerebral palsy appear late and progress over the first 2 years of life.

Characteristics of seizure-induced signal changes on MRI in patients with first seizures.

PubMed

Kim, Si Eun; Lee, Byung In; Shin, Kyong Jin; Ha, Sam Yeol; Park, JinSe; Park, Kang Min; Kim, Hyung Chan; Lee, Joonwon; Bae, Soo-Young; Lee, Dongah; Kim, Sung Eun

2017-05-01

The aim of this study was to investigate the predictive factors and identify the characteristics of the seizure-induced signal changes on MRI (SCM) in patients with first seizures. We conducted a retrospective study of patients with first seizures from March 2010 to August 2014. The inclusion criteria for this study were patients with 1) first seizures, and 2) MRI and EEG performed within 24h of the first seizures. The definition of SCM was hyper-intensities in the brain not applying to cerebral arterial territories. Multivariate logistic regression was performed with or without SCM as a dependent variable. Of 431 patients with seizures visiting the ER, 69 patients met the inclusion criteria. Of 69 patients, 11 patients (15.9%) had SCM. Epileptiform discharge on EEG (OR 29.7, 95% CI 1.79-493.37, p=0.018) was an independently significant variable predicting the presence of SCM in patients with first seizures. In addition, the topography of SCM was as follows; i) ipsilateral hippocampus, thalamus and cerebral cortex (5/11), ii) unilateral cortex (4/11), iii) ipsilateral thalamus and cerebral cortex (1/11), iv) bilateral hippocampus (1/11). Moreover, 6 out of 7 patients who underwent both perfusion CT and MRI exhibited unilateral cortical hyperperfusion with ipsilateral thalamic involvement reflecting unrestricted vascular territories. There is an association between epileptiform discharges and SCM. Additionally, the involvement of the unilateral cortex and ipsilateral thalamus in SCM and its hyperperfusion state could be helpful in differentiating the consequences of epileptic seizures from other pathologies. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

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

Unilateral Recession-Resection Surgery for Infantile Esotropia: Survival of Motor Outcomes and Postoperative Drifts.

PubMed

Chatzistefanou, Klio I; Brouzas, Dimitrios; Droutsas, Konstantinos D; Koutsandrea, Chryssanthi; Chimonidou, Eleutheria

2017-05-10

To outline the short- and long-term motor outcomes of unilateral medial rectus muscle recession and lateral rectus muscle resection for the correction of moderate angle infantile esotropia. A retrospective study of 109 consecutive patients with moderate angle infantile esotropia treated with graded unilateral recession-resection surgery. Criteria for successful motor outcome included alignment ±10Δ from orthophoria. Outcome evaluation was a comparison of successful alignment versus an overcorrection or undercorrection at eight weeks postoperatively as well as on the final follow-up examination. The mean preoperative deviation was 35.5 prism diopters (Δ) and mean follow-up time was 4.9 years. At the eight-week postoperative examination, 99 patients (89.9%) were successfully aligned, as opposed to 75 of 95 patients (78.9%) at the final postoperative visit (P=0.041). There was no statistically significant difference between the rate of early versus late undercorrections (7.3% versus 12.5%, P=0.267) or overcorrections (2.7% versus 8.3%, P=0.125). Ten patients had an esotropic drift over time and 10 patients had an exotropic drift. Recurrent esotropia was associated with high hyperopia and presumed infantile esotropia diagnostic entity. The Kaplan-Meier estimate of survivorship of a successful motor outcome was 75.5% at five years and 71% at 15 years postoperatively. The mean response to surgery was 2.9Δ per mm of muscle recessed and resected and was positively related to the preoperative angle of deviation (R=0.615). The unilateral recession-resection procedure for the correction of infantile esotropia is shown to be associated with a favorable survival of motor outcomes and a relatively balanced rate of undercorrections versus overcorrections tending to be maintained through the follow-up period.

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

Reliability of lower limb transcranial magnetic stimulation outcomes in the ipsi- and contralesional hemispheres of adults with chronic stroke.

PubMed

Beaulieu, Louis-David; Massé-Alarie, Hugo; Ribot-Ciscar, Edith; Schneider, Cyril

2017-07-01

To investigate the ability of transcranial magnetic stimulation (TMS) outcomes in the chronic stroke population to (i) track individual plastic changes and (ii) detect differences between individuals. To this end, intrarater "test-retest" reliability (relative and absolute) was tested for the ipsilesional and contralesional hemispheres. Thirteen participants with a unilateral stroke (≥6months ago) and sensorimotor impairments were enrolled. Single and paired-pulse TMS outcomes were obtained from the primary motor cortex (M1) representation of the tibialis anterior muscle in both hemispheres and at two sessions separated by one week. The standard error of the measurement (SEM eas ), minimal detectable change (MDC) and intraclass correlation coefficient (ICC) were studied. Active motor threshold and latency of motor evoked potentials provided the lowest SEM eas and highest ICCs for both ipsi- and contralesional hemispheres. However, MDC were generally large, thus questioning the use of TMS outcomes to track individual plastic changes of M1. Our study provided supporting evidence of good to excellent intrarater reliability for a few TMS outcomes and proposed recommendations on the interpretation and the use of that knowledge in future work. Psychometric properties of TMS measures should be further addressed in order to better understand how to refine their use in clinical settings. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

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

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

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.

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.

A brain-spine interface alleviating gait deficits after spinal cord injury in primates.

PubMed

Capogrosso, Marco; Milekovic, Tomislav; Borton, David; Wagner, Fabien; Moraud, Eduardo Martin; Mignardot, Jean-Baptiste; Buse, Nicolas; Gandar, Jerome; Barraud, Quentin; Xing, David; Rey, Elodie; Duis, Simone; Jianzhong, Yang; Ko, Wai Kin D; Li, Qin; Detemple, Peter; Denison, Tim; Micera, Silvestro; Bezard, Erwan; Bloch, Jocelyne; Courtine, Grégoire

2016-11-10

Spinal cord injury disrupts the communication between the brain and the spinal circuits that orchestrate movement. To bypass the lesion, brain-computer interfaces have directly linked cortical activity to electrical stimulation of muscles, and have thus restored grasping abilities after hand paralysis. Theoretically, this strategy could also restore control over leg muscle activity for walking. However, replicating the complex sequence of individual muscle activation patterns underlying natural and adaptive locomotor movements poses formidable conceptual and technological challenges. Recently, it was shown in rats that epidural electrical stimulation of the lumbar spinal cord can reproduce the natural activation of synergistic muscle groups producing locomotion. Here we interface leg motor cortex activity with epidural electrical stimulation protocols to establish a brain-spine interface that alleviated gait deficits after a spinal cord injury in non-human primates. Rhesus monkeys (Macaca mulatta) were implanted with an intracortical microelectrode array in the leg area of the motor cortex and with a spinal cord stimulation system composed of a spatially selective epidural implant and a pulse generator with real-time triggering capabilities. We designed and implemented wireless control systems that linked online neural decoding of extension and flexion motor states with stimulation protocols promoting these movements. These systems allowed the monkeys to behave freely without any restrictions or constraining tethered electronics. After validation of the brain-spine interface in intact (uninjured) monkeys, we performed a unilateral corticospinal tract lesion at the thoracic level. As early as six days post-injury and without prior training of the monkeys, the brain-spine interface restored weight-bearing locomotion of the paralysed leg on a treadmill and overground. The implantable components integrated in the brain-spine interface have all been approved for investigational applications in similar human research, suggesting a practical translational pathway for proof-of-concept studies in people with spinal cord injury.

A Brain–Spinal Interface Alleviating Gait Deficits after Spinal Cord Injury in Primates

PubMed Central

Capogrosso, Marco; Milekovic, Tomislav; Borton, David; Wagner, Fabien; Moraud, Eduardo Martin; Mignardot, Jean-Baptiste; Buse, Nicolas; Gandar, Jerome; Barraud, Quentin; Xing, David; Rey, Elodie; Duis, Simone; Jianzhong, Yang; Ko, Wai Kin D.; Li, Qin; Detemple, Peter; Denison, Tim; Micera, Silvestro; Bezard, Erwan; Bloch, Jocelyne; Courtine, Grégoire

2016-01-01

Spinal cord injury disrupts the communication between the brain and the spinal circuits that orchestrate movement. To bypass the lesion, brain–computer interfaces1–3 have directly linked cortical activity to electrical stimulation of muscles, which have restored grasping abilities after hand paralysis1,4. Theoretically, this strategy could also restore control over leg muscle activity for walking5. However, replicating the complex sequence of individual muscle activation patterns underlying natural and adaptive locomotor movements poses formidable conceptual and technological challenges6,7. Recently, we showed in rats that epidural electrical stimulation of the lumbar spinal cord can reproduce the natural activation of synergistic muscle groups producing locomotion8–10. Here, we interfaced leg motor cortex activity with epidural electrical stimulation protocols to establish a brain–spinal interface that alleviated gait deficits after a spinal cord injury in nonhuman primates. Rhesus monkeys were implanted with an intracortical microelectrode array into the leg area of motor cortex; and a spinal cord stimulation system composed of a spatially selective epidural implant and a pulse generator with real-time triggering capabilities. We designed and implemented wireless control systems that linked online neural decoding of extension and flexion motor states with stimulation protocols promoting these movements. These systems allowed the monkeys to behave freely without any restrictions or constraining tethered electronics. After validation of the brain–spinal interface in intact monkeys, we performed a unilateral corticospinal tract lesion at the thoracic level. As early as six days post-injury and without prior training of the monkeys, the brain–spinal interface restored weight-bearing locomotion of the paralyzed leg on a treadmill and overground. The implantable components integrated in the brain–spinal interface have all been approved for investigational applications in similar human research, suggesting a practical translational pathway for proof-of-concept studies in people with spinal cord injury. PMID:27830790

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.

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

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.

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

Examining Differences in Patterns of Sensory and Motor Recovery After Stroke With Robotics.

PubMed

Semrau, Jennifer A; Herter, Troy M; Scott, Stephen H; Dukelow, Sean P

2015-12-01

Developing a better understanding of the trajectory and timing of stroke recovery is critical for developing patient-centered rehabilitation approaches. Here, we quantified proprioceptive and motor deficits using robotic technology during the first 6 months post stroke to characterize timing and patterns in recovery. We also make comparisons of robotic assessments to traditional clinical measures. One hundred sixteen subjects with unilateral stroke were studied at 4 time points: 1, 6, 12, and 26 weeks post stroke. Subjects performed robotic assessments of proprioceptive (position sense and kinesthesia) and motor function (unilateral reaching task and bimanual object hit task), as well as several clinical measures (Functional Independence Measure, Purdue Pegboard, and Chedoke-McMaster Stroke Assessment). One week post stroke, many subjects displayed proprioceptive (48% position sense and 68% kinesthesia) and motor impairments (80% unilateral reaching and 85% bilateral movement). Interindividual recovery on robotic measures was highly variable. However, we characterized recovery as early (normal by 6 weeks post stroke), late (normal by 26 weeks post stroke), or incomplete (impaired at 26 weeks post stroke). Proprioceptive and motor recovery often followed different timelines. Across all time points, robotic measures were correlated with clinical measures. These results highlight the need for more sensitive, targeted identification of sensory and motor deficits to optimize rehabilitation after stroke. Furthermore, the trajectory of recovery for some individuals with mild to moderate stroke may be much longer than previously considered. © 2015 American Heart Association, Inc.

Contralateral peripheral neurotization for a hemiplegic hindlimb after central neurological injury.

PubMed

Zheng, Mou-Xiong; Hua, Xu-Yun; Jiang, Su; Qiu, Yan-Qun; Shen, Yun-Dong; Xu, Wen-Dong

2018-01-01

OBJECTIVE Contralateral peripheral neurotization surgery has been successfully applied to rescue motor function of the hemiplegic upper extremity in patients with central neurological injury (CNI). It may contribute to strengthened neural pathways between the contralesional cortex and paretic limbs. However, the effect of this surgery in the lower extremities remains unknown. In the present study the authors explored the effectiveness and safety of contralateral peripheral neurotization in treating a hemiplegic lower extremity following CNI in adult rats. METHODS Controlled cortical impact (CCI) was performed on the hindlimb motor cortex of 36 adult Sprague-Dawley rats to create severe unilateral traumatic brain injury models. These CCI rats were randomly divided into 3 groups. At 1 month post-CCI, the experimental group (Group 1, 12 rats) underwent contralateral L-6 to L-6 transfer, 1 control group (Group 2, 12 rats) underwent bilateral L-6 nerve transection, and another control group (Group 3, 12 rats) underwent an L-6 laminectomy without injuring the L-6 nerves. Bilateral L-6 nerve transection rats without CCI (Group 4, 12 rats) and naïve rats (Group 5, 12 rats) were used as 2 additional control groups. Beam and ladder rung walking tests and CatWalk gait analysis were performed in each rat at baseline and at 0.5, 1, 2, 4, 6, 8, and 10 months to detect the skilled walking functions and gait parameters of both hindlimbs. Histological and electromyography studies were used at the final followup to verify establishment of the traumatic brain injury model and regeneration of the L6-L6 neural pathway. RESULTS In behavioral tests, comparable motor injury in the paretic hindlimbs was observed after CCI in Groups 1-3. Group 1 started to show significantly lower slip and error rates in the beam and ladder rung walking tests than Groups 2 and 3 at 6 months post-CCI (p < 0.05). In the CatWalk analysis, Group 1 also showed a higher mean intensity and swing speed after 8 months post-CCI and a longer stride length after 6 months post-CCI than Groups 2 and 3 (p < 0.05). Transection of L-6 resulted in transient skilled walking impairment in the intact hindlimbs in Groups 1 and 2 (compared with Group 3) and in the bilateral hindlimbs in Group 4 (compared with Group 5). All recovered to baseline level within 2 months. Histological study of the rat brains verified comparable injured volumes among Groups 1-3 at final examinations, and electromyography and toluidine blue staining indicated successful regeneration of the L6-L6 neural pathways in Group 1. CONCLUSIONS Contralateral L-6 neurotization could be a promising and safe surgical approach for improving motor recovery of the hemiplegic hindlimb after unilateral CNI in adult rats. Further investigations are needed before extrapolating the present conclusions to humans.

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…

Strengths and challenges faced by school-aged children with unilateral CP described by the Five To Fifteen parental questionnaire.

PubMed

Forsman, Lea; Eliasson, Ann-Christin

2016-12-01

The purpose of this study was to describe motor and non-motor (e.g. cognitive, social, and behavioral) challenges faced in daily life by children with unilateral cerebral palsy (UCP). In this cross-sectional study, parents completed the Five to Fifteen questionnaire and provided demographic information for 46 children aged 6-15 years (mean 11.01 ± 2.89 SD). Most children were reported to have problems in both motor and non-motor domains, ranging from 20 to 92% depending on the domain. Perception and learning were the non-motor functions most commonly reported as challenging (63 and 65%, respectively). The total number of problems was significantly higher in age groups above 9 years. The correlation between all domains was high, but was consistently higher with the fine motor sub-domain, which could be used to predict executive function, perception, memory, and learning outcomes (R 2 =0.502, 0.642, 0.192, 0.192). Most children with CP have everyday challenges beyond their primary motor deficiencies.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Parkinsonian gait improves with bilateral subthalamic nucleus deep brain stimulation during cognitive multi-tasking.

PubMed

Chenji, Gaurav; Wright, Melissa L; Chou, Kelvin L; Seidler, Rachael D; Patil, Parag G

2017-05-01

Gait impairment in Parkinson's disease reduces mobility and increases fall risk, particularly during cognitive multi-tasking. Studies suggest that bilateral subthalamic deep brain stimulation, a common surgical therapy, degrades motor performance under cognitive dual-task conditions, compared to unilateral stimulation. To measure the impact of bilateral versus unilateral subthalamic deep brain stimulation on walking kinematics with and without cognitive dual-tasking. Gait kinematics of seventeen patients with advanced Parkinson's disease who had undergone bilateral subthalamic deep brain stimulation were examined off medication under three stimulation states (bilateral, unilateral left, unilateral right) with and without a cognitive challenge, using an instrumented walkway system. Consistent with earlier studies, gait performance declined for all six measured parameters under cognitive dual-task conditions, independent of stimulation state. However, bilateral stimulation produced greater improvements in step length and double-limb support time than unilateral stimulation, and achieved similar performance for other gait parameters. Contrary to expectations from earlier studies of dual-task motor performance, bilateral subthalamic deep brain stimulation may assist in maintaining temporal and spatial gait performance under cognitive dual-task conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Chinese patient with pusher syndrome and unilateral spatial neglect syndrome.

PubMed

Chen, Xiao-Wei; Lin, Cheng-He; Zheng, Hua; Lin, Zhen-Lan

2014-07-01

To observe clinical manifestations, behavioral characteristics, and effects of rehabilitation on a patient with pusher syndrome and unilateral spatial neglect caused by right thalamic hemorrhage. Assessment of pusher syndrome was made by the Scale for Contraversive pushing (SCP), and unilateral spatial neglect syndrome was diagnosed using line cancellation, letter and star cancellation, line bisection tests and copy and continuation of graphic sequence test. Behavioral therapy, occupational therapy, reading training and traditional Chinese medicine methods were adopted for treatment of pusher syndrome and unilateral spatial neglect. The patient showed typical pusher syndrome and unilateral spatial neglect symptoms. The pusher syndrome and unilateral spatial neglect symptoms were significantly improved following rehabilitation treatments. Pusher syndrome and unilateral spatial neglect syndrome occurred simultaneously after right thalamic hemorrhage. Early rehabilitation therapy can reduce the symptoms of pusher syndrome and unilateral spatial neglect syndrome and improve motor function.

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.

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

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

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.

[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.

Priming Hand Motor Training with Repetitive Stimulation of the Fingertips; Performance Gain and Functional Imaging of Training Effects.

PubMed

Lotze, Martin; Ladda, Aija Marie; Roschka, Sybille; Platz, Thomas; Dinse, Hubert R

Application of repetitive electrical stimulation (rES) of the fingers has been shown to improve tactile perception and sensorimotor performance in healthy individuals. To increase motor performance by priming the effects of active motor training (arm ability training; AAT) using rES. We compared the performance gain for the training increase of the averaged AAT tasks of both hands in two groups of strongly right-handed healthy volunteers. Functional Magnetic Resonance Imaging (fMRI) before and after AAT was assessed using three tasks for each hand separately: finger sequence tapping, visually guided grip force modulation, and writing. Performance during fMRI was controlled for preciseness and frequency. A total of 30 participants underwent a two-week unilateral left hand AAT, 15 participants with 20 minutes of rES priming of all fingertips of the trained hand, and 15 participants without rES priming. rES-primed AAT improved the trained left-hand performance across all training tasks on average by 32.9%, non-primed AAT improved by 29.5%. This gain in AAT performance with rES priming was predominantly driven by an increased finger tapping velocity. Functional imaging showed comparable changes for both training groups over time. Across all participants, improved AAT performance was associated with a higher contralateral primary somatosensory cortex (S1) fMRI activation magnitude during the grip force modulation task. This study highlights the importance of S1 for hand motor training gain. In addition, it suggests the usage of rES of the fingertips for priming active hand motor training. Copyright © 2016 Elsevier Inc. All rights reserved.

Remote effects of intermittent theta burst stimulation of the human pharyngeal motor system

PubMed Central

Mistry, Satish; Michou, Emilia; Rothwell, John; Hamdy, Shaheen

2015-01-01

Intermittent theta burst stimulation (iTBS) is a novel, non-invasive form of brain stimulation capable of facilitating excitability of the human primary motor cortex with therapeutic potential in the treatment of neurological conditions, such as multiple sclerosis. The objectives of this study were to evaluate the effects of iTBS on cortical properties in the human pharyngeal motor system. Transcranial magnetic stimulation (TMS)-evoked pharyngeal motor responses were recorded via a swallowed intra-luminal catheter and used to assess motor cortical pathways to the pharynx in both hemispheres before and for up to 90 min after iTBS in 15 healthy adults (nine male/six female, 22–59 years old). Active/sham iTBS comprised 600 intermittent repetitive TMS pulses, delivered in a double-blind pseudo-randomised order over each hemisphere on separate days at least 1 week apart. Abductor pollicis brevis (APB) recordings were used as control. Hemispheric interventional data were compared with sham using repeated-measures anova. iTBS was delivered at an average intensity of 43 ± 1% of stimulator output. Compared with sham, iTBS to the hemisphere with stronger pharyngeal projections induced increased responses only in the contralateral weaker projection 60–90 min post-iTBS (maximum 54 ± 19%, P ≤ 0.007), with no change in stronger hemisphere responses. By contrast, iTBS to weaker projections had no significant effects (P = 0.39) on either hemisphere. APB responses similarly did not change significantly (P = 0.78) across all study arms. We conclude that iTBS can induce remote changes in corticobulbar excitability. While further studies will clarify the extent of these changes, iTBS holds promise as a potential treatment for dysphagia after unilateral brain damage. PMID:22640033

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

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.

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.

Persistent post-stroke depression in mice following unilateral medial prefrontal cortical stroke

PubMed Central

Vahid-Ansari, F; Lagace, D C; Albert, P R

2016-01-01

Post-stroke depression (PSD) is a common outcome following stroke that is associated with poor recovery. To develop a preclinical model of PSD, we targeted a key node of the depression–anxiety circuitry by inducing a unilateral ischemic lesion to the medial prefrontal cortex (mPFC) stroke. Microinjection of male C57/BL6 mice with endothelin-1 (ET-1, 1600 pmol) induced a small (1 mm3) stroke consistently localized within the left mPFC. Compared with sham control mice, the stroke mice displayed a robust behavioral phenotype in four validated tests of anxiety including the elevated plus maze, light–dark, open-field and novelty-suppressed feeding tests. In addition, the stroke mice displayed depression-like behaviors in both the forced swim and tail suspension test. In contrast, there was no effect on locomotor activity or sensorimotor function in the horizontal ladder, or cylinder and home cage activity tests, indicating a silent stroke due to the absence of motor abnormalities. When re-tested at 6 weeks post stroke, the stroke mice retained both anxiety and depression phenotypes. Surprisingly, at 6 weeks post stroke the lesion site was infiltrated by neurons, suggesting that the ET-1-induced neuronal loss in the mPFC was reversible over time, but was insufficient to promote behavioral recovery. In summary, unilateral ischemic lesion of the mPFC results in a pronounced and persistent anxiety and depression phenotype with no evident sensorimotor deficits. This precise lesion of the depression circuitry provides a reproducible model to study adaptive cellular changes and preclinical efficacy of novel interventions to alleviate PSD symptoms. PMID:27483381

Estimation of distal arm joint angles from EMG and shoulder orientation for transhumeral prostheses.

PubMed

Akhtar, Aadeel; Aghasadeghi, Navid; Hargrove, Levi; Bretl, Timothy

2017-08-01

In this paper, we quantify the extent to which shoulder orientation, upper-arm electromyography (EMG), and forearm EMG are predictors of distal arm joint angles during reaching in eight subjects without disability as well as three subjects with a unilateral transhumeral amputation and targeted reinnervation. Prior studies have shown that shoulder orientation and upper-arm EMG, taken separately, are predictors of both elbow flexion/extension and forearm pronation/supination. We show that, for eight subjects without disability, shoulder orientation and upper-arm EMG together are a significantly better predictor of both elbow flexion/extension during unilateral (R 2 =0.72) and mirrored bilateral (R 2 =0.72) reaches and of forearm pronation/supination during unilateral (R 2 =0.77) and mirrored bilateral (R 2 =0.70) reaches. We also show that adding forearm EMG further improves the prediction of forearm pronation/supination during unilateral (R 2 =0.82) and mirrored bilateral (R 2 =0.75) reaches. In principle, these results provide the basis for choosing inputs for control of transhumeral prostheses, both by subjects with targeted motor reinnervation (when forearm EMG is available) and by subjects without target motor reinnervation (when forearm EMG is not available). In particular, we confirm that shoulder orientation and upper-arm EMG together best predict elbow flexion/extension (R 2 =0.72) for three subjects with unilateral transhumeral amputations and targeted motor reinnervation. However, shoulder orientation alone best predicts forearm pronation/supination (R 2 =0.88) for these subjects, a contradictory result that merits further study. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

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

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.

Characteristics of bilateral hand function in individuals with unilateral dystonia due to perinatal stroke: sensory and motor aspects.

PubMed

de Campos, Ana Carolina; Kukke, Sahana N; Hallett, Mark; Alter, Katharine E; Damiano, Diane L

2014-05-01

The authors assessed bilateral motor and sensory function in individuals with upper limb dystonia due to unilateral perinatal stroke and explored interrelationships of motor function and sensory ability. Reach kinematics and tactile sensation were measured in 7 participants with dystonia and 9 healthy volunteers. The dystonia group had poorer motor (hold time, reach time, shoulder/elbow correlation) and sensory (spatial discrimination, stereognosis) outcomes than the control group on the nondominant side. On the dominant side, only sensation (spatial discrimination, stereognosis) was poorer in the dystonia group compared with the control group. In the dystonia group, although sensory and motor outcomes were uncorrelated, dystonia severity was related to poorer stereognosis, longer hold and reach times, and decreased shoulder/elbow coordination. Findings of bilateral sensory deficits in dystonia can be explained by neural reorganization. Visual compensation for somatosensory changes in the nonstroke hemisphere may explain the lack of bilateral impairments in reaching.

Characteristics of bilateral hand function in individuals with unilateral dystonia due to perinatal stroke: sensory and motor aspects

PubMed Central

de Campos, Ana Carolina; Kukke, Sahana N.; Hallett, Mark; Alter, Katharine E.; Damiano, Diane L.

2014-01-01

We assessed bilateral motor and sensory function in individuals with upper limb dystonia due to unilateral perinatal stroke and explored interrelationships of motor function and sensory ability. Reach kinematics and tactile sensation were measured in seven participants with dystonia and nine healthy volunteers. The dystonia group had poorer motor (hold time, reach time, shoulder/elbow correlation) and sensory (spatial discrimination, stereognosis) outcomes than the control group on the non-dominant side. On the dominant side, only sensation (spatial discrimination, stereognosis) was poorer in the dystonia group compared to the control group. In the dystonia group, although sensory and motor outcomes were uncorrelated, dystonia severity was related to poorer stereognosis, longer hold and reach times, and decreased shoulder/elbow coordination. Findings of bilateral sensory deficits in dystonia may be explained by neural reorganization. Visual compensation for somatosensory changes in the non-stroke hemisphere may explain the lack of bilateral impairments in reaching. PMID:24396131

Coherence of neuronal firing of the entopeduncular nucleus with motor cortex oscillatory activity in the 6-OHDA rat model of Parkinson's disease with levodopa-induced dyskinesias.

PubMed

Jin, Xingxing; Schwabe, Kerstin; Krauss, Joachim K; Alam, Mesbah

2016-04-01

The pathophysiological mechanisms leading to dyskinesias in Parkinson's disease (PD) after long-term treatment with levodopa remain unclear. This study investigates the neuronal firing characteristics of the entopeduncular nucleus (EPN), the rat equivalent of the human globus pallidus internus and output nucleus of the basal ganglia, and its coherence with the motor cortex (MCx) field potentials in the unilateral 6-OHDA rat model of PD with and without levodopa-induced dyskinesias (LID). 6-hydroxydopamine-lesioned hemiparkinsonian (HP) rats, 6-OHDA-lesioned HP rats with LID (HP-LID) rats, and naïve controls were used for recording of single-unit activity under urethane (1.4 g/kg, i.p) anesthesia in the EPN "on" and "off" levodopa. Over the MCx, the electrocorticogram output was recorded. Analysis of single-unit activity in the EPN showed enhanced firing rates, burst activity, and irregularity compared to naïve controls, which did not differ between drug-naïve HP and HP-LID rats. Analysis of EPN spike coherence and phase-locked ratio with MCx field potentials showed a shift of low (12-19 Hz) and high (19-30 Hz) beta oscillatory activity between HP and HP-LID groups. EPN theta phase-locked ratio was only enhanced in HP-LID compared to HP rats. Overall, levodopa injection had no stronger effect in HP-LID rats than in HP rats. Altered coherence and changes in the phase lock ratio of spike and local field potentials in the beta range may play a role for the development of LID.

Whisker motor cortex reorganization after superior colliculus output suppression in adult rats.

PubMed

Veronesi, Carlo; Maggiolini, Emma; Franchi, Gianfranco

2013-10-01

The effect of unilateral superior colliculus (SC) output suppression on the ipsilateral whisker motor cortex (WMC) was studied at different time points after tetrodotoxin and quinolinic acid injections, in adult rats. The WMC output was assessed by mapping the movement evoked by intracortical microstimulation (ICMS) and by recording the ICMS-evoked electromyographic (EMG) responses from contralateral whisker muscles. At 1 h after SC injections, the WMC showed: (i) a strong decrease in contralateral whisker sites, (ii) a strong increase in ipsilateral whisker sites and in ineffective sites, and (iii) a strong increase in threshold current values. At 6 h after injections, the WMC size had shrunk to 60% of the control value and forelimb representation had expanded into the lateral part of the normal WMC. Thereafter, the size of the WMC recovered, returning to nearly normal 12 h later (94% of control) and persisted unchanged over time (1-3 weeks). The ICMS-evoked EMG response area decreased at 1 h after SC lesion and had recovered its baseline value 12 h later. Conversely, the latency of ICMS-evoked EMG responses had increased by 1 h and continued to increase for as long as 3 weeks following the lesion. These findings provide physiological evidence that SC output suppression persistently withdrew the direct excitatory drive from whisker motoneurons and induced changes in the WMC. We suggest that the changes in the WMC are a form of reversible short-term reorganization that is induced by SC lesion. The persistent latency increase in the ICMS-evoked EMG response suggested that the recovery of basic WMC excitability did not take place with the recovery of normal explorative behaviour. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Traumatic brain injury causes long-term behavioral changes related to region-specific increases of cerebral blood flow.

PubMed

Pöttker, Bruno; Stöber, Franziska; Hummel, Regina; Angenstein, Frank; Radyushkin, Konstantin; Goldschmidt, Jürgen; Schäfer, Michael K E

2017-12-01

Traumatic brain injury (TBI) is a leading cause of disability and death and survivors often suffer from long-lasting motor impairment, cognitive deficits, anxiety disorders and epilepsy. Few experimental studies have investigated long-term sequelae after TBI and relations between behavioral changes and neural activity patterns remain elusive. We examined these issues in a murine model of TBI combining histology, behavioral analyses and single-photon emission computed tomography (SPECT) imaging of regional cerebral blood flow (CBF) as a proxy for neural activity. Adult C57Bl/6N mice were subjected to unilateral cortical impact injury and investigated at early (15-57 days after lesion, dal) and late (184-225 dal) post-traumatic time points. TBI caused pronounced tissue loss of the parietal cortex and subcortical structures and enduring neurological deficits. Marked perilesional astro- and microgliosis was found at 57 dal and declined at 225 dal. Motor and gait pattern deficits occurred at early time points after TBI and improved over the time. In contrast, impaired performance in the Morris water maze test and decreased anxiety-like behavior persisted together with an increased susceptibility to pentylenetetrazole-induced seizures suggesting alterations in neural activity patterns. Accordingly, SPECT imaging of CBF indicated asymmetric hemispheric baseline neural activity patterns. In the ipsilateral hemisphere, increased baseline neural activity was found in the amygdala. In the contralateral hemisphere, homotopic to the structural brain damage, the hippocampus and distinct cortex regions displayed increased baseline neural activity. Thus, regionally elevated CBF along with behavioral alterations indicate that increased neural activity is critically involved in the long-lasting consequences of TBI.

Acetylcholinesterase inhibition and locomotor function after motor-sensory cortex impact injury.

PubMed

Holschneider, Daniel P; Guo, Yumei; Roch, Margareth; Norman, Keith M; Scremin, Oscar U

2011-09-01

Traumatic brain injury (TBI) induces transient or persistent dysfunction of gait and balance. Enhancement of cholinergic transmission has been reported to accelerate recovery of cognitive function after TBI, but the effects of this intervention on locomotor activity remain largely unexplored. The hypothesis that enhancement of cholinergic function by inhibition of acetylcholinesterase (AChE) improves locomotion following TBI was tested in Sprague-Dawley male rats after a unilateral controlled cortical impact (CCI) injury of the motor-sensory cortex. Locomotion was tested by time to fall on the constant speed and accelerating Rotarod, placement errors and time to cross while walking through a horizontal ladder, activity monitoring in the home cages, and rearing behavior. Assessments were performed the 1st and 2nd day and the 1st, 2nd, and 3rd week after TBI. The AChE inhibitor physostigmine hemisulfate (PHY) was administered continuously via osmotic minipumps implanted subcutaneously at the rates of 1.6-12.8 μmol/kg/day. All measures of locomotion were impaired by TBI and recovered to initial levels between 1 and 3 weeks post-TBI, with the exception of the maximum speed achievable on the accelerating Rotarod, as well as rearing in the open field. PHY improved performance in the accelerating Rotarod at 1.6 and 3.2 μmol/kg/day (AChE activity 95 and 78% of control, respectively), however, higher doses induced progressive deterioration. No effect or worsening of outcomes was observed at all PHY doses for home cage activity, rearing, and horizontal ladder walking. Potential benefits of cholinesterase inhibition on locomotor function have to be weighed against the evidence of the narrow range of useful doses.

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.

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.

Does ipsilateral corticospinal excitability play a decisive role in the cross-education effect caused by unilateral resistance training? A systematic review.

PubMed

Colomer-Poveda, D; Romero-Arenas, S; Hortobagyi, T; Márquez, G

2018-01-02

Unilateral resistance training has been shown to improve muscle strength in both the trained and the untrained limb. One of the most widely accepted theories is that this improved performance is due to nervous system adaptations, specifically in the primary motor cortex. According to this hypothesis, increased corticospinal excitability (CSE), measured with transcranial magnetic stimulation, is one of the main adaptations observed following prolonged periods of training. The principal aim of this review is to determine the degree of adaptation of CSE and its possible functional association with increased strength in the untrained limb. We performed a systematic literature review of studies published between January 1970 and December 2016, extracted from Medline (via PubMed), Ovid, Web of Science, and Science Direct online databases. The search terms were as follows: (transcranial magnetic stimulation OR excitability) AND (strength training OR resistance training OR force) AND (cross transfer OR contralateral limb OR cross education). A total of 10 articles were found. Results regarding increased CSE were inconsistent. Although the possibility that the methodology had a role in this inconsistency cannot be ruled out, the results appear to suggest that there may not be a functional association between increases in muscle strength and in CSE. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

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

Strong Functional Connectivity among Homotopic Brain Areas Is Vital for Motor Control in Unilateral Limb Movement.

PubMed

Wei, Pengxu; Zhang, Zuting; Lv, Zeping; Jing, Bin

2017-01-01

The mechanism underlying brain region organization for motor control in humans remains poorly understood. In this functional magnetic resonance imaging (fMRI) study, right-handed volunteers were tasked to maintain unilateral foot movements on the right and left sides as consistently as possible. We aimed to identify the similarities and differences between brain motor networks of the two conditions. We recruited 18 right-handed healthy volunteers aged 25 ± 2.3 years and used a whole-body 3T system for magnetic resonance (MR) scanning. Image analysis was performed using SPM8, Conn toolbox and Brain Connectivity Toolbox. We determined a craniocaudally distributed, mirror-symmetrical modular structure. The functional connectivity between homotopic brain areas was generally stronger than the intrahemispheric connections, and such strong connectivity led to the abovementioned modular structure. Our findings indicated that the interhemispheric functional interaction between homotopic brain areas is more intensive than the interaction along the conventional top-down and bottom-up pathways within the brain during unilateral limb movement. The detected strong interhemispheric horizontal functional interaction is an important aspect of motor control but often neglected or underestimated. The strong interhemispheric connectivity may explain the physiological phenomena and effects of promising therapeutic approaches. Further accurate and effective therapeutic methods may be developed on the basis of our findings.

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

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.

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.

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.

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.

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.

Differential sensitivity of cranial and limb motor function to nigrostriatal dopamine depletion

PubMed Central

Plowman, Emily K.; Maling, Nicholas; Rivera, Benjamin J.; Larson, Krista; Thomas, Nagheme J.; Fowler, Stephen C.; Manfredsson, Fredric P.; Shrivastav, Rahul; Kleim, Jeffrey A.

2012-01-01

The present study determined the differential effects of unilateral striatal dopamine depletion on cranial motor versus limb motor function. Forty male Long Evans rats were first trained on a comprehensive motor testing battery that dissociated cranial versus limb motor function and included: cylinder forepaw placement, single pellet reaching, vermicelli pasta handling; sunflower seed opening, pasta biting acoustics, and a licking task. Following baseline testing, animals were randomized to either a 6-hydroxydopamine (6-OHDA) (n = 20) or control (n = 20) group. Animals in the 6-OHDA group received unilateral intrastriatal 6-OHDA infusions to induce striatal dopamine depletion. Six-weeks following infusion, all animals were re-tested on the same battery of motor tests. Near infrared densitometry was performed on sections taken through the striatum that were immunohistochemically stained for tyrosine hydroxylase (TH). Animals in the 6-OHDA condition showed a mean reduction in TH staining of 88.27%. Although 6-OHDA animals were significantly impaired on all motor tasks, limb motor deficits were more severe than cranial motor impairments. Further, performance on limb motor tasks was correlated with degree of TH depletion while performance on cranial motor impairments showed no significant correlation. These results suggest that limb motor function may be more sensitive to striatal dopaminergic depletion than cranial motor function and is consistent with the clinical observation that therapies targeting the nigrostriatal dopaminergic system in Parkinson’s disease are more effective for limb motor symptoms than cranial motor impairments. PMID:23018122

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.

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.

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

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.

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

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.

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.

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.

Effects of Unilateral Transcranial Direct Current Stimulation of Left Prefrontal Cortex on Processing and Memory of Emotional Visual Stimuli.

PubMed

Balzarotti, Stefania; Colombo, Barbara

2016-01-01

The dorsolateral prefrontal cortex (DLPFC) is generally thought to be involved in affect and emotional processing; however, the specific contribution of each hemisphere continues to be debated. In the present study, we employed unilateral tDCS to test the unique contribution of left DLPFC in the encoding and retrieval of emotional stimuli in healthy subjects. Forty-two right handed undergraduate students received either anodal, cathodal or sham stimulation of left DLPFC while viewing neutral, pleasant, and unpleasant pictures. After completing a filler task, participants were asked to remember as many pictures as possible. Results showed that participants were able to remember a larger amount of emotional (both pleasant and unpleasant) pictures than of neutral ones, regardless of the type of tDCS condition. Participants who received anodal stimulation recalled a significantly higher number of pleasant images than participants in the sham and cathodal conditions, while no differences emerged in the recall of neutral and unpleasant pictures. We conclude that our results provide some support to the role of left prefrontal cortex in the encoding and retrieval of pleasant stimuli.

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

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.

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.

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.

[Low dose isobaric, hyperbaric, or hypobaric bupivacaine for unilateral spinal anesthesia.].

PubMed

Imbelloni, Luiz Eduardo; Beato, Lúcia; Gouveia, Marildo A; Cordeiro, José Antônio

2007-06-01

Unilateral spinal anesthesia has its advantages, especially in patients undergoing outpatient basis surgeries. Low dose, slow speed of administration, and the lateral positioning make easier the unilateral distribution in spinal anesthesia. Isobaric, hyperbaric, and hypobaric solutions of bupivacaine were compared in the unilateral spinal anesthesia in patients undergoing outpatient basis orthopedic surgeries. One hundred and fifty patients were randomly divided in three groups to receive 5 mg of 0.5% isobaric bupivacaine (Iso Group), 5 mg of 0.5% hyperbaric bupivacaine (Hyper Group), or 5 mg of 0.15% hypobaric bupivacaine (Hypo Group). The solutions were administered in the L3-L4 space with the patient in the lateral decubitus and remaining in this position for 20 minutes. Sensitive anesthesia was evaluated by the pin prick test. Motor blockade was determined by the modified Bromage scale. Both blockades were compared with the opposite side and among themselves. There was a significant difference between the side of the surgery and the opposite side in all three groups at 20 minutes, but the frequency of unilateral spinal anesthesia was greater with the hyperbaric and hypobaric solutions. Sensitive and motor blockades were observed in 14 patients in the Iso Group, 38 patients in the Hyper Group, and 40 patients in the Hypo Group. Patients did not develop any hemodynamic changes. Postpuncture headache and transitory neurological symptoms were not observed. Spinal anesthesia with hypobaric and hyperbaric solutions present a higher frequency of unilateral anesthesia. After 20 minutes, isobaric bupivacaine mobilized into cerebrospinal fluid (CSF) resulted in unilateral spinal anesthesia in only 28% of the patients.

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…

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…

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

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.

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.

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…

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.

Dopaminergic stimulation in unilateral neglect

PubMed Central

Geminiani, G.; Bottini, G.; Sterzi, R.

1998-01-01

OBJECTIVE—To explore the hypothesis that dopaminergic circuits play a part in the premotor components of the unilateral neglect syndrome, the effects of acute dopaminergic stimulation in patients with neglect were studied.
METHODS—Two tasks were evaluated before and after subcutaneous administration of apomorphine and placebo: a circle crossing test and a test of target exploration (a modified version of the bell test), performed both in perceptual (counting) and in perceptual-motor (pointing) conditions.
SUBJECTS—Four patients with left neglect.
RESULTS—After dopaminergic stimulation, a significant improvement was found compared with placebo administration and baseline evaluation, in the performance of the two tests. Three of the patients had a more marked improvement in the perceptual-motor condition (pointing) of the task than the perceptual condition (counting).
CONCLUSIONS—The findings suggest that dopaminergic neuronal networks may mediate, in different ways, both perceptive and premotor components of the unilateral neglect syndrome. 

 PMID:9728946

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.

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.

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

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

Restoration of visual orienting into a cortically blind hemifield by reversible deactivation of posterior parietal cortex or the superior colliculus.

PubMed

Lomber, Stephen G; Payne, Bertram R; Hilgetag, Claus C; Rushmore, JarrettR

2002-02-01

A contralateral hemineglect of the visual field can be induced by unilateral cooling deactivation of posterior middle suprasylvian (pMS) sulcal cortex of the posterior parietal region, and this neglect can be reversed by additional cooling deactivation of pMS cortex in the opposite hemisphere. The purpose of the present study was to test whether an enduring hemianopia induced by removal of all contiguous visual cortical areas of one hemisphere could be reversed by local cooling of pMS cortex in the opposite hemisphere. Two cats sustained large unilateral ablations of the contiguous visual areas, and cooling loops were placed in the pMS sulcus, and in contact with adjacent area 7 or posterior ectosylvian (PE) cortex of the opposite hemisphere. In both instances cooling of pMS cortex, but neither area 7 nor PE, restored a virtually normal level of orienting performance to stimuli presented anywhere in the previously hemianopic field. The reversal was highly sensitive to the extent of cooling deactivation. In a third cat, cooling deactivation of the superficial layers of the contralateral superior colliculus also restored orienting performance to a cortical ablation-induced hemianopia. This reversal was graded from center-to-periphery in a temperature-dependent manner. Neither the cortical ablation nor any of the cooling deactivations had any impact on an auditory detection and orienting task. The deactivations were localized and confirmed by reduced uptake of radiolabeled 2-deoxyglucose to be limited to the immediate vicinity of each cooling loop. The results are discussed in terms of excitation and disinhibition of visual circuits.

Hemispheric Dominance for Stereognosis in a Patient With an Infarct of the Left Postcentral Sensory Hand Area.

PubMed

Moll, Jorge; de Oliveira-Souza, Ricardo

2017-09-01

The concept of left hemispheric dominance for praxis, speech, and language has been one of the pillars of neurology since the mid-19th century. In 1906, Hermann Oppenheim reported a patient with bilateral stereoagnosia (astereognosis) caused by a left parietal lobe tumor and proposed that the left hemisphere was also dominant for stereognosis. Surprisingly, few cases of bilateral stereoagnosia caused by a unilateral cerebral lesion have been documented in the literature since then. Here we report a 75-year-old right-handed man who developed bilateral stereoagnosia after suffering a small infarct in the crown of the left postcentral gyrus. He could not recognize objects with either hand, but retained the ability to localize stimuli applied to the palm of his left (ipsilesional) hand. He was severely disabled in ordinary activities requiring the use of his hands. The lesion corresponded to Brodmann area 1, where probabilistic anatomic, functional, and electrophysiologic studies have located one of the multiple somatosensory representations of the hand. The lesion was in a strategic position to interrupt both the processing of afferent tactile information issuing from the primary somatosensory cortex (areas 3a and 3b) and the forward higher-order processing in area 2, the secondary sensory cortex, and the contralateral area 1. The lesion also deprived the motor hand area of its afferent regulation from the sensory hand area (grasping), while leaving intact the visuomotor projections from the occipital cortex (reaching). Our patient supports Oppenheim's proposal that the left postcentral gyrus of some individuals is dominant for stereognosis.

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.

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.

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.

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.

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.

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.

Home-based bimanual training based on motor learning principles in children with unilateral cerebral palsy and their parents (the COAD-study): rationale and protocols.

PubMed

Schnackers, Marlous; Beckers, Laura; Janssen-Potten, Yvonne; Aarts, Pauline; Rameckers, Eugène; van der Burg, Jan; de Groot, Imelda; Smeets, Rob; Geurts, Sander; Steenbergen, Bert

2018-04-18

Home-based training is considered an important intervention in rehabilitation of children with unilateral cerebral palsy. Despite consensus on the value of home-based upper limb training, no evidence-based best practice exists. Promoting compliance of children to adhere to an intensive program while keeping parental stress levels low is an important challenge when designing home-based training programs. Incorporating implicit motor learning principles emerges to be a promising method to resolve this challenge. Here we describe two protocols for home-based bimanual training programs, one based on implicit motor learning principles and one based on explicit motor learning principles, for children with unilateral spastic cerebral palsy aged 2 through 7 years. Children receive goal-oriented, task-specific bimanual training in their home environment from their parents for 3.5 h/week for 12 weeks according to an individualized program. Parents will be intensively coached by a multidisciplinary team, consisting of a pediatric therapist and remedial educationalist. Both programs consist of a preparation phase (goal setting, introductory meetings with coaching professionals, design of individualized program, instruction of parents, home visit) and home-based training phase (training, video-recordings, registrations, and telecoaching and home visits by the coaching team). The programs contrast with respect to the teaching strategy, i.e. how the parents support their child during training. In both programs parents provide their child with instructions and feedback that focus on the activity (i.e. task-oriented) or the result of the activity (i.e. result-oriented). However, in the explicit program parents are in addition instructed to give exact instructions and feedback on the motor performance of the bimanual activities, whereas in the implicit program the use of both hands and the appropriate motor performance of the activity are elicited via manipulation of the organization of the activities. With the protocols described here, we aim to take a next step in the development of much needed evidence-based home-based training programs for children with unilateral cerebral palsy.

Structural-metabolic organization of field 4 of the cat brain in normal conditions and after unilateral enucleation of the eye.

PubMed

Zykin, P A

2005-01-01

Comparative data on the structural-metabolic organization of field 4 of the cat brain in normal conditions and after unilateral enucleation of the eye are presented. Cytochrome oxidase was detected histochemically. Data were processed by a computerized method using an original video capture system. Data were obtained demonstrating the uneven distribution of enzyme along sublayer IlIb of field 4 in animals with unilateral enucleation. A hypothesis based on published data is suggested whereby the alternation of high- and low-reactive areas is evidence for the ordering of the retinal representations of the right and left eyes in the sensorimotor cortex.

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

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.

Does Somatosensory Discrimination Activate Different Brain Areas in Children with Unilateral Cerebral Palsy Compared to Typically Developing Children? An fMRI Study

ERIC Educational Resources Information Center

Van de Winckel, Ann; Verheyden, Geert; Wenderoth, Nici; Peeters, Ron; Sunaert, Stefan; Van Hecke, Wim; De Cock, Paul; Desloovere, Kaat; Eyssen, Maria; Feys, Hilde

2013-01-01

Aside from motor impairment, many children with unilateral cerebral palsy (CP) experience altered tactile, proprioceptive, and kinesthetic awareness. Sensory deficits are addressed in rehabilitation programs, which include somatosensory discrimination exercises. In contrast to adult stroke patients, data on brain activation, occurring during…

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…

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…

A re-assessment of the effects of intracortical delivery of inosine on transmidline growth of corticospinal tract axons after unilateral lesions of the medullary pyramid

PubMed Central

Steward, Oswald; Sharp, Kelli; Yee, Kelly Matsudaira

2011-01-01

This study was undertaken as part of the NIH “Facilities of Research Excellence-Spinal Cord Injury”, which supports independent replication of published studies. Here, we repeat an experiment reporting that intracortical delivery of inosine promoted trans-midline growth of corticospinal tract (CST) axons in the spinal cord after unilateral injury to the medullary pyramid. Rats received unilateral transections of the medullary pyramid and 1 day later, a cannula assembly was implanted into the sensorimotor cortex contralateral to the pyramidotomy to deliver either inosine or vehicle. The cannula assembly was attached to an osmotic minipump that was implanted sub-cutaneously. Seventeen or 18 days post-injury, the CST was traced by making multiple injections of miniruby-BDA into the sensorimotor cortex. Rats were killed for tract tracing 14 days after the BDA injections. Sections through the cervical spinal cord were stained for BDA and immunostained for GAP43 and GFAP. Our results revealed no evidence for enhanced growth of CST axons across the midline of the dorsal column in rats that received intracortical infusion of inosine. Possible reasons for the failure to replicate are discussed. PMID:21946267

Changes in regional blood flow induced by unilateral subthalamic nucleus stimulation in patients with Parkinson's disease.

PubMed

Tanei, Takafumi; Kajita, Yasukazu; Nihashi, Takashi; Kaneoke, Yoshiki; Takebayashi, Shigenori; Nakatsubo, Daisuke; Wakabayashi, Toshihiko

2009-11-01

Changes in regional cerebral blood flow (rCBF) induced by unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) were investigated in 7 consecutive patients with Parkinson's disease, 4 men and 3 women (mean age 62.3 +/- 8.1 years), who underwent rCBF measurement by N-isopropyl-p-(iodine-123)-iodoamphetamine single photon emission computed tomography at rest before and after unilateral STN DBS preoperatively in the on-drug condition, and postoperatively in the on-drug and on-stimulation condition. Statistical parametric mapping was used to identify significant changes in rCBF from the preoperative to the postoperative conditions. rCBF was increased in the bilateral cingulate cortices and bilateral cerebellar hemispheres. rCBF was decreased in the bilateral medial frontal cortices and left superior temporal cortex. Unilateral STN DBS produced rCBF changes in the bilateral cingulate cortices, cerebellar hemispheres, and medial frontal cortices. These findings indicate that unilateral STN DBS affects rCBF in both hemispheres.

Function Lateralization via Measuring Coherence Laterality

PubMed Central

Wang, Ze; Mechanic-Hamilton, Dawn; Pluta, John; Glynn, Simon; Detre, John A.

2009-01-01

A data-driven approach for lateralization of brain function based on the spatial coherence difference of functional MRI (fMRI) data in homologous regions-of-interest (ROI) in each hemisphere is proposed. The utility of using coherence laterality (CL) to determine function laterality was assessed first by examining motor laterality using normal subjects’ data acquired both at rest and with a simple unilateral motor task and subsequently by examining mesial temporal lobe memory laterality in normal subjects and patients with temporal lobe epilepsy. The motor task was used to demonstrate that CL within motor ROI correctly lateralized functional stimulation. In patients with unilateral epilepsy studied during a scene-encoding task, CL in a hippocampus-parahippocampus-fusiform (HPF) ROI was concordant with lateralization based on task activation, and the CL index (CLI) significantly differentiated the right side group to the left side group. By contrast, normal controls showed a symmetric HPF CLI distribution. Additionally, similar memory laterality prediction results were still observed using CL in epilepsy patients with unilateral seizures after the memory encoding effect was removed from the data, suggesting the potential for lateralization of pathological brain function based on resting fMRI data. A better lateralization was further achieved via a combination of the proposed approach and the standard activation based approach, demonstrating that assessment of spatial coherence changes provides a complementary approach to quantifying task-correlated activity for lateralizing brain function. PMID:19345736

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

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.

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

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.

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.

Activation of the prefrontal cortex by unilateral transcranial direct current stimulation leads to an asymmetrical effect on risk preference in frames of gain and loss.

PubMed

Ye, Hang; Huang, Daqiang; Wang, Siqi; Zheng, Haoli; Luo, Jun; Chen, Shu

2016-10-01

Previous brain imaging and brain stimulation studies have suggested that the dorsolateral prefrontal cortex may be critical in regulating risk-taking behavior, although its specific causal effect on people's risk preference remains controversial. This paper studied the independent modulation of the activity of the right and left dorsolateral prefrontal cortex using various configurations of transcranial direct current stimulation. We designed a risk-measurement table and adopted a within-subject design to compare the same participant's risk preference before and after unilateral stimulation when presented with different frames of gain and loss. The results confirmed a hemispheric asymmetry and indicated that the right dorsolateral prefrontal cortex has an asymmetric effect on risk preference regarding frames of gain and loss. Enhancing the activity of the right dorsolateral prefrontal cortex significantly decreased the participants' degree of risk aversion in the gain frame, whereas it increased the participants' degree of risk aversion in the loss frame. Our findings provide important information regarding the impact of transcranial direct current stimulation on the risk preference of healthy participants. The effects observed in our experiment compared with those of previous studies provide further evidence of the effects of hemispheric and frame-dependent asymmetry. These findings may be helpful in understanding the neural basis of risk preference in humans, especially when faced with decisions involving possible gain or loss relative to the status quo. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

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

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

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.

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

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

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.

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.

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

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

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

[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.

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

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.

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.

Human cortical activity related to unilateral movements. A high resolution EEG study.

PubMed

Urbano, A; Babiloni, C; Onorati, P; Babiloni, F

1996-12-20

In the present study a modern high resolution electroencephalography (EEG) technique was used to investigate the dynamic functional topography of human cortical activity related to simple unilateral internally triggered finger movements. The sensorimotor area (M1-S1) contralateral to the movement as well as the supplementary motor area (SMA) and to a lesser extent the ipsilateral M1-S1 were active during the preparation and execution of these movements. These findings suggest that both hemispheres may cooperate in both planning and production of simple unilateral volitional acts.

A low-dose bupivacaine: a comparison of hyperbaric and hypobaric solutions for unilateral spinal anesthesia.

PubMed

Kaya, Menşure; Oğuz, Selma; Aslan, Kemal; Kadioğullari, Nihal

2004-01-01

The injection of small doses of local anesthetic solutions through pencil-point directional needles and maintaining the lateral decubitus position for 15 to 30 minutes after the injection have been suggested to facilitate the unilateral distribution of spinal anesthesia. We evaluated the effects of hypobaric and hyperbaric bupivacaine in attempting to achieve unilateral spinal anesthesia for patients undergoing lower limb orthopedic surgery. Fifty patients were randomly allocated into 2 groups to receive either 1.5 mL hyperbaric bupivacaine 0.5% (7.5 mg; n = 25) or 4.2 mL hypobaric bupivacaine 0.18% (7.5 mg; n = 25). Drugs were administered at the L3-4 interspace with the patient in the lateral position. Patients remained in this position for 15 minutes before turning supine for the operation. Spinal block was assessed by pinprick and modified Bromage scale on both sides. Unilateral spinal block was observed in 20 patients in the hyperbaric group (80%) and in 19 patients in the hypobaric group (76%) while in the lateral position. However, 15 minutes after patients were turned supine, unilateral spinal anesthesia decreased to 68% of cases in the hyperbaric group and 24% of cases in the hypobaric group (P <.05). The motor block was more intense during the first 5 and 10 minutes (P <.05), but at the end of operation there was no difference between the groups. The hemodynamic changes were similar between the groups. As a result, unilateral spinal anesthesia with hyperbaric and hypobaric bupivacaine provided a rapid motor and sensory recovery and good hemodynamic stability, but more unilateral spinal block was achieved in patients in the hyperbaric group when compared with patients in the hypobaric group.

Bee Venom Alleviates Motor Deficits and Modulates the Transfer of Cortical Information through the Basal Ganglia in Rat Models of Parkinson's Disease.

PubMed

Maurice, Nicolas; Deltheil, Thierry; Melon, Christophe; Degos, Bertrand; Mourre, Christiane; Amalric, Marianne; Kerkerian-Le Goff, Lydia

2015-01-01

Recent evidence points to a neuroprotective action of bee venom on nigral dopamine neurons in animal models of Parkinson's disease (PD). Here we examined whether bee venom also displays a symptomatic action by acting on the pathological functioning of the basal ganglia in rat PD models. Bee venom effects were assessed by combining motor behavior analyses and in vivo electrophysiological recordings in the substantia nigra pars reticulata (SNr, basal ganglia output structure) in pharmacological (neuroleptic treatment) and lesional (unilateral intranigral 6-hydroxydopamine injection) PD models. In the hemi-parkinsonian 6-hydroxydopamine lesion model, subchronic bee venom treatment significantly alleviates contralateral forelimb akinesia and apomorphine-induced rotations. Moreover, a single injection of bee venom reverses haloperidol-induced catalepsy, a pharmacological model reminiscent of parkinsonian akinetic deficit. This effect is mimicked by apamin, a blocker of small conductance Ca2+-activated K+ (SK) channels, and blocked by CyPPA, a positive modulator of these channels, suggesting the involvement of SK channels in the bee venom antiparkinsonian action. In vivo electrophysiological recordings in the substantia nigra pars reticulata (basal ganglia output structure) showed no significant effect of BV on the mean neuronal discharge frequency or pathological bursting activity. In contrast, analyses of the neuronal responses evoked by motor cortex stimulation show that bee venom reverses the 6-OHDA- and neuroleptic-induced biases in the influence exerted by the direct inhibitory and indirect excitatory striatonigral circuits. These data provide the first evidence for a beneficial action of bee venom on the pathological functioning of the cortico-basal ganglia circuits underlying motor PD symptoms with potential relevance to the symptomatic treatment of this disease.

Blood Oxygenation Level-Dependent Functional Magnetic Resonance Imaging in Early Days: Correlation between Passive Activation and Motor Recovery After Unilateral Striatocapsular Cerebral Infarction.

PubMed

Zhou, Long-Jiang; Wang, Wei; Zhao, Yi; Liu, Chun-Feng; Zhang, Xin-Jiang; Liu, Zhen-Sheng; Li, Hua-Dong

2017-11-01

This study aimed to investigate the correlation between the functional magnetic resonance imaging (fMRI) pattern and the motor function recovery of an affected limb during the passive movement of the affected limb at an early stage of the striatocapsular infarction (SCI). A total of 17 patients with an acute stage of SCI and 3 healthy volunteers as controls were included in this study. fMRI scans of passive movement were performed on the affected limbs of stroke patients within 1 week of onset. Follow-ups were carried out for the motor functions of the affected limbs (before fMRI scan, 1 month, and 3 months after the scan). The control group showed that the activation was mainly located in the contralateral sensorimotor cortex (SMC) and the bilateral supplementary motor area (SMA). The fMRI scan region of interest for stroke patients can be divided into 3 types: type I includes mainly the affected side, bilateral SMC, and SMA with activation; type II includes SMC on the affected side and SMA with activation; type III includes only SMC on the affected side or M1 with activation. The recovery of type I patients was better and faster, while the recovery of type II patients was better but slower, but recovery of type III patients was poorer and slower. Multiple cortical activation patterns were noted during the passive movement of the affected limbs at an early stage of SCI, and a correlation was found between the different activation patterns and the clinical prognosis of patients. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Bee Venom Alleviates Motor Deficits and Modulates the Transfer of Cortical Information through the Basal Ganglia in Rat Models of Parkinson’s Disease

PubMed Central

Maurice, Nicolas; Deltheil, Thierry; Melon, Christophe; Degos, Bertrand; Mourre, Christiane

2015-01-01

Recent evidence points to a neuroprotective action of bee venom on nigral dopamine neurons in animal models of Parkinson’s disease (PD). Here we examined whether bee venom also displays a symptomatic action by acting on the pathological functioning of the basal ganglia in rat PD models. Bee venom effects were assessed by combining motor behavior analyses and in vivo electrophysiological recordings in the substantia nigra pars reticulata (SNr, basal ganglia output structure) in pharmacological (neuroleptic treatment) and lesional (unilateral intranigral 6-hydroxydopamine injection) PD models. In the hemi-parkinsonian 6-hydroxydopamine lesion model, subchronic bee venom treatment significantly alleviates contralateral forelimb akinesia and apomorphine-induced rotations. Moreover, a single injection of bee venom reverses haloperidol-induced catalepsy, a pharmacological model reminiscent of parkinsonian akinetic deficit. This effect is mimicked by apamin, a blocker of small conductance Ca2+-activated K+ (SK) channels, and blocked by CyPPA, a positive modulator of these channels, suggesting the involvement of SK channels in the bee venom antiparkinsonian action. In vivo electrophysiological recordings in the substantia nigra pars reticulata (basal ganglia output structure) showed no significant effect of BV on the mean neuronal discharge frequency or pathological bursting activity. In contrast, analyses of the neuronal responses evoked by motor cortex stimulation show that bee venom reverses the 6-OHDA- and neuroleptic-induced biases in the influence exerted by the direct inhibitory and indirect excitatory striatonigral circuits. These data provide the first evidence for a beneficial action of bee venom on the pathological functioning of the cortico-basal ganglia circuits underlying motor PD symptoms with potential relevance to the symptomatic treatment of this disease. PMID:26571268

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.

Spontaneous brain activity in the sensorimotor cortex in amyotrophic lateral sclerosis can be negatively regulated by corticospinal fiber integrity.

PubMed

Sako, Wataru; Abe, Takashi; Izumi, Yuishin; Yamazaki, Hiroki; Matsui, Naoko; Harada, Masafumi; Kaji, Ryuji

2017-05-01

Previous studies failed to detect reduced value of the amplitude of low frequency fluctuation (ALFF) derived from resting state functional magnetic resonance imaging in the primary motor cortex in amyotrophic lateral sclerosis (ALS) though primary motor cortex was mainly affected with ALS. We aimed to investigate the cause of masking the abnormality in the primary motor cortex in ALS and usefulness of ALFF for differential diagnosis among diseases showing muscle weakness. We enrolled ten patients with ALS and eleven disease controls showing muscle weakness. Voxel-wise analysis revealed that significant reduction of ALFF value was present in the right sensorimotor cortex in ALS. There was a significant negative correlation between ALFF value in the right sensorimotor cortex and fractional anisotropy (FA) value in the posterior limbs of the internal capsule (PLIC). For a diagnostic tool, the area under receiver operating characteristic curve improved if the ALS patients with disease duration >1 year were excluded. The present findings raised the possibility of usefulness of ALFF value in the sensorimotor cortex for differential diagnosis of ALS, and supported the notion that adjustment for FA value in the PLIC could improve accuracy.

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.

Primary motor cortex activity reduction under the regulation of SMA by real-time fMRI

NASA Astrophysics Data System (ADS)

Guo, Jia; Zhao, Xiaojie; Li, Yi; Yao, Li; Chen, Kewei

2012-03-01

Real-time fMRI (rtfMRI) is a new technology which allows human subjects to observe and control their own BOLD signal change from one or more localized brain regions during scanning. Current rtfMRI-neurofeedback studies mainly focused on the target region itself without considering other related regions influenced by the real-time feedback. However, there always exits important directional influence between many of cooperative regions. On the other hand, rtfMRI based on motor imagery mainly aimed at somatomotor cortex or primary motor area, whereas supplement motor area (SMA) was a relatively more integrated and pivotal region. In this study, we investigated whether the activities of SMA can be controlled utilizing different motor imagery strategies, and whether there exists any possible impact on an unregulated but related region, primary motor cortex (M1). SMA was first localized using overt finger tapping task, the activities of SMA were feedback to subjects visually on line during each of two subsequent imagery motor movement sessions. All thirteen healthy participants were found to be able to successfully control their SMA activities by self-fit imagery strategies which involved no actual motor movements. The activation of right M1 was also found to be significantly reduced in both intensity and extent with the neurofeedback process targeted at SMA, suggestive that not only the part of motor cortex activities were influenced under the regulation of a key region SMA, but also the increased difference between SMA and M1 might reflect the potential learning effect.

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).

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

An fMRI study of differences in brain activity among elite, expert, and novice archers at the moment of optimal aiming.

PubMed

Kim, Woojong; Chang, Yongmin; Kim, Jingu; Seo, Jeehye; Ryu, Kwangmin; Lee, Eunkyung; Woo, Minjung; Janelle, Christopher M

2014-12-01

We investigated brain activity in elite, expert, and novice archers during a simulated archery aiming task to determine whether neural correlates of performance differ by skill level. Success in shooting sports depends on complex mental routines just before the shot, when the brain prepares to execute the movement. During functional magnetic resonance imaging, 40 elite, expert, or novice archers aimed at a simulated 70-meter-distant target and pushed a button when they mentally released the bowstring. At the moment of optimal aiming, the elite and expert archers relied primarily on a dorsal pathway, with greatest activity in the occipital lobe, temporoparietal lobe, and dorsolateral pre-motor cortex. The elites showed activity in the supplementary motor area, temporoparietal area, and cerebellar dentate, while the experts showed activity only in the superior frontal area. The novices showed concurrent activity in not only the dorsolateral pre-motor cortex but also the ventral pathways linked to the ventrolateral pre-motor cortex. The novices exhibited broad activity in the superior frontal area, inferior frontal area, ventral prefrontal cortex, primary motor cortex, superior parietal lobule, and primary somatosensory cortex. The more localized neural activity of elite and expert archers than novices permits greater efficiency in the complex processes subserved by these regions. The elite group's high activity in the cerebellar dentate indicates that the cerebellum is involved in automating simultaneous movements by integrating the sensorimotor memory enabled by greater expertise in self-paced aiming tasks. A companion article comments on and generalizes our findings.

Opposite hemispheric lateralization effects during speaking and singing at motor cortex, insula and cerebellum.

PubMed

Riecker, A; Ackermann, H; Wildgruber, D; Dogil, G; Grodd, W

2000-06-26

Aside from spoken language, singing represents a second mode of acoustic (auditory-vocal) communication in humans. As a new aspect of brain lateralization, functional magnetic resonance imaging (fMRI) revealed two complementary cerebral networks subserving singing and speaking. Reproduction of a non-lyrical tune elicited activation predominantly in the right motor cortex, the right anterior insula, and the left cerebellum whereas the opposite response pattern emerged during a speech task. In contrast to the hemodynamic responses within motor cortex and cerebellum, activation of the intrasylvian cortex turned out to be bound to overt task performance. These findings corroborate the assumption that the left insula supports the coordination of speech articulation. Similarly, the right insula might mediate temporo-spatial control of vocal tract musculature during overt singing. Both speech and melody production require the integration of sound structure or tonal patterns, respectively, with a speaker's emotions and attitudes. Considering the widespread interconnections with premotor cortex and limbic structures, the insula is especially suited for this task.

The motor cortex: a network tuned to 7-14 Hz

PubMed Central

Castro-Alamancos, Manuel A.

2013-01-01

The neocortex or six layer cortex consists of at least 52 cytoarchitectonically distinct areas in humans, and similar areas can be distinguished in rodents. Each of these areas has a defining set of extrinsic connections, identifiable functional roles, a distinct laminar arrangement, etc. Thus, neocortex is extensively subdivided into areas of anatomical and functional specialization, but less is known about the specialization of cellular and network physiology across areas. The motor cortex appears to have a distinct propensity to oscillate in the 7–14 Hz frequency range. Augmenting responses, normal mu and beta oscillations, and abnormal oscillations or after discharges caused by enhancing excitation or suppressing inhibition are all expressed around this frequency range. The substrate for this activity may be an excitatory network that is unique to the motor cortex or that is more strongly suppressed in other areas, such as somatosensory cortex. Interestingly, augmenting responses are dependent on behavioral state. They are abolished during behavioral arousal. Here, I briefly review this evidence. PMID:23439785

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…

Prism adaptation enhances activity of intact fronto-parietal areas in both hemispheres in neglect patients.

PubMed

Saj, Arnaud; Cojan, Yann; Vocat, Roland; Luauté, Jacques; Vuilleumier, Patrik

2013-01-01

Unilateral spatial neglect involves a failure to report or orient to stimuli in the contralesional (left) space due to right brain damage, with severe handicap in everyday activities and poor rehabilitation outcome. Because behavioral studies suggest that prism adaptation may reduce spatial neglect, we investigated the neural mechanisms underlying prism effects on visuo-spatial processing in neglect patients. We used functional magnetic resonance imaging (fMRI) to examine the effect of (right-deviating) prisms on seven patients with left neglect, by comparing brain activity while they performed three different spatial tasks on the same visual stimuli (bisection, search, and memory), before and after a single prism-adaptation session. Following prism adaptation, fMRI data showed increased activation in bilateral parietal, frontal, and occipital cortex during bisection and visual search, but not during the memory task. These increases were associated with significant behavioral improvement in the same two tasks. Changes in neural activity and behavior were seen only after prism adaptation, but not attributable to mere task repetition. These results show for the first time the neural substrates underlying the therapeutic benefits of prism adaptation, and demonstrate that visuo-motor adaptation induced by prism exposure can restore activation in bilateral brain networks controlling spatial attention and awareness. This bilateral recruitment of fronto-parietal networks may counteract the pathological biases produced by unilateral right hemisphere damage, consistent with recent proposals that neglect may reflect lateralized deficits induced by bilateral hemispheric dysfunction. Copyright © 2011 Elsevier Ltd. All rights reserved.

Axonal remodeling for motor recovery after traumatic brain injury requires downregulation of γ-aminobutyric acid signaling

PubMed Central

Lee, S; Ueno, M; Yamashita, T

2011-01-01

Remodeling of the remnant neuronal network after brain injury possibly mediates spontaneous functional recovery; however, the mechanisms inducing axonal remodeling during spontaneous recovery remain unclear. Here, we show that altered γ-aminobutyric acid (GABA) signaling is crucial for axonal remodeling of the contralesional cortex after traumatic brain injury. After injury to the sensorimotor cortex in mice, we found a significant decrease in the expression of GABAAR-α1 subunits in the intact sensorimotor cortex for 2 weeks. Motor functions, assessed by grid walk and cylinder tests, spontaneously improved in 4 weeks after the injury to the sensorimotor cortex. With motor recovery, corticospinal tract (CST) axons from the contralesional cortex sprouted into the denervated side of the cervical spinal cord at 2 and 4 weeks after the injury. To determine the functional implications of the changes in the expression of GABAAR-α1 subunits, we infused muscimol, a GABA R agonist, into the contralesional cortex for a week after the injury. Compared with the vehicle-treated mice, we noted significantly inhibited recovery in the muscimol-treated mice. Further, muscimol infusion greatly suppressed the axonal sprouting into the denervated side of the cervical spinal cord. In conclusion, recovery of motor function and axonal remodeling of the CST following cortical injury requires suppressed GABAAR subunit expression and decreased GABAergic signaling. PMID:21412279

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.

Global dysrhythmia of cerebro-basal ganglia-cerebellar networks underlies motor tics following striatal disinhibition.

PubMed

McCairn, Kevin W; Iriki, Atsushi; Isoda, Masaki

2013-01-09

Motor tics, a cardinal symptom of Tourette syndrome (TS), are hypothesized to arise from abnormalities within cerebro-basal ganglia circuits. Yet noninvasive neuroimaging of TS has previously identified robust activation in the cerebellum. To date, electrophysiological properties of cerebellar activation and its role in basal ganglia-mediated tic expression remain unknown. We performed multisite, multielectrode recordings of single-unit activity and local field potentials from the cerebellum, basal ganglia, and primary motor cortex using a pharmacologic monkey model of motor tics/TS. Following microinjections of bicuculline into the sensorimotor putamen, periodic tics occurred predominantly in the orofacial region, and a sizable number of cerebellar neurons showed phasic changes in activity associated with tic episodes. Specifically, 64% of the recorded cerebellar cortex neurons exhibited increases in activity, and 85% of the dentate nucleus neurons displayed excitatory, inhibitory, or multiphasic responses. Critically, abnormal discharges of cerebellar cortex neurons and excitatory-type dentate neurons mostly preceded behavioral tic onset, indicating their central origins. Latencies of pathological activity in the cerebellum and primary motor cortex substantially overlapped, suggesting that aberrant signals may be traveling along divergent pathways to these structures from the basal ganglia. Furthermore, the occurrence of tic movement was most closely associated with local field potential spikes in the cerebellum and primary motor cortex, implying that these structures may function as a gate to release overt tic movements. These findings indicate that tic-generating networks in basal ganglia mediated tic disorders extend beyond classical cerebro-basal ganglia circuits, leading to global network dysrhythmia including cerebellar circuits.

Adaptive behaviour and motor skills in children with upper limb deficiency.

PubMed

Mano, Hiroshi; Fujiwara, Sayaka; Haga, Nobuhiko

2018-04-01

The dysfunction of individuals with upper limb deficiencies affects their daily lives and social participation. To clarify the adaptive behaviours and motor skills of children with upper limb deficiencies. Cross-sectional survey. The subjects were 10 children ranging from 1 to 6 years of age with unilateral upper limb deficiencies at the level distal to the elbow who were using only cosmetic or passive prostheses or none at all. To measure their adaptive behaviour and motor skills, the Vineland Adaptive Behavior Scales, Second Edition was used. They were evaluated on the domains of communication, daily living skills, socialization and motor skills. We also examined the relationship of the scores with age. There were no statistically significant scores for domains or subdomains. The domain standard score of motor skills was significantly lower than the median scores of the domains and was negatively correlated with age. Children with upper limb deficiencies have individual weaknesses in motor skill behaviours, and these weaknesses increase with age. It may be helpful in considering approaches to rehabilitation and the prescription of prostheses to consider the characteristics and course of children's motor skill behaviours. Clinical relevance Even if children with unilateral upper limb deficiencies seem to compensate well for their affected limb function, they have or will experience individual weaknesses in motor skills. We should take this into consideration to develop better strategies for rehabilitation and prostheses prescriptions.

Effects of Unilateral Transcranial Direct Current Stimulation of Left Prefrontal Cortex on Processing and Memory of Emotional Visual Stimuli

PubMed Central

Balzarotti, Stefania

2016-01-01

The dorsolateral prefrontal cortex (DLPFC) is generally thought to be involved in affect and emotional processing; however, the specific contribution of each hemisphere continues to be debated. In the present study, we employed unilateral tDCS to test the unique contribution of left DLPFC in the encoding and retrieval of emotional stimuli in healthy subjects. Forty-two right handed undergraduate students received either anodal, cathodal or sham stimulation of left DLPFC while viewing neutral, pleasant, and unpleasant pictures. After completing a filler task, participants were asked to remember as many pictures as possible. Results showed that participants were able to remember a larger amount of emotional (both pleasant and unpleasant) pictures than of neutral ones, regardless of the type of tDCS condition. Participants who received anodal stimulation recalled a significantly higher number of pleasant images than participants in the sham and cathodal conditions, while no differences emerged in the recall of neutral and unpleasant pictures. We conclude that our results provide some support to the role of left prefrontal cortex in the encoding and retrieval of pleasant stimuli. PMID:27433807

Prenatal alcohol exposure reduces the size of the forelimb representation in motor cortex in rat: an intracortical microstimulation (ICMS) mapping study.

PubMed

Xie, Ni; Yang, Qiuhong; Chappell, Tyson D; Li, Cheng-Xiang; Waters, Robert S

2010-03-01

Children with fetal alcohol spectrum disorder (FASD) often exhibit sensorimotor dysfunctions that include deficits in motor coordination and fine motor control. Although the underlying causes for these motor abnormalities are unknown, they likely involve interactions between sensory and motor systems. Rodent animal models have been used to study the effects of prenatal alcohol exposure (PAE) on skilled reaching and on the development and organization of somatosensory barrel field cortex. To this end, PAE delayed the development of somatosensory cortex, reduced the size of whisker and forelimb representations in somatosensory barrel field cortex, and delayed acquisition time to learn a skilled reaching task. However, whether PAE also affects the motor cortex (MI) remains to be determined. In the present study, we investigated the effect of PAE on the size of the forelimb representation in rat MI, thresholds for activation, and the overlap between motor and sensory cortical forelimb maps in sensorimotor cortex. Pregnant Sprague-Dawley rats were assigned to alcohol (Alc), pair-fed (PF), and chow-fed (CF) groups on gestation day 1 (GD1). Rats in the Alc group (n=4) were chronically intubated daily with binge doses of alcohol (6g/kg body weight) from GD1 to GD20 that resulted in averaged blood alcohol levels measured on GD10 (mean=191.5+/-41.9mg/dL) and on GD17 (mean=247.0+/-72.4mg/dL). PF (n=2) and CF (n=3) groups of pregnant rats served as controls. The effect of PAE on the various dependent measures was obtained from multiple male offspring from each dam within treatment groups, and litter means were compared between the groups from alcohol-treated and control (Ct: CF and PF) dams. At approximately 8 weeks of age, rats were anesthetized with ketamine/xylazine and the skull opened over sensorimotor cortex. A tungsten microelectrode was then inserted into the depths of layer V and intracortical microstimulation was used to deliver trains of pulses to evoke muscle contractions and/or movements; maximum stimulating < or =100microA. When a motor response was observed, the threshold for movement was measured and the motor receptive field projected to the cortical surface to serve as representative point for that location. A motor map for the forelimb representation was generated by systematically stimulating at adjacent sites until current thresholds reached the maximum and/or motor responses were no longer evoked. The major findings in this study were as follows: (1) PAE significantly reduced the area of the forelimb representation in the Alc offspring (6.01mm(2), standard error of the mean=+/-0.278) compared with the Ct offspring (8.03mm(2)+/-0.586), (2) PAE did not significantly reduce the averaged threshold for activation of movements between groups, (3) PAE significantly reduced the percent overlap (Alc=31.1%, Ct=55.4%) between the forelimb representation in sensory and motor cortices, and (4) no significant differences were observed in averaged body weight, hemisphere weight, or age of animal between treatment groups. These findings suggest that the effects of PAE are not restricted to somatosensory barrel field cortex but also involve the MI and may underlie deficits in motor control and sensorimotor integration observed among children with FASD. 2010. Published by Elsevier Inc.

Spinogenesis in spinal cord motor neurons following pharmacological lesions to the rat motor cortex.

PubMed

Martínez-Torres, N I; González-Tapia, D; Flores-Soto, M; Vázquez-Hernández, N; Salgado-Ceballos, H; González-Burgos, I

2018-03-16

Motor function is impaired in multiple neurological diseases associated with corticospinal tract degeneration. Motor impairment has been linked to plastic changes at both the presynaptic and postsynaptic levels. However, there is no evidence of changes in information transmission from the cortex to spinal motor neurons. We used kainic acid to induce stereotactic lesions to the primary motor cortex of female adult rats. Fifteen days later, we evaluated motor function with the BBB scale and the rotarod and determined the density of thin, stubby, and mushroom spines of motor neurons from a thoracolumbar segment of the spinal cord. Spinophilin, synaptophysin, and β iii-tubulin expression was also measured. Pharmacological lesions resulted in poor motor performance. Spine density and the proportion of thin and stubby spines were greater. We also observed increased expression of the 3 proteins analysed. The clinical symptoms of neurological damage secondary to Wallerian degeneration of the corticospinal tract are associated with spontaneous, compensatory plastic changes at the synaptic level. Based on these findings, spontaneous plasticity is a factor to consider when designing more efficient strategies in the early phase of rehabilitation. Copyright © 2018 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Sensorimotor state of the contralateral leg affects ipsilateral muscle coordination of pedaling.

PubMed

Ting, L H; Raasch, C C; Brown, D A; Kautz, S A; Zajac, F E

1998-09-01

The objective of this study was to determine if independent central pattern generating elements controlling the legs in bipedal and unipedal locomotion is a viable theory for locomotor propulsion in humans. Coordinative coupling of the limbs could then be accomplished through mechanical interactions and ipsilateral feedback control rather than through central interlimb neural pathways. Pedaling was chosen as the locomotor task to study because interlimb mechanics can be significantly altered, as pedaling can be executed with the use of either one leg or two legs (cf. walking) and because the load on the limb can be well-controlled. Subjects pedaled a modified bicycle ergometer in a two-legged (bilateral) and a one-legged (unilateral) pedaling condition. The loading on the leg during unilateral pedaling was designed to be identical to the loading experienced by the leg during bilateral pedaling. This loading was achieved by having a trained human "motor" pedal along with the subject and exert on the opposite crank the torque that the subject's contralateral leg generated in bilateral pedaling. The human "motor" was successful at reproducing each subject's one-leg crank torque. The shape of the motor's torque trajectory was similar to that of subjects, and the amount of work done during extension and flexion was not significantly different. Thus the same muscle coordination pattern would allow subjects to pedal successfully in both the bilateral and unilateral conditions, and the afferent signals from the pedaling leg could be the same for both conditions. Although the overall work done by each leg did not change, an 86% decrease in retarding (negative) crank torque during limb flexion was measured in all 11 subjects during the unilateral condition. This corresponded to an increase in integrated electromyography of tibialis anterior (70%), rectus femoris (43%), and biceps femoris (59%) during flexion. Even given visual torque feedback in the unilateral condition, subjects still showed a 33% decrease in negative torque during flexion. These results are consistent with the existence of an inhibitory pathway from elements controlling extension onto contralateral flexion elements, with the pathway operating during two-legged pedaling but not during one-legged pedaling, in which case flexor activity increases. However, this centrally mediated coupling can be overcome with practice, as the human "motor" was able to effectively match the bilateral crank torque after a longer practice regimen. We conclude that the sensorimotor control of a unipedal task is affected by interlimb neural pathways. Thus a task performed unilaterally is not performed with the same muscle coordination utilized in a bipedal condition, even if such coordination would be equally effective in the execution of the unilateral task.

Mesenchymal stem cells restore orientation and exploratory behavior of rats after brain injury.

PubMed

Sokolova, I B; Fedotova, O R; Tsikunov, S G; Polyntsev, D G

2011-05-01

We studied the effects of intravenous and intracerebral transplantation of MSC on restoration of orientation and exploratory behavior of Wistar-Kyoto rats after removal of the left motor cortex. Removal of the motor cortex led to a significant reduction of the number of behavioral acts in the open field test. Two weeks after removal of the motor cortex and intravenous transplantation, the animals were as inhibited as the controls, but during the next 10 weeks, the behavioral status of these rats remained unchanged, while controls exhibited further behavioral degradation. After injection of MSC into the brain, the behavior of rats with trauma did not change in comparison with intact rats over 10 weeks.

Lower layers in the motor cortex are more effective targets for penetrating microelectrodes in cortical prostheses

NASA Astrophysics Data System (ADS)

Parikh, Hirak; Marzullo, Timothy C.; Kipke, Daryl R.

2009-04-01

Improving cortical prostheses requires the development of recording neural interfaces that are efficient in terms of providing maximal control information with minimal interface complexity. While the typical approaches have targeted neurons in the motor cortex with multiple penetrating shanks, an alternative approach is to determine an efficient distribution of electrode sites within the layers of the cortex with fewer penetrating shanks. The objective of this study was to compare unit activity in the upper and lower layers of the cortex with respect to movement and direction in order to inform the design of penetrating microelectrodes. Four rats were implanted bilaterally with multi-site single-shank silicon microelectrode arrays in the neck/shoulder region of the motor cortex. We simultaneously recorded unit activity across all layers of the motor cortex while the animal was engaged in a movement direction task. Localization of the electrode array within the different layers of the cortex was determined by histology. We denoted units from layers 2 and 3 and units as upper layer units, and units from layers 5 and 6 as lower layer units. Analysis of unit spiking activity demonstrated that both the upper and lower layers encode movement and direction information. Unit responses in either cortical layer of the cortex were not preferentially associated with contralateral or ipsilateral movement. Aggregate analysis (633 neurons) and best session analysis (75 neurons) indicated that units in the lower layers (layers 5, 6) are more likely to encode direction information when compared to units in the upper layers (layers 2, 3) (p< 0.05). These results suggest that electrode sites clustered in the lower layers provide access to more salient control information for cortical neuroprostheses.

Infralimbic cortex controls core body temperature in a histamine dependent manner.

PubMed

Riveros, M E; Perdomo, G; Torrealba, F

2014-04-10

An increase in body temperature accelerates biochemical reactions and behavioral and physiological responses. A mechanism to actively increase body temperature would be beneficial during motivated behaviors. The prefrontal cortex is implicated in organizing motivated behavior; the infralimbic cortex, a subregion of the medial prefrontal cortex, has the necessary connectivity to serve the role of initiating such thermogenic mechanism at the beginning of the appetitive phase of motivated behavior; further, this cortex is active during motivated behavior and its disinhibition produces a marked behavioral and vegetative arousal increase, together with increases in histamine levels. We wanted to explore if this arousal was related to histaminergic activation after pharmacological infralimbic disinhibition and during the appetitive phase of motivated behavior. We measured core temperature and motor activity in response to picrotoxin injection in the infralimbic cortex, as well as during food-related appetitive behavior, evoked by enticing hungry rats with food. Pretreatment with the H1 receptor antagonist pyrilamine decreased thermal response to picrotoxin and enticement and completely blunted motor response to enticement. Motor and temperature responses to enticement were also completely abolished by infralimbic cortex inhibition with muscimol. To assess if this histamine dependent temperature increase was produced by an active sympathetic mediated thermogenic mechanism or was just a consequence of increased locomotor activity, we injected propranolol (i.p.), a β adrenergic receptor blocker, before picrotoxin injection into the infralimbic cortex. Propranolol reduced the temperature increase without affecting locomotor activity. Altogether, these results suggest that infralimbic activation is necessary for appetitive behavior by inducing a motor and a vegetative arousal increase mediated by central histamine. Copyright © 2014 Elsevier Inc. All rights reserved.

Cognitive-motor interactions of the basal ganglia in development

PubMed Central

Leisman, Gerry; Braun-Benjamin, Orit; Melillo, Robert

2014-01-01

Neural circuits linking activity in anatomically segregated populations of neurons in subcortical structures and the neocortex throughout the human brain regulate complex behaviors such as walking, talking, language comprehension, and other cognitive functions associated with frontal lobes. The basal ganglia, which regulate motor control, are also crucial elements in the circuits that confer human reasoning and adaptive function. The basal ganglia are key elements in the control of reward-based learning, sequencing, discrete elements that constitute a complete motor act, and cognitive function. Imaging studies of intact human subjects and electrophysiologic and tracer studies of the brains and behavior of other species confirm these findings. We know that the relation between the basal ganglia and the cerebral cortical region allows for connections organized into discrete circuits. Rather than serving as a means for widespread cortical areas to gain access to the motor system, these loops reciprocally interconnect a large and diverse set of cerebral cortical areas with the basal ganglia. Neuronal activity within the basal ganglia associated with motor areas of the cerebral cortex is highly correlated with parameters of movement. Neuronal activity within the basal ganglia and cerebellar loops associated with the prefrontal cortex is related to the aspects of cognitive function. Thus, individual loops appear to be involved in distinct behavioral functions. Damage to the basal ganglia of circuits with motor areas of the cortex leads to motor symptoms, whereas damage to the subcortical components of circuits with non-motor areas of the cortex causes higher-order deficits. In this report, we review some of the anatomic, physiologic, and behavioral findings that have contributed to a reappraisal of function concerning the basal ganglia and cerebellar loops with the cerebral cortex and apply it in clinical applications to attention deficit/hyperactivity disorder (ADHD) with biomechanics and a discussion of retention of primitive reflexes being highly associated with the condition. PMID:24592214

Plastic changes to dendritic spines on layer V pyramidal neurons are involved in the rectifying role of the prefrontal cortex during the fast period of motor learning.

PubMed

González-Tapia, David; Martínez-Torres, Nestor I; Hernández-González, Marisela; Guevara, Miguel Angel; González-Burgos, Ignacio

2016-02-01

The prefrontal cortex participates in the rectification of information related to motor activity that favors motor learning. Dendritic spine plasticity is involved in the modifications of motor patterns that underlie both motor activity and motor learning. To study this association in more detail, adult male rats were trained over six days in an acrobatic motor learning paradigm and they were subjected to a behavioral evaluation on each day of training. Also, a Golgi-based morphological study was carried out to determine the spine density and the proportion of the different spine types. In the learning paradigm, the number of errors diminished as motor training progressed. Concomitantly, spine density increased on days 1 and 3 of training, particularly reflecting an increase in the proportion of thin (day 1), stubby (day 1) and branched (days 1, 2 and 5) spines. Conversely, mushroom spines were less prevalent than in the control rats on days 5 and 6, as were stubby spines on day 6, together suggesting that this plasticity might enhance motor learning. The increase in stubby spines on day 1 suggests a regulation of excitability related to the changes in synaptic input to the prefrontal cortex. The plasticity to thin spines observed during the first 3 days of training could be related to the active rectification induced by the information relayed to the prefrontal cortex -as the behavioral findings indeed showed-, which in turn could be linked to the lower proportion of mushroom and stubby spines seen in the last days of training. Copyright © 2015 Elsevier B.V. All rights reserved.

Changes of the directional brain networks related with brain plasticity in patients with long-term unilateral sensorineural hearing loss.

PubMed

Zhang, G-Y; Yang, M; Liu, B; Huang, Z-C; Li, J; Chen, J-Y; Chen, H; Zhang, P-P; Liu, L-J; Wang, J; Teng, G-J

2016-01-28

Previous studies often report that early auditory deprivation or congenital deafness contributes to cross-modal reorganization in the auditory-deprived cortex, and this cross-modal reorganization limits clinical benefit from cochlear prosthetics. However, there are inconsistencies among study results on cortical reorganization in those subjects with long-term unilateral sensorineural hearing loss (USNHL). It is also unclear whether there exists a similar cross-modal plasticity of the auditory cortex for acquired monaural deafness and early or congenital deafness. To address this issue, we constructed the directional brain functional networks based on entropy connectivity of resting-state functional MRI and researched changes of the networks. Thirty-four long-term USNHL individuals and seventeen normally hearing individuals participated in the test, and all USNHL patients had acquired deafness. We found that certain brain regions of the sensorimotor and visual networks presented enhanced synchronous output entropy connectivity with the left primary auditory cortex in the left long-term USNHL individuals as compared with normally hearing individuals. Especially, the left USNHL showed more significant changes of entropy connectivity than the right USNHL. No significant plastic changes were observed in the right USNHL. Our results indicate that the left primary auditory cortex (non-auditory-deprived cortex) in patients with left USNHL has been reorganized by visual and sensorimotor modalities through cross-modal plasticity. Furthermore, the cross-modal reorganization also alters the directional brain functional networks. The auditory deprivation from the left or right side generates different influences on the human brain. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Motor Cortex Stimulation Reverses Maladaptive Plasticity Following Spinal Cord Injury

DTIC Science & Technology

2012-09-01

pp 74–85. Austin: Landes Biosciences. 3. Abstracts o Mechanisms of Pain Relief Following Motor Cortex Stimulation: An fMRI Study. Society for...Neuroscience Meeting. Washington, DC. 2012. o Resting State fMRI in a Rat Model of Spinal Cord Injury Neuropathic Pain: A Longitudinal Study. Society...2601–2610. 16. Stefanacci L, Reber P, Costanza J, Wong E, Buxton R, Zola S, Squire L, Albright T. fMRI of monkey visual cortex. Neuron 1998;20:1051

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.

Theta burst stimulation over the primary motor cortex does not induce cortical plasticity in Parkinson's disease.

PubMed

Eggers, Carsten; Fink, Gereon R; Nowak, Dennis A

2010-10-01

The purpose of this study was to investigate whether a period of continuous theta burst stimulation (cTBS) induces cortical plasticity and thus improves bradykinesia of the upper limb in Parkinson's disease. In eight patients with Parkinson's disease (two females; mean age: 68.5 ± 5 years; disease duration: 4 ± 3 years) electrophysiological (motor evoked potentials, contralateral and ipsilateral silent period) and behavioural (Purdue pegboard test, UPDRS motor subscore) parameters were evaluated before (baseline condition) and after a 40-s period of (1) real or (2) sham continuous theta burst stimulation over the primary motor cortex contralateral to the more affected body side off dopaminergic drugs. Compared to baseline, cTBS did change neither measures of cortical excitability nor behavioural measures. cTBS over the primary motor cortex does not impact on cortical excitability or motor function of the upper limb in Parkinson's disease. We interpret these data to reflect impaired cortical plasticity in Parkinson's disease. This study is an important contribution to the knowledge about impaired plasticity in Parkinson's disease.

Does intrinsic motivation enhance motor cortex excitability?

PubMed

Radel, Rémi; Pjevac, Dusan; Davranche, Karen; d'Arripe-Longueville, Fabienne; Colson, Serge S; Lapole, Thomas; Gruet, Mathieu

2016-11-01

Intrinsic motivation (IM) is often viewed as a spontaneous tendency for action. Recent behavioral and neuroimaging evidence indicate that IM, in comparison to extrinsic motivation (EM), solicits the motor system. Accordingly, we tested whether IM leads to greater excitability of the motor cortex than EM. To test this hypothesis, we used two different tasks to induce the motivational orientation using either words representing each motivational orientation or pictures previously linked to each motivational orientation through associative learning. Single-pulse transcranial magnetic stimulation over the motor cortex was applied when viewing the stimuli. Electromyographic activity was recorded on the contracted first dorsal interosseous muscle. Two indexes of corticospinal excitability (the amplitude of motor-evoked potential and the length of cortical silent period) were obtained through unbiased automatic detection and analyzed using a mixed model that provided both statistical power and a high level of control over all important individual, task, and stimuli characteristics. Across the two tasks and the two indices of corticospinal excitability, the exposure to IM-related stimuli did not lead to a greater corticospinal excitability than EM-related stimuli or than stimuli with no motivational valence (ps > .20). While these results tend to dismiss the advantage of IM at activating the motor cortex, we suggest alternative hypotheses to explain this lack of effect, which deserves further research. © 2016 Society for Psychophysiological Research.

Feedforward motor information enhances somatosensory responses and sharpens angular tuning of rat S1 barrel cortex neurons.

PubMed

Khateb, Mohamed; Schiller, Jackie; Schiller, Yitzhak

2017-01-06

The primary vibrissae motor cortex (vM1) is responsible for generating whisking movements. In parallel, vM1 also sends information directly to the sensory barrel cortex (vS1). In this study, we investigated the effects of vM1 activation on processing of vibrissae sensory information in vS1 of the rat. To dissociate the vibrissae sensory-motor loop, we optogenetically activated vM1 and independently passively stimulated principal vibrissae. Optogenetic activation of vM1 supra-linearly amplified the response of vS1 neurons to passive vibrissa stimulation in all cortical layers measured. Maximal amplification occurred when onset of vM1 optogenetic activation preceded vibrissa stimulation by 20 ms. In addition to amplification, vM1 activation also sharpened angular tuning of vS1 neurons in all cortical layers measured. Our findings indicated that in addition to output motor signals, vM1 also sends preparatory signals to vS1 that serve to amplify and sharpen the response of neurons in the barrel cortex to incoming sensory input signals.

Neuroprotective Effect of Melatonin Against PCBs Induced Behavioural, Molecular and Histological Changes in Cerebral Cortex of Adult Male Wistar Rats.

PubMed

Bavithra, S; Selvakumar, K; Sundareswaran, L; Arunakaran, J

2017-02-01

There is ample evidence stating Polychlorinated biphenyls (PCBs) as neurotoxins. In the current study, we have analyzed the behavioural impact of PCBs exposure in adult rats and assessed the simultaneous effect of antioxidant melatonin against the PCBs action. The rats were grouped into four and treated intraperitoneally with vehicle, PCBs, PCBs + melatonin and melatonin alone for 30 days, respectively. After the treatment period the rats were tested for locomotor activity and anxiety behaviour analysis. We confirmed the neuronal damage in the cerebral cortex by molecular and histological analysis. Our data indicates that there is impairment in locomotor activity and behaviour of PCBs treated rats compared to control. The simultaneous melatonin treated rat shows increased motor coordination and less anxiety like behaviour compared to PCBs treated rats. Molecular and histological analysis supports that, the impaired motor coordination in PCBs treated rats is due to neurodegeneration in motor cortex region. The results proved that melatonin treatment improved the motor co-ordination and reduced anxiety behaviour, prevented neurodegeneration in the cerebral cortex of PCBs-exposed adult male rats.

Motor Deficits Are Produced By Removing Some Cortical Transplants Grafted Into Injured Sensorimotor Cortex of Neonatal Rats

PubMed Central

Sandor, Rick; Gonzalez, Manuel F.; Moseley, Michael; Sharp, Frank R.

1991-01-01

Fetal frontal cortex was transplanted into cavities formed in the right, motor cortex of neonatal rats. As adults, the animals were trained to press two levers in rapid succession with their left forelimb to receive food rewards. Once they had reached an optimal level of performance, the effect of removing their transplants was assessed. Surgical removal of transplants significantly impaired the performance of 2 of 4 subjects. Placing a crossstrain skin graft to induce the immunological rejection of the transplants produced a behavioral deficit in 1 of 2 subjects with complete transplant removal. Skin grafts produced no behavioral effects in four subjects that had surviving transplants. Since the motor deficit produced by transplant removal resembled those observed following the removal of normal motor cortex, we propose that these three transplants functioned within the host brain. Histology Showed that the procedures used to remove cortical grafts did not injure any host brains. Therefore, host brain damage is unlikely to account for the behavioral deterioration that followed transplant removals. PMID:1782254

A θ-γ oscillation code for neuronal coordination during motor behavior.

PubMed

Igarashi, Jun; Isomura, Yoshikazu; Arai, Kensuke; Harukuni, Rie; Fukai, Tomoki

2013-11-20

Sequential motor behavior requires a progression of discrete preparation and execution states. However, the organization of state-dependent activity in neuronal ensembles of motor cortex is poorly understood. Here, we recorded neuronal spiking and local field potential activity from rat motor cortex during reward-motivated movement and observed robust behavioral state-dependent coordination between neuronal spiking, γ oscillations, and θ oscillations. Slow and fast γ oscillations appeared during distinct movement states and entrained neuronal firing. γ oscillations, in turn, were coupled to θ oscillations, and neurons encoding different behavioral states fired at distinct phases of θ in a highly layer-dependent manner. These findings indicate that θ and nested dual band γ oscillations serve as the temporal structure for the selection of a conserved set of functional channels in motor cortical layer activity during animal movement. Furthermore, these results also suggest that cross-frequency couplings between oscillatory neuronal ensemble activities are part of the general coding mechanism in cortex.

Grasping Ideas with the Motor System: Semantic Somatotopy in Idiom Comprehension

PubMed Central

Hauk, Olaf; Pulvermüller, Friedemann

2009-01-01

Single words and sentences referring to bodily actions activate the motor cortex. However, this semantic grounding of concrete language does not address the critical question whether the sensory–motor system contributes to the processing of abstract meaning and thought. We examined functional magnetic resonance imaging activation to idioms and literal sentences including arm- and leg-related action words. A common left fronto-temporal network was engaged in sentence reading, with idioms yielding relatively stronger activity in (pre)frontal and middle temporal cortex. Crucially, somatotopic activation along the motor strip, in central and precentral cortex, was elicited by idiomatic and literal sentences, reflecting the body part reference of the words embedded in the sentences. Semantic somatotopy was most pronounced after sentence ending, thus reflecting sentence-level processing rather than that of single words. These results indicate that semantic representations grounded in the sensory–motor system play a role in the composition of sentence-level meaning, even in the case of idioms. PMID:19068489

State-dependent effects of transcranial oscillatory currents on the motor system: what you think matters.

PubMed

Feurra, Matteo; Pasqualetti, Patrizio; Bianco, Giovanni; Santarnecchi, Emiliano; Rossi, Alessandro; Rossi, Simone

2013-10-30

Imperceptible transcranial alternating current stimulation (tACS) changes the endogenous cortical oscillatory activity in a frequency-specific manner. In the human motor system, tACS coincident with the idling beta rhythm of the quiescent motor cortex increased the corticospinal output. We reasoned that changing the initial state of the brain (i.e., from quiescence to a motor imagery task that desynchronizes the local beta rhythm) might also change the susceptibility of the corticospinal system to resonance effects induced by beta-tACS. We tested this hypothesis by delivering tACS at different frequencies (theta, alpha, beta, and gamma) on the primary motor cortex at rest and during motor imagery. Motor-evoked potentials (MEPs) were obtained by transcranial magnetic stimulation (TMS) on the primary motor cortex with an online-navigated TMS-tACS setting. During motor imagery, the increase of corticospinal excitability was maximal with theta-tACS, likely reflecting a reinforcement of working memory processes required to mentally process and "execute" the cognitive task. As expected, the maximal MEPs increase with subjects at rest was instead obtained with beta-tACS, substantiating previous evidence. This dissociation provides new evidence of state and frequency dependency of tACS effects on the motor system and helps discern the functional role of different oscillatory frequencies of this brain region. These findings may be relevant for rehabilitative neuromodulatory interventions.

Source analysis of beta-synchronisation and cortico-muscular coherence after movement termination based on high resolution electroencephalography.

PubMed

Muthuraman, Muthuraman; Tamás, Gertrúd; Hellriegel, Helge; Deuschl, Günther; Raethjen, Jan

2012-01-01

We hypothesized that post-movement beta synchronization (PMBS) and cortico-muscular coherence (CMC) during movement termination relate to each other and have similar role in sensorimotor integration. We calculated the parameters and estimated the sources of these phenomena.We measured 64-channel EEG simultaneously with surface EMG of the right first dorsal interosseus muscle in 11 healthy volunteers. In Task1, subjects kept a medium-strength contraction continuously; in Task2, superimposed on this movement, they performed repetitive self-paced short contractions. In Task3 short contractions were executed alone. Time-frequency analysis of the EEG and CMC was performed with respect to the offset of brisk movements and averaged in each subject. Sources of PMBS and CMC were also calculated.High beta power in Task1, PMBS in Task2-3, and CMC in Task1-2 could be observed in the same individual frequency bands. While beta synchronization in Task1 and PMBS in Task2-3 appeared bilateral with contralateral predominance, CMC in Task1-2 was strictly a unilateral phenomenon; their main sources did not differ contralateral to the movement in the primary sensorimotor cortex in 7 of 11 subjects in Task1, and in 6 of 9 subjects in Task2. In Task2, CMC and PMBS had the same latency but their amplitudes did not correlate with each other. In Task2, weaker PMBS source was found bilaterally within the secondary sensory cortex, while the second source of CMC was detected in the premotor cortex, contralateral to the movement. In Task3, weaker sources of PMBS could be estimated in bilateral supplementary motor cortex and in the thalamus. PMBS and CMC appear simultaneously at the end of a phasic movement possibly suggesting similar antikinetic effects, but they may be separate processes with different active functions. Whereas PMBS seems to reset the supraspinal sensorimotor network, cortico-muscular coherence may represent the recalibration of cortico-motoneuronal and spinal systems.

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.

Studies on the cellular localization of spinal cord substance P receptors.

PubMed

Helke, C J; Charlton, C G; Wiley, R G

1986-10-01

Substance P-immunoreactivity and specific substance P binding sites are present in the spinal cord. Receptor autoradiography showed the discrete localization of substance P binding sites in both sensory and motor regions of the spinal cord and functional studies suggested an important role for substance P receptor activation in autonomic outflow, nociception, respiration and somatic motor function. In the current studies, we investigated the cellular localization of substance P binding sites in rat spinal cord using light microscopic autoradiography combined with several lesioning techniques. Unilateral injections of the suicide transport agent, ricin, into the superior cervical ganglion reduced substance P binding and cholinesterase-stained preganglionic sympathetic neurons in the intermediolateral cell column. However, unilateral electrolytic lesions of ventral medullary substance P neurons which project to the intermediolateral cell column did not alter the density of substance P binding in the intermediolateral cell column. Likewise, 6-hydroxydopamine and 5,7-dihydroxytryptamine, which destroy noradrenergic and serotonergic nerve terminals, did not reduce the substance P binding in the intermediolateral cell column. It appears, therefore, that the substance P binding sites are located postsynaptically on preganglionic sympathetic neurons rather than presynaptically on substance P-immunoreactive processes (i.e. as autoreceptors) or on monoamine nerve terminals. Unilateral injections of ricin into the phrenic nerve resulted in the unilateral destruction of phrenic motor neurons in the cervical spinal cord and caused a marked reduction in the substance P binding in the nucleus. Likewise, sciatic nerve injections of ricin caused a loss of associated motor neurons in the lateral portion of the ventral horn of the lumbar spinal cord and a reduction in the substance P binding. Sciatic nerve injections of ricin also destroyed afferent nerves of the associated dorsal root ganglia and increased the density of substance P binding in the dorsal horn. Capsaicin, which destroys small diameter primary sensory neurons, similarly increased the substance P binding in the dorsal horn. These studies show that the cellular localization of substance P binding sites can be determined by analysis of changes in substance P binding to discrete regions of spinal cord after selective lesions of specific groups of neurons. The data show the presence of substance P binding sites on preganglionic sympathetic neurons in the intermediolateral cell column and on somatic motor neurons in the ventral horn, including the phrenic motor nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)

Different expression patterns of Ngb and EPOR in the cerebral cortex and hippocampus revealed distinctive therapeutic effects of intranasal delivery of Neuro-EPO for ischemic insults to the gerbil brain.

PubMed

Gao, Yan; Mengana, Yuneidis; Cruz, Yamila Rodríguez; Muñoz, Adriana; Testé, Iliana Sosa; García, Jorge Daniel; Wu, Yonghong; Rodríguez, Julio César García; Zhang, Chenggang

2011-02-01

The purpose of this study was to evaluate the neuroprotective effects of intranasally delivered recombinant human neuronal erythropoietin (Neuro-EPO) on brain injury induced by unilateral permanent ischemia in the Mongolian gerbil. Expression of EPO receptor (EPOR) and neuroglobin (Ngb) over 5 weeks after intranasal treatment with Neuro-EPO was determined using immunohistochemistry. Mortality of Neuro-EPO-treated gerbils decreased after surgery, and the sensory and motor function was significantly improved. Histopathological mapping showed that Neuro-EPO significantly reduced delayed neuronal death in the brain. Expression of Ngb was upregulated in the cerebral cortex at most time points (expect for 10 min and 48 hr) and in the hippocampus at 10 min and from 48 hr to 5 weeks, whereas EPOR was almost downregulated or unchanged in the brain (expect for 48 hr). The 10 min and 48 hr seemed to be two time points for the brain to switch the expression of both Ngb and EPOR to early and late recovery phase, respectively. In addition, there were two phases, 10 min to 1 hr and 24 hr to 72 hr, respectively, closing to the "golden hour" of about 60 min and the "silver day" of 1 to 3 days, for the brain to recover from stroke onset with intranasal Neuro-EPO treatment. Therefore, the results suggest that the intranasal administration of Neuro-EPO is effective in the treatment of acute brain ischemia. The different expression patterns of Ngb and EPOR is probably due to ischemic tolerance in the cerebral cortex and ischemic sensitivity in the hippocampus.

Different Expression Patterns of Ngb and EPOR in the Cerebral Cortex and Hippocampus Revealed Distinctive Therapeutic Effects of Intranasal Delivery of Neuro-EPO for Ischemic Insults to the Gerbil Brain

PubMed Central

Gao, Yan; Mengana, Yuneidis; Cruz, Yamila Rodríguez; Muñoz, Adriana; Testé, Iliana Sosa; García, Jorge Daniel; Wu, Yonghong; Rodríguez, Julio César García; Zhang, Chenggang

2011-01-01

The purpose of this study was to evaluate the neuroprotective effects of intranasally delivered recombinant human neuronal erythropoietin (Neuro-EPO) on brain injury induced by unilateral permanent ischemia in the Mongolian gerbil. Expression of EPO receptor (EPOR) and neuroglobin (Ngb) over 5 weeks after intranasal treatment with Neuro-EPO was determined using immunohistochemistry. Mortality of Neuro-EPO-treated gerbils decreased after surgery, and the sensory and motor function was significantly improved. Histopathological mapping showed that Neuro-EPO significantly reduced delayed neuronal death in the brain. Expression of Ngb was upregulated in the cerebral cortex at most time points (expect for 10 min and 48 hr) and in the hippocampus at 10 min and from 48 hr to 5 weeks, whereas EPOR was almost downregulated or unchanged in the brain (expect for 48 hr). The 10 min and 48 hr seemed to be two time points for the brain to switch the expression of both Ngb and EPOR to early and late recovery phase, respectively. In addition, there were two phases, 10 min to 1 hr and 24 hr to 72 hr, respectively, closing to the “golden hour” of about 60 min and the “silver day” of 1 to 3 days, for the brain to recover from stroke onset with intranasal Neuro-EPO treatment. Therefore, the results suggest that the intranasal administration of Neuro-EPO is effective in the treatment of acute brain ischemia. The different expression patterns of Ngb and EPOR is probably due to ischemic tolerance in the cerebral cortex and ischemic sensitivity in the hippocampus. PMID:21339183

Intermanual transfer and bilateral cortical plasticity is maintained in older adults after skilled motor training with simple and complex tasks

PubMed Central

Dickins, Daina S. E.; Sale, Martin V.; Kamke, Marc R.

2015-01-01

Intermanual transfer refers to the phenomenon whereby unilateral motor training induces performance gains in both the trained limb and in the opposite, untrained limb. Evidence indicates that intermanual transfer is attenuated in older adults following training on a simple ballistic movement task, but not after training on a complex task. This study investigated whether differences in plasticity in bilateral motor cortices underlie these differential intermanual transfer effects in older adults. Twenty young (<35 years-old) and older adults (>65 years) trained on a simple (repeated ballistic thumb abduction) and complex (sequential finger-thumb opposition) task in separate sessions. Behavioral performance was used to quantify intermanual transfer between the dominant (trained) and non-dominant (untrained) hands. The amplitude of motor-evoked potentials induced by single pulse transcranial magnetic stimulation was used to investigate excitability changes in bilateral motor cortices. Contrary to predictions, both age groups exhibited performance improvements in both hands after unilateral skilled motor training with simple and complex tasks. These performance gains were accompanied by bilateral increases in cortical excitability in both groups for the simple but not the complex task. The findings suggest that advancing age does not necessarily influence the capacity for intermanual transfer after training with the dominant hand. PMID:25999856

WNT-C59, a Small-Molecule WNT Inhibitor, Efficiently Induces Anterior Cortex That Includes Cortical Motor Neurons From Human Pluripotent Stem Cells.

PubMed

Motono, Makoto; Ioroi, Yoshihiko; Ogura, Takenori; Takahashi, Jun

2016-04-01

The recapitulation of human neural development in a controlled, defined manner from pluripotent stem cells (PSCs) has considerable potential for studies of human neural development, circuit formation and function, and the construction of in vitro models of neurological diseases. The inhibition of Wnt signaling, often by the recombinant protein DKK1, is important for the induction of cortical neurons. Here, we report a novel differentiation method using a small-molecule WNT inhibitor, WNT-C59 (C59), to efficiently induce human anterior cortex. We compared two types of small molecules, C59 and XAV939 (XAV), as substitutes for DKK1 to induce cortical neurons from PSCs in serum-free embryoid body-like aggregate culture. DKK1 and XAV inhibited only the canonical pathway of Wnt signaling, whereas C59 inhibited both the canonical and noncanonical pathways. C59 efficiently induced CTIP2+/COUP-TF1- cells, which are characteristic of the cells found in the anterior cortex. In addition, when grafted into the cortex of adult mice, the C59-induced cells showed abundant axonal fiber extension toward the spinal cord. These results raise the possibility of C59 contributing to cell replacement therapy for motor neuron diseases or insults. For a cell therapy against damaged corticospinal tract caused by neurodegenerative diseases or insults, cortical motor neurons are needed. Currently, their induction from pluripotent stem cells is considered very promising; however, an efficient protocol to induce motor neurons is not available. For efficient induction of anterior cortex, where motor neurons are located, various WNT inhibitors were investigated. It was found that one of them could induce anterior cortical cells efficiently. In addition, when grafted into the cortex of adult mice, the induced cells showed more abundant axonal fiber extension toward spinal cord. These results raise the possibility that this inhibitor contributes to a cell-replacement therapy for motor neuron diseases or insults. ©AlphaMed Press.

A Potential Biomarker in Amyotrophic Lateral Sclerosis: Can Assessment of Brain Iron Deposition with SWI and Corticospinal Tract Degeneration with DTI Help?

PubMed

Sheelakumari, R; Madhusoodanan, M; Radhakrishnan, A; Ranjith, G; Thomas, B

2016-02-01

Iron-mediated oxidative stress plays a pivotal role in the pathogenesis of amyotrophic lateral sclerosis. This study aimed to assess iron deposition qualitatively and quantitatively by using SWI and microstructural changes in the corticospinal tract by using DTI in patients with amyotrophic lateral sclerosis. Seventeen patients with amyotrophic lateral sclerosis and 15 age- and sex-matched controls underwent brain MR imaging with SWI and DTI. SWI was analyzed for both signal-intensity scoring and quantitative estimation of iron deposition in the anterior and posterior banks of the motor and sensory cortices and deep gray nuclei. The diffusion measurements along the corticospinal tract at the level of pons and medulla were obtained by ROI analysis. Patients with amyotrophic lateral sclerosis showed reduced signal-intensity grades in the posterior bank of the motor cortex bilaterally. Quantitative analysis confirmed significantly higher iron content in the posterior bank of the motor cortex in patients with amyotrophic lateral sclerosis. In contrast, no significant differences were noted for the anterior bank of the motor cortex, anterior and posterior banks of the sensory cortex, and deep nuclei. Receiver operating characteristic comparison showed a cutoff of 35μg Fe/g of tissue with an area under the curve of 0.78 (P = .008) for the posterior bank of the motor cortex in discriminating patients with amyotrophic lateral sclerosis from controls. Fractional anisotropy was lower in the pyramidal tracts of patients with amyotrophic lateral sclerosis at the pons and medulla on either side, along with higher directionally averaged mean diffusivity values. The combination of SWI and DTI revealed an area under the curve of 0.784 for differentiating patients with amyotrophic lateral sclerosis from controls. Measurements of motor cortex iron deposition and diffusion tensor parameters of the corticospinal tract may be useful biomarkers for the diagnosis of clinically suspected amyotrophic lateral sclerosis. © 2016 by American Journal of Neuroradiology.

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.

The mammalian neocortex new pyramidal neuron: a new conception.

PubMed

Marín-Padilla, Miguel

2014-01-06

The new cerebral cortex (neocortex) and the new type of pyramidal neuron are mammalian innovations that have evolved for operating their increasing motor capabilities while essentially using analogous anatomical and neural makeups. The human neocortex starts to develop in 6-week-old embryos with the establishment of a primordial cortical organization, which resembles the primitive cortices of amphibian and reptiles. From the 8th to the 15th week of age, new pyramidal neurons, of ependymal origin, are progressively incorporated within this primordial cortex forming a cellular plate that divides its components into those above it (neocortex first layer) and those below it (neocortex subplate zone). From the 16th week of age to birth and postnatally, the new pyramidal neurons continue to elongate functionally their apical dendrite by adding synaptic membrane to incorporate the needed sensory information for operating its developing motor activities. The new pyramidal neuron' distinguishing feature is the capacity of elongating anatomically and functionally its apical dendrite (its main receptive surface) without losing its original attachment to first layer or the location of its soma and, hence, retaining its essential nature. The number of pyramidal cell functional strata established in the motor cortex increases and reflects each mammalian species motor capabilities: the hedgehog needs two pyramidal cell functional strata to carry out all its motor activities, the mouse 3, cat 4, primates 5 and humans 6. The presence of six pyramidal cell functional strata distinguish the human motor cortex from that of others primates. Homo sapiens represent a new evolutionary stage that have transformed his primate brain for operating his unique motor capabilities, such as speaking, writing, painting, sculpturing and thinking as a premotor activity. Words used in language are the motor expression of thoughts and represent sounds produced by maneuvering the column of expiratory air by coordinated motor quivering as it passes through the larynx, pharynx, mouth, tongue, and lips. Homo sapiens cerebrum has developed new motor centers to communicate mental thoughts (and/or intention) through motor actions.

Production of verbs related to body movement in amyotrophic lateral sclerosis (ALS) and Parkinson's Disease (PD).

PubMed

Cousins, Katheryn A Q; Ash, Sharon; Grossman, Murray

2018-03-01

Theories of grounded cognition propose that action verb knowledge relies in part on motor processing regions, including premotor cortex. Accordingly, impaired action verb knowledge in patients with amyotrophic lateral sclerosis (ALS) and Parkinson's Disease (PD) is thought to be due to motor system degeneration. Upper motor neuron disease in ALS degrades the motor cortex and related pyramidal motor system, while disease in PD is centered in the basal ganglia and can spread to frontostriatal areas that are important to language functioning. These anatomical distinctions in disease may yield subtle differences in the action verb impairment between patient groups. Here we compare verbs where the body is the agent of the action to verbs where the body is the theme. To examine the role of motor functioning in body verb production, we split patient groups into patients with high motor impairment (HMI) and those with low motor impairment (LMI), using disease-specific measures of motor impairment. Regression analyses assessed how verb production in ALS and PD was related to motor system atrophy. We find a dissociation between agent- and theme-body verbs in ALS: ALS HMI were impaired for agent body verbs but not theme verbs, compared to ALS LMI. This dissociation was not present in PD patients, who instead show depressed production for all body verbs. Although patients with cognitive impairment were excluded from this study, cognitive performance significantly correlated with the production of theme verbs in ALS and cognitive/stative verbs in PD. Finally, regression analyses related the agent-theme dissociation in ALS to grey matter atrophy of premotor cortex. These findings support the view that motor dysfunction and disease in premotor cortex contributes to the agent body verb deficit in ALS, and begin to identify some distinct characteristics of impairment for verbs in ALS and PD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Remote effects of intermittent theta burst stimulation of the human pharyngeal motor system.

PubMed

Mistry, Satish; Michou, Emilia; Rothwell, John; Hamdy, Shaheen

2012-08-01

Intermittent theta burst stimulation (iTBS) is a novel, non-invasive form of brain stimulation capable of facilitating excitability of the human primary motor cortex with therapeutic potential in the treatment of neurological conditions, such as multiple sclerosis. The objectives of this study were to evaluate the effects of iTBS on cortical properties in the human pharyngeal motor system. Transcranial magnetic stimulation (TMS)-evoked pharyngeal motor responses were recorded via a swallowed intra-luminal catheter and used to assess motor cortical pathways to the pharynx in both hemispheres before and for up to 90 min after iTBS in 15 healthy adults (nine male/six female, 22-59 years old). Active/sham iTBS comprised 600 intermittent repetitive TMS pulses, delivered in a double-blind pseudo-randomised order over each hemisphere on separate days at least 1 week apart. Abductor pollicis brevis (APB) recordings were used as control. Hemispheric interventional data were compared with sham using repeated-measures anova. iTBS was delivered at an average intensity of 43±1% of stimulator output. Compared with sham, iTBS to the hemisphere with stronger pharyngeal projections induced increased responses only in the contralateral weaker projection 60-90 min post-iTBS (maximum 54±19%, P≤0.007), with no change in stronger hemisphere responses. By contrast, iTBS to weaker projections had no significant effects (P=0.39) on either hemisphere. APB responses similarly did not change significantly (P=0.78) across all study arms. We conclude that iTBS can induce remote changes in corticobulbar excitability. While further studies will clarify the extent of these changes, iTBS holds promise as a potential treatment for dysphagia after unilateral brain damage. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

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.

Cortical activity in the null space: permitting preparation without movement

PubMed Central

Kaufman, Matthew T.; Churchland, Mark M.; Ryu, Stephen I.; Shenoy, Krishna V.

2014-01-01

Neural circuits must perform computations and then selectively output the results to other circuits. Yet synapses do not change radically at millisecond timescales. A key question then is: how is communication between neural circuits controlled? In motor control, brain areas directly involved in driving movement are active well before movement begins. Muscle activity is some readout of neural activity, yet remains largely unchanged during preparation. Here we find that during preparation, while the monkey holds still, changes in motor cortical activity cancel out at the level of these population readouts. Motor cortex can thereby prepare the movement without prematurely causing it. Further, we found evidence that this mechanism also operates in dorsal premotor cortex (PMd), largely accounting for how preparatory activity is attenuated in primary motor cortex (M1). Selective use of “output-null” vs. “output-potent” patterns of activity may thus help control communication to the muscles and between these brain areas. PMID:24487233

Expression of Kv3.1b potassium channel is widespread in macaque motor cortex pyramidal cells: A histological comparison between rat and macaque

PubMed Central

Soares, David; Goldrick, Isabelle; Lemon, Roger N.; Kraskov, Alexander; Greensmith, Linda

2017-01-01

Abstract There are substantial differences across species in the organization and function of the motor pathways. These differences extend to basic electrophysiological properties. Thus, in rat motor cortex, pyramidal cells have long duration action potentials, while in the macaque, some pyramidal neurons exhibit short duration “thin” spikes. These differences may be related to the expression of the fast potassium channel Kv3.1b, which in rat interneurons is associated with generation of thin spikes. Rat pyramidal cells typically lack these channels, while there are reports that they are present in macaque pyramids. Here we made a systematic, quantitative comparison of the Kv3.1b expression in sections from macaque and rat motor cortex, using two different antibodies (NeuroMab, Millipore). As our standard reference, we examined, in the same sections, Kv3.1b staining in parvalbumin‐positive interneurons, which show strong Kv3.1b immunoreactivity. In macaque motor cortex, a large sample of pyramidal neurons were nearly all found to express Kv3.1b in their soma membranes. These labeled neurons were identified as pyramidal based either by expression of SMI32 (a pyramidal marker), or by their shape and size, and lack of expression of parvalbumin (a marker for some classes of interneuron). Large (Betz cells), medium, and small pyramidal neurons all expressed Kv3.1b. In rat motor cortex, SMI32‐postive pyramidal neurons expressing Kv3.1b were very rare and weakly stained. Thus, there is a marked species difference in the immunoreactivity of Kv3.1b in pyramidal neurons, and this may be one of the factors explaining the pronounced electrophysiological differences between rat and macaque pyramidal neurons. PMID:28213922

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.

Dissociation between sustained single-neuron spiking and transient β-LFP oscillations in primate motor cortex

PubMed Central

Rule, Michael E.; Vargas-Irwin, Carlos E.; Donoghue, John P.

2017-01-01

Determining the relationship between single-neuron spiking and transient (20 Hz) β-local field potential (β-LFP) oscillations is an important step for understanding the role of these oscillations in motor cortex. We show that whereas motor cortex firing rates and beta spiking rhythmicity remain sustained during steady-state movement preparation periods, β-LFP oscillations emerge, in contrast, as short transient events. Single-neuron mean firing rates within and outside transient β-LFP events showed no differences, and no consistent correlation was found between the beta oscillation amplitude and firing rates, as was the case for movement- and visual cue-related β-LFP suppression. Importantly, well-isolated single units featuring beta-rhythmic spiking (43%, 125/292) showed no apparent or only weak phase coupling with the transient β-LFP oscillations. Similar results were obtained for the population spiking. These findings were common in triple microelectrode array recordings from primary motor (M1), ventral (PMv), and dorsal premotor (PMd) cortices in nonhuman primates during movement preparation. Although beta spiking rhythmicity indicates strong membrane potential fluctuations in the beta band, it does not imply strong phase coupling with β-LFP oscillations. The observed dissociation points to two different sources of variation in motor cortex β-LFPs: one that impacts single-neuron spiking dynamics and another related to the generation of mesoscopic β-LFP signals. Furthermore, our findings indicate that rhythmic spiking and diverse neuronal firing rates, which encode planned actions during movement preparation, may naturally limit the ability of different neuronal populations to strongly phase-couple to a single dominant oscillation frequency, leading to the observed spiking and β-LFP dissociation. NEW & NOTEWORTHY We show that whereas motor cortex spiking rates and beta (~20 Hz) spiking rhythmicity remain sustained during steady-state movement preparation periods, β-local field potential (β-LFP) oscillations emerge, in contrast, as transient events. Furthermore, the β-LFP phase at which neurons spike drifts: phase coupling is typically weak or absent. This dissociation points to two sources of variation in the level of motor cortex beta: one that impacts single-neuron spiking and another related to the generation of measured mesoscopic β-LFPs. PMID:28100654

Responses of primate frontal cortex neurons during natural vocal communication.

PubMed

Miller, Cory T; Thomas, A Wren; Nummela, Samuel U; de la Mothe, Lisa A

2015-08-01

The role of primate frontal cortex in vocal communication and its significance in language evolution have a controversial history. While evidence indicates that vocalization processing occurs in ventrolateral prefrontal cortex neurons, vocal-motor activity has been conjectured to be primarily subcortical and suggestive of a distinctly different neural architecture from humans. Direct evidence of neural activity during natural vocal communication is limited, as previous studies were performed in chair-restrained animals. Here we recorded the activity of single neurons across multiple regions of prefrontal and premotor cortex while freely moving marmosets engaged in a natural vocal behavior known as antiphonal calling. Our aim was to test whether neurons in marmoset frontal cortex exhibited responses during vocal-signal processing and/or vocal-motor production in the context of active, natural communication. We observed motor-related changes in single neuron activity during vocal production, but relatively weak sensory responses for vocalization processing during this natural behavior. Vocal-motor responses occurred both prior to and during call production and were typically coupled to the timing of each vocalization pulse. Despite the relatively weak sensory responses a population classifier was able to distinguish between neural activity that occurred during presentations of vocalization stimuli that elicited an antiphonal response and those that did not. These findings are suggestive of the role that nonhuman primate frontal cortex neurons play in natural communication and provide an important foundation for more explicit tests of the functional contributions of these neocortical areas during vocal behaviors. Copyright © 2015 the American Physiological Society.

Responses of primate frontal cortex neurons during natural vocal communication

PubMed Central

Thomas, A. Wren; Nummela, Samuel U.; de la Mothe, Lisa A.

2015-01-01

The role of primate frontal cortex in vocal communication and its significance in language evolution have a controversial history. While evidence indicates that vocalization processing occurs in ventrolateral prefrontal cortex neurons, vocal-motor activity has been conjectured to be primarily subcortical and suggestive of a distinctly different neural architecture from humans. Direct evidence of neural activity during natural vocal communication is limited, as previous studies were performed in chair-restrained animals. Here we recorded the activity of single neurons across multiple regions of prefrontal and premotor cortex while freely moving marmosets engaged in a natural vocal behavior known as antiphonal calling. Our aim was to test whether neurons in marmoset frontal cortex exhibited responses during vocal-signal processing and/or vocal-motor production in the context of active, natural communication. We observed motor-related changes in single neuron activity during vocal production, but relatively weak sensory responses for vocalization processing during this natural behavior. Vocal-motor responses occurred both prior to and during call production and were typically coupled to the timing of each vocalization pulse. Despite the relatively weak sensory responses a population classifier was able to distinguish between neural activity that occurred during presentations of vocalization stimuli that elicited an antiphonal response and those that did not. These findings are suggestive of the role that nonhuman primate frontal cortex neurons play in natural communication and provide an important foundation for more explicit tests of the functional contributions of these neocortical areas during vocal behaviors. PMID:26084912

An Extended Motor Network Generates Beta and Gamma Oscillatory Perturbations during Development

ERIC Educational Resources Information Center

Wilson, Tony W.; Slason, Erin; Asherin, Ryan; Kronberg, Eugene; Reite, Martin L.; Teale, Peter D.; Rojas, Donald C.

2010-01-01

This study examines the time course and neural generators of oscillatory beta and gamma motor responses in typically-developing children. Participants completed a unilateral flexion-extension task using each index finger as whole-head magnetoencephalography (MEG) data were acquired. These MEG data were imaged in the frequency-domain using spatial…

[The neuronal level of motor activity: determination of motor cortex excitability by TMS].

PubMed

Eichhammer, Peter; Langguth, Berthold; Müller, Jürgen; Hajak, Göran

2005-04-01

Transcranial magnetic stimulation as mapping method offers the possibility to measure aspects of motor cortex excitability painlessly and non-invasively. Using this neurophysiological tool, new insights into the effects of central-acting drugs are possible. Particularly striking seems to be the potential of this approach to gain new insights into neurobiological processes associated with neuropsychiatric diseases like schizophrenia or major depression. In combination with genetic aspects, TMS is able to bridge the gap between molecular research and clinical approach.

Sex-related differences in effects of progesterone following neonatal hypoxic brain injury.

PubMed

Peterson, Bethany L; Won, Soonmi; Geddes, Rastafa I; Sayeed, Iqbal; Stein, Donald G

2015-06-01

There is no satisfactory therapeutic intervention for neonatal hypoxic-ischemic (HI) encephalopathy. Progesterone is known to be effective in treating traumatic brain injury in adult animals but its effects in neonatal brains have not been reported. Brain injuries were induced by a unilateral common carotid artery ligation plus hypoxia exposure. Progesterone was administered immediately after hypoxia and daily for 5 days at 8 mg/kg, followed by a tapered dose for two days. At six weeks post-injury, lesion size and inflammatory factors were evaluated. Progesterone-treated, HI-injured male animals, but not females, showed significant long-term tissue protection compared to vehicle, suggesting an important sex difference in neuroprotection. Progesterone-treated, HI-injured male rats had fewer activated microglia in the cortex and hippocampus compared to controls. The rats were tested for neurological reflexes, motor asymmetry, and cognitive performance at multiple time points. The injured animals exhibited few detectable motor deficits, suggesting a high level of age- and injury-related neuroplasticity. There were substantial sex differences on several behavioral tests, indicating that immature males and females should be analyzed separately. Progesterone-treated animals showed modest beneficial effects in both sexes compared to vehicle-treated injured animals. Sham animals given progesterone did not behave differently from vehicle-treated sham animals on any measures. Copyright © 2015 Elsevier B.V. All rights reserved.

The Contribution of Primary Motor Cortex Is Essential for Probabilistic Implicit Sequence Learning: Evidence from Theta Burst Magnetic Stimulation

ERIC Educational Resources Information Center

Wilkinson, Leonora; Teo, James T.; Obeso, Ignacio; Rothwell, John C.; Jahanshahi, Marjan

2010-01-01

Theta burst transcranial magnetic stimulation (TBS) is considered to produce plastic changes in human motor cortex. Here, we examined the inhibitory and excitatory effects of TBS on implicit sequence learning using a probabilistic serial reaction time paradigm. We investigated the involvement of several cortical regions associated with implicit…

Representation of the Speech Effectors in the Human Motor Cortex: Somatotopy or Overlap?

ERIC Educational Resources Information Center

Takai, Osamu; Brown, Steven; Liotti, Mario

2010-01-01

Somatotopy within the orofacial region of the human motor cortex has been a central concept in interpreting the results of neuroimaging and transcranial magnetic stimulation studies of normal and disordered speech. Yet, somatotopy has been challenged by studies showing overlap among the effectors within the homunculus. In order to address this…

Body Topography Parcellates Human Sensory and Motor Cortex.

PubMed

Kuehn, Esther; Dinse, Juliane; Jakobsen, Estrid; Long, Xiangyu; Schäfer, Andreas; Bazin, Pierre-Louis; Villringer, Arno; Sereno, Martin I; Margulies, Daniel S

2017-07-01

The cytoarchitectonic map as proposed by Brodmann currently dominates models of human sensorimotor cortical structure, function, and plasticity. According to this model, primary motor cortex, area 4, and primary somatosensory cortex, area 3b, are homogenous areas, with the major division lying between the two. Accumulating empirical and theoretical evidence, however, has begun to question the validity of the Brodmann map for various cortical areas. Here, we combined in vivo cortical myelin mapping with functional connectivity analyses and topographic mapping techniques to reassess the validity of the Brodmann map in human primary sensorimotor cortex. We provide empirical evidence that area 4 and area 3b are not homogenous, but are subdivided into distinct cortical fields, each representing a major body part (the hand and the face). Myelin reductions at the hand-face borders are cortical layer-specific, and coincide with intrinsic functional connectivity borders as defined using large-scale resting state analyses. Our data extend the Brodmann model in human sensorimotor cortex and suggest that body parts are an important organizing principle, similar to the distinction between sensory and motor processing. © The Author 2017. Published by Oxford University Press.

Transient shifts in frontal and parietal circuits scale with enhanced visual feedback and changes in force variability and error

PubMed Central

Poon, Cynthia; Coombes, Stephen A.; Corcos, Daniel M.; Christou, Evangelos A.

2013-01-01

When subjects perform a learned motor task with increased visual gain, error and variability are reduced. Neuroimaging studies have identified a corresponding increase in activity in parietal cortex, premotor cortex, primary motor cortex, and extrastriate visual cortex. Much less is understood about the neural processes that underlie the immediate transition from low to high visual gain within a trial. This study used 128-channel electroencephalography to measure cortical activity during a visually guided precision grip task, in which the gain of the visual display was changed during the task. Force variability during the transition from low to high visual gain was characterized by an inverted U-shape, whereas force error decreased from low to high gain. Source analysis identified cortical activity in the same structures previously identified using functional magnetic resonance imaging. Source analysis also identified a time-varying shift in the strongest source activity. Superior regions of the motor and parietal cortex had stronger source activity from 300 to 600 ms after the transition, whereas inferior regions of the extrastriate visual cortex had stronger source activity from 500 to 700 ms after the transition. Force variability and electrical activity were linearly related, with a positive relation in the parietal cortex and a negative relation in the frontal cortex. Force error was nonlinearly related to electrical activity in the parietal cortex and frontal cortex by a quadratic function. This is the first evidence that force variability and force error are systematically related to a time-varying shift in cortical activity in frontal and parietal cortex in response to enhanced visual gain. PMID:23365186

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

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.

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.

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

Does unilateral basal ganglia activity functionally influence the contralateral side? What we can learn from STN stimulation in patients with Parkinson's disease.

PubMed

Brun, Yohann; Karachi, Carine; Fernandez-Vidal, Sara; Jodoin, Nicolas; Grabli, David; Bardinet, Eric; Mallet, Luc; Agid, Yves; Yelnik, Jerome; Welter, Marie-Laure

2012-09-01

In humans, the control of voluntary movement, in which the corticobasal ganglia (BG) circuitry participates, is mainly lateralized. However, several studies have suggested that both the contralateral and ipsilateral BG systems are implicated during unilateral movement. Bilateral improvement of motor signs in patients with Parkinson's disease (PD) has been reported with unilateral lesion or high-frequency stimulation (HFS) of the internal part of the globus pallidus or the subthalamic nucleus (STN-HFS). To decipher the mechanisms of production of ipsilateral movements induced by the modulation of unilateral BG circuitry activity, we recorded left STN neuronal activity during right STN-HFS in PD patients operated for bilateral deep brain stimulation. Left STN single cells were recorded in the operating room during right STN-HFS while patients experienced, or did not experience, right stimulation-induced dyskinesias. Most of the left-side STN neurons (64%) associated with the presence of right dyskinesias were inhibited, with a significant decrease in burst and intraburst frequencies. In contrast, left STN neurons not associated with right dyskinesias were mainly activated (48%), with a predominant increase 4-5 ms after the stimulation pulse and a decrease in oscillatory activity. This suggests that unilateral neuronal STN modulation is associated with changes in the activity of the contralateral STN. The fact that one side of the BG system can influence the functioning of the other could explain the occurrence of bilateral dyskinesias and motor improvement observed in PD patients during unilateral STN-HFS, as a result of a bilateral disruption of the pathological activity in the corticosubcortical circuitry.

Event-related Potentials During Target-response Tasks to Study Cognitive Processes of Upper Limb Use in Children with Unilateral Cerebral Palsy.

PubMed

Zielinski, Ingar Marie; Steenbergen, Bert; Baas, C Marjolein; Aarts, Pauline; Jongsma, Marijtje L A

2016-01-11

Unilateral Cerebral Palsy (CP) is a neurodevelopmental disorder that is a very common cause of disability in childhood. It is characterized by unilateral motor impairments that are frequently dominated in the upper limb. In addition to a reduced movement capacity of the affected upper limb, several children with unilateral CP show a reduced awareness of the remaining movement capacity of that limb. This phenomenon of disregarding the preserved capacity of the affected upper limb is regularly referred to as Developmental Disregard (DD). Different theories have been postulated to explain DD, each suggesting slightly different guidelines for therapy. Still, cognitive processes that might additionally contribute to DD in children with unilateral CP have never been directly studied. The current protocol was developed to study cognitive aspects involved in upper limb control in children with unilateral CP with and without DD. This was done by recording event-related potentials (ERPs) extracted from the ongoing EEG during target-response tasks asking for a hand-movement response. ERPs consist of several components, each of them associated with a well-defined cognitive process (e.g., the N1 with early attention processes, the N2 with cognitive control and the P3 with cognitive load and mental effort). Due to its excellent temporal resolution, the ERP technique enables to study several covert cognitive processes preceding overt motor responses and thus allows insight into the cognitive processes that might contribute to the phenomenon of DD. Using this protocol adds a new level of explanation to existing behavioral studies and opens new avenues to the broader implementation of research on cognitive aspects of developmental movement restrictions in children.

Recovery-related indicators of motor network plasticity according to impairment severity after stroke.

PubMed

Lee, J; Park, E; Lee, A; Chang, W H; Kim, D-S; Kim, Y-H

2017-10-01

Brain connectivity analysis has been widely used to investigate brain plasticity and recovery-related indicators of patients with stroke. However, results remain controversial because of interindividual variability of initial impairment and subsequent recovery of function. In this study, we aimed to investigate the differences in network plasticity and motor recovery-related indicators according to initial severity. We divided participants (16 males and 14 females, aged 54.2 ± 12.0 years) into groups of different severity by Fugl-Mayer Assessment score, i.e. moderate (50-84), severe (20-49) and extremely severe (<20) impairment groups. Longitudinal resting-state functional magnetic resonance imaging data were acquired at 2 weeks and 3 months after onset. The differences in network plasticity and recovery-related indicators between groups were investigated using network distance and graph measurements. As the level of impairment increased, the network balance was more disrupted. Network balance, interhemispheric connectivity and network efficiency were recovered at 3 months only in the moderate impairment group. However, this was not the case in the extremely severe impairment group. A single connection strength between the ipsilesional primary motor cortex and ventral premotor cortex was implicated in the recovery of motor function for the extremely severe impairment group. The connections of the ipsilesional primary motor cortex-ventral premotor cortex were positively associated with motor recovery as the patients were more severely impaired. Differences in plasticity and recovery-related indicators of motor networks were noted according to impairment severity. Our results may suggest meaningful implications for recovery prediction and treatment strategies in future stroke research. © 2017 EAN.

Robust tactile sensory responses in finger area of primate motor cortex relevant to prosthetic control

NASA Astrophysics Data System (ADS)

Schroeder, Karen E.; Irwin, Zachary T.; Bullard, Autumn J.; Thompson, David E.; Bentley, J. Nicole; Stacey, William C.; Patil, Parag G.; Chestek, Cynthia A.

2017-08-01

Objective. Challenges in improving the performance of dexterous upper-limb brain-machine interfaces (BMIs) have prompted renewed interest in quantifying the amount and type of sensory information naturally encoded in the primary motor cortex (M1). Previous single unit studies in monkeys showed M1 is responsive to tactile stimulation, as well as passive and active movement of the limbs. However, recent work in this area has focused primarily on proprioception. Here we examined instead how tactile somatosensation of the hand and fingers is represented in M1. Approach. We recorded multi- and single units and thresholded neural activity from macaque M1 while gently brushing individual finger pads at 2 Hz. We also recorded broadband neural activity from electrocorticogram (ECoG) grids placed on human motor cortex, while applying the same tactile stimulus. Main results. Units displaying significant differences in firing rates between individual fingers (p  <  0.05) represented up to 76.7% of sorted multiunits across four monkeys. After normalizing by the number of channels with significant motor finger responses, the percentage of electrodes with significant tactile responses was 74.9%  ±  24.7%. No somatotopic organization of finger preference was obvious across cortex, but many units exhibited cosine-like tuning across multiple digits. Sufficient sensory information was present in M1 to correctly decode stimulus position from multiunit activity above chance levels in all monkeys, and also from ECoG gamma power in two human subjects. Significance. These results provide some explanation for difficulties experienced by motor decoders in clinical trials of cortically controlled prosthetic hands, as well as the general problem of disentangling motor and sensory signals in primate motor cortex during dextrous tasks. Additionally, examination of unit tuning during tactile and proprioceptive inputs indicates cells are often tuned differently in different contexts, reinforcing the need for continued refinement of BMI training and decoding approaches to closed-loop BMI systems for dexterous grasping.

Reduced Motor Cortex Activity during Movement Preparation following a Period of Motor Skill Practice

PubMed Central

Wright, David J.; Holmes, Paul; Di Russo, Francesco; Loporto, Michela; Smith, Dave

2012-01-01

Experts in a skill produce movement-related cortical potentials (MRCPs) of smaller amplitude and later onset than novices. This may indicate that, following long-term training, experts require less effort to plan motor skill performance. However, no longitudinal evidence exists to support this claim. To address this, EEG was used to study the effect of motor skill training on cortical activity related to motor planning. Ten non-musicians took part in a 5-week training study learning to play guitar. At week 1, the MRCP was recorded from motor areas whilst participants played the G Major scale. Following a period of practice of the scale, the MRCP was recorded again at week 5. Results showed that the amplitude of the later pre-movement components were smaller at week 5 compared to week 1. This may indicate that, following training, less activity at motor cortex sites is involved in motor skill preparation. This supports claims for a more efficient motor preparation following motor skill training. PMID:23251647

The posterior parietal cortex (PPC) mediates anticipatory motor control.

PubMed

Krause, Vanessa; Weber, Juliane; Pollok, Bettina

2014-01-01

Flexible and precisely timed motor control is based on functional interaction within a cortico-subcortical network. The left posterior parietal cortex (PPC) is supposed to be crucial for anticipatory motor control by sensorimotor feedback matching. Intention of the present study was to disentangle the specific relevance of the left PPC for anticipatory motor control using transcranial direct current stimulation (tDCS) since a causal link remains to be established. Anodal vs. cathodal tDCS was applied for 10 min over the left PPC in 16 right-handed subjects in separate sessions. Left primary motor cortex (M1) tDCS served as control condition and was applied in additional 15 subjects. Prior to and immediately after tDCS, subjects performed three tasks demanding temporal motor precision with respect to an auditory stimulus: sensorimotor synchronization as measure of anticipatory motor control, interval reproduction and simple reaction. Left PPC tDCS affected right hand synchronization but not simple reaction times. Motor anticipation was deteriorated by anodal tDCS, while cathodal tDCS yielded the reverse effect. The variability of interval reproduction was increased by anodal left M1 tDCS, whereas it was reduced by cathodal tDCS. No significant effects on simple reaction times were found. The present data support the hypothesis that left PPC is causally involved in right hand anticipatory motor control exceeding pure motor implementation as processed by M1 and possibly indicating subjective timing. Since M1 tDCS particularly affects motor implementation, the observed PPC effects are not likely to be explained by alterations of motor-cortical excitability. Copyright © 2014 Elsevier Inc. All rights reserved.

Interaction of paired cortical and peripheral nerve stimulation on human motor neurons.

PubMed

Poon, David E; Roy, Francois D; Gorassini, Monica A; Stein, Richard B

2008-06-01

This paper contrasts responses in the soleus muscle of normal human subjects to two major inputs: the tibial nerve (TN) and the corticospinal tract. Paired transcranial magnetic stimulation (TMS) of the motor cortex at intervals of 10-25 ms strongly facilitated the motor evoked potential (MEP) produced by the second stimulus. In contrast, paired TN stimulation produced a depression of the reflex response to the second stimulus. Direct activation of the pyramidal tract did not facilitate a second response, suggesting that the MEP facilitation observed using paired TMS occurred in the cortex. A TN stimulus also depressed a subsequent MEP. Since the TN stimulus depressed both inputs, the mechanism is probably post-synaptic, such as afterhyperpolarization of motor neurons. Presynaptic mechanisms, such as homosynaptic depression, would only affect the pathway used as a conditioning stimulus. When TN and TMS pulses were paired, the largest facilitation occurred when TMS preceded TN by about 5 ms, which is optimal for summation of the two pathways at the level of the spinal motor neurons. A later, smaller facilitation occurred when a single TN stimulus preceded TMS by 50-60 ms, an interval that allows enough time for the sensory afferent input to reach the sensory cortex and be relayed to the motor cortex. Other work indicates that repetitively pairing nerve stimuli and TMS at these intervals, known as paired associative stimulation, produces long-term increases in the MEP and may be useful in strengthening residual pathways after damage to the central nervous system.

Motor cortical representation of the pelvic floor muscles.

PubMed

Schrum, A; Wolff, S; van der Horst, C; Kuhtz-Buschbeck, J P

2011-07-01

Pelvic floor muscle training involves rhythmical voluntary contractions of the external urethral sphincter and ancillary pelvic floor muscles. The representation of these muscles in the motor cortex has not been located precisely and unambiguously. We used functional magnetic resonance imaging to determine brain activity during slow and fast pelvic floor contractions. Cerebral responses were recorded in 17 healthy male volunteers, 21 to 47 years old, with normal bladder control. Functional magnetic resonance imaging was performed during metronome paced slow (0.25 Hertz) and fast (0.7 Hertz) contractions of the pelvic floor that mimicked the interruption of voiding. To study the somatotopy of the cortical representations, flexion-extension movements of the right toes were performed as a control task. Functional magnetic resonance imaging during pelvic floor contractions detected activity of the supplementary motor area in the medial wall and of the midcingulate cortex, insula, posterior parietal cortex, putamen, thalamus, cerebellar vermis and upper ventral pons. There were no significant differences in activation between slow and fast contractions. Toe movements involved significantly stronger activity of the paracentral lobule (ie the medial primary motor cortex) than did the pelvic floor contractions. Otherwise the areas active during pelvic floor and leg muscle contractions overlapped considerably. The motor cortical representation of pelvic floor muscles is located mostly in the supplementary motor area. It extends further ventrally and anteriorly than the representation of distal leg muscles. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Linear summation of outputs in a balanced network model of motor cortex.

PubMed

Capaday, Charles; van Vreeswijk, Carl

2015-01-01

Given the non-linearities of the neural circuitry's elements, we would expect cortical circuits to respond non-linearly when activated. Surprisingly, when two points in the motor cortex are activated simultaneously, the EMG responses are the linear sum of the responses evoked by each of the points activated separately. Additionally, the corticospinal transfer function is close to linear, implying that the synaptic interactions in motor cortex must be effectively linear. To account for this, here we develop a model of motor cortex composed of multiple interconnected points, each comprised of reciprocally connected excitatory and inhibitory neurons. We show how non-linearities in neuronal transfer functions are eschewed by strong synaptic interactions within each point. Consequently, the simultaneous activation of multiple points results in a linear summation of their respective outputs. We also consider the effects of reduction of inhibition at a cortical point when one or more surrounding points are active. The network response in this condition is linear over an approximately two- to three-fold decrease of inhibitory feedback strength. This result supports the idea that focal disinhibition allows linear coupling of motor cortical points to generate movement related muscle activation patterns; albeit with a limitation on gain control. The model also explains why neural activity does not spread as far out as the axonal connectivity allows, whilst also explaining why distant cortical points can be, nonetheless, functionally coupled by focal disinhibition. Finally, we discuss the advantages that linear interactions at the cortical level afford to motor command synthesis.

fMRI reveals two distinct cerebral networks subserving speech motor control.

PubMed

Riecker, A; Mathiak, K; Wildgruber, D; Erb, M; Hertrich, I; Grodd, W; Ackermann, H

2005-02-22

There are few data on the cerebral organization of motor aspects of speech production and the pathomechanisms of dysarthric deficits subsequent to brain lesions and diseases. The authors used fMRI to further examine the neural basis of speech motor control. In eight healthy volunteers, fMRI was performed during syllable repetitions synchronized to click trains (2 to 6 Hz; vs a passive listening task). Bilateral hemodynamic responses emerged at the level of the mesiofrontal and sensorimotor cortex, putamen/pallidum, thalamus, and cerebellum (two distinct activation spots at either side). In contrast, dorsolateral premotor cortex and anterior insula showed left-sided activation. Calculation of rate/response functions revealed a negative linear relationship between repetition frequency and blood oxygen level-dependent (BOLD) signal change within the striatum, whereas both cerebellar hemispheres exhibited a step-wise increase of activation at approximately 3 Hz. Analysis of the temporal dynamics of the BOLD effect found the various cortical and subcortical brain regions engaged in speech motor control to be organized into two separate networks (medial and dorsolateral premotor cortex, anterior insula, and superior cerebellum vs sensorimotor cortex, basal ganglia, and inferior cerebellum). These data provide evidence for two levels of speech motor control bound, most presumably, to motor preparation and execution processes. They also help to explain clinical observations such as an unimpaired or even accelerated speaking rate in Parkinson disease and slowed speech tempo, which does not fall below a rate of 3 Hz, in cerebellar disorders.

Effects of intermittent theta-burst stimulation on practice-related changes in fast finger movements in healthy subjects.

PubMed

Agostino, Rocco; Iezzi, Ennio; Dinapoli, Loredana; Suppa, Antonio; Conte, Antonella; Berardelli, Alfredo

2008-08-01

In this paper we investigated the effects of intermittent theta-burst stimulation (iTBS) applied to the primary motor cortex on practice-related changes in motor performance. Seventeen healthy subjects underwent two experimental sessions, one testing real iTBS and the other testing sham iTBS. Before and after both iTBS sessions, the subjects practiced fast right index-finger abductions for a few minutes. As measures of cortical excitability we calculated resting motor threshold and motor-evoked potential amplitude. As measures of practice-related changes we evaluated the mean movement amplitude, peak velocity and peak acceleration values for each block. When subjects practiced the movement task, the three variables measuring practice-related changes improved to a similar extent during real and sham iTBS whereas cortical excitability increased only during real iTBS. In a further group of five healthy subjects we investigated the effect of real and sham iTBS on changes in motor performance after a longer task practice and found no significant changes in motor performance and retention after real and sham iTBS. From our results overall we conclude that in healthy subjects iTBS applied to the primary motor cortex leaves practice-related changes in an index finger abduction task unaffected. We suggest that iTBS delivered over the primary motor cortex is insufficient to alter motor performance because early motor learning probably engages a wide cortical and subcortical network.

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.

Mapping Horizontal Spread of Activity in Monkey Motor Cortex Using Single Pulse Microstimulation

PubMed Central

Riehle, Alexa; Brochier, Thomas G.

2016-01-01

Anatomical studies have demonstrated that distant cortical points are interconnected through long range axon collaterals of pyramidal cells. However, the functional properties of these intrinsic synaptic connections, especially their relationship with the cortical representations of body movements, have not been systematically investigated. To address this issue, we used multielectrode arrays chronically implanted in the motor cortex of two rhesus monkeys to analyze the effects of single-pulse intracortical microstimulation (sICMS) applied at one electrode on the neuronal activities recorded at all other electrodes. The temporal and spatial distribution of the evoked responses of single and multiunit activities was quantified to determine the properties of horizontal propagation. The typical responses were characterized by a brief excitatory peak followed by inhibition of longer duration. Significant excitatory responses to sICMS could be evoked up to 4 mm away from the stimulation site, but the strength of the response decreased exponentially and its latency increased linearly with the distance. We then quantified the direction and strength of the propagation in relation to the somatotopic organization of the motor cortex. We observed that following sICMS the propagation of neural activity is mainly directed rostro-caudally near the central sulcus but follows medio-lateral direction at the most anterior electrodes. The fact that these interactions are not entirely symmetrical may characterize a critical functional property of the motor cortex for the control of upper limb movements. Overall, these results support the assumption that the motor cortex is not functionally homogeneous but forms a complex network of interacting subregions. PMID:28018182

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.

Neural Population Dynamics during Reaching Are Better Explained by a Dynamical System than Representational Tuning

PubMed Central

Dann, Benjamin

2016-01-01

Recent models of movement generation in motor cortex have sought to explain neural activity not as a function of movement parameters, known as representational models, but as a dynamical system acting at the level of the population. Despite evidence supporting this framework, the evaluation of representational models and their integration with dynamical systems is incomplete in the literature. Using a representational velocity-tuning based simulation of center-out reaching, we show that incorporating variable latency offsets between neural activity and kinematics is sufficient to generate rotational dynamics at the level of neural populations, a phenomenon observed in motor cortex. However, we developed a covariance-matched permutation test (CMPT) that reassigns neural data between task conditions independently for each neuron while maintaining overall neuron-to-neuron relationships, revealing that rotations based on the representational model did not uniquely depend on the underlying condition structure. In contrast, rotations based on either a dynamical model or motor cortex data depend on this relationship, providing evidence that the dynamical model more readily explains motor cortex activity. Importantly, implementing a recurrent neural network we demonstrate that both representational tuning properties and rotational dynamics emerge, providing evidence that a dynamical system can reproduce previous findings of representational tuning. Finally, using motor cortex data in combination with the CMPT, we show that results based on small numbers of neurons or conditions should be interpreted cautiously, potentially informing future experimental design. Together, our findings reinforce the view that representational models lack the explanatory power to describe complex aspects of single neuron and population level activity. PMID:27814352

Neural Population Dynamics during Reaching Are Better Explained by a Dynamical System than Representational Tuning.

PubMed

Michaels, Jonathan A; Dann, Benjamin; Scherberger, Hansjörg

2016-11-01

Recent models of movement generation in motor cortex have sought to explain neural activity not as a function of movement parameters, known as representational models, but as a dynamical system acting at the level of the population. Despite evidence supporting this framework, the evaluation of representational models and their integration with dynamical systems is incomplete in the literature. Using a representational velocity-tuning based simulation of center-out reaching, we show that incorporating variable latency offsets between neural activity and kinematics is sufficient to generate rotational dynamics at the level of neural populations, a phenomenon observed in motor cortex. However, we developed a covariance-matched permutation test (CMPT) that reassigns neural data between task conditions independently for each neuron while maintaining overall neuron-to-neuron relationships, revealing that rotations based on the representational model did not uniquely depend on the underlying condition structure. In contrast, rotations based on either a dynamical model or motor cortex data depend on this relationship, providing evidence that the dynamical model more readily explains motor cortex activity. Importantly, implementing a recurrent neural network we demonstrate that both representational tuning properties and rotational dynamics emerge, providing evidence that a dynamical system can reproduce previous findings of representational tuning. Finally, using motor cortex data in combination with the CMPT, we show that results based on small numbers of neurons or conditions should be interpreted cautiously, potentially informing future experimental design. Together, our findings reinforce the view that representational models lack the explanatory power to describe complex aspects of single neuron and population level activity.

Stuttering as a trait or state - an ALE meta-analysis of neuroimaging studies.

PubMed

Belyk, Michel; Kraft, Shelly Jo; Brown, Steven

2015-01-01

Stuttering is a speech disorder characterised by repetitions, prolongations and blocks that disrupt the forward movement of speech. An earlier meta-analysis of brain imaging studies of stuttering (Brown et al., 2005) revealed a general trend towards rightward lateralization of brain activations and hyperactivity in the larynx motor cortex bilaterally. The present study sought not only to update that meta-analysis with recent work but to introduce an important distinction not present in the first study, namely the difference between 'trait' and 'state' stuttering. The analysis of trait stuttering compares people who stutter (PWS) with people who do not stutter when behaviour is controlled for, i.e., when speech is fluent in both groups. In contrast, the analysis of state stuttering examines PWS during episodes of stuttered speech compared with episodes of fluent speech. Seventeen studies were analysed using activation likelihood estimation. Trait stuttering was characterised by the well-known rightward shift in lateralization for language and speech areas. State stuttering revealed a more diverse pattern. Abnormal activation of larynx and lip motor cortex was common to the two analyses. State stuttering was associated with overactivation in the right hemisphere larynx and lip motor cortex. Trait stuttering was associated with overactivation of lip motor cortex in the right hemisphere but underactivation of larynx motor cortex in the left hemisphere. These results support a large literature highlighting laryngeal and lip involvement in the symptomatology of stuttering, and disambiguate two possible sources of activation in neuroimaging studies of persistent developmental stuttering. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Surmounting retraining limits in musicians' dystonia by transcranial stimulation.

PubMed

Furuya, Shinichi; Nitsche, Michael A; Paulus, Walter; Altenmüller, Eckart

2014-05-01

Abnormal cortical excitability is evident in various movement disorders that compromise fine motor control. Here we tested whether skilled finger movements can be restored in musicians with focal hand dystonia through behavioral training assisted by transcranial direct current stimulation to the motor cortex of both hemispheres. The bilateral motor cortices of 20 pianists (10 with focal dystonia, 10 healthy controls) were electrically stimulated noninvasively during bimanual mirrored finger movements. We found improvement in the rhythmic accuracy of sequential finger movements with the affected hand during and after cathodal stimulation over the affected cortex and simultaneous anodal stimulation over the unaffected cortex. The improvement was retained 4 days after intervention. Neither a stimulation with the reversed montage of electrodes nor sham stimulation yielded any improvement. Furthermore, the amount of improvement was positively correlated with the severity of the symptoms. Bihemispheric stimulation without concurrent motor training failed to improve fine motor control, underlining the importance of combined retraining and stimulation for restoring the dystonic symptoms. For the healthy pianists, none of the stimulation protocols enhanced movement accuracy. These results suggest a therapeutic potential of behavioral training assisted by bihemispheric, noninvasive brain stimulation in restoring fine motor control in focal dystonia. © 2014 American Neurological Association.

Primary motor cortex functionally contributes to language comprehension: An online rTMS study.

PubMed

Vukovic, Nikola; Feurra, Matteo; Shpektor, Anna; Myachykov, Andriy; Shtyrov, Yury

2017-02-01

Among various questions pertinent to grounding human cognitive functions in a neurobiological substrate, the association between language and motor brain structures is a particularly debated one in neuroscience and psychology. While many studies support a broadly distributed model of language and semantics grounded, among other things, in the general modality-specific systems, theories disagree as to whether motor and sensory cortex activity observed during language processing is functional or epiphenomenal. Here, we assessed the role of motor areas in linguistic processing by investigating the responses of 28 healthy volunteers to different word types in semantic and lexical decision tasks, following repetitive transcranial magnetic stimulation (rTMS) of primary motor cortex. We found that early rTMS (delivered within 200ms of word onset) produces a left-lateralised and meaning-specific change in reaction speed, slowing down behavioural responses to action-related words, and facilitating abstract words - an effect present only during semantic, but not lexical, decision. We interpret these data in light of action-perception theory of language, bolstering the claim that motor cortical areas play a functional role in language comprehension. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chronic ethanol exposure during adolescence in rats induces motor impairments and cerebral cortex damage associated with oxidative stress.

PubMed

Teixeira, Francisco Bruno; Santana, Luana Nazaré da Silva; Bezerra, Fernando Romualdo; De Carvalho, Sabrina; Fontes-Júnior, Enéas Andrade; Prediger, Rui Daniel; Crespo-López, Maria Elena; Maia, Cristiane Socorro Ferraz; Lima, Rafael Rodrigues

2014-01-01

Binge drinking is common among adolescents, and this type of ethanol exposure may lead to long-term nervous system damage. In the current study, we evaluated motor performance and tissue alterations in the cerebral cortex of rats subjected to intermittent intoxication with ethanol from adolescence to adulthood. Adolescent male Wistar rats (35 days old) were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v) during 55 days by gavage to complete 90 days of age. The open field, inclined plane and the rotarod tests were used to assess the spontaneous locomotor activity and motor coordination performance in adult animals. Following completion of behavioral tests, half of animals were submitted to immunohistochemical evaluation of NeuN (marker of neuronal bodies), GFAP (a marker of astrocytes) and Iba1 (microglia marker) in the cerebral cortex while the other half of the animals were subjected to analysis of oxidative stress markers by biochemical assays. Chronic ethanol intoxication in rats from adolescence to adulthood induced significant motor deficits including impaired spontaneous locomotion, coordination and muscle strength. These behavioral impairments were accompanied by marked changes in all cellular populations evaluated as well as increased levels of nitrite and lipid peroxidation in the cerebral cortex. These findings indicate that continuous ethanol intoxication from adolescence to adulthood is able to provide neurobehavioral and neurodegenerative damage to cerebral cortex.

[The effect of the iontophoretic administration of glutamate on the organization of interneuronal interactions in the rabbit motor cortex].

PubMed

Khokhlova, V N

1999-01-01

The multiunit activity of neurons in the motor cortex was recorded in 6 rabbits during glutamate (or physiological saline) iontophoretic application. Interaction between the neighboring neurons was evaluated by means of statistical cross-correlation analysis of spike trains. It was found that glutamate did not produce significant changes in cross-correlations.

Aberrant Neuromagnetic Activation in the Motor Cortex in Children with Acute Migraine: A Magnetoencephalography Study

PubMed Central

Guo, Xinyao; Xiang, Jing; Wang, Yingying; O’Brien, Hope; Kabbouche, Marielle; Horn, Paul; Powers, Scott W.; Hershey, Andrew D.

2012-01-01

Migraine attacks have been shown to interfere with normal function in the brain such as motor or sensory function. However, to date, there has been no clinical neurophysiology study focusing on the motor function in children with migraine during headache attacks. To investigate the motor function in children with migraine, twenty-six children with acute migraine, meeting International Classification of Headache Disorders criteria and age- and gender-matched healthy children were studied using a 275-channel magnetoencephalography system. A finger-tapping paradigm was designed to elicit neuromagnetic activation in the motor cortex. Children with migraine showed significantly prolonged latency of movement-evoked magnetic fields (MEF) during finger movement compared with the controls. The correlation coefficient of MEF latency and age in children with migraine was significantly different from that in healthy controls. The spectral power of high gamma (65–150 Hz) oscillations during finger movement in the primary motor cortex is also significantly higher in children with migraine than in controls. The alteration of responding latency and aberrant high gamma oscillations suggest that the developmental trajectory of motor function in children with migraine is impaired during migraine attacks and/or developmentally delayed. This finding indicates that childhood migraine may affect the development of brain function and result in long-term problems. PMID:23185541

Reduced activation and altered laterality in two neuroleptic-naive catatonic patients during a motor task in functional MRI.

PubMed

Northoff, G; Braus, D F; Sartorius, A; Khoram-Sefat, D; Russ, M; Eckert, J; Herrig, M; Leschinger, A; Bogerts, B; Henn, F A

1999-07-01

Catatonia, a symptom complex with motor, affective and cognitive symptoms seen in a variety of psychotic conditions and with organic disease, was examined using a motor task using functional magnetic resonance imaging (fMRI). Two acute catatonic patients and two age- and sex-matched healthy controls performed sequential finger opposition (SFO) after being medicated with 2 mg of lorazepam (i.v.). Functional magnetic resonance images were collected using a gradient echo pulse sequence (EPI). Patients with catatonia showed reduced motor activation of the contralateral motor cortex during SFO of the right hand, ipsilateral activation was similar for patients and controls. There were no differences in the activation of the SMA. During left hand activation the right-handed catatonic patients showed more activation in the ipsilateral cortex, a reversal from the normal pattern of activation in which the contralateral side shows four to five times more activation than the ipsilateral side. In catatonic patients there is a decreased activation in motor cortex during a motor task compared to matched medicated healthy controls. In addition activation of the non-dominant side, left-handed activity in right-handed patients, results in a total reversal of the normal pattern of lateral activation suggesting a disturbance in hemispheric localization of activity during a catatonic state.

Pain Relief in CRPS-II after Spinal Cord and Motor Cortex Simultaneous Dual Stimulation.

PubMed

Lopez, William Oc; Barbosa, Danilo C; Teixera, Manoel J; Paiz, Martin; Moura, Leonardo; Monaco, Bernardo A; Fonoff, Erich T

2016-05-01

We describe a case of a 30-year-old woman who suffered a traumatic injury of the right brachial plexus, developing severe complex regional pain syndrome type II (CRPS-II). After clinical treatment failure, spinal cord stimulation (SCS) was indicated with initial positive pain control. However, after 2 years her pain progressively returned to almost baseline intensity before SCS. Additional motor cortex electrode implant was then proposed as a rescue therapy and connected to the same pulse generator. This method allowed simultaneous stimulation of the motor cortex and SCS in cycling mode with independent stimulation parameters in each site. At 2 years follow-up, the patient reported sustained improvement in pain with dual stimulation, reduction of painful crises, and improvement in quality of life. The encouraging results in this case suggests that this can be an option as add-on therapy over SCS as a possible rescue therapy in the management of CRPS-II. However, comparative studies must be performed in order to determine the effectiveness of this therapy. Chronic neuropathic pain, Complex regional pain syndrome Type II, brachial plexus injury, motor cortex stimulation, spinal cord stimulation.

Attentional load and sensory competition in human vision: modulation of fMRI responses by load at fixation during task-irrelevant stimulation in the peripheral visual field.

PubMed

Schwartz, Sophie; Vuilleumier, Patrik; Hutton, Chloe; Maravita, Angelo; Dolan, Raymond J; Driver, Jon

2005-06-01

Perceptual suppression of distractors may depend on both endogenous and exogenous factors, such as attentional load of the current task and sensory competition among simultaneous stimuli, respectively. We used functional magnetic resonance imaging (fMRI) to compare these two types of attentional effects and examine how they may interact in the human brain. We varied the attentional load of a visual monitoring task performed on a rapid stream at central fixation without altering the central stimuli themselves, while measuring the impact on fMRI responses to task-irrelevant peripheral checkerboards presented either unilaterally or bilaterally. Activations in visual cortex for irrelevant peripheral stimulation decreased with increasing attentional load at fixation. This relative decrease was present even in V1, but became larger for successive visual areas through to V4. Decreases in activation for contralateral peripheral checkerboards due to higher central load were more pronounced within retinotopic cortex corresponding to 'inner' peripheral locations relatively near the central targets than for more eccentric 'outer' locations, demonstrating a predominant suppression of nearby surround rather than strict 'tunnel vision' during higher task load at central fixation. Contralateral activations for peripheral stimulation in one hemifield were reduced by competition with concurrent stimulation in the other hemifield only in inferior parietal cortex, not in retinotopic areas of occipital visual cortex. In addition, central attentional load interacted with competition due to bilateral versus unilateral peripheral stimuli specifically in posterior parietal and fusiform regions. These results reveal that task-dependent attentional load, and interhemifield stimulus-competition, can produce distinct influences on the neural responses to peripheral visual stimuli within the human visual system. These distinct mechanisms in selective visual processing may be integrated within posterior parietal areas, rather than earlier occipital cortex.

Reticular formation responses to magnetic brain stimulation of primary motor cortex

PubMed Central

Fisher, Karen M; Zaaimi, Boubker; Baker, Stuart N

2012-01-01

Transcranial magnetic stimulation (TMS) of cerebral cortex is a popular technique for the non-invasive investigation of motor function. TMS is often assumed to influence spinal circuits solely via the corticospinal tract. We were interested in possible trans-synaptic effects of cortical TMS on the ponto-medullary reticular formation in the brainstem, which is the source of the reticulospinal tract and could also generate spinal motor output. We recorded from 210 single units in the reticular formation of three anaesthetized macaque monkeys whilst TMS was performed over primary motor cortex. Short latency responses were observed consistent with activation of a cortico-reticular pathway. However, we also demonstrated surprisingly powerful responses at longer latency, which often appeared at lower threshold than the earlier effects. These late responses seemed to be generated partly as a consequence of the sound click made by coil discharge, and changed little with coil location. This novel finding has implications for the design of future studies using TMS, as well as suggesting a means of non-invasively probing an otherwise inaccessible important motor centre. PMID:22674723

Reticular formation responses to magnetic brain stimulation of primary motor cortex.

PubMed

Fisher, Karen M; Zaaimi, Boubker; Baker, Stuart N

2012-08-15

Transcranial magnetic stimulation (TMS) of cerebral cortex is a popular technique for the non-invasive investigation of motor function. TMS is often assumed to influence spinal circuits solely via the corticospinal tract. We were interested in possible trans-synaptic effects of cortical TMS on the ponto-medullary reticular formation in the brainstem, which is the source of the reticulospinal tract and could also generate spinal motor output. We recorded from 210 single units in the reticular formation of three anaesthetized macaque monkeys whilst TMS was performed over primary motor cortex. Short latency responses were observed consistent with activation of a cortico-reticular pathway. However, we also demonstrated surprisingly powerful responses at longer latency, which often appeared at lower threshold than the earlier effects. These late responses seemed to be generated partly as a consequence of the sound click made by coil discharge, and changed little with coil location. This novel finding has implications for the design of future studies using TMS, as well as suggesting a means of non-invasively probing an otherwise inaccessible important motor centre.

Regional microstructural organization of the cerebral cortex is affected by preterm birth.

PubMed

Bouyssi-Kobar, Marine; Brossard-Racine, Marie; Jacobs, Marni; Murnick, Jonathan; Chang, Taeun; Limperopoulos, Catherine

2018-01-01

To compare regional cerebral cortical microstructural organization between preterm infants at term-equivalent age (TEA) and healthy full-term newborns, and to examine the impact of clinical risk factors on cerebral cortical micro-organization in the preterm cohort. We prospectively enrolled very preterm infants (gestational age (GA) at birth<32 weeks; birthweight<1500 g) and healthy full-term controls. Using non-invasive 3T diffusion tensor imaging (DTI) metrics, we quantified regional micro-organization in ten cerebral cortical areas: medial/dorsolateral prefrontal cortex, anterior/posterior cingulate cortex, insula, posterior parietal cortex, motor/somatosensory/auditory/visual cortex. ANCOVA analyses were performed controlling for sex and postmenstrual age at MRI. We studied 91 preterm infants at TEA and 69 full-term controls. Preterm infants demonstrated significantly higher diffusivity in the prefrontal, parietal, motor, somatosensory, and visual cortices suggesting delayed maturation of these cortical areas. Additionally, postnatal hydrocortisone treatment was related to accelerated microstructural organization in the prefrontal and somatosensory cortices. Preterm birth alters regional microstructural organization of the cerebral cortex in both neurocognitive brain regions and areas with primary sensory/motor functions. We also report for the first time a potential protective effect of postnatal hydrocortisone administration on cerebral cortical development in preterm infants.

Impact of Intensive Upper Limb Rehabilitation on Quality of Life: A Randomized Trial in Children with Unilateral Cerebral Palsy

ERIC Educational Resources Information Center

Sakzewski, Leanne; Carlon, Stacey; Shields, Nora; Ziviani, Jenny; Ware, Robert S.; Boyd, Roslyn N.

2012-01-01

Aim: The aim of this study was to determine whether constraint-induced movement therapy is more effective than bimanual training in improving the quality of life of children with unilateral cerebral palsy (CP). Method: Sixty-three children (mean age 10y 2mo [SD 2y 6mo]; 33 males, 30 females) with CP of the spastic motor type (n = 59) or with…

Motor Learning Curve and Long-Term Effectiveness of Modified Constraint-Induced Movement Therapy in Children with Unilateral Cerebral Palsy: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Geerdink, Yvonne; Aarts, Pauline; Geurts, Alexander C.

2013-01-01

The goal of this study was to determine the progression of manual dexterity during 6 weeks (54 h) (modified) constraint-induced movement therapy ((m)CIMT) followed by 2 weeks (18 h) bimanual training (BiT) in children with unilateral spastic cerebral palsy (CP), to establish whether and when a maximal training effect was reached and which factors…

Effect of streptozotocin-induced diabetes on motor representations in the motor cortex and corticospinal tract in rats.

PubMed

Muramatsu, Ken; Ikutomo, Masako; Tamaki, Toru; Shimo, Satoshi; Niwa, Masatoshi

2018-02-01

Motor disorders in patients with diabetes are associated with diabetic peripheral neuropathy, which can lead to symptoms such as lower extremity weakness. However, it is unclear whether central motor system disorders can disrupt motor function in patients with diabetes. In a streptozotocin-induced rat model of type 1 diabetes, we used intracortical microstimulation to evaluate motor representations in the motor cortex, recorded antidromic motor cortex responses to spinal cord stimulation to evaluate the function of corticospinal tract (CST) axons, and used retrograde labeling to evaluate morphological alterations of CST neurons. The diabetic rats exhibited size reductions in the hindlimb area at 4 weeks and in trunk and forelimb areas after 13 weeks, with the hindlimb and trunk area reductions being the most severe. Other areas were unaffected. Additionally, we observed reduced antidromic responses in CST neurons with axons projecting to lumbar spinal segments (CST-L) but not in those with axons projecting to cervical segments (CST-C). This was consistent with the observation that retrograde-labeled CST-L neurons were decreased in number following tracer injection into the spinal cord in diabetic animals but that CST-C neurons were preserved. These results show that diabetes disrupts the CST system components controlling hindlimb and trunk movement. This disruption may contribute to lower extremity weakness in patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Representation of the speech effectors in the human motor cortex: somatotopy or overlap?

PubMed

Takai, Osamu; Brown, Steven; Liotti, Mario

2010-04-01

Somatotopy within the orofacial region of the human motor cortex has been a central concept in interpreting the results of neuroimaging and transcranial magnetic stimulation studies of normal and disordered speech. Yet, somatotopy has been challenged by studies showing overlap among the effectors within the homunculus. In order to address this dichotomy, we performed four voxel-based meta-analyses of 54 functional neuroimaging studies of non-speech tasks involving respiration, lip movement, tongue movement, and swallowing, respectively. While the centers of mass of the clusters supported the classic homuncular view of the motor cortex, there was significant variability in the locations of the activation-coordinates among studies, resulting in an overlapping arrangement. This "somatotopy with overlap" might reflect the intrinsic functional interconnectedness of the oral effectors for speech production.

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.

Primary motor and premotor cortex in implicit sequence learning--evidence for competition between implicit and explicit human motor memory systems.

PubMed

Kantak, Shailesh S; Mummidisetty, Chaithanya K; Stinear, James W

2012-09-01

Implicit and explicit memory systems for motor skills compete with each other during and after motor practice. Primary motor cortex (M1) is known to be engaged during implicit motor learning, while dorsal premotor cortex (PMd) is critical for explicit learning. To elucidate the neural substrates underlying the interaction between implicit and explicit memory systems, adults underwent a randomized crossover experiment of anodal transcranial direct current stimulation (AtDCS) applied over M1, PMd or sham stimulation during implicit motor sequence (serial reaction time task, SRTT) practice. We hypothesized that M1-AtDCS during practice will enhance online performance and offline learning of the implicit motor sequence. In contrast, we also hypothesized that PMd-AtDCS will attenuate performance and retention of the implicit motor sequence. Implicit sequence performance was assessed at baseline, at the end of acquisition (EoA), and 24 h after practice (retention test, RET). M1-AtDCS during practice significantly improved practice performance and supported offline stabilization compared with Sham tDCS. Performance change from EoA to RET revealed that PMd-AtDCS during practice attenuated offline stabilization compared with M1-AtDCS and sham stimulation. The results support the role of M1 in implementing online performance gains and offline stabilization for implicit motor sequence learning. In contrast, enhancing the activity within explicit motor memory network nodes such as the PMd during practice may be detrimental to offline stabilization of the learned implicit motor sequence. These results support the notion of competition between implicit and explicit motor memory systems and identify underlying neural substrates that are engaged in this competition. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Motor cortex hand area and speech: implications for the development of language.

PubMed

Meister, Ingo Gerrit; Boroojerdi, Babak; Foltys, Henrik; Sparing, Roland; Huber, Walter; Töpper, Rudolf

2003-01-01

Recently a growing body of evidence has suggested that a functional link exists between the hand motor area of the language dominant hemisphere and the regions subserving language processing. We examined the excitability of the hand motor area and the leg motor area during reading aloud and during non-verbal oral movements using transcranial magnetic stimulation (TMS). During reading aloud, but not before or afterwards, excitability was increased in the hand motor area of the dominant hemisphere. This reading effect was found to be independent of the duration of speech. No such effect could be found in the contralateral hemisphere. The excitability of the leg area of the motor cortex remained unchanged during reading aloud. The excitability during non-verbal oral movements was slightly increased in both hemispheres. Our results are consistent with previous findings and may indicate a specific functional connection between the hand motor area and the cortical language network.

Event-related near-infrared spectroscopy detects conflict in the motor cortex in a Stroop task.

PubMed

Szűcs, Dénes; Killikelly, Clare; Cutini, Simone

2012-10-05

The Stroop effect is one of the most popular models of conflict processing in neuroscience and psychology. The response conflict theory of the Stroop effect explains decreased performance in the incongruent condition of Stroop tasks by assuming that the task-relevant and the task-irrelevant stimulus features elicit conflicting response tendencies. However, to date, there is not much explicit neural evidence supporting this theory. Here we used functional near-infrared imaging (fNIRS) to examine whether conflict at the level of the motor cortex can be detected in the incongruent relative to the congruent condition of a Stroop task. Response conflict was determined by comparing the activity of the hemisphere ipsilateral to the response hand in the congruent and incongruent conditions. First, results provided explicit hemodynamic evidence supporting the response conflict theory of the Stroop effect: there was greater motor cortex activation in the hemisphere ipsilateral to the response hand in the incongruent than in the congruent condition during the initial stage of the hemodynamic response. Second, as fNIRS is still a relatively novel technology, it is methodologically significant that our data shows that fNIRS is able to detect a brief and transient increase in hemodynamic activity localized to the motor cortex, which in this study is related to subthreshold motor response activation. Copyright © 2012 Elsevier B.V. All rights reserved.

Multiple forebrain systems converge on motor neurons innervating the thyroarytenoid muscle

PubMed Central

Van Daele, Douglas J.; Cassell, Martin D.

2009-01-01

The present study investigated the central connections of motor neurons innervating the thyroarytenoid laryngeal muscle that is active in swallowing, respiration and vocalization. In both intact and sympathectomized rats, the pseudorabies virus (PRV) was inoculated into the muscle. After initial infection of laryngomotor neurons in the ipsilateral loose division of the nucleus ambiguous (NA) by 3 days post-inoculation., PRV spread to the ipsilateral compact portion of the NA, the central and intermediate divisions of the nucleus tractus solitarii (NTS), the Botzinger complex, and the parvocellular reticular formation by 4 days. Infection was subsequently expanded to include the ipsilateral granular and dysgranular parietal insular cortex, the ipsilateral medial division of the central nucleus of the amygdala, the lateral, paraventricular, ventrolateral and medial preoptic nuclei of the hypothalamus (generally bilaterally), the lateral periaqueductal gray, the A7 and oral and caudal pontine nuclei. At the latest time points sampled post-inoculation (5 days), infected neurons were identified in the ipsilateral agranular insular cortex, the caudal parietal insular cortex, the anterior cingulate cortex, and the contralateral motor cortex. In the amygdala, infection had spread to the lateral central nucleus and the parvocellular portion of the basolateral nucleus. Hypothalamic infection was largely characterized by an increase in the number of infected cells in earlier infected regions though the posterior, dorsomedial, tuberomammillary and mammillary nuclei contained infected cells. Comparison with previous connectional data suggest PRV followed three interconnected systems originating in the forebrain; a bilateral system including the ventral anterior cingulate cortex, periaqueductal gray and ventral respiratory group; an ipsilateral system involving the parietal insular cortex, central nucleus of the amygdala and parvicellular reticular formation, and a minor contralateral system originating in motor cortex. Hypothalamic innervation involved several functionally specific nuclei. Overall, the data imply complex central nervous system control over the multi-functional thyroarytenoid muscle.[297 words] PMID:19426785

Millisecond-timescale local network coding in the rat primary somatosensory cortex.

PubMed

Eldawlatly, Seif; Oweiss, Karim G

2011-01-01

Correlation among neocortical neurons is thought to play an indispensable role in mediating sensory processing of external stimuli. The role of temporal precision in this correlation has been hypothesized to enhance information flow along sensory pathways. Its role in mediating the integration of information at the output of these pathways, however, remains poorly understood. Here, we examined spike timing correlation between simultaneously recorded layer V neurons within and across columns of the primary somatosensory cortex of anesthetized rats during unilateral whisker stimulation. We used bayesian statistics and information theory to quantify the causal influence between the recorded cells with millisecond precision. For each stimulated whisker, we inferred stable, whisker-specific, dynamic bayesian networks over many repeated trials, with network similarity of 83.3±6% within whisker, compared to only 50.3±18% across whiskers. These networks further provided information about whisker identity that was approximately 6 times higher than what was provided by the latency to first spike and 13 times higher than what was provided by the spike count of individual neurons examined separately. Furthermore, prediction of individual neurons' precise firing conditioned on knowledge of putative pre-synaptic cell firing was 3 times higher than predictions conditioned on stimulus onset alone. Taken together, these results suggest the presence of a temporally precise network coding mechanism that integrates information across neighboring columns within layer V about vibrissa position and whisking kinetics to mediate whisker movement by motor areas innervated by layer V.

Regional specificity of aberrant thalamocortical connectivity in autism.

PubMed

Nair, Aarti; Carper, Ruth A; Abbott, Angela E; Chen, Colleen P; Solders, Seraphina; Nakutin, Sarah; Datko, Michael C; Fishman, Inna; Müller, Ralph-Axel

2015-11-01

Preliminary evidence suggests aberrant (mostly reduced) thalamocortical (TC) connectivity in autism spectrum disorder (ASD), but despite the crucial role of thalamus in sensorimotor functions and its extensive connectivity with cerebral cortex, relevant evidence remains limited. We performed a comprehensive investigation of region-specific TC connectivity in ASD. Resting-state functional MRI and diffusion tensor imaging (DTI) data were acquired for 60 children and adolescents with ASD (ages 7-17 years) and 45 age, sex, and IQ-matched typically developing (TD) participants. We examined intrinsic functional connectivity (iFC) and anatomical connectivity (probabilistic tractography) with thalamus, using 68 unilateral cerebral cortical regions of interest (ROIs). For frontal and parietal lobes, iFC was atypically reduced in the ASD group for supramodal association cortices, but was increased for cingulate gyri and motor cortex. Temporal iFC was characterized by overconnectivity for auditory cortices, but underconnectivity for amygdalae. Occipital iFC was broadly reduced in the ASD group. DTI indices (such as increased radial diffusion) for regions with group differences in iFC further indicated compromised anatomical connectivity, especially for frontal ROIs, in the ASD group. Our findings highlight the regional specificity of aberrant TC connectivity in ASD. Their overall pattern can be largely accounted for by functional overconnectivity with limbic and sensorimotor regions, but underconnectivity with supramodal association cortices. This could be related to comparatively early maturation of limbic and sensorimotor regions in the context of early overgrowth in ASD, at the expense of TC connectivity with later maturing cortical regions. © 2015 Wiley Periodicals, Inc.

Early growth hormone (GH) treatment promotes relevant motor functional improvement after severe frontal cortex lesion in adult rats.

PubMed

Heredia, Margarita; Fuente, A; Criado, J; Yajeya, J; Devesa, J; Riolobos, A S

2013-06-15

A number of studies, in animals and humans, describe the positive effects of the growth hormone (GH) treatment combined with rehabilitation on brain reparation after brain injury. We examined the effect of GH treatment and rehabilitation in adult rats with severe frontal motor cortex ablation. Thirty-five male rats were trained in the paw-reaching-for-food task and the preferred forelimb was recorded. Under anesthesia, the motor cortex contralateral to the preferred forelimb was aspirated or sham-operated. Animals were then treated with GH (0.15 mg/kg/day, s.c) or vehicle during 5 days, commencing immediately or 6 days post-lesion. Rehabilitation was applied at short- and long-term after GH treatment. Behavioral data were analized by ANOVA following Bonferroni post hoc test. After sacrifice, immunohistochemical detection of glial fibrillary acid protein (GFAP) and nestin were undertaken in the brain of all groups. Animal group treated with GH immediately after the lesion, but not any other group, showed a significant improvement of the motor impairment induced by the motor lesion, and their performances in the motor test were no different from sham-operated controls. GFAP immunolabeling and nestin immunoreactivity were observed in the perilesional area in all injured animals; nestin immunoreactivity was higher in GH-treated injured rats (mainly in animals GH-treated 6 days post-lesion). GFAP immunoreactivity was similar among injured rats. Interestingly, nestin re-expression was detected in the contralateral undamaged motor cortex only in GH-treated injured rats, being higher in animals GH-treated immediately after the lesion than in animals GH-treated 6 days post-lesion. Early GH treatment induces significant recovery of the motor impairment produced by frontal cortical ablation. GH effects include increased neurogenesis for reparation (perilesional area) and for increased brain plasticity (contralateral motor area). Copyright © 2013 Elsevier B.V. All rights reserved.

Nonparetic arm force does not overinhibit the paretic arm in chronic poststroke hemiparesis.

PubMed

Dimyan, Michael A; Perez, Monica A; Auh, Sungyoung; Tarula, Erick; Wilson, Matthew; Cohen, Leonardo G

2014-05-01

To determine whether nonparetic arm force overinhibits the paretic arm in patients with chronic unilateral poststroke hemiparesis. Case-control neurophysiological and behavioral study of patients with chronic stroke. Research institution. Eighty-six referred patients were screened to enroll 9 participants (N=9) with a >6 month history of 1 unilateral ischemic infarct that resulted in arm hemiparesis with residual ability to produce 1Nm of wrist flexion torque and without contraindication to transcranial magnetic stimulation. Eight age- and handedness-matched healthy volunteers without neurologic diagnosis were studied for comparison. Not applicable. Change in interhemispheric inhibition targeting the ipsilesional primary motor cortex (M1) during nonparetic arm force. We hypothesized that interhemispheric inhibition would increase more in healthy controls than in patients with hemiparesis. Healthy age-matched controls had significantly greater increases in inhibition from their active to resting M1 than patients with stroke from their active contralesional to resting ipsilesional M1 in the same scenario (20%±7% vs -1%±4%, F1,12=6.61, P=.025). Patients with greater increases in contralesional to ipsilesional inhibition were better performers on the 9-hole peg test of paretic arm function. Our findings reveal that producing force with the nonparetic arm does not necessarily overinhibit the paretic arm. Though our study is limited in generalizability by the small sample size, we found that greater active contralesional to resting ipsilesional M1 inhibition was related with better recovery in this subset of patients with chronic poststroke. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Clinical Characteristics and Lesions Responsible for Swallowing Hesitation After Acute Cerebral Infarction.

PubMed

Saito, Tsukasa; Hayashi, Keisuke; Nakazawa, Hajime; Ota, Tetsuo

2016-08-01

Some stroke patients with a unilateral lesion demonstrate acute dysphagia characterized by a markedly prolonged swallowing time, making us think they are reluctant to swallow. In order to clarify the clinical characteristics and causative lesions of delayed swallowing, we conducted a retrospective analysis of 20 right-handed patients without a history of swallowing dysfunction who underwent videofluorography on suspicion of dysphagia after a first ischemic stroke. The oral processing time plus the postfaucial aggregation time required to swallow jelly for patients classified as having delayed swallowing was over 10 s. The time required for swallowing jelly was significantly longer than that without the hesitation (median value, 24.1 vs. 8.9 s, P < 0.001). The oral processing time plus the postfaucial aggregation time required for patients with delayed swallowing to swallow thickened water was largely over 5 s and significantly longer than that of patients without swallowing hesitation (median value, 10.2 vs. 3.3 s, P < 0.001). Swallowing hesitation caused by acute unilateral infarction could be separated into two different patterns. Because four of the five patients with a rippling tongue movement in the swallowing hesitation pattern had a lesion in the left primary motor cortex, which induces some kinds of apraxia, swallowing hesitation with a rippling tongue movement seems to be a representative characteristic of apraxia. The patients with swallowing hesitation with a temporary stasis of the tongue in this study tended to have broad lesions in the frontal lobe, especially in the middle frontal gyrus, which is thought to be involved in higher cognition.

Neural Signatures of Value Comparison in Human Cingulate Cortex during Decisions Requiring an Effort-Reward Trade-off

PubMed Central

Kennerley, Steven W.; Friston, Karl; Bestmann, Sven

2016-01-01

Integrating costs and benefits is crucial for optimal decision-making. Although much is known about decisions that involve outcome-related costs (e.g., delay, risk), many of our choices are attached to actions and require an evaluation of the associated motor costs. Yet how the brain incorporates motor costs into choices remains largely unclear. We used human fMRI during choices involving monetary reward and physical effort to identify brain regions that serve as a choice comparator for effort-reward trade-offs. By independently varying both options' effort and reward levels, we were able to identify the neural signature of a comparator mechanism. A network involving supplementary motor area and the caudal portion of dorsal anterior cingulate cortex encoded the difference in reward (positively) and effort levels (negatively) between chosen and unchosen choice options. We next modeled effort-discounted subjective values using a novel behavioral model. This revealed that the same network of regions involving dorsal anterior cingulate cortex and supplementary motor area encoded the difference between the chosen and unchosen options' subjective values, and that activity was best described using a concave model of effort-discounting. In addition, this signal reflected how precisely value determined participants' choices. By contrast, separate signals in supplementary motor area and ventromedial prefrontal cortex correlated with participants' tendency to avoid effort and seek reward, respectively. This suggests that the critical neural signature of decision-making for choices involving motor costs is found in human cingulate cortex and not ventromedial prefrontal cortex as typically reported for outcome-based choice. Furthermore, distinct frontal circuits seem to drive behavior toward reward maximization and effort minimization. SIGNIFICANCE STATEMENT The neural processes that govern the trade-off between expected benefits and motor costs remain largely unknown. This is striking because energetic requirements play an integral role in our day-to-day choices and instrumental behavior, and a diminished willingness to exert effort is a characteristic feature of a range of neurological disorders. We use a new behavioral characterization of how humans trade off reward maximization with effort minimization to examine the neural signatures that underpin such choices, using BOLD MRI neuroimaging data. We find the critical neural signature of decision-making, a signal that reflects the comparison of value between choice options, in human cingulate cortex, whereas two distinct brain circuits drive behavior toward reward maximization or effort minimization. PMID:27683898

Neural Signatures of Value Comparison in Human Cingulate Cortex during Decisions Requiring an Effort-Reward Trade-off.

PubMed

Klein-Flügge, Miriam C; Kennerley, Steven W; Friston, Karl; Bestmann, Sven

2016-09-28

Integrating costs and benefits is crucial for optimal decision-making. Although much is known about decisions that involve outcome-related costs (e.g., delay, risk), many of our choices are attached to actions and require an evaluation of the associated motor costs. Yet how the brain incorporates motor costs into choices remains largely unclear. We used human fMRI during choices involving monetary reward and physical effort to identify brain regions that serve as a choice comparator for effort-reward trade-offs. By independently varying both options' effort and reward levels, we were able to identify the neural signature of a comparator mechanism. A network involving supplementary motor area and the caudal portion of dorsal anterior cingulate cortex encoded the difference in reward (positively) and effort levels (negatively) between chosen and unchosen choice options. We next modeled effort-discounted subjective values using a novel behavioral model. This revealed that the same network of regions involving dorsal anterior cingulate cortex and supplementary motor area encoded the difference between the chosen and unchosen options' subjective values, and that activity was best described using a concave model of effort-discounting. In addition, this signal reflected how precisely value determined participants' choices. By contrast, separate signals in supplementary motor area and ventromedial prefrontal cortex correlated with participants' tendency to avoid effort and seek reward, respectively. This suggests that the critical neural signature of decision-making for choices involving motor costs is found in human cingulate cortex and not ventromedial prefrontal cortex as typically reported for outcome-based choice. Furthermore, distinct frontal circuits seem to drive behavior toward reward maximization and effort minimization. The neural processes that govern the trade-off between expected benefits and motor costs remain largely unknown. This is striking because energetic requirements play an integral role in our day-to-day choices and instrumental behavior, and a diminished willingness to exert effort is a characteristic feature of a range of neurological disorders. We use a new behavioral characterization of how humans trade off reward maximization with effort minimization to examine the neural signatures that underpin such choices, using BOLD MRI neuroimaging data. We find the critical neural signature of decision-making, a signal that reflects the comparison of value between choice options, in human cingulate cortex, whereas two distinct brain circuits drive behavior toward reward maximization or effort minimization. Copyright © 2016 Klein-Flügge et al.

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

Spatially dynamic recurrent information flow across long-range dorsal motor network encodes selective motor goals.

PubMed

Yoo, Peter E; Hagan, Maureen A; John, Sam E; Opie, Nicholas L; Ordidge, Roger J; O'Brien, Terence J; Oxley, Thomas J; Moffat, Bradford A; Wong, Yan T

2018-06-01

Performing voluntary movements involves many regions of the brain, but it is unknown how they work together to plan and execute specific movements. We recorded high-resolution ultra-high-field blood-oxygen-level-dependent signal during a cued ankle-dorsiflexion task. The spatiotemporal dynamics and the patterns of task-relevant information flow across the dorsal motor network were investigated. We show that task-relevant information appears and decays earlier in the higher order areas of the dorsal motor network then in the primary motor cortex. Furthermore, the results show that task-relevant information is encoded in general initially, and then selective goals are subsequently encoded in specifics subregions across the network. Importantly, the patterns of recurrent information flow across the network vary across different subregions depending on the goal. Recurrent information flow was observed across all higher order areas of the dorsal motor network in the subregions encoding for the current goal. In contrast, only the top-down information flow from the supplementary motor cortex to the frontoparietal regions, with weakened recurrent information flow between the frontoparietal regions and bottom-up information flow from the frontoparietal regions to the supplementary cortex were observed in the subregions encoding for the opposing goal. We conclude that selective motor goal encoding and execution rely on goal-dependent differences in subregional recurrent information flow patterns across the long-range dorsal motor network areas that exhibit graded functional specialization. © 2018 Wiley Periodicals, Inc.

Decreased spinal synaptic inputs to phrenic motor neurons elicit localized inactivity-induced phrenic motor facilitation

PubMed Central

Streeter, K.A.; Baker-Herman, T.L.

2014-01-01

Phrenic motor neurons receive rhythmic synaptic inputs throughout life. Since even brief disruption in phrenic neural activity is detrimental to life, on-going neural activity may play a key role in shaping phrenic motor output. To test the hypothesis that spinal mechanisms sense and respond to reduced phrenic activity, anesthetized, ventilated rats received micro-injections of procaine in the C2 ventrolateral funiculus (VLF) to transiently (~30 min) block axon conduction in bulbospinal axons from medullary respiratory neurons that innervate one phrenic motor pool; during procaine injections, contralateral phrenic neural activity was maintained. Once axon conduction resumed, a prolonged increase in phrenic burst amplitude was observed in the ipsilateral phrenic nerve, demonstrating inactivity-induced phrenic motor facilitation (iPMF). Inhibition of tumor necrosis factor alpha (TNFα) and atypical PKC (aPKC) activity in spinal segments containing the phrenic motor nucleus impaired ipsilateral iPMF, suggesting a key role for spinal TNFα and aPKC in iPMF following unilateral axon conduction block. A small phrenic burst amplitude facilitation was also observed contralateral to axon conduction block, indicating crossed spinal phrenic motor facilitation (csPMF). csPMF was independent of spinal TNFα and aPKC. Ipsilateral iPMF and csPMF following unilateral withdrawal of phrenic synaptic inputs were associated with proportional increases in phrenic responses to chemoreceptor stimulation (hypercapnia), suggesting iPMF and csPMF increase phrenic dynamic range. These data suggest that local, spinal mechanisms sense and respond to reduced synaptic inputs to phrenic motor neurons. We hypothesize that iPMF and csPMF may represent compensatory mechanisms that assure adequate motor output is maintained in a physiological system in which prolonged inactivity ends life. PMID:24681155

Motor cortex and spinal cord neuromodulation promote corticospinal tract axonal outgrowth and motor recovery after cervical contusion spinal cord injury.

PubMed

Zareen, N; Shinozaki, M; Ryan, D; Alexander, H; Amer, A; Truong, D Q; Khadka, N; Sarkar, A; Naeem, S; Bikson, M; Martin, J H

2017-11-01

Cervical injuries are the most common form of SCI. In this study, we used a neuromodulatory approach to promote skilled movement recovery and repair of the corticospinal tract (CST) after a moderately severe C4 midline contusion in adult rats. We used bilateral epidural intermittent theta burst (iTBS) electrical stimulation of motor cortex to promote CST axonal sprouting and cathodal trans-spinal direct current stimulation (tsDCS) to enhance spinal cord activation to motor cortex stimulation after injury. We used Finite Element Method (FEM) modeling to direct tsDCS to the cervical enlargement. Combined iTBS-tsDCS was delivered for 30min daily for 10days. We compared the effect of stimulation on performance in the horizontal ladder and the Irvine Beattie and Bresnahan forepaw manipulation tasks and CST axonal sprouting in injury-only and injury+stimulation animals. The contusion eliminated the dorsal CST in all animals. tsDCS significantly enhanced motor cortex evoked responses after C4 injury. Using this combined spinal-M1 neuromodulatory approach, we found significant recovery of skilled locomotion and forepaw manipulation skills compared with injury-only controls. The spared CST axons caudal to the lesion in both animal groups derived mostly from lateral CST axons that populated the contralateral intermediate zone. Stimulation enhanced injury-dependent CST axonal outgrowth below and above the level of the injury. This dual neuromodulatory approach produced partial recovery of skilled motor behaviors that normally require integration of posture, upper limb sensory information, and intent for performance. We propose that the motor systems use these new CST projections to control movements better after injury. Copyright © 2017 Elsevier Inc. All rights reserved.

Linking physics with physiology in TMS: a sphere field model to determine the cortical stimulation site in TMS.

PubMed

Thielscher, Axel; Kammer, Thomas

2002-11-01

A fundamental problem of transcranial magnetic stimulation (TMS) is determining the site and size of the stimulated cortical area. In the motor system, the most common procedure for this is motor mapping. The obtained two-dimensional distribution of coil positions with associated muscle responses is used to calculate a center of gravity on the skull. However, even in motor mapping the exact stimulation site on the cortex is not known and only rough estimates of its size are possible. We report a new method which combines physiological measurements with a physical model used to predict the electric field induced by the TMS coil. In four subjects motor responses in a small hand muscle were mapped with 9-13 stimulation sites at the head perpendicular to the central sulcus in order to keep the induced current direction constant in a given cortical region of interest. Input-output functions from these head locations were used to determine stimulator intensities that elicit half-maximal muscle responses. Based on these stimulator intensities the field distribution on the individual cortical surface was calculated as rendered from anatomical MR data. The region on the cortical surface in which the different stimulation sites produced the same electric field strength (minimal variance, 4.2 +/- 0.8%.) was determined as the most likely stimulation site on the cortex. In all subjects, it was located at the lateral part of the hand knob in the motor cortex. Comparisons of model calculations with the solutions obtained in this manner reveal that the stimulated cortex area innervating the target muscle is substantially smaller than the size of the electric field induced by the coil. Our results help to resolve fundamental questions raised by motor mapping studies as well as motor threshold measurements.

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.

Anodal transcranial direct current stimulation enhances the effects of motor imagery training in a finger tapping task.

PubMed

Saimpont, Arnaud; Mercier, Catherine; Malouin, Francine; Guillot, Aymeric; Collet, Christian; Doyon, Julien; Jackson, Philip L

2016-01-01

Motor imagery (MI) training and anodal transcranial direct current stimulation (tDCS) applied over the primary motor cortex can independently improve hand motor function. The main objective of this double-blind, sham-controlled study was to examine whether anodal tDCS over the primary motor cortex could enhance the effects of MI training on the learning of a finger tapping sequence. Thirty-six right-handed young human adults were assigned to one of three groups: (i) who performed MI training combined with anodal tDCS applied over the primary motor cortex; (ii) who performed MI training combined with sham tDCS; and (iii) who received tDCS while reading a book. The MI training consisted of mentally rehearsing an eight-item complex finger sequence for 13 min. Before (Pre-test), immediately after (Post-test 1), and at 90 min after (Post-test 2) MI training, the participants physically repeated the sequence as fast and as accurately as possible. An anova showed that the number of sequences correctly performed significantly increased between Pre-test and Post-test 1 and remained stable at Post-test 2 in the three groups (P < 0.001). Furthermore, the percentage increase in performance between Pre-test and Post-test 1 and Post-test 2 was significantly greater in the group that performed MI training combined with anodal tDCS compared with the other two groups (P < 0.05). As a potential physiological explanation, the synaptic strength within the primary motor cortex could have been reinforced by the association of MI training and tDCS compared with MI training alone and tDCS alone. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Effect of sensory and motor connectivity on hand function in pediatric hemiplegia.

PubMed

Gupta, Disha; Barachant, Alexandre; Gordon, Andrew M; Ferre, Claudio; Kuo, Hsing-Ching; Carmel, Jason B; Friel, Kathleen M

2017-11-01

We tested the hypothesis that somatosensory system injury would more strongly affect movement than motor system injury in children with unilateral cerebral palsy (USCP). This hypothesis was based on how somatosensory and corticospinal circuits adapt to injury during development; whereas the motor system can maintain connections to the impaired hand from the uninjured hemisphere, this does not occur in the somatosensory system. As a corollary, cortical injury strongly impairs sensory function, so we hypothesized that cortical lesions would impair hand function more than subcortical lesions. Twenty-four children with unilateral cerebral palsy had physiological and anatomical measures of the motor and somatosensory systems and lesion classification. Motor physiology was performed with transcranial magnetic stimulation and somatosensory physiology with vibration-evoked electroencephalographic potentials. Tractography of the corticospinal tract and the medial lemniscus was performed with diffusion tensor imaging, and lesions were classified by magnetic resonance imaging. Anatomical and physiological results were correlated with measures of hand function using 2 independent statistical methods. Children with disruptions in the somatosensory connectivity and cortical lesions had the most severe upper extremity impairments, particularly somatosensory function. Motor system connectivity was significantly correlated with bimanual function, but not unimanual function or somatosensory function. Both sensory and motor connectivity impact hand function in children with USCP. Somatosensory connectivity could be an important target for recovery of hand function in children with USCP. Ann Neurol 2017;82:766-780. © 2017 American Neurological Association.

The effects of sufentanil added to low-dose hyperbaric bupivacaine in unilateral spinal anaesthesia for outpatients undergoing knee arthroscopy.

PubMed

Sertöz, Nezih; Aysel, İnan; Uyar, Meltem

2014-01-01

The aim of this study is to examine the effects of sufentanil added to low-dose hyperbaric bupivacaine in unilateral spinal anaesthesia for outpatients undergoing knee arthroscopy. Sixty two patients (ASA I-II) aged 20 to 50 who were planning on undergoing a knee arthroscopy were enrolled in this study. Patients were randomly divided into two groups. Unilateral spinal anaesthesia with 1ml 0.5% hyperbaric bupivacaine was administered to Group B (n=33); and unilateral spinal anaesthesia with 0.5ml (2.5µg) sufentanil added to 1ml hyperbaric bupivacaine was administered to Group BS (n=29). There were no statistically significant differences observed between the groups in terms of demographic data, hemodynamic parameters, maximum sensorial, sympathetic and motor block levels, time to motor block resolution, and time of discharge (p>0.05). There were statistically significant differences between the groups in terms of two segments regression time (Group B=52 min., Group BS=59 min.), ambulation time (Group B=147 min., Group BS=157 min.) and urination time (Group B=136 min., Group BS=149 min.) (p<0.05). In this study, no itching was observed in Group B, whereas seven patients in Group BS were observed as having postoperative itching (p<0.05). All patients were successfully given unilateral spinal anaesthesia with sufentanil added to low-dose hyperbaric bupivacaine for an outpatient knee arthroscopy, without affecting the time of discharge. However, for one-day interventions such as arthroscopy, it was concluded that administration of only low-dose hyperbaric bupivacaine was sufficient.

Unilateral and bilateral upper extremity weight-bearing effect on upper extremity impairment and functional performance after brain injury

PubMed Central

REISTETTER, TIMOTHY; ABREU, BEATRIZ C.; BEAR-LEHMAN, JANE; OTTENBACHER, KENNETH J.

2010-01-01

The purpose of the study was to investigate the effect of upper extremity (UE) weight bearing on UE impairment functional performance of persons with acquired brain injury (BI). A quasi-experimental design was used to examine a convenience sample of 99 persons with acquired BI and 22 without BI (WBI) living in a community re-entry centre. A computerized force-sensing array pressure map system was used to determine the UE pressure during unilateral and bilateral conditions. Differences between groups were examined using t-tests. Correlations were computed between UE weight bearing and hand function, and functional performance as measured by the Fugl-Meyer scale and functional independence measure (FIM) scale. The group of people with BI exerted significantly lower UE weight bearing during unilateral conditions as compared with persons WBI [left: t (119) = 2.34, p = 0.021; right: t (119) = 4.79, p = 0.043). UE weight-bearing measures correlated strongly with FIM motor scores with bilateral UE conditions yielded the highest significant correlation (bilateral left r = 0.487, p < 0.001; bilateral right r = 0.469, p < 0.01). The results indicated that UE weight-bearing pressure differs in unilateral and bilateral conditions, between persons with and WBI and between persons with stroke and traumatic brain injury. These findings may have implications for occupational therapists that use unilateral versus bilateral motor training for rehabilitation. There is a need to replicate the study design with a randomized and stratified sample of persons with BI. PMID:19551694

Adaptability of the Immature Ocular Motor Control System: Unilateral IGF-1 Medial Rectus Treatment.

PubMed

Willoughby, Christy L; Fleuriet, Jérome; Walton, Mark M; Mustari, Michael J; McLoon, Linda K

2015-06-01

Unilateral treatment with sustained release IGF-1 to one medial rectus muscle in infant monkeys was performed to test the hypothesis that strabismus would develop as a result of changes in extraocular muscles during the critical period of development of binocularity. Sustained release IGF-1 pellets were implanted unilaterally on one medial rectus muscle in normal infant monkeys during the first 2 weeks of life. Eye position was monitored using standard photographic methods. After 3 months of treatment, myofiber and neuromuscular size, myosin composition, and innervation density were quantified in all rectus muscles and compared to those in age-matched controls. Sustained unilateral IGF-1 treatments resulted in strabismus for all treated subjects; 3 of the 4 subjects had a clinically significant strabismus of more than 10°. Both the treated medial rectus and the untreated ipsilateral antagonist lateral rectus muscles had significantly larger myofibers. No adaptation in myofiber size occurred in the contralateral functionally yoked lateral rectus or in myosin composition, neuromuscular junction size, or nerve density. Sustained unilateral IGF-1 treatment to extraocular muscles during the sensitive period of development of orthotropic eye alignment and binocularity was sufficient to disturb ocular motor development, resulting in strabismus in infant monkeys. This could be due to altering fusion of gaze during the early sensitive period. Serial measurements of eye alignment suggested the IGF-1-treated infants received insufficient coordinated binocular experience, preventing the establishment of normal eye alignment. Our results uniquely suggest that abnormal signaling by the extraocular muscles may be a cause of strabismus.

Adaptability of the Immature Ocular Motor Control System: Unilateral IGF-1 Medial Rectus Treatment

PubMed Central

Willoughby, Christy L.; Fleuriet, Jérome; Walton, Mark M.; Mustari, Michael J.; McLoon, Linda K.

2015-01-01

Purpose. Unilateral treatment with sustained release IGF-1 to one medial rectus muscle in infant monkeys was performed to test the hypothesis that strabismus would develop as a result of changes in extraocular muscles during the critical period of development of binocularity. Methods. Sustained release IGF-1 pellets were implanted unilaterally on one medial rectus muscle in normal infant monkeys during the first 2 weeks of life. Eye position was monitored using standard photographic methods. After 3 months of treatment, myofiber and neuromuscular size, myosin composition, and innervation density were quantified in all rectus muscles and compared to those in age-matched controls. Results. Sustained unilateral IGF-1 treatments resulted in strabismus for all treated subjects; 3 of the 4 subjects had a clinically significant strabismus of more than 10°. Both the treated medial rectus and the untreated ipsilateral antagonist lateral rectus muscles had significantly larger myofibers. No adaptation in myofiber size occurred in the contralateral functionally yoked lateral rectus or in myosin composition, neuromuscular junction size, or nerve density. Conclusions. Sustained unilateral IGF-1 treatment to extraocular muscles during the sensitive period of development of orthotropic eye alignment and binocularity was sufficient to disturb ocular motor development, resulting in strabismus in infant monkeys. This could be due to altering fusion of gaze during the early sensitive period. Serial measurements of eye alignment suggested the IGF-1-treated infants received insufficient coordinated binocular experience, preventing the establishment of normal eye alignment. Our results uniquely suggest that abnormal signaling by the extraocular muscles may be a cause of strabismus. PMID:26030103

Tinnitus Intensity Dependent Gamma Oscillations of the Contralateral Auditory Cortex

PubMed Central

van der Loo, Elsa; Gais, Steffen; Congedo, Marco; Vanneste, Sven; Plazier, Mark; Menovsky, Tomas; Van de Heyning, Paul; De Ridder, Dirk

2009-01-01

Background Non-pulsatile tinnitus is considered a subjective auditory phantom phenomenon present in 10 to 15% of the population. Tinnitus as a phantom phenomenon is related to hyperactivity and reorganization of the auditory cortex. Magnetoencephalography studies demonstrate a correlation between gamma band activity in the contralateral auditory cortex and the presence of tinnitus. The present study aims to investigate the relation between objective gamma-band activity in the contralateral auditory cortex and subjective tinnitus loudness scores. Methods and Findings In unilateral tinnitus patients (N = 15; 10 right, 5 left) source analysis of resting state electroencephalographic gamma band oscillations shows a strong positive correlation with Visual Analogue Scale loudness scores in the contralateral auditory cortex (max r = 0.73, p<0.05). Conclusion Auditory phantom percepts thus show similar sound level dependent activation of the contralateral auditory cortex as observed in normal audition. In view of recent consciousness models and tinnitus network models these results suggest tinnitus loudness is coded by gamma band activity in the contralateral auditory cortex but might not, by itself, be responsible for tinnitus perception. PMID:19816597

From motor cortex to visual cortex: the application of noninvasive brain stimulation to amblyopia.

PubMed

Thompson, Benjamin; Mansouri, Behzad; Koski, Lisa; Hess, Robert F

2012-04-01

Noninvasive brain stimulation is a technique for inducing changes in the excitability of discrete neural populations in the human brain. A current model of the underlying pathological processes contributing to the loss of motor function after stroke has motivated a number of research groups to investigate the potential therapeutic application of brain stimulation to stroke rehabilitation. The loss of motor function is modeled as resulting from a combination of reduced excitability in the lesioned motor cortex and an increased inhibitory drive from the nonlesioned hemisphere over the lesioned hemisphere. This combination of impaired neural function and pathological suppression resonates with current views on the cause of the visual impairment in amblyopia. Here, we discuss how the rationale for using noninvasive brain stimulation in stroke rehabilitation can be applied to amblyopia, review a proof-of-principle study demonstrating that brain stimulation can temporarily improve amblyopic eye function, and propose future research avenues. Copyright © 2010 Wiley Periodicals, Inc.

HO-1 induction in motor cortex and intestinal dysfunction in TDP-43 A315T transgenic mice.

PubMed

Guo, Yansu; Wang, Qian; Zhang, Kunxi; An, Ting; Shi, Pengxiao; Li, Zhongyao; Duan, Weisong; Li, Chunyan

2012-06-15

TAR DNA-binding protein 43 (TDP-43) has been found to be related to the pathogenesis of amyotrophic lateral sclerosis (ALS). TDP-43 A315T transgenic mice develop degeneration of specific motor neurons, and accumulation of ubiquitinated proteins has been observed in the pyramidal cells of motor cortex of these mice. In this study, we found stress-responsive HO-1 induction and no autophagic alteration in motor cortex of TDP-43 A315T transgenic mice. Glial activation, especially astrocytic proliferation, occurred in cortical layer 5 and sub-meningeal region. Interestingly, we noticed that progressively thinned colon, swollen small intestine and reduced food intake, rather than severe muscle weakness, contributed to the death of TDP-43 A315T transgenic mice. Increased TDP-43 accumulation in the myenteric nerve plexus and increased thickness of muscular layer of colon were related to the intestinal dysfunction. Copyright © 2012 Elsevier B.V. All rights reserved.

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

Abnormal short-latency synaptic plasticity in the motor cortex of subjects with Becker muscular dystrophy: a rTMS study.

PubMed

Golaszewski, Stefan; Schwenker, Kerstin; Bergmann, Jürgen; Brigo, Francesco; Christova, Monica; Trinka, Eugen; Nardone, Raffaele

2016-01-01

We used repetitive transcranial magnetic stimulation (rTMS) to further investigate motor cortex excitability in 13 patients with Becker muscular dystrophy (BMD), six of them with slight mental retardation. RTMS delivered at 5Hz frequency and suprathreshold intensity progressively increases the size of motor evoked potentials (MEPs) in healthy subjects; the rTMS-induced facilitation of MEPs was significantly reduced in the BMD patients mentally retarded or classified as borderline when compared with age-matched control subjects and the BMD patients with normal intelligence. The increase in the duration of the cortical silent period was similar in both patient groups and controls. These findings suggest an altered cortical short-term synaptic plasticity in glutamate-dependent excitatory circuits within the motor cortex in BMD patients with intellectual disabilities. RTMS studies may shed new light on the physiological mechanisms of cortical involvement in dystrophinopathies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Evolution of the dynamic properties of the cortex-basal ganglia network after dopaminergic depletion in rats.

PubMed

Dejean, Cyril; Nadjar, Agnes; Le Moine, Catherine; Bioulac, Bernard; Gross, Christian E; Boraud, Thomas

2012-05-01

It is well established that parkinsonian syndrome is associated with alterations of neuronal activity temporal pattern basal ganglia (BG). An increase in synchronized oscillations has been observed in different BG nuclei in Parkinson's disease patients as well as animal models such as 6-hydroxydopamine treated rats. We recently demonstrated that this increase in oscillatory synchronization is present during high-voltage spindles (HVS) probably underpinned by the disorganization of cortex-BG interactions. Here we investigated the time course of both oscillatory and motor alterations. For that purpose we performed daily simultaneous recordings of neuronal activity in motor cortex, striatum and substantia nigra pars reticulata (SNr), before and after 6-hydroxydopamine lesion in awake rats. After a brief non-dopamine-specific desynchronization, oscillatory activity first increased during HVS followed by progressive motor impairment and the shortening of SNr activation delay. While the oscillatory firing increase reflects dopaminergic depletion, response alteration in SNr neurons is closely related to motor symptom. Copyright © 2012 Elsevier Inc. All rights reserved.

Altered cortico-basal ganglia motor pathways reflect reduced volitional motor activity in schizophrenia.

PubMed

Bracht, Tobias; Schnell, Susanne; Federspiel, Andrea; Razavi, Nadja; Horn, Helge; Strik, Werner; Wiest, Roland; Dierks, Thomas; Müller, Thomas J; Walther, Sebastian

2013-02-01

Little is known about the neurobiology of hypokinesia in schizophrenia. Therefore, the aim of this study was to investigate alterations of white matter motor pathways in schizophrenia and to relate our findings to objectively measured motor activity. We examined 21 schizophrenia patients and 21 healthy controls using diffusion tensor imaging and actigraphy. We applied a probabilistic fibre tracking approach to investigate pathways connecting the dorsolateral prefrontal cortex (dlPFC), the rostral anterior cingulate cortex (rACC), the pre-supplementary motor area (pre-SMA), the supplementary motor area proper (SMA-proper), the primary motor cortex (M1), the caudate nucleus, the striatum, the pallidum and the thalamus. Schizophrenia patients had lower activity levels than controls. In schizophrenia we found higher probability indices forming part of a bundle of interest (PIBI) in pathways connecting rACC, pre-SMA and SMA-proper as well as in pathways connecting M1 and pre-SMA with caudate nucleus, putamen, pallidum and thalamus and a reduced spatial extension of motor pathways in schizophrenia. There was a positive correlation between PIBI and activity level in the right pre-SMA-pallidum and the left M1-thalamus connection in healthy controls, and in the left pre-SMA-SMA-proper pathway in schizophrenia. Our results point to reduced volitional motor activity and altered motor pathway organisation in schizophrenia. The identified associations between the amount of movement and structural connectivity of motor pathways suggest dysfunction of cortico-basal ganglia pathways in the pathophysiology of hypokinesia in schizophrenia. Schizophrenia patients may use cortical pathways involving the supplementary motor area to compensate for basal ganglia dysfunction. Copyright © 2012 Elsevier B.V. All rights reserved.

Action perception in individuals with congenital blindness or deafness: how does the loss of a sensory modality from birth affect perception-induced motor facilitation?

PubMed

Alaerts, Kaat; Swinnen, Stephan P; Wenderoth, Nicole

2011-05-01

Seeing or hearing manual actions activates the mirror neuron system, that is, specialized neurons within motor areas which fire when an action is performed but also when it is passively perceived. Using TMS, it was shown that motor cortex of typically developed subjects becomes facilitated not only from seeing others' actions, but also from merely hearing action-related sounds. In the present study, TMS was used for the first time to explore the "auditory" and "visual" responsiveness of motor cortex in individuals with congenital blindness or deafness. TMS was applied over left primary motor cortex (M1) to measure cortico-motor facilitation while subjects passively perceived manual actions (either visually or aurally). Although largely unexpected, congenitally blind or deaf subjects displayed substantially lower resonant motor facilitation upon action perception compared to seeing/hearing control subjects. Moreover, muscle-specific changes in cortico-motor excitability within M1 appeared to be absent in individuals with profound blindness or deafness. Overall, these findings strongly argue against the hypothesis that an increased reliance on the remaining sensory modality in blind or deaf subjects is accompanied by an increased responsiveness of the "auditory" or "visual" perceptual-motor "mirror" system, respectively. Moreover, the apparent lack of resonant motor facilitation for the blind and deaf subjects may challenge the hypothesis of a unitary mirror system underlying human action recognition and may suggest that action perception in blind and deaf subjects engages a mode of action processing that is different from the human action recognition system recruited in typically developed subjects.

Linear summation of outputs in a balanced network model of motor cortex

PubMed Central

Capaday, Charles; van Vreeswijk, Carl

2015-01-01

Given the non-linearities of the neural circuitry's elements, we would expect cortical circuits to respond non-linearly when activated. Surprisingly, when two points in the motor cortex are activated simultaneously, the EMG responses are the linear sum of the responses evoked by each of the points activated separately. Additionally, the corticospinal transfer function is close to linear, implying that the synaptic interactions in motor cortex must be effectively linear. To account for this, here we develop a model of motor cortex composed of multiple interconnected points, each comprised of reciprocally connected excitatory and inhibitory neurons. We show how non-linearities in neuronal transfer functions are eschewed by strong synaptic interactions within each point. Consequently, the simultaneous activation of multiple points results in a linear summation of their respective outputs. We also consider the effects of reduction of inhibition at a cortical point when one or more surrounding points are active. The network response in this condition is linear over an approximately two- to three-fold decrease of inhibitory feedback strength. This result supports the idea that focal disinhibition allows linear coupling of motor cortical points to generate movement related muscle activation patterns; albeit with a limitation on gain control. The model also explains why neural activity does not spread as far out as the axonal connectivity allows, whilst also explaining why distant cortical points can be, nonetheless, functionally coupled by focal disinhibition. Finally, we discuss the advantages that linear interactions at the cortical level afford to motor command synthesis. PMID:26097452

Human Subthalamic Nucleus in Movement Error Detection and Its Evaluation during Visuomotor Adaptation

PubMed Central

Zavala, Baltazar; Pogosyan, Alek; Ashkan, Keyoumars; Zrinzo, Ludvic; Foltynie, Thomas; Limousin, Patricia; Brown, Peter

2014-01-01

Monitoring and evaluating movement errors to guide subsequent movements is a critical feature of normal motor control. Previously, we showed that the postmovement increase in electroencephalographic (EEG) beta power over the sensorimotor cortex reflects neural processes that evaluate motor errors consistent with Bayesian inference (Tan et al., 2014). Whether such neural processes are limited to this cortical region or involve the basal ganglia is unclear. Here, we recorded EEG over the cortex and local field potential (LFP) activity in the subthalamic nucleus (STN) from electrodes implanted in patients with Parkinson's disease, while they moved a joystick-controlled cursor to visual targets displayed on a computer screen. After movement offsets, we found increased beta activity in both local STN LFP and sensorimotor cortical EEG and in the coupling between the two, which was affected by both error magnitude and its contextual saliency. The postmovement increase in the coupling between STN and cortex was dominated by information flow from sensorimotor cortex to STN. However, an information drive appeared from STN to sensorimotor cortex in the first phase of the adaptation, when a constant rotation was applied between joystick inputs and cursor outputs. The strength of the STN to cortex drive correlated with the degree of adaption achieved across subjects. These results suggest that oscillatory activity in the beta band may dynamically couple the sensorimotor cortex and basal ganglia after movements. In particular, beta activity driven from the STN to cortex indicates task-relevant movement errors, information that may be important in modifying subsequent motor responses. PMID:25505327

Recruitment of the prefrontal cortex and cerebellum in Parkinsonian rats following skilled aerobic exercise.

PubMed

Wang, Zhuo; Guo, Yumei; Myers, Kalisa G; Heintz, Ryan; Holschneider, Daniel P

2015-05-01

Exercise modality and complexity play a key role in determining neurorehabilitative outcome in Parkinson's disease (PD). Exercise training (ET) that incorporates both motor skill training and aerobic exercise has been proposed to synergistically improve cognitive and automatic components of motor control in PD patients. Here we introduced such a skilled aerobic ET paradigm in a rat model of dopaminergic deafferentation. Rats with bilateral, intra-striatal 6-hydroxydopamine lesions were exposed to forced ET for 4weeks, either on a simple running wheel (non-skilled aerobic exercise, NSAE) or on a complex wheel with irregularly spaced rungs (skilled aerobic exercise, SAE). Cerebral perfusion was mapped during horizontal treadmill walking or at rest using [(14)C]-iodoantipyrine 1week after the completion of ET. Regional cerebral blood flow (rCBF) was quantified by autoradiography and analyzed in 3-dimensionally reconstructed brains by statistical parametric mapping. SAE compared to NSAE resulted in equal or greater recovery in motor deficits, as well as greater increases in rCBF during walking in the prelimbic area of the prefrontal cortex, broad areas of the somatosensory cortex, and the cerebellum. NSAE compared to SAE animals showed greater activation in the dorsal caudate-putamen and dorsal hippocampus. Seed correlation analysis revealed enhanced functional connectivity in SAE compared to NSAE animals between the prelimbic cortex and motor areas, as well as altered functional connectivity between midline cerebellum and sensorimotor regions. Our study provides the first evidence for functional brain reorganization following skilled aerobic exercise in Parkinsonian rats, and suggests that SAE compared to NSAE results in enhancement of prefrontal cortex- and cerebellum-mediated control of motor function. Copyright © 2015 Elsevier Inc. All rights reserved.

Rehabilitative skilled forelimb training enhances axonal remodeling in the corticospinal pathway but not the brainstem-spinal pathways after photothrombotic stroke in the primary motor cortex.

PubMed

Okabe, Naohiko; Himi, Naoyuki; Maruyama-Nakamura, Emi; Hayashi, Norito; Narita, Kazuhiko; Miyamoto, Osamu

2017-01-01

Task-specific rehabilitative training is commonly used for chronic stroke patients. Axonal remodeling is believed to be one mechanism underlying rehabilitation-induced functional recovery, and significant roles of the corticospinal pathway have previously been demonstrated. Brainstem-spinal pathways, as well as the corticospinal tract, have been suggested to contribute to skilled motor function and functional recovery after brain injury. However, whether axonal remodeling in the brainstem-spinal pathways is a critical component for rehabilitation-induced functional recovery is not known. In this study, rats were subjected to photothrombotic stroke in the caudal forelimb area of the primary motor cortex and received rehabilitative training with a skilled forelimb reaching task for 4 weeks. After completion of the rehabilitative training, the retrograde tracer Fast blue was injected into the contralesional lower cervical spinal cord. Fast blue-positive cells were counted in 32 brain areas located in the cerebral cortex, hypothalamus, midbrain, pons, and medulla oblongata. Rehabilitative training improved motor performance in the skilled forelimb reaching task but not in the cylinder test, ladder walk test, or staircase test, indicating that rehabilitative skilled forelimb training induced task-specific recovery. In the histological analysis, rehabilitative training significantly increased the number of Fast blue-positive neurons in the ipsilesional rostral forelimb area and secondary sensory cortex. However, rehabilitative training did not alter the number of Fast blue-positive neurons in any areas of the brainstem. These results indicate that rehabilitative skilled forelimb training enhances axonal remodeling selectively in the corticospinal pathway, which suggests a critical role of cortical plasticity, rather than brainstem plasticity, in task-specific recovery after subtotal motor cortex destruction.

Recruitment of the prefrontal cortex and cerebellum in Parkinsonian rats following skilled aerobic exercise

PubMed Central

Wang, Zhuo; Guo, Yumei; Myers, Kalisa G.; Heintz, Ryan; Holschneider, Daniel P.

2015-01-01

Exercise modality and complexity play a key role in determining neurorehabilitative outcome in Parkinson’s disease (PD). Exercise training (ET) that incorporates both motor skill training and aerobic exercise has been proposed to synergistically improve cognitive and automatic components of motor control in PD patients. Here we introduced such a skilled aerobic ET paradigm in a rat model of dopaminergic deafferentation. Rats with bilateral, intra-striatal 6-hydroxydopamine lesions were exposed to forced ET for 4 weeks, either on a simple running wheel (non-skilled aerobic exercise, NSAE) or on a complex wheel with irregularly spaced rungs (skilled aerobic exercise, SAE). Cerebral perfusion was mapped during horizontal treadmill walking or at rest using [14C]-iodoantipyrine 1 week after the completion of ET. Regional cerebral blood flow (rCBF) was quantified by autoradiography and analyzed in 3-dimensionally reconstructed brains by statistical parametric mapping. SAE compared to NSAE resulted in equal or greater recovery in motor deficits, as well as greater increases in rCBF during walking in the prelimbic area of the prefrontal cortex, broad areas of the somatosensory cortex, and the cerebellum. NSAE compared to SAE animals showed greater activation in the dorsal caudate-putamen and dorsal hippocampus. Seed correlation analysis revealed enhanced functional connectivity in SAE compared to NSAE animals between the prelimbic cortex and motor areas, as well as altered functional connectivity between midline cerebellum and sensorimotor regions. Our study provides the first evidence for functional brain reorganization following skilled aerobic exercise in Parkinsonian rats, and suggests that SAE compared to NSAE results in enhancement of prefrontal cortex- and cerebellum-mediated control of motor function. PMID:25747184

Rehabilitative skilled forelimb training enhances axonal remodeling in the corticospinal pathway but not the brainstem-spinal pathways after photothrombotic stroke in the primary motor cortex

PubMed Central

Himi, Naoyuki; Maruyama-Nakamura, Emi; Hayashi, Norito; Narita, Kazuhiko; Miyamoto, Osamu

2017-01-01

Task-specific rehabilitative training is commonly used for chronic stroke patients. Axonal remodeling is believed to be one mechanism underlying rehabilitation-induced functional recovery, and significant roles of the corticospinal pathway have previously been demonstrated. Brainstem-spinal pathways, as well as the corticospinal tract, have been suggested to contribute to skilled motor function and functional recovery after brain injury. However, whether axonal remodeling in the brainstem-spinal pathways is a critical component for rehabilitation-induced functional recovery is not known. In this study, rats were subjected to photothrombotic stroke in the caudal forelimb area of the primary motor cortex and received rehabilitative training with a skilled forelimb reaching task for 4 weeks. After completion of the rehabilitative training, the retrograde tracer Fast blue was injected into the contralesional lower cervical spinal cord. Fast blue-positive cells were counted in 32 brain areas located in the cerebral cortex, hypothalamus, midbrain, pons, and medulla oblongata. Rehabilitative training improved motor performance in the skilled forelimb reaching task but not in the cylinder test, ladder walk test, or staircase test, indicating that rehabilitative skilled forelimb training induced task-specific recovery. In the histological analysis, rehabilitative training significantly increased the number of Fast blue-positive neurons in the ipsilesional rostral forelimb area and secondary sensory cortex. However, rehabilitative training did not alter the number of Fast blue-positive neurons in any areas of the brainstem. These results indicate that rehabilitative skilled forelimb training enhances axonal remodeling selectively in the corticospinal pathway, which suggests a critical role of cortical plasticity, rather than brainstem plasticity, in task-specific recovery after subtotal motor cortex destruction. PMID:29095902

Complex Regional Pain Syndrome Type I Affects Brain Structure in Prefrontal and Motor Cortex

PubMed Central

Pleger, Burkhard; Draganski, Bogdan; Schwenkreis, Peter; Lenz, Melanie; Nicolas, Volkmar; Maier, Christoph; Tegenthoff, Martin

2014-01-01

The complex regional pain syndrome (CRPS) is a rare but debilitating pain disorder that mostly occurs after injuries to the upper limb. A number of studies indicated altered brain function in CRPS, whereas possible influences on brain structure remain poorly investigated. We acquired structural magnetic resonance imaging data from CRPS type I patients and applied voxel-by-voxel statistics to compare white and gray matter brain segments of CRPS patients with matched controls. Patients and controls were statistically compared in two different ways: First, we applied a 2-sample ttest to compare whole brain white and gray matter structure between patients and controls. Second, we aimed to assess structural alterations specifically of the primary somatosensory (S1) and motor cortex (M1) contralateral to the CRPS affected side. To this end, MRI scans of patients with left-sided CRPS (and matched controls) were horizontally flipped before preprocessing and region-of-interest-based group comparison. The unpaired ttest of the “non-flipped” data revealed that CRPS patients presented increased gray matter density in the dorsomedial prefrontal cortex. The same test applied to the “flipped” data showed further increases in gray matter density, not in the S1, but in the M1 contralateral to the CRPS-affected limb which were inversely related to decreased white matter density of the internal capsule within the ipsilateral brain hemisphere. The gray-white matter interaction between motor cortex and internal capsule suggests compensatory mechanisms within the central motor system possibly due to motor dysfunction. Altered gray matter structure in dorsomedial prefrontal cortex may occur in response to emotional processes such as pain-related suffering or elevated analgesic top-down control. PMID:24416397

Understanding the role of the primary somatosensory cortex: Opportunities for rehabilitation

PubMed Central

Borich, M.R.; Brodie, S.M.; Gray, W.A.; Ionta, S.; Boyd, L.A.

2016-01-01

Emerging evidence indicates impairments in somatosensory function may be a major contributor to motor dysfunction associated with neurologic injury or disorders. However, the neuroanatomical substrates underlying the connection between aberrant sensory input and ineffective motor output are still under investigation. The primary somatosensory cortex (S1) plays a critical role in processing afferent somatosensory input and contributes to the integration of sensory and motor signals necessary for skilled movement. Neuroimaging and neurostimulation approaches provide unique opportunities to non-invasively study S1 structure and function including connectivity with other cortical regions. These research techniques have begun to illuminate casual contributions of abnormal S1 activity and connectivity to motor dysfunction and poorer recovery of motor function in neurologic patient populations. This review synthesizes recent evidence illustrating the role of S1 in motor control, motor learning and functional recovery with an emphasis on how information from these investigations may be exploited to inform stroke rehabilitation to reduce motor dysfunction and improve therapeutic outcomes. PMID:26164474

Toward more versatile and intuitive cortical brain machine interfaces

PubMed Central

Andersen, Richard A.; Kellis, Spencer; Klaes, Christian; Aflalo, Tyson

2015-01-01

Brain machine interfaces have great potential in neuroprosthetic applications to assist patients with brain injury and neurodegenerative diseases. One type of BMI is a cortical motor prosthetic which is used to assist paralyzed subjects. Motor prosthetics to date have typically used the motor cortex as a source of neural signals for controlling external devices. The review will focus on several new topics in the arena of cortical prosthetics. These include using 1) recordings from cortical areas outside motor cortex; 2) local field potentials (LFPs) as a source of recorded signals; 3) somatosensory feedback for more dexterous control of robotics; and 4) new decoding methods that work in concert to form an ecology of decode algorithms. These new advances hold promise in greatly accelerating the applicability and ease of operation of motor prosthetics. PMID:25247368

Useful signals from motor cortex

PubMed Central

Schwartz, Andrew B

2007-01-01

Historically, the motor cortical function has been explained as a funnel to muscle activation. This invokes the idea that motor cortical neurons, or ‘upper motoneurons’, directly cause muscle contraction just like spinal motoneurons. Thus, the motor cortex and muscle activity are inextricably entwined like a puppet master and his marionette. Recently, this concept has been challenged by current experimentation showing that many behavioural aspects of action are represented in motor cortical activity. Although this activity may still be related to muscle activation, the relation between the two is likely to be indirect and complex, whereas the relation between cortical activity and kinematic parameters is simple and robust. These findings show how to extract useful signals that help explain the underlying process that generates behaviour and to harness these signals for potentially therapeutic applications. PMID:17255162

Chronic catatonic schizophrenia treated successfully with right unilateral ultrabrief pulse electroconvulsive therapy: case report.

PubMed

Cupina, Denise; Patil, Sachin; Loo, Colleen

2013-06-01

Catatonia is a syndrome with prominent motor and behavioral symptoms commonly seen in acutely ill psychiatric patients. Catatonic symptoms have been considered as positive predictors of response to electroconvulsive therapy (ECT); however, few studies so far have addressed the role of ECT treatment technique in schizophrenia. We present the case of a 41-year-old woman with chronic catatonic schizophrenia who was treated successfully with a course of ultrabrief right unilateral ECT.

Constriction of the buccal branch of the facial nerve produces unilateral craniofacial allodynia.

PubMed

Lewis, Susannah S; Grace, Peter M; Hutchinson, Mark R; Maier, Steven F; Watkins, Linda R

2017-08-01

Despite pain being a sensory experience, studies of spinal cord ventral root damage have demonstrated that motor neuron injury can induce neuropathic pain. Whether injury of cranial motor nerves can also produce nociceptive hypersensitivity has not been addressed. Herein, we demonstrate that chronic constriction injury (CCI) of the buccal branch of the facial nerve results in long-lasting, unilateral allodynia in the rat. An anterograde and retrograde tracer (3000MW tetramethylrhodamine-conjugated dextran) was not transported to the trigeminal ganglion when applied to the injury site, but was transported to the facial nucleus, indicating that this nerve branch is not composed of trigeminal sensory neurons. Finally, intracisterna magna injection of interleukin-1 (IL-1) receptor antagonist reversed allodynia, implicating the pro-inflammatory cytokine IL-1 in the maintenance of neuropathic pain induced by facial nerve CCI. These data extend the prior evidence that selective injury to motor axons can enhance pain to supraspinal circuits by demonstrating that injury of a facial nerve with predominantly motor axons is sufficient for neuropathic pain, and that the resultant pain has a neuroimmune component. Copyright © 2016 Elsevier Inc. All rights reserved.

Neuroanatomical and behavioural factors associated with the effectiveness of two weekly sessions of prism adaptation in the treatment of unilateral neglect.

PubMed

Gutierrez-Herrera, Maria; Eger, Simone; Keller, Ingo; Hermsdörfer, Joachim; Saevarsson, Styrmir

2018-06-03

Among the different interventions to alleviate the symptoms of unilateral neglect, prism adaptation (PA) appears especially promising. To elucidate the contribution of some neuroanatomical and behavioural factors to PA's effectiveness, we conducted a study combining neuropsychological and lesion mapping methods on a group of 19 neglect patients who underwent two sessions of PA during one week and assessed their improvement relative to the baseline until the following week (7-8 days later). Correlation analyses revealed a significant positive relationship between the magnitude of the proprioceptive after-effect and the improvement at the follow-up session in two perceptual tasks requiring motor responses. Conversely, no correlation was found between the proprioceptive after-effect and the improvement in a perceptual task with no motor involvement. This finding suggests that patients' potential to show a prism-related improvement in motor-related tasks might be indicated by the strength of their proprioceptive response (proprioceptive after-effect). As for the neuroanatomical basis of this relationship, subtraction analyses suggested that patients' improvement in perceptual tasks with high motor involvement might be facilitated by the integrity of temporo-parietal areas and the damage of frontal and subcortical areas.

Complexity vs. unity in unilateral spatial neglect.

PubMed

Rode, G; Fourtassi, M; Pagliari, C; Pisella, L; Rossetti, Y

Unilateral spatial neglect constitutes a heterogeneous syndrome characterized by two main entangled components: a contralesional bias of spatial attention orientation; and impaired building and/or exploration of mental representations of space. These two components are present in different subtypes of unilateral spatial neglect (visual, auditory, somatosensory, motor, allocentric, egocentric, personal, representational and productive manifestations). Detailed anatomical and clinical analyses of these conditions and their underlying disorders show the complexity of spatial cognitive deficits and the difficulty of proposing just one explanation. This complexity is in contrast, however, to the widely acknowledged effectiveness of rehabilitation of the various symptoms and subtypes of unilateral spatial neglect, exemplified in the case of prism adaptation. These common effects are reflections of the unity of the physiotherapeutic mechanisms behind the higher brain functions related to multisensory integration and spatial representations, whereas the paradoxical aspects of unilateral spatial neglect emphasize the need for a greater understanding of spatial cognitive disorders. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Cerebral blood flow changes induced by pedunculopontine nucleus stimulation in patients with advanced Parkinson's disease: a [(15)O] H2O PET study.

PubMed

Ballanger, Benedicte; Lozano, Andres M; Moro, Elena; van Eimeren, Thilo; Hamani, Clement; Chen, Robert; Cilia, Roberto; Houle, Sylvain; Poon, Yu Yan; Lang, Anthony E; Strafella, Antonio P

2009-12-01

Patients with advanced Parkinson's disease (PD) develop disabling axial symptoms, including gait disturbances, freezing and postural instability poorly responsive to levodopa replacement therapy. The pedunculopontine nucleus (PPN) is involved in locomotion, control of posture, and behavioral states [i.e. wakefulness, rapid eye movement sleep]. Recent reports suggested that PPN modulation with deep brain stimulation (DBS) may be beneficial in the treatment of axial symptoms. However, the mechanisms underlying these effects are still unknown. We used [(15)O] H(2)O PET to investigate regional cerebral blood flow in three patients with advanced PD who underwent a new experimental surgical procedure with implantation of unilateral PPN-DBS. Patients were studied Off-medication with stimulator Off and On, both at rest and during a self-paced alternating motor task of the lower limbs. We used SPM2 for imaging data analysis, threshold P < 0.05 corrected at the cluster level. Stimulation induced significant regional cerebral blood flow increment in subcortical regions such as the thalamus (P < 0.006), cerebellum (P < 0.001), and midbrain region (P < 0.001) as well as different cortical areas involving medial sensorimotor cortex extending into caudal supplementary motor area (BA 4/6; P < 0.001). PPN-DBS in advanced PD resulted in blood flow and presumably neuronal activity changes in subcortical and cortical areas involved in balance and motor control, including the mesencephalic locomotor region (e.g. PPN) and closely interconnected structures within the cerebello-(rubro)-thalamo-cortical circuit. Whether these findings are associated with the DBS-PPN clinical effect remains to be proven. However, they suggest that PPN modulation may induce functional changes in neural networks associated with the control of lower limb movements. 2009 Wiley-Liss, Inc.

Motor cortical encoding of serial order in a context-recall task.

PubMed

Carpenter, A F; Georgopoulos, A P; Pellizzer, G

1999-03-12

The neural encoding of serial order was studied in the motor cortex of monkeys performing a context-recall memory scanning task. Up to five visual stimuli were presented successively on a circle (list presentation phase), and then one of them (test stimulus) changed color; the monkeys had to make a single motor response toward the stimulus that immediately followed the test stimulus in the list. Correct performance in this task depends on memorization of the serial order of the stimuli during their presentation. It was found that changes in neural activity during the list presentation phase reflected the serial order of the stimuli; the effect on cell activity of the serial order of stimuli during their presentation was at least as strong as the effect of motor direction on cell activity during the execution of the motor response. This establishes the serial order of stimuli in a motor task as an important determinant of motor cortical activity during stimulus presentation and in the absence of changes in peripheral motor events, in contrast to the commonly held view of the motor cortex as just an "upper motor neuron."

Expression of Kv3.1b potassium channel is widespread in macaque motor cortex pyramidal cells: A histological comparison between rat and macaque.

PubMed

Soares, David; Goldrick, Isabelle; Lemon, Roger N; Kraskov, Alexander; Greensmith, Linda; Kalmar, Bernadett

2017-06-15

There are substantial differences across species in the organization and function of the motor pathways. These differences extend to basic electrophysiological properties. Thus, in rat motor cortex, pyramidal cells have long duration action potentials, while in the macaque, some pyramidal neurons exhibit short duration "thin" spikes. These differences may be related to the expression of the fast potassium channel Kv3.1b, which in rat interneurons is associated with generation of thin spikes. Rat pyramidal cells typically lack these channels, while there are reports that they are present in macaque pyramids. Here we made a systematic, quantitative comparison of the Kv3.1b expression in sections from macaque and rat motor cortex, using two different antibodies (NeuroMab, Millipore). As our standard reference, we examined, in the same sections, Kv3.1b staining in parvalbumin-positive interneurons, which show strong Kv3.1b immunoreactivity. In macaque motor cortex, a large sample of pyramidal neurons were nearly all found to express Kv3.1b in their soma membranes. These labeled neurons were identified as pyramidal based either by expression of SMI32 (a pyramidal marker), or by their shape and size, and lack of expression of parvalbumin (a marker for some classes of interneuron). Large (Betz cells), medium, and small pyramidal neurons all expressed Kv3.1b. In rat motor cortex, SMI32-postive pyramidal neurons expressing Kv3.1b were very rare and weakly stained. Thus, there is a marked species difference in the immunoreactivity of Kv3.1b in pyramidal neurons, and this may be one of the factors explaining the pronounced electrophysiological differences between rat and macaque pyramidal neurons. © 2017 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

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