Cobtorin target analysis reveals that pectin functions in the deposition of cellulose microfibrils in parallel with cortical microtubules.

PubMed

Yoneda, Arata; Ito, Takuya; Higaki, Takumi; Kutsuna, Natsumaro; Saito, Tamio; Ishimizu, Takeshi; Osada, Hiroyuki; Hasezawa, Seiichiro; Matsui, Minami; Demura, Taku

2010-11-01

Cellulose and pectin are major components of primary cell walls in plants, and it is believed that their mechanical properties are important for cell morphogenesis. It has been hypothesized that cortical microtubules guide the movement of cellulose microfibril synthase in a direction parallel with the microtubules, but the mechanism by which this alignment occurs remains unclear. We have previously identified cobtorin as an inhibitor that perturbs the parallel relationship between cortical microtubules and nascent cellulose microfibrils. In this study, we searched for the protein target of cobtorin, and we found that overexpression of pectin methylesterase and polygalacturonase suppressed the cobtorin-induced cell-swelling phenotype. Furthermore, treatment with polygalacturonase restored the deposition of cellulose microfibrils in the direction parallel with cortical microtubules, and cobtorin perturbed the distribution of methylated pectin. These results suggest that control over the properties of pectin is important for the deposition of cellulose microfibrils and/or the maintenance of their orientation parallel with the cortical microtubules. © 2010 The Authors. The Plant Journal © 2010 Blackwell Publishing Ltd.

The neural networks of inhibitory control in posttraumatic stress disorder

PubMed Central

Falconer, Erin; Bryant, Richard; Felmingham, Kim L.; Kemp, Andrew H.; Gordon, Evian; Peduto, Anthony; Olivieri, Gloria; Williams, Leanne M.

2008-01-01

Objective Posttraumatic stress disorder (PTSD) involves deficits in information processing that may reflect hypervigilence and deficient inhibitory control. To date, however, no PTSD neuroimaging study has directly examined PTSD-related changes in executive inhibition. Our objective was to investigate the hypothesis that executive inhibitory control networks are compromised in PTSD. Methods Functional magnetic resonance imaging (fMRI) was used during a Go/No-Go inhibition task completed by a sample of patients with PTSD (n = 23), a matched sample of healthy (i.e. without trauma exposure) control participants (n = 23) and a sample of control participants with trauma exposure who did not meet criteria for PTSD (n = 17). Results Participants with PTSD showed more inhibition-related errors than did individuals without trauma exposure. During inhibition, control participants activated a right-lateralized cortical inhibitory network, whereas patients with PTSD activated only the left lateral frontal cortex. PTSD was associated with a reduction in right cortical activation and increased activation of striatal and somatosensory regions. Conclusion The increased inhibitory error and reduced right frontal cortical activation are consistent with compromised inhibitory control in PTSD, while the increased activation of brain regions associated with sensory processing and a greater demand on inhibitory control may reflect enhanced stimulus processing in PTSD, which may undermine cortical control mechanisms. PMID:18787658

Cholinergic Neuromodulation Controls Directed Temporal Communication in Neocortex in Vitro

PubMed Central

Roopun, Anita K.; LeBeau, Fiona E.N.; Rammell, James; Cunningham, Mark O.; Traub, Roger D.; Whittington, Miles A.

2010-01-01

Acetylcholine is the primary neuromodulator involved in cortical arousal in mammals. Cholinergic modulation is involved in conscious awareness, memory formation and attention – processes that involve intercommunication between different cortical regions. Such communication is achieved in part through temporal structuring of neuronal activity by population rhythms, particularly in the beta and gamma frequency ranges (12–80 Hz). Here we demonstrate, using in vitro and in silico models, that spectrally identical patterns of beta2 and gamma rhythms are generated in primary sensory areas and polymodal association areas by fundamentally different local circuit mechanisms: Glutamatergic excitation induced beta2 frequency population rhythms only in layer 5 association cortex whereas cholinergic neuromodulation induced this rhythm only in layer 5 primary sensory cortex. This region-specific sensitivity of local circuits to cholinergic modulation allowed for control of the extent of cortical temporal interactions. Furthermore, the contrasting mechanisms underlying these beta2 rhythms produced a high degree of directionality, favouring an influence of association cortex over primary auditory cortex. PMID:20407636

Functional MRI reveals expert-novice differences during sport-related anticipation.

PubMed

Wright, Michael J; Bishop, Daniel T; Jackson, Robin C; Abernethy, Bruce

2010-01-27

We examined the effect of expertise on cortical activation during sports anticipation using functional MRI. In experiment 1, recreational players predicted badminton stroke direction and the pattern of active clusters was consistent with a proposed perception-of-action network. This pattern was not replicated in a stimulus-matched, action-unrelated control task. In experiment 2, players of three different skill levels anticipated stroke direction from clips occluded either 160 ms before or 80 ms after racquet-shuttle contact. Early-occluded sequences produced more activation than late-occluded sequences overall, in most cortical regions of interest, but experts showed an additional enhancement in medial, dorsolateral and ventrolateral frontal cortex. Anticipation in open-skill sports engages cortical areas integral to observing and understanding others' actions; such activity is enhanced in experts.

Tracking the voluntary control of auditory spatial attention with event-related brain potentials.

PubMed

Störmer, Viola S; Green, Jessica J; McDonald, John J

2009-03-01

A lateralized event-related potential (ERP) component elicited by attention-directing cues (ADAN) has been linked to frontal-lobe control but is often absent when spatial attention is deployed in the auditory modality. Here, we tested the hypothesis that ERP activity associated with frontal-lobe control of auditory spatial attention is distributed bilaterally by comparing ERPs elicited by attention-directing cues and neutral cues in a unimodal auditory task. This revealed an initial ERP positivity over the anterior scalp and a later ERP negativity over the parietal scalp. Distributed source analysis indicated that the anterior positivity was generated primarily in bilateral prefrontal cortices, whereas the more posterior negativity was generated in parietal and temporal cortices. The anterior ERP positivity likely reflects frontal-lobe attentional control, whereas the subsequent ERP negativity likely reflects anticipatory biasing of activity in auditory cortex.

Neurobiology of Self-Awareness in Schizophrenia: an fMRI Study

PubMed Central

Shad, Mujeeb U.; Keshavan, Matcheri S.; Steinberg, Joel L.; Mihalakos, Perry; Thomas, Binu P.; Motes, Michael A.; Soares, Jair C.; Tamminga, Carol A.

2012-01-01

Self-awareness (SA) is one of the core domains of higher cortical functions and is frequently compromised in schizophrenia. Deficits in SA have been associated with functional and psychosocial impairment in this patient population. However, despite its clinical significance, only a few studies have examined the neural substrates of self-referential processing in schizophrenia. The aim of this study was to assess self-awareness in schizophrenia using a functional magnetic resonance imaging (fMRI) paradigm designed to elicit judgments of self-reference in a simulated social context. While scanned, volunteers looked at visually-displayed sentences that had the volunteer’s own first name (self-directed sentence-stimulus) or an unknown other person’s first name (other-directed sentence stimulus) as the grammatical subject of the sentence. The volunteers were asked to discern whether each sentence-stimulus was about the volunteer personally (during a self-referential cue epoch) or asked whether each statement was about someone else (during an other-referential cue epoch). We predicted that individuals with schizophrenia would demonstrate altered functional activation to self- and other-directed sentence-stimuli as compared to controls. Fifteen controls and seventeen schizophrenia volunteers completed clinical assessments and SA fMRI task on a 3T Philips 3.0 T Achieva system. The results showed significantly greater activation in schizophrenia compared to controls for cortical midline structures in response to self- vs. other-directed sentence-stimuli. These findings support results from earlier studies and demonstrate selective alteration in the activation of cortical midline structures associated with evaluations of self-reference in schizophrenia as compared to controls. PMID:22480958

Neurobiology of self-awareness in schizophrenia: an fMRI study.

PubMed

Shad, Mujeeb U; Keshavan, Matcheri S; Steinberg, Joel L; Mihalakos, Perry; Thomas, Binu P; Motes, Michael A; Soares, Jair C; Tamminga, Carol A

2012-07-01

Self-awareness (SA) is one of the core domains of higher cortical functions and is frequently compromised in schizophrenia. Deficits in SA have been associated with functional and psychosocial impairment in this patient population. However, despite its clinical significance, only a few studies have examined the neural substrates of self-referential processing in schizophrenia. The aim of this study was to assess self-awareness in schizophrenia using a functional magnetic resonance imaging (fMRI) paradigm designed to elicit judgments of self-reference in a simulated social context. While scanned, volunteers looked at visually-displayed sentences that had the volunteer's own first name (self-directed sentence-stimulus) or an unknown other person's first name (other-directed sentence stimulus) as the grammatical subject of the sentence. The volunteers were asked to discern whether each sentence-stimulus was about the volunteer personally (during a self-referential cue epoch) or asked whether each statement was about someone else (during an other-referential cue epoch). We predicted that individuals with schizophrenia would demonstrate altered functional activation to self- and other-directed sentence-stimuli as compared to controls. Fifteen controls and seventeen schizophrenia volunteers completed clinical assessments and SA fMRI task on a 3T Philips 3.0 T Achieva system. The results showed significantly greater activation in schizophrenia compared to controls for cortical midline structures in response to self- vs. other-directed sentence-stimuli. These findings support results from earlier studies and demonstrate selective alteration in the activation of cortical midline structures associated with evaluations of self-reference in schizophrenia as compared to controls. Copyright © 2012 Elsevier B.V. All rights reserved.

Structural Brain Changes after Traditional and Robot-Assisted Multi-Domain Cognitive Training in Community-Dwelling Healthy Elderly

PubMed Central

Kim, Geon Ha; Jeon, Seun; Im, Kiho; Kwon, Hunki; Lee, Byung Hwa; Kim, Ga Young; Jeong, Hana; Han, Noh Eul; Seo, Sang Won; Cho, Hanna; Noh, Young; Park, Sang Eon; Kim, Hojeong; Hwang, Jung Won; Yoon, Cindy W.; Kim, Hee Jin; Ye, Byoung Seok; Chin, Ju Hee; Kim, Jung-Hyun; Suh, Mee Kyung; Lee, Jong Min; Kim, Sung Tae; Choi, Mun-Taek; Kim, Mun Sang; Heilman, Kenneth M; Jeong, Jee Hyang; Na, Duk L.

2015-01-01

The purpose of this study was to investigate if multi-domain cognitive training, especially robot-assisted training, alters cortical thickness in the brains of elderly participants. A controlled trial was conducted with 85 volunteers without cognitive impairment who were 60 years old or older. Participants were first randomized into two groups. One group consisted of 48 participants who would receive cognitive training and 37 who would not receive training. The cognitive training group was randomly divided into two groups, 24 who received traditional cognitive training and 24 who received robot-assisted cognitive training. The training for both groups consisted of daily 90-min-session, five days a week for a total of 12 weeks. The primary outcome was the changes in cortical thickness. When compared to the control group, both groups who underwent cognitive training demonstrated attenuation of age related cortical thinning in the frontotemporal association cortices. When the robot and the traditional interventions were directly compared, the robot group showed less cortical thinning in the anterior cingulate cortices. Our results suggest that cognitive training can mitigate age-associated structural brain changes in the elderly. Trial Registration ClnicalTrials.gov NCT01596205 PMID:25898367

Neuroprosthetic limb control with electrocorticography: approaches and challenges.

PubMed

Thakor, Nitish V; Fifer, Matthew S; Hotson, Guy; Benz, Heather L; Newman, Geoffrey I; Milsap, Griffin W; Crone, Nathan E

2014-01-01

Advanced upper limb prosthetics, such as the Johns Hopkins Applied Physics Lab Modular Prosthetic Limb (MPL), are now available for research and preliminary clinical applications. Research attention has shifted to developing means of controlling these prostheses. Penetrating microelectrode arrays are often used in animal and human models to decode action potentials for cortical control. These arrays may suffer signal loss over the long-term and therefore should not be the only implant type investigated for chronic BMI use. Electrocorticographic (ECoG) signals from electrodes on the cortical surface may provide more stable long-term recordings. Several studies have demonstrated ECoG's potential for decoding cortical activity. As a result, clinical studies are investigating ECoG encoding of limb movement, as well as its use for interfacing with and controlling advanced prosthetic arms. This overview presents the technical state of the art in the use of ECoG in controlling prostheses. Technical limitations of the current approach and future directions are also presented.

Motor control and the management of musculoskeletal dysfunction.

PubMed

van Vliet, Paulette M; Heneghan, Nicola R

2006-08-01

This paper aims to develop understanding of three important motor control issues--feedforward mechanisms, cortical plasticity and task-specificity and assess the implications for musculoskeletal practice. A model of control for the reach-to-grasp movement illustrates how the central nervous system integrates sensorimotor processes to control complex movements. Feedforward mechanisms, an essential element of motor control, are altered in neurologically intact patients with chronic neck pain and low back pain. In healthy subjects, cortical mapping studies using transcranial magnetic stimulation have demonstrated that neural pathways adapt according to what and how much is practised. Neuroplasticity has also been demonstrated in a number of musculoskeletal conditions, where cortical maps are altered compared to normal. Behavioural and neurophysiological studies indicate that environmental and task constraints such as the goal of the task and an object's shape and size, are determinants of the motor schema for reaching and other movements. Consideration of motor control issues as well as signs and symptoms, may facilitate management of musculoskeletal conditions and improve outcome. Practice of entire everyday tasks at an early stage and systematic variation of the task is recommended. Training should be directed with the aim of re-educating feedforward mechanisms where necessary and the amount of practice should be sufficient to cause changes in cortical activity.

The effect of a concurrent cognitive task on cortical potentials evoked by unpredictable balance perturbations

PubMed Central

Quant, Sylvia; Adkin, Allan L; Staines, W Richard; Maki, Brian E; McIlroy, William E

2004-01-01

Background Although previous studies suggest that postural control requires attention and other cognitive resources, the central mechanisms responsible for this relationship remain unclear. To address this issue, we examined the effects of altered attention on cortical activity and postural responses following mechanical perturbations to upright stance. We hypothesized that cortical activity would be attenuated but not delayed when mechanical perturbations were applied during a concurrent performance of a cognitive task (i.e. when attention was directed away from the perturbation). We also hypothesized that these cortical changes would be accompanied by alterations in the postural response, as evidenced by increases in the magnitude of anteroposterior (AP) centre of pressure (COP) peak displacements and tibialis anterior (TA) muscle activity. Healthy young adults (n = 7) were instructed to continuously track (cognitive task) or not track (control task) a randomly moving visual target using a hand-held joystick. During each of these conditions, unpredictable translations of a moving floor evoked cortical and postural responses. Scalp-recorded cortical activity, COP, and TA electromyographic (EMG) measures were collected. Results Results revealed a significant decrease in the magnitude of early cortical activity (the N1 response, the first negative peak after perturbation onset) during the tracking task compared to the control condition. More pronounced AP COP peak displacements and EMG magnitudes were also observed for the tracking task and were possibly related to changes in the N1 response. Conclusion Based on previous notions that the N1 response represents sensory processing of the balance disturbance, we suggest that the attenuation of the N1 response is an important central mechanism that may provide insight into the relationship between attention and postural control. PMID:15147586

The effect of a concurrent cognitive task on cortical potentials evoked by unpredictable balance perturbations.

PubMed

Quant, Sylvia; Adkin, Allan L; Staines, W Richard; Maki, Brian E; McIlroy, William E

2004-05-17

Although previous studies suggest that postural control requires attention and other cognitive resources, the central mechanisms responsible for this relationship remain unclear. To address this issue, we examined the effects of altered attention on cortical activity and postural responses following mechanical perturbations to upright stance. We hypothesized that cortical activity would be attenuated but not delayed when mechanical perturbations were applied during a concurrent performance of a cognitive task (i.e. when attention was directed away from the perturbation). We also hypothesized that these cortical changes would be accompanied by alterations in the postural response, as evidenced by increases in the magnitude of anteroposterior (AP) centre of pressure (COP) peak displacements and tibialis anterior (TA) muscle activity. Healthy young adults (n = 7) were instructed to continuously track (cognitive task) or not track (control task) a randomly moving visual target using a hand-held joystick. During each of these conditions, unpredictable translations of a moving floor evoked cortical and postural responses. Scalp-recorded cortical activity, COP, and TA electromyographic (EMG) measures were collected. Results revealed a significant decrease in the magnitude of early cortical activity (the N1 response, the first negative peak after perturbation onset) during the tracking task compared to the control condition. More pronounced AP COP peak displacements and EMG magnitudes were also observed for the tracking task and were possibly related to changes in the N1 response. Based on previous notions that the N1 response represents sensory processing of the balance disturbance, we suggest that the attenuation of the N1 response is an important central mechanism that may provide insight into the relationship between attention and postural control.

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.

A direct GABAergic output from the basal ganglia to frontal cortex

PubMed Central

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

2014-01-01

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

[Bioelectric brain activity in patients with neurotic disorders].

PubMed

Golubev, V L; Korabel'nikova, E A; Kudriavtseva, E P

2006-01-01

Seventy-three patients with neurotic disorders, aged 14-35 years, and 33 healthy controls have been examined using electroencephalographic method with spectral analysis of EEG, which has been conducted on the Brain Surfing system by the algorithm of direct Fourier transformation. The patients had changes of brain electric activity manifesting as insufficiency of thalamo-cortical synchronizing systems that caused an excessive activating effect of reticular formation on the cortex realized through extrathalamic reticular cortical and septo-hippocampal activation paths. Determinative in electrophysiological brain organization was the theta-rhythm, a marker of excessive emotional and autonomic activation, which directly correlated with an extent of personality accentuation and severity of neurotic state.

Neonatal Restriction of Tactile Inputs Leads to Long-Lasting Impairments of Cross-Modal Processing

PubMed Central

Röder, Brigitte; Hanganu-Opatz, Ileana L.

2015-01-01

Optimal behavior relies on the combination of inputs from multiple senses through complex interactions within neocortical networks. The ontogeny of this multisensory interplay is still unknown. Here, we identify critical factors that control the development of visual-tactile processing by combining in vivo electrophysiology with anatomical/functional assessment of cortico-cortical communication and behavioral investigation of pigmented rats. We demonstrate that the transient reduction of unimodal (tactile) inputs during a short period of neonatal development prior to the first cross-modal experience affects feed-forward subcortico-cortical interactions by attenuating the cross-modal enhancement of evoked responses in the adult primary somatosensory cortex. Moreover, the neonatal manipulation alters cortico-cortical interactions by decreasing the cross-modal synchrony and directionality in line with the sparsification of direct projections between primary somatosensory and visual cortices. At the behavioral level, these functional and structural deficits resulted in lower cross-modal matching abilities. Thus, neonatal unimodal experience during defined developmental stages is necessary for setting up the neuronal networks of multisensory processing. PMID:26600123

A chronometric functional sub-network in the thalamo-cortical system regulates the flow of neural information necessary for conscious cognitive processes.

PubMed

León-Domínguez, Umberto; Vela-Bueno, Antonio; Froufé-Torres, Manuel; León-Carrión, Jose

2013-06-01

The thalamo-cortical system has been defined as a neural network associated with consciousness. While there seems to be wide agreement that the thalamo-cortical system directly intervenes in vigilance and arousal, a divergence of opinion persists regarding its intervention in the control of other cognitive processes necessary for consciousness. In the present manuscript, we provide a review of recent scientific findings on the thalamo-cortical system and its role in the control and regulation of the flow of neural information necessary for conscious cognitive processes. We suggest that the axis formed by the medial prefrontal cortex and different thalamic nuclei (reticular nucleus, intralaminar nucleus, and midline nucleus), represents a core component for consciousness. This axis regulates different cerebral structures which allow basic cognitive processes like attention, arousal and memory to emerge. In order to produce a synchronized coherent response, neural communication between cerebral structures must have exact timing (chronometry). Thus, a chronometric functional sub-network within the thalamo-cortical system keeps us in an optimal and continuous functional state, allowing high-order cognitive processes, essential to awareness and qualia, to take place. Copyright © 2013 Elsevier Ltd. All rights reserved.

Neural control of computer cursor velocity by decoding motor cortical spiking activity in humans with tetraplegia*

PubMed Central

Kim, Sung-Phil; Simeral, John D; Hochberg, Leigh R; Donoghue, John P; Black, Michael J

2010-01-01

Computer-mediated connections between human motor cortical neurons and assistive devices promise to improve or restore lost function in people with paralysis. Recently, a pilot clinical study of an intracortical neural interface system demonstrated that a tetraplegic human was able to obtain continuous two-dimensional control of a computer cursor using neural activity recorded from his motor cortex. This control, however, was not sufficiently accurate for reliable use in many common computer control tasks. Here, we studied several central design choices for such a system including the kinematic representation for cursor movement, the decoding method that translates neuronal ensemble spiking activity into a control signal and the cursor control task used during training for optimizing the parameters of the decoding method. In two tetraplegic participants, we found that controlling a cursor's velocity resulted in more accurate closed-loop control than controlling its position directly and that cursor velocity control was achieved more rapidly than position control. Control quality was further improved over conventional linear filters by using a probabilistic method, the Kalman filter, to decode human motor cortical activity. Performance assessment based on standard metrics used for the evaluation of a wide range of pointing devices demonstrated significantly improved cursor control with velocity rather than position decoding. PMID:19015583

Training in cortical control of neuroprosthetic devices improves signal extraction from small neuronal ensembles.

PubMed

Helms Tillery, S I; Taylor, D M; Schwartz, A B

2003-01-01

We have recently developed a closed-loop environment in which we can test the ability of primates to control the motion of a virtual device using ensembles of simultaneously recorded neurons /29/. Here we use a maximum likelihood method to assess the information about task performance contained in the neuronal ensemble. We trained two animals to control the motion of a computer cursor in three dimensions. Initially the animals controlled cursor motion using arm movements, but eventually they learned to drive the cursor directly from cortical activity. Using a population vector (PV) based upon the relation between cortical activity and arm motion, the animals were able to control the cursor directly from the brain in a closed-loop environment, but with difficulty. We added a supervised learning method that modified the parameters of the PV according to task performance (adaptive PV), and found that animals were able to exert much finer control over the cursor motion from brain signals. Here we describe a maximum likelihood method (ML) to assess the information about target contained in neuronal ensemble activity. Using this method, we compared the information about target contained in the ensemble during arm control, during brain control early in the adaptive PV, and during brain control after the adaptive PV had settled and the animal could drive the cursor reliably and with fine gradations. During the arm-control task, the ML was able to determine the target of the movement in as few as 10% of the trials, and as many as 75% of the trials, with an average of 65%. This average dropped when the animals used a population vector to control motion of the cursor. On average we could determine the target in around 35% of the trials. This low percentage was also reflected in poor control of the cursor, so that the animal was unable to reach the target in a large percentage of trials. Supervised adjustment of the population vector parameters produced new weighting coefficients and directional tuning parameters for many neurons. This produced a much better performance of the brain-controlled cursor motion. It was also reflected in the maximum likelihood measure of cell activity, producing the correct target based only on neuronal activity in over 80% of the trials on average. The changes in maximum likelihood estimates of target location based on ensemble firing show that an animal's ability to regulate the motion of a cortically controlled device is not crucially dependent on the experimenter's ability to estimate intention from neuronal activity.

Cortical mechanisms of mirror therapy after stroke.

PubMed

Rossiter, Holly E; Borrelli, Mimi R; Borchert, Robin J; Bradbury, David; Ward, Nick S

2015-06-01

Mirror therapy is a new form of stroke rehabilitation that uses the mirror reflection of the unaffected hand in place of the affected hand to augment movement training. The mechanism of mirror therapy is not known but is thought to involve changes in cerebral organization. We used magnetoencephalography (MEG) to measure changes in cortical activity during mirror training after stroke. In particular, we examined movement-related changes in the power of cortical oscillations in the beta (15-30 Hz) frequency range, known to be involved in movement. Ten stroke patients with upper limb paresis and 13 healthy controls were recorded using MEG while performing bimanual hand movements in 2 different conditions. In one, subjects looked directly at their affected hand (or dominant hand in controls), and in the other, they looked at a mirror reflection of their unaffected hand in place of their affected hand. The movement-related beta desynchronization was calculated in both primary motor cortices. Movement-related beta desynchronization was symmetrical during bilateral movement and unaltered by the mirror condition in controls. In the patients, movement-related beta desynchronization was generally smaller than in controls, but greater in contralesional compared to ipsilesional motor cortex. This initial asymmetry in movement-related beta desynchronization between hemispheres was made more symmetrical by the presence of the mirror. Mirror therapy could potentially aid stroke rehabilitation by normalizing an asymmetrical pattern of movement-related beta desynchronization in primary motor cortices during bilateral movement. © The Author(s) 2014.

The Controlled Cortical Impact Model: Applications, Considerations for Researchers, and Future Directions

PubMed Central

Osier, Nicole D.; Dixon, C. Edward

2016-01-01

Controlled cortical impact (CCI) is a mechanical model of traumatic brain injury (TBI) that was developed nearly 30 years ago with the goal of creating a testing platform to determine the biomechanical properties of brain tissue exposed to direct mechanical deformation. Initially used to model TBIs produced by automotive crashes, the CCI model rapidly transformed into a standardized technique to study TBI mechanisms and evaluate therapies. CCI is most commonly produced using a device that rapidly accelerates a rod to impact the surgically exposed cortical dural surface. The tip of the rod can be varied in size and geometry to accommodate scalability to difference species. Typically, the rod is actuated by a pneumatic piston or electromagnetic actuator. With some limits, CCI devices can control the velocity, depth, duration, and site of impact. The CCI model produces morphologic and cerebrovascular injury responses that resemble certain aspects of human TBI. Commonly observed are graded histologic and axonal derangements, disruption of the blood–brain barrier, subdural and intra-parenchymal hematoma, edema, inflammation, and alterations in cerebral blood flow. The CCI model also produces neurobehavioral and cognitive impairments similar to those observed clinically. In contrast to other TBI models, the CCI device induces a significantly pronounced cortical contusion, but is limited in the extent to which it models the diffuse effects of TBI; a related limitation is that not all clinical TBI cases are characterized by a contusion. Another perceived limitation is that a non-clinically relevant craniotomy is performed. Biomechanically, this is irrelevant at the tissue level. However, craniotomies are not atraumatic and the effects of surgery should be controlled by including surgical sham control groups. CCI devices have also been successfully used to impact closed skulls to study mild and repetitive TBI. Future directions for CCI research surround continued refinements to the model through technical improvements in the devices (e.g., minimizing mechanical sources of variation). Like all TBI models, publications should report key injury parameters as outlined in the NIH common data elements (CDEs) for pre-clinical TBI. PMID:27582726

Outcome of transarterial treatment of dural arteriovenous fistulas with direct or indirect cortical venous drainage.

PubMed

Mantilla, Daniel; Le Corre, Marine; Cagnazzo, Federico; Gascou, Gregory; Eker, Omer; Machi, Paolo; Riquelme, Carlos; Dargazanli, Cyril; Costalat, Vincent; Bonafe, Alain; Lefevre, Pierre-Henri

2018-01-30

Transarterial Onyx embolization is an effective treatment for patients with intracranial dural arteriovenous fistula (DAVF). A study was performed to determine whether the clinical and radiological outcomes after transarterial Onyx treatment were affected by the type of cortical venous drainage (direct vs indirect) of high-grade DAVF. Between May 2006 and December 2014, demographic data, clinical presentation, angiographic characteristics, and treatment-related outcomes were collected for 54 patients divided into two groups (intracranial DAVF with direct and indirect cortical venous drainage). Continuous variables were compared with the two-tailed t test and categorical variables with the χ 2 test. Statistical significance was set at P<0.05. Fifty-two patients (71% with direct and 29% with indirect cortical venous drainage) underwent Onyx embolization. Immediate complete occlusion after treatment was observed in about 55% of patients without between-group difference. During the long-term follow-up, complete angiographic occlusion was achieved in 83% of patients. Specifically, 15 additional patients (40%) in the direct cortical venous drainage group progressed to complete occlusion, but only one (6%) in the indirect cortical venous drainage group. Overall, the rate of complete occlusion was higher in patients with DAVF with direct cortical venous drainage (92%) than in those with DAVF with indirect cortical venous drainage (62.5%) (P=0.01). The rate of permanent treatment-related complications was 4%, mostly related to ischemic events. Overall, 80.5% of patients had a good neurological outcome (modified Rankin Scale score 0-2). Transarterial Onyx embolization of intracranial high-grade DAVF is safe and effective, particularly for lesions with direct cortical venous drainage. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

[Origin of cortical interneurons: basic concepts and clinical implications].

PubMed

Marín, O

Introduction and development. GABAergic interneurons play a prominent role in the function of the cerebral cortex, since they allow the synchronization of pyramidal neurons and greatly influence their differentiation and maturation during development. Until recently it has been thought that cortical interneurons and pyramidal neurons originate from progenitor cells located in the dorsal region of the telencephalon, the pallium. Recent studies, however, have demonstrated that a large number of cortical GABAergic neurons arise from progenitors located in the subpallium the region of the telencephalon that gives rise to the basal ganglia, and that they arise in the cerebral cortex after a long tangential migration. Aims. In this review I have summarized our current knowledge of the factors that control the specification of cortical interneurons, as well as the mechanisms that direct their migration to the cortex.

Network interactions: non-geniculate input to V1.

PubMed

Muckli, Lars; Petro, Lucy S

2013-04-01

The strongest connections to V1 are fed back from neighbouring area V2 and from a network of higher cortical areas (e.g. V3, V5, LOC, IPS and A1), transmitting the results of cognitive operations such as prediction, attention and imagination. V1 is therefore at the receiving end of a complex cortical processing cascade and not only at the entrance stage of cortical processing of retinal input. One elegant strategy to investigate this information-rich feedback to V1 is to eliminate feedforward input, that is, exploit V1's retinotopic organisation to isolate subregions receiving no direct bottom-up stimulation. We highlight the diverse mechanisms of cortical feedback, ranging from gain control to predictive coding, and conclude that V1 is involved in rich internal communication processes. Copyright © 2013 Elsevier Ltd. All rights reserved.

Regulation of radial glial survival by signals from the meninges

PubMed Central

Radakovits, Randor; Barros, Claudia S.; Belvindrah, Richard; Patton, Bruce; Müller, Ulrich

2009-01-01

Summary Radial glial cells (RGCs) in the developing cerebral cortex are progenitors for neurons and glia and their processes serve as guideposts for migrating neurons. So far, it has remained unclear whether RGC processes also control the function of RGCs more directly. Here we show that RGC numbers and cortical size are reduced in mice lacking β1 integrins in RGCs. TUNEL stainings and time-lapse video recordings demonstrate that β1-deficient RGCs processes detach from the meningeal BM followed by apoptotic death of RGCs. Apoptosis is also induced by surgical removal of the meninges. Finally, mice lacking the BM components laminin α2 and α4 show defects in the attachment of RGC processes at the meninges, a reduction in cortical size, and enhanced apoptosis of RGC cells. Our findings demonstrate that attachment of RGC processes at the meninges is important for RGC survival and the control of cortical size. PMID:19535581

Regulation of radial glial survival by signals from the meninges.

PubMed

Radakovits, Randor; Barros, Claudia S; Belvindrah, Richard; Patton, Bruce; Müller, Ulrich

2009-06-17

Radial glial cells (RGCs) in the developing cerebral cortex are progenitors for neurons and glia, and their processes serve as guideposts for migrating neurons. So far, it has remained unclear whether RGC processes also control the function of RGCs more directly. Here, we show that RGC numbers and cortical size are reduced in mice lacking beta1 integrins in RGCs. TUNEL stainings and time-lapse video recordings demonstrate that beta1-deficient RGCs processes detach from the meningeal basement membrane (BM) followed by apoptotic death of RGCs. Apoptosis is also induced by surgical removal of the meninges. Finally, mice lacking the BM components laminin alpha2 and alpha4 show defects in the attachment of RGC processes at the meninges, a reduction in cortical size, and enhanced apoptosis of RGC cells. Our findings demonstrate that attachment of RGC processes at the meninges is important for RGC survival and the control of cortical size.

2D and 3D Stem Cell Models of Primate Cortical Development Identify Species-Specific Differences in Progenitor Behavior Contributing to Brain Size.

PubMed

Otani, Tomoki; Marchetto, Maria C; Gage, Fred H; Simons, Benjamin D; Livesey, Frederick J

2016-04-07

Variation in cerebral cortex size and complexity is thought to contribute to differences in cognitive ability between humans and other animals. Here we compare cortical progenitor cell output in humans and three nonhuman primates using directed differentiation of pluripotent stem cells (PSCs) in adherent two-dimensional (2D) and organoid three-dimensional (3D) culture systems. Clonal lineage analysis showed that primate cortical progenitors proliferate for a protracted period of time, during which they generate early-born neurons, in contrast to rodents, where this expansion phase largely ceases before neurogenesis begins. The extent of this additional cortical progenitor expansion differs among primates, leading to differences in the number of neurons generated by each progenitor cell. We found that this mechanism for controlling cortical size is regulated cell autonomously in culture, suggesting that primate cerebral cortex size is regulated at least in part at the level of individual cortical progenitor cell clonal output. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

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

Causal evidence for retina dependent and independent visual motion computations in mouse cortex

PubMed Central

Hillier, Daniel; Fiscella, Michele; Drinnenberg, Antonia; Trenholm, Stuart; Rompani, Santiago B.; Raics, Zoltan; Katona, Gergely; Juettner, Josephine; Hierlemann, Andreas; Rozsa, Balazs; Roska, Botond

2017-01-01

How neuronal computations in the sensory periphery contribute to computations in the cortex is not well understood. We examined this question in the context of visual-motion processing in the retina and primary visual cortex (V1) of mice. We disrupted retinal direction selectivity – either exclusively along the horizontal axis using FRMD7 mutants or along all directions by ablating starburst amacrine cells – and monitored neuronal activity in layer 2/3 of V1 during stimulation with visual motion. In control mice, we found an overrepresentation of cortical cells preferring posterior visual motion, the dominant motion direction an animal experiences when it moves forward. In mice with disrupted retinal direction selectivity, the overrepresentation of posterior-motion-preferring cortical cells disappeared, and their response at higher stimulus speeds was reduced. This work reveals the existence of two functionally distinct, sensory-periphery-dependent and -independent computations of visual motion in the cortex. PMID:28530661

Neural feedback for instantaneous spatiotemporal modulation of afferent pathways in bi-directional brain-machine interfaces.

PubMed

Liu, Jianbo; Khalil, Hassan K; Oweiss, Karim G

2011-10-01

In bi-directional brain-machine interfaces (BMIs), precisely controlling the delivery of microstimulation, both in space and in time, is critical to continuously modulate the neural activity patterns that carry information about the state of the brain-actuated device to sensory areas in the brain. In this paper, we investigate the use of neural feedback to control the spatiotemporal firing patterns of neural ensembles in a model of the thalamocortical pathway. Control of pyramidal (PY) cells in the primary somatosensory cortex (S1) is achieved based on microstimulation of thalamic relay cells through multiple-input multiple-output (MIMO) feedback controllers. This closed loop feedback control mechanism is achieved by simultaneously varying the stimulation parameters across multiple stimulation electrodes in the thalamic circuit based on continuous monitoring of the difference between reference patterns and the evoked responses of the cortical PY cells. We demonstrate that it is feasible to achieve a desired level of performance by controlling the firing activity pattern of a few "key" neural elements in the network. Our results suggest that neural feedback could be an effective method to facilitate the delivery of information to the cortex to substitute lost sensory inputs in cortically controlled BMIs.

Three Types of Cortical L5 Neurons that Differ in Brain-Wide Connectivity and Function

PubMed Central

Kim, Euiseok J.; Juavinett, Ashley L.; Kyubwa, Espoir M.; Jacobs, Matthew W.; Callaway, Edward M.

2015-01-01

SUMMARY Cortical layer 5 (L5) pyramidal neurons integrate inputs from many sources and distribute outputs to cortical and subcortical structures. Previous studies demonstrate two L5 pyramid types: cortico-cortical (CC) and cortico-subcortical (CS). We characterize connectivity and function of these cell types in mouse primary visual cortex and reveal a new subtype. Unlike previously described L5 CC and CS neurons, this new subtype does not project to striatum [cortico-cortical, non-striatal (CC-NS)] and has distinct morphology, physiology and visual responses. Monosynaptic rabies tracing reveals that CC neurons preferentially receive input from higher visual areas, while CS neurons receive more input from structures implicated in top-down modulation of brain states. CS neurons are also more direction-selective and prefer faster stimuli than CC neurons. These differences suggest distinct roles as specialized output channels, with CS neurons integrating information and generating responses more relevant to movement control and CC neurons being more important in visual perception. PMID:26671462

Three Types of Cortical Layer 5 Neurons That Differ in Brain-wide Connectivity and Function.

PubMed

Kim, Euiseok J; Juavinett, Ashley L; Kyubwa, Espoir M; Jacobs, Matthew W; Callaway, Edward M

2015-12-16

Cortical layer 5 (L5) pyramidal neurons integrate inputs from many sources and distribute outputs to cortical and subcortical structures. Previous studies demonstrate two L5 pyramid types: cortico-cortical (CC) and cortico-subcortical (CS). We characterize connectivity and function of these cell types in mouse primary visual cortex and reveal a new subtype. Unlike previously described L5 CC and CS neurons, this new subtype does not project to striatum [cortico-cortical, non-striatal (CC-NS)] and has distinct morphology, physiology, and visual responses. Monosynaptic rabies tracing reveals that CC neurons preferentially receive input from higher visual areas, while CS neurons receive more input from structures implicated in top-down modulation of brain states. CS neurons are also more direction-selective and prefer faster stimuli than CC neurons. These differences suggest distinct roles as specialized output channels, with CS neurons integrating information and generating responses more relevant to movement control and CC neurons being more important in visual perception. Copyright © 2015 Elsevier Inc. All rights reserved.

Enhanced limbic/impaired cortical-loop connection onto the hippocampus of NHE rats: Application of resting-state functional connectivity in a preclinical ADHD model.

PubMed

Zoratto, F; Palombelli, G M; Ruocco, L A; Carboni, E; Laviola, G; Sadile, A G; Adriani, W; Canese, R

2017-08-30

Due to a hyperfunctioning mesocorticolimbic system, Naples-High-Excitability (NHE) rats have been proposed to model for the meso-cortical variant of attention deficit/hyperactivity disorder (ADHD). Compared to Naples Random-Bred (NRB) controls, NHE rats show hyperactivity, impaired non-selective attention (Aspide et al., 1998), and impaired selective spatial attention (Ruocco et al., 2009a, 2014). Alteration in limbic functions has been proposed; however, resulting unbalance among forebrain areas has not been assessed yet. By resting-state functional Magnetic-Resonance Imaging (fMRI) in vivo, we investigated the connectivity of neuronal networks belonging to limbic vs. cortical loops in NHE and NRB rats (n=10 each). Notably, resting-state fMRI was applied using a multi-slice sagittal, gradient-echo sequence. Voxel-wise connectivity maps at rest, based on temporal correlation among fMRI time-series, were computed by seeding the hippocampus (Hip), nucleus accumbens (NAcc), dorsal striatum (dStr), amygdala (Amy) and dorsal/medial prefrontal cortex (PFC), both hemispheres. To summarize patterns of altered connection, clearly directional connectivity was evident within the cortical loop: bilaterally and specularly, from orbital and dorsal PFCs through dStr and hence towards Hip. Such network communication was reduced in NHE rats (also, with less mesencephalic/pontine innervation). Conversely, enhanced network activity emerged within the limbic loop of NHE rats: from left PFC, both through the NAcc and directly, to the Hip (all of which received greater ventral tegmental innervation, likely dopamine). Together with tuned-down cortical loop, this potentiated limbic loop may serve a major role in controlling ADHD-like behavioral symptoms in NHE rats. Copyright © 2017 Elsevier B.V. All rights reserved.

Slow-Frequency Pulsed Transcranial Electrical Stimulation for Modulation of Cortical Plasticity Based on Reciprocity Targeting with Precision Electrical Head Modeling

PubMed Central

Luu, Phan; Essaki Arumugam, Easwara Moorthy; Anderson, Erik; Gunn, Amanda; Rech, Dennis; Turovets, Sergei; Tucker, Don M.

2016-01-01

In pain management as well as other clinical applications of neuromodulation, it is important to consider the timing parameters influencing activity-dependent plasticity, including pulsed versus sustained currents, as well as the spatial action of electrical currents as they polarize the complex convolutions of the cortical mantle. These factors are of course related; studying temporal factors is not possible when the spatial resolution of current delivery to the cortex is so uncertain to make it unclear whether excitability is increased or decreased with anodal vs. cathodal current flow. In the present study we attempted to improve the targeting of specific cortical locations by applying current through flexible source-sink configurations of 256 electrodes in a geodesic array. We constructed a precision electric head model for 12 healthy individuals. Extraction of the individual’s cortical surface allowed computation of the component of the induced current that is normal to the target cortical surface. In an effort to replicate the long-term depression (LTD) induced with pulsed protocols in invasive animal research and transcranial magnetic stimulation studies, we applied 100 ms pulses at 1.9 s intervals either in cortical-surface-anodal or cortical-surface-cathodal directions, with a placebo (sham) control. The results showed significant LTD of the motor evoked potential as a result of the cortical-surface-cathodal pulses in contrast to the placebo control, with a smaller but similar LTD effect for anodal pulses. The cathodal LTD after-effect was sustained over 90 min following current injection. These results support the feasibility of pulsed protocols with low total charge in non-invasive neuromodulation when the precision of targeting is improved with a dense electrode array and accurate head modeling. PMID:27531976

The role of cortical oscillations in a spiking neural network model of the basal ganglia.

PubMed

Fountas, Zafeirios; Shanahan, Murray

2017-01-01

Although brain oscillations involving the basal ganglia (BG) have been the target of extensive research, the main focus lies disproportionally on oscillations generated within the BG circuit rather than other sources, such as cortical areas. We remedy this here by investigating the influence of various cortical frequency bands on the intrinsic effective connectivity of the BG, as well as the role of the latter in regulating cortical behaviour. To do this, we construct a detailed neural model of the complete BG circuit based on fine-tuned spiking neurons, with both electrical and chemical synapses as well as short-term plasticity between structures. As a measure of effective connectivity, we estimate information transfer between nuclei by means of transfer entropy. Our model successfully reproduces firing and oscillatory behaviour found in both the healthy and Parkinsonian BG. We found that, indeed, effective connectivity changes dramatically for different cortical frequency bands and phase offsets, which are able to modulate (or even block) information flow in the three major BG pathways. In particular, alpha (8-12Hz) and beta (13-30Hz) oscillations activate the direct BG pathway, and favour the modulation of the indirect and hyper-direct pathways via the subthalamic nucleus-globus pallidus loop. In contrast, gamma (30-90Hz) frequencies block the information flow from the cortex completely through activation of the indirect pathway. Finally, below alpha, all pathways decay gradually and the system gives rise to spontaneous activity generated in the globus pallidus. Our results indicate the existence of a multimodal gating mechanism at the level of the BG that can be entirely controlled by cortical oscillations, and provide evidence for the hypothesis of cortically-entrained but locally-generated subthalamic beta activity. These two findings suggest new insights into the pathophysiology of specific BG disorders.

Effect of micromorphology of cortical bone tissue on crack propagation under dynamic loading

NASA Astrophysics Data System (ADS)

Wang, Mayao; Gao, Xing; Abdel-Wahab, Adel; Li, Simin; Zimmermann, Elizabeth A.; Riedel, Christoph; Busse, Björn; Silberschmidt, Vadim V.

2015-09-01

Structural integrity of bone tissue plays an important role in daily activities of humans. However, traumatic incidents such as sports injuries, collisions and falls can cause bone fracture, servere pain and mobility loss. In addition, ageing and degenerative bone diseases such as osteoporosis can increase the risk of fracture [1]. As a composite-like material, a cortical bone tissue is capable of tolerating moderate fracture/cracks without complete failure. The key to this is its heterogeneously distributed microstructural constituents providing both intrinsic and extrinsic toughening mechanisms. At micro-scale level, cortical bone can be considered as a four-phase composite material consisting of osteons, Haversian canals, cement lines and interstitial matrix. These microstructural constituents can directly affect local distributions of stresses and strains, and, hence, crack initiation and propagation. Therefore, understanding the effect of micromorphology of cortical bone on crack initiation and propagation, especially under dynamic loading regimes is of great importance for fracture risk evaluation. In this study, random microstructures of a cortical bone tissue were modelled with finite elements for four groups: healthy (control), young age, osteoporosis and bisphosphonate-treated, based on osteonal morphometric parameters measured from microscopic images for these groups. The developed models were loaded under the same dynamic loading conditions, representing a direct impact incident, resulting in progressive crack propagation. An extended finite-element method (X-FEM) was implemented to realize solution-dependent crack propagation within the microstructured cortical bone tissues. The obtained simulation results demonstrate significant differences due to micromorphology of cortical bone, in terms of crack propagation characteristics for different groups, with the young group showing highest fracture resistance and the senior group the lowest.

Direct cortical hemodynamic mapping of somatotopy of pig nostril sensation by functional near-infrared cortical imaging (fNCI).

PubMed

Uga, Minako; Saito, Toshiyuki; Sano, Toshifumi; Yokota, Hidenori; Oguro, Keiji; Rizki, Edmi Edison; Mizutani, Tsutomu; Katura, Takusige; Dan, Ippeita; Watanabe, Eiju

2014-05-01

Functional near-infrared spectroscopy (fNIRS) is a neuroimaging technique for the noninvasive monitoring of human brain activation states utilizing the coupling between neural activity and regional cerebral hemodynamics. Illuminators and detectors, together constituting optodes, are placed on the scalp, but due to the presence of head tissues, an inter-optode distance of more than 2.5cm is necessary to detect cortical signals. Although direct cortical monitoring with fNIRS has been pursued, a high-resolution visualization of hemodynamic changes associated with sensory, motor and cognitive neural responses directly from the cortical surface has yet to be realized. To acquire robust information on the hemodynamics of the cortex, devoid of signal complications in transcranial measurement, we devised a functional near-infrared cortical imaging (fNCI) technique. Here we demonstrate the first direct functional measurement of temporal and spatial patterns of cortical hemodynamics using the fNCI technique. For fNCI, inter-optode distance was set at 5mm, and light leakage from illuminators was prevented by a special optode holder made of a light-shielding rubber sheet. fNCI successfully detected the somatotopy of pig nostril sensation, as assessed in comparison with concurrent and sequential somatosensory-evoked potential (SEP) measurements on the same stimulation sites. Accordingly, the fNCI system realized a direct cortical hemodynamic measurement with a spatial resolution comparable to that of SEP mapping on the rostral region of the pig brain. This study provides an important initial step toward realizing functional cortical hemodynamic monitoring during neurosurgery of human brains. Copyright © 2014. Published by Elsevier Inc.

Chronic lead exposure reduces doublecortin-expressing immature neurons in young adult guinea pig cerebral cortex.

PubMed

Huang, JuFang; Huang, Kai; Shang, Lei; Wang, Hui; Zhang, Mengqi; Fan, Chun-Ling; Chen, Dan; Yan, Xiaoxin; Xiong, Kun

2012-07-19

Chronic lead (Pb) poisoning remains an environmental risk especially for the pediatric population, and it may affect brain development. Immature neurons expressing doublecortin (DCX+) exist around cortical layer II in various mammals, including adult guinea pigs and humans. Using young adult guinea pigs as an experimental model, the present study explored if chronic Pb exposure affects cortical DCX + immature neurons and those around the subventricular and subgranular zones (SVZ, SGZ). Two month-old guinea pigs were treated with 0.2% lead acetate in drinking water for 2, 4 and 6 months. Blood Pb levels in these animals reached 10.27 ± 0.62, 16.25 ± 0.78 and 19.03 ± 0.86 μg/dL at the above time points, respectively, relative to ~3 μg/dL in vehicle controls. The density of DCX + neurons was significantly reduced around cortical layer II, SVZ and SGZ in Pb-treated animals surviving 4 and 6 months relative to controls. Bromodeoxyuridine (BrdU) pulse-chasing studies failed to find cellular colocalization of this DNA synthesis indicator in DCX + cells around layer II in Pb-treated and control animals. These cortical immature neurons were not found to coexist with active caspase-3 or Fluoro-Jade C labeling. Chronic Pb exposure can lead to significant reduction in the number of the immature neurons around cortical layer II and in the conventional neurogenic sites in young adult guinea pigs. No direct evidence could be identified to link the reduced cortical DCX expression with alteration in local neurogenesis or neuronal death.

The efference cascade, consciousness, and its self: naturalizing the first person pivot of action control

PubMed Central

Merker, Bjorn

2013-01-01

The 20 billion neurons of the neocortex have a mere hundred thousand motor neurons by which to express cortical contents in overt behavior. Implemented through a staggered cortical “efference cascade” originating in the descending axons of layer five pyramidal cells throughout the neocortical expanse, this steep convergence accomplishes final integration for action of cortical information through a system of interconnected subcortical way stations. Coherent and effective action control requires the inclusion of a continually updated joint “global best estimate” of current sensory, motivational, and motor circumstances in this process. I have previously proposed that this running best estimate is extracted from cortical probabilistic preliminaries by a subcortical neural “reality model” implementing our conscious sensory phenomenology. As such it must exhibit first person perspectival organization, suggested to derive from formating requirements of the brain's subsystem for gaze control, with the superior colliculus at its base. Gaze movements provide the leading edge of behavior by capturing targets of engagement prior to contact. The rotation-based geometry of directional gaze movements places their implicit origin inside the head, a location recoverable by cortical probabilistic source reconstruction from the rampant primary sensory variance generated by the incessant play of collicularly triggered gaze movements. At the interface between cortex and colliculus lies the dorsal pulvinar. Its unique long-range inhibitory circuitry may precipitate the brain's global best estimate of its momentary circumstances through multiple constraint satisfaction across its afferents from numerous cortical areas and colliculus. As phenomenal content of our sensory awareness, such a global best estimate would exhibit perspectival organization centered on a purely implicit first person origin, inherently incapable of appearing as a phenomenal content of the sensory space it serves. PMID:23950750

Cortical activation patterns correlate with speech understanding after cochlear implantation

PubMed Central

Olds, Cristen; Pollonini, Luca; Abaya, Homer; Larky, Jannine; Loy, Megan; Bortfeld, Heather; Beauchamp, Michael S.; Oghalai, John S.

2015-01-01

Objectives Cochlear implants are a standard therapy for deafness, yet the ability of implanted patients to understand speech varies widely. To better understand this variability in outcomes, we used functional near-infrared spectroscopy (fNIRS) to image activity within regions of the auditory cortex and compare the results to behavioral measures of speech perception. Design We studied 32 deaf adults hearing through cochlear implants and 35 normal-hearing controls. We used fNIRS to measure responses within the lateral temporal lobe and the superior temporal gyrus to speech stimuli of varying intelligibility. The speech stimuli included normal speech, channelized speech (vocoded into 20 frequency bands), and scrambled speech (the 20 frequency bands were shuffled in random order). We also used environmental sounds as a control stimulus. Behavioral measures consisted of the Speech Reception Threshold, CNC words, and AzBio Sentence tests measured in quiet. Results Both control and implanted participants with good speech perception exhibited greater cortical activations to natural speech than to unintelligible speech. In contrast, implanted participants with poor speech perception had large, indistinguishable cortical activations to all stimuli. The ratio of cortical activation to normal speech to that of scrambled speech directly correlated with the CNC Words and AzBio Sentences scores. This pattern of cortical activation was not correlated with auditory threshold, age, side of implantation, or time after implantation. Turning off the implant reduced cortical activations in all implanted participants. Conclusions Together, these data indicate that the responses we measured within the lateral temporal lobe and the superior temporal gyrus correlate with behavioral measures of speech perception, demonstrating a neural basis for the variability in speech understanding outcomes after cochlear implantation. PMID:26709749

Effect of direct eye contact in PTSD related to interpersonal trauma: an fMRI study of activation of an innate alarm system.

PubMed

Steuwe, Carolin; Daniels, Judith K; Frewen, Paul A; Densmore, Maria; Pannasch, Sebastian; Beblo, Thomas; Reiss, Jeffrey; Lanius, Ruth A

2014-01-01

In healthy individuals, direct eye contact initially leads to activation of a fast subcortical pathway, which then modulates a cortical route eliciting social cognitive processes. The aim of this study was to gain insight into the neurobiological effects of direct eye-to-eye contact using a virtual reality paradigm in individuals with posttraumatic stress disorder (PTSD) related to prolonged childhood abuse. We examined 16 healthy comparison subjects and 16 patients with a primary diagnosis of PTSD using a virtual reality functional magnetic resonance imaging paradigm involving direct vs averted gaze (happy, sad, neutral) as developed by Schrammel et al. in 2009. Irrespective of the displayed emotion, controls exhibited an increased blood oxygenation level-dependent response during direct vs averted gaze within the dorsomedial prefrontal cortex, left temporoparietal junction and right temporal pole. Under the same conditions, individuals with PTSD showed increased activation within the superior colliculus (SC)/periaqueductal gray (PAG) and locus coeruleus. Our findings suggest that healthy controls react to the exposure of direct gaze with an activation of a cortical route that enhances evaluative 'top-down' processes underlying social interactions. In individuals with PTSD, however, direct gaze leads to sustained activation of a subcortical route of eye-contact processing, an innate alarm system involving the SC and the underlying circuits of the PAG.

Effect of direct eye contact in PTSD related to interpersonal trauma: an fMRI study of activation of an innate alarm system

PubMed Central

Steuwe, Carolin; Daniels, Judith K.; Frewen, Paul A.; Densmore, Maria; Pannasch, Sebastian; Beblo, Thomas; Reiss, Jeffrey; Lanius, Ruth A.

2014-01-01

In healthy individuals, direct eye contact initially leads to activation of a fast subcortical pathway, which then modulates a cortical route eliciting social cognitive processes. The aim of this study was to gain insight into the neurobiological effects of direct eye-to-eye contact using a virtual reality paradigm in individuals with posttraumatic stress disorder (PTSD) related to prolonged childhood abuse. We examined 16 healthy comparison subjects and 16 patients with a primary diagnosis of PTSD using a virtual reality functional magnetic resonance imaging paradigm involving direct vs averted gaze (happy, sad, neutral) as developed by Schrammel et al. in 2009. Irrespective of the displayed emotion, controls exhibited an increased blood oxygenation level-dependent response during direct vs averted gaze within the dorsomedial prefrontal cortex, left temporoparietal junction and right temporal pole. Under the same conditions, individuals with PTSD showed increased activation within the superior colliculus (SC)/periaqueductal gray (PAG) and locus coeruleus. Our findings suggest that healthy controls react to the exposure of direct gaze with an activation of a cortical route that enhances evaluative ‘top–down’ processes underlying social interactions. In individuals with PTSD, however, direct gaze leads to sustained activation of a subcortical route of eye-contact processing, an innate alarm system involving the SC and the underlying circuits of the PAG. PMID:22977200

Chemical genetic screening identifies a novel inhibitor of parallel alignment of cortical microtubules and cellulose microfibrils.

PubMed

Yoneda, Arata; Higaki, Takumi; Kutsuna, Natsumaro; Kondo, Yoichi; Osada, Hiroyuki; Hasezawa, Seiichiro; Matsui, Minami

2007-10-01

It is a well-known hypothesis that cortical microtubules control the direction of cellulose microfibril deposition, and that the parallel cellulose microfibrils determine anisotropic cell expansion and plant cell morphogenesis. However, the molecular mechanism by which cortical microtubules regulate the orientation of cellulose microfibrils is still unclear. To investigate this mechanism, chemical genetic screening was performed. From this screening, 'SS compounds' were identified that induced a spherical swelling phenotype in tobacco BY-2 cells. The SS compounds could be categorized into three classes: those that disrupted the cortical microtubules; those that reduced cellulose microfibril content; and thirdly those that had neither of these effects. In the last class, a chemical designated 'cobtorin' was found to induce the spherical swelling phenotype at the lowest concentration, suggesting strong binding activity to the putative target. Examining cellulose microfibril regeneration using taxol-treated protoplasts revealed that the cobtorin compound perturbed the parallel alignment of pre-existing cortical microtubules and nascent cellulose microfibrils. Thus, cobtorin could be a novel inhibitor and an attractive tool for further investigation of the mechanism that enables cortical microtubules to guide the parallel deposition of cellulose microfibrils.

Cortical and Subcortical Coordination of Visual Spatial Attention Revealed by Simultaneous EEG-fMRI Recording.

PubMed

Green, Jessica J; Boehler, Carsten N; Roberts, Kenneth C; Chen, Ling-Chia; Krebs, Ruth M; Song, Allen W; Woldorff, Marty G

2017-08-16

Visual spatial attention has been studied in humans with both electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) individually. However, due to the intrinsic limitations of each of these methods used alone, our understanding of the systems-level mechanisms underlying attentional control remains limited. Here, we examined trial-to-trial covariations of concurrently recorded EEG and fMRI in a cued visual spatial attention task in humans, which allowed delineation of both the generators and modulators of the cue-triggered event-related oscillatory brain activity underlying attentional control function. The fMRI activity in visual cortical regions contralateral to the cued direction of attention covaried positively with occipital gamma-band EEG, consistent with activation of cortical regions representing attended locations in space. In contrast, fMRI activity in ipsilateral visual cortical regions covaried inversely with occipital alpha-band oscillations, consistent with attention-related suppression of the irrelevant hemispace. Moreover, the pulvinar nucleus of the thalamus covaried with both of these spatially specific, attention-related, oscillatory EEG modulations. Because the pulvinar's neuroanatomical geometry makes it unlikely to be a direct generator of the scalp-recorded EEG, these covariational patterns appear to reflect the pulvinar's role as a regulatory control structure, sending spatially specific signals to modulate visual cortex excitability proactively. Together, these combined EEG/fMRI results illuminate the dynamically interacting cortical and subcortical processes underlying spatial attention, providing important insight not realizable using either method alone. SIGNIFICANCE STATEMENT Noninvasive recordings of changes in the brain's blood flow using functional magnetic resonance imaging and electrical activity using electroencephalography in humans have individually shown that shifting attention to a location in space produces spatially specific changes in visual cortex activity in anticipation of a stimulus. The mechanisms controlling these attention-related modulations of sensory cortex, however, are poorly understood. Here, we recorded these two complementary measures of brain activity simultaneously and examined their trial-to-trial covariations to gain insight into these attentional control mechanisms. This multi-methodological approach revealed the attention-related coordination of visual cortex modulation by the subcortical pulvinar nucleus of the thalamus while also disentangling the mechanisms underlying the attentional enhancement of relevant stimulus input and those underlying the concurrent suppression of irrelevant input. Copyright © 2017 the authors 0270-6474/17/377803-08$15.00/0.

Effect of transcranial direct current stimulation on vestibular-ocular and vestibulo-perceptual thresholds.

PubMed

Kyriakareli, Artemis; Cousins, Sian; Pettorossi, Vito E; Bronstein, Adolfo M

2013-10-02

Transcranial direct current stimulation (tDCS) was used in 17 normal individuals to modulate vestibulo-ocular reflex (VOR) and self-motion perception rotational thresholds. The electrodes were applied over the temporoparietal junction bilaterally. Both vestibular nystagmic and perceptual thresholds were increased during as well as after tDCS stimulation. Body rotation was labeled as ipsilateral or contralateral to the anode side, but no difference was observed depending on the direction of rotation or hemisphere polarity. Threshold increase during tDCS was greater for VOR than for motion perception. 'Sham' stimulation had no effect on thresholds. We conclude that tDCS produces an immediate and sustained depression of cortical regions controlling VOR and movement perception. Temporoparietal areas appear to be involved in vestibular threshold modulation but the differential effects observed between VOR and perception suggest a partial dissociation between cortical processing of reflexive and perceptual responses.

Perisylvian GABA levels in schizophrenia and bipolar disorder

PubMed Central

ATAGÜN, Murat İlhan; ŞIKOĞLU, Elif Muazzez; SOYKAN, Çağlar; CAN, Serdar Süleyman; ULUSOY-KAYMAK, Semra; ÇAYKÖYLÜ, Ali; ALGIN, Oktay; PHILLIPS, Mary Louise; ÖNGÜR, Dost; MOORE, Constance Mary

2016-01-01

The aim of this study is to measure GABA levels of perisylvian cortices in schizophrenia and bipolar disorder patients, using proton magnetic resonance spectroscopy (1H-MRS). Patients with schizophrenia (n=25), bipolar I disorder (BD-I; n=28) and bipolar II disorder (BD-II; n=20) were compared with healthy controls (n=30). 1H-MRS data was acquired using a Siemens 3 Tesla whole body scanner to quantify right and left perisylvian structures’ (including superior temporal lobes) GABA levels. Right perisylvian GABA values differed significantly between groups [χ2=9.62, df: 3, p = 0.022]. GABA levels were significantly higher in the schizophrenia group compared with the healthy control group (p=0.002). Furthermore, Chlorpromazine equivalent doses of antipsychotics correlated with right hemisphere GABA levels (r2=0.68, p=0.006, n=33). GABA levels are elevated in the right hemisphere in patients with schizophrenia in comparison to bipolar disorder and healthy controls. The balance between excitatory and inhibitory controls over the cortical circuits may have direct relationship with GABAergic functions in auditory cortices. In addition, GABA levels may be altered by brain regions of interest, psychotropic medications, and clinical stage in schizophrenia and bipolar disorder. PMID:27890741

Direct sensorimotor corticospinal modulation of dorsal horn neuronal C-fiber responses in the rat.

PubMed

Rojas-Piloni, Gerardo; Martínez-Lorenzana, Guadalupe; Condés-Lara, Miguel; Rodríguez-Jiménez, Javier

2010-09-10

Clinically, the stimulation of motor cortical areas has been used to alleviate certain pain conditions. However, the attempts to understand the mechanisms of cortical nociceptive modulation at the spinal cord level have yielded controversial results. The objectives of the present work were to: 1) determine the effects of activating and suppressing the activity of sensorimotor cortical neurons on the nociceptive electrophysiological responses of the segmental C-fibers, and 2) evaluate the contribution of direct and indirect corticospinal projections in segmental nociceptive modulation. By means of a bipolar matrix of stimulation electrodes we mapped the stimulation of cortical areas that modulate C-fiber evoked field potentials in the dorsal horn. In addition, suppressing the cortical activity by means of cortical spreading depression, we observed that the C-fiber evoked field potentials in the dorsal horn are facilitated when cortical activity is suppressed specifically in sensorimotor cortex. Moreover, the C-fiber evoked field potentials were inhibited during spontaneous activation of cortical projecting neurons. Furthermore, after a lesion of the pyramidal tract contralateral to the spinal cord recording sites, the cortical action was suppressed. Our results show that corticospinal tract fibers arising from the sensorimotor cortex modulate directly the nociceptive C-fiber evoked responses of the dorsal horn. 2010. Published by Elsevier B.V.

The dynamics of plus end polarization and microtubule assembly during Xenopus cortical rotation

PubMed Central

Olson, David J.; Oh, Denise

2015-01-01

The self-organization of dorsally-directed microtubules during cortical rotation in the Xenopus egg is essential for dorsal axis formation. The mechanisms controlling this process have been problematic to analyze, owing to difficulties in visualizing microtubules in living egg. Also, the order of events occurring at the onset of cortical rotation have not been satisfactorily visualized in vivo and have been inferred from staged fixed samples. To address these issues, we have characterized the dynamics of total microtubule and plus end behavior continuously throughout cortical rotation, as well as in oocytes and unfertilized eggs. Here, we show that the nascent microtubule network forms in the cortex but associates with the deep cytoplasm at the start of rotation. Importantly, plus ends remain cortical and become increasingly more numerous and active prior to rotation, with dorsal polarization occurring rapidly after the onset of rotation. Additionally, we show that vegetally localized Trim36 is required to attenuate dynamic plus end growth, suggesting that vegetal factors are needed to locally coordinate growth in the cortex. PMID:25753733

Identification of Glutathione S-Transferase Pi as a Protein Involved in Parkinson Disease Progression

PubMed Central

Shi, Min; Bradner, Joshua; Bammler, Theo K.; Eaton, David L.; Zhang, JianPeng; Ye, ZuCheng; Wilson, Angela M.; Montine, Thomas J.; Pan, Catherine; Zhang, Jing

2009-01-01

Parkinson disease (PD) typically affects the cortical regions during the later stages of disease, with neuronal loss, gliosis, and formation of diffuse cortical Lewy bodies in a significant portion of patients with dementia. To identify novel proteins involved in PD progression, we prepared synaptosomal fractions from the frontal cortices of pathologically verified PD patients at different stages along with age-matched controls. Protein expression profiles were compared using a robust quantitative proteomic technique. Approximately 100 proteins displayed significant differences in their relative abundances between PD patients at various stages and controls; three of these proteins were validated using independent techniques. One of the confirmed proteins, glutathione S-transferase Pi, was further investigated in cellular models of PD, demonstrating that its level was intimately associated with several critical cellular processes that are directly related to neurodegeneration in PD. These results have, for the first time, suggested that the levels of glutathione S-transferase Pi may play an important role in modulating the progression of PD. PMID:19498008

Warts phosphorylates Mud to promote Pins-mediated mitotic spindle orientation in Drosophila independent of Yorkie

PubMed Central

Dewey, Evan B.; Sanchez, Desiree; Johnston, Christopher A.

2015-01-01

SUMMARY Multicellular animals have evolved conserved signaling pathways that translate cell polarity cues into mitotic spindle positioning to control the orientation of cell division within complex tissue structures. These oriented cell divisions are essential for the development of cell diversity and the maintenance of tissue homeostasis. Despite intense efforts, the molecular mechanisms that control spindle orientation remain incompletely defined. Here we describe a role for the Hippo (Hpo) kinase complex in promoting Partner of Inscuteable (Pins)-mediated spindle orientation. Knockdown of Hpo, Salvador (Sav), or Warts (Wts) each result in a partial loss of spindle orientation, a phenotype previously described following loss of the Pins-binding protein Mushroom body defect (Mud). Similar to orthologs spanning yeast to mammals, Wts kinase localizes to mitotic spindle poles, a prominent site of Mud localization. Wts directly phosphorylates Mud in vitro within its C-terminal coiled-coil domain. This Mud coiled-coil domain directly binds the adjacent Pins-binding domain to dampen the Pins/Mud interaction, and Wts-mediated phosphorylation uncouples this intramolecular Mud interaction. Loss of Wts prevents cortical Pins/Mud association without affecting Mud accumulation at spindle poles, suggesting phosphorylation acts as a molecular switch to specifically activate cortical Mud function. Finally, loss of Wts in Drosophila imaginal disc epithelial cells results in diminished cortical Mud and defective planar spindle orientation. Our results provide new insights into the molecular basis for dynamic regulation of the cortical Pins/Mud spindle positioning complex and highlight a novel link with an essential, evolutionarily-conserved cell proliferation pathway. PMID:26592339

Projections of Somatosensory Cortex and Frontal Eye Fields onto Incertotectal Neurons in the Cat

PubMed Central

Perkins, Eddie; Warren, Susan; Lin, Rick C.-S.; May, Paul J.

2014-01-01

The goal of this study was to determine whether the input-output characteristics of the zona incerta (ZI) are appropriate for it to serve as a conduit for cortical control over saccade-related activity in the superior colliculus. The study utilized the neuronal tracers wheat germ agglutinin-horseradish peroxidase (WGA-HRP) and biotinylated dextran amine (BDA) in the cat. Injections of WGA-HRP into primary somatosensory cortex (SI) revealed sparse, widespread nontopographic projections throughout ZI. In addition, region-specific areas of more intense termination were present in ventral ZI, although strict topography was not observed. In comparison, the frontal eye fields (FEF) also projected sparsely throughout ZI, but terminated more heavily, medially, along the border between the two sublaminae. Furthermore, retrogradely labeled incertocortical neurons were observed in both experiments. The relationship of these two cortical projections to incertotectal cells was also directly examined by retrogradely labeling incertotectal cells with WGA-HRP in animals that had also received cortical BDA injections. Labeled axonal arbors from both SI and FEF had thin, sparsely branched axons with numerous en passant boutons. They formed numerous close associations with the somata and dendrites of WGA-HRP-labeled incertotectal cells. In summary, these results indicate that both sensory and motor cortical inputs to ZI display similar morphologies and distributions. In addition, both display close associations with incertotectal cells, suggesting direct synaptic contact. From these data, we conclude that inputs from somatosensory and FEF cortex both play a role in controlling gaze-related activity in the superior colliculus by way of the inhibitory incertotectal projection. PMID:17083121

Warts phosphorylates mud to promote pins-mediated mitotic spindle orientation in Drosophila, independent of Yorkie.

PubMed

Dewey, Evan B; Sanchez, Desiree; Johnston, Christopher A

2015-11-02

Multicellular animals have evolved conserved signaling pathways that translate cell polarity cues into mitotic spindle positioning to control the orientation of cell division within complex tissue structures. These oriented cell divisions are essential for the development of cell diversity and the maintenance of tissue homeostasis. Despite intense efforts, the molecular mechanisms that control spindle orientation remain incompletely defined. Here, we describe a role for the Hippo (Hpo) kinase complex in promoting Partner of Inscuteable (Pins)-mediated spindle orientation. Knockdown of Hpo, Salvador (Sav), or Warts (Wts) each result in a partial loss of spindle orientation, a phenotype previously described following loss of the Pins-binding protein Mushroom body defect (Mud). Similar to orthologs spanning yeast to mammals, Wts kinase localizes to mitotic spindle poles, a prominent site of Mud localization. Wts directly phosphorylates Mud in vitro within its C-terminal coiled-coil domain. This Mud coiled-coil domain directly binds the adjacent Pins-binding domain to dampen the Pins/Mud interaction, and Wts-mediated phosphorylation uncouples this intramolecular Mud interaction. Loss of Wts prevents cortical Pins/Mud association without affecting Mud accumulation at spindle poles, suggesting phosphorylation acts as a molecular switch to specifically activate cortical Mud function. Finally, loss of Wts in Drosophila imaginal disc epithelial cells results in diminished cortical Mud and defective planar spindle orientation. Our results provide new insights into the molecular basis for dynamic regulation of the cortical Pins/Mud spindle positioning complex and highlight a novel link with an essential, evolutionarily conserved cell proliferation pathway. Copyright © 2015 Elsevier Ltd. All rights reserved.

Right temporal cortical hypertrophy in resilience to trauma: an MRI study

PubMed Central

Nilsen, André Sevenius; Hilland, Eva; Kogstad, Norunn; Heir, Trond; Hauff, Edvard; Lien, Lars; Endestad, Tor

2016-01-01

Background In studies employing physiological measures such as magnetic resonance imaging (MRI), it is often hard to distinguish what constitutes risk-resilience factors to posttraumatic stress disorder (PTSD) following trauma exposure and what the effects of trauma exposure and PTSD are. Objective We aimed to investigate whether there were observable morphological differences in cortical and sub-cortical regions of the brain, 7–8 years after a single potentially traumatic event. Methods Twenty-four participants, who all directly experienced the 2004 Indian Ocean Tsunami, and 25 controls, underwent structural MRI using a 3T scanner. We generated cortical thickness maps and parcellated sub-cortical volumes for analysis. Results We observed greater cortical thickness for the trauma-exposed participants relative to controls, in a right lateralized temporal lobe region including anterior fusiform gyrus, and superior, middle, and inferior temporal gyrus. Conclusions We observed greater thickness in the right temporal lobe which might indicate that the region could be implicated in resilience to the long-term effects of a traumatic event. We hypothesize this is due to altered emotional semantic memory processing. However, several methodological and confounding issues warrant caution in interpretation of the results. Highlights of the article Following a traumatic event, most people do not develop long-lasting trauma-related symptoms.In a group who experienced a traumatic event 8 years prior, but showed low levels of trauma-related symptoms, we observed increased cortical thickness in the right temporal lobe.The right temporal lobe is implicated in emotional semantic memory processing, and thus might be associated with resilience to the long-term effects of a traumatic event. PMID:27473521

Neural control of computer cursor velocity by decoding motor cortical spiking activity in humans with tetraplegia

NASA Astrophysics Data System (ADS)

Kim, Sung-Phil; Simeral, John D.; Hochberg, Leigh R.; Donoghue, John P.; Black, Michael J.

2008-12-01

Computer-mediated connections between human motor cortical neurons and assistive devices promise to improve or restore lost function in people with paralysis. Recently, a pilot clinical study of an intracortical neural interface system demonstrated that a tetraplegic human was able to obtain continuous two-dimensional control of a computer cursor using neural activity recorded from his motor cortex. This control, however, was not sufficiently accurate for reliable use in many common computer control tasks. Here, we studied several central design choices for such a system including the kinematic representation for cursor movement, the decoding method that translates neuronal ensemble spiking activity into a control signal and the cursor control task used during training for optimizing the parameters of the decoding method. In two tetraplegic participants, we found that controlling a cursor's velocity resulted in more accurate closed-loop control than controlling its position directly and that cursor velocity control was achieved more rapidly than position control. Control quality was further improved over conventional linear filters by using a probabilistic method, the Kalman filter, to decode human motor cortical activity. Performance assessment based on standard metrics used for the evaluation of a wide range of pointing devices demonstrated significantly improved cursor control with velocity rather than position decoding. Disclosure. JPD is the Chief Scientific Officer and a director of Cyberkinetics Neurotechnology Systems (CYKN); he holds stock and receives compensation. JDS has been a consultant for CYKN. LRH receives clinical trial support from CYKN.

Locally induced neuronal synchrony precisely propagates to specific cortical areas without rhythm distortion.

PubMed

Toda, Haruo; Kawasaki, Keisuke; Sato, Sho; Horie, Masao; Nakahara, Kiyoshi; Bepari, Asim K; Sawahata, Hirohito; Suzuki, Takafumi; Okado, Haruo; Takebayashi, Hirohide; Hasegawa, Isao

2018-05-16

Propagation of oscillatory spike firing activity at specific frequencies plays an important role in distributed cortical networks. However, there is limited evidence for how such frequency-specific signals are induced or how the signal spectra of the propagating signals are modulated during across-layer (radial) and inter-areal (tangential) neuronal interactions. To directly evaluate the direction specificity of spectral changes in a spiking cortical network, we selectively photostimulated infragranular excitatory neurons in the rat primary visual cortex (V1) at a supra-threshold level with various frequencies, and recorded local field potentials (LFPs) at the infragranular stimulation site, the cortical surface site immediately above the stimulation site in V1, and cortical surface sites outside V1. We found a significant reduction of LFP powers during radial propagation, especially at high-frequency stimulation conditions. Moreover, low-gamma-band dominant rhythms were transiently induced during radial propagation. Contrastingly, inter-areal LFP propagation, directed to specific cortical sites, accompanied no significant signal reduction nor gamma-band power induction. We propose an anisotropic mechanism for signal processing in the spiking cortical network, in which the neuronal rhythms are locally induced/modulated along the radial direction, and then propagate without distortion via intrinsic horizontal connections for spatiotemporally precise, inter-areal communication.

Effects of Transcranial Direct Current Stimulation, Transcranial Pulsed Current Stimulation, and Their Combination on Brain Oscillations in Patients with Chronic Visceral Pain: A Pilot Crossover Randomized Controlled Study.

PubMed

Thibaut, Aurore; Russo, Cristina; Hurtado-Puerto, Aura Maria; Morales-Quezada, Jorge Leon; Deitos, Alícia; Petrozza, John Christopher; Freedman, Steven; Fregni, Felipe

2017-01-01

Chronic visceral pain (CVP) syndromes are persistently painful disorders with a remarkable lack of effective treatment options. This study aimed at evaluating the effects of different neuromodulation techniques in patients with CVP on cortical activity, through electreocephalography (EEG) and on pain perception, through clinical tests. A pilot crossover randomized controlled study. Out-patient. Adults with CVP (>3 months). Participants received four interventions in a randomized order: (1) transcranial pulsed current stimulation (tPCS) and active transcranial direct current stimulation (tDCS) combined, (2) tPCS alone, (3) tDCS alone, and (4) sham condition. Resting state quantitative electroencephalography (qEEG) and pain assessments were performed before and after each intervention. Results were compared with a cohort of 47 healthy controls. We enrolled six patients with CVP for a total of 21 visits completed. Compared with healthy participants, patients with CVP showed altered cortical activity characterized by increased power in theta, alpha and beta bands, and a significant reduction in the alpha/beta ratio. Regarding tES, the combination of tDCS with tPCS had no effect on power in any of the bandwidths, nor brain regions. Comparing tPCS with tDCS alone, we found that tPCS induced higher increase in power within the theta and alpha bandwidths. This study confirms that patients with CVP present abnormal EEG-indexed cortical activity compared with healthy controls. Moreover, we showed that combining two types of neurostimulation techniques had no effect, whereas the two interventions, when applied individually, have different neural signatures.

Synchronizing theta oscillations with direct-current stimulation strengthens adaptive control in the human brain.

PubMed

Reinhart, Robert M G; Zhu, Julia; Park, Sohee; Woodman, Geoffrey F

2015-07-28

Executive control and flexible adjustment of behavior following errors are essential to adaptive functioning. Loss of adaptive control may be a biomarker of a wide range of neuropsychiatric disorders, particularly in the schizophrenia spectrum. Here, we provide support for the view that oscillatory activity in the frontal cortex underlies adaptive adjustments in cognitive processing following errors. Compared with healthy subjects, patients with schizophrenia exhibited low frequency oscillations with abnormal temporal structure and an absence of synchrony over medial-frontal and lateral-prefrontal cortex following errors. To demonstrate that these abnormal oscillations were the origin of the impaired adaptive control in patients with schizophrenia, we applied noninvasive dc electrical stimulation over the medial-frontal cortex. This noninvasive stimulation descrambled the phase of the low-frequency neural oscillations that synchronize activity across cortical regions. Following stimulation, the behavioral index of adaptive control was improved such that patients were indistinguishable from healthy control subjects. These results provide unique causal evidence for theories of executive control and cortical dysconnectivity in schizophrenia.

A cortical-spinal prosthesis for targeted limb movement in paralyzed primate avatars

PubMed Central

Shanechi, Maryam M.; Hu, Rollin C.; Williams, Ziv M.

2014-01-01

Motor paralysis is among the most disabling aspects of injury to the central nervous system. Here we develop and test a target-based cortical-spinal neural prosthesis that employs neural activity recorded from pre-motor neurons to control limb movements in functionally paralyzed primate avatars. Given the complexity by which muscle contractions are naturally controlled, we approach the problem of eliciting goal-directed limb movement in paralyzed animals by focusing on the intended targets of movement rather than their intermediate trajectories. We then match this information in real-time with spinal cord and muscle stimulation parameters that produce free planar limb movements to those intended target locations. We demonstrate that both the decoded activities of pre-motor populations and their adaptive responses can be used, after brief training, to effectively direct an avatar’s limb to distinct targets variably displayed on a screen. These findings advance the future possibility of reconstituting targeted limb movement in paralyzed subjects. PMID:24549394

Restoring voluntary control of locomotion after paralyzing spinal cord injury.

PubMed

van den Brand, Rubia; Heutschi, Janine; Barraud, Quentin; DiGiovanna, Jack; Bartholdi, Kay; Huerlimann, Michèle; Friedli, Lucia; Vollenweider, Isabel; Moraud, Eduardo Martin; Duis, Simone; Dominici, Nadia; Micera, Silvestro; Musienko, Pavel; Courtine, Grégoire

2012-06-01

Half of human spinal cord injuries lead to chronic paralysis. Here, we introduce an electrochemical neuroprosthesis and a robotic postural interface designed to encourage supraspinally mediated movements in rats with paralyzing lesions. Despite the interruption of direct supraspinal pathways, the cortex regained the capacity to transform contextual information into task-specific commands to execute refined locomotion. This recovery relied on the extensive remodeling of cortical projections, including the formation of brainstem and intraspinal relays that restored qualitative control over electrochemically enabled lumbosacral circuitries. Automated treadmill-restricted training, which did not engage cortical neurons, failed to promote translesional plasticity and recovery. By encouraging active participation under functional states, our training paradigm triggered a cortex-dependent recovery that may improve function after similar injuries in humans.

Thalamocortical integration of instrumental learning and performance and their disintegration in addiction.

PubMed

Balleine, Bernard W; Morris, Richard W; Leung, Beatrice K

2015-12-02

A recent focus of addiction research has been on the effect of drug exposure on the neural processes that mediate the acquisition and performance of goal-directed instrumental actions. Deficits in goal-directed control and a consequent dysregulation of habit learning processes have been described as resulting in compulsive drug seeking. Similarly, considerable research has focussed on the motivational and emotional changes that drugs produce and that result in changes in the incentive processes that modulate goal-directed performance. Although these areas have developed independently, we argue that the effects they described are likely not independent. Here we hypothesize that these changes result from a core deficit in the way the learning and performance factors that support goal-directed action are integrated at a neural level to maintain behavioural control. A dorsal basal ganglia stream mediating goal-directed learning and a ventral stream mediating various performance factors find several points of integration in the cortical basal ganglia system, most notably in the thalamocortical network linking basal ganglia output to a variety of cortical control centres. Recent research in humans and other animals is reviewed suggesting that learning and performance factors are integrated in a network centred on the mediodorsal thalamus and that disintegration in this network may provide the basis for a 'switch' from recreational to dysregulated drug seeking resulting in the well documented changes associated with addiction. Copyright © 2014 Elsevier B.V. All rights reserved.

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

PubMed

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

2001-08-01

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

Pre-cue Fronto-Occipital Alpha Phase and Distributed Cortical Oscillations Predict Failures of Cognitive Control

PubMed Central

Hamm, Jordan P.; Dyckman, Kara A.; McDowell, Jennifer E.; Clementz, Brett A.

2012-01-01

Cognitive control is required for correct performance on antisaccade tasks, including the ability to inhibit an externally driven ocular motor repsonse (a saccade to a peripheral stimulus) in favor of an internally driven ocular motor goal (a saccade directed away from a peripheral stimulus). Healthy humans occasionally produce errors during antisaccade tasks, but the mechanisms associated with such failures of cognitive control are uncertain. Most research on cognitive control failures focuses on post-stimulus processing, although a growing body of literature highlights a role of intrinsic brain activity in perceptual and cognitive performance. The current investigation used dense array electroencephalography and distributed source analyses to examine brain oscillations across a wide frequency bandwidth in the period prior to antisaccade cue onset. Results highlight four important aspects of ongoing and preparatory brain activations that differentiate error from correct antisaccade trials: (i) ongoing oscillatory beta (20–30Hz) power in anterior cingulate prior to trial initiation (lower for error trials), (ii) instantaneous phase of ongoing alpha-theta (7Hz) in frontal and occipital cortices immediately before trial initiation (opposite between trial types), (iii) gamma power (35–60Hz) in posterior parietal cortex 100 ms prior to cue onset (greater for error trials), and (iv) phase locking of alpha (5–12Hz) in parietal and occipital cortices immediately prior to cue onset (lower for error trials). These findings extend recently reported effects of pre-trial alpha phase on perception to cognitive control processes, and help identify the cortical generators of such phase effects. PMID:22593071

Prox1 Regulates the Subtype-Specific Development of Caudal Ganglionic Eminence-Derived GABAergic Cortical Interneurons

PubMed Central

Young, Allison; Petros, Timothy; Karayannis, Theofanis; McKenzie Chang, Melissa; Lavado, Alfonso; Iwano, Tomohiko; Nakajima, Miho; Taniguchi, Hiroki; Huang, Z. Josh; Heintz, Nathaniel; Oliver, Guillermo; Matsuzaki, Fumio; Machold, Robert P.

2015-01-01

Neurogliaform (RELN+) and bipolar (VIP+) GABAergic interneurons of the mammalian cerebral cortex provide critical inhibition locally within the superficial layers. While these subtypes are known to originate from the embryonic caudal ganglionic eminence (CGE), the specific genetic programs that direct their positioning, maturation, and integration into the cortical network have not been elucidated. Here, we report that in mice expression of the transcription factor Prox1 is selectively maintained in postmitotic CGE-derived cortical interneuron precursors and that loss of Prox1 impairs the integration of these cells into superficial layers. Moreover, Prox1 differentially regulates the postnatal maturation of each specific subtype originating from the CGE (RELN, Calb2/VIP, and VIP). Interestingly, Prox1 promotes the maturation of CGE-derived interneuron subtypes through intrinsic differentiation programs that operate in tandem with extrinsically driven neuronal activity-dependent pathways. Thus Prox1 represents the first identified transcription factor specifically required for the embryonic and postnatal acquisition of CGE-derived cortical interneuron properties. SIGNIFICANCE STATEMENT Despite the recognition that 30% of GABAergic cortical interneurons originate from the caudal ganglionic eminence (CGE), to date, a specific transcriptional program that selectively regulates the development of these populations has not yet been identified. Moreover, while CGE-derived interneurons display unique patterns of tangential and radial migration and preferentially populate the superficial layers of the cortex, identification of a molecular program that controls these events is lacking. Here, we demonstrate that the homeodomain transcription factor Prox1 is expressed in postmitotic CGE-derived cortical interneuron precursors and is maintained into adulthood. We found that Prox1 function is differentially required during both embryonic and postnatal stages of development to direct the migration, differentiation, circuit integration, and maintenance programs within distinct subtypes of CGE-derived interneurons. PMID:26377473

Brain cortical thickness in male adolescents with serious substance use and conduct problems.

PubMed

Chumachenko, Serhiy Y; Sakai, Joseph T; Dalwani, Manish S; Mikulich-Gilbertson, Susan K; Dunn, Robin; Tanabe, Jody; Young, Susan; McWilliams, Shannon K; Banich, Marie T; Crowley, Thomas J

2015-01-01

Adolescents with substance use disorder (SUD) and conduct problems exhibit high levels of impulsivity and poor self-control. Limited work to date tests for brain cortical thickness differences in these youths. To investigate differences in cortical thickness between adolescents with substance use and conduct problems and controls. We recruited 25 male adolescents with SUD, and 19 male adolescent controls, and completed structural 3T magnetic resonance brain imaging. Using the surface-based morphometry software FreeSurfer, we completed region-of-interest (ROI) analyses for group cortical thickness differences in left, and separately right, inferior frontal gyrus (IFG), orbitofrontal cortex (OFC) and insula. Using FreeSurfer, we completed whole-cerebrum analyses of group differences in cortical thickness. Versus controls, the SUD group showed no cortical thickness differences in ROI analyses. Controlling for age and IQ, no regions with cortical thickness differences were found using whole-cerebrum analyses (though secondary analyses co-varying IQ and whole-cerebrum cortical thickness yielded a between-group cortical thickness difference in the left posterior cingulate/precuneus). Secondary findings showed that the SUD group, relative to controls, demonstrated significantly less right > left asymmetry in IFG, had weaker insular-to-whole-cerebrum cortical thickness correlations, and showed a positive association between conduct disorder symptom count and cortical thickness in a superior temporal gyrus cluster. Functional group differences may reflect a more nuanced cortical morphometric difference than ROI cortical thickness. Further investigation of morphometric differences is needed. If replicable findings can be established, they may aid in developing improved diagnostic or more targeted treatment approaches.

Brain cortical thickness in male adolescents with serious substance use and conduct problems

PubMed Central

Chumachenko, Serhiy Y.; Sakai, Joseph T.; Dalwani, Manish S.; Mikulich-Gilbertson, Susan K.; Dunn, Robin; Tanabe, Jody; Young, Susan; McWilliams, Shannon K.; Banich, Marie T.; Crowley, Thomas J.

2016-01-01

Background Adolescents with substance use disorder (SUD) and conduct problems exhibit high levels of impulsivity and poor self-control. Limited work to date tests for brain cortical thickness differences in these youths. Objectives To investigate differences in cortical thickness between adolescents with substance use and conduct problems and controls. Methods We recruited 25 male adolescents with SUD, and 19 male adolescent controls, and completed structural 3T magnetic resonance brain imaging. Using the surface-based morphometry software FreeSurfer, we completed region-of-interest (ROI) analyses for group cortical thickness differences in left, and separately right, inferior frontal gyrus (IFG), orbitofrontal cortex (OFC) and insula. Using FreeSurfer, we completed whole-cerebrum analyses of group differences in cortical thickness. Results Versus controls, the SUD group showed no cortical thickness differences in ROI analyses. Controlling for age and IQ, no regions with cortical thickness differences were found using whole-cerebrum analyses (though secondary analyses co-varying IQ and whole-cerebrum cortical thickness yielded a between-group cortical thickness difference in the left posterior cingulate/precuneus). Secondary findings showed that the SUD group, relative to controls, demonstrated significantly less right>left asymmetry in IFG, had weaker insular-to-whole-cerebrum cortical thickness correlations, and showed a positive association between conduct disorder symptom count and cortical thickness in a superior temporal gyrus cluster. Conclusion Functional group differences may reflect a more nuanced cortical morphometric difference than ROI cortical thickness. Further investigation of morphometric differences is needed. If replicable findings can be established, they may aid in developing improved diagnostic or more targeted treatment approaches. PMID:26337200

Thresholds of cortical activation of muscle spindles and α motoneurones of the baboon's hand

PubMed Central

Koeze, T. H.; Phillips, C. G.; Sheridan, J. D.

1968-01-01

1. Much current thinking about voluntary movement assumes that the segmental γ loops can function as a servomechanism operated by the brain. However, the α motoneurones of the baboon's hand receive a powerful monosynaptic (CM) projection from the precentral gyrus. If servo-driving from the same cortical area is to be possible, it must project independently to the fusimotor neurones and have sufficient power to increase the afferent signalling from the muscle spindles. The cortical thresholds for contraction of m. extensor digitorum communis and for acceleration of the discharges of its muscle spindles have therefore been compared. 2. Significant results in this context require that the spindles studied be coupled in parallel with the responding extrafusal muscle fibres. Many spindles were not unloaded by the submaximal contractions evoked by cortical stimulation, although all so tested were unloaded by maximal motor nerve twitches. Reasons are given for thinking that such apparent lack of parallel coupling is an artifact of complex intramuscular anatomy and limitation of shortening by `isometric' myography. 3. A brief burst of corticospinal volleys at 500/sec, which is specially effective in exciting α motoneurones over the CM projection, failed to excite spindle afferents at or below the threshold for a cortical `twitch'. 4. In a few epileptiform discharges, bursts of spindle acceleration occurred independently of the clonic contractions. A relatively direct and independent cortico-fusimotor (CF) projection may therefore exist. 5. Prolonged near-threshold stimulation at 50-100/sec, which allows time for temporal summation in the less direct projections (e.g. cortico-interneuronal, cortico-rubro-spinal) and does not cause frequency-potentiation at CM synapses, gives abundant evidence of independent α and fusimotor projections, whose actions hardly outlast the stimulation period. 6. Although independent CF projections would permit servo-driving in natural movements of the hand (given adequate loop gain), there has been no evidence of servo-driving by cortical stimulation or in the spontaneous contractions of light anaesthesia. 7. Independent projections would provide for controlled αγ co-excitation in the servo-governing of natural movements (Matthews, 1964). 8. Evidence is reviewed that the CM projection itself may be part of an important control loop for voluntary movement in primates. A corollary would be a diminished importance of CF projections for segmental loops and an increased importance for maintaining the spindle input to cortical loops. PMID:4231033

Unimodal primary sensory cortices are directly connected by long-range horizontal projections in the rat sensory cortex.

PubMed

Stehberg, Jimmy; Dang, Phat T; Frostig, Ron D

2014-01-01

Research based on functional imaging and neuronal recordings in the barrel cortex subdivision of primary somatosensory cortex (SI) of the adult rat has revealed novel aspects of structure-function relationships in this cortex. Specifically, it has demonstrated that single whisker stimulation evokes subthreshold neuronal activity that spreads symmetrically within gray matter from the appropriate barrel area, crosses cytoarchitectural borders of SI and reaches deeply into other unimodal primary cortices such as primary auditory (AI) and primary visual (VI). It was further demonstrated that this spread is supported by a spatially matching underlying diffuse network of border-crossing, long-range projections that could also reach deeply into AI and VI. Here we seek to determine whether such a network of border-crossing, long-range projections is unique to barrel cortex or characterizes also other primary, unimodal sensory cortices and therefore could directly connect them. Using anterograde (BDA) and retrograde (CTb) tract-tracing techniques, we demonstrate that such diffuse horizontal networks directly and mutually connect VI, AI and SI. These findings suggest that diffuse, border-crossing axonal projections connecting directly primary cortices are an important organizational motif common to all major primary sensory cortices in the rat. Potential implications of these findings for topics including cortical structure-function relationships, multisensory integration, functional imaging, and cortical parcellation are discussed.

Unimodal primary sensory cortices are directly connected by long-range horizontal projections in the rat sensory cortex

PubMed Central

Stehberg, Jimmy; Dang, Phat T.; Frostig, Ron D.

2014-01-01

Research based on functional imaging and neuronal recordings in the barrel cortex subdivision of primary somatosensory cortex (SI) of the adult rat has revealed novel aspects of structure-function relationships in this cortex. Specifically, it has demonstrated that single whisker stimulation evokes subthreshold neuronal activity that spreads symmetrically within gray matter from the appropriate barrel area, crosses cytoarchitectural borders of SI and reaches deeply into other unimodal primary cortices such as primary auditory (AI) and primary visual (VI). It was further demonstrated that this spread is supported by a spatially matching underlying diffuse network of border-crossing, long-range projections that could also reach deeply into AI and VI. Here we seek to determine whether such a network of border-crossing, long-range projections is unique to barrel cortex or characterizes also other primary, unimodal sensory cortices and therefore could directly connect them. Using anterograde (BDA) and retrograde (CTb) tract-tracing techniques, we demonstrate that such diffuse horizontal networks directly and mutually connect VI, AI and SI. These findings suggest that diffuse, border-crossing axonal projections connecting directly primary cortices are an important organizational motif common to all major primary sensory cortices in the rat. Potential implications of these findings for topics including cortical structure-function relationships, multisensory integration, functional imaging, and cortical parcellation are discussed. PMID:25309339

Long-Term Stability of Motor Cortical Activity: Implications for Brain Machine Interfaces and Optimal Feedback Control.

PubMed

Flint, Robert D; Scheid, Michael R; Wright, Zachary A; Solla, Sara A; Slutzky, Marc W

2016-03-23

The human motor system is capable of remarkably precise control of movements--consider the skill of professional baseball pitchers or surgeons. This precise control relies upon stable representations of movements in the brain. Here, we investigated the stability of cortical activity at multiple spatial and temporal scales by recording local field potentials (LFPs) and action potentials (multiunit spikes, MSPs) while two monkeys controlled a cursor either with their hand or directly from the brain using a brain-machine interface. LFPs and some MSPs were remarkably stable over time periods ranging from 3 d to over 3 years; overall, LFPs were significantly more stable than spikes. We then assessed whether the stability of all neural activity, or just a subset of activity, was necessary to achieve stable behavior. We showed that projections of neural activity into the subspace relevant to the task (the "task-relevant space") were significantly more stable than were projections into the task-irrelevant (or "task-null") space. This provides cortical evidence in support of the minimum intervention principle, which proposes that optimal feedback control (OFC) allows the brain to tightly control only activity in the task-relevant space while allowing activity in the task-irrelevant space to vary substantially from trial to trial. We found that the brain appears capable of maintaining stable movement representations for extremely long periods of time, particularly so for neural activity in the task-relevant space, which agrees with OFC predictions. It is unknown whether cortical signals are stable for more than a few weeks. Here, we demonstrate that motor cortical signals can exhibit high stability over several years. This result is particularly important to brain-machine interfaces because it could enable stable performance with infrequent recalibration. Although we can maintain movement accuracy over time, movement components that are unrelated to the goals of a task (such as elbow position during reaching) often vary from trial to trial. This is consistent with the minimum intervention principle of optimal feedback control. We provide evidence that the motor cortex acts according to this principle: cortical activity is more stable in the task-relevant space and more variable in the task-irrelevant space. Copyright © 2016 the authors 0270-6474/16/363623-10$15.00/0.

The neurobiological role of the dorsolateral prefrontal cortex in recovery from trauma. Longitudinal brain imaging study among survivors of the South Korean subway disaster.

PubMed

Lyoo, In Kyoon; Kim, Jieun E; Yoon, Sujung J; Hwang, Jaeuk; Bae, Sujin; Kim, Dajung J

2011-07-01

A multiwave longitudinal neuroimaging study in a cohort of direct survivors of a South Korean subway disaster, most of whom recovered from posttraumatic stress disorder 5 years after trauma, provided a unique opportunity to investigate the brain correlates of recovery from a severe psychological trauma. To investigate region-specific brain mobilization during successful recovery from posttraumatic stress disorder by assessing cortical thickness multiple times from early after trauma to recovery, and to examine whether a brain-derived neurotrophic factor gene polymorphism was associated with this brain mobilization. Five-year follow-up case-control study conducted from 2003-2007. Seoul National University and Hospital. Thirty psychologically traumatized disaster survivors and 36 age- and sex-matched control group members recruited from the disaster registry and local community, respectively, who contributed 156 high-resolution brain magnetic resonance images during 3 waves of assessments. Cerebral cortical thickness measured in high-resolution anatomic magnetic resonance images using a validated cortical thickness analysis tool and its prospective changes from early after trauma to recovery in trauma-exposed individuals and controls. Trauma-exposed individuals had greater dorsolateral prefrontal cortical (DLPFC) thickness 1.42 years after trauma (right DLPFC, 5.4%; left superior frontal cortex, 5.8%; and left inferior frontal cortex, 5.3% [all clusters, P ≤ .01]) relative to controls. Thicknesses gradually normalized over time during recovery. We found a positive linear trend, with trauma-exposed individuals with a valine/valine genotype having the greatest DLPFC cortical thickness, followed by those with a methionine genotype and controls (P < .001 for trend). Greater DLPFC thickness was associated with greater posttraumatic stress disorder symptom reductions and better recovery. The DLPFC region might play an important role in psychological recovery from a severely traumatic event in humans.

The role of cortical oscillations in a spiking neural network model of the basal ganglia

PubMed Central

Fountas, Zafeirios; Shanahan, Murray

2017-01-01

Although brain oscillations involving the basal ganglia (BG) have been the target of extensive research, the main focus lies disproportionally on oscillations generated within the BG circuit rather than other sources, such as cortical areas. We remedy this here by investigating the influence of various cortical frequency bands on the intrinsic effective connectivity of the BG, as well as the role of the latter in regulating cortical behaviour. To do this, we construct a detailed neural model of the complete BG circuit based on fine-tuned spiking neurons, with both electrical and chemical synapses as well as short-term plasticity between structures. As a measure of effective connectivity, we estimate information transfer between nuclei by means of transfer entropy. Our model successfully reproduces firing and oscillatory behaviour found in both the healthy and Parkinsonian BG. We found that, indeed, effective connectivity changes dramatically for different cortical frequency bands and phase offsets, which are able to modulate (or even block) information flow in the three major BG pathways. In particular, alpha (8–12Hz) and beta (13–30Hz) oscillations activate the direct BG pathway, and favour the modulation of the indirect and hyper-direct pathways via the subthalamic nucleus—globus pallidus loop. In contrast, gamma (30–90Hz) frequencies block the information flow from the cortex completely through activation of the indirect pathway. Finally, below alpha, all pathways decay gradually and the system gives rise to spontaneous activity generated in the globus pallidus. Our results indicate the existence of a multimodal gating mechanism at the level of the BG that can be entirely controlled by cortical oscillations, and provide evidence for the hypothesis of cortically-entrained but locally-generated subthalamic beta activity. These two findings suggest new insights into the pathophysiology of specific BG disorders. PMID:29236724

Spatial and polarity precision of concentric high-definition transcranial direct current stimulation (HD-tDCS).

PubMed

Alam, Mahtab; Truong, Dennis Q; Khadka, Niranjan; Bikson, Marom

2016-06-21

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique that applies low amplitude current via electrodes placed on the scalp. Rather than directly eliciting a neuronal response, tDCS is believed to modulate excitability-enhancing or suppressing neuronal activity in regions of the brain depending on the polarity of stimulation. The specificity of tDCS to any therapeutic application derives in part from how electrode configuration determines the brain regions that are stimulated. Conventional tDCS uses two relatively large pads (>25 cm(2)) whereas high-definition tDCS (HD-tDCS) uses arrays of smaller electrodes to enhance brain targeting. The 4  ×  1 concentric ring HD-tDCS (one center electrode surrounded by four returns) has been explored in application where focal targeting of cortex is desired. Here, we considered optimization of concentric ring HD-tDCS for targeting: the role of electrodes in the ring and the ring's diameter. Finite element models predicted cortical electric field generated during tDCS. High resolution MRIs were segmented into seven tissue/material masks of varying conductivities. Computer aided design (CAD) model of electrodes, gel, and sponge pads were incorporated into the segmentation. Volume meshes were generated and the Laplace equation ([Formula: see text] · (σ [Formula: see text] V)  =  0) was solved for cortical electric field, which was interpreted using physiological assumptions to correlate with stimulation and modulation. Cortical field intensity was predicted to increase with increasing ring diameter at the cost of focality while uni-directionality decreased. Additional surrounding ring electrodes increased uni-directionality while lowering cortical field intensity and increasing focality; though, this effect saturated and more than 4 surround electrode would not be justified. Using a range of concentric HD-tDCS montages, we showed that cortical region of influence can be controlled while balancing other design factors such as intensity at the target and uni-directionality. Furthermore, the evaluated concentric HD-tDCS approaches can provide categorical improvements in targeting compared to conventional tDCS. Hypothesis driven clinical trials, based on specific target engagement, would benefit by this more precise method of stimulation that could avoid potentially confounding brain regions.

Perisylvian GABA levels in schizophrenia and bipolar disorder.

PubMed

Atagün, Murat İlhan; Şıkoğlu, Elif Muazzez; Soykan, Çağlar; Serdar Süleyman, Can; Ulusoy-Kaymak, Semra; Çayköylü, Ali; Algın, Oktay; Phillips, Mary Louise; Öngür, Dost; Moore, Constance Mary

2017-01-10

The aim of this study is to measure GABA levels of perisylvian cortices in schizophrenia and bipolar disorder patients, using proton magnetic resonance spectroscopy ( 1 H-MRS). Patients with schizophrenia (n=25), bipolar I disorder (BD-I; n=28) and bipolar II disorder (BD-II; n=20) were compared with healthy controls (n=30). 1 H-MRS data was acquired using a Siemens 3T whole body scanner to quantify right and left perisylvian structures' (including superior temporal lobes) GABA levels. Right perisylvian GABA values differed significantly between groups [χ 2 =9.62, df: 3, p=0.022]. GABA levels were significantly higher in the schizophrenia group compared with the healthy control group (p=0.002). Furthermore, Chlorpromazine equivalent doses of antipsychotics correlated with right hemisphere GABA levels (r 2 =0.68, p=0.006, n=33). GABA levels are elevated in the right hemisphere in patients with schizophrenia in comparison to bipolar disorder and healthy controls. The balance between excitatory and inhibitory controls over the cortical circuits may have direct relationship with GABAergic functions in auditory cortices. In addition, GABA levels may be altered by brain regions of interest, psychotropic medications, and clinical stage in schizophrenia and bipolar disorder. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Cerebello-cortical network fingerprints differ between essential, Parkinson's and mimicked tremors.

PubMed

Muthuraman, Muthuraman; Raethjen, Jan; Koirala, Nabin; Anwar, Abdul Rauf; Mideksa, Kidist G; Elble, Rodger; Groppa, Sergiu; Deuschl, Günter

2018-06-01

Cerebello-thalamo-cortical loops play a major role in the emergence of pathological tremors and voluntary rhythmic movements. It is unclear whether these loops differ anatomically or functionally in different types of tremor. We compared age- and sex-matched groups of patients with Parkinson's disease or essential tremor and healthy controls (n = 34 per group). High-density 256-channel EEG and multi-channel EMG from extensor and flexor muscles of both wrists were recorded simultaneously while extending the hands against gravity with the forearms supported. Tremor was thereby recorded from patients, and voluntarily mimicked tremor was recorded from healthy controls. Tomographic maps of EEG-EMG coherence were constructed using a beamformer algorithm coherent source analysis. The direction and strength of information flow between different coherent sources were estimated using time-resolved partial-directed coherence analyses. Tremor severity and motor performance measures were correlated with connection strengths between coherent sources. The topography of oscillatory coherent sources in the cerebellum differed significantly among the three groups, but the cortical sources in the primary sensorimotor region and premotor cortex were not significantly different. The cerebellar and cortical source combinations matched well with known cerebello-thalamo-cortical connections derived from functional MRI resting state analyses according to the Buckner-atlas. The cerebellar sources for Parkinson's tremor and essential tremor mapped primarily to primary sensorimotor cortex, but the cerebellar source for mimicked tremor mapped primarily to premotor cortex. Time-resolved partial-directed coherence analyses revealed activity flow mainly from cerebellum to sensorimotor cortex in Parkinson's tremor and essential tremor and mainly from cerebral cortex to cerebellum in mimicked tremor. EMG oscillation flowed mainly to the cerebellum in mimicked tremor, but oscillation flowed mainly from the cerebellum to EMG in Parkinson's and essential tremor. The topography of cerebellar involvement differed among Parkinson's, essential and mimicked tremors, suggesting different cerebellar mechanisms in tremorogenesis. Indistinguishable areas of sensorimotor cortex and premotor cerebral cortex were involved in all three tremors. Information flow analyses suggest that sensory feedback and cortical efferent copy input to cerebellum are needed to produce mimicked tremor, but tremor in Parkinson's disease and essential tremor do not depend on these mechanisms. Despite the subtle differences in cerebellar source topography, we found no evidence that the cerebellum is the source of oscillation in essential tremor or that the cortico-bulbo-cerebello-thalamocortical loop plays different tremorogenic roles in Parkinson's and essential tremor. Additional studies are needed to decipher the seemingly subtle differences in cerebellocortical function in Parkinson's and essential tremors.

What Is the Evidence for Inter-laminar Integration in a Prefrontal Cortical Minicolumn?

PubMed

Opris, Ioan; Chang, Stephano; Noga, Brian R

2017-01-01

The objective of this perspective article is to examine columnar inter-laminar integration during the executive control of behavior. The integration hypothesis posits that perceptual and behavioral signals are integrated within the prefrontal cortical inter-laminar microcircuits. Inter-laminar minicolumnar activity previously recorded from the dorsolateral prefrontal cortex (dlPFC) of nonhuman primates, trained in a visual delay match-to-sample (DMS) task, was re-assessed from an integrative perspective. Biomorphic multielectrode arrays (MEAs) played a unique role in the in vivo recording of columnar cell firing in the dlPFC layers 2/3 and 5/6. Several integrative aspects stem from these experiments: 1. Functional integration of perceptual and behavioral signals across cortical layers during executive control. The integrative effect of dlPFC minicolumns was shown by: (i) increased correlated firing on correct vs. error trials; (ii) decreased correlated firing when the number of non-matching images increased; and (iii) similar spatial firing preference across cortical-striatal cells during spatial-trials, and less on object-trials. 2. Causal relations to integration of cognitive signals by the minicolumnar turbo-engines. The inter-laminar integration between the perceptual and executive circuits was facilitated by stimulating the infra-granular layers with firing patterns obtained from supra-granular layers that enhanced spatial preference of percent correct performance on spatial trials. 3. Integration across hierarchical levels of the brain. The integration of intention signals (visual spatial, direction) with movement preparation (timing, velocity) in striatum and with the motor command and posture in midbrain is also discussed. These findings provide evidence for inter-laminar integration of executive control signals within brain's prefrontal cortical microcircuits.

Bicycling and Walking are Associated with Different Cortical Oscillatory Dynamics

PubMed Central

Storzer, Lena; Butz, Markus; Hirschmann, Jan; Abbasi, Omid; Gratkowski, Maciej; Saupe, Dietmar; Schnitzler, Alfons; Dalal, Sarang S.

2016-01-01

Although bicycling and walking involve similar complex coordinated movements, surprisingly Parkinson’s patients with freezing of gait typically remain able to bicycle despite severe difficulties in walking. This observation suggests functional differences in the motor networks subserving bicycling and walking. However, a direct comparison of brain activity related to bicycling and walking has never been performed, neither in healthy participants nor in patients. Such a comparison could potentially help elucidating the cortical involvement in motor control and the mechanisms through which bicycling ability may be preserved in patients with freezing of gait. The aim of this study was to contrast the cortical oscillatory dynamics involved in bicycling and walking in healthy participants. To this end, EEG and EMG data of 14 healthy participants were analyzed, who cycled on a stationary bicycle at a slow cadence of 40 revolutions per minute (rpm) and walked at 40 strides per minute (spm), respectively. Relative to walking, bicycling was associated with a stronger power decrease in the high beta band (23–35 Hz) during movement initiation and execution, followed by a stronger beta power increase after movement termination. Walking, on the other hand, was characterized by a stronger and persisting alpha power (8–12 Hz) decrease. Both bicycling and walking exhibited movement cycle-dependent power modulation in the 24–40 Hz range that was correlated with EMG activity. This modulation was significantly stronger in walking. The present findings reveal differential cortical oscillatory dynamics in motor control for two types of complex coordinated motor behavior, i.e., bicycling and walking. Bicycling was associated with a stronger sustained cortical activation as indicated by the stronger high beta power decrease during movement execution and less cortical motor control within the movement cycle. We speculate this to be due to the more continuous nature of bicycling demanding less phase-dependent sensory processing and motor planning, as opposed to walking. PMID:26924977

Neural Correlates of Lyrical Improvisation: An fMRI Study of Freestyle Rap

PubMed Central

Liu, Siyuan; Chow, Ho Ming; Xu, Yisheng; Erkkinen, Michael G.; Swett, Katherine E.; Eagle, Michael W.; Rizik-Baer, Daniel A.; Braun, Allen R.

2012-01-01

The neural correlates of creativity are poorly understood. Freestyle rap provides a unique opportunity to study spontaneous lyrical improvisation, a multidimensional form of creativity at the interface of music and language. Here we use functional magnetic resonance imaging to characterize this process. Task contrast analyses indicate that improvised performance is characterized by dissociated activity in medial and dorsolateral prefrontal cortices, providing a context in which stimulus-independent behaviors may unfold in the absence of conscious monitoring and volitional control. Connectivity analyses reveal widespread improvisation-related correlations between medial prefrontal, cingulate motor, perisylvian cortices and amygdala, suggesting the emergence of a network linking motivation, language, affect and movement. Lyrical improvisation appears to be characterized by altered relationships between regions coupling intention and action, in which conventional executive control may be bypassed and motor control directed by cingulate motor mechanisms. These functional reorganizations may facilitate the initial improvisatory phase of creative behavior. PMID:23155479

Neural correlates of lyrical improvisation: an FMRI study of freestyle rap.

PubMed

Liu, Siyuan; Chow, Ho Ming; Xu, Yisheng; Erkkinen, Michael G; Swett, Katherine E; Eagle, Michael W; Rizik-Baer, Daniel A; Braun, Allen R

2012-01-01

The neural correlates of creativity are poorly understood. Freestyle rap provides a unique opportunity to study spontaneous lyrical improvisation, a multidimensional form of creativity at the interface of music and language. Here we use functional magnetic resonance imaging to characterize this process. Task contrast analyses indicate that improvised performance is characterized by dissociated activity in medial and dorsolateral prefrontal cortices, providing a context in which stimulus-independent behaviors may unfold in the absence of conscious monitoring and volitional control. Connectivity analyses reveal widespread improvisation-related correlations between medial prefrontal, cingulate motor, perisylvian cortices and amygdala, suggesting the emergence of a network linking motivation, language, affect and movement. Lyrical improvisation appears to be characterized by altered relationships between regions coupling intention and action, in which conventional executive control may be bypassed and motor control directed by cingulate motor mechanisms. These functional reorganizations may facilitate the initial improvisatory phase of creative behavior.

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

Disorganization of Cortical Microtubules Stimulates Tangential Expansion and Reduces the Uniformity of Cellulose Microfibril Alignment among Cells in the Root of Arabidopsis1

PubMed Central

Baskin, Tobias I.; Beemster, Gerrit T.S.; Judy-March, Jan E.; Marga, Françoise

2004-01-01

To test the role of cortical microtubules in aligning cellulose microfibrils and controlling anisotropic expansion, we exposed Arabidopsis thaliana roots to moderate levels of the microtubule inhibitor, oryzalin. After 2 d of treatment, roots grow at approximately steady state. At that time, the spatial profiles of relative expansion rate in length and diameter were quantified, and roots were cryofixed, freeze-substituted, embedded in plastic, and sectioned. The angular distribution of microtubules as a function of distance from the tip was quantified from antitubulin immunofluorescence images. In alternate sections, the overall amount of alignment among microfibrils and their mean orientation as a function of position was quantified with polarized-light microscopy. The spatial profiles of relative expansion show that the drug affects relative elongation and tangential expansion rates independently. The microtubule distributions averaged to transverse in the growth zone for all treatments, but on oryzalin the distributions became broad, indicating poorly organized arrays. At a subcellular scale, cellulose microfibrils in oryzalin-treated roots were as well aligned as in controls; however, the mean alignment direction, while consistently transverse in the controls, was increasingly variable with oryzalin concentration, meaning that microfibril orientation in one location tended to differ from that of a neighboring location. This conclusion was confirmed by direct observations of microfibrils with field-emission scanning electron microscopy. Taken together, these results suggest that cortical microtubules ensure microfibrils are aligned consistently across the organ, thereby endowing the organ with a uniform mechanical structure. PMID:15299138

Attentional Gain Control of Ongoing Cortical Speech Representations in a “Cocktail Party”

PubMed Central

Kerlin, Jess R.; Shahin, Antoine J.; Miller, Lee M.

2010-01-01

Normal listeners possess the remarkable perceptual ability to select a single speech stream among many competing talkers. However, few studies of selective attention have addressed the unique nature of speech as a temporally extended and complex auditory object. We hypothesized that sustained selective attention to speech in a multi-talker environment would act as gain control on the early auditory cortical representations of speech. Using high-density electroencephalography and a template-matching analysis method, we found selective gain to the continuous speech content of an attended talker, greatest at a frequency of 4–8 Hz, in auditory cortex. In addition, the difference in alpha power (8–12 Hz) at parietal sites across hemispheres indicated the direction of auditory attention to speech, as has been previously found in visual tasks. The strength of this hemispheric alpha lateralization, in turn, predicted an individual’s attentional gain of the cortical speech signal. These results support a model of spatial speech stream segregation, mediated by a supramodal attention mechanism, enabling selection of the attended representation in auditory cortex. PMID:20071526

Direct visuomotor mapping for fast visually-evoked arm movements.

PubMed

Reynolds, Raymond F; Day, Brian L

2012-12-01

In contrast to conventional reaction time (RT) tasks, saccadic RT's to visual targets are very fast and unaffected by the number of possible targets. This can be explained by the sub-cortical circuitry underlying eye movements, which involves direct mapping between retinal input and motor output in the superior colliculus. Here we asked if the choice-invariance established for the eyes also applies to a special class of fast visuomotor responses of the upper limb. Using a target-pointing paradigm we observed very fast reaction times (<150 ms) which were completely unaffected as the number of possible target choices was increased from 1 to 4. When we introduced a condition of altered stimulus-response mapping, RT went up and a cost of choice was observed. These results can be explained by direct mapping between visual input and motor output, compatible with a sub-cortical pathway for visual control of the upper limb. Copyright © 2012 Elsevier Ltd. All rights reserved.

Trait-Related Cortical-Subcortical Dissociation in Bipolar Disorder: Analysis of Network Degree Centrality.

PubMed

Zhou, Qian; Womer, Fay Y; Kong, Lingtao; Wu, Feng; Jiang, Xiaowei; Zhou, Yifang; Wang, Dahai; Bai, Chuan; Chang, Miao; Fan, Guoguang; Xu, Ke; He, Yong; Tang, Yanqing; Wang, Fei

2017-05-01

Bipolar disorder is a systemic brain disorder. Accumulated evidence suggested that cortical-subcortical imbalance could be a trait-related pathogenic factor of bipolar disorder. Degree centrality, a robust index of focal connectivity in which the number of direct connections from one node to all nodes is counted, has not previously been studied in bipolar disorder as a whole. Resting state functional magnetic resonance imaging was performed on 52 patients with DSM-IV bipolar I disorder and 70 healthy controls recruited between September 2009 and July 2014. Degree centrality was calculated within cerebral gray matter for each subject and compared between patients with bipolar disorder and healthy controls. Hub distributions of both groups were explored. Effects of medication exposure and mood state on degree centrality, as well as cortical-subcortical degree centrality correlations, were explored. Compared to healthy controls, patients with bipolar disorder exhibited significant decrease in degree centrality in cortical regions, including the middle temporal pole, inferior temporal gyrus, and ventral prefrontal cortex, but showed significant increase in degree centrality mainly in subcortical regions, including caudate, thalamus, parahippocampal gyrus, hippocampi, anterior cingulate, insula, and amygdala, and a small portion of cortical regions, such as superior and middle frontal gyrus (P < .05, corrected). Spatial distributions of the 2 groups were very similar. No significant effects of medication exposure or mood state on degree centrality were found. Patients with bipolar disorder also showed significant decrease in cortical-subcortical degree centrality correlation (P = .003). These findings further contribute to the mounting evidence of cortical-subcortical dissociation in bipolar disorder pathophysiology. In addition, this study supports the continued development and implementation of graph-based techniques to enhance our understanding of the underlying neural mechanisms in mental disorders such as bipolar disorder, which are increasingly viewed as systemic brain disorders rather than disorders arising from disruption within a single structure or a limited number of structures. Due to the heterogeneity of our sample, as well as the small sample size of each medication and mood state subgroups, further investigation is needed to support our findings. © Copyright 2016 Physicians Postgraduate Press, Inc.

The Effect of Binaural Beats on Visuospatial Working Memory and Cortical Connectivity.

PubMed

Beauchene, Christine; Abaid, Nicole; Moran, Rosalyn; Diana, Rachel A; Leonessa, Alexander

2016-01-01

Binaural beats utilize a phenomenon that occurs within the cortex when two different frequencies are presented separately to each ear. This procedure produces a third phantom binaural beat, whose frequency is equal to the difference of the two presented tones and which can be manipulated for non-invasive brain stimulation. The effects of binaural beats on working memory, the system in control of temporary retention and online organization of thoughts for successful goal directed behavior, have not been well studied. Furthermore, no studies have evaluated the effects of binaural beats on brain connectivity during working memory tasks. In this study, we determined the effects of different acoustic stimulation conditions on participant response accuracy and cortical network topology, as measured by EEG recordings, during a visuospatial working memory task. Three acoustic stimulation control conditions and three binaural beat stimulation conditions were used: None, Pure Tone, Classical Music, 5Hz binaural beats, 10Hz binaural beats, and 15Hz binaural beats. We found that listening to 15Hz binaural beats during a visuospatial working memory task not only increased the response accuracy, but also modified the strengths of the cortical networks during the task. The three auditory control conditions and the 5Hz and 10Hz binaural beats all decreased accuracy. Based on graphical network analyses, the cortical activity during 15Hz binaural beats produced networks characteristic of high information transfer with consistent connection strengths throughout the visuospatial working memory task.

The Effect of Binaural Beats on Visuospatial Working Memory and Cortical Connectivity

PubMed Central

Abaid, Nicole; Moran, Rosalyn; Diana, Rachel A.; Leonessa, Alexander

2016-01-01

Binaural beats utilize a phenomenon that occurs within the cortex when two different frequencies are presented separately to each ear. This procedure produces a third phantom binaural beat, whose frequency is equal to the difference of the two presented tones and which can be manipulated for non-invasive brain stimulation. The effects of binaural beats on working memory, the system in control of temporary retention and online organization of thoughts for successful goal directed behavior, have not been well studied. Furthermore, no studies have evaluated the effects of binaural beats on brain connectivity during working memory tasks. In this study, we determined the effects of different acoustic stimulation conditions on participant response accuracy and cortical network topology, as measured by EEG recordings, during a visuospatial working memory task. Three acoustic stimulation control conditions and three binaural beat stimulation conditions were used: None, Pure Tone, Classical Music, 5Hz binaural beats, 10Hz binaural beats, and 15Hz binaural beats. We found that listening to 15Hz binaural beats during a visuospatial working memory task not only increased the response accuracy, but also modified the strengths of the cortical networks during the task. The three auditory control conditions and the 5Hz and 10Hz binaural beats all decreased accuracy. Based on graphical network analyses, the cortical activity during 15Hz binaural beats produced networks characteristic of high information transfer with consistent connection strengths throughout the visuospatial working memory task. PMID:27893766

The effects of anaesthetic agents on cortical mapping during neurosurgical procedures involving eloquent areas of the brain.

PubMed

Adhikary, Sanjib D; Thiruvenkatarajan, Venkatesan; Babu, K Srinivasa; Tharyan, Prathap

2011-11-09

In patients presenting for surgical resection of lesions involving, or adjacent to, the functionally important eloquent cortical areas, it is vital to achieve complete or near complete resection of the pathology without damaging the healthy surrounding tissues.The eloquent areas that the surgeons are concerned with are the primary motor, premotor cortex, supplementary motor cortex and speech areas. If the lesions are within these regions surgeons could either take a biopsy or do a intracapsular decompression without damaging the mentioned areas to avoid postoperative dysfunction. If the lesions are adjacent to the above mentioned areas, the normal anatomy would get distorted. However, proper identification of the above mentioned areas would enable the surgeon to radically remove the tumours. Intraoperative mapping of the cortex with stimulating and recording electrodes is termed as electrophysiological (EP) mapping.The EP mapping of motor, sensory and language cortex is widely employed in the resection of lesions involving or adjacent to the eloquent areas. Both intravenous and inhalational agents are known to affect these EP mapping techniques. The aim of this review was to evaluate the effect of anaesthetic agents on intra-operative EP mapping in patients undergoing neurosurgical procedures involving, or adjacent to, the functional areas of the cortex under general anaesthesia. We searched the Cochrane Epilepsy Group Specialized Register (7 March 2011), The Cochrane Central Register of Controlled Trials (CENTRAL issue 1 of 4, The Cochrane Library 2011), MEDLINE (Ovid, 1948 to February week 4, 2011), PsycINFO (EBSCOhost, 7 March 2011), and the National Research Register Archive and UK Clinical Research Network (7 March 2011). We also contacted other researchers in the field in an attempt to ascertain unpublished studies. We planned to include randomised and quasi randomised controlled trials irrespective of blinding in patients of any age or gender undergoing neurosurgery under general anaesthesia where cortical mapping was attempted to identify eloquent areas using either somatosensory evoked potentials (SSEPs), or direct cortical stimulation (DCS) triggered muscle motor evoked potentials (mMEPs), or both. We excluded patients from trials where the anaesthetic effects were evaluated during spinal cord surgery or where MEPs were recorded from modes other than direct cortical stimulation such as transcranial electrical stimulation (TcMEPs), MEPs derived from epidural electrodes (D waves) and magnetic stimulation and trials involving awake craniotomies or the asleep-awake-asleep technique during cortical mapping. Two review authors planned to independently apply the inclusion criteria and extract data. No RCTs were found for this study population. This review highlights the need for well-designed randomised controlled trials to assess the effect of anaesthetic agents on cortical mapping during neurosurgical procedures involving eloquent areas of the brain.

No Effects of Bilateral tDCS over Inferior Frontal Gyrus on Response Inhibition and Aggression

PubMed Central

Lobbestael, Jill; Arntz, Arnoud; Brugman, Suzanne; Sack, Alexander T.

2015-01-01

Response inhibition is defined as the capacity to adequately withdraw pre-planned responses. It has been shown that individuals with deficits in inhibiting pre-planned responses tend to display more aggressive behaviour. The prefrontal cortex is involved in both, response inhibition and aggression. While response inhibition is mostly associated with predominantly right prefrontal activity, the neural components underlying aggression seem to be left-lateralized. These differences in hemispheric dominance are conceptualized in cortical asymmetry theories on motivational direction, which assign avoidance motivation (relevant to inhibit responses) to the right and approach motivation (relevant for aggressive actions) to the left prefrontal cortex. The current study aimed to directly address the inverse relationship between response inhibition and aggression by assessing them within one experiment. Sixty-nine healthy participants underwent bilateral transcranial Direct Current Stimulation (tDCS) to the inferior frontal cortex. In one group we induced right-hemispheric fronto-cortical dominance by means of a combined right prefrontal anodal and left prefrontal cathodal tDCS montage. In a second group we induced left-hemispheric fronto-cortical dominance by means of a combined left prefrontal anodal and right prefrontal cathodal tDCS montage. A control group received sham stimulation. Response inhibition was assessed with a go/no-go task (GNGT) and aggression with the Taylor Aggression Paradigm (TAP). We revealed that participants with poorer performance in the GNGT displayed more aggression during the TAP. No effects of bilateral prefrontal tDCS on either response inhibition or aggression were observed. This is at odds with previous brain stimulation studies applying unilateral protocols. Our results failed to provide evidence in support of the prefrontal cortical asymmetry model in the domain of response inhibition and aggression. The absence of tDCS effects might also indicate that the methodological approach of shifting cortical asymmetry by means of bilateral tDCS protocols has failed. PMID:26161664

Estimation of Locomotion States of a Rat by Neural Signals from the Motor Cortices Based on a Linear Correlation Model

NASA Astrophysics Data System (ADS)

Fukayama, Osamu; Taniguchi, Noriyuki; Suzuki, Takafumi; Mabuchi, Kunihiko

We are developing a brain-machine interface (BMI) called “RatCar," a small vehicle controlled by the neural signals of a rat's brain. An unconfined adult rat with a set of bundled neural electrodes in the brain rides on the vehicle. Each bundle consists of four tungsten wires isolated with parylene polymer. These bundles were implanted in the primary motor and premotor cortices in both hemispheres of the brain. In this paper, methods and results for estimating locomotion speed and directional changes are described. Neural signals were recorded as the rat moved in a straight line and as it changed direction in a curve. Spike-like waveforms were then detected and classified into several clusters to calculate a firing rate for each neuron. The actual locomotion velocity and directional changes of the rat were recorded concurrently. Finally, the locomotion states were correlated with the neural firing rates using a simple linear model. As a result, the abstract estimation of the locomotion velocity and directional changes were achieved.

The effect of binaural beats on verbal working memory and cortical connectivity.

PubMed

Beauchene, Christine; Abaid, Nicole; Moran, Rosalyn; Diana, Rachel A; Leonessa, Alexander

2017-04-01

Synchronization in activated regions of cortical networks affect the brain's frequency response, which has been associated with a wide range of states and abilities, including memory. A non-invasive method for manipulating cortical synchronization is binaural beats. Binaural beats take advantage of the brain's response to two pure tones, delivered independently to each ear, when those tones have a small frequency mismatch. The mismatch between the tones is interpreted as a beat frequency, which may act to synchronize cortical oscillations. Neural synchrony is particularly important for working memory processes, the system controlling online organization and retention of information for successful goal-directed behavior. Therefore, manipulation of synchrony via binaural beats provides a unique window into working memory and associated connectivity of cortical networks. In this study, we examined the effects of different acoustic stimulation conditions during an N-back working memory task, and we measured participant response accuracy and cortical network topology via EEG recordings. Six acoustic stimulation conditions were used: None, Pure Tone, Classical Music, 5 Hz binaural beats, 10 Hz binaural beats, and 15 Hz binaural beats. We determined that listening to 15 Hz binaural beats during an N-Back working memory task increased the individual participant's accuracy, modulated the cortical frequency response, and changed the cortical network connection strengths during the task. Only the 15 Hz binaural beats produced significant change in relative accuracy compared to the None condition. Listening to 15 Hz binaural beats during the N-back task activated salient frequency bands and produced networks characterized by higher information transfer as compared to other auditory stimulation conditions.

Why do parallel cortical systems exist for the perception of static form and moving form?

PubMed

Grossberg, S

1991-02-01

This article analyzes computational properties that clarify why the parallel cortical systems V1----V2, V1----MT, and V1----V2----MT exist for the perceptual processing of static visual forms and moving visual forms. The article describes a symmetry principle, called FM symmetry, that is predicted to govern the development of these parallel cortical systems by computing all possible ways of symmetrically gating sustained cells with transient cells and organizing these sustained-transient cells into opponent pairs of on-cells and off-cells whose output signals are insensitive to direction of contrast. This symmetric organization explains how the static form system (static BCS) generates emergent boundary segmentations whose outputs are insensitive to direction of contrast and insensitive to direction of motion, whereas the motion form system (motion BCS) generates emergent boundary segmentations whose outputs are insensitive to direction of contrast but sensitive to direction of motion. FM symmetry clarifies why the geometries of static and motion form perception differ--for example, why the opposite orientation of vertical is horizontal (90 degrees), but the opposite direction of up is down (180 degrees). Opposite orientations and directions are embedded in gated dipole opponent processes that are capable of antagonistic rebound. Negative afterimages, such as the MacKay and waterfall illusions, are hereby explained as are aftereffects of long-range apparent motion. These antagonistic rebounds help to control a dynamic balance between complementary perceptual states of resonance and reset. Resonance cooperatively links features into emergent boundary segmentations via positive feedback in a CC loop, and reset terminates a resonance when the image changes, thereby preventing massive smearing of percepts. These complementary preattentive states of resonance and reset are related to analogous states that govern attentive feature integration, learning, and memory search in adaptive resonance theory. The mechanism used in the V1----MT system to generate a wave of apparent motion between discrete flashes may also be used in other cortical systems to generate spatial shifts of attention. The theory suggests how the V1----V2----MT cortical stream helps to compute moving form in depth and how long-range apparent motion of illusory contours occurs. These results collectively argue against vision theories that espouse independent processing modules. Instead, specialized subsystems interact to overcome computational uncertainties and complementary deficiencies, to cooperatively bind features into context-sensitive resonances, and to realize symmetry principles that are predicted to govern the development of the visual cortex.

Changes in cortical thickness during the course of illness in schizophrenia.

PubMed

van Haren, Neeltje E M; Schnack, Hugo G; Cahn, Wiepke; van den Heuvel, Martijn P; Lepage, Claude; Collins, Louis; Evans, Alan C; Hulshoff Pol, Hilleke E; Kahn, René S

2011-09-01

Whether cortical thickness changes in schizophrenia over time are more pronounced relative to the changes that can be attributed to normal aging has not been studied. To compare patients with schizophrenia and healthy control participants on cortical thickness change. A 5-year longitudinal study comparing schizophrenic patients and healthy controls using 2 magnetic resonance images of the brain. Patients were recruited from the Department of Psychiatry at the University Medical Centre Utrecht and from other psychiatric hospitals in the Netherlands. Healthy controls were recruited via advertisement in newspapers and notice boards. Ninety-six schizophrenic patients and 113 healthy controls aged 16 to 56 years. Cortical thickness and change in cortical thickness on a vertex-by-vertex basis across the cortical mantle, measures of functional and symptomatic outcome, and cumulative intake of antipsychotics during the scan interval. At baseline, the schizophrenic patients had thinner left orbitofrontal and right parahippocampal and superior temporal cortices and a thicker superior parietal lobule and occipital pole compared with the controls. Mean cortical thickness did not differ between the groups. Over time, excessive cortical thinning was found in widespread areas on the cortical mantle, most pronounced bilaterally in the temporal cortex and in the left frontal area. Poor outcome in patients was associated with more pronounced cortical thinning. Higher cumulative intake of typical antipsychotics during the scan interval was associated with more pronounced cortical thinning, whereas higher cumulative intake of atypical antipsychotic medication was associated with less pronounced cortical thinning. In schizophrenia, the cortex shows excessive thinning over time in widespread areas of the brain, most pronounced in the frontal and temporal areas, and progresses across the entire course of the illness. The excessive thinning of the cortex appears related to outcome and medication intake.

The Neural Substrates for Letter String Readings in The Normal and Reverse Directions: An fMRI Study

NASA Astrophysics Data System (ADS)

Ge, Sheng; Saito, Takashi; Wu, Jing-Long; Ogasawara, Jun-Ichi; Yamauchi, Shuichi; Matsunaga, Naofumi; Iramina, Keiji

In order to investigate the difference in cortical activations between reading letter strings in the normal direction and the reverse direction, an fMRI study was conducted. In this study, the cortical activations elicited by Japanese letter string reading and Chinese letter string reading were investigated. The subjects performed the normal direction reading task (read letter strings from left to right), and the reverse direction reading task (read letter strings from right to left). According to the experimental results, the activated brain regions during the normal and the reverse direction reading tasks were compared. It was found that visuospatial transformation was involved in the reverse direction reading task, while this function was not significant during the normal direction reading task. Furthermore, we found that there was no significant difference in cortical activation between Japanese and Chinese letter string readings.

Myosin-II controls cellular branching morphogenesis and migration in 3D by minimizing cell surface curvature

PubMed Central

Elliott, Hunter; Fischer, Robert A.; Myers, Kenneth A.; Desai, Ravi A.; Gao, Lin; Chen, Christopher S.; Adelstein, Robert; Waterman, Clare M.; Danuser, Gaudenz

2014-01-01

In many cases cell function is intimately linked to cell shape control. We utilized endothelial cell branching morphogenesis as a model to understand the role of myosin-II in shape control of invasive cells migrating in 3D collagen gels. We applied principles of differential geometry and mathematical morphology to 3D image sets to parameterize cell branch structure and local cell surface curvature. We find that Rho/ROCK-stimulated myosin-II contractility minimizes cell-scale branching by recognizing and minimizing local cell surface curvature. Utilizing micro-fabrication to constrain cell shape identifies a positive feedback mechanism in which low curvature stabilizes myosin-II cortical association, where it acts to maintain minimal curvature. The feedback between myosin-II regulation by and control of curvature drives cycles of localized cortical myosin-II assembly and disassembly. These cycles in turn mediate alternating phases of directionally biased branch initiation and retraction to guide 3D cell migration. PMID:25621949

Theta dynamics reveal domain-specific control over stimulus and response conflict.

PubMed

Nigbur, Roland; Cohen, Michael X; Ridderinkhof, K Richard; Stürmer, Birgit

2012-05-01

Cognitive control allows us to adjust to environmental changes. The medial frontal cortex (MFC) is thought to detect conflicts and recruit additional resources from other brain areas including the lateral prefrontal cortices. Here we investigated how the MFC acts in concert with visual, motor, and lateral prefrontal cortices to support adaptations of goal-directed behavior. Physiologically, these interactions may occur through local and long-range synchronized oscillation dynamics, particularly in the theta range (4-8 Hz). A speeded flanker task allowed us to investigate conflict-type-specific control networks for perceptual and response conflicts. Theta power over MFC was sensitive to both perceptual and response conflict. Interareal theta phase synchrony, however, indicated a selective enhancement specific for response conflicts between MFC and left frontal cortex as well as between MFC and the presumed motor cortex contralateral to the response hand. These findings suggest that MFC theta-band activity is both generally involved in conflict processing and specifically involved in linking a neural network controlling response conflict.

A GPU-accelerated cortical neural network model for visually guided robot navigation.

PubMed

Beyeler, Michael; Oros, Nicolas; Dutt, Nikil; Krichmar, Jeffrey L

2015-12-01

Humans and other terrestrial animals use vision to traverse novel cluttered environments with apparent ease. On one hand, although much is known about the behavioral dynamics of steering in humans, it remains unclear how relevant perceptual variables might be represented in the brain. On the other hand, although a wealth of data exists about the neural circuitry that is concerned with the perception of self-motion variables such as the current direction of travel, little research has been devoted to investigating how this neural circuitry may relate to active steering control. Here we present a cortical neural network model for visually guided navigation that has been embodied on a physical robot exploring a real-world environment. The model includes a rate based motion energy model for area V1, and a spiking neural network model for cortical area MT. The model generates a cortical representation of optic flow, determines the position of objects based on motion discontinuities, and combines these signals with the representation of a goal location to produce motor commands that successfully steer the robot around obstacles toward the goal. The model produces robot trajectories that closely match human behavioral data. This study demonstrates how neural signals in a model of cortical area MT might provide sufficient motion information to steer a physical robot on human-like paths around obstacles in a real-world environment, and exemplifies the importance of embodiment, as behavior is deeply coupled not only with the underlying model of brain function, but also with the anatomical constraints of the physical body it controls. Copyright © 2015 Elsevier Ltd. All rights reserved.

A Novel Plasma Membrane-Anchored Protein Regulates Xylem Cell-Wall Deposition through Microtubule-Dependent Lateral Inhibition of Rho GTPase Domains.

PubMed

Sugiyama, Yuki; Wakazaki, Mayumi; Toyooka, Kiminori; Fukuda, Hiroo; Oda, Yoshihisa

2017-08-21

Spatial control of cell-wall deposition is essential for determining plant cell shape [1]. Rho-type GTPases, together with the cortical cytoskeleton, play central roles in regulating cell-wall patterning [2]. In metaxylem vessel cells, which are the major components of xylem tissues, active ROP11 Rho GTPases form oval plasma membrane domains that locally disrupt cortical microtubules, thereby directing the formation of oval pits in secondary cell walls [3-5]. However, the regulatory mechanism that determines the planar shape of active Rho of Plants (ROP) domains is still unknown. Here we show that IQD13 associates with cortical microtubules and the plasma membrane to laterally restrict the localization of ROP GTPase domains, thereby directing the formation of oval secondary cell-wall pits. Loss and overexpression of IQD13 led to the formation of abnormally round and narrow secondary cell-wall pits, respectively. Ectopically expressed IQD13 increased the presence of parallel cortical microtubules by promoting microtubule rescue. A reconstructive approach revealed that IQD13 confines the area of active ROP domains within the lattice of the cortical microtubules, causing narrow ROP domains to form. This activity required the interaction of IQD13 with the plasma membrane. These findings suggest that IQD13 positively regulates microtubule dynamics as well as their linkage to the plasma membrane, which synergistically confines the area of active ROP domains, leading to the formation of oval secondary cell-wall pits. This finding sheds light on the role of microtubule-plasma membrane linkage as a lateral fence that determines the planar shape of Rho GTPase domains. Copyright © 2017 Elsevier Ltd. All rights reserved.

The incorporation of fluoride and strontium in hydroxyapatite affects the composition, structure, and mechanical properties of human cortical bone.

PubMed

Riedel, Christoph; Zimmermann, Elizabeth A; Zustin, Jozef; Niecke, Manfred; Amling, Michael; Grynpas, Marc; Busse, Björn

2017-02-01

Strontium ranelate and fluoride salts are therapeutic options to reduce fracture risk in osteoporosis. Incorporation of these elements in the physiological hydroxyapatite matrix of bone is accompanied by changes in bone remodeling, composition, and structure. However, a direct comparison of the effectiveness of strontium and fluoride treatment in human cortical bone with a focus on the resulting mechanical properties remains to be established. Study groups are composed of undecalcified specimens from healthy controls, treatment-naïve osteoporosis cases, and strontium ranelate or fluoride-treated osteoporosis cases. Concentrations of both elements were determined using instrumental neutron activation analysis (INAA). Backscattered electron imaging was carried out to investigate the calcium content and the cortical microstructure. In comparison to osteoporotic patients, fluoride and strontium-treated patients have a lower cortical porosity indicating an improvement in bone microstructure. Mechanical properties were assessed via reference point indentation as a measure of bone's resistance to deformation. The strontium-incorporation led to significantly lower total indentation distance values compared to osteoporotic cases; controls have the highest resistance to indentation. In conclusion, osteoporosis treatment with strontium and fluoride showed positive effects on the microstructure and the mechanical characteristics of bone in comparison to treatment-naïve osteoporotic bone. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 433-442, 2017. © 2016 Wiley Periodicals, Inc.

A gradient in cortical pathology in multiple sclerosis by in vivo quantitative 7 T imaging

PubMed Central

Louapre, Céline; Govindarajan, Sindhuja T.; Giannì, Costanza; Nielsen, A. Scott; Cohen-Adad, Julien; Sloane, Jacob; Kinkel, Revere P.

2015-01-01

We used a surface-based analysis of T2* relaxation rates at 7 T magnetic resonance imaging, which allows sampling quantitative T2* throughout the cortical width, to map in vivo the spatial distribution of intracortical pathology in multiple sclerosis. Ultra-high resolution quantitative T2* maps were obtained in 10 subjects with clinically isolated syndrome/early multiple sclerosis (≤3 years disease duration), 18 subjects with relapsing-remitting multiple sclerosis (≥4 years disease duration), 13 subjects with secondary progressive multiple sclerosis, and in 17 age-matched healthy controls. Quantitative T2* maps were registered to anatomical cortical surfaces for sampling T2* at 25%, 50% and 75% depth from the pial surface. Differences in laminar quantitative T2* between each patient group and controls were assessed using general linear model (P < 0.05 corrected for multiple comparisons). In all 41 multiple sclerosis cases, we tested for associations between laminar quantitative T2*, neurological disability, Multiple Sclerosis Severity Score, cortical thickness, and white matter lesions. In patients, we measured, T2* in intracortical lesions and in the intracortical portion of leukocortical lesions visually detected on 7 T scans. Cortical lesional T2* was compared with patients’ normal-appearing cortical grey matter T2* (paired t-test) and with mean cortical T2* in controls (linear regression using age as nuisance factor). Subjects with multiple sclerosis exhibited relative to controls, independent from cortical thickness, significantly increased T2*, consistent with cortical myelin and iron loss. In early disease, T2* changes were focal and mainly confined at 25% depth, and in cortical sulci. In later disease stages T2* changes involved deeper cortical laminae, multiple cortical areas and gyri. In patients, T2* in intracortical and leukocortical lesions was increased compared with normal-appearing cortical grey matter (P < 10−10 and P < 10−7), and mean cortical T2* in controls (P < 10−5 and P < 10−6). In secondary progressive multiple sclerosis, T2* in normal-appearing cortical grey matter was significantly increased relative to controls (P < 0.001). Laminar T2* changes may, thus, result from cortical pathology within and outside focal cortical lesions. Neurological disability and Multiple Sclerosis Severity Score correlated each with the degree of laminar quantitative T2* changes, independently from white matter lesions, the greatest association being at 25% depth, while they did not correlate with cortical thickness and volume. These findings demonstrate a gradient in the expression of cortical pathology throughout stages of multiple sclerosis, which was associated with worse disability and provides in vivo evidence for the existence of a cortical pathological process driven from the pial surface. PMID:25681411

14-3-3 coordinates microtubules, Rac, and myosin II to control cell mechanics and cytokinesis

PubMed Central

Zhou, Qiongqiong; Kee, Yee-Seir; Poirier, Christopher C.; Jelinek, Christine; Osborne, Jonathan; Divi, Srikanth; Surcel, Alexandra; Will, Marie E.; Eggert, Ulrike S.; Müller-Taubenberger, Annette; Iglesias, Pablo A.; Cotter, Robert J.; Robinson, Douglas N.

2010-01-01

Summary Background During cytokinesis, regulatory signals are presumed to emanate from the mitotic spindle. However, what these signals are and how they lead to the spatiotemporal changes in the cortex structure, mechanics, and regional contractility are not well understood in any system. Results To investigate pathways that link the microtubule network to the cortical changes that promote cytokinesis, we used chemical genetics in Dictyostelium to identify genetic suppressors of nocodazole, a microtubule depolymerizer. We identified 14-3-3 and found that it is enriched in the cortex, helps maintain steady state microtubule length, contributes to normal cortical tension, modulates actin wave formation, and controls the symmetry and kinetics of cleavage furrow contractility during cytokinesis. Furthermore, 14-3-3 acts downstream of a Rac small GTPase (RacE), associates with myosin II heavy chain and is needed to promote myosin II bipolar thick filament remodeling. Conclusion 14-3-3 connects microtubules, Rac and myosin II to control several aspects of cortical dynamics, mechanics, and cytokinesis cell shape change. Further, 14-3-3 interacts directly with myosin II heavy chain to promote bipolar thick filament remodeling and distribution. Overall, 14-3-3 appears to integrate several critical cytoskeletal elements that drive two important processes cytokinesis shape change and cell mechanics. PMID:20951045

Cortical bone deficit and fat infiltration of bone marrow and skeletal muscle in ambulatory children with mild spastic cerebral palsy

PubMed Central

Whitney, Daniel G.; Singh, Harshvardhan; Miller, Freeman; Barbe, Mary F.; Slade, Jill M.; Pohlig, Ryan T.; Modlesky, Christopher M.

2016-01-01

Introduction Nonambulatory children with severe cerebral palsy (CP) have an underdeveloped bone architecture, low bone strength and a high degree of fat infiltration in the lower extremity musculature. The present study aims to determine if such a profile exists in ambulatory children with mild CP and if excess fat infiltration extends into the bone marrow. Materials and methods Ambulatory children with mild spastic CP and typically developing children (4 to 11 years; 12/group) were tested. Magnetic resonance imaging was used to estimate cortical, medullary and total bone volume and width, bone strength [i.e., section modulus (Z) and polar moment of inertia (J)], and bone marrow fat concentration in the midtibia, and muscle volume, intermuscular, subfascial, and subcutaneous adipose tissue (AT) volume and intramuscular fat concentration in the midleg. Physical activity monitors worn on the ankle were used to assess physical activity. Results There were no group differences in age, height, body mass, body mass percentile, BMI, BMI percentile or tibia length, but children with CP had lower height percentile (19th vs. 50th percentile) and total physical activity counts (44 %) than controls (both p < 0.05). Children with CP also had lower cortical volume (30 %), cortical width in the posterior (16 %) and medial (32 %) portion of the shaft, total bone width in the medial-lateral direction (15 %), Z in the medial-lateral direction (34 %), J (39 %) and muscle volume (39 %), and higher bone marrow fat concentration (82.1 ± 1.8 % vs. 80.5 ± 1.9 %), subfascial AT volume (3.3 fold) and intramuscular fat concentration (25.0 ± 8.0 % vs. 16.1 ± 3.3 %) than controls (all p < 0.05). When tibia length was statistically controlled, all group differences in bone architecture, bone strength, muscle volume and fat infiltration estimates, except posterior cortical width, were still present (all p < 0.05). Furthermore, a higher intermuscular AT volume in children with CP compared to controls emerged (p < 0.05). Conclusions Ambulatory children with mild CP exhibit an underdeveloped bone architecture and low bone strength in the midtibia and a greater infiltration of fat in the bone marrow and surrounding musculature compared to typically developing children. Whether the deficit in the musculoskeletal system of children with CP is associated with higher chronic disease risk and whether the deficit can be mitigated requires further investigation. PMID:27732905

Cortical bone deficit and fat infiltration of bone marrow and skeletal muscle in ambulatory children with mild spastic cerebral palsy.

PubMed

Whitney, Daniel G; Singh, Harshvardhan; Miller, Freeman; Barbe, Mary F; Slade, Jill M; Pohlig, Ryan T; Modlesky, Christopher M

2017-01-01

Nonambulatory children with severe cerebral palsy (CP) have underdeveloped bone architecture, low bone strength and a high degree of fat infiltration in the lower extremity musculature. The present study aims to determine if such a profile exists in ambulatory children with mild CP and if excess fat infiltration extends into the bone marrow. Ambulatory children with mild spastic CP and typically developing children (4 to 11years; 12/group) were compared. Magnetic resonance imaging was used to estimate cortical bone, bone marrow and total bone volume and width, bone strength [i.e., section modulus (Z) and polar moment of inertia (J)], and bone marrow fat concentration in the midtibia, and muscle volume, intermuscular, subfascial, and subcutaneous adipose tissue (AT) volume and intramuscular fat concentration in the midleg. Accelerometer-based activity monitors worn on the ankle were used to assess physical activity. There were no group differences in age, height, body mass, body mass percentile, BMI, BMI percentile or tibia length, but children with CP had lower height percentile (19th vs. 50th percentile) and total physical activity counts (44%) than controls (both p<0.05). Children with CP also had lower cortical bone volume (30%), cortical bone width in the posterior (16%) and medial (32%) portions of the shaft, total bone width in the medial-lateral direction (15%), Z in the medial-lateral direction (34%), J (39%) and muscle volume (39%), and higher bone marrow fat concentration (82.1±1.8% vs. 80.5±1.9%), subfascial AT volume (3.3 fold) and intramuscular fat concentration (25.0±8.0% vs. 16.1±3.3%) than controls (all p<0.05). When tibia length was statistically controlled, all group differences in bone architecture, bone strength, muscle volume and fat infiltration estimates, except posterior cortical bone width, were still present (all p<0.05). Furthermore, a higher intermuscular AT volume in children with CP compared to controls emerged (p<0.05). Ambulatory children with mild spastic CP exhibit an underdeveloped bone architecture and low bone strength in the midtibia and a greater infiltration of fat in the bone marrow and surrounding musculature compared to typically developing children. Whether the deficit in the musculoskeletal system of children with CP is associated with higher chronic disease risk and whether the deficit can be mitigated requires further investigation. Copyright © 2016 Elsevier Inc. All rights reserved.

Lateral Spread of Orientation Selectivity in V1 is Controlled by Intracortical Cooperativity

PubMed Central

Chavane, Frédéric; Sharon, Dahlia; Jancke, Dirk; Marre, Olivier; Frégnac, Yves; Grinvald, Amiram

2011-01-01

Neurons in the primary visual cortex receive subliminal information originating from the periphery of their receptive fields (RF) through a variety of cortical connections. In the cat primary visual cortex, long-range horizontal axons have been reported to preferentially bind to distant columns of similar orientation preferences, whereas feedback connections from higher visual areas provide a more diverse functional input. To understand the role of these lateral interactions, it is crucial to characterize their effective functional connectivity and tuning properties. However, the overall functional impact of cortical lateral connections, whatever their anatomical origin, is unknown since it has never been directly characterized. Using direct measurements of postsynaptic integration in cat areas 17 and 18, we performed multi-scale assessments of the functional impact of visually driven lateral networks. Voltage-sensitive dye imaging showed that local oriented stimuli evoke an orientation-selective activity that remains confined to the cortical feedforward imprint of the stimulus. Beyond a distance of one hypercolumn, the lateral spread of cortical activity gradually lost its orientation preference approximated as an exponential with a space constant of about 1 mm. Intracellular recordings showed that this loss of orientation selectivity arises from the diversity of converging synaptic input patterns originating from outside the classical RF. In contrast, when the stimulus size was increased, we observed orientation-selective spread of activation beyond the feedforward imprint. We conclude that stimulus-induced cooperativity enhances the long-range orientation-selective spread. PMID:21629708

The effect of binaural beats on verbal working memory and cortical connectivity

NASA Astrophysics Data System (ADS)

Beauchene, Christine; Abaid, Nicole; Moran, Rosalyn; Diana, Rachel A.; Leonessa, Alexander

2017-04-01

Objective. Synchronization in activated regions of cortical networks affect the brain’s frequency response, which has been associated with a wide range of states and abilities, including memory. A non-invasive method for manipulating cortical synchronization is binaural beats. Binaural beats take advantage of the brain’s response to two pure tones, delivered independently to each ear, when those tones have a small frequency mismatch. The mismatch between the tones is interpreted as a beat frequency, which may act to synchronize cortical oscillations. Neural synchrony is particularly important for working memory processes, the system controlling online organization and retention of information for successful goal-directed behavior. Therefore, manipulation of synchrony via binaural beats provides a unique window into working memory and associated connectivity of cortical networks. Approach. In this study, we examined the effects of different acoustic stimulation conditions during an N-back working memory task, and we measured participant response accuracy and cortical network topology via EEG recordings. Six acoustic stimulation conditions were used: None, Pure Tone, Classical Music, 5 Hz binaural beats, 10 Hz binaural beats, and 15 Hz binaural beats. Main results. We determined that listening to 15 Hz binaural beats during an N-Back working memory task increased the individual participant’s accuracy, modulated the cortical frequency response, and changed the cortical network connection strengths during the task. Only the 15 Hz binaural beats produced significant change in relative accuracy compared to the None condition. Significance. Listening to 15 Hz binaural beats during the N-back task activated salient frequency bands and produced networks characterized by higher information transfer as compared to other auditory stimulation conditions.

Suppression of autophagy in osteocytes does not modify the adverse effects of glucocorticoids on cortical bone.

PubMed

Piemontese, Marilina; Onal, Melda; Xiong, Jinhu; Wang, Yiying; Almeida, Maria; Thostenson, Jeff D; Weinstein, Robert S; Manolagas, Stavros C; O'Brien, Charles A

2015-06-01

Glucocorticoid excess decreases bone mass and strength in part by acting directly on osteoblasts and osteocytes, but the mechanisms remain unclear. Macroautophagy (herein referred to as autophagy) is a lysosome-based recycling pathway that promotes the turnover of intracellular components and can promote cell function and survival under stressful conditions. Recent studies have shown that glucocorticoids stimulate autophagy in osteocytes, suggesting that autophagy may oppose the negative actions of glucocorticoids on this cell type. To address this possibility, we compared the impact of prednisolone administration on the skeletons of adult mice in which autophagy was suppressed in osteocytes, via deletion of Atg7 with a Dmp1-Cre transgene, to their control littermates. In control mice, prednisolone increased autophagic flux in osteocyte-enriched bone as measured by LC3 conversion, but this change did not occur in the mice lacking Atg7 in osteocytes. Nonetheless, prednisolone reduced femoral cortical thickness, increased cortical porosity, and reduced bone strength to similar extents in mice with and without autophagy in osteocytes. Prednisolone also suppressed osteoblast number and bone formation in the cancellous bone of control mice. As shown previously, Atg7 deletion in osteocytes reduced osteoblast number and bone formation in cancellous bone, but these parameters were not further reduced by prednisolone administration. In cortical bone, prednisolone elevated osteoclast number to a similar extent in both genotypes. Taken together, these results demonstrate that although glucocorticoids stimulate autophagy in osteocytes, suppression of autophagy in this cell type does not worsen the negative impact of glucocorticoids on the skeleton. Published by Elsevier Inc.

Suppression of Autophagy in Osteocytes Does Not Modify the Adverse Effects of Glucocorticoids on Cortical Bone

PubMed Central

Piemontese, Marilina; Onal, Melda; Xiong, Jinhu; Wang, Yiying; Almeida, Maria; Thostenson, Jeff D.; Weinstein, Robert S.; Manolagas, Stavros C.; O’Brien, Charles A.

2015-01-01

Glucocorticoid excess decreases bone mass and strength in part by acting directly on osteoblasts and osteocytes, but the mechanisms remain unclear. Macroautophagy (herein referred to as autophagy) is a lysosome-based recycling pathway that promotes the turnover of intracellular components and can promote cell function and survival under stressful conditions. Recent studies have shown that glucocorticoids stimulate autophagy in osteocytes, suggesting that autophagy may oppose the negative actions of glucocorticoids on this cell type. To address this possibility, we compared the impact of prednisolone administration on the skeletons of adult mice in which autophagy was suppressed in osteocytes, via deletion of Atg7 with a Dmp1-Cre transgene, to their control littermates. In control mice, prednisolone increased autophagic flux in osteocyte-enriched bone as measured by LC3 conversion, but this change did not occur in the mice lacking Atg7 in osteocytes. Nonetheless, prednisolone reduced femoral cortical thickness, increased cortical porosity, and reduced bone strength to similar extents in mice with and without autophagy in osteocytes. Prednisolone also suppressed osteoblast number and bone formation in the cancellous bone of control mice. As shown previously, Atg7 deletion in osteocytes reduced osteoblast number and bone formation in cancellous bone, but these parameters were not further reduced by prednisolone administration. In cortical bone, prednisolone elevated osteoclast number to a similar extent in both genotypes. Taken together, these results demonstrate that although glucocorticoids stimulate autophagy in osteocytes, suppression of autophagy in this cell type does not worsen the negative impact of glucocorticoids on the skeleton. PMID:25700544

Non-invasive cortical stimulation improves post-stroke attention decline.

PubMed

Kang, Eun Kyoung; Baek, Min Jae; Kim, Sangyun; Paik, Nam-Jong

2009-01-01

Attention decline after stroke is common and hampers the rehabilitation process, and non-invasive transcranial direct current stimulation (tDCS) has the potential to elicit behavioral changes by modulating cortical excitability. The authors tested the hypothesis that a single session of non-invasive cortical stimulation with excitatory anodal tDCS applied to the left dorsolateral prefrontal cortex (DLPFC) can improve attention in stroke patients. Ten patients with post-stroke cognitive decline (MMSE 25) and 10 age-matched healthy controls participated in this double blind, sham-controlled, crossover study involving the administration of real (2 mA for 20 min) or sham stimulation (2 mA for 1 min) to the left DLPFC. Attention was measured using a computerized Go/No-Go test before and after intervention. Improvements in accuracy and speed after stimulation relative to baseline were compared for real and sham stimulations. In healthy controls, no significant improvement in Go/No-Go test was observed after either real or sham stimulation. However, in stroke patients, tDCS led to a significant improvement in response accuracy at 1 hour post-stimulation relative to baseline, and this improvement was maintained until 3 hours post-stimulation (P< 0.05), whereas sham stimulation did not lead to a significant improvement in response accuracy (P> 0.05). Changes in reaction times were comparable for the two stimulations (P> 0.05). Non invasive anodal tDCS applied to the left DLPFC was found to improve attention versus sham stimulation in stroke patients, which suggests that non-invasive cortical intervention could potentially be used during rehabilitative training to improve attention.

Local domains of motor cortical activity revealed by fiber-optic calcium recordings in behaving nonhuman primates.

PubMed

Adelsberger, Helmuth; Zainos, Antonio; Alvarez, Manuel; Romo, Ranulfo; Konnerth, Arthur

2014-01-07

Brain mapping experiments involving electrical microstimulation indicate that the primary motor cortex (M1) directly regulates muscle contraction and thereby controls specific movements. Possibly, M1 contains a small circuit "map" of the body that is formed by discrete local networks that code for specific movements. Alternatively, movements may be controlled by distributed, larger-scale overlapping circuits. Because of technical limitations, it remained unclear how movement-determining circuits are organized in M1. Here we introduce a method that allows the functional mapping of small local neuronal circuits in awake behaving nonhuman primates. For this purpose, we combined optic-fiber-based calcium recordings of neuronal activity and cortical microstimulation. The method requires targeted bulk loading of synthetic calcium indicators (e.g., OGB-1 AM) for the staining of neuronal microdomains. The tip of a thin (200 µm) optical fiber can detect the coherent activity of a small cluster of neurons, but is insensitive to the asynchronous activity of individual cells. By combining such optical recordings with microstimulation at two well-separated sites of M1, we demonstrate that local cortical activity was tightly associated with distinct and stereotypical simple movements. Increasing stimulation intensity increased both the amplitude of the movements and the level of neuronal activity. Importantly, the activity remained local, without invading the recording domain of the second optical fiber. Furthermore, there was clear response specificity at the two recording sites in a trained behavioral task. Thus, the results provide support for movement control in M1 by local neuronal clusters that are organized in discrete cortical domains.

Exploring thermal anisotropy of cortical bone using temperature measurements in drilling.

PubMed

Alam, Khurshid

2016-05-12

Bone drilling is widely used in orthopaedics for fracture treatment, reconstructive surgery and bone biopsy. Heat generation in bone drilling can cause rise in bone temperature resulting in prolonged healing time or loosening of fixation. The purpose of this study was to investigate thermal anisotropy of bone by measuring the level of temperature in bone drilling with and without cooling conditions in two anatomical directions. Drilling tests were performed on bovine cortical bone. A total of fifteen specimens were used to obtain data for statistical analysis. Temperature near the cutting zone was measured in two anatomical directions. i.e. along the longitudinal and circumferential direction. Temperature distribution was also found in the two prescribed directions. Analysis of variance (ANOVA) was used to identify significant drilling parameter affecting bone temperature. Drilling speed, feed rate and drill size were found influential parameters affecting bone temperature. Higher drilling speed, feed rate, and large drill size were found to cause elevated temperature in bone. Much lower temperature was measured in bone when cooling fluid was supplied to the drilling region. Experimental results revealed lower temperatures in the circumferential direction compared to the longitudinal direction. Thermal anisotropy for heat transport was found in the bone. This study recommends lower drilling speed and feed rate and cooling for controlling rise in bone temperature.

Technical principles of direct bipolar electrostimulation for cortical and subcortical mapping in awake craniotomy.

PubMed

Pallud, J; Mandonnet, E; Corns, R; Dezamis, E; Parraga, E; Zanello, M; Spena, G

2017-06-01

Intraoperative application of electrical current to the brain is a standard technique during brain surgery for inferring the function of the underlying brain. The purpose of intraoperative functional mapping is to reliably identify cortical areas and subcortical pathways involved in eloquent functions, especially motor, sensory, language and cognitive functions. The aim of this article is to review the rationale and the electrophysiological principles of the use of direct bipolar electrostimulation for cortical and subcortical mapping under awake conditions. Direct electrical stimulation is a window into the whole functional network that sustains a particular function. It is an accurate (spatial resolution of about 5mm) and a reproducible technique particularly adapted to clinical practice for brain resection in eloquent areas. If the procedure is rigorously applied, the sensitivity of direct electrical stimulation for the detection of cortical and subcortical eloquent areas is nearly 100%. The main disadvantage of this technique is its suboptimal specificity. Another limitation is the identification of eloquent areas during surgery, which, however, could have been functionally compensated postoperatively if removed surgically. Direct electrical stimulation is an easy, accurate, reliable and safe invasive technique for the intraoperative detection of both cortical and subcortical functional brain connectivity for clinical purpose. In our opinion, it is the optimal technique for minimizing the risk of neurological sequelae when resecting in eloquent brain areas. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Applications of cortical signals to neuroprosthetic control: a critical review.

PubMed

Lauer, R T; Peckham, P H; Kilgore, K L; Heetderks, W J

2000-06-01

Cortical signals might provide a potential means of interfacing with a neuroprosthesis. Guidelines regarding the necessary control features in terms of both performance characteristics and user requirements are presented, and their implications for the design of a first generation cortical control interface for a neuroprosthesis are discussed.

EEG-Based Quantification of Cortical Current Density and Dynamic Causal Connectivity Generalized across Subjects Performing BCI-Monitored Cognitive Tasks

PubMed Central

Courellis, Hristos; Mullen, Tim; Poizner, Howard; Cauwenberghs, Gert; Iversen, John R.

2017-01-01

Quantification of dynamic causal interactions among brain regions constitutes an important component of conducting research and developing applications in experimental and translational neuroscience. Furthermore, cortical networks with dynamic causal connectivity in brain-computer interface (BCI) applications offer a more comprehensive view of brain states implicated in behavior than do individual brain regions. However, models of cortical network dynamics are difficult to generalize across subjects because current electroencephalography (EEG) signal analysis techniques are limited in their ability to reliably localize sources across subjects. We propose an algorithmic and computational framework for identifying cortical networks across subjects in which dynamic causal connectivity is modeled among user-selected cortical regions of interest (ROIs). We demonstrate the strength of the proposed framework using a “reach/saccade to spatial target” cognitive task performed by 10 right-handed individuals. Modeling of causal cortical interactions was accomplished through measurement of cortical activity using (EEG), application of independent component clustering to identify cortical ROIs as network nodes, estimation of cortical current density using cortically constrained low resolution electromagnetic brain tomography (cLORETA), multivariate autoregressive (MVAR) modeling of representative cortical activity signals from each ROI, and quantification of the dynamic causal interaction among the identified ROIs using the Short-time direct Directed Transfer function (SdDTF). The resulting cortical network and the computed causal dynamics among its nodes exhibited physiologically plausible behavior, consistent with past results reported in the literature. This physiological plausibility of the results strengthens the framework's applicability in reliably capturing complex brain functionality, which is required by applications, such as diagnostics and BCI. PMID:28566997

Bone Parameters in Anorexia Nervosa and Athletic Amenorrhea: Comparison of Two Hypothalamic Amenorrhea States.

PubMed

Kandemir, Nurgun; Slattery, Meghan; Ackerman, Kathryn E; Tulsiani, Shreya; Bose, Amita; Singhal, Vibha; Baskaran, Charumathi; Ebrahimi, Seda; Goldstein, Mark; Eddy, Kamryn; Klibanski, Anne; Misra, Madhusmita

2018-04-05

We have reported low bone mineral density (BMD), impaired bone structure, and increased fracture risk in anorexia nervosa (AN) and normal-weight, oligo-amenorrheic athletes (OA). However, data directly comparing compartment-specific bone parameters in AN, OA and controls are lacking. 426 females 14-21.9 years old were included; 231 AN, 94 OA and 101 normal-weight eumenorrheic controls. Dual energy x-ray absorptiometry was used to assess areal BMD (aBMD) of the whole body less head (WBLH), spine, and hip. High resolution peripheral quantitative CT was used to assess volumetric BMD (vBMD), bone geometry and structure at the non-weight bearing distal radius and weight-bearing distal tibia. AN had lower WBLH and hip aBMD Z-scores than OA and controls (p<0.0001). AN and OA had lower spine aBMD Z-scores than controls (p<0.01). At the radius, total and cortical vBMD, percent cortical area and thickness were lower in AN and OA vs. controls (p≤0.04); trabecular vBMD was lower in AN than controls. At the tibia, AN had lower measures for most parameters vs. OA and controls (p<0.05); OA had lower cortical vBMD than controls (p=0.002). AN and OA had higher fracture rates vs. controls. Stress fracture prevalence was highest in OA (p<0.0001); non-stress fracture prevalence was highest in AN (p<0.05). AN is deleterious to bone at all sites and both bone compartments. A high stress fracture rate in OA, who have comparable WBLH and hip aBMD measures to controls, indicates that BMD in these women may need to be even higher to avoid fractures.

Dietary Restriction Affects Neuronal Response Property and GABA Synthesis in the Primary Visual Cortex.

PubMed

Yang, Jinfang; Wang, Qian; He, Fenfen; Ding, Yanxia; Sun, Qingyan; Hua, Tianmiao; Xi, Minmin

2016-01-01

Previous studies have reported inconsistent effects of dietary restriction (DR) on cortical inhibition. To clarify this issue, we examined the response properties of neurons in the primary visual cortex (V1) of DR and control groups of cats using in vivo extracellular single-unit recording techniques, and assessed the synthesis of inhibitory neurotransmitter GABA in the V1 of cats from both groups using immunohistochemical and Western blot techniques. Our results showed that the response of V1 neurons to visual stimuli was significantly modified by DR, as indicated by an enhanced selectivity for stimulus orientations and motion directions, decreased visually-evoked response, lowered spontaneous activity and increased signal-to-noise ratio in DR cats relative to control cats. Further, it was shown that, accompanied with these changes of neuronal responsiveness, GABA immunoreactivity and the expression of a key GABA-synthesizing enzyme GAD67 in the V1 were significantly increased by DR. These results demonstrate that DR may retard brain aging by increasing the intracortical inhibition effect and improve the function of visual cortical neurons in visual information processing. This DR-induced elevation of cortical inhibition may favor the brain in modulating energy expenditure based on food availability.

Dietary Restriction Affects Neuronal Response Property and GABA Synthesis in the Primary Visual Cortex

PubMed Central

Sun, Qingyan; Hua, Tianmiao; Xi, Minmin

2016-01-01

Previous studies have reported inconsistent effects of dietary restriction (DR) on cortical inhibition. To clarify this issue, we examined the response properties of neurons in the primary visual cortex (V1) of DR and control groups of cats using in vivo extracellular single-unit recording techniques, and assessed the synthesis of inhibitory neurotransmitter GABA in the V1 of cats from both groups using immunohistochemical and Western blot techniques. Our results showed that the response of V1 neurons to visual stimuli was significantly modified by DR, as indicated by an enhanced selectivity for stimulus orientations and motion directions, decreased visually-evoked response, lowered spontaneous activity and increased signal-to-noise ratio in DR cats relative to control cats. Further, it was shown that, accompanied with these changes of neuronal responsiveness, GABA immunoreactivity and the expression of a key GABA-synthesizing enzyme GAD67 in the V1 were significantly increased by DR. These results demonstrate that DR may retard brain aging by increasing the intracortical inhibition effect and improve the function of visual cortical neurons in visual information processing. This DR-induced elevation of cortical inhibition may favor the brain in modulating energy expenditure based on food availability. PMID:26863207

Computational and experimental analysis of TMS-induced electric field vectors critical to neuronal activation

NASA Astrophysics Data System (ADS)

Krieg, Todd D.; Salinas, Felipe S.; Narayana, Shalini; Fox, Peter T.; Mogul, David J.

2015-08-01

Objective. Transcranial magnetic stimulation (TMS) represents a powerful technique to noninvasively modulate cortical neurophysiology in the brain. However, the relationship between the magnetic fields created by TMS coils and neuronal activation in the cortex is still not well-understood, making predictable cortical activation by TMS difficult to achieve. Our goal in this study was to investigate the relationship between induced electric fields and cortical activation measured by blood flow response. Particularly, we sought to discover the E-field characteristics that lead to cortical activation. Approach. Subject-specific finite element models (FEMs) of the head and brain were constructed for each of six subjects using magnetic resonance image scans. Positron emission tomography (PET) measured each subject’s cortical response to image-guided robotically-positioned TMS to the primary motor cortex. FEM models that employed the given coil position, orientation, and stimulus intensity in experimental applications of TMS were used to calculate the electric field (E-field) vectors within a region of interest for each subject. TMS-induced E-fields were analyzed to better understand what vector components led to regional cerebral blood flow (CBF) responses recorded by PET. Main results. This study found that decomposing the E-field into orthogonal vector components based on the cortical surface geometry (and hence, cortical neuron directions) led to significant differences between the regions of cortex that were active and nonactive. Specifically, active regions had significantly higher E-field components in the normal inward direction (i.e., parallel to pyramidal neurons in the dendrite-to-axon orientation) and in the tangential direction (i.e., parallel to interneurons) at high gradient. In contrast, nonactive regions had higher E-field vectors in the outward normal direction suggesting inhibitory responses. Significance. These results provide critical new understanding of the factors by which TMS induces cortical activation necessary for predictive and repeatable use of this noninvasive stimulation modality.

Evolution of brain-computer interfaces: going beyond classic motor physiology

PubMed Central

Leuthardt, Eric C.; Schalk, Gerwin; Roland, Jarod; Rouse, Adam; Moran, Daniel W.

2010-01-01

The notion that a computer can decode brain signals to infer the intentions of a human and then enact those intentions directly through a machine is becoming a realistic technical possibility. These types of devices are known as brain-computer interfaces (BCIs). The evolution of these neuroprosthetic technologies could have significant implications for patients with motor disabilities by enhancing their ability to interact and communicate with their environment. The cortical physiology most investigated and used for device control has been brain signals from the primary motor cortex. To date, this classic motor physiology has been an effective substrate for demonstrating the potential efficacy of BCI-based control. However, emerging research now stands to further enhance our understanding of the cortical physiology underpinning human intent and provide further signals for more complex brain-derived control. In this review, the authors report the current status of BCIs and detail the emerging research trends that stand to augment clinical applications in the future. PMID:19569892

Regulation of cerebral cortical neurogenesis by the Pax6 transcription factor

PubMed Central

Manuel, Martine N.; Mi, Da; Mason, John O.; Price, David J.

2015-01-01

Understanding brain development remains a major challenge at the heart of understanding what makes us human. The neocortex, in evolutionary terms the newest part of the cerebral cortex, is the seat of higher cognitive functions. Its normal development requires the production, positioning, and appropriate interconnection of very large numbers of both excitatory and inhibitory neurons. Pax6 is one of a relatively small group of transcription factors that exert high-level control of cortical development, and whose mutation or deletion from developing embryos causes major brain defects and a wide range of neurodevelopmental disorders. Pax6 is very highly conserved between primate and non-primate species, is expressed in a gradient throughout the developing cortex and is essential for normal corticogenesis. Our understanding of Pax6’s functions and the cellular processes that it regulates during mammalian cortical development has significantly advanced in the last decade, owing to the combined application of genetic and biochemical analyses. Here, we review the functional importance of Pax6 in regulating cortical progenitor proliferation, neurogenesis, and formation of cortical layers and highlight important differences between rodents and primates. We also review the pathological effects of PAX6 mutations in human neurodevelopmental disorders. We discuss some aspects of Pax6’s molecular actions including its own complex transcriptional regulation, the distinct molecular functions of its splice variants and some of Pax6’s known direct targets which mediate its actions during cortical development. PMID:25805971

Altered regional cortical thickness and subcortical volume in women with primary dysmenorrhoea.

PubMed

Liu, P; Yang, J; Wang, G; Liu, Y; Liu, X; Jin, L; Liang, F; Qin, W; Calhoun, V D

2016-04-01

There is emerging evidence that primary dysmenorrhoea (PDM) is associated with altered brain function and structure. However, few studies have investigated changes in regional cortical thickness and subcortical volumes in PDM patients. The purpose of this study was to characterize differences in both cortical thickness and subcortical volumes between PDM patients and healthy controls (HCs). T1-weighted magnetic resonance images were obtained from 44 PDM patients and 32 HCs matched for age and handedness. Cortical thickness was compared in multiple locations across the continuous cortical surface, and subcortical volumes were compared on a structure-by-structure basis. Correlation analysis was then used to evaluate relationships between the clinical symptoms and abnormal brain structure in PDM. PDM patients had significantly increased cortical thickness in the orbitofrontal cortex (OFC), insula (IN), primary/secondary sensory area (SI/SII), superior temporal cortex (STC), precuneus (pCUN) and posterior cingulate cortex (PCC). Meanwhile, significantly decreased subcortical volumes of the caudate, thalamus and amygdala were found in PDM patients. Moreover, there were significant positive correlations between the PDM-related duration and the OFC, SFC, STC and IN. The MPQ scores were positively correlated with the pCUN. These findings provide further evidence for grey matter changes in patients with PDM, and in addition, the results support relationships between the structural abnormalities and their role in symptom production. All these results are likely to be potential valuable to provide us with direct information about the neural basis of PDM. © 2015 European Pain Federation - EFIC®

Coup-TF1 and Coup-TF2 control subtype and laminar identity of MGE-derived neocortical interneurons.

PubMed

Hu, Jia Sheng; Vogt, Daniel; Lindtner, Susan; Sandberg, Magnus; Silberberg, Shanni N; Rubenstein, John L R

2017-08-01

Distinct cortical interneuron (CIN) subtypes have unique circuit functions; dysfunction in specific subtypes is implicated in neuropsychiatric disorders. Somatostatin- and parvalbumin-expressing (SST + and PV + ) interneurons are the two major subtypes generated by medial ganglionic eminence (MGE) progenitors. Spatial and temporal mechanisms governing their cell-fate specification and differential integration into cortical layers are largely unknown. We provide evidence that Coup-TF1 and Coup-TF2 ( Nr2f1 and Nr2f2 ) transcription factor expression in an arc-shaped progenitor domain within the MGE promotes time-dependent survival of this neuroepithelium and the time-dependent specification of layer V SST + CINs. Coup-TF1 and Coup-TF2 autonomously repress PV + fate in MGE progenitors, in part through directly driving Sox6 expression. These results have identified, in mouse, a transcriptional pathway that controls SST-PV fate. © 2017. Published by The Company of Biologists Ltd.

Preliminary Findings Show Maternal Hypothyroidism May Contribute to Abnormal Cortical Morphology in Offspring

PubMed Central

Lischinsky, Julieta E.; Skocic, Jovanka; Clairman, Hayyah; Rovet, Joanne

2016-01-01

In rodents, insufficient thyroid hormone (TH) gestationally has adverse effects on cerebral cortex development. Comparable studies of humans examining how TH insufficiency affects cortical morphology are limited to children with congenital hypothyroidism or offspring of hypothyroxinemic women; effects on cortex of children born to women with clinically diagnosed hypothyroidism are not known. We studied archived MRI scans from 22 children aged 10–12 years born to women treated for preexisting or de novo hypothyroidism in pregnancy (HYPO) and 24 similar age and sex controls from euthyroid women. FreeSurfer Image Analysis Suite software was used to measure cortical thickness (CT) and a vertex-based approach served to compare HYPO versus control groups and Severe versus Mild HYPO subgroups as well as to perform regression analyses examining effects of trimester-specific maternal TSH on CT. Results showed that relative to controls, HYPO had multiple regions of both cortical thinning and thickening, which differed for left and right hemispheres. In HYPO, thinning was confined to medial and mid-lateral regions of each hemisphere and thickening to superior regions (primarily frontal) of the left hemisphere and inferior regions (particularly occipital and temporal) of the right. The Severe HYPO subgroup showed more thinning than Mild in frontal and temporal regions and more thickening in bilateral posterior and frontal regions. Maternal TSH values predicted degree of thinning and thickening within multiple brain regions, with the pattern and direction of correlations differing by trimester. Notably, some correlations remained when cases born to women with severe hypothyroidism were removed from the analyses, suggesting that mild variations of maternal TH may permanently affect offspring cortex. We conclude that maternal hypothyroidism during pregnancy has long-lasting manifestations on the cortical morphology of their offspring with specific effects reflecting both severity and timing of maternal TH insufficiency. PMID:26941710

Effects of repetitive transcranial magnetic stimulation and trans-spinal direct current stimulation associated with treadmill exercise in spinal cord and cortical excitability of healthy subjects: A triple-blind, randomized and sham-controlled study

PubMed Central

Albuquerque, Plínio Luna; Campêlo, Mayara; Mendonça, Thyciane; Fontes, Luís Augusto Mendes; Brito, Rodrigo de Mattos

2018-01-01

Repetitive transcranial magnetic stimulation (rTMS) over motor cortex and trans-spinal direct current stimulation (tsDCS) modulate corticospinal circuits in healthy and injured subjects. However, their associated effects with physical exercise is still not defined. This study aimed to investigate the effect of three different settings of rTMS and tsDCS combined with treadmill exercise on spinal cord and cortical excitability of healthy subjects. We performed a triple blind, randomized, sham-controlled crossover study with 12 healthy volunteers who underwent single sessions of rTMS (1Hz, 20Hz and Sham) and tsDCS (anodal, cathodal and Sham) associated with 20 minutes of treadmill walking. Cortical excitability was assessed by motor evoked potential (MEP) and spinal cord excitability by the Hoffmann reflex (Hr), nociceptive flexion reflex (NFR) and homosynaptic depression (HD). All measures were assessed before, immediately, 30 and 60 minutes after the experimental procedures. Our results demonstrated that anodal tsDCS/treadmill exercise reduced MEP’s amplitude and NFR’s area compared to sham condition, conversely, cathodal tsDCS/treadmill exercise increased NFR’s area. High-frequency rTMS increased MEP’s amplitude and NFR’s area compared to sham condition. Anodal tsDCS/treadmill exercise and 20Hz rTMS/treadmill exercise reduced Hr amplitude up to 30 minutes after stimulation offset and no changes were observed in HD measures. We demonstrated that tsDCS and rTMS combined with treadmill exercise modulated cortical and spinal cord excitability through different mechanisms. tsDCS modulated spinal reflexes in a polarity-dependent way acting at local spinal circuits while rTMS probably promoted changes in the presynaptic inhibition of spinal motoneurons. In addition, the association of two neuromodulatory techniques induced long-lasting changes. PMID:29596524

Effects of repetitive transcranial magnetic stimulation and trans-spinal direct current stimulation associated with treadmill exercise in spinal cord and cortical excitability of healthy subjects: A triple-blind, randomized and sham-controlled study.

PubMed

Albuquerque, Plínio Luna; Campêlo, Mayara; Mendonça, Thyciane; Fontes, Luís Augusto Mendes; Brito, Rodrigo de Mattos; Monte-Silva, Katia

2018-01-01

Repetitive transcranial magnetic stimulation (rTMS) over motor cortex and trans-spinal direct current stimulation (tsDCS) modulate corticospinal circuits in healthy and injured subjects. However, their associated effects with physical exercise is still not defined. This study aimed to investigate the effect of three different settings of rTMS and tsDCS combined with treadmill exercise on spinal cord and cortical excitability of healthy subjects. We performed a triple blind, randomized, sham-controlled crossover study with 12 healthy volunteers who underwent single sessions of rTMS (1Hz, 20Hz and Sham) and tsDCS (anodal, cathodal and Sham) associated with 20 minutes of treadmill walking. Cortical excitability was assessed by motor evoked potential (MEP) and spinal cord excitability by the Hoffmann reflex (Hr), nociceptive flexion reflex (NFR) and homosynaptic depression (HD). All measures were assessed before, immediately, 30 and 60 minutes after the experimental procedures. Our results demonstrated that anodal tsDCS/treadmill exercise reduced MEP's amplitude and NFR's area compared to sham condition, conversely, cathodal tsDCS/treadmill exercise increased NFR's area. High-frequency rTMS increased MEP's amplitude and NFR's area compared to sham condition. Anodal tsDCS/treadmill exercise and 20Hz rTMS/treadmill exercise reduced Hr amplitude up to 30 minutes after stimulation offset and no changes were observed in HD measures. We demonstrated that tsDCS and rTMS combined with treadmill exercise modulated cortical and spinal cord excitability through different mechanisms. tsDCS modulated spinal reflexes in a polarity-dependent way acting at local spinal circuits while rTMS probably promoted changes in the presynaptic inhibition of spinal motoneurons. In addition, the association of two neuromodulatory techniques induced long-lasting changes.

Regional reduction in cortical blood flow among cognitively impaired adults with relapsing-remitting multiple sclerosis patients

PubMed Central

Hojjat, Seyed-Parsa; Cantrell, Charles Grady; Vitorino, Rita; Feinstein, Anthony; Shirzadi, Zahra; MacIntosh, Bradley J.; Crane, David E.; Zhang, Lying; Morrow, Sarah A; Lee, Liesly; O’Connor, Paul; Carroll, Timothy J.; Aviv, Richard I.

2015-01-01

Purpose Detection of cortical abnormalities in relapsing-remitting multiple sclerosis (RRMS) remains elusive. Structural MRI measures of cortical integrity are limited, although functional techniques such as pseudocontinuous Arterial Spin Labeling (pCASL) show promise as a surrogate marker of disease severity. We sought to determine the utility of pCASL to assess cortical cerebral blood flow (CBF) in RRMS patients with (RRMS-I) and without (RRMS-NI) cognitive impairment. Methods 19 age-matched healthy controls and 39 RRMS patients were prospectively recruited. Cognition was assessed using the MACFIMS battery. Cortical CBF was compared between groups using a mass univariate voxel-based morphometric analysis accounting for demographic and structural variable covariates. Results Cognitive impairment was present in 51.3% of patients. Significant CBF reduction was present in the RRMS-I compared to other groups in left frontal and right superior frontal cortex. Compared to healthy controls, RRMS-I displayed reduced CBF in the frontal, limbic, parietal and temporal cortex and putamen/thalamus. RRMS-I demonstrated reduced left superior frontal lobe cortical CBF compared to RRMS-NI. No significant cortical CBF differences were present between healthy controls and RRMS-NI. Conclusion Significant cortical CBF reduction occurs in RRMS-I compared to healthy controls and RRMS-NI in anatomically significant regions after controlling for structural and demographic differences. PMID:26754799

Suberoylanilide hydroxamic acid increases progranulin production in iPSC-derived cortical neurons of frontotemporal dementia patients.

PubMed

Almeida, Sandra; Gao, Fuying; Coppola, Giovanni; Gao, Fen-Biao

2016-06-01

Mutations in the granulin (GRN) gene cause frontotemporal dementia (FTD) due to progranulin haploinsufficiency. Compounds that can increase progranulin production and secretion may be considered as potential therapeutic drugs; however, very few of them have been directly tested on human cortical neurons. To this end, we differentiated 9 induced pluripotent stem cell lines derived from a control subject, a sporadic FTD case and an FTD patient with progranulin S116X mutation. Treatment with 1 μM suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, increased the production of progranulin in cortical neurons of all subjects at both the mRNA and protein levels without affecting their viability. Microarray analysis revealed that SAHA treatment not only reversed some gene expression changes caused by progranulin haploinsufficiency but also caused massive alterations in the overall transcriptome. Thus, histone deacetylase inhibitors may be considered as therapeutic drugs for GRN mutation carriers. However, this class of drugs also causes drastic changes in overall gene expression in human cortical neurons and their side effects and potential impacts on other pathways should be carefully evaluated. Copyright © 2016 Elsevier Inc. All rights reserved.

Amphetamine Dependence and Co-Morbid Alcohol Abuse: Associations to Brain Cortical Thickness

PubMed Central

2010-01-01

Background Long-term amphetamine and methamphetamine dependence has been linked to cerebral blood perfusion, metabolic, and white matter abnormalities. Several studies have linked methamphetamine abuse to cortical grey matter reduction, though with divergent findings. Few publications investigate unmethylated amphetamine's potential effects on cortical grey matter. This work investigated if amphetamine dependent patients showed reduced cortical grey matter thickness. Subjects were 40 amphetamine dependent subjects and 40 healthy controls. While all subjects were recruited to be free of alcohol dependence, structured clinical interviews revealed significant patterns of alcohol use in the patients. Structural magnetic resonance brain images were obtained from the subjects using a 1.5 Tesla GE Signa machine. Brain cortical thickness was measured with submillimeter precision at multiple finely spaced cortical locations using semi-automated post-processing (FreeSurfer). Contrast analysis of a general linear model was used to test for differences between the two groups at each cortical location. In addition to contrasting patients with controls, a number of analyses sought to identify possible confounding effects from alcohol. Results No significant cortical thickness differences were observed between the full patient group and controls, nor between non-drinking patients and controls. Patients with a history of co-morbid heavy alcohol use (n = 29) showed reductions in the superior-frontal right hemisphere and pre-central left hemisphere when compared to healthy controls (n = 40). Conclusions Amphetamine usage was associated with reduced cortical thickness only in patients co-morbid for heavy alcohol use. Since cortical thickness is but one measure of brain structure and does not capture brain function, further studies of brain structure and function in amphetamine dependence are warranted. PMID:20487539

Goal-directed control with cortical units that are gated by both top-down feedback and oscillatory coherence.

PubMed

Kerr, Robert R; Grayden, David B; Thomas, Doreen A; Gilson, Matthieu; Burkitt, Anthony N

2014-01-01

The brain is able to flexibly select behaviors that adapt to both its environment and its present goals. This cognitive control is understood to occur within the hierarchy of the cortex and relies strongly on the prefrontal and premotor cortices, which sit at the top of this hierarchy. Pyramidal neurons, the principal neurons in the cortex, have been observed to exhibit much stronger responses when they receive inputs at their soma/basal dendrites that are coincident with inputs at their apical dendrites. This corresponds to inputs from both lower-order regions (feedforward) and higher-order regions (feedback), respectively. In addition to this, coherence between oscillations, such as gamma oscillations, in different neuronal groups has been proposed to modulate and route communication in the brain. In this paper, we develop a simple, but novel, neural mass model in which cortical units (or ensembles) exhibit gamma oscillations when they receive coherent oscillatory inputs from both feedforward and feedback connections. By forming these units into circuits that can perform logic operations, we identify the different ways in which operations can be initiated and manipulated by top-down feedback. We demonstrate that more sophisticated and flexible top-down control is possible when the gain of units is modulated by not only top-down feedback but by coherence between the activities of the oscillating units. With these types of units, it is possible to not only add units to, or remove units from, a higher-level unit's logic operation using top-down feedback, but also to modify the type of role that a unit plays in the operation. Finally, we explore how different network properties affect top-down control and processing in large networks. Based on this, we make predictions about the likely connectivities between certain brain regions that have been experimentally observed to be involved in goal-directed behavior and top-down attention.

Goal-directed control with cortical units that are gated by both top-down feedback and oscillatory coherence

PubMed Central

Kerr, Robert R.; Grayden, David B.; Thomas, Doreen A.; Gilson, Matthieu; Burkitt, Anthony N.

2014-01-01

The brain is able to flexibly select behaviors that adapt to both its environment and its present goals. This cognitive control is understood to occur within the hierarchy of the cortex and relies strongly on the prefrontal and premotor cortices, which sit at the top of this hierarchy. Pyramidal neurons, the principal neurons in the cortex, have been observed to exhibit much stronger responses when they receive inputs at their soma/basal dendrites that are coincident with inputs at their apical dendrites. This corresponds to inputs from both lower-order regions (feedforward) and higher-order regions (feedback), respectively. In addition to this, coherence between oscillations, such as gamma oscillations, in different neuronal groups has been proposed to modulate and route communication in the brain. In this paper, we develop a simple, but novel, neural mass model in which cortical units (or ensembles) exhibit gamma oscillations when they receive coherent oscillatory inputs from both feedforward and feedback connections. By forming these units into circuits that can perform logic operations, we identify the different ways in which operations can be initiated and manipulated by top-down feedback. We demonstrate that more sophisticated and flexible top-down control is possible when the gain of units is modulated by not only top-down feedback but by coherence between the activities of the oscillating units. With these types of units, it is possible to not only add units to, or remove units from, a higher-level unit's logic operation using top-down feedback, but also to modify the type of role that a unit plays in the operation. Finally, we explore how different network properties affect top-down control and processing in large networks. Based on this, we make predictions about the likely connectivities between certain brain regions that have been experimentally observed to be involved in goal-directed behavior and top-down attention. PMID:25152715

Development of hypersynchrony in the cortical network during chemoconvulsant-induced epileptic seizures in vivo.

PubMed

Cymerblit-Sabba, Adi; Schiller, Yitzhak

2012-03-01

The prevailing view of epileptic seizures is that they are caused by increased hypersynchronous activity in the cortical network. However, this view is based mostly on electroencephalography (EEG) recordings that do not directly monitor neuronal synchronization of action potential firing. In this study, we used multielectrode single-unit recordings from the hippocampus to investigate firing of individual CA1 neurons and directly monitor synchronization of action potential firing between neurons during the different ictal phases of chemoconvulsant-induced epileptic seizures in vivo. During the early phase of seizures manifesting as low-amplitude rhythmic β-electrocorticography (ECoG) activity, the firing frequency of most neurons markedly increased. To our surprise, the average overall neuronal synchronization as measured by the cross-correlation function was reduced compared with control conditions with ~60% of neuronal pairs showing no significant correlated firing. However, correlated firing was not uniform and a minority of neuronal pairs showed a high degree of correlated firing. Moreover, during the early phase of seizures, correlated firing between 9.8 ± 5.1% of all stably recorded pairs increased compared with control conditions. As seizures progressed and high-frequency ECoG polyspikes developed, the firing frequency of neurons further increased and enhanced correlated firing was observed between virtually all neuronal pairs. These findings indicated that epileptic seizures represented a hyperactive state with widespread increase in action potential firing. Hypersynchrony also characterized seizures. However, it initially developed in a small subset of neurons and gradually spread to involve the entire cortical network only in the later more intense ictal phases.

Frontal transcranial direct current stimulation (tDCS) abolishes list-method directed forgetting.

PubMed

Silas, Jonathan; Brandt, Karen R

2016-03-11

It is a point of controversy as to whether directed forgetting effects are a result of active inhibition or a change of context initiated by the instruction to forget. In this study we test the causal role of active inhibition in directed forgetting. By applying cathodal transcranial direct current stimulation (tDCS) over the right prefrontal cortex we suppressed cortical activity commonly associated with inhibitory control. Participants who underwent real brain stimulation before completing the directed forgetting paradigm showed no directed forgetting effects. Conversely, those who underwent sham brain stimulation demonstrated classical directed forgetting effects. We argue that these findings suggest that inhibition is the primary mechanism that results in directed forgetting costs and benefits. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Individual differences in attentional modulation of cortical responses correlate with selective attention performance

PubMed Central

Choi, Inyong; Wang, Le; Bharadwaj, Hari; Shinn-Cunningham, Barbara

2014-01-01

Many studies have shown that attention modulates the cortical representation of an auditory scene, emphasizing an attended source while suppressing competing sources. Yet, individual differences in the strength of this attentional modulation and their relationship with selective attention ability are poorly understood. Here, we ask whether differences in how strongly attention modulates cortical responses reflect differences in normal-hearing listeners’ selective auditory attention ability. We asked listeners to attend to one of three competing melodies and identify its pitch contour while we measured cortical electroencephalographic responses. The three melodies were either from widely separated pitch ranges (“easy trials”), or from a narrow, overlapping pitch range (“hard trials”). The melodies started at slightly different times; listeners attended either the leading or lagging melody. Because of the timing of the onsets, the leading melody drew attention exogenously. In contrast, attending the lagging melody required listeners to direct top-down attention volitionally. We quantified how attention amplified auditory N1 response to the attended melody and found large individual differences in the N1 amplification, even though only correctly answered trials were used to quantify the ERP gain. Importantly, listeners with the strongest amplification of N1 response to the lagging melody in the easy trials were the best performers across other types of trials. Our results raise the possibility that individual differences in the strength of top-down gain control reflect inherent differences in the ability to control top-down attention. PMID:24821552

Low cortical bone density measured by computed tomography in children and adolescents with untreated hyperthyroidism.

PubMed

Numbenjapon, Nawaporn; Costin, Gertrude; Gilsanz, Vicente; Pitukcheewanont, Pisit

2007-05-01

To determine whether increased thyroid hormones levels have an effect on various bone components (cortical vs cancellous bone). The anthropometric and 3-dimensional quantitative computed tomography (CT) bone measurements, including bone density (BD), cross-sectional area (CSA) of the lumbar spine and femur, and cortical bone area (CBA) of the femur, of 18 children and adolescents with untreated hyperthyroidism were reviewed and compared with those of age-, sex-, and ethnicity-matched historical controls. No significant differences in height, weight, body mass index (BMI), or pubertal staging between patients and controls were found. Cortical BD was significantly lower (P < .001) in children and adolescents with hyperthyroidism compared with historical controls. After adjusting for weight and height, no difference in femur CSA between hyperthyroid children and historical controls was evident. No significant correlations among thyroid hormone levels, antithyroid antibody levels, and cortical BD values were found. As determined by CT, cortical bone is the preferential site of bone loss in children and adolescents with untreated hyperthyroidism.

Effects of Hypocretin/Orexin and Major Transmitters of Arousal on Fast Spiking Neurons in Mouse Cortical Layer 6B

PubMed Central

Wenger Combremont, Anne-Laure; Bayer, Laurence; Dupré, Anouk; Mühlethaler, Michel; Serafin, Mauro

2016-01-01

Fast spiking (FS) GABAergic neurons are thought to be involved in the generation of high-frequency cortical rhythms during the waking state. We previously showed that cortical layer 6b (L6b) was a specific target for the wake-promoting transmitter, hypocretin/orexin (hcrt/orx). Here, we have investigated whether L6b FS cells were sensitive to hcrt/orx and other transmitters associated with cortical activation. Recordings were thus made from L6b FS cells in either wild-type mice or in transgenic mice in which GFP-positive GABAergic cells are parvalbumin positive. Whereas in a control condition hcrt/orx induced a strong increase in the frequency, but not amplitude, of spontaneous synaptic currents, in the presence of TTX, it had no effect at all on miniature synaptic currents. Hcrt/orx effect was thus presynaptic although not by an action on glutamatergic terminals but rather on neighboring cells. In contrast, noradrenaline and acetylcholine depolarized and excited these cells through a direct postsynaptic action. Neurotensin, which is colocalized in hcrt/orx neurons, also depolarized and excited these cells but the effect was indirect. Morphologically, these cells exhibited basket-like features. These results suggest that hcrt/orx, noradrenaline, acetylcholine, and neurotensin could contribute to high-frequency cortical activity through an action on L6b GABAergic FS cells. PMID:27235100

Cortical motor activity and reorganization following upper-limb amputation and subsequent targeted reinnervation.

PubMed

Chen, Albert; Yao, Jun; Kuiken, Todd; Dewald, Julius P A

2013-01-01

Previous studies have postulated that the amount of brain reorganization following peripheral injuries may be correlated with negative symptoms or consequences. However, it is unknown whether restoring effective limb function may then be associated with further changes in the expression of this reorganization. Recently, targeted reinnervation (TR), a surgical technique that restores a direct neural connection from amputated sensorimotor nerves to new peripheral targets such as muscle, has been successfully applied to upper-limb amputees. It has been shown to be effective in restoring both peripheral motor and sensory functions via the reinnervated nerves as soon as a few months after the surgery. However, it was unclear whether TR could also restore normal cortical motor representations for control of the missing limb. To answer this question, we used high-density electroencephalography (EEG) to localize cortical activity related to cued motor tasks generated by the intact and missing limb. Using a case study of 3 upper-limb amputees, 2 of whom went through pre and post-TR experiments, we present unique quantitative evidence for the re-mapping of motor representations for the missing limb closer to their original locations following TR. This provides evidence that an effective restoration of peripheral function from TR can be linked to the return of more normal cortical expression for the missing limb. Therefore, cortical mapping may be used as a potential guide for monitoring rehabilitation following peripheral injuries.

Crossmodal Connections of Primary Sensory Cortices Largely Vanish During Normal Aging

PubMed Central

Henschke, Julia U.; Ohl, Frank W.; Budinger, Eike

2018-01-01

During aging, human response times (RTs) to unisensory and crossmodal stimuli decrease. However, the elderly benefit more from crossmodal stimulus representations than younger people. The underlying short-latency multisensory integration process is mediated by direct crossmodal connections at the level of primary sensory cortices. We investigate the age-related changes of these connections using a rodent model (Mongolian gerbil), retrograde tracer injections into the primary auditory (A1), somatosensory (S1), and visual cortex (V1), and immunohistochemistry for markers of apoptosis (Caspase-3), axonal plasticity (Growth associated protein 43, GAP 43), and a calcium-binding protein (Parvalbumin, PV). In adult animals, primary sensory cortices receive a substantial number of direct thalamic inputs from nuclei of their matched, but also from nuclei of non-matched sensory modalities. There are also direct intracortical connections among primary sensory cortices and connections with secondary sensory cortices of other modalities. In very old animals, the crossmodal connections strongly decrease in number or vanish entirely. This is likely due to a retraction of the projection neuron axonal branches rather than ongoing programmed cell death. The loss of crossmodal connections is also accompanied by changes in anatomical correlates of inhibition and excitation in the sensory thalamus and cortex. Together, the loss and restructuring of crossmodal connections during aging suggest a shift of multisensory processing from primary cortices towards other sensory brain areas in elderly individuals. PMID:29551970

Crossmodal Connections of Primary Sensory Cortices Largely Vanish During Normal Aging.

PubMed

Henschke, Julia U; Ohl, Frank W; Budinger, Eike

2018-01-01

During aging, human response times (RTs) to unisensory and crossmodal stimuli decrease. However, the elderly benefit more from crossmodal stimulus representations than younger people. The underlying short-latency multisensory integration process is mediated by direct crossmodal connections at the level of primary sensory cortices. We investigate the age-related changes of these connections using a rodent model (Mongolian gerbil), retrograde tracer injections into the primary auditory (A1), somatosensory (S1), and visual cortex (V1), and immunohistochemistry for markers of apoptosis (Caspase-3), axonal plasticity (Growth associated protein 43, GAP 43), and a calcium-binding protein (Parvalbumin, PV). In adult animals, primary sensory cortices receive a substantial number of direct thalamic inputs from nuclei of their matched, but also from nuclei of non-matched sensory modalities. There are also direct intracortical connections among primary sensory cortices and connections with secondary sensory cortices of other modalities. In very old animals, the crossmodal connections strongly decrease in number or vanish entirely. This is likely due to a retraction of the projection neuron axonal branches rather than ongoing programmed cell death. The loss of crossmodal connections is also accompanied by changes in anatomical correlates of inhibition and excitation in the sensory thalamus and cortex. Together, the loss and restructuring of crossmodal connections during aging suggest a shift of multisensory processing from primary cortices towards other sensory brain areas in elderly individuals.

Differential effects of cannabis dependence on cortical inhibition in patients with schizophrenia and non-psychiatric controls.

PubMed

Goodman, Michelle S; Bridgman, Alanna C; Rabin, Rachel A; Blumberger, Daniel M; Rajji, Tarek K; Daskalakis, Zafiris J; George, Tony P; Barr, Mera S

Cannabis is the most commonly used illicit substance among patients with schizophrenia. Cannabis exacerbates psychotic symptoms and leads to poor functional outcomes. Dysfunctional cortical inhibition has been implicated in the pathophysiology of schizophrenia; however, the effects of cannabis on this mechanism have been relatively unexamined. The goal of this study was to index cortical inhibition from the motor cortex among 4 groups: schizophrenia patients and non-psychiatric controls dependent on cannabis as well as cannabis-free schizophrenia patients and non-psychiatric controls. In this cross-sectional study, GABA-mediated cortical inhibition was index with single- and paired-pulse transcranial magnetic stimulation (TMS) paradigms to the left motor cortex in 12 cannabis dependent and 11 cannabis-free schizophrenia patients, and in 10 cannabis dependent and 13 cannabis-free controls. Cannabis-dependent patients with schizophrenia displayed greater short-interval cortical inhibition (SICI) compared to cannabis-free schizophrenia patients (p = 0.029), while cannabis-dependent controls displayed reduced SICI compared to cannabis-free controls (p = 0.004). SICI did not differ between cannabis dependent patients and cannabis-free controls, or between dependent schizophrenia patients compared to dependent controls. No significant differences were found for long-interval cortical inhibition (LICI) or intra-cortical facilitation (ICF) receptor function, suggesting a selective effect on SICI. These findings suggest that cannabis dependence may have selective and differing effects on SICI in schizophrenia patients compared to controls, which may provide insight into the pathophysiology of co-morbid cannabis dependence in schizophrenia. Copyright © 2016 Elsevier Inc. All rights reserved.

Emergence of a Stable Cortical Map for Neuroprosthetic Control

PubMed Central

Ganguly, Karunesh; Carmena, Jose M.

2009-01-01

Cortical control of neuroprosthetic devices is known to require neuronal adaptations. It remains unclear whether a stable cortical representation for prosthetic function can be stored and recalled in a manner that mimics our natural recall of motor skills. Especially in light of the mixed evidence for a stationary neuron-behavior relationship in cortical motor areas, understanding this relationship during long-term neuroprosthetic control can elucidate principles of neural plasticity as well as improve prosthetic function. Here, we paired stable recordings from ensembles of primary motor cortex neurons in macaque monkeys with a constant decoder that transforms neural activity to prosthetic movements. Proficient control was closely linked to the emergence of a surprisingly stable pattern of ensemble activity, indicating that the motor cortex can consolidate a neural representation for prosthetic control in the presence of a constant decoder. The importance of such a cortical map was evident in that small perturbations to either the size of the neural ensemble or to the decoder could reversibly disrupt function. Moreover, once a cortical map became consolidated, a second map could be learned and stored. Thus, long-term use of a neuroprosthetic device is associated with the formation of a cortical map for prosthetic function that is stable across time, readily recalled, resistant to interference, and resembles a putative memory engram. PMID:19621062

When anger leads to aggression: induction of relative left frontal cortical activity with transcranial direct current stimulation increases the anger–aggression relationship

PubMed Central

Hortensius, Ruud; Schutter, Dennis J. L. G.

2012-01-01

The relationship between anger and aggression is imperfect. Based on work on the neuroscience of anger, we predicted that anger associated with greater relative left frontal cortical activation would be more likely to result in aggression. To test this hypothesis, we combined transcranial direct current stimulation (tDCS) over the frontal cortex with interpersonal provocation. Participants received insulting feedback after 15 min of tDCS and were able to aggress by administering noise blasts to the insulting participant. Individuals who received tDCS to increase relative left frontal cortical activity behaved more aggressively when they were angry. No relation between anger and aggression was observed in the increase relative right frontal cortical activity or sham condition. These results concur with the motivational direction model of frontal asymmetry, in which left frontal activity is associated with anger. We propose that anger with approach motivational tendencies is more likely to result in aggression. PMID:21421731

Shared motion signals for human perceptual decisions and oculomotor actions

NASA Technical Reports Server (NTRS)

Stone, Leland S.; Krauzlis, Richard J.

2003-01-01

A fundamental question in primate neurobiology is to understand to what extent motor behaviors are driven by shared neural signals that also support conscious perception or by independent subconscious neural signals dedicated to motor control. Although it has clearly been established that cortical areas involved in processing visual motion support both perception and smooth pursuit eye movements, it remains unknown whether the same or different sets of neurons within these structures perform these two functions. Examination of the trial-by-trial variation in human perceptual and pursuit responses during a simultaneous psychophysical and oculomotor task reveals that the direction signals for pursuit and perception are not only similar on average but also co-vary on a trial-by-trial basis, even when performance is at or near chance and the decisions are determined largely by neural noise. We conclude that the neural signal encoding the direction of target motion that drives steady-state pursuit and supports concurrent perceptual judgments emanates from a shared ensemble of cortical neurons.

Distribution of Longitudinal Wave Velocities in Bovine Cortical Bone in vitro

NASA Astrophysics Data System (ADS)

Yamato, Yu; Kataoka, Hideo; Matsukawa, Mami; Yamazaki, Kaoru; Otani, Takahiko; Nagano, Akira

2005-06-01

The distribution of longitudinal wave velocities and longitudinal moduli in a bovine femoral cortical bone was experimentally investigated. In all parts of the long cylindrical bone, the velocities and longitudinal moduli in the axial direction were the highest. In the anterior (A) part, the velocities in the axial direction were high and almost constant, whereas the velocities in the proximal postero medial (PM) and distal postero lateral (PL) parts markedly decreased. Classifying the cortical bone into three structures (plexiform, Haversian, and porotic), we clarify the velocity distributions in the bone with discussion from an anatomical point of view.

Imaging derived cortical thickness reduction in high-functioning autism: key regions and temporal slope.

PubMed

Scheel, Christian; Rotarska-Jagiela, Anna; Schilbach, Leonhard; Lehnhardt, Fritz G; Krug, Barbara; Vogeley, Kai; Tepest, Ralf

2011-09-15

Cortical thickness (CT) changes possibly contribute to the complex symptomatology of autism. The aberrant developmental trajectories underlying such differences in certain brain regions and their continuation in adulthood are a matter of intense debate. We studied 28 adults with high-functioning autism (HFA) and 28 control subjects matched for age, gender, IQ and handedness. A surface-based whole brain analysis utilizing FreeSurfer was employed to detect CT differences between the two diagnostic groups and to investigate the time course of age-related changes. Direct comparison with control subjects revealed thinner cortex in HFA in the posterior superior temporal sulcus (pSTS) of the left hemisphere. Considering the time course of CT development we found clusters around the pSTS and cuneus in the left and the paracentral lobule in the right hemisphere to be thinner in HFA with comparable age-related slopes in patients and controls. Conversely, we found clusters around the supramarginal gyrus and inferior parietal lobule (IPL) in the left and the precentral and postcentral gyrus in the right hemisphere to be thinner in HFA, but with different age-related slopes in patients and controls. In the latter regions CT showed a steady decrease in controls but no analogous thinning in HFA. CT analyses contribute in characterizing neuroanatomical correlates of HFA. Reduced CT is present in brain regions involved in social cognition. Furthermore, our results demonstrate that aberrant brain development leading to such differences is proceeding throughout adulthood. Discrepancies in prior morphometric studies may be induced by the complex time course of cortical changes. Copyright © 2011 Elsevier Inc. All rights reserved.

Cortical Silent Period Reveals Differences Between Adductor Spasmodic Dysphonia and Muscle Tension Dysphonia.

PubMed

Samargia, Sharyl; Schmidt, Rebekah; Kimberley, Teresa Jacobson

2016-03-01

The pathophysiology of adductor spasmodic dysphonia (AdSD), like other focal dystonias, is largely unknown. The purposes of this study were to determine (a) cortical excitability differences between AdSD, muscle tension dysphonia (MTD), and healthy controls; (b) distribution of potential differences in cranial or skeletal muscle; and (c) if cortical excitability measures assist in the differential diagnosis of AdSD and MTD. Ten participants with adductor spasmodic dysphonia, 8 with muscle tension dysphonia, and 10 healthy controls received single and paired pulse transcranial magnetic stimulation (TMS) to the primary motor cortex contralateral to tested muscles, first dorsal interosseus (FDI), and masseter. We tested the hypothesis that cortical excitability measures in AdSD would be significantly different from those in MTD and healthy controls. In addition, we hypothesized that there would be a correlation between cortical excitability measures and clinical voice severity in AdSD. Cortical silent period duration in masseter and FDI was significantly shorter in AdSD than MTD and healthy controls. Other measures failed to demonstrate differences. There are differences in cortical excitability between AdSD, MTD, and healthy controls. These differences in the cortical measure of both the FDI and masseter muscles in AdSD suggest widespread dysfunction of the GABAB mechanism may be a pathophysiologic feature of AdSD, similar to other forms of focal dystonia. Further exploration of the use of TMS to assist in the differential diagnosis of AdSD and MTD is warranted. © The Author(s) 2015.

Early development of synchrony in cortical activations in the human.

PubMed

Koolen, N; Dereymaeker, A; Räsänen, O; Jansen, K; Vervisch, J; Matic, V; Naulaers, G; De Vos, M; Van Huffel, S; Vanhatalo, S

2016-05-13

Early intermittent cortical activity is thought to play a crucial role in the growth of neuronal network development, and large scale brain networks are known to provide the basis for higher brain functions. Yet, the early development of the large scale synchrony in cortical activations is unknown. Here, we tested the hypothesis that the early intermittent cortical activations seen in the human scalp EEG show a clear developmental course during the last trimester of pregnancy, the period of intensive growth of cortico-cortical connections. We recorded scalp EEG from altogether 22 premature infants at post-menstrual age between 30 and 44 weeks, and the early cortical synchrony was quantified using recently introduced activation synchrony index (ASI). The developmental correlations of ASI were computed for individual EEG signals as well as anatomically and mathematically defined spatial subgroups. We report two main findings. First, we observed a robust and statistically significant increase in ASI in all cortical areas. Second, there were significant spatial gradients in the synchrony in fronto-occipital and left-to-right directions. These findings provide evidence that early cortical activity is increasingly synchronized across the neocortex. The ASI-based metrics introduced in our work allow direct translational comparison to in vivo animal models, as well as hold promise for implementation as a functional developmental biomarker in future research on human neonates. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Cortical Thickness Abnormalities in Late Adolescence with Online Gaming Addiction

PubMed Central

Yuan, Kai; Cheng, Ping; Dong, Tao; Bi, Yanzhi; Xing, Lihong; Yu, Dahua; Zhao, Limei; Dong, Minghao; von Deneen, Karen M.; Liu, Yijun; Qin, Wei; Tian, Jie

2013-01-01

Online gaming addiction, as the most popular subtype of Internet addiction, had gained more and more attention from the whole world. However, the structural differences in cortical thickness of the brain between adolescents with online gaming addiction and healthy controls are not well unknown; neither was its association with the impaired cognitive control ability. High-resolution magnetic resonance imaging scans from late adolescence with online gaming addiction (n = 18) and age-, education- and gender-matched controls (n = 18) were acquired. The cortical thickness measurement method was employed to investigate alterations of cortical thickness in individuals with online gaming addiction. The color-word Stroop task was employed to investigate the functional implications of the cortical thickness abnormalities. Imaging data revealed increased cortical thickness in the left precentral cortex, precuneus, middle frontal cortex, inferior temporal and middle temporal cortices in late adolescence with online gaming addiction; meanwhile, the cortical thicknesses of the left lateral orbitofrontal cortex (OFC), insula, lingual gyrus, the right postcentral gyrus, entorhinal cortex and inferior parietal cortex were decreased. Correlation analysis demonstrated that the cortical thicknesses of the left precentral cortex, precuneus and lingual gyrus correlated with duration of online gaming addiction and the cortical thickness of the OFC correlated with the impaired task performance during the color-word Stroop task in adolescents with online gaming addiction. The findings in the current study suggested that the cortical thickness abnormalities of these regions may be implicated in the underlying pathophysiology of online gaming addiction. PMID:23326379

Cortical thickness abnormalities in late adolescence with online gaming addiction.

PubMed

Yuan, Kai; Cheng, Ping; Dong, Tao; Bi, Yanzhi; Xing, Lihong; Yu, Dahua; Zhao, Limei; Dong, Minghao; von Deneen, Karen M; Liu, Yijun; Qin, Wei; Tian, Jie

2013-01-01

Online gaming addiction, as the most popular subtype of Internet addiction, had gained more and more attention from the whole world. However, the structural differences in cortical thickness of the brain between adolescents with online gaming addiction and healthy controls are not well unknown; neither was its association with the impaired cognitive control ability. High-resolution magnetic resonance imaging scans from late adolescence with online gaming addiction (n = 18) and age-, education- and gender-matched controls (n = 18) were acquired. The cortical thickness measurement method was employed to investigate alterations of cortical thickness in individuals with online gaming addiction. The color-word Stroop task was employed to investigate the functional implications of the cortical thickness abnormalities. Imaging data revealed increased cortical thickness in the left precentral cortex, precuneus, middle frontal cortex, inferior temporal and middle temporal cortices in late adolescence with online gaming addiction; meanwhile, the cortical thicknesses of the left lateral orbitofrontal cortex (OFC), insula, lingual gyrus, the right postcentral gyrus, entorhinal cortex and inferior parietal cortex were decreased. Correlation analysis demonstrated that the cortical thicknesses of the left precentral cortex, precuneus and lingual gyrus correlated with duration of online gaming addiction and the cortical thickness of the OFC correlated with the impaired task performance during the color-word Stroop task in adolescents with online gaming addiction. The findings in the current study suggested that the cortical thickness abnormalities of these regions may be implicated in the underlying pathophysiology of online gaming addiction.

Evidence for increased glutamatergic cortical facilitation in children and adolescents with major depressive disorder.

PubMed

Croarkin, Paul E; Nakonezny, Paul A; Husain, Mustafa M; Melton, Tabatha; Buyukdura, Jeylan S; Kennard, Betsy D; Emslie, Graham J; Kozel, F Andrew; Daskalakis, Zafiris J

2013-03-01

Converging lines of evidence implicate the glutamate and γ-aminobutyric acid neurotransmitter systems in the pathophysiology of major depressive disorder. Transcranial magnetic stimulation cortical excitability and inhibition paradigms have been used to assess cortical glutamatergic and γ-aminobutyric acid-mediated tone in adults with major depressive disorder, but not in children and adolescents. To compare measures of cortical excitability and inhibition with 4 different paradigms in a group of children and adolescents with major depressive disorder vs healthy controls. Cross-sectional study examining medication-free children and adolescents (aged 9-17 years) with major depressive disorder compared with healthy controls. Cortical excitability was assessed with motor threshold and intracortical facilitation measures. Cortical inhibition was measured with cortical silent period and intracortical inhibition paradigms. University-based child and adolescent psychiatry clinic and neurostimulation laboratory. Twenty-four participants with major depressive disorder and 22 healthy controls matched for age and sex. Patients with major depressive disorder were medication naive and had moderate to severe symptoms based on an evaluation with a child and adolescent psychiatrist and scores on the Children's Depression Rating Scale-Revised. Motor threshold, intracortical facilitation, cortical silent period, and intracortical inhibition. Compared with healthy controls, depressed patients had significantly increased intracortical facilitation at interstimulus intervals of 10 and 15 milliseconds bilaterally. There were no significant group differences in cortical inhibition measures. These findings suggest that major depressive disorder in children and adolescents is associated with increased intracortical facilitation and excessive glutamatergic activity.

Catechol-o-methyl transferase (COMT) val158met polymorphism and adolescent cortical development in patients with childhood-onset schizophrenia, their non-psychotic siblings, and healthy controls

PubMed Central

Raznahan, Armin; Greenstein, Deanna; Lee, Yohan; Long, Robert; Clasen, Liv; Gochman, Pete; Addington, Anjene; Giedd, Jay N.; Rapoport, Judith L.; Gogtay, Nitin

2012-01-01

Non-psychotic individuals at increased risk for schizophrenia show alterations in fronto-striatal dopamine signaling and cortical gray matter maturation reminiscent of those seen in schizophrenia. It remains unclear however if variations in dopamine signaling influence rates of structural cortical maturation in typically developing individuals, and whether such influences are disrupted in patients with schizophrenia and their non-psychotic siblings. We sought to address these issues by relating a functional Val→Met polymorphism within the gene encoding catechol-o-methyltransferase (COMT)—a key enzymatic regulator of cortical dopamine levels—to longitudinal structural neuroimaging measures of cortical gray matter thickness. We included a total of 792 magnetic resonance imaging brain scans, acquired between ages 9 and 22 years from patients with childhood-onset schizophrenia (COS), their non-psychotic full siblings, and matched healthy controls. Whereas greater Val allele dose (which confers enhanced dopamine catabolism and is proposed to aggravate cortical deficits in schizophrenia) accelerated adolescent cortical thinning in both schizophrenia probands and their siblings, it attenuated cortical thinning in healthy controls. This similarity between COS patients and their siblings was accompanied by differences between the two groups in the timing and spatial distribution of disrupted COMT influences on cortical maturation. Consequently, whereas greater Val “dose” conferred persistent dorsolateral prefrontal cortical deficits amongst affected probands by adulthood, cortical thickness differences associated with varying Val dose in non-psychotic siblings resolved over the age-range studied. These findings suggest that cortical abnormalities in pedigrees affected by schizophrenia may be contributed to by a disruption of dopaminergic infleunces on cortical maturation. PMID:21620981

Restoring balance in focal limb dystonia with botulinum toxin.

PubMed

Sheean, Geoffrey

2007-12-15

Focal task-specific dystonia of the hand is rare in the general population, where it usually manifests as writer's cramp, but seems relatively common among musicians. The disability may be so severe as to prevent writing altogether or to end a professional musician's career. The cause is usually unknown but it is thought to be primarily a basal ganglia disorder with dysfunction of cortical-striatothalamic-cortical circuits. Abnormalities have been found in cortical movement preparation, intracortical inhibition, sensory and motor maps, and patterns of cortical activation during movement. Much evidence supports disordered processing of sensory information with disturbed sensorimotor integration. Underlying this may be maladaptive neural plasticity mechanisms. Treatment is difficult. Oral medications are generally ineffective and have troublesome side-effects. Intensive rehabilitation techniques based on neural plasticity theory show promise but are rarely available and are time-intensive. Botulinum toxin injections appear to be effective in writer's cramp and musician's dystonia, at least initially; long-term benefit is less common. Despite definite improvement, some patients abandon treatment because the gain is insufficient for meaningful function: this is particularly so for musicians. Much of the benefit from botulinum toxin injection comes from simply reducing muscle overactivity through muscle paralysis, restoring balance to motor control. However, some evidence suggests that botulinum toxin injections can produce transient improvement in some of the various cortical abnormalities described, probably through alteration of sensory input from the periphery, by direct and indirect means. These changes in cortical function might be usefully combined with those brought about by sensorimotor retraining programs, but such studies are awaited.

Cortical thickness and surface area in neonates at high risk for schizophrenia.

PubMed

Li, Gang; Wang, Li; Shi, Feng; Lyall, Amanda E; Ahn, Mihye; Peng, Ziwen; Zhu, Hongtu; Lin, Weili; Gilmore, John H; Shen, Dinggang

2016-01-01

Schizophrenia is a neurodevelopmental disorder associated with subtle abnormal cortical thickness and cortical surface area. However, it is unclear whether these abnormalities exist in neonates associated with genetic risk for schizophrenia. To this end, this preliminary study was conducted to identify possible abnormalities of cortical thickness and surface area in the high-genetic-risk neonates. Structural magnetic resonance images were acquired from offspring of mothers (N = 21) who had schizophrenia (N = 12) or schizoaffective disorder (N = 9), and also matched healthy neonates of mothers who were free of psychiatric illness (N = 26). Neonatal cortical surfaces were reconstructed and parcellated as regions of interest (ROIs), and cortical thickness for each vertex was computed as the shortest distance between the inner and outer surfaces. Comparisons were made for the average cortical thickness and total surface area in each of 68 cortical ROIs. After false discovery rate (FDR) correction, it was found that the female high-genetic-risk neonates had significantly thinner cortical thickness in the right lateral occipital cortex than the female control neonates. Before FDR correction, the high-genetic-risk neonates had significantly thinner cortex in the left transverse temporal gyrus, left banks of superior temporal sulcus, left lingual gyrus, right paracentral cortex, right posterior cingulate cortex, right temporal pole, and right lateral occipital cortex, compared with the control neonates. Before FDR correction, in comparison with control neonates, male high-risk neonates had significantly thicker cortex in the left frontal pole, left cuneus cortex, and left lateral occipital cortex; while female high-risk neonates had significantly thinner cortex in the bilateral paracentral, bilateral lateral occipital, left transverse temporal, left pars opercularis, right cuneus, and right posterior cingulate cortices. The high-risk neonates also had significantly smaller cortical surface area in the right pars triangularis (before FDR correction), compared with control neonates. This preliminary study provides the first evidence that early development of cortical thickness and surface area might be abnormal in the neonates at genetic risk for schizophrenia.

A direct translaminar inhibitory circuit tunes cortical output

PubMed Central

Pluta, Scott; Naka, Alexander; Veit, Julia; Telian, Gregory; Yao, Lucille; Hakim, Richard; Taylor, David; Adesnik, Hillel

2015-01-01

Summary Anatomical and physiological experiments have outlined a blueprint for the feed-forward flow of activity in cortical circuits: signals are thought to propagate primarily from the middle cortical layer, L4, up to L2/3, and down to the major cortical output layer, L5. Pharmacological manipulations, however, have contested this model and suggested that L4 may not be critical for sensory responses of neurons in either superficial or deep layers. To address these conflicting models we reversibly manipulated L4 activity in awake, behaving mice using cell-type specific optogenetics. In contrast to both prevailing models, we show that activity in L4 directly suppresses L5, in part by activating deep, fast spiking inhibitory neurons. Our data suggest that the net impact of L4 activity is to sharpen the spatial representations of L5 neurons. Thus we establish a novel translaminar inhibitory circuit in the sensory cortex that acts to enhance the feature selectivity of cortical output. PMID:26414615

Treatment of Memory Disorders in Gulf War Illness with High-Definition Transcranial Direct Cortical Stimulation

DTIC Science & Technology

2017-10-01

AWARD NUMBER: W81XWH-16-1-0521 TITLE: Treatment of Memory Disorders in Gulf War Illness with High - Definition Transcranial Direct Cortical...Approved for Public Release; Distribution Unlimited The views, opinions and/or findings contained in this report are those of the author(s) and should...Sep 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Treatment of Memory Disorders in Gulf War Illness with High -Definition Transcranial Direct

Differential impact of partial cortical blindness on gaze strategies when sitting and walking - an immersive virtual reality study

PubMed Central

Iorizzo, Dana B.; Riley, Meghan E.; Hayhoe, Mary; Huxlin, Krystel R.

2011-01-01

The present experiments aimed to characterize the visual performance of subjects with long-standing, unilateral cortical blindness when walking in a naturalistic, virtual environment. Under static, seated testing conditions, cortically blind subjects are known to exhibit compensatory eye movement strategies. However, they still complain of significant impairment in visual detection during navigation. To assess whether this is due to a change in compensatory eye movement strategy between sitting and walking, we measured eye and head movements in subjects asked to detect peripherally-presented, moving basketballs. When seated, cortically blind subjects detected ~80% of balls, while controls detected almost all balls. Seated blind subjects did not make larger head movements than controls, but they consistently biased their fixation distribution towards their blind hemifield. When walking, head movements were similar in the two groups, but the fixation bias decreased to the point that fixation distribution in cortically blind subjects became similar to that in controls - with one major exception: at the time of basketball appearance, walking controls looked primarily at the far ground, in upper quadrants of the virtual field of view; cortically blind subjects looked significantly more at the near ground, in lower quadrants of the virtual field. Cortically blind subjects detected only 58% of the balls when walking while controls detected ~90%. Thus, the adaptive gaze strategies adopted by cortically blind individuals as a compensation for their visual loss are strongest and most effective when seated and stationary. Walking significantly alters these gaze strategies in a way that seems to favor walking performance, but impairs peripheral target detection. It is possible that this impairment underlies the experienced difficulty of those with cortical blindness when navigating in real life. PMID:21414339

Differential impact of partial cortical blindness on gaze strategies when sitting and walking - an immersive virtual reality study.

PubMed

Iorizzo, Dana B; Riley, Meghan E; Hayhoe, Mary; Huxlin, Krystel R

2011-05-25

The present experiments aimed to characterize the visual performance of subjects with long-standing, unilateral cortical blindness when walking in a naturalistic, virtual environment. Under static, seated testing conditions, cortically blind subjects are known to exhibit compensatory eye movement strategies. However, they still complain of significant impairment in visual detection during navigation. To assess whether this is due to a change in compensatory eye movement strategy between sitting and walking, we measured eye and head movements in subjects asked to detect peripherally-presented, moving basketballs. When seated, cortically blind subjects detected ∼80% of balls, while controls detected almost all balls. Seated blind subjects did not make larger head movements than controls, but they consistently biased their fixation distribution towards their blind hemifield. When walking, head movements were similar in the two groups, but the fixation bias decreased to the point that fixation distribution in cortically blind subjects became similar to that in controls - with one major exception: at the time of basketball appearance, walking controls looked primarily at the far ground, in upper quadrants of the virtual field of view; cortically blind subjects looked significantly more at the near ground, in lower quadrants of the virtual field. Cortically blind subjects detected only 58% of the balls when walking while controls detected ∼90%. Thus, the adaptive gaze strategies adopted by cortically blind individuals as a compensation for their visual loss are strongest and most effective when seated and stationary. Walking significantly alters these gaze strategies in a way that seems to favor walking performance, but impairs peripheral target detection. It is possible that this impairment underlies the experienced difficulty of those with cortical blindness when navigating in real life. Copyright © 2011 Elsevier Ltd. All rights reserved.

Cortical brain development in nonpsychotic siblings of patients with childhood-onset schizophrenia.

PubMed

Gogtay, Nitin; Greenstein, Deanna; Lenane, Marge; Clasen, Liv; Sharp, Wendy; Gochman, Pete; Butler, Philip; Evans, Alan; Rapoport, Judith

2007-07-01

Cortical gray matter (GM) loss is marked and progressive in childhood-onset schizophrenia (COS) during adolescence but becomes more circumscribed by early adulthood. Nonpsychotic siblings of COS probands could help evaluate whether the cortical GM abnormalities are familial/trait markers. To map cortical development in nonpsychotic siblings of COS probands. Using an automated measurement and prospectively acquired anatomical brain magnetic resonance images, we mapped cortical GM thickness in healthy full siblings (n = 52, 113 scans; age 8 through 28 years) of patients with COS, contrasting them with age-, sex-, and scan interval-matched healthy controls (n = 52, 108 scans). The false-discovery rate procedure was used to control for type I errors due to multiple comparisons. An ongoing COS study at the National Institute of Mental Health. Fifty-two healthy full siblings of patients with COS, aged 8 through 28 years, and 52 healthy controls. Longitudinal trajectories of cortical GM development in healthy siblings of patients with COS compared with matched healthy controls and exploratory measure of the relationship between developmental GM trajectories and the overall functioning as defined by the Global Assessment Scale (GAS) score. Younger, healthy siblings of patients with COS showed significant GM deficits in the left prefrontal and bilateral temporal cortices and smaller deficits in the right prefrontal and inferior parietal cortices compared with the controls. These cortical deficits in siblings disappeared by age 20 years and the process of deficit reduction correlated with overall functioning (GAS scores) at the last scan. Prefrontal and temporal GM loss in COS appears to be a familial/trait marker. Amelioration of regional GM deficits in healthy siblings was associated with higher global functioning (GAS scores), suggesting a relationship between brain plasticity and functional outcome for these nonpsychotic, nonspectrum siblings.

Preliminary Evidence That Excitatory Transcranial Direct Current Stimulation Extends Time to Task Failure of a Sustained, Submaximal Muscular Contraction in Older Adults.

PubMed

Oki, Kentaro; Mahato, Niladri K; Nakazawa, Masato; Amano, Shinichi; France, Christopher R; Russ, David W; Clark, Brian C

2016-08-01

Decreased cortical excitability has been proposed as a potential mechanism underlying task failure during sustained muscular contractions, and cortical excitability may decrease with old age. We tested the hypothesis that transcranial direct current stimulation, which has been reported to raise cortical excitability, would prolong the time to task failure during a sustained muscular contraction in older adults. Thirteen older adults (68.3±2.0 years; eight women and five men) performed isometric, elbow flexions to failure while receiving sham or anodal transcranial direct current stimulation. Order of stimulation was randomized, and the subjects and investigators were blinded to condition. Time to task failure was measured alongside selected psychological indices of perceived exertion and affect. Anodal transcranial direct current stimulation prolonged mean time to task failure by approximately 15% (16.9±2.2 vs 14.7±1.8 minutes) and slowed the rate of increase in rating of perceived exertion (0.29±0.03 vs 0.31±0.03) relative to the sham condition. These preliminary findings suggest that anodal transcranial direct current stimulation enhances time to task failure of a sustained, submaximal contraction in older adults by potentially increasing cortical excitability and/or influencing the perception of exertion. These results raise the question of whether interventions that acutely increase cortical excitability could enhance physical function and/or exercise-induced adaptations in older adults. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Protein phosphatase 2ACα gene knock-out results in cortical atrophy through activating hippo cascade in neuronal progenitor cells.

PubMed

Liu, Bo; Sun, Li-Hua; Huang, Yan-Fei; Guo, Li-Jun; Luo, Li-Shu

2018-02-01

Protein phosphatase 2ACα (PP2ACα), a vital member of the protein phosphatase family, has been studied primarily as a regulator for the development, growth and protein synthesis of a lot of cell types. Dysfunction of PP2ACα protein results in neurodegenerative disease; however, this finding has not been directly confirmed in the mouse model with PP2ACα gene knock-out. Therefore, in this study presented here, we generated the PP2ACα gene knock-out mouse model by the Cre-loxP targeting gene system, with the purpose to directly observe the regulatory role of PP2ACα gene in the development of mouse's cerebral cortex. We observe that knocking-out PP2ACα gene in the central nervous system (CNS) results in cortical neuronal shrinkage, synaptic plasticity impairments, and learning/memory deficits. Further study reveals that PP2ACα gene knock-out initiates Hippo cascade in cortical neuroprogenitor cells (NPCs), which blocks YAP translocation into the nuclei of NPCs. Notably, p73, directly targeted by Hippo cascade, can bind to the promoter of glutaminase2 (GLS2) that plays a dominant role in the enzymatic regulation of glutamate/glutamine cycle. Finally, we find that PP2ACα gene knock-out inhibits the glutamine synthesis through up-regulating the activity of phosphorylated-p73 in cortical NPCs. Taken together, it concludes that PP2ACα critically supports cortical neuronal growth and cognitive function via regulating the signaling transduction of Hippo-p73 cascade. And PP2ACα indirectly modulates the glutamine synthesis of cortical NPCs through targeting p73 that plays a direct transcriptional regulatory role in the gene expression of GLS2. Copyright © 2017 Elsevier Ltd. All rights reserved.

An online brain-machine interface using decoding of movement direction from the human electrocorticogram

NASA Astrophysics Data System (ADS)

Milekovic, Tomislav; Fischer, Jörg; Pistohl, Tobias; Ruescher, Johanna; Schulze-Bonhage, Andreas; Aertsen, Ad; Rickert, Jörn; Ball, Tonio; Mehring, Carsten

2012-08-01

A brain-machine interface (BMI) can be used to control movements of an artificial effector, e.g. movements of an arm prosthesis, by motor cortical signals that control the equivalent movements of the corresponding body part, e.g. arm movements. This approach has been successfully applied in monkeys and humans by accurately extracting parameters of movements from the spiking activity of multiple single neurons. We show that the same approach can be realized using brain activity measured directly from the surface of the human cortex using electrocorticography (ECoG). Five subjects, implanted with ECoG implants for the purpose of epilepsy assessment, took part in our study. Subjects used directionally dependent ECoG signals, recorded during active movements of a single arm, to control a computer cursor in one out of two directions. Significant BMI control was achieved in four out of five subjects with correct directional decoding in 69%-86% of the trials (75% on average). Our results demonstrate the feasibility of an online BMI using decoding of movement direction from human ECoG signals. Thus, to achieve such BMIs, ECoG signals might be used in conjunction with or as an alternative to intracortical neural signals.

The Current Status of Somatostatin-Interneurons in Inhibitory Control of Brain Function and Plasticity

PubMed Central

2016-01-01

The mammalian neocortex contains many distinct inhibitory neuronal populations to balance excitatory neurotransmission. A correct excitation/inhibition equilibrium is crucial for normal brain development, functioning, and controlling lifelong cortical plasticity. Knowledge about how the inhibitory network contributes to brain plasticity however remains incomplete. Somatostatin- (SST-) interneurons constitute a large neocortical subpopulation of interneurons, next to parvalbumin- (PV-) and vasoactive intestinal peptide- (VIP-) interneurons. Unlike the extensively studied PV-interneurons, acknowledged as key components in guiding ocular dominance plasticity, the contribution of SST-interneurons is less understood. Nevertheless, SST-interneurons are ideally situated within cortical networks to integrate unimodal or cross-modal sensory information processing and therefore likely to be important mediators of experience-dependent plasticity. The lack of knowledge on SST-interneurons partially relates to the wide variety of distinct subpopulations present in the sensory neocortex. This review informs on those SST-subpopulations hitherto described based on anatomical, molecular, or electrophysiological characteristics and whose functional roles can be attributed based on specific cortical wiring patterns. A possible role for these subpopulations in experience-dependent plasticity will be discussed, emphasizing on learning-induced plasticity and on unimodal and cross-modal plasticity upon sensory loss. This knowledge will ultimately contribute to guide brain plasticity into well-defined directions to restore sensory function and promote lifelong learning. PMID:27403348

Large-scale cortical volume correlation networks reveal disrupted small world patterns in Parkinson's disease.

PubMed

Wu, Qiong; Gao, Yang; Liu, Ai-Shi; Xie, Li-Zhi; Qian, Long; Yang, Xiao-Guang

2018-01-01

To date, the most frequently reported neuroimaging biomarkers in Parkinson's disease (PD) are direct brain imaging measurements focusing on local disrupted regions. However, the notion that PD is related to abnormal functional and structural connectivity has received support in the past few years. Here, we employed graph theory to analyze the structural co-variance networks derived from 50 PD patients and 48 normal controls (NC). Then, the small world properties of brain networks were assessed in the structural networks that were constructed based on cortical volume data. Our results showed that both the PD and NC groups had a small world architecture in brain structural networks. However, the PD patients had a higher characteristic path length and clustering coefficients compared with the NC group. With regard to the nodal centrality, 11 regions, including 3 association cortices, 5 paralimbic cortices, and 3 subcortical regions were identified as hubs in the PD group. In contrast, 10 regions, including 7 association cortical regions, 2 paralimbic cortical regions, and the primary motor cortex region, were identified as hubs. Moreover, the regional centrality was profoundly affected in PD patients, including decreased nodal centrality in the right inferior occipital gyrus and the middle temporal gyrus and increased nodal centrality in the right amygdala, the left caudate and the superior temporal gyrus. In addition, the structural cortical network of PD showed reduced topological stability for targeted attacks. Together, this study shows that the coordinated patterns of cortical volume network are widely altered in PD patients with a decrease in the efficiency of parallel information processing. These changes provide structural evidence to support the concept that the core pathophysiology of PD is associated with disruptive alterations in the coordination of large-scale brain networks that underlie high-level cognition. Copyright © 2017. Published by Elsevier B.V.

Transcranial Direct Current Stimulation Targeting Primary Motor Versus Dorsolateral Prefrontal Cortices: Proof-of-Concept Study Investigating Functional Connectivity of Thalamocortical Networks Specific to Sensory-Affective Information Processing.

PubMed

Sankarasubramanian, Vishwanath; Cunningham, David A; Potter-Baker, Kelsey A; Beall, Erik B; Roelle, Sarah M; Varnerin, Nicole M; Machado, Andre G; Jones, Stephen E; Lowe, Mark J; Plow, Ela B

2017-04-01

The pain matrix is comprised of an extensive network of brain structures involved in sensory and/or affective information processing. The thalamus is a key structure constituting the pain matrix. The thalamus serves as a relay center receiving information from multiple ascending pathways and relating information to and from multiple cortical areas. However, it is unknown how thalamocortical networks specific to sensory-affective information processing are functionally integrated. Here, in a proof-of-concept study in healthy humans, we aimed to understand this connectivity using transcranial direct current stimulation (tDCS) targeting primary motor (M1) or dorsolateral prefrontal cortices (DLPFC). We compared changes in functional connectivity (FC) with DLPFC tDCS to changes in FC with M1 tDCS. FC changes were also compared to further investigate its relation with individual's baseline experience of pain. We hypothesized that resting-state FC would change based on tDCS location and would represent known thalamocortical networks. Ten right-handed individuals received a single application of anodal tDCS (1 mA, 20 min) to right M1 and DLPFC in a single-blind, sham-controlled crossover study. FC changes were studied between ventroposterolateral (VPL), the sensory nucleus of thalamus, and cortical areas involved in sensory information processing and between medial dorsal (MD), the affective nucleus, and cortical areas involved in affective information processing. Individual's perception of pain at baseline was assessed using cutaneous heat pain stimuli. We found that anodal M1 tDCS and anodal DLPFC tDCS both increased FC between VPL and sensorimotor cortices, although FC effects were greater with M1 tDCS. Similarly, anodal M1 tDCS and anodal DLPFC tDCS both increased FC between MD and motor cortices, but only DLPFC tDCS modulated FC between MD and affective cortices, like DLPFC. Our findings suggest that M1 stimulation primarily modulates FC of sensory networks, whereas DLPFC stimulation modulates FC of both sensory and affective networks. Our findings when replicated in a larger group of individuals could provide useful evidence that may inform future studies on pain to differentiate between effects of M1 and DLPFC stimulation. Notably, our finding that individuals with high baseline pain thresholds experience greater FC changes with DLPFC tDCS implies the role of DLPFC in pain modulation, particularly pain tolerance.

Transcranial Direct Current Stimulation Targeting Primary Motor Versus Dorsolateral Prefrontal Cortices: Proof-of-Concept Study Investigating Functional Connectivity of Thalamocortical Networks Specific to Sensory-Affective Information Processing

PubMed Central

Sankarasubramanian, Vishwanath; Cunningham, David A.; Potter-Baker, Kelsey A.; Beall, Erik B.; Roelle, Sarah M.; Varnerin, Nicole M.; Machado, Andre G.; Jones, Stephen E.; Lowe, Mark J.

2017-01-01

Abstract The pain matrix is comprised of an extensive network of brain structures involved in sensory and/or affective information processing. The thalamus is a key structure constituting the pain matrix. The thalamus serves as a relay center receiving information from multiple ascending pathways and relating information to and from multiple cortical areas. However, it is unknown how thalamocortical networks specific to sensory-affective information processing are functionally integrated. Here, in a proof-of-concept study in healthy humans, we aimed to understand this connectivity using transcranial direct current stimulation (tDCS) targeting primary motor (M1) or dorsolateral prefrontal cortices (DLPFC). We compared changes in functional connectivity (FC) with DLPFC tDCS to changes in FC with M1 tDCS. FC changes were also compared to further investigate its relation with individual's baseline experience of pain. We hypothesized that resting-state FC would change based on tDCS location and would represent known thalamocortical networks. Ten right-handed individuals received a single application of anodal tDCS (1 mA, 20 min) to right M1 and DLPFC in a single-blind, sham-controlled crossover study. FC changes were studied between ventroposterolateral (VPL), the sensory nucleus of thalamus, and cortical areas involved in sensory information processing and between medial dorsal (MD), the affective nucleus, and cortical areas involved in affective information processing. Individual's perception of pain at baseline was assessed using cutaneous heat pain stimuli. We found that anodal M1 tDCS and anodal DLPFC tDCS both increased FC between VPL and sensorimotor cortices, although FC effects were greater with M1 tDCS. Similarly, anodal M1 tDCS and anodal DLPFC tDCS both increased FC between MD and motor cortices, but only DLPFC tDCS modulated FC between MD and affective cortices, like DLPFC. Our findings suggest that M1 stimulation primarily modulates FC of sensory networks, whereas DLPFC stimulation modulates FC of both sensory and affective networks. Our findings when replicated in a larger group of individuals could provide useful evidence that may inform future studies on pain to differentiate between effects of M1 and DLPFC stimulation. Notably, our finding that individuals with high baseline pain thresholds experience greater FC changes with DLPFC tDCS implies the role of DLPFC in pain modulation, particularly pain tolerance. PMID:28142257

Transforming growth factor-beta production in anti-glomerular basement membrane disease in the rabbit.

PubMed Central

Coimbra, T.; Wiggins, R.; Noh, J. W.; Merritt, S.; Phan, S. H.

1991-01-01

The purpose of this study was to assay for the presence of collagen synthesis stimulatory activity in the kidney during immune-induced renal injury that results in severe fibrosis in both glomerular and interstitial compartments. A model of antiglomerular basement (anti-GBM) disease in the rabbit was induced on day 0 by the injection of anti-GBM antibody and renal cortex tissues were then sampled at various time points. Only conditioned media prepared from diseased renal cortical samples showed collagen synthesis stimulatory activity when tested on rabbit mesangial cells. The activity had an estimated molecular weight range of 16 to 25 kd and was neutralized by antibody to transforming growth factor-beta (TGF-beta). A standard assay for TGF-beta using a mink lung epithelial cell line confirmed the increase in TGF-beta activity in conditioned media of diseased cortex from day 7 and day 14 animals, which was not significantly activated by previous acidification. This suggests that most of the TGF-beta present in renal conditioned media was in the active form. The increase in renal cortical secretion of active TGF-beta was accompanied by increases in renal cortical TGF-beta mRNA content on days 4 and 7 after induction, with subsequent return to control levels. A similar increase in TGF-beta activity was present in nonacidified conditioned media of purified glomeruli from diseased days 7 and 14 animals, which was also accompanied by significant increases in TGF-beta mRNA. However with acidification no significant differences were noted between control and diseased samples, suggesting the presence of substantial latent TGF-beta activity in control glomerular conditioned media. These same control-conditioned media contained inhibitor activity for added exogenous TGF-beta. These results support the conclusion that the association between increased TGF-beta secretion and increased renal cortical collagen synthesis in this model is consistent with a role for this cytokine in directing fibrogenesis in the kidney. Images Figure 6 PMID:1987768

On the asynchronously continuous control of mobile robot movement by motor cortical spiking activity.

PubMed

Xu, Zhiming; So, Rosa Q; Toe, Kyaw Kyar; Ang, Kai Keng; Guan, Cuntai

2014-01-01

This paper presents an asynchronously intracortical brain-computer interface (BCI) which allows the subject to continuously drive a mobile robot. This system has a great implication for disabled patients to move around. By carefully designing a multiclass support vector machine (SVM), the subject's self-paced instantaneous movement intents are continuously decoded to control the mobile robot. In particular, we studied the stability of the neural representation of the movement directions. Experimental results on the nonhuman primate showed that the overt movement directions were stably represented in ensemble of recorded units, and our SVM classifier could successfully decode such movements continuously along the desired movement path. However, the neural representation of the stop state for the self-paced control was not stably represented and could drift.

Plasma-sprayed titanium coating to polyetheretherketone improves the bone-implant interface.

PubMed

Walsh, William R; Bertollo, Nicky; Christou, Chrisopher; Schaffner, Dominik; Mobbs, Ralph J

2015-05-01

Rapid and stable fixation at the bone-implant interface would be regarded as one of the primary goals to achieve clinical efficacy, regardless of the surgical site. Although mechanical and physical properties of polyetheretherketone (PEEK) provide advantages for implant devices, the hydrophobic nature and the lack of direct bone contact remains a limitation. To examine the effects of a plasma-sprayed titanium coated PEEK on the mechanical and histologic properties at the bone-implant interface. A preclinical laboratory study. Polyetheretherketone and plasma-sprayed titanium coated PEEK implants (Ti-bond; Spinal Elements, Carlsbad, CA, USA) were placed in a line-to-line manner in cortical bone and in a press-fit manner in cancellous bone of adult sheep using an established ovine model. Shear strength was assessed in the cortical sites at 4 and 12 weeks, whereas histology was performed in cortical and cancellous sites at both time points. The titanium coating dramatically improved the shear strength at the bone-implant interface at 4 weeks and continued to improve with time compared with PEEK. Direct bone ongrowth in cancellous and cortical sites can be achieved using a plasma-sprayed titanium coating on PEEK. Direct bone to implant bonding can be achieved on PEEK in spite of its hydrophobic nature using a plasma-sprayed titanium coating. The plasma-sprayed titanium coating improved mechanical properties in the cortical sites and the histology in cortical and cancellous sites. Copyright © 2015 Elsevier Inc. All rights reserved.

Preconditioning of Spatial and Auditory Cues: Roles of the Hippocampus, Frontal Cortex, and Cue-Directed Attention

PubMed Central

Talk, Andrew C.; Grasby, Katrina L.; Rawson, Tim; Ebejer, Jane L.

2016-01-01

Loss of function of the hippocampus or frontal cortex is associated with reduced performance on memory tasks, in which subjects are incidentally exposed to cues at specific places in the environment and are subsequently asked to recollect the location at which the cue was experienced. Here, we examined the roles of the rodent hippocampus and frontal cortex in cue-directed attention during encoding of memory for the location of a single incidentally experienced cue. During a spatial sensory preconditioning task, rats explored an elevated platform while an auditory cue was incidentally presented at one corner. The opposite corner acted as an unpaired control location. The rats demonstrated recollection of location by avoiding the paired corner after the auditory cue was in turn paired with shock. Damage to either the dorsal hippocampus or the frontal cortex impaired this memory ability. However, we also found that hippocampal lesions enhanced attention directed towards the cue during the encoding phase, while frontal cortical lesions reduced cue-directed attention. These results suggest that the deficit in spatial sensory preconditioning caused by frontal cortical damage may be mediated by inattention to the location of cues during the latent encoding phase, while deficits following hippocampal damage must be related to other mechanisms such as generation of neural plasticity. PMID:27999366

Intrinsic Connections of the Core Auditory Cortical Regions and Rostral Supratemporal Plane in the Macaque Monkey

PubMed Central

Scott, Brian H.; Leccese, Paul A.; Saleem, Kadharbatcha S.; Kikuchi, Yukiko; Mullarkey, Matthew P.; Fukushima, Makoto; Mishkin, Mortimer; Saunders, Richard C.

2017-01-01

Abstract In the ventral stream of the primate auditory cortex, cortico-cortical projections emanate from the primary auditory cortex (AI) along 2 principal axes: one mediolateral, the other caudorostral. Connections in the mediolateral direction from core, to belt, to parabelt, have been well described, but less is known about the flow of information along the supratemporal plane (STP) in the caudorostral dimension. Neuroanatomical tracers were injected throughout the caudorostral extent of the auditory core and rostral STP by direct visualization of the cortical surface. Auditory cortical areas were distinguished by SMI-32 immunostaining for neurofilament, in addition to established cytoarchitectonic criteria. The results describe a pathway comprising step-wise projections from AI through the rostral and rostrotemporal fields of the core (R and RT), continuing to the recently identified rostrotemporal polar field (RTp) and the dorsal temporal pole. Each area was strongly and reciprocally connected with the areas immediately caudal and rostral to it, though deviations from strictly serial connectivity were observed. In RTp, inputs converged from core, belt, parabelt, and the auditory thalamus, as well as higher order cortical regions. The results support a rostrally directed flow of auditory information with complex and recurrent connections, similar to the ventral stream of macaque visual cortex. PMID:26620266

Skeletal muscle contractions uncoupled from gravitational loading directly increase cortical bone blood flow rates in vivo.

PubMed

Caulkins, Carrie; Ebramzadeh, Edward; Winet, Howard

2009-05-01

The direct and indirect effects of muscle contraction on bone microcirculation and fluid flow are neither well documented nor explained. However, skeletal muscle contractions may affect the acquisition and maintenance of bone via stimulation of bone circulatory and interstitial fluid flow parameters. The purposes of this study were to assess the effects of transcutaneous electrical neuromuscular stimulation (TENS)-induced muscle contractions on cortical bone blood flow and bone mineral content, and to demonstrate that alterations in blood flow could occur independently of mechanical loading and systemic circulatory mechanisms. Bone chamber implants were used in a rabbit model to observe real-time blood flow rates and TENS-induced muscle contractions. Video recording of fluorescent microspheres injected into the blood circulation was used to calculate changes in cortical blood flow rates. TENS-induced repetitive muscle contractions uncoupled from mechanical loading instantaneously increased cortical microcirculatory flow, directly increased bone blood flow rates by 130%, and significantly increased bone mineral content over 7 weeks. Heart rates and blood pressure did not significantly increase due to TENS treatment. Our findings suggest that muscle contraction therapies have potential clinical applications for improving blood flow to cortical bone in the appendicular skeleton. Copyright 2008 Orthopaedic Research Society

Localized Cortical Thinning in Patients with Obstructive Sleep Apnea Syndrome

PubMed Central

Joo, Eun Yeon; Jeon, Seun; Kim, Sung Tae; Lee, Jong-Min; Hong, Seung Bong

2013-01-01

Study Objectives: To investigate differences in cortical thickness in patients with obstructive sleep apnea (OSA) syndrome and healthy controls. Design: Cortical thickness was measured using a three-dimensional surface-based method that enabled more accurate measurement in deep sulci and localized regional mapping. Setting: University hospital. Patients: Thirty-eight male patients with severe OSA (mean apnea-hypopnea index > 30/h) and 36 age-matched male healthy controls were enrolled. Interventions: Cortical thickness was obtained at 81,924 vertices across the entire brain by reconstructing inner and outer cortical surfaces using an automated anatomical pipeline. Measurements: Group difference in cortical thickness and correlation between patients' data and thickness were analyzed by a general linear model. Results: Localized cortical thinning in patients was found in the orbitorectal gyri, dorsolateral/ventromedial prefrontal regions, pericentral gyri, anterior cingulate, insula, inferior parietal lobule, uncus, and basolateral temporal regions at corrected P < 0.05. Patients with OSA showed impaired attention and learning difficulty in memory tests compared to healthy controls. Higher number of respiratory arousals was related to cortical thinning of the anterior cingulate and inferior parietal lobule. A significant correlation was observed between the longer apnea maximum duration and the cortical thinning of the dorsolateral prefrontal regions, pericentral gyri, and insula. Retention scores in visual memory tests were associated with cortical thickness of parahippocampal gyrus and uncus. Conclusions: Brain regions with cortical thinning may provide elucidations for prefrontal cognitive dysfunction, upper airway sensorimotor dysregulation, and cardiovascular disturbances in OSA patients, that experience sleep disruption including sleep fragmentation and oxygen desaturation. Citation: Joo EY; Jeon S; Kim ST; Lee JM; Hong SB. Localized cortical thinning in patients with obstructive sleep apnea syndrome. SLEEP 2013;36(8):1153-1162. PMID:23904675

Use of functional near-infrared spectroscopy to monitor cortical plasticity induced by transcranial direct current stimulation

NASA Astrophysics Data System (ADS)

Khan, Bilal; Hervey, Nathan; Stowe, Ann; Hodics, Timea; Alexandrakis, George

2013-03-01

Electrical stimulation of the human cortex in conjunction with physical rehabilitation has been a valuable approach in facilitating the plasticity of the injured brain. One such method is transcranial direct current stimulation (tDCS) which is a non-invasive method to elicit neural stimulation by delivering current through electrodes placed on the scalp. In order to better understand the effects tDCS has on cortical plasticity, neuroimaging techniques have been used pre and post tDCS stimulation. Recently, neuroimaging methods have discovered changes in resting state cortical hemodynamics after the application of tDCS on human subjects. However, analysis of the cortical hemodynamic activity for a physical task during and post tDCS stimulation has not been studied to our knowledge. A viable and sensitive neuroimaging method to map changes in cortical hemodynamics during activation is functional near-infrared spectroscopy (fNIRS). In this study, the cortical activity during an event-related, left wrist curl task was mapped with fNIRS before, during, and after tDCS stimulation on eight healthy adults. Along with the fNIRS optodes, two electrodes were placed over the sensorimotor hand areas of both brain hemispheres to apply tDCS. Changes were found in both resting state cortical connectivity and cortical activation patterns that occurred during and after tDCS. Additionally, changes to surface electromyography (sEMG) measurements of the wrist flexor and extensor of both arms during the wrist curl movement, acquired concurrently with fNIRS, were analyzed and related to the transient cortical plastic changes induced by tDCS.

Mapping 22q11.2 Gene Dosage Effects on Brain Morphometry.

PubMed

Lin, Amy; Ching, Christopher R K; Vajdi, Ariana; Sun, Daqiang; Jonas, Rachel K; Jalbrzikowski, Maria; Kushan-Wells, Leila; Pacheco Hansen, Laura; Krikorian, Emma; Gutman, Boris; Dokoru, Deepika; Helleman, Gerhard; Thompson, Paul M; Bearden, Carrie E

2017-06-28

Reciprocal chromosomal rearrangements at the 22q11.2 locus are associated with elevated risk of neurodevelopmental disorders. The 22q11.2 deletion confers the highest known genetic risk for schizophrenia, but a duplication in the same region is strongly associated with autism and is less common in schizophrenia cases than in the general population. Here we conducted the first study of 22q11.2 gene dosage effects on brain structure in a sample of 143 human subjects: 66 with 22q11.2 deletions (22q-del; 32 males), 21 with 22q11.2 duplications (22q-dup; 14 males), and 56 age- and sex-matched controls (31 males). 22q11.2 gene dosage varied positively with intracranial volume, gray and white matter volume, and cortical surface area (deletion < control < duplication). In contrast, gene dosage varied negatively with mean cortical thickness (deletion > control > duplication). Widespread differences were observed for cortical surface area with more localized effects on cortical thickness. These diametric patterns extended into subcortical regions: 22q-dup carriers had a significantly larger right hippocampus, on average, but lower right caudate and corpus callosum volume, relative to 22q-del carriers. Novel subcortical shape analysis revealed greater radial distance (thickness) of the right amygdala and left thalamus, and localized increases and decreases in subregions of the caudate, putamen, and hippocampus in 22q-dup relative to 22q-del carriers. This study provides the first evidence that 22q11.2 is a genomic region associated with gene-dose-dependent brain phenotypes. Pervasive effects on cortical surface area imply that this copy number variant affects brain structure early in the course of development. SIGNIFICANCE STATEMENT Probing naturally occurring reciprocal copy number variation in the genome may help us understand mechanisms underlying deviations from typical brain and cognitive development. The 22q11.2 genomic region is particularly susceptible to chromosomal rearrangements and contains many genes crucial for neuronal development and migration. Not surprisingly, reciprocal genomic imbalances at this locus confer some of the highest known genetic risks for developmental neuropsychiatric disorders. Here we provide the first evidence that brain morphology differs meaningfully as a function of reciprocal genomic variation at the 22q11.2 locus. Cortical thickness and surface area were affected in opposite directions with more widespread effects of gene dosage on cortical surface area. Copyright © 2017 the authors 0270-6474/17/376184-17$15.00/0.

Synergistic effect of combined transcranial direct current stimulation/constraint-induced movement therapy in children and young adults with hemiparesis: study protocol.

PubMed

Gillick, Bernadette; Menk, Jeremiah; Mueller, Bryon; Meekins, Gregg; Krach, Linda E; Feyma, Timothy; Rudser, Kyle

2015-11-12

Perinatal stroke occurs in more than 1 in 2,500 live births and resultant congenital hemiparesis necessitates investigation into interventions which may improve long-term function and decreased burden of care beyond current therapies ( http://www.cdc.gov/ncbddd/cp/data.html ). Constraint-Induced Movement Therapy (CIMT) is recognized as an effective hemiparesis rehabilitation intervention. Transcranial direct current stimulation as an adjunct treatment to CIMT may potentiate neuroplastic responses and improve motor function. The methodology of a clinical trial in children designed as a placebo-controlled, serial -session, non-invasive brain stimulation trial incorporating CIMT is described here. The primary hypotheses are 1) that no serious adverse events will occur in children receiving non-invasive brain stimulation and 2) that children in the stimulation intervention group will show significant improvements in hand motor function compared to children in the placebo stimulation control group. A randomized, controlled, double-blinded clinical trial. Twenty children and/or young adults (ages 8-21) with congenital hemiparesis, will be enrolled. The intervention group will receive ten 2-hour sessions of transcranial direct current stimulation combined with constraint-induced movement therapy and the control group will receive sham stimulation with CIMT. The primary outcome measure is safety assessment of transcranial direct current stimulation by physician evaluation, vital sign monitoring and symptom reports. Additionally, hand function will be evaluated using the Assisting Hand Assessment, grip strength and assessment of goals using the Canadian Occupational Performance Measure. Neuroimaging will confirm diagnoses, corticospinal tract integrity and cortical activation. Motor cortical excitability will also be examined using transcranial magnetic stimulation techniques. Combining non-invasive brain stimulation and CIMT interventions has the potential to improve motor function in children with congenital hemiparesis beyond each intervention independently. Such a combined intervention has the potential to benefit an individual throughout their lifetime. Clinicaltrials.gov, NCT02250092 Registered 18 September 2014.

Coordinated roles of motivation and perception in the regulation of intergroup responses: frontal cortical asymmetry effects on the P2 event-related potential and behavior.

PubMed

Amodio, David M

2010-11-01

Self-regulation is believed to involve changes in motivation and perception that function to promote goal-driven behavior. However, little is known about the way these processes interact during the on-line engagement of self-regulation. The present study examined the coordination of motivation, perception, and action control in White American participants as they regulated responses on a racial stereotyping task. Electroencephalographic indices of approach motivation (left frontal cortical asymmetry) and perceptual attention to Black versus White faces (the P2 event-related potential) were assessed during task performance. Action control was modeled from task behavior using the process-dissociation procedure. A pattern of moderated mediation emerged, such that stronger left frontal activity predicted larger P2 responses to race, which in turn predicted better action control, especially for participants holding positive racial attitudes. Results supported the hypothesis that motivation tunes perception to facilitate goal-directed action. Implications for theoretical models of intergroup response regulation, the P2 component, and the relation between motivation and perception are discussed.

Signal transfer within a cultured asymmetric cortical neuron circuit

NASA Astrophysics Data System (ADS)

Isomura, Takuya; Shimba, Kenta; Takayama, Yuzo; Takeuchi, Akimasa; Kotani, Kiyoshi; Jimbo, Yasuhiko

2015-12-01

Objective. Simplified neuronal circuits are required for investigating information representation in nervous systems and for validating theoretical neural network models. Here, we developed patterned neuronal circuits using micro fabricated devices, comprising a micro-well array bonded to a microelectrode-array substrate. Approach. The micro-well array consisted of micrometre-scale wells connected by tunnels, all contained within a silicone slab called a micro-chamber. The design of the micro-chamber confined somata to the wells and allowed axons to grow through the tunnels bidirectionally but with a designed, unidirectional bias. We guided axons into the point of the arrow structure where one of the two tunnel entrances is located, making that the preferred direction. Main results. When rat cortical neurons were cultured in the wells, their axons grew through the tunnels and connected to neurons in adjoining wells. Unidirectional burst transfers and other asymmetric signal-propagation phenomena were observed via the substrate-embedded electrodes. Seventy-nine percent of burst transfers were in the forward direction. We also observed rapid propagation of activity from sites of local electrical stimulation, and significant effects of inhibitory synapse blockade on bursting activity. Significance. These results suggest that this simple, substrate-controlled neuronal circuit can be applied to develop in vitro models of the function of cortical microcircuits or deep neural networks, better to elucidate the laws governing the dynamics of neuronal networks.

Signal transfer within a cultured asymmetric cortical neuron circuit.

PubMed

Isomura, Takuya; Shimba, Kenta; Takayama, Yuzo; Takeuchi, Akimasa; Kotani, Kiyoshi; Jimbo, Yasuhiko

2015-12-01

Simplified neuronal circuits are required for investigating information representation in nervous systems and for validating theoretical neural network models. Here, we developed patterned neuronal circuits using micro fabricated devices, comprising a micro-well array bonded to a microelectrode-array substrate. The micro-well array consisted of micrometre-scale wells connected by tunnels, all contained within a silicone slab called a micro-chamber. The design of the micro-chamber confined somata to the wells and allowed axons to grow through the tunnels bidirectionally but with a designed, unidirectional bias. We guided axons into the point of the arrow structure where one of the two tunnel entrances is located, making that the preferred direction. When rat cortical neurons were cultured in the wells, their axons grew through the tunnels and connected to neurons in adjoining wells. Unidirectional burst transfers and other asymmetric signal-propagation phenomena were observed via the substrate-embedded electrodes. Seventy-nine percent of burst transfers were in the forward direction. We also observed rapid propagation of activity from sites of local electrical stimulation, and significant effects of inhibitory synapse blockade on bursting activity. These results suggest that this simple, substrate-controlled neuronal circuit can be applied to develop in vitro models of the function of cortical microcircuits or deep neural networks, better to elucidate the laws governing the dynamics of neuronal networks.

Partially non-linear stimulation intensity-dependent effects of direct current stimulation on motor cortex excitability in humans.

PubMed

Batsikadze, G; Moliadze, V; Paulus, W; Kuo, M-F; Nitsche, M A

2013-04-01

Transcranial direct current stimulation (tDCS) of the human motor cortex at an intensity of 1 mA with an electrode size of 35 cm(2) has been shown to induce shifts of cortical excitability during and after stimulation. These shifts are polarity-specific with cathodal tDCS resulting in a decrease and anodal stimulation in an increase of cortical excitability. In clinical and cognitive studies, stronger stimulation intensities are used frequently, but their physiological effects on cortical excitability have not yet been explored. Therefore, here we aimed to explore the effects of 2 mA tDCS on cortical excitability. We applied 2 mA anodal or cathodal tDCS for 20 min on the left primary motor cortex of 14 healthy subjects. Cathodal tDCS at 1 mA and sham tDCS for 20 min was administered as control session in nine and eight healthy subjects, respectively. Motor cortical excitability was monitored by transcranial magnetic stimulation (TMS)-elicited motor-evoked potentials (MEPs) from the right first dorsal interosseous muscle. Global corticospinal excitability was explored via single TMS pulse-elicited MEP amplitudes, and motor thresholds. Intracortical effects of stimulation were obtained by cortical silent period (CSP), short latency intracortical inhibition (SICI) and facilitation (ICF), and I wave facilitation. The above-mentioned protocols were recorded both before and immediately after tDCS in randomized order. Additionally, single-pulse MEPs, motor thresholds, SICI and ICF were recorded every 30 min up to 2 h after stimulation end, evening of the same day, next morning, next noon and next evening. Anodal as well as cathodal tDCS at 2 mA resulted in a significant increase of MEP amplitudes, whereas 1 mA cathodal tDCS decreased corticospinal excitability. A significant shift of SICI and ICF towards excitability enhancement after both 2 mA cathodal and anodal tDCS was observed. At 1 mA, cathodal tDCS reduced single-pulse TMS-elicited MEP amplitudes and shifted SICI and ICF towards inhibition. No significant changes were observed in the other protocols. Sham tDCS did not induce significant MEP alterations. These results suggest that an enhancement of tDCS intensity does not necessarily increase efficacy of stimulation, but might also shift the direction of excitability alterations. This should be taken into account for applications of the stimulation technique using different intensities and durations in order to achieve stronger or longer lasting after-effects.

Alterations in cortical and extrastriatal subcortical dopamine function in schizophrenia: systematic review and meta-analysis of imaging studies.

PubMed

Kambeitz, Joseph; Abi-Dargham, Anissa; Kapur, Shitij; Howes, Oliver D

2014-06-01

The hypothesis that cortical dopaminergic alterations underlie aspects of schizophrenia has been highly influential. To bring together and evaluate the imaging evidence for dopaminergic alterations in cortical and other extrastriatal regions in schizophrenia. Electronic databases were searched for in vivo molecular studies of extrastriatal dopaminergic function in schizophrenia. Twenty-three studies (278 patients and 265 controls) were identified. Clinicodemographic and imaging variables were extracted and effect sizes determined for the dopaminergic measures. There were sufficient data to permit meta-analyses for the temporal cortex, thalamus and substantia nigra but not for other regions. The meta-analysis of dopamine D2/D3 receptor availability found summary effect sizes of d = -0.32 (95% CI -0.68 to 0.03) for the thalamus, d = -0.23 (95% CI -0.54 to 0.07) for the temporal cortex and d = 0.04 (95% CI -0.92 to 0.99) for the substantia nigra. Confidence intervals were wide and all included no difference between groups. Evidence for other measures/regions is limited because of the small number of studies and in some instances inconsistent findings, although significant differences were reported for D2/D3 receptors in the cingulate and uncus, for D1 receptors in the prefrontal cortex and for dopamine transporter availability in the thalamus. There is a relative paucity of direct evidence for cortical dopaminergic alterations in schizophrenia, and findings are inconclusive. This is surprising given the wide influence of the hypothesis. Large, well-controlled studies in drug-naive patients are warranted to definitively test this hypothesis. Royal College of Psychiatrists.

Visual discrimination training improves Humphrey perimetry in chronic cortically induced blindness.

PubMed

Cavanaugh, Matthew R; Huxlin, Krystel R

2017-05-09

To assess if visual discrimination training improves performance on visual perimetry tests in chronic stroke patients with visual cortex involvement. 24-2 and 10-2 Humphrey visual fields were analyzed for 17 chronic cortically blind stroke patients prior to and following visual discrimination training, as well as in 5 untrained, cortically blind controls. Trained patients practiced direction discrimination, orientation discrimination, or both, at nonoverlapping, blind field locations. All pretraining and posttraining discrimination performance and Humphrey fields were collected with online eye tracking, ensuring gaze-contingent stimulus presentation. Trained patients recovered ∼108 degrees 2 of vision on average, while untrained patients spontaneously improved over an area of ∼16 degrees 2 . Improvement was not affected by patient age, time since lesion, size of initial deficit, or training type, but was proportional to the amount of training performed. Untrained patients counterbalanced their improvements with worsening of sensitivity over ∼9 degrees 2 of their visual field. Worsening was minimal in trained patients. Finally, although discrimination performance improved at all trained locations, changes in Humphrey sensitivity occurred both within trained regions and beyond, extending over a larger area along the blind field border. In adults with chronic cortical visual impairment, the blind field border appears to have enhanced plastic potential, which can be recruited by gaze-controlled visual discrimination training to expand the visible field. Our findings underscore a critical need for future studies to measure the effects of vision restoration approaches on perimetry in larger cohorts of patients. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Impairment in Emotional Modulation of Attention and Memory in Schizophrenia

PubMed Central

Walsh-Messinger, Julie; Ramirez, Paul Michael; Wong, Philip; Antonius, Daniel; Aujero, Nicole; McMahon, Kevin; Opler, Lewis A.; Malaspina, Dolores

2014-01-01

Emotion plays a critical role in cognition and goal-directed behavior via complex interconnections between the emotional and motivational systems. It has been hypothesized that the impairment in goal-directed behavior widely noted in schizophrenia may result from defects in the interaction between the neural (ventral) emotional system and (rostral) cortical processes. The present study examined the impact of emotion on attention and memory in schizophrenia. Twenty-five individuals with schizophrenia related psychosis and 25 healthy control subjects were administered a computerized task in which they were asked to search for target images during a rapid serial visual presentation of pictures. Target stimuli were either positive, negative, or neutral images presented at either 200ms or 700ms lag. Additionally, a visual hedonics task was used to assess differences between the schizophrenia group and controls on ratings of valence and arousal from the picture stimuli. Compared to controls, individuals with schizophrenia detected fewer emotional images under both the 200ms and 700ms lag conditions. Multivariate analyses showed that the schizophrenia group also detected fewer positive images under the 700 lag condition and fewer negative images under the 200 lag condition. Individuals with schizophrenia reported higher pleasantness and unpleasantness ratings than controls in response to neutral stimuli, while controls reported higher arousal ratings for neutral and positive stimuli compared to the schizophrenia group. These results highlight dysfunction in the neural modulation of emotion, attention, and cortical processing in schizophrenia, adding to the growing but mixed body of literature on emotion processing in the disorder. PMID:24910446

Impairment in emotional modulation of attention and memory in schizophrenia.

PubMed

Walsh-Messinger, Julie; Ramirez, Paul Michael; Wong, Philip; Antonius, Daniel; Aujero, Nicole; McMahon, Kevin; Opler, Lewis A; Malaspina, Dolores

2014-08-01

Emotion plays a critical role in cognition and goal-directed behavior via complex interconnections between the emotional and motivational systems. It has been hypothesized that the impairment in goal-directed behavior widely noted in schizophrenia may result from defects in the interaction between the neural (ventral) emotional system and (rostral) cortical processes. The present study examined the impact of emotion on attention and memory in schizophrenia. Twenty-five individuals with schizophrenia related psychosis and 25 healthy control subjects were administered a computerized task in which they were asked to search for target images during a Rapid Serial Visual Presentation of pictures. Target stimuli were either positive or negative, or neutral images presented at either 200ms or 700ms lag. Additionally, a visual hedonic task was used to assess differences between the schizophrenia group and controls on ratings of valence and arousal from the picture stimuli. Compared to controls, individuals with schizophrenia detected fewer emotional images under both the 200ms and 700ms lag conditions. Multivariate analyses showed that the schizophrenia group also detected fewer positive images under the 700ms lag condition and fewer negative images under the 200ms lag condition. Individuals with schizophrenia reported higher pleasantness and unpleasantness ratings than controls in response to neutral stimuli, while controls reported higher arousal ratings for neutral and positive stimuli compared to the schizophrenia group. These results highlight dysfunction in the neural modulation of emotion, attention, and cortical processing in schizophrenia, adding to the growing but mixed body of literature on emotion processing in the disorder. Published by Elsevier B.V.

Reduced cortical complexity in children with Prader-Willi Syndrome and its association with cognitive impairment and developmental delay.

PubMed

Lukoshe, Akvile; Hokken-Koelega, Anita C; van der Lugt, Aad; White, Tonya

2014-01-01

Prader-Willi Syndrome (PWS) is a complex neurogenetic disorder with symptoms involving not only hypothalamic, but also a global, central nervous system dysfunction. Previously, qualitative studies reported polymicrogyria in adults with PWS. However, there have been no quantitative neuroimaging studies of cortical morphology in PWS and no studies to date in children with PWS. Thus, our aim was to investigate and quantify cortical complexity in children with PWS compared to healthy controls. In addition, we investigated differences between genetic subtypes of PWS and the relationship between cortical complexity and intelligence within the PWS group. High-resolution structural magnetic resonance images were acquired in 24 children with genetically confirmed PWS (12 carrying a deletion (DEL), 12 with maternal uniparental disomy (mUPD)) and 11 age- and sex-matched typically developing siblings as healthy controls. Local gyrification index (lGI) was obtained using the FreeSurfer software suite. Four large clusters, two in each hemisphere, comprising frontal, parietal and temporal lobes, had lower lGI in children with PWS, compared to healthy controls. Clusters with lower lGI also had significantly lower cortical surface area in children with PWS. No differences in cortical thickness of the clusters were found between the PWS and healthy controls. lGI correlated significantly with cortical surface area, but not with cortical thickness. Within the PWS group, lGI in both hemispheres correlated with Total IQ and Verbal IQ, but not with Performance IQ. Children with mUPD, compared to children with DEL, had two small clusters with lower lGI in the right hemisphere. lGI of these clusters correlated with cortical surface area, but not with cortical thickness or IQ. These results suggest that lower cortical complexity in children with PWS partially underlies cognitive impairment and developmental delay, probably due to alterations in gene networks that play a prominent role in early brain development.

Reduced Cortical Complexity in Children with Prader-Willi Syndrome and Its Association with Cognitive Impairment and Developmental Delay

PubMed Central

Lukoshe, Akvile; Hokken-Koelega, Anita C.; van der Lugt, Aad; White, Tonya

2014-01-01

Background Prader-Willi Syndrome (PWS) is a complex neurogenetic disorder with symptoms involving not only hypothalamic, but also a global, central nervous system dysfunction. Previously, qualitative studies reported polymicrogyria in adults with PWS. However, there have been no quantitative neuroimaging studies of cortical morphology in PWS and no studies to date in children with PWS. Thus, our aim was to investigate and quantify cortical complexity in children with PWS compared to healthy controls. In addition, we investigated differences between genetic subtypes of PWS and the relationship between cortical complexity and intelligence within the PWS group. Methods High-resolution structural magnetic resonance images were acquired in 24 children with genetically confirmed PWS (12 carrying a deletion (DEL), 12 with maternal uniparental disomy (mUPD)) and 11 age- and sex-matched typically developing siblings as healthy controls. Local gyrification index (lGI) was obtained using the FreeSurfer software suite. Results Four large clusters, two in each hemisphere, comprising frontal, parietal and temporal lobes, had lower lGI in children with PWS, compared to healthy controls. Clusters with lower lGI also had significantly lower cortical surface area in children with PWS. No differences in cortical thickness of the clusters were found between the PWS and healthy controls. lGI correlated significantly with cortical surface area, but not with cortical thickness. Within the PWS group, lGI in both hemispheres correlated with Total IQ and Verbal IQ, but not with Performance IQ. Children with mUPD, compared to children with DEL, had two small clusters with lower lGI in the right hemisphere. lGI of these clusters correlated with cortical surface area, but not with cortical thickness or IQ. Conclusions These results suggest that lower cortical complexity in children with PWS partially underlies cognitive impairment and developmental delay, probably due to alterations in gene networks that play a prominent role in early brain development. PMID:25226172

FERMT2 links cortical actin structures, plasma membrane tension and focal adhesion function to stabilize podocyte morphology.

PubMed

Yasuda-Yamahara, M; Rogg, M; Frimmel, J; Trachte, P; Helmstaedter, M; Schroder, P; Schiffer, M; Schell, C; Huber, T B

2018-01-11

Simplification and retraction of podocyte protrusions, generally termed as foot process effacement, is a uniform pathological pattern observed in the majority of glomerular disease, including focal segmental glomerulosclerosis. However, it is still incompletely understood how the interaction of cortical actin structures, actomyosin contractility and focal adhesions, is being orchestrated to control foot process morphology in health and disease. By uncovering the functional role of fermitin family member 2 (FERMT2 or kindlin-2) in podocytes, we provide now evidence, how cell-extracellular matrix (ECM) interactions modulate membrane tension and actomyosin contractility. A genetic modeling approach was applied by deleting FERMT2 in a set of in vivo systems as well as in CRISPR/Cas9 modified human podocytes. Loss of FERMT2 results in altered cortical actin composition, cell cortex destabilization associated with plasma membrane blebbing and a remodeling of focal adhesions. We further show that FERMT2 knockout podocytes have high levels of RhoA activation and concomitantly increased actomyosin contractility. Inhibition of actomyosin tension reverses the membrane blebbing phenotype. Thus, our findings establish a direct link between cell-matrix adhesions, cortical actin structures and plasma membrane tension allowing to better explain cell morphological changes in foot process effacement. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Real-time prediction of hand trajectory by ensembles of cortical neurons in primates

NASA Astrophysics Data System (ADS)

Wessberg, Johan; Stambaugh, Christopher R.; Kralik, Jerald D.; Beck, Pamela D.; Laubach, Mark; Chapin, John K.; Kim, Jung; Biggs, S. James; Srinivasan, Mandayam A.; Nicolelis, Miguel A. L.

2000-11-01

Signals derived from the rat motor cortex can be used for controlling one-dimensional movements of a robot arm. It remains unknown, however, whether real-time processing of cortical signals can be employed to reproduce, in a robotic device, the kind of complex arm movements used by primates to reach objects in space. Here we recorded the simultaneous activity of large populations of neurons, distributed in the premotor, primary motor and posterior parietal cortical areas, as non-human primates performed two distinct motor tasks. Accurate real-time predictions of one- and three-dimensional arm movement trajectories were obtained by applying both linear and nonlinear algorithms to cortical neuronal ensemble activity recorded from each animal. In addition, cortically derived signals were successfully used for real-time control of robotic devices, both locally and through the Internet. These results suggest that long-term control of complex prosthetic robot arm movements can be achieved by simple real-time transformations of neuronal population signals derived from multiple cortical areas in primates.

Reproducibility of Direct Quantitative Measures of Cortical Bone Micro-architecture of the Distal Radius and Tibia by HR-pQCT

PubMed Central

Burghardt, Andrew J.; Buie, Helen R.; Laib, Andres; Majumdar, Sharmila; Boyd, Steven K.

2010-01-01

Quantitative cortical micro-architectural endpoints are important for understanding structure-function relations in the context of fracture risk and therapeutic efficacy. This technique study details new image-processing methods to automatically segment and directly quantify cortical density, geometry, and micro-architecture from HR-pQCT images of the distal radius and tibia. An automated segmentation technique was developed to identify the periosteal and endosteal margins of the distal radius and tibia, and detect intra-cortical pore space morphologically consistent with Haversian canals. The reproducibility of direct quantitative cortical bone indices based on this method was assessed in a pooled dataset of 56 subjects with two repeat acquisitions for each site. The in vivo precision error was characterized using root mean square coefficient of variation (RMSCV%) from which, the least significant change (LSC) was calculated. Bland-Altman plots were used to characterize bias in the precision estimates. The reproducibility of cortical density and cross-sectional area measures was high (RMSCV <1% and <1.5%, respectively) with good agreement between young and elder medians. The LSC for cortical porosity (Ct.Po) was somewhat smaller in the radius (0.58%) compared with the distal tibia (0.84%) and significantly different between young and elder medians in the distal tibia (LSC: 0.75% vs. 0.92%; p<0.001). The LSC for pore diameter and distribution (Po.Dm and Po.Dm.SD) ranged between 15 and 23μm. Bland-Altman analysis revealed moderate bias for integral measures of area and volume, but not density nor microarchitecture. This study indicates HR-pQCT measures of cortical bone density and architecture can be measured in vivo with high reproducibility and limited bias across a biologically relevant range of values. The results of this study provide informative data for the design of future clinical studies of bone quality. PMID:20561906

Brain abnormalities in murderers indicated by positron emission tomography.

PubMed

Raine, A; Buchsbaum, M; LaCasse, L

1997-09-15

Murderers pleading not guilty by reason of insanity (NGRI) are thought to have brain dysfunction, but there have been no previous studies reporting direct measures of both cortical and subcortical brain functioning in this specific group. Positron emission tomography brain imaging using a continuous performance challenge task was conducted on 41 murderers pleading not guilty by reason of insanity and 41 age- and sex-matched controls. Murderers were characterized by reduced glucose metabolism in the prefrontal cortex, superior parietal gyrus, left angular gyrus, and the corpus callosum, while abnormal asymmetries of activity (left hemisphere lower than right) were also found in the amygdala, thalamus, and medial temporal lobe. These preliminary findings provide initial indications of a network of abnormal cortical and subcortical brain processes that may predispose to violence in murderers pleading NGRI.

Alteration of Oriented Deposition of Cellulose Microfibrils by Mutation of a Katanin-Like Microtubule-Severing Protein

PubMed Central

Burk, David H.; Ye, Zheng-Hua

2002-01-01

It has long been hypothesized that cortical microtubules (MTs) control the orientation of cellulose microfibril deposition, but no mutants with alterations of MT orientation have been shown to affect this process. We have shown previously that in Arabidopsis, the fra2 mutation causes aberrant cortical MT orientation and reduced cell elongation, and the gene responsible for the fra2 mutation encodes a katanin-like protein. In this study, using field emission scanning electron microscopy, we found that the fra2 mutation altered the normal orientation of cellulose microfibrils in walls of expanding cells. Although cellulose microfibrils in walls of wild-type cells were oriented transversely along the elongation axis, cellulose microfibrils in walls of fra2 cells often formed bands and ran in different directions. The fra2 mutation also caused aberrant deposition of cellulose microfibrils in secondary walls of fiber cells. The aberrant orientation of cellulose microfibrils was shown to be correlated with disorganized cortical MTs in several cell types examined. In addition, the thickness of both primary and secondary cell walls was reduced significantly in the fra2 mutant. These results indicate that the katanin-like protein is essential for oriented cellulose microfibril deposition and normal cell wall biosynthesis. We further demonstrated that the Arabidopsis katanin-like protein possessed MT-severing activity in vitro; thus, it is an ortholog of animal katanin. We propose that the aberrant MT orientation caused by the mutation of katanin results in the distorted deposition of cellulose microfibrils, which in turn leads to a defect in cell elongation. These findings strongly support the hypothesis that cortical MTs regulate the oriented deposition of cellulose microfibrils that determines the direction of cell elongation. PMID:12215512

Alteration of oriented deposition of cellulose microfibrils by mutation of a katanin-like microtubule-severing protein.

PubMed

Burk, David H; Ye, Zheng-Hua

2002-09-01

It has long been hypothesized that cortical microtubules (MTs) control the orientation of cellulose microfibril deposition, but no mutants with alterations of MT orientation have been shown to affect this process. We have shown previously that in Arabidopsis, the fra2 mutation causes aberrant cortical MT orientation and reduced cell elongation, and the gene responsible for the fra2 mutation encodes a katanin-like protein. In this study, using field emission scanning electron microscopy, we found that the fra2 mutation altered the normal orientation of cellulose microfibrils in walls of expanding cells. Although cellulose microfibrils in walls of wild-type cells were oriented transversely along the elongation axis, cellulose microfibrils in walls of fra2 cells often formed bands and ran in different directions. The fra2 mutation also caused aberrant deposition of cellulose microfibrils in secondary walls of fiber cells. The aberrant orientation of cellulose microfibrils was shown to be correlated with disorganized cortical MTs in several cell types examined. In addition, the thickness of both primary and secondary cell walls was reduced significantly in the fra2 mutant. These results indicate that the katanin-like protein is essential for oriented cellulose microfibril deposition and normal cell wall biosynthesis. We further demonstrated that the Arabidopsis katanin-like protein possessed MT-severing activity in vitro; thus, it is an ortholog of animal katanin. We propose that the aberrant MT orientation caused by the mutation of katanin results in the distorted deposition of cellulose microfibrils, which in turn leads to a defect in cell elongation. These findings strongly support the hypothesis that cortical MTs regulate the oriented deposition of cellulose microfibrils that determines the direction of cell elongation.

Nigrostriatal lesion induces D2-modulated phase-locked activity in the basal ganglia of rats.

PubMed

Zold, Camila L; Ballion, Bérangère; Riquelme, Luis A; Gonon, François; Murer, M Gustavo

2007-04-01

There is a debate as to what modifications of neuronal activity underlie the clinical manifestations of Parkinson's disease and the efficacy of antiparkinsonian pharmacotherapy. Previous studies suggest that release of GABAergic striatopallidal neurons from D2 receptor-mediated inhibition allows spreading of cortical rhythms to the globus pallidus (GP) in rats with 6-hydroxydopamine-induced nigrostriatal lesions. Here this abnormal spreading was thoroughly investigated. In control urethane-anaesthetized rats most GP neurons were excited during the active part of cortical slow waves ('direct-phase' neurons). Two neuronal populations having opposite phase relationships with cortical and striatal activity coexisted in the GP of 6-hydroxydopamine-lesioned rats. 'Inverse-phase' GP units exhibited reduced firing coupled to striatal activation during slow waves, suggesting that this GP oscillation was driven by striatopallidal hyperactivity. Half of the pallidonigral neurons identified by antidromic stimulation exhibited inverse-phase activity. Therefore, spreading of inverse-phase oscillations through pallidonigral axons might contribute to the abnormal direct-phase cortical entrainment of basal ganglia output described previously. Systemic administration of the D2 agonist quinpirole to 6-hydroxydopamine-lesioned rats reduced GP inverse-phase coupling with slow waves, and this effect was reversed by the D2 antagonist eticlopride. Because striatopallidal hyperactivity was only slightly reduced by quinpirole, other mechanisms might have contributed to the effect of quinpirole on GP oscillations. These results suggest that antiparkinsonian efficacy may rely on other actions of D2 agonists on basal ganglia activity. However, abnormal slow rhythms may promote enduring changes in functional connectivity along the striatopallidal axis, contributing to D2 agonist-resistant clinical signs of parkinsonism.

Prefrontal cortex-projecting glutamatergic thalamic paraventricular nucleus-excited by hypocretin: a feedforward circuit that may enhance cognitive arousal.

PubMed

Huang, Hao; Ghosh, Prabhat; van den Pol, Anthony N

2006-03-01

The paraventricular thalamic nucleus (PVT) receives one of the most dense innervations by hypothalamic hypocretin/orexin (Hcrt) neurons, which play important roles in sleep-wakefulness, attention, and autonomic function. The PVT projects to several loci, including the medial prefrontal cortex (mPFC), a cortical region involved in associative function and attention. To study the effect of Hcrt on excitatory PVT neurons that project to the mPFC, we used a new line of transgenic mice expressing green fluorescent protein (GFP) under the control of the vesicular glutamate-transporter-2 promoter. These neurons were retrogradely labeled with cholera toxin subunit B that had been microinjected into the mPFC. Membrane characteristics and responses to hypocretin-1 and -2 (Hcrt-1 and -2) were studied using whole cell recording (n > 300). PVT neurons showed distinct membrane properties including inward rectification, H-type potassium currents, low threshold spikes, and spike frequency adaptation. Cortically projecting neurons were depolarized and excited by Hcrt-2. Hcrt-2 actions were stronger than those of Hcrt-1, and the action persisted in TTX and in low calcium/high magnesium artificial cerebrospinal fluid, consistent with direct actions mediated by Hcrt receptor-2. Two mechanisms of Hcrt excitation were found: an increase in input resistance caused by closure of potassium channels and activation of nonselective cation channels. The robust excitation evoked by Hcrt-2 on cortically projecting glutamate PVT neurons could generate substantial excitation in multiple layers of the mPFC, adding to the more selective direct excitatory actions of Hcrt in the mPFC and potentially increasing cortical arousal and attention to limbic or visceral states.

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

Cortical silent period reveals differences between adductor spasmodic dysphonia and muscle tension dysphonia

PubMed Central

Samargia, Sharyl; Schmidt, Rebekah; Kimberley, Teresa Jacobson

2015-01-01

Background The pathophysiology of adductor spasmodic dysphonia (AdSD), like other focal dystonias, is largely unknown. Objective The purposes of this study were to determine 1) cortical excitability differences between AdSD, muscle tension dysphonia (MTD) and healthy controls 2) distribution of potential differences in cranial or skeletal muscle, and 3) if cortical excitability measures assist in the differential diagnosis of AdSD and MTD. Methods 10 participants with adductor spasmodic dysphonia, 8 with muscle tension dysphonia and 10 healthy controls received single and paired pulse transcranial magnetic stimulation (TMS) to the primary motor cortex contralateral to tested muscles, first dorsal interosseus (FDI) and masseter. We tested the hypothesis that cortical excitability measures in AdSD would be significantly different than in MTD and healthy. In addition, we hypothesized there would be a correlation between cortical excitability measures and clinical voice severity in AdSD. Results Cortical silent period (CSP) duration in masseter and FDI was significantly shorter in AdSD than MTD and healthy controls. Other measures failed to demonstrate differences. Conclusion There are differences in cortical excitability between AdSD, MTD and healthy controls. These differences in the cortical measure of both the FDI and masseter muscles in AdSD suggest widespread dysfunction of the GABAB mechanism may be a pathophysiologic feature of AdSD, similar to other forms of focal dystonia. Further exploration of the use of TMS to assist in the differential diagnosis of AdSD and MTD is warranted. PMID:26089309

Drug Addiction: Updating Actions to Habits to Compulsions Ten Years On.

PubMed

Everitt, Barry J; Robbins, Trevor W

2016-01-01

A decade ago, we hypothesized that drug addiction can be viewed as a transition from voluntary, recreational drug use to compulsive drug-seeking habits, neurally underpinned by a transition from prefrontal cortical to striatal control over drug seeking and taking as well as a progression from the ventral to the dorsal striatum. Here, in the light of burgeoning, supportive evidence, we reconsider and elaborate this hypothesis, in particular the refinements in our understanding of ventral and dorsal striatal mechanisms underlying goal-directed and habitual drug seeking, the influence of drug-associated Pavlovian-conditioned stimuli on drug seeking and relapse, and evidence for impairments in top-down prefrontal cortical inhibitory control over this behavior. We further review animal and human studies that have begun to define etiological factors and individual differences in the propensity to become addicted to drugs, leading to the description of addiction endophenotypes, especially for cocaine addiction. We consider the prospect of novel treatments for addiction that promote abstinence from and relapse to drug use.

Direct Inhibitory Effect of Hypercalcemia on Renal Actions of Parathyroid Hormone

PubMed Central

Beck, Nama; Singh, Harbans; Reed, Sarah W.; Davis, Bernard B.

1974-01-01

The effects of calcium on the renal actions of parathyroid hormone (PTH) were studied in vivo and in vitro. In parathyroidectomized rats, variable levels of blood calcium concentration were induced by intravenous infusion of calcium. The renal responses to the injected PTH, i.e. phosphate and cyclic AMP excretion, were compared in these animals. After PTH injection, the increases of both phosphate and cyclic AMP excretion were less in the calcium-infused animals than in the control group without calcium infusion. There was an inverse correlation between the renal responses to PTH and plasma calcium concentration of 4.2-13.5 mg/100 ml. But calcium had no effect on phosphate excretion induced by infusion of dibutyryl cyclic AMP. In the in vitro experiments, the increase of cyclic AMP concentration in response to PTH was less in renal cortical slices taken from the calcium-infused animals than in ones from the control group without calcium infusion. Calcium also inhibited the activation of renal cortical adenylate cyclase in response to PTH, but calcium had no effect on phosphodiesterase. The data indicate that calcium directly inhibits renal actions of PTH both in vivo and in vitro. Such inhibitory mechanism is probably at or before the step of PTH-dependent cyclic AMP generation in the kidney. PMID:4359938

Genetic and epigenetic contributions to the cortical phenotype in mammals☆

PubMed Central

Larsen, DeLaine D.; Krubitzer, Leah

2008-01-01

One aspect of cortical organization, cortical field size, is variable both within and across species. The observed variability arises from a variety of sources, including genes intrinsic to the neocortex and a number of extrinsic and epigenetic factors. Genes intrinsic to the cortex are directly involved in the development and specification of cortical fields and are regulated from both signaling centers located outside of the neocortex, which secrete diffusible molecules, and the expression of transcription factors within the neocortex. In addition, extrinsic factors such as the type, location and density of sensory receptor arrays and how these receptor arrays are utilized, are also strongly related to cortical field size. Epigenetic factors including the relative activity patterns generated by the different types of physical stimuli in a given environment also contribute to differences in cortical organization, including cortical field size. Since both genetic and epigenetic factors contribute to cortical organization, some aspects of the cortical phenotype evolve, while other aspects of the cortical phenotype persist only if the environment in which an individual develops is relatively stable. PMID:18331904

Effects of education on aging-related cortical thinning among cognitively normal individuals.

PubMed

Kim, Jun Pyo; Seo, Sang Won; Shin, Hee Young; Ye, Byoung Seok; Yang, Jin-Ju; Kim, Changsoo; Kang, Mira; Jeon, Seun; Kim, Hee Jin; Cho, Hanna; Kim, Jung-Hyun; Lee, Jong-Min; Kim, Sung Tae; Na, Duk L; Guallar, Eliseo

2015-09-01

We aimed to investigate the relationship between education and cortical thickness in cognitively normal individuals to determine whether education attenuated the association of advanced aging and cortical thinning. A total of 1,959 participants, in whom education levels were available, were included in the final analysis. Cortical thickness was measured on high-resolution MRIs using a surface-based method. Multiple linear regression analysis was performed for education level and cortical thickness, after controlling for possible confounders. High levels of education were correlated with increased mean cortical thickness throughout the entire cortex (p = 0.003). This association persisted after controlling for vascular risk factors. Statistical maps of cortical thickness showed that the high levels of education were correlated with increased cortical thickness in the bilateral premotor areas, anterior cingulate cortices, perisylvian areas, right superior parietal lobule, left lingual gyrus, and occipital pole. There were also interactive effects of age and education on the mean cortical thickness (p = 0.019). Our findings suggest the protective effect of education on cortical thinning in cognitively normal older individuals, regardless of vascular risk factors. This effect was found only in the older participants, suggesting that the protective effects of education on cortical thickness might be achieved by increased resistance to structural loss from aging rather than by simply providing a fixed advantage in the brain. © 2015 American Academy of Neurology.

Cortical Photostimulation Technology for Vision Prosthesis

DTIC Science & Technology

2017-05-01

Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions...SUPPLEMENTARY NOTES 14. ABSTRACT The overall goal of the project is to evaluate the feasibility of using photochemical stimulation of cortical neurons as the...glutamate, which can directly stimulate cortical neurons. The new caged molecule has an absorption peak in the visible wavelength range, at 458 nm

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.

Cortical Thickness and Episodic Memory Impairment in Systemic Lupus Erythematosus.

PubMed

Bizzo, Bernardo Canedo; Sanchez, Tiago Arruda; Tukamoto, Gustavo; Zimmermann, Nicolle; Netto, Tania Maria; Gasparetto, Emerson Leandro

2017-01-01

The purpose of this study was to investigate differences in brain cortical thickness of systemic lupus erythematosus (SLE) patients with and without episodic memory impairment and healthy controls. We studied 51 patients divided in 2 groups (SLE with episodic memory deficit, n = 17; SLE without episodic memory deficit, n = 34) by the Rey Auditory Verbal Learning Test and 34 healthy controls. Groups were paired based on sex, age, education, Mini-Mental State Examination score, and accumulation of disease burden. Cortical thickness from magnetic resonance imaging scans was determined using the FreeSurfer software package. SLE patients with episodic memory deficits presented reduced cortical thickness in the left supramarginal cortex and superior temporal gyrus when compared to the control group and in the right superior frontal, caudal, and rostral middle frontal and precentral gyri when compared to the SLE group without episodic memory impairment considering time since diagnosis of SLE as covaried. There were no significant differences in the cortical thickness between the SLE without episodic memory and control groups. Different memory-related cortical regions thinning were found in the episodic memory deficit group when individually compared to the groups of patients without memory impairment and healthy controls. Copyright © 2016 by the American Society of Neuroimaging.

Differential sensory fMRI signatures in autism and schizophrenia: Analysis of amplitude and trial-to-trial variability.

PubMed

Haigh, Sarah M; Gupta, Akshat; Barb, Scott M; Glass, Summer A F; Minshew, Nancy J; Dinstein, Ilan; Heeger, David J; Eack, Shaun M; Behrmann, Marlene

2016-08-01

Autism and schizophrenia share multiple phenotypic and genotypic markers, and there is ongoing debate regarding the relationship of these two disorders. To examine whether cortical dynamics are similar across these disorders, we directly compared fMRI responses to visual, somatosensory and auditory stimuli in adults with autism (N=15), with schizophrenia (N=15), and matched controls (N=15). All participants completed a one-back letter detection task presented at fixation (to control attention) while task-irrelevant sensory stimulation was delivered to the different modalities. We focused specifically on the response amplitudes and the variability in sensory fMRI responses of the two groups, given the evidence of greater trial-to-trial variability in adults with autism. Both autism and schizophrenia individuals showed weaker signal-to-noise ratios (SNR) in sensory-evoked responses compared to controls (d>0.42), but for different reasons. For the autism group, the fMRI response amplitudes were indistinguishable from controls but were more variable trial-to-trial (d=0.47). For the schizophrenia group, response amplitudes were smaller compared to autism (d=0.44) and control groups (d=0.74), but were not significantly more variable (d<0.29). These differential group profiles suggest (1) that greater trial-to-trial variability in cortical responses may be specific to autism and is not a defining characteristic of schizophrenia, and (2) that blunted response amplitudes may be characteristic of schizophrenia. The relationship between the amplitude and the variability of cortical activity might serve as a specific signature differentiating these neurodevelopmental disorders. Identifying the neural basis of these responses and their relationship to the underlying genetic bases may substantially enlighten the understanding of both disorders. Copyright © 2016 Elsevier B.V. All rights reserved.

Cortical Feedback Regulates Feedforward Retinogeniculate Refinement

PubMed Central

Thompson, Andrew D; Picard, Nathalie; Min, Lia; Fagiolini, Michela; Chen, Chinfei

2016-01-01

SUMMARY According to the prevailing view of neural development, sensory pathways develop sequentially in a feedforward manner, whereby each local microcircuit refines and stabilizes before directing the wiring of its downstream target. In the visual system, retinal circuits are thought to mature first and direct refinement in the thalamus, after which cortical circuits refine with experience-dependent plasticity. In contrast, we now show that feedback from cortex to thalamus critically regulates refinement of the retinogeniculate projection during a discrete window in development, beginning at postnatal day 20 in mice. Disrupting cortical activity during this window, pharmacologically or chemogenetically, increases the number of retinal ganglion cells innervating each thalamic relay neuron. These results suggest that primary sensory structures develop through the concurrent and interdependent remodeling of subcortical and cortical circuits in response to sensory experience, rather than through a simple feedforward process. Our findings also highlight an unexpected function for the corticothalamic projection. PMID:27545712

O6.5. LINKING CORTICAL AND CONNECTIONAL PATHOLOGY IN SCHIZOPHRENIA

PubMed Central

Di Biase, Maria; Cropley, Vanessa; Cocchi, Luca; Fornito, Alexander; Calamante, Fernando; Ganella, Eleni; Pantelis, Christos; Zalesky, Andrew

2018-01-01

Abstract Background Schizophrenia is associated with cortical thinning and breakdown in white matter microstructure. Whether these pathological processes are related remains unclear. We used multimodal neuroimaging to investigate the relation between regional cortical thinning and breakdown in adjacent infracortical white matter as a function of age and illness duration. Methods Structural magnetic resonance and diffusion images were acquired in 218 schizophrenia patients and 167 age-matched healthy controls to map cortical thickness (CT) and fractional anisotropy (FA) in regionally adjacent infracortical white matter at various cortical depths. Results Between-group differences in CT and infracortical FA were inversely correlated across cortical regions (r=−0.5, p<0.0001), such that the most anisotropic infracortical white matter was found adjacent to regions with extensive cortical thinning. This pattern was evident in early (20 years: r=−0.3, p=0.005) and middle life (30 years: r=−0.4, p=0.004, 40 years: r=−0.3, p=0.04), but not beyond 50 years (p>0.05). Frontal pathology contributed most to this pattern, with extensive cortical thinning in patients compared to controls at all ages (p<0.05); in contrast to initially increased frontal infracortical FA in patients at 30 years, followed by rapid decline in frontal FA with age (rate of annual decline; patients: 0.0012, controls 0.0006, p<0.001). Discussion Cortical thinning and breakdown in white matter anisotropy are inversely related in young schizophrenia patients, with abnormally elevated white matter myelination found adjacent to frontal regions with extensive cortical thinning. We argue that elevated frontal anisotropy reflects regionally-specific, compensatory responses to cortical thinning, which are eventually overwhelmed with increasing illness duration.

Altered cortical thickness and attentional deficits in adolescent girls and women with bulimia nervosa

PubMed Central

Stefan, Mihaela; Lee, Seonjoo; Wang, Zhishun; Terranova, Kate; Attia, Evelyn; Marsh, Rachel

2018-01-01

Background Frontostriatal and frontoparietal abnormalities likely contribute to deficits in control and attentional processes in individuals with bulimia nervosa and to the persistence of dysregulated eating across development. This study assessed these processes and cortical thickness in a large sample of adolescent girls and women with bulimia nervosa compared with healthy controls. Methods We collected anatomical MRI data from adolescent girls and women (ages 12–38 yr) with full or subthreshold bulimia nervosa and age-matched healthy controls who also completed the Conners Continuous Performance Test-II (CPT-II). Groups were compared on task performance and cortical thickness. Mediation analyses explored associations among cortical thickness, CPT-II variables, bulimia nervosa symptoms and age. Results We included 60 girls and women with bulimia nervosa and 54 controls in the analyses. Compared with healthy participants, those with bulimia nervosa showed increased impulsivity and inattention on the CPT-II, along with reduced thickness of the right pars triangularis, right superior parietal and left dorsal posterior cingulate cortices. In the bulimia nervosa group, exploratory analyses revealed that binge eating frequency correlated inversely with cortical thickness of frontoparietal and insular regions and that reduced frontoparietal thickness mediated the association between age and increased symptom severity and inattention. Binge eating frequency also mediated the association between age and lower prefrontal cortical thickness. Limitations These findings are applicable to only girls and women with bulimia nervosa, and our cross-sectional design precludes understanding of whether cortical thickness alterations precede or result from bulimia nervosa symptoms. Conclusion Structural abnormalities in the frontoparietal and posterior cingulate regions comprising circuits that support control and attentional processes should be investigated as potential contributors to the maintenance of bulimia nervosa and useful targets for novel interventions. PMID:29688871

Cortical Thickness of Neural Substrates Supporting Cognitive Empathy in Individuals with Schizophrenia

PubMed Central

Massey, Suena H.; Stern, Daniel; Alden, Eva C.; Petersen, Julie E.; Cobia, Derin J.; Wang, Lei; Csernansky, John G.; Smith, Matthew J.

2016-01-01

Background Cognitive empathy is supported by the inferior frontal gyrus (IFG), anterior mid-cingulate cortex (aMCC), insula (INS), supplementary motor area (SMA), medial prefrontal cortex (mPFC), right temporo-parietal junction (TPJ), and precuneus (PREC). In healthy controls, cortical thickness in these regions has been linked to cognitive empathy. As cognitive empathy is impaired in schizophrenia, we examined whether reduced cortical thickness in these regions was associated with poorer cognitive empathy in this population. Methods 41 clinically-stable community-dwelling individuals with schizophrenia and 46 healthy controls group-matched on demographic variables completed self-report empathy questionnaires, a cognitive empathy task, and structural magnetic resonance imaging. We examined between-group differences in study variables using t-tests and analyses of variance. Next, we used Pearson correlations to evaluate the relationship between cognitive empathy and cortical thickness in the mPFC, IFG, aMCC, INS, SMA, TPJ, and PREC in both groups. Results Individuals with schizophrenia demonstrated cortical thinning in the IFG, INS, SMA, TPJ, and PREC (all p<0.05) and impaired cognitive empathy across all measures (all p<0.01) relative to controls. While cortical thickness in the mPFC, IFC, aMCC, and INS (all p<0.05) was related to cognitive empathy in controls, we did not observe these relationships in individuals with schizophrenia (all p>0.10). Conclusions Individuals with schizophrenia have reduced cortical thickness in empathy-related neural regions and significant impairments in cognitive empathy. Interestingly, cortical thickness was related to cognitive empathy in controls but not in the schizophrenia group. We discuss other mechanisms that may account for cognitive empathy impairment in schizophrenia. PMID:27665257

Cortical thickness of neural substrates supporting cognitive empathy in individuals with schizophrenia.

PubMed

Massey, Suena H; Stern, Daniel; Alden, Eva C; Petersen, Julie E; Cobia, Derin J; Wang, Lei; Csernansky, John G; Smith, Matthew J

2017-01-01

Cognitive empathy is supported by the medial prefrontal cortex (mPFC), inferior frontal gyrus (IFG), anterior mid-cingulate cortex (aMCC), insula (INS), supplementary motor area (SMA), right temporo-parietal junction (TPJ), and precuneus (PREC). In healthy controls, cortical thickness in these regions has been linked to cognitive empathy. As cognitive empathy is impaired in schizophrenia, we examined whether reduced cortical thickness in these regions was associated with poorer cognitive empathy in this population. 41 clinically-stable community-dwelling individuals with schizophrenia and 46 healthy controls group-matched on demographic variables completed self-report empathy questionnaires, a cognitive empathy task, and structural magnetic resonance imaging. We examined between-group differences in study variables using t-tests and analyses of variance. Next, we used Pearson correlations to evaluate the relationship between cognitive empathy and cortical thickness in the mPFC, IFG, aMCC, INS, SMA, TPJ, and PREC in both groups. Individuals with schizophrenia demonstrated cortical thinning in the IFG, INS, SMA, TPJ, and PREC (all p<0.05) and impaired cognitive empathy across all measures (all p<0.01) relative to controls. While cortical thickness in the mPFC, IFC, aMCC, and INS (all p<0.05) was related to cognitive empathy in controls, we did not observe these relationships in individuals with schizophrenia (all p>0.10). Individuals with schizophrenia have reduced cortical thickness in empathy-related neural regions and significant impairments in cognitive empathy. Interestingly, cortical thickness was related to cognitive empathy in controls but not in the schizophrenia group. We discuss other mechanisms that may account for cognitive empathy impairment in schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

Negative correlation of cortical thickness with the severity and duration of abdominal pain in Asian women with irritable bowel syndrome.

PubMed

Chua, Chian Sem; Bai, Chyi-Huey; Shiao, Chen-Yu; Hsu, Chien-Yeh; Cheng, Chiao-Wen; Yang, Kuo-Ching; Chiu, Hung-Wen; Hsu, Jung-Lung

2017-01-01

Irritable bowel syndrome (IBS) manifests as chronic abdominal pain. One pathophysiological theory states that the brain-gut axis is responsible for pain control in the intestine. Although several studies have discussed the structural changes in the brain of IBS patients, most of these studies have been conducted in Western populations. Different cultures and sexes experience different pain sensations and have different pain responses. Accordingly, we aimed to identify the specific changes in the cortical thickness of Asian women with IBS and to compare these data to those of non-Asian women with IBS. Thirty Asian female IBS patients (IBS group) and 39 healthy individuals (control group) were included in this study. Brain structural magnetic resonance imaging was performed. We used FreeSurfer to analyze the differences in the cortical thickness and their correlations with patient characteristics. The left cuneus, left rostral middle frontal cortex, left supramarginal cortex, right caudal anterior cingulate cortex, and bilateral insula exhibited cortical thinning in the IBS group compared with those in the controls. Furthermore, the brain cortical thickness correlated negatively the severity as well as duration of abdominal pain. Some of our findings differ from those of Western studies. In our study, all of the significant brain regions in the IBS group exhibited cortical thinning compared with those in the controls. The differences in cortical thickness between the IBS patients and controls may provide useful information to facilitate regulating abdominal pain in IBS patients. These findings offer insights into the association of different cultures and sexes with differences in cortical thinning in patients with IBS.

Altered cortical thickness and attentional deficits in adolescent girls and women with bulimia nervosa.

PubMed

Berner, Laura A; Stefan, Mihaela; Lee, Seonjoo; Wang, Zhishun; Terranova, Kate; Attia, Evelyn; Marsh, Rachel

2018-05-01

Frontostriatal and frontoparietal abnormalities likely contribute to deficits in control and attentional processes in individuals with bulimia nervosa and to the persistence of dysregulated eating across development. This study assessed these processes and cortical thickness in a large sample of adolescent girls and women with bulimia nervosa compared with healthy controls. We collected anatomical MRI data from adolescent girls and women (ages 12-38 yr) with full or subthreshold bulimia nervosa and age-matched healthy controls who also completed the Conners Continuous Performance Test-II (CPT-II). Groups were compared on task performance and cortical thickness. Mediation analyses explored associations among cortical thickness, CPT-II variables, bulimia nervosa symptoms and age. We included 60 girls and women with bulimia nervosa and 54 controls in the analyses. Compared with healthy participants, those with bulimia nervosa showed increased impulsivity and inattention on the CPT-II, along with reduced thickness of the right pars triangularis, right superior parietal and left dorsal posterior cingulate cortices. In the bulimia nervosa group, exploratory analyses revealed that binge eating frequency correlated inversely with cortical thickness of frontoparietal and insular regions and that reduced frontoparietal thickness mediated the association between age and increased symptom severity and inattention. Binge eating frequency also mediated the association between age and lower prefrontal cortical thickness. These findings are applicable to only girls and women with bulimia nervosa, and our cross-sectional design precludes understanding of whether cortical thickness alterations precede or result from bulimia nervosa symptoms. Structural abnormalities in the frontoparietal and posterior cingulate regions comprising circuits that support control and attentional processes should be investigated as potential contributors to the maintenance of bulimia nervosa and useful targets for novel interventions.

Altered cortical thickness and attentional deficits in adolescent girls and women with bulimia nervosa.

PubMed

Berner, Laura A; Stefan, Mihaela; Lee, Seonjoo; Wang, Zhishun; Terranova, Kate; Attia, Evelyn; Marsh, Rachel

2018-01-12

Frontostriatal and frontoparietal abnormalities likely contribute to deficits in control and attentional processes in individuals with bulimia nervosa and to the persistence of dysregulated eating across development. This study assessed these processes and cortical thickness in a large sample of adolescent girls and women with bulimia nervosa compared with healthy controls. We collected anatomical MRI data from adolescent girls and women (ages 12-38 yr) with full or subthreshold bulimia nervosa and age-matched healthy controls who also completed the Conners Continuous Performance Test-II (CPT-II). Groups were compared on task performance and cortical thickness. Mediation analyses explored associations among cortical thickness, CPT-II variables, bulimia nervosa symptoms and age. We included 60 girls and women with bulimia nervosa and 54 controls in the analyses. Compared with healthy participants, those with bulimia nervosa showed increased impulsivity and inattention on the CPT-II, along with reduced thickness of the right pars triangularis, right superior parietal and left dorsal posterior cingulate cortices. In the bulimia nervosa group, exploratory analyses revealed that binge eating frequency correlated inversely with cortical thickness of frontoparietal and insular regions and that reduced frontoparietal thickness mediated the association between age and increased symptom severity and inattention. Binge eating frequency also mediated the association between age and lower prefrontal cortical thickness. These findings are applicable to only girls and women with bulimia nervosa, and our cross-sectional design precludes understanding of whether cortical thickness alterations precede or result from bulimia nervosa symptoms. Structural abnormalities in the frontoparietal and posterior cingulate regions comprising circuits that support control and attentional processes should be investigated as potential contributors to the maintenance of bulimia nervosa and useful targets for novel interventions.

Cortical cholinergic signaling controls the detection of cues

PubMed Central

Gritton, Howard J.; Howe, William M.; Mallory, Caitlin S.; Hetrick, Vaughn L.; Berke, Joshua D.; Sarter, Martin

2016-01-01

The cortical cholinergic input system has been described as a neuromodulator system that influences broadly defined behavioral and brain states. The discovery of phasic, trial-based increases in extracellular choline (transients), resulting from the hydrolysis of newly released acetylcholine (ACh), in the cortex of animals reporting the presence of cues suggests that ACh may have a more specialized role in cognitive processes. Here we expressed channelrhodopsin or halorhodopsin in basal forebrain cholinergic neurons of mice with optic fibers directed into this region and prefrontal cortex. Cholinergic transients, evoked in accordance with photostimulation parameters determined in vivo, were generated in mice performing a task necessitating the reporting of cue and noncue events. Generating cholinergic transients in conjunction with cues enhanced cue detection rates. Moreover, generating transients in noncued trials, where cholinergic transients normally are not observed, increased the number of invalid claims for cues. Enhancing hits and generating false alarms both scaled with stimulation intensity. Suppression of endogenous cholinergic activity during cued trials reduced hit rates. Cholinergic transients may be essential for synchronizing cortical neuronal output driven by salient cues and executing cue-guided responses. PMID:26787867

Lhx2 Expression in Postmitotic Cortical Neurons Initiates Assembly of the Thalamocortical Somatosensory Circuit.

PubMed

Wang, Chia-Fang; Hsing, Hsiang-Wei; Zhuang, Zi-Hui; Wen, Meng-Hsuan; Chang, Wei-Jen; Briz, Carlos G; Nieto, Marta; Shyu, Bai Chuang; Chou, Shen-Ju

2017-01-24

Cortical neurons must be specified and make the correct connections during development. Here, we examine a mechanism initiating neuronal circuit formation in the barrel cortex, a circuit comprising thalamocortical axons (TCAs) and layer 4 (L4) neurons. When Lhx2 is selectively deleted in postmitotic cortical neurons using conditional knockout (cKO) mice, L4 neurons in the barrel cortex are initially specified but fail to form cellular barrels or develop polarized dendrites. In Lhx2 cKO mice, TCAs from the thalamic ventral posterior nucleus reach the barrel cortex but fail to further arborize to form barrels. Several activity-regulated genes and genes involved in regulating barrel formation are downregulated in the Lhx2 cKO somatosensory cortex. Among them, Btbd3, an activity-regulated gene controlling dendritic development, is a direct downstream target of Lhx2. We find that Lhx2 confers neuronal competency for activity-dependent dendritic development in L4 neurons by inducing the expression of Btbd3. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Nano-structural, compositional and micro-architectural signs of cortical bone fragility at the superolateral femoral neck in elderly hip fracture patients vs. healthy aged controls.

PubMed

Milovanovic, Petar; Rakocevic, Zlatko; Djonic, Danijela; Zivkovic, Vladimir; Hahn, Michael; Nikolic, Slobodan; Amling, Michael; Busse, Bjoern; Djuric, Marija

2014-07-01

To unravel the origins of decreased bone strength in the superolateral femoral neck, we assessed bone structural features across multiple length scales at this cortical fracture initiating region in postmenopausal women with hip fracture and in aged-matched controls. Our combined methodological approach encompassed atomic force microscopy (AFM) characterization of cortical bone nano-structure, assessment of mineral content/distribution via quantitative backscattered electron imaging (qBEI), measurement of bone material properties by reference point indentation, as well as evaluation of cortical micro-architecture and osteocyte lacunar density. Our findings revealed a wide range of differences between the fracture group and the controls, suggesting a number of detrimental changes at various levels of cortical bone hierarchical organization that may render bone fragile. Namely, mineral crystals at external cortical bone surfaces of the fracture group were larger (65.22nm±41.21nm vs. 36.75nm±18.49nm, p<0.001), and a shift to a higher mineral content and more homogenous mineralization profile as revealed via qBEI were found in the bone matrix of the fracture group. Fracture cases showed nearly 35% higher cortical porosity and showed significantly reduced osteocyte lacunar density compared to controls (226±27 vs. 247±32#/mm(2), p=0.05). Along with increased crystal size, a shift towards higher mineralization and a tendency to increased cortical porosity and reduced osteocyte lacunar number delineate that cortical bone of the superolateral femoral neck bears distinct signs of fragility at various levels of its structural organization. These results contribute to the understanding of hierarchical bone structure changes in age-related fragility. Copyright © 2014 Elsevier Inc. All rights reserved.

NMDA receptor blockade in the prelimbic cortex activates the mesolimbic system and dopamine-dependent opiate reward signaling.

PubMed

Tan, Huibing; Rosen, Laura G; Ng, Garye A; Rushlow, Walter J; Laviolette, Steven R

2014-12-01

N-Methyl-D-aspartate (NMDA) receptors in the medial prefrontal cortex (mPFC) are involved in opiate reward processing and modulate sub-cortical dopamine (DA) activity. NMDA receptor blockade in the prelimbic (PLC) division of the mPFC strongly potentiates the rewarding behavioural properties of normally sub-reward threshold doses of opiates. However, the possible functional interactions between cortical NMDA and sub-cortical DAergic motivational neural pathways underlying these effects are not understood. This study examines how NMDA receptor modulation in the PLC influences opiate reward processing via interactions with sub-cortical DAergic transmission. We further examined whether direct intra-PLC NMDA receptor modulation may activate DA-dependent opiate reward signaling via interactions with the ventral tegmental area (VTA). Using an unbiased place conditioning procedure (CPP) in rats, we performed bilateral intra-PLC microinfusions of the competitive NMDA receptor antagonist, (2R)-amino-5-phosphonovaleric acid (AP-5), prior to behavioural morphine place conditioning and challenged the rewarding effects of morphine with DA receptor blockade. We next examined the effects of intra-PLC NMDA receptor blockade on the spontaneous activity patterns of presumptive VTA DA or GABAergic neurons, using single-unit, extracellular in vivo neuronal recordings. We show that intra-PLC NMDA receptor blockade strongly activates sub-cortical DA neurons within the VTA while inhibiting presumptive non-DA GABAergic neurons. Behaviourally, NMDA receptor blockade activates a DA-dependent opiate reward system, as pharmacological blockade of DA transmission blocked morphine reward only in the presence of intra-PLC NMDA receptor antagonism. These findings demonstrate a cortical NMDA-mediated mechanism controlling mesolimbic DAergic modulation of opiate reward processing.

Effects of vitamin K2 on cortical and cancellous bone mass, cortical osteocyte and lacunar system, and porosity in sciatic neurectomized rats.

PubMed

Iwamoto, Jun; Matsumoto, Hideo; Takeda, Tsuyoshi; Sato, Yoshihiro; Yeh, James K

2010-09-01

The purpose of the present study was to examine the effects of vitamin K2 on cortical and cancellous bone mass, cortical osteocyte and lacunar system, and porosity in sciatic neurectomized rats. Thirty-four female Sprague-Dawley retired breeder rats were randomized into three groups: age-matched control, sciatic neurectomy (NX), and NX + vitamin K2 administration (menatetrenone, 30 mg/kg/day p.o., three times a week). At the end of the 8-week experiment, bone histomorphometric analysis was performed on cortical and cancellous bone of the tibial diaphysis and proximal metaphysis, respectively, and osteocyte lacunar system and porosity were evaluated on cortical bone of the tibial diaphysis. NX decreased cortical and cancellous bone mass compared with age-matched controls as a result of increased endocortical and trabecular bone erosion and decreased trabecular mineral apposition rate (MAR). Vitamin K2 ameliorated the NX-induced increase in bone erosion, prevented the NX-induced decrease in MAR, and increased bone formation rate (BFR/bone surface) in cancellous bone, resulting in an attenuation of NX-induced cancellous bone loss. However, vitamin K2 did not significantly influence cortical bone mass. NX also decreased osteocyte density and lacunar occupancy and increased porosity in cortical bone compared with age-matched controls. Vitamin K2 ameliorated the NX-induced decrease in lacunar occupancy by viable osteocytes and the NX-induced increase in porosity. The present study showed the efficacy of vitamin K2 for cancellous bone mass and cortical lacunar occupancy by viable osteocytes and porosity in sciatic NX rats.

Bone microarchitecture and estimated bone strength in men with active acromegaly.

PubMed

Silva, Paula P B; Amlashi, Fatemeh G; Yu, Elaine W; Pulaski-Liebert, Karen J; Gerweck, Anu V; Fazeli, Pouneh K; Lawson, Elizabeth; Nachtigall, Lisa B; Biller, Beverly M K; Miller, Karen K; Klibanski, Anne; Bouxsein, Mary; Tritos, Nicholas A

2017-11-01

Both acromegaly and adult growth hormone deficiency (GHD) are associated with increased fracture risk. Sufficient data are lacking regarding cortical bone microarchitecture and bone strength, as assessed by microfinite element analysis (µFEA). To elucidate both cortical and trabecular bone microarchitecture and estimated bone strength in men with active acromegaly or GHD compared to healthy controls. Cross-sectional study at a clinical research center, including 48 men (16 with acromegaly, 16 with GHD and 16 healthy controls). Areal bone mineral density (aBMD), cortical and trabecular bone microarchitecture and estimated bone strength (µFEA) at the radius and tibia. aBMD was not different between the 3 groups at any skeletal site. At the radius, patients with acromegaly had greater cortical area ( P  < 0.0001), cortical thickness ( P  = 0.0038), cortical pore volume ( P  < 0.0001) and cortical porosity ( P  = 0.0008), but lower trabecular bone density ( P  = 0.0010) compared to controls. At the tibia, patients with acromegaly had lower trabecular bone density ( P  = 0.0082), but no differences in cortical bone microstructure. Compressive strength and failure load did not significantly differ between groups. These findings persisted after excluding patients with hypogonadism. Bone microarchitecture was not deficient in patients with GHD. Both cortical and trabecular microarchitecture are altered in men with acromegaly. Our data indicate that GH excess is associated with distinct effects in cortical vs trabecular bone compartments. Our observations also affirm the limitations of aBMD testing in the evaluation of patients with acromegaly. © 2017 European Society of Endocrinology.

ERP Modulation during Observation of Abstract Paintings by Franz Kline

PubMed Central

Sbriscia-Fioretti, Beatrice; Berchio, Cristina; Freedberg, David; Gallese, Vittorio; Umiltà, Maria Alessandra

2013-01-01

The aim of this study was to test the involvement of sensorimotor cortical circuits during the beholding of the static consequences of hand gestures devoid of any meaning.In order to verify this hypothesis we performed an EEG experiment presenting to participants images of abstract works of art with marked traces of brushstrokes. The EEG data were analyzed by using Event Related Potentials (ERPs). We aimed to demonstrate a direct involvement of sensorimotor cortical circuits during the beholding of these selected works of abstract art. The stimuli consisted of three different abstract black and white paintings by Franz Kline. Results verified our experimental hypothesis showing the activation of premotor and motor cortical areas during stimuli observation. In addition, abstract works of art observation elicited the activation of reward-related orbitofrontal areas, and cognitive categorization-related prefrontal areas. The cortical sensorimotor activation is a fundamental neurophysiological demonstration of the direct involvement of the cortical motor system in perception of static meaningless images belonging to abstract art. These results support the role of embodied simulation of artist’s gestures in the perception of works of art. PMID:24130693

Cortico-Striatal-Thalamic Loop Circuits of the Salience Network: A Central Pathway in Psychiatric Disease and Treatment.

PubMed

Peters, Sarah K; Dunlop, Katharine; Downar, Jonathan

2016-01-01

The salience network (SN) plays a central role in cognitive control by integrating sensory input to guide attention, attend to motivationally salient stimuli and recruit appropriate functional brain-behavior networks to modulate behavior. Mounting evidence suggests that disturbances in SN function underlie abnormalities in cognitive control and may be a common etiology underlying many psychiatric disorders. Such functional and anatomical abnormalities have been recently apparent in studies and meta-analyses of psychiatric illness using functional magnetic resonance imaging (fMRI) and voxel-based morphometry (VBM). Of particular importance, abnormal structure and function in major cortical nodes of the SN, the dorsal anterior cingulate cortex (dACC) and anterior insula (AI), have been observed as a common neurobiological substrate across a broad spectrum of psychiatric disorders. In addition to cortical nodes of the SN, the network's associated subcortical structures, including the dorsal striatum, mediodorsal thalamus and dopaminergic brainstem nuclei, comprise a discrete regulatory loop circuit. The SN's cortico-striato-thalamo-cortical loop increasingly appears to be central to mechanisms of cognitive control, as well as to a broad spectrum of psychiatric illnesses and their available treatments. Functional imbalances within the SN loop appear to impair cognitive control, and specifically may impair self-regulation of cognition, behavior and emotion, thereby leading to symptoms of psychiatric illness. Furthermore, treating such psychiatric illnesses using invasive or non-invasive brain stimulation techniques appears to modulate SN cortical-subcortical loop integrity, and these effects may be central to the therapeutic mechanisms of brain stimulation treatments in many psychiatric illnesses. Here, we review clinical and experimental evidence for abnormalities in SN cortico-striatal-thalamic loop circuits in major depression, substance use disorders (SUD), anxiety disorders, schizophrenia and eating disorders (ED). We also review emergent therapeutic evidence that novel invasive and non-invasive brain stimulation treatments may exert therapeutic effects by normalizing abnormalities in the SN loop, thereby restoring the capacity for cognitive control. Finally, we consider a series of promising directions for future investigations on the role of SN cortico-striatal-thalamic loop circuits in the pathophysiology and treatment of psychiatric disorders.

Cortico-Striatal-Thalamic Loop Circuits of the Salience Network: A Central Pathway in Psychiatric Disease and Treatment

PubMed Central

Peters, Sarah K.; Dunlop, Katharine; Downar, Jonathan

2016-01-01

The salience network (SN) plays a central role in cognitive control by integrating sensory input to guide attention, attend to motivationally salient stimuli and recruit appropriate functional brain-behavior networks to modulate behavior. Mounting evidence suggests that disturbances in SN function underlie abnormalities in cognitive control and may be a common etiology underlying many psychiatric disorders. Such functional and anatomical abnormalities have been recently apparent in studies and meta-analyses of psychiatric illness using functional magnetic resonance imaging (fMRI) and voxel-based morphometry (VBM). Of particular importance, abnormal structure and function in major cortical nodes of the SN, the dorsal anterior cingulate cortex (dACC) and anterior insula (AI), have been observed as a common neurobiological substrate across a broad spectrum of psychiatric disorders. In addition to cortical nodes of the SN, the network’s associated subcortical structures, including the dorsal striatum, mediodorsal thalamus and dopaminergic brainstem nuclei, comprise a discrete regulatory loop circuit. The SN’s cortico-striato-thalamo-cortical loop increasingly appears to be central to mechanisms of cognitive control, as well as to a broad spectrum of psychiatric illnesses and their available treatments. Functional imbalances within the SN loop appear to impair cognitive control, and specifically may impair self-regulation of cognition, behavior and emotion, thereby leading to symptoms of psychiatric illness. Furthermore, treating such psychiatric illnesses using invasive or non-invasive brain stimulation techniques appears to modulate SN cortical-subcortical loop integrity, and these effects may be central to the therapeutic mechanisms of brain stimulation treatments in many psychiatric illnesses. Here, we review clinical and experimental evidence for abnormalities in SN cortico-striatal-thalamic loop circuits in major depression, substance use disorders (SUD), anxiety disorders, schizophrenia and eating disorders (ED). We also review emergent therapeutic evidence that novel invasive and non-invasive brain stimulation treatments may exert therapeutic effects by normalizing abnormalities in the SN loop, thereby restoring the capacity for cognitive control. Finally, we consider a series of promising directions for future investigations on the role of SN cortico-striatal-thalamic loop circuits in the pathophysiology and treatment of psychiatric disorders. PMID:28082874

Intrinsic Connections of the Core Auditory Cortical Regions and Rostral Supratemporal Plane in the Macaque Monkey.

PubMed

Scott, Brian H; Leccese, Paul A; Saleem, Kadharbatcha S; Kikuchi, Yukiko; Mullarkey, Matthew P; Fukushima, Makoto; Mishkin, Mortimer; Saunders, Richard C

2017-01-01

In the ventral stream of the primate auditory cortex, cortico-cortical projections emanate from the primary auditory cortex (AI) along 2 principal axes: one mediolateral, the other caudorostral. Connections in the mediolateral direction from core, to belt, to parabelt, have been well described, but less is known about the flow of information along the supratemporal plane (STP) in the caudorostral dimension. Neuroanatomical tracers were injected throughout the caudorostral extent of the auditory core and rostral STP by direct visualization of the cortical surface. Auditory cortical areas were distinguished by SMI-32 immunostaining for neurofilament, in addition to established cytoarchitectonic criteria. The results describe a pathway comprising step-wise projections from AI through the rostral and rostrotemporal fields of the core (R and RT), continuing to the recently identified rostrotemporal polar field (RTp) and the dorsal temporal pole. Each area was strongly and reciprocally connected with the areas immediately caudal and rostral to it, though deviations from strictly serial connectivity were observed. In RTp, inputs converged from core, belt, parabelt, and the auditory thalamus, as well as higher order cortical regions. The results support a rostrally directed flow of auditory information with complex and recurrent connections, similar to the ventral stream of macaque visual cortex. Published by Oxford University Press 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Localizing and tracking electrodes using stereovision in epilepsy cases

NASA Astrophysics Data System (ADS)

Fan, Xiaoyao; Ji, Songbai; Roberts, David W.; Paulsen, Keith D.

2015-03-01

In epilepsy cases, subdural electrodes are often implanted to acquire intracranial EEG (iEEG) for seizure localization and resection planning. However, the electrodes may shift significantly between implantation and resection, during the time that the patient is monitored for iEEG recording. As a result, the accuracy of surgical planning based on electrode locations at the time of resection can be compromised. Previous studies have only quantified the electrode shift with respect to the skull, but not with respect to the cortical surface, because tracking cortical shift between surgeries is challenging. In this study, we use an intraoperative stereovision (iSV) system to visualize and localize the cortical surface as well as electrodes, record three-dimensional (3D) locations of the electrodes in MR space at the time of implantation and resection, respectively, and quantify the raw displacements, i.e., with respect to the skull. Furthermore, we track the cortical surface and quantify the shift between surgeries using an optical flow (OF) based motion-tracking algorithm. Finally, we compute the electrode shift with respect to the cortical surface by subtracting the cortical shift from raw measured displacements. We illustrate the method using one patient example. In this particular patient case, the results show that the electrodes not only shifted significantly with respect to the skull (8.79 +/- 3.00 mm in the lateral direction, ranging from 2.88 mm to 12.87 mm), but also with respect to the cortical surface (7.20 +/- 3.58 mm), whereas the cortical surface did not shift significantly in the lateral direction between surgeries (2.23 +/- 0.76 mm).

Wavelet decomposition of transmitted ultrasound wave through a 1-D muscle-bone system.

PubMed

Buchanan, James L; Gilbert, Robert P; Ou, Miao-jung Y

2011-01-11

In the attempt for using ultrasound as a diagnostic device for osteoporosis, several authors have described the result of the in vitro experiment in which ultrasound is passed through a cancellous bone specimen placed in a water tank. However, in the in vivo setting, a patient's cancellous bone is surrounded by cortical and muscle layers. This paper considers in the one-dimensional case (1) what effect the cortical bone segments surrounding the cancellous segment would have on the received signal and (2) what the received signal would be when a source and receiver are placed on opposite sides of a structure consisting of a cancellous segment surrounded by cortical and muscle layers. Mathematically this is accomplished by representing the received signal as a sum of wavelets which go through different reflection-transmission histories at the muscle-cortical bone and cortical-cancellous bone interfaces. The muscle and cortical bone are modeled as elastic materials and the cancellous bone as a poroelastic material described by the Biot-Johnson-Koplik-Dashen model. The approach presented here permits the assessment of which possible paths of transmission and reflection through the cortical-cancellous or muscle-cortical-cancellous complex will result in significant contributions to the received waveform. This piece of information can be useful for solving the inverse problem of non-destructive assessment of material properties of bone. Our methodology can be generalized to three-dimensional parallelly layered structure by first applying Fourier transform in the directions perpendicular to the transverse direction. Copyright © 2010 Elsevier Ltd. All rights reserved.

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

Alterations of whole-brain cortical area and thickness in mild cognitive impairment and Alzheimer's disease.

PubMed

Li, Chuanming; Wang, Jian; Gui, Li; Zheng, Jian; Liu, Chen; Du, Hanjian

2011-01-01

Gray matter volume and density of several brain regions, determined by magnetic resonance imaging (MRI), are decreased in Alzheimer's disease (AD). Animal studies have indicated that changes in cortical area size is relevant to thinking and behavior, but alterations of cortical area and thickness in the brains of individuals with AD or its likely precursor, mild cognitive impairment (MCI), have not been reported. In this study, 25 MCI subjects, 30 AD subjects, and 30 age-matched normal controls were recruited for brain MRI scans and Functional Activities Questionnaire (FAQ) assessments. Based on the model using FreeSurfer software, two brain lobes were divided into various regions according to the Desikan-Killiany atlas and the cortical area and thickness of every region was compared and analyzed. We found a significant increase in cortical area of several regions in the frontal and temporal cortices, which correlated negatively with MMSE scores, and a significant decrease in cortical area of several regions in the parietal cortex and the cingulate gyrus in AD subjects. Increased cortical area was also seen in some regions of the frontal and temporal cortices in MCI subjects, whereas the cortical thickness of the same regions was decreased. Our observations suggest characteristic differences of the cortical area and thickness in MCI, AD, and normal control subjects, and these changes may help diagnose both MCI and AD.

Stimulating thought: a functional MRI study of transcranial direct current stimulation in schizophrenia.

PubMed

Orlov, Natasza D; O'Daly, Owen; Tracy, Derek K; Daniju, Yusuf; Hodsoll, John; Valdearenas, Lorena; Rothwell, John; Shergill, Sukhi S

2017-09-01

Individuals with schizophrenia typically suffer a range of cognitive deficits, including prominent deficits in working memory and executive function. These difficulties are strongly predictive of functional outcomes, but there is a paucity of effective therapeutic interventions targeting these deficits. Transcranial direct current stimulation is a novel neuromodulatory technique with emerging evidence of potential pro-cognitive effects; however, there is limited understanding of its mechanism. This was a double-blind randomized sham controlled pilot study of transcranial direct current stimulation on a working memory (n-back) and executive function (Stroop) task in 28 individuals with schizophrenia using functional magnetic resonance imaging. Study participants received 30 min of real or sham transcranial direct current stimulation applied to the left frontal cortex. The 'real' and 'sham' groups did not differ in online working memory task performance, but the transcranial direct current stimulation group demonstrated significant improvement in performance at 24 h post-transcranial direct current stimulation. Transcranial direct current stimulation was associated with increased activation in the medial frontal cortex beneath the anode; showing a positive correlation with consolidated working memory performance 24 h post-stimulation. There was reduced activation in the left cerebellum in the transcranial direct current stimulation group, with no change in the middle frontal gyrus or parietal cortices. Improved performance on the executive function task was associated with reduced activity in the anterior cingulate cortex. Transcranial direct current stimulation modulated functional activation in local task-related regions, and in more distal nodes in the network. Transcranial direct current stimulation offers a potential novel approach to altering frontal cortical activity and exerting pro-cognitive effects in schizophrenia. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The association of cognitive impairment with gray matter atrophy and cortical lesion load in clinically isolated syndrome.

PubMed

Diker, Sevda; Has, Arzu Ceylan; Kurne, Aslı; Göçmen, Rahşan; Oğuz, Kader Karlı; Karabudak, Rana

2016-11-01

Multiple sclerosis can impair cognition from the early stages and has been shown to be associated with gray matter damage in addition to white matter pathology. To investigate the profile of cognitive impairment in clinically isolated syndrome (CIS), and the contribution of cortical inflammation, cortical and deep gray matter atrophy, and white matter lesions to cognitive decline. Thirty patients with clinically isolated syndrome and twenty demographically- matched healthy controls underwent neuropsychologic assessment through the Rao Brief Repeatable Battery, and brain magnetic resonance imaging with double inversion recovery using a 3T scanner. Patients with clinically isolated syndrome performed significantly worse than healthy controls on tests that evaluated verbal memory, visuospatial learning and memory, and verbal fluency. Significant deep gray matter atrophy was found in the patients but cortical volume was not lower than the controls. Visual memory tests correlated with the volume of the hippocampus, cerebral white matter and deep gray matter structures and with cerebellar cortical atrophy. Cortical or white matter lesion load did not affect cognitive test results. In our patients with CIS, it was shown that cognitive impairment was mainly related to cerebral white matter, cerebellar cortical and deep gray matter atrophy, but not with cortical inflammation, at least in the early stage of disease. Copyright © 2016 Elsevier B.V. All rights reserved.

Abnormalities of hippocampal-cortical connectivity in temporal lobe epilepsy patients with hippocampal sclerosis

NASA Astrophysics Data System (ADS)

Li, Wenjing; He, Huiguang; Lu, Jingjing; Wang, Chunheng; Li, Meng; Lv, Bin; Jin, Zhengyu

2011-03-01

Hippocampal sclerosis (HS) is the most common damage seen in the patients with temporal lobe epilepsy (TLE). In the present study, the hippocampal-cortical connectivity was defined as the correlation between the hippocampal volume and cortical thickness at each vertex throughout the whole brain. We aimed to investigate the differences of ipsilateral hippocampal-cortical connectivity between the unilateral TLE-HS patients and the normal controls. In our study, the bilateral hippocampal volumes were first measured in each subject, and we found that the ipsilateral hippocampal volume significantly decreased in the left TLE-HS patients. Then, group analysis showed significant thinner average cortical thickness of the whole brain in the left TLE-HS patients compared with the normal controls. We found significantly increased ipsilateral hippocampal-cortical connectivity in the bilateral superior temporal gyrus, the right cingulate gyrus and the left parahippocampal gyrus of the left TLE-HS patients, which indicated structural vulnerability related to the hippocampus atrophy in the patient group. However, for the right TLE-HS patients, no significant differences were found between the patients and the normal controls, regardless of the ipsilateral hippocampal volume, the average cortical thickness or the patterns of hippocampal-cortical connectivity, which might be related to less atrophies observed in the MRI scans. Our study provided more evidence for the structural abnormalities in the unilateral TLE-HS patients.

Reduced Cortical Thickness in Mental Retardation

PubMed Central

Wang, Chao; Wang, Jiaojian; Zhang, Yun; Yu, Chunshui; Jiang, Tianzi

2011-01-01

Mental retardation is a developmental disorder associated with impaired cognitive functioning and deficits in adaptive behaviors. Many studies have addressed white matter abnormalities in patients with mental retardation, while the changes of the cerebral cortex have been studied to a lesser extent. Quantitative analysis of cortical integrity using cortical thickness measurement may provide new insights into the gray matter pathology. In this study, cortical thickness was compared between 13 patients with mental retardation and 26 demographically matched healthy controls. We found that patients with mental retardation had significantly reduced cortical thickness in multiple brain regions compared with healthy controls. These regions include the bilateral lingual gyrus, the bilateral fusiform gyrus, the bilateral parahippocampal gyrus, the bilateral temporal pole, the left inferior temporal gyrus, the right lateral orbitofrontal cortex and the right precentral gyrus. The observed cortical thickness reductions might be the anatomical substrates for the impaired cognitive functioning and deficits in adaptive behaviors in patients with mental retardation. Cortical thickness measurement might provide a sensitive prospective surrogate marker for clinical trials of neuroprotective medications. PMID:22216343

Visual Network Asymmetry and Default Mode Network Function in ADHD: An fMRI Study

PubMed Central

Hale, T. Sigi; Kane, Andrea M.; Kaminsky, Olivia; Tung, Kelly L.; Wiley, Joshua F.; McGough, James J.; Loo, Sandra K.; Kaplan, Jonas T.

2014-01-01

Background: A growing body of research has identified abnormal visual information processing in attention-deficit hyperactivity disorder (ADHD). In particular, slow processing speed and increased reliance on visuo-perceptual strategies have become evident. Objective: The current study used recently developed fMRI methods to replicate and further examine abnormal rightward biased visual information processing in ADHD and to further characterize the nature of this effect; we tested its association with several large-scale distributed network systems. Method: We examined fMRI BOLD response during letter and location judgment tasks, and directly assessed visual network asymmetry and its association with large-scale networks using both a voxelwise and an averaged signal approach. Results: Initial within-group analyses revealed a pattern of left-lateralized visual cortical activity in controls but right-lateralized visual cortical activity in ADHD children. Direct analyses of visual network asymmetry confirmed atypical rightward bias in ADHD children compared to controls. This ADHD characteristic was atypically associated with reduced activation across several extra-visual networks, including the default mode network (DMN). We also found atypical associations between DMN activation and ADHD subjects’ inattentive symptoms and task performance. Conclusion: The current study demonstrated rightward VNA in ADHD during a simple letter discrimination task. This result adds an important novel consideration to the growing literature identifying abnormal visual processing in ADHD. We postulate that this characteristic reflects greater perceptual engagement of task-extraneous content, and that it may be a basic feature of less efficient top-down task-directed control over visual processing. We additionally argue that abnormal DMN function may contribute to this characteristic. PMID:25076915

Using human extra-cortical local field potentials to control a switch

NASA Astrophysics Data System (ADS)

Kennedy, Philip; Andreasen, Dinal; Ehirim, Princewill; King, Brandon; Kirby, Todd; Mao, Hui; Moore, Melody

2004-06-01

Individuals with profound paralysis and mutism require a communication channel. Traditional assistive technology devices eventually fail, especially in the case of amyotrophic lateral sclerosis (ALS) subjects who gradually become totally locked-in. A direct brain-to-computer interface that provides switch functions can provide a direct communication channel to the external world. Electroencephalographic (EEG) signals recorded from scalp electrodes are significantly degraded due to skull and scalp attenuation and ambient noise. The present system using conductive skull screws allows more reliable access to cortical local field potentials (LFPs) without entering the brain itself. We describe an almost locked-in human subject with ALS who activated a switch using online time domain detection techniques. Frequency domain analysis of his LFP activity demonstrates this to be an alternative method of detecting switch activation intentions. With this brain communicator system it is reasonable to expect that locked-in, but cognitively intact, humans will always be able to communicate. Financial disclosure. Authors PK and DA may derive some financial gain from the sale of this device. A patent has been applied under US and international law: 10/675,703.

Dia-Interacting Protein (DIP) Imposes Migratory Plasticity in mDia2-Dependent Tumor Cells in Three-Dimensional Matrices

PubMed Central

Wyse, Meghan M.; Lei, Jun; Nestor-Kalinoski, Andrea L.; Eisenmann, Kathryn M.

2012-01-01

Tumor cells rely upon membrane pliancy to escape primary lesions and invade secondary metastatic sites. This process relies upon localized assembly and disassembly cycles of F-actin that support and underlie the plasma membrane. Dynamic actin generates both spear-like and bleb structures respectively characterizing mesenchymal and amoeboid motility programs utilized by metastatic cells in three-dimensional matrices. The molecular mechanism and physiological trigger(s) driving membrane plasticity are poorly understood. mDia formins are F-actin assembly factors directing membrane pliancy in motile cells. mDia2 is functionally coupled with its binding partner DIP, regulating cortical actin and inducing membrane blebbing in amoeboid cells. Here we show that mDia2 and DIP co-tether to nascent blebs and this linkage is required for bleb formation. DIP controls mesenchymal/amoeboid cell interconvertability, while CXCL12 induces assembly of mDia2:DIP complexes to bleb cortices in 3D matrices. These results demonstrate how DIP-directed mDia2-dependent F-actin dynamics regulate morphological plasticity in motile cancer cells. PMID:23024796

Visual hallucinations in dementia with Lewy bodies: transcranial magnetic stimulation study

PubMed Central

Taylor, John-Paul; Firbank, Michael; Barnett, Nicola; Pearce, Sarah; Livingstone, Anthea; Mosimann, Urs; Eyre, Janet; McKeith, Ian G.; O’Brien, John T.

2011-01-01

Background The aetiology of visual hallucinations is poorly understood in dementia with Lewy bodies. Pathological alterations in visual cortical excitability may be one contributory mechanism. Aims To determine visual cortical excitability in people with dementia with Lewy bodies compared with aged-matched controls and also the relationship between visual cortical excitability and visual hallucinations in dementia with Lewy bodies. Method Visual cortical excitability was determined by using transcranial magnetic stimulation (TMS) applied to the occiput to elicit phosphenes (transient subjective visual responses) in 21 patients with dementia with Lewy bodies and 19 age-matched controls. Results Phosphene parameters were similar between both groups. However, in the patients with dementia with Lewy bodies, TMS measures of visual cortical excitability correlated strongly with the severity of visual hallucinations (P = 0.005). Six patients with dementia with Lewy bodies experienced visual hallucination-like phosphenes (for example, seeing people or figures on stimulation) compared with none of the controls (P = 0.02). Conclusions Increased visual cortical excitability in dementia with Lewy bodies does not appear to explain visual hallucinations but it may be a marker for their severity. PMID:22016436

BDNF-Val66Met-Polymorphism Impact on Cortical Plasticity in Schizophrenia Patients: A Proof-of-Concept Study

PubMed Central

Nitsche, Michael A.; Wobrock, Thomas; Bunse, Tilmann; Rein, Bettina; Herrmann, Maximiliane; Schmitt, Andrea; Nieratschker, Vanessa; Witt, Stephanie H.; Rietschel, Marcella; Falkai, Peter; Hasan, Alkomiet

2015-01-01

Background: Brain-derived neurotrophic factor (BDNF) has been shown to be a moderator of neuroplasticity. A frequent BDNF-polymorphism (Val66Met) is associated with impairments of cortical plasticity. In patients with schizophrenia, reduced neuroplastic responses following non-invasive brain stimulation have been reported consistently. Various studies have indicated a relationship between the BDNF-Val66Met-polymorphism and motor-cortical plasticity in healthy individuals, but schizophrenia patients have yet to be investigated. The aim of this proof-of-concept study was, therefore, to test the impact of the BDNF-Val66Met-polymorphism on inhibitory and facilitatory cortical plasticity in schizophrenia patients. Methods: Cortical plasticity was investigated in 22 schizophrenia patients and 35 healthy controls using anodal and cathodal transcranial direct-current stimulation (tDCS) applied to the left primary motor cortex. Animal and human research indicates that excitability shifts following anodal and cathodal tDCS are related to molecular long-term potentiation and long-term depression. To test motor-cortical excitability before and after tDCS, well-established single- and paired-pulse transcranial magnetic stimulation protocols were applied. Results: Our analysis revealed increased glutamate-mediated intracortical facilitation in met-heterozygotes compared to val-homozygotes at baseline. Following cathodal tDCS, schizophrenia met-heterozygotes had reduced gamma-amino-butyric-acid-mediated short-interval intracortical inhibition, whereas healthy met-heterozygotes displayed the opposite effect. The BDNF-Val66Met-polymorphism did not influence single-pulse motor-evoked potential amplitudes after tDCS. Conclusions: These preliminary findings support the notion of an association of the BDNF-Val66Met-polymorphism with observable alterations in plasticity following cathodal tDCS in schizophrenia patients. This indicates a complex interaction between inhibitory intracortical interneuron-networks, cortical plasticity, and the BDNF-Val66Met-polymorphism. Further replication and validation need to be dedicated to this question to confirm this relationship. PMID:25612896

M30. Cortical Thickness Patterns of Cognitive Impairment in Schizophrenia

PubMed Central

Pinnock, Farena; Hanford, Lindsay; Heinrichs, R. Walter

2017-01-01

Abstract Background: Schizophrenia is characterized by both psychotic illness and cognitive impairment, but it is unclear whether they represent related yet distinct disease processes. There is evidence to suggest dissociation. For example, cognitive impairment occurs in schizophrenia patients during both active psychosis and symptom remission. However, the shared or nonshared neural underpinnings of cognition and psychotic psychopathology are also unclear despite findings of multi-focal cortical thinning in the illness. Accordingly, this study sampled patients and controls with a broad range of cognitive ability to examine relations between cortical thickness and cognitive performance with and without the presence of psychotic illness. Our basic questions were: do regional thickness values primarily index the psychotic disease process or cognitive performance and to what extent do disease and performance interact? Methods: Cognitive functioning of patients diagnosed with schizophrenia or schizoaffective disorder (n = 61) and healthy controls (n = 40) were assessed with the MATRICS Consensus Cognitive Battery (MCCB). Neuroimaging data were obtained with a 3T General Electric System MRI scanner, and cortical thickness was calculated using Freesurfer. General linear models were conducted to examine relations and interactions between cortical thickness, diagnosis, and cognition. Results: Cortical thickness and cognitive performance on MCCB subscales and overall composite score were positively correlated in 34 brain regions, predominantly in the frontal, parietal, and temporal brain areas, irrespective of diagnostic status. Patients showed the same cortical thickness-cognitive performance relationship as controls, but had significantly reduced thickness in 27/34 of these regions despite similar behavioral performance. An interaction of diagnosis, cognition, and cortical thickness was found in the parahippocampal and left caudal middle frontal gyri only. Lastly, there were several regions of reduced cortical thickness among patients with no corresponding relationship to cognitive performance. Conclusion: These findings suggest that despite their high rates of co-occurrence, cognitive impairment and psychosis may be partially independent pathologies of the schizophrenia disease process. Cortical thickness varies with cognition in both schizophrenia patients and healthy controls, but remains significantly reduced in patients. This occurs even when cognitive performance is largely equalized between patients and controls. These findings are consistent with recent neurogenetic research linking liability to schizophrenia with cortical abnormalities including thinning, reduced synaptic structure and excessive pruning. The results point to the importance of studying cognition and psychotic symptoms as potentially separable processes that may also represent independent treatment targets.

Cortical Abnormalities Associated With Pediatric and Adult Obsessive-Compulsive Disorder: Findings From the ENIGMA Obsessive-Compulsive Disorder Working Group.

PubMed

Boedhoe, Premika S W; Schmaal, Lianne; Abe, Yoshinari; Alonso, Pino; Ameis, Stephanie H; Anticevic, Alan; Arnold, Paul D; Batistuzzo, Marcelo C; Benedetti, Francesco; Beucke, Jan C; Bollettini, Irene; Bose, Anushree; Brem, Silvia; Calvo, Anna; Calvo, Rosa; Cheng, Yuqi; Cho, Kang Ik K; Ciullo, Valentina; Dallaspezia, Sara; Denys, Damiaan; Feusner, Jamie D; Fitzgerald, Kate D; Fouche, Jean-Paul; Fridgeirsson, Egill A; Gruner, Patricia; Hanna, Gregory L; Hibar, Derrek P; Hoexter, Marcelo Q; Hu, Hao; Huyser, Chaim; Jahanshad, Neda; James, Anthony; Kathmann, Norbert; Kaufmann, Christian; Koch, Kathrin; Kwon, Jun Soo; Lazaro, Luisa; Lochner, Christine; Marsh, Rachel; Martínez-Zalacaín, Ignacio; Mataix-Cols, David; Menchón, José M; Minuzzi, Luciano; Morer, Astrid; Nakamae, Takashi; Nakao, Tomohiro; Narayanaswamy, Janardhanan C; Nishida, Seiji; Nurmi, Erika; O'Neill, Joseph; Piacentini, John; Piras, Fabrizio; Piras, Federica; Reddy, Y C Janardhan; Reess, Tim J; Sakai, Yuki; Sato, Joao R; Simpson, H Blair; Soreni, Noam; Soriano-Mas, Carles; Spalletta, Gianfranco; Stevens, Michael C; Szeszko, Philip R; Tolin, David F; van Wingen, Guido A; Venkatasubramanian, Ganesan; Walitza, Susanne; Wang, Zhen; Yun, Je-Yeon; Thompson, Paul M; Stein, Dan J; van den Heuvel, Odile A

2018-05-01

Brain imaging studies of structural abnormalities in OCD have yielded inconsistent results, partly because of limited statistical power, clinical heterogeneity, and methodological differences. The authors conducted meta- and mega-analyses comprising the largest study of cortical morphometry in OCD ever undertaken. T 1 -weighted MRI scans of 1,905 OCD patients and 1,760 healthy controls from 27 sites worldwide were processed locally using FreeSurfer to assess cortical thickness and surface area. Effect sizes for differences between patients and controls, and associations with clinical characteristics, were calculated using linear regression models controlling for age, sex, site, and intracranial volume. In adult OCD patients versus controls, we found a significantly lower surface area for the transverse temporal cortex and a thinner inferior parietal cortex. Medicated adult OCD patients also showed thinner cortices throughout the brain. In pediatric OCD patients compared with controls, we found significantly thinner inferior and superior parietal cortices, but none of the regions analyzed showed significant differences in surface area. However, medicated pediatric OCD patients had lower surface area in frontal regions. Cohen's d effect sizes varied from -0.10 to -0.33. The parietal cortex was consistently implicated in both adults and children with OCD. More widespread cortical thickness abnormalities were found in medicated adult OCD patients, and more pronounced surface area deficits (mainly in frontal regions) were found in medicated pediatric OCD patients. These cortical measures represent distinct morphological features and may be differentially affected during different stages of development and illness, and possibly moderated by disease profile and medication.

Language Mapping Using fMRI and Direct Cortical Stimulation for Brain Tumor Surgery

PubMed Central

Brennan, Nicole Petrovich; Peck, Kyung K.; Holodny, Andrei

2016-01-01

Language functional magnetic resonance imaging for neurosurgical planning is a useful but nuanced technique. Consideration of primary and secondary language anatomy, task selection, and data analysis choices all impact interpretation. In the following chapter, we consider practical considerations and nuances alike for language functional magnetic resonance imaging in the support of and comparison with the neurosurgical gold standard, direct cortical stimulation. Pitfalls and limitations are discussed. PMID:26848555

Adaptive neuron-to-EMG decoder training for FES neuroprostheses

NASA Astrophysics Data System (ADS)

Ethier, Christian; Acuna, Daniel; Solla, Sara A.; Miller, Lee E.

2016-08-01

Objective. We have previously demonstrated a brain-machine interface neuroprosthetic system that provided continuous control of functional electrical stimulation (FES) and restoration of grasp in a primate model of spinal cord injury (SCI). Predicting intended EMG directly from cortical recordings provides a flexible high-dimensional control signal for FES. However, no peripheral signal such as force or EMG is available for training EMG decoders in paralyzed individuals. Approach. Here we present a method for training an EMG decoder in the absence of muscle activity recordings; the decoder relies on mapping behaviorally relevant cortical activity to the inferred EMG activity underlying an intended action. Monkeys were trained at a 2D isometric wrist force task to control a computer cursor by applying force in the flexion, extension, ulnar, and radial directions and execute a center-out task. We used a generic muscle force-to-endpoint force model based on muscle pulling directions to relate each target force to an optimal EMG pattern that attained the target force while minimizing overall muscle activity. We trained EMG decoders during the target hold periods using a gradient descent algorithm that compared EMG predictions to optimal EMG patterns. Main results. We tested this method both offline and online. We quantified both the accuracy of offline force predictions and the ability of a monkey to use these real-time force predictions for closed-loop cursor control. We compared both offline and online results to those obtained with several other direct force decoders, including an optimal decoder computed from concurrently measured neural and force signals. Significance. This novel approach to training an adaptive EMG decoder could make a brain-control FES neuroprosthesis an effective tool to restore the hand function of paralyzed individuals. Clinical implementation would make use of individualized EMG-to-force models. Broad generalization could be achieved by including data from multiple grasping tasks in the training of the neuron-to-EMG decoder. Our approach would make it possible for persons with SCI to grasp objects with their own hands, using near-normal motor intent.

Electrophysiological Mapping of Novel Prefrontal – Cerebellar Pathways

PubMed Central

Watson, Thomas C.; Jones, Matthew W.; Apps, Richard

2009-01-01

Whilst the cerebellum is predominantly considered a sensorimotor control structure, accumulating evidence suggests that it may also subserve non-motor functions during cognition. However, this possibility is not universally accepted, not least because the nature and pattern of links between higher cortical structures and the cerebellum are poorly characterized. We have therefore used in vivo electrophysiological methods in anaesthetized rats to directly investigate connectivity between the medial prefrontal cortex (prelimbic subdivision, PrL) and the cerebellum. Stimulation of deep layers of PrL evoked distinct field potentials in the cerebellar cortex with a mean latency to peak of approximately 35 ms. These responses showed a well-defined topography, and were maximal in lobule VII of the contralateral vermis (a known oculomotor centre); they were not attenuated by local anaesthesia of the overlying M2 motor cortex, though M2 stimulation did evoke field potentials in lobule VII with a shorter latency (approximately 30 ms). Single unit recordings showed that prelimbic cortical stimulation elicits complex spikes in lobule VII Purkinje cells, indicating transmission via a previously undescribed cerebro-olivocerebellar pathway. Our results therefore establish a physiological basis for communication between PrL and the cerebellum. The role(s) of this pathway remain to be resolved, but presumably relate to control of eye movements and/or distributed networks associated with integrated prefrontal cortical functions. PMID:19738932

Estimation of locomotion speed and directions changes to control a vehicle using neural signals from the motor cortex of rat.

PubMed

Fukayama, Osamu; Taniguchi, Noriyuki; Suzuki, Takafumi; Mabuchi, Kunihiko

2006-01-01

We have developed a brain-machine interface (BMI) in the form of a small vehicle, which we call the RatCar. In this system, we implanted wire electrodes in the motor cortices of rat's brain to continuously record neural signals. We applied a linear model to estimate the locomotion state (e.g., speed and directions) of a rat using a weighted summation model for the neural firing rates. With this information, we then determined the approximate movement of a rat. Although the estimation is still imprecise, results suggest that our model is able to control the system to some degree. In this paper, we give an overview of our system and describe the methods used, which include continuous neural recording, spike detection and a discrimination algorithm, and a locomotion estimation model minimizes the square error of the locomotion speed and changes in direction.

Does an intraneural interface short-term implant for robotic hand control modulate sensorimotor cortical integration? An EEG-TMS co-registration study on a human amputee.

PubMed

Ferreri, F; Ponzo, D; Vollero, L; Guerra, A; Di Pino, G; Petrichella, S; Benvenuto, A; Tombini, M; Rossini, L; Denaro, L; Micera, S; Iannello, G; Guglielmelli, E; Denaro, V; Rossini, P M

2014-01-01

Following limb amputation, central and peripheral nervous system relays partially maintain their functions and can be exploited for interfacing prostheses. The aim of this study is to investigate, for the first time by means of an EEG-TMS co-registration study, whether and how direct bidirectional connection between brain and hand prosthesis impacts on sensorimotor cortical topography. Within an experimental protocol for robotic hand control, a 26 years-old, left-hand amputated male was selected to have implanted four intrafascicular electrodes (tf-LIFEs-4) in the median and ulnar nerves of the stump for 4 weeks. Before tf-LIFE-4s implant (T0) and after the training period, once electrodes have been removed (T1), experimental subject's cortico-cortical excitability, connectivity and plasticity were tested via a neuronavigated EEG-TMS experiment. The statistical analysis clearly demonstrated a significant modulation (with t-test p < 0.0001) of EEG activity between 30 and 100 ms post-stimulus for the stimulation of the right hemisphere. When studying individual latencies in that time range, a global amplitude modulation was found in most of the TMS-evoked potentials; particularly, the GEE analysis showed significant differences between T0 and T1 condition at 30 ms (p < 0.0404), 46 ms (p < 0.0001) and 60 ms (p < 0.007) latencies. Finally, also a clear local decrement in N46 amplitude over C4 was evident. No differences between conditions were observed for the stimulation of the left hemisphere. The results of this study confirm the hypothesis that bidirectional neural interface could redirect cortical areas -deprived of their original input/output functions- toward restorative neuroplasticity. This reorganization strongly involves bi-hemispheric networks and intracortical and transcortical modulation of GABAergic inhibition.

Cortical inhibitory and excitatory function in drug-naive generalized anxiety disorder.

PubMed

Li, Cheng-Ta; Lu, Chia-Feng; Lin, Hui-Ching; Huang, Ying-Zu; Juan, Chi-Hung; Su, Tung-Ping; Bai, Ya-Mei; Chen, Mu-Hong; Lin, Wei-Chen

A growing body of evidence suggests that deficits in GABAergic inhibitory and glutamatergic excitatory neurotransmission may be involved in the core pathophysiology of generalized anxiety disorder (GAD), a disease characterized by pathological anxious worrying. The aim of the present study was to measure motor cortical excitability by paired-pulse transcranial magnetic stimulation (ppTMS) in patients with GAD. ppTMS measurements of excitation and inhibition from bilateral motor cortices were investigated in 26 right-handed GAD patients who were drug-naïve (half of them with a comorbidity of major depressive disorder) and 35 right-handed age- and sex-matched healthy controls. Short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), and long-interval intracortical inhibition (LICI) were studied; evidence indicated that these are mainly mediated by GABA-A receptors, glutamate receptors, and GABA-B receptors, respectively. After correcting for multiple comparisons, GAD patients had significantly lower left ICF (p < 0.001, Cohen's d = 1.348) and right ICF (p = 0.001, Cohen's d = 0.963), but not SICI and LICI, than did healthy controls. No significant difference of the ICF values was found between GAD with and without depressive disorders. Multivariate linear regression analysis revealed that left ICF (B = -4.990, 95% CI = -8.821 to -1.039, p = 0.007) and group (B = 13.179, 95% CI = 10.208 to 16.149, p = 0.001) predicted anxiety symptoms significantly. The present study provided direct evidence to support that generalized anxiety disorder is characterized by impaired intra-cortical facilitation of motor cortex, suggesting glutamate-related excitatory dysfunction may play a key role in pathological anxiety. Copyright © 2016 Elsevier Inc. All rights reserved.

The effects of cutting parameters on cutting forces and heat generation when drilling animal bone and biomechanical test materials.

PubMed

Cseke, Akos; Heinemann, Robert

2018-01-01

The research presented in this paper investigated the effects of spindle speed and feed rate on the resultant cutting forces (thrust force and torque) and temperatures while drilling SawBones ® biomechanical test materials and cadaveric cortical bone (bovine and porcine femur) specimens. It also investigated cortical bone anisotropy on the cutting forces, when drilling in axial and radial directions. The cutting forces are only affected by the feed rate, whereas the cutting temperature in contrast is affected by both spindle speed and feed rate. The temperature distribution indicates friction as the primary heat source, which is caused by the rubbing of the tool margins and the already cut chips over the borehole wall. Cutting forces were considerably higher when drilling animal cortical bone, in comparison to cortical test material. Drilling direction, and therewith anisotropy, appears to have a negligible effect on the cutting forces. The results suggest that this can be attributed to the osteons being cut at an angle rather than in purely axial or radial direction, as a result of a twist drill's point angle. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

Brain-derived neurotrophic factor promoter methylation and cortical thickness in recurrent major depressive disorder.

PubMed

Na, Kyoung-Sae; Won, Eunsoo; Kang, June; Chang, Hun Soo; Yoon, Ho-Kyoung; Tae, Woo Suk; Kim, Yong-Ku; Lee, Min-Soo; Joe, Sook-Haeng; Kim, Hyun; Ham, Byung-Joo

2016-02-15

Recent studies have reported that methylation of the brain-derived neurotrophic factor (BDNF) gene promoter is associated with major depressive disorder (MDD). This study aimed to investigate the association between cortical thickness and methylation of BDNF promoters as well as serum BDNF levels in MDD. The participants consisted of 65 patients with recurrent MDD and 65 age- and gender-matched healthy controls. Methylation of BDNF promoters and cortical thickness were compared between the groups. The right medial orbitofrontal, right lingual, right lateral occipital, left lateral orbitofrontal, left pars triangularis, and left lingual cortices were thinner in patients with MDD than in healthy controls. Among the MDD group, right pericalcarine, right medical orbitofrontal, right rostral middle frontal, right postcentral, right inferior temporal, right cuneus, right precuneus, left frontal pole, left superior frontal, left superior temporal, left rostral middle frontal and left lingual cortices had inverse correlations with methylation of BDNF promoters. Higher levels of BDNF promoter methylation may be closely associated with the reduced cortical thickness among patients with MDD. Serum BDNF levels were significantly lower in MDD, and showed an inverse relationship with BDNF methylation only in healthy controls. Particularly the prefrontal and occipital cortices seem to indicate key regions in which BDNF methylation has a significant effect on structure.

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.

Auditory cortical function during verbal episodic memory encoding in Alzheimer's disease.

PubMed

Dhanjal, Novraj S; Warren, Jane E; Patel, Maneesh C; Wise, Richard J S

2013-02-01

Episodic memory encoding of a verbal message depends upon initial registration, which requires sustained auditory attention followed by deep semantic processing of the message. Motivated by previous data demonstrating modulation of auditory cortical activity during sustained attention to auditory stimuli, we investigated the response of the human auditory cortex during encoding of sentences to episodic memory. Subsequently, we investigated this response in patients with mild cognitive impairment (MCI) and probable Alzheimer's disease (pAD). Using functional magnetic resonance imaging, 31 healthy participants were studied. The response in 18 MCI and 18 pAD patients was then determined, and compared to 18 matched healthy controls. Subjects heard factual sentences, and subsequent retrieval performance indicated successful registration and episodic encoding. The healthy subjects demonstrated that suppression of auditory cortical responses was related to greater success in encoding heard sentences; and that this was also associated with greater activity in the semantic system. In contrast, there was reduced auditory cortical suppression in patients with MCI, and absence of suppression in pAD. Administration of a central cholinesterase inhibitor (ChI) partially restored the suppression in patients with pAD, and this was associated with an improvement in verbal memory. Verbal episodic memory impairment in AD is associated with altered auditory cortical function, reversible with a ChI. Although these results may indicate the direct influence of pathology in auditory cortex, they are also likely to indicate a partially reversible impairment of feedback from neocortical systems responsible for sustained attention and semantic processing. Copyright © 2012 American Neurological Association.

Cellular and laminar expression of Dab-1 during the postnatal critical period in cat visual cortex and the effects of dark rearing.

PubMed

Kiser, Paul J; Liu, Zijing; Wilt, Steven D; Mower, George D

2011-04-06

This study describes postnatal critical period changes in cellular and laminar expression of Dab-1, a gene shown to play a role in controlling neuronal positioning during embryonic brain development, in cat visual cortex and the effects of dark rearing (DR). At 1week, there is dense cellular staining which is uniform across cortical layers and very light neuropil staining. At the peak of the critical period (5weeks), dense cell staining is largely restricted to large pyramidal cells of deep layer III and layer V, there is faint cell body staining throughout all cortical layers, neuropil staining is markedly increased and uniform in layers III to VI. This dramatic change in laminar and cellular labeling is independent of visual input, since immunostaining is similar in 5-week DR cats. By 10weeks, the mature laminar and cellular staining pattern is established and the major subsequent change is a further reduction in the density of cellular staining in all cortical layers. Neuropil staining is pronounced and uniform across cortical layers. These developmental changes are altered by DR. Quantification by cell counts indicated that age and DR interact such that differences in cellular expression are opposite in direction between 5- and 20-week-old cats. This bidirectional regulation of cellular expression is the same in all cortical laminae. The bidirectional regulation of cellular expression matches the effects of age and DR on physiological plasticity during the critical period as assessed by ocular dominance shifts in response to monocular deprivation. Copyright © 2011 Elsevier B.V. All rights reserved.

The frequency modulated auditory evoked response (FMAER), a technical advance for study of childhood language disorders: cortical source localization and selected case studies

PubMed Central

2013-01-01

Background Language comprehension requires decoding of complex, rapidly changing speech streams. Detecting changes of frequency modulation (FM) within speech is hypothesized as essential for accurate phoneme detection, and thus, for spoken word comprehension. Despite past demonstration of FM auditory evoked response (FMAER) utility in language disorder investigations, it is seldom utilized clinically. This report's purpose is to facilitate clinical use by explaining analytic pitfalls, demonstrating sites of cortical origin, and illustrating potential utility. Results FMAERs collected from children with language disorders, including Developmental Dysphasia, Landau-Kleffner syndrome (LKS), and autism spectrum disorder (ASD) and also normal controls - utilizing multi-channel reference-free recordings assisted by discrete source analysis - provided demonstratrions of cortical origin and examples of clinical utility. Recordings from inpatient epileptics with indwelling cortical electrodes provided direct assessment of FMAER origin. The FMAER is shown to normally arise from bilateral posterior superior temporal gyri and immediate temporal lobe surround. Childhood language disorders associated with prominent receptive deficits demonstrate absent left or bilateral FMAER temporal lobe responses. When receptive language is spared, the FMAER may remain present bilaterally. Analyses based upon mastoid or ear reference electrodes are shown to result in erroneous conclusions. Serial FMAER studies may dynamically track status of underlying language processing in LKS. FMAERs in ASD with language impairment may be normal or abnormal. Cortical FMAERs can locate language cortex when conventional cortical stimulation does not. Conclusion The FMAER measures the processing by the superior temporal gyri and adjacent cortex of rapid frequency modulation within an auditory stream. Clinical disorders associated with receptive deficits are shown to demonstrate absent left or bilateral responses. Serial FMAERs may be useful for tracking language change in LKS. Cortical FMAERs may augment invasive cortical language testing in epilepsy surgical patients. The FMAER may be normal in ASD and other language disorders when pathology spares the superior temporal gyrus and surround but presumably involves other brain regions. Ear/mastoid reference electrodes should be avoided and multichannel, reference free recordings utilized. Source analysis may assist in better understanding of complex FMAER findings. PMID:23351174

Cortical inhibition deficits in recent onset PTSD after a single prolonged trauma exposure☆

PubMed Central

Qi, Shun; Mu, Yunfeng; Liu, Kang; Zhang, Jian; Huan, Yi; Tan, Qingrong; Shi, Mei; Wang, Qiang; Chen, Yunchun; Wang, Huaihai; Wang, Huaning; Zhang, Nanyin; Zhang, Xiaoliang; Xiong, Lize; Yin, Hong

2013-01-01

A variety of structural abnormalities have been described in post traumatic stress disorder (PTSD), but only a few studies have focused on cortical thickness alterations in recent onset PTSD. In this study, we adopted surface-based morphometry (SBM), which enables an exploration of global structural changes throughout the brain, in order to compare cortical thickness alterations in recent onset PTSD patients, trauma-exposed subjects but without PTSD, and normal controls. Moreover, we used region of interest (ROI) partial correlation analysis to evaluate the correlation among PTSD symptom severity and significant changes of cortical thickness. The widespread cortical thickness reduction relative to the normal controls were found in bilateral inferior and superior parietal lobes, frontal lobes, hippocampus, cingulate cortex, and right lateral occipital lobes in trauma survivors, whereas cortical thickness was only increased in left calcarine cortex in PTSD group. The average cortical thickness of hippocampus and cingulate cortex decreased by 10.75% and 9.09% in PTSD, 3.48% and 2.86% in non PTSD. We further demonstrated that the cortical thicknesses of bilateral ACC and PCC, superior frontal lobes, and hippocampus are negatively correlated with CAPS scores in all trauma survivors. Our study results suggest that stress widens cortical thinning regions and causes more serious effect in recent onset PTSD than non PTSD. It also shows that the cortical thinning in recent onset PTSD predicts the symptom severity. PMID:24273707

Structural Alteration of the Dorsal Visual Network in DLB Patients with Visual Hallucinations: A Cortical Thickness MRI Study

PubMed Central

Delli Pizzi, Stefano; Franciotti, Raffaella; Tartaro, Armando; Caulo, Massimo; Thomas, Astrid; Onofrj, Marco; Bonanni, Laura

2014-01-01

Visual hallucinations (VH) represent one of the core features in discriminating dementia with Lewy bodies (DLB) from Alzheimer’s Disease (AD). Previous studies reported that in DLB patients functional alterations of the parieto-occipital regions were correlated with the presence of VH. The aim of our study was to assess whether morphological changes in specific cortical regions of DLB could be related to the presence and severity of VH. We performed a cortical thickness analysis on magnetic resonance imaging data in a cohort including 18 DLB patients, 15 AD patients and 14 healthy control subjects. Relatively to DLB group, correlation analysis between the cortical thickness and the Neuropsychiatric Inventory (NPI) hallucination item scores was also performed. Cortical thickness was reduced bilaterally in DLB compared to controls in the pericalcarine and lingual gyri, cuneus, precuneus, superior parietal gyrus. Cortical thinning was found bilaterally in AD compared to controls in temporal cortex including the superior and middle temporal gyrus, part of inferior temporal cortex, temporal pole and insula. Inferior parietal and supramarginal gyri were also affected bilaterally in AD as compared to controls. The comparison between DLB and AD evidenced cortical thinning in DLB group in the right posterior regions including superior parietal gyrus, precuneus, cuneus, pericalcarine and lingual gyri. Furthermore, the correlation analysis between cortical thickness and NPI hallucination item scores showed that the structural alteration in the dorsal visual regions including superior parietal gyrus and precuneus closely correlated with the occurrence and severity of VH. We suggest that structural changes in key regions of the dorsal visual network may play a crucial role in the physiopathology of VH in DLB patients. PMID:24466177

Control of Somatosensory Cortical Processing by Thalamic Posterior Medial Nucleus: A New Role of Thalamus in Cortical Function

PubMed Central

Castejon, Carlos; Barros-Zulaica, Natali; Nuñez, Angel

2016-01-01

Current knowledge of thalamocortical interaction comes mainly from studying lemniscal thalamic systems. Less is known about paralemniscal thalamic nuclei function. In the vibrissae system, the posterior medial nucleus (POm) is the corresponding paralemniscal nucleus. POm neurons project to L1 and L5A of the primary somatosensory cortex (S1) in the rat brain. It is known that L1 modifies sensory-evoked responses through control of intracortical excitability suggesting that L1 exerts an influence on whisker responses. Therefore, thalamocortical pathways targeting L1 could modulate cortical firing. Here, using a combination of electrophysiology and pharmacology in vivo, we have sought to determine how POm influences cortical processing. In our experiments, single unit recordings performed in urethane-anesthetized rats showed that POm imposes precise control on the magnitude and duration of supra- and infragranular barrel cortex whisker responses. Our findings demonstrated that L1 inputs from POm imposed a time and intensity dependent regulation on cortical sensory processing. Moreover, we found that blocking L1 GABAergic inhibition or blocking P/Q-type Ca2+ channels in L1 prevents POm adjustment of whisker responses in the barrel cortex. Additionally, we found that POm was also controlling the sensory processing in S2 and this regulation was modulated by corticofugal activity from L5 in S1. Taken together, our data demonstrate the determinant role exerted by the POm in the adjustment of somatosensory cortical processing and in the regulation of cortical processing between S1 and S2. We propose that this adjustment could be a thalamocortical gain regulation mechanism also present in the processing of information between cortical areas. PMID:26820514

Motor Cortical Plasticity to Training Started in Childhood: The Example of Piano Players.

PubMed

Chieffo, Raffaella; Straffi, Laura; Inuggi, Alberto; Gonzalez-Rosa, Javier J; Spagnolo, Francesca; Coppi, Elisabetta; Nuara, Arturo; Houdayer, Elise; Comi, Giancarlo; Leocani, Letizia

2016-01-01

Converging evidence suggest that motor training is associated with early and late changes of the cortical motor system. Transcranial magnetic stimulation (TMS) offers the possibility to study plastic rearrangements of the motor system in physiological and pathological conditions. We used TMS to characterize long-term changes in upper limb motor cortical representation and interhemispheric inhibition associated with bimanual skill training in pianists who started playing in an early age. Ipsilateral silent period (iSP) and cortical TMS mapping of hand muscles were obtained from 30 strictly right-handed subjects (16 pianists, 14 naïve controls), together with electromyographic recording of mirror movements (MMs) to voluntary hand movements. In controls, motor cortical representation of hand muscles was larger on the dominant (DH) than on the non-dominant hemisphere (NDH). On the contrary, pianists showed symmetric cortical output maps, being their DH less represented than in controls. In naïve subjects, the iSP was smaller on the right vs left abductor pollicis brevis (APB) indicating a weaker inhibition from the NDH to the DH. In pianists, interhemispheric inhibition was more symmetric as their DH was better inhibited than in controls. Electromyographic MMs were observed only in naïve subjects (7/14) and only to voluntary movement of the non-dominant hand. Subjects with MM had a lower iSP area on the right APB compared with all the others. Our findings suggest a more symmetrical motor cortex organization in pianists, both in terms of muscle cortical representation and interhemispheric inhibition. Although we cannot disentangle training-related from preexisting conditions, it is possible that long-term bimanual practice may reshape motor cortical representation and rebalance interhemispheric interactions, which in naïve right-handed subjects would both tend to favour the dominant hemisphere.

Motor Cortical Plasticity to Training Started in Childhood: The Example of Piano Players

PubMed Central

Inuggi, Alberto; Gonzalez-Rosa, Javier J.; Spagnolo, Francesca; Coppi, Elisabetta; Nuara, Arturo; Houdayer, Elise; Comi, Giancarlo; Leocani, Letizia

2016-01-01

Converging evidence suggest that motor training is associated with early and late changes of the cortical motor system. Transcranial magnetic stimulation (TMS) offers the possibility to study plastic rearrangements of the motor system in physiological and pathological conditions. We used TMS to characterize long-term changes in upper limb motor cortical representation and interhemispheric inhibition associated with bimanual skill training in pianists who started playing in an early age. Ipsilateral silent period (iSP) and cortical TMS mapping of hand muscles were obtained from 30 strictly right-handed subjects (16 pianists, 14 naïve controls), together with electromyographic recording of mirror movements (MMs) to voluntary hand movements. In controls, motor cortical representation of hand muscles was larger on the dominant (DH) than on the non-dominant hemisphere (NDH). On the contrary, pianists showed symmetric cortical output maps, being their DH less represented than in controls. In naïve subjects, the iSP was smaller on the right vs left abductor pollicis brevis (APB) indicating a weaker inhibition from the NDH to the DH. In pianists, interhemispheric inhibition was more symmetric as their DH was better inhibited than in controls. Electromyographic MMs were observed only in naïve subjects (7/14) and only to voluntary movement of the non-dominant hand. Subjects with MM had a lower iSP area on the right APB compared with all the others. Our findings suggest a more symmetrical motor cortex organization in pianists, both in terms of muscle cortical representation and interhemispheric inhibition. Although we cannot disentangle training-related from preexisting conditions, it is possible that long-term bimanual practice may reshape motor cortical representation and rebalance interhemispheric interactions, which in naïve right-handed subjects would both tend to favour the dominant hemisphere. PMID:27336584

Cortical atrophy patterns in early Parkinson's disease patients using hierarchical cluster analysis.

PubMed

Uribe, Carme; Segura, Barbara; Baggio, Hugo Cesar; Abos, Alexandra; Garcia-Diaz, Anna Isabel; Campabadal, Anna; Marti, Maria Jose; Valldeoriola, Francesc; Compta, Yaroslau; Tolosa, Eduard; Junque, Carme

2018-05-01

Cortical brain atrophy detectable with MRI in non-demented advanced Parkinson's disease (PD) is well characterized, but its presence in early disease stages is still under debate. We aimed to investigate cortical atrophy patterns in a large sample of early untreated PD patients using a hypothesis-free data-driven approach. Seventy-seven de novo PD patients and 50 controls from the Parkinson's Progression Marker Initiative database with T1-weighted images in a 3-tesla Siemens scanner were included in this study. Mean cortical thickness was extracted from 360 cortical areas defined by the Human Connectome Project Multi-Modal Parcellation version 1.0, and a hierarchical cluster analysis was performed using Ward's linkage method. A general linear model with cortical thickness data was then used to compare clustering groups using FreeSurfer software. We identified two patterns of cortical atrophy. Compared with controls, patients grouped in pattern 1 (n = 33) were characterized by cortical thinning in bilateral orbitofrontal, anterior cingulate, and lateral and medial anterior temporal gyri. Patients in pattern 2 (n = 44) showed cortical thinning in bilateral occipital gyrus, cuneus, superior parietal gyrus, and left postcentral gyrus, and they showed neuropsychological impairment in memory and other cognitive domains. Even in the early stages of PD, there is evidence of cortical brain atrophy. Neuroimaging clustering analysis is able to detect two subgroups of cortical thinning, one with mainly anterior atrophy, and the other with posterior predominance and worse cognitive performance. Copyright © 2018 Elsevier Ltd. All rights reserved.

Wireless Cortical Brain-Machine Interface for Whole-Body Navigation in Primates

NASA Astrophysics Data System (ADS)

Rajangam, Sankaranarayani; Tseng, Po-He; Yin, Allen; Lehew, Gary; Schwarz, David; Lebedev, Mikhail A.; Nicolelis, Miguel A. L.

2016-03-01

Several groups have developed brain-machine-interfaces (BMIs) that allow primates to use cortical activity to control artificial limbs. Yet, it remains unknown whether cortical ensembles could represent the kinematics of whole-body navigation and be used to operate a BMI that moves a wheelchair continuously in space. Here we show that rhesus monkeys can learn to navigate a robotic wheelchair, using their cortical activity as the main control signal. Two monkeys were chronically implanted with multichannel microelectrode arrays that allowed wireless recordings from ensembles of premotor and sensorimotor cortical neurons. Initially, while monkeys remained seated in the robotic wheelchair, passive navigation was employed to train a linear decoder to extract 2D wheelchair kinematics from cortical activity. Next, monkeys employed the wireless BMI to translate their cortical activity into the robotic wheelchair’s translational and rotational velocities. Over time, monkeys improved their ability to navigate the wheelchair toward the location of a grape reward. The navigation was enacted by populations of cortical neurons tuned to whole-body displacement. During practice with the apparatus, we also noticed the presence of a cortical representation of the distance to reward location. These results demonstrate that intracranial BMIs could restore whole-body mobility to severely paralyzed patients in the future.

Abnormal neural activities of directional brain networks in patients with long-term bilateral hearing loss.

PubMed

Xu, Long-Chun; Zhang, Gang; Zou, Yue; Zhang, Min-Feng; Zhang, Dong-Sheng; Ma, Hua; Zhao, Wen-Bo; Zhang, Guang-Yu

2017-10-13

The objective of the study is to provide some implications for rehabilitation of hearing impairment by investigating changes of neural activities of directional brain networks in patients with long-term bilateral hearing loss. Firstly, we implemented neuropsychological tests of 21 subjects (11 patients with long-term bilateral hearing loss, and 10 subjects with normal hearing), and these tests revealed significant differences between the deaf group and the controls. Then we constructed the individual specific virtual brain based on functional magnetic resonance data of participants by utilizing effective connectivity and multivariate regression methods. We exerted the stimulating signal to the primary auditory cortices of the virtual brain and observed the brain region activations. We found that patients with long-term bilateral hearing loss presented weaker brain region activations in the auditory and language networks, but enhanced neural activities in the default mode network as compared with normally hearing subjects. Especially, the right cerebral hemisphere presented more changes than the left. Additionally, weaker neural activities in the primary auditor cortices were also strongly associated with poorer cognitive performance. Finally, causal analysis revealed several interactional circuits among activated brain regions, and these interregional causal interactions implied that abnormal neural activities of the directional brain networks in the deaf patients impacted cognitive function.

Cortical thickness and folding deficits in conduct-disordered adolescents

PubMed Central

Hyatt, Christopher J.; Haney-Caron, Emily; Stevens, Michael C.

2012-01-01

Background Studies of pediatric conduct disorder (CD) have described frontal and temporal lobe structural abnormalities that parallel findings in antisocial adults. The purpose of this study was to examine previously unexplored cortical thickness and folding as markers for brain abnormalities in “pure CD”-diagnosed adolescents. Based on current fronto-temporal theories, we hypothesized that CD youth would have thinner cortex or less cortical folding in temporal and frontal lobes than control subjects. Methods We obtained T1-weighted brain structure images from n=24 control and n=19 CD participants aged 12–18 years, matched by overall gender and age. We measured group differences in cortical thickness and local gyrification index (regional cortical folding measure) using surface-based morphometry with clusterwise correction for multiple comparisons. Results CD participants, when compared with controls, showed both reduced cortical thickness and folding. Thinner cortex was located primarily in posterior brain regions, including left superior temporal and parietal lobes, temporoparietal junction and paracentral lobule, right superior temporal and parietal lobes, temporoparietal junction and precuneus. Folding deficits were located mainly in anterior brain regions and included left insula, ventro- and dorsomedial prefrontal, anterior cingulate and orbitofrontal cortices, temporal lobe, right superior frontal and parietal lobes and paracentral lobule. Conclusions Our findings generally agree with previous CD volumetric studies, but here show the unique contributions of cortical thickness and folding to gray matter reductions in pure CD in different brain regions. PMID:22209639

Brain-Computer Interface with Inhibitory Neurons Reveals Subtype-Specific Strategies.

PubMed

Mitani, Akinori; Dong, Mingyuan; Komiyama, Takaki

2018-01-08

Brain-computer interfaces have seen an increase in popularity due to their potential for direct neuroprosthetic applications for amputees and disabled individuals. Supporting this promise, animals-including humans-can learn even arbitrary mapping between the activity of cortical neurons and movement of prosthetic devices [1-4]. However, the performance of neuroprosthetic device control has been nowhere near that of limb control in healthy individuals, presenting a dire need to improve the performance. One potential limitation is the fact that previous work has not distinguished diverse cell types in the neocortex, even though different cell types possess distinct functions in cortical computations [5-7] and likely distinct capacities to control brain-computer interfaces. Here, we made a first step in addressing this issue by tracking the plastic changes of three major types of cortical inhibitory neurons (INs) during a neuron-pair operant conditioning task using two-photon imaging of IN subtypes expressing GCaMP6f. Mice were rewarded when the activity of the positive target neuron (N+) exceeded that of the negative target neuron (N-) beyond a set threshold. Mice improved performance with all subtypes, but the strategies were subtype specific. When parvalbumin (PV)-expressing INs were targeted, the activity of N- decreased. However, targeting of somatostatin (SOM)- and vasoactive intestinal peptide (VIP)-expressing INs led to an increase of the N+ activity. These results demonstrate that INs can be individually modulated in a subtype-specific manner and highlight the versatility of neural circuits in adapting to new demands by using cell-type-specific strategies. Copyright © 2017 Elsevier Ltd. All rights reserved.

A lexical semantic hub for heteromodal naming in middle fusiform gyrus.

PubMed

Forseth, Kiefer James; Kadipasaoglu, Cihan Mehmet; Conner, Christopher Richard; Hickok, Gregory; Knight, Robert Thomas; Tandon, Nitin

2018-07-01

Semantic memory underpins our understanding of objects, people, places, and ideas. Anomia, a disruption of semantic memory access, is the most common residual language disturbance and is seen in dementia and following injury to temporal cortex. While such anomia has been well characterized by lesion symptom mapping studies, its pathophysiology is not well understood. We hypothesize that inputs to the semantic memory system engage a specific heteromodal network hub that integrates lexical retrieval with the appropriate semantic content. Such a network hub has been proposed by others, but has thus far eluded precise spatiotemporal delineation. This limitation in our understanding of semantic memory has impeded progress in the treatment of anomia. We evaluated the cortical structure and dynamics of the lexical semantic network in driving speech production in a large cohort of patients with epilepsy using electrocorticography (n = 64), functional MRI (n = 36), and direct cortical stimulation (n = 30) during two generative language processes that rely on semantic knowledge: visual picture naming and auditory naming to definition. Each task also featured a non-semantic control condition: scrambled pictures and reversed speech, respectively. These large-scale data of the left, language-dominant hemisphere uniquely enable convergent, high-resolution analyses of neural mechanisms characterized by rapid, transient dynamics with strong interactions between distributed cortical substrates. We observed three stages of activity during both visual picture naming and auditory naming to definition that were serially organized: sensory processing, lexical semantic processing, and articulation. Critically, the second stage was absent in both the visual and auditory control conditions. Group activity maps from both electrocorticography and functional MRI identified heteromodal responses in middle fusiform gyrus, intraparietal sulcus, and inferior frontal gyrus; furthermore, the spectrotemporal profiles of these three regions revealed coincident activity preceding articulation. Only in the middle fusiform gyrus did direct cortical stimulation disrupt both naming tasks while still preserving the ability to repeat sentences. These convergent data strongly support a model in which a distinct neuroanatomical substrate in middle fusiform gyrus provides access to object semantic information. This under-appreciated locus of semantic processing is at risk in resections for temporal lobe epilepsy as well as in trauma and strokes that affect the inferior temporal cortex-it may explain the range of anomic states seen in these conditions. Further characterization of brain network behaviour engaging this region in both healthy and diseased states will expand our understanding of semantic memory and further development of therapies directed at anomia.

Hunger-Dependent Enhancement of Food Cue Responses in Mouse Postrhinal Cortex and Lateral Amygdala.

PubMed

Burgess, Christian R; Ramesh, Rohan N; Sugden, Arthur U; Levandowski, Kirsten M; Minnig, Margaret A; Fenselau, Henning; Lowell, Bradford B; Andermann, Mark L

2016-09-07

The needs of the body can direct behavioral and neural processing toward motivationally relevant sensory cues. For example, human imaging studies have consistently found specific cortical areas with biased responses to food-associated visual cues in hungry subjects, but not in sated subjects. To obtain a cellular-level understanding of these hunger-dependent cortical response biases, we performed chronic two-photon calcium imaging in postrhinal association cortex (POR) and primary visual cortex (V1) of behaving mice. As in humans, neurons in mouse POR, but not V1, exhibited biases toward food-associated cues that were abolished by satiety. This emergent bias was mirrored by the innervation pattern of amygdalo-cortical feedback axons. Strikingly, these axons exhibited even stronger food cue biases and sensitivity to hunger state and trial history. These findings highlight a direct pathway by which the lateral amygdala may contribute to state-dependent cortical processing of motivationally relevant sensory cues. Published by Elsevier Inc.

Ultrasonic Wave Properties in Bone Axis Direction of Bovine Cortical Bone

NASA Astrophysics Data System (ADS)

Yamamoto, Kazufumi; Yaoi, Yuichiro; Yamato, Yu; Yanagitan, Takahiko; Matsukawa, Mami; Yamazaki, Kaoru

2008-05-01

Quantitative ultrasonography (QUS) is a good method for measuring elastic properties of bone in vivo. Bovine cortical bone has two typical microstructures, plexiform and Haversian. In this study, the relationship between the speed of sound (SOS) and the hydroxyapatite (HAp) crystallite orientation in the axial direction was investigated in two different aged bovine cortical bones. The dependence of attenuation on anatomical position was also investigated. Two ring-permanent hyphen shaped cortical bone samples were obtained from 36- and 24-month-old bovine femurs. SOS was measured with a conventional ultrasonic pulse system. The integrated intensity of the (0002) peak obtained by X-ray diffraction was determine to evaluate the amount of preferred orientation. Regardless of the age of the bovine femurs, a significant correlation between SOS and the preferred orientation of HAp crystallites was observed in parts of the plexiform structure, and the gradient of the relationship showed a similar tendency. Attenuation seemed to depend on bone microstructure.

Association of IQ Changes and Progressive Brain Changes in Patients With Schizophrenia.

PubMed

Kubota, Manabu; van Haren, Neeltje E M; Haijma, Sander V; Schnack, Hugo G; Cahn, Wiepke; Hulshoff Pol, Hilleke E; Kahn, René S

2015-08-01

Although schizophrenia is characterized by impairments in intelligence and the loss of brain volume, the relationship between changes in IQ and brain measures is not clear. To investigate the association between IQ and brain measures in patients with schizophrenia across time. Case-control longitudinal study at the Department of Psychiatry at the University Medical Center Utrecht, Utrecht, the Netherlands, comparing patients with schizophrenia and healthy control participants between September 22, 2004, and April 17, 2008. Magnetic resonance imaging of the brain and IQ scores were obtained at baseline and the 3-year follow-up. Participants included 84 patients with schizophrenia (mean illness duration, 4.35 years) and 116 age-matched healthy control participants. Associations between changes in IQ and the total brain, cerebral gray matter, cerebral white matter, lateral ventricular, third ventricles, cortical, and subcortical volumes; cortical thickness; and cortical surface area. Cerebral gray matter volume (P = .006) and cortical volume (P = .03) and thickness (P = .02) decreased more in patients with schizophrenia across time compared with control participants. Patients showed additional loss in cortical volume and thickness of the right supramarginal, posterior superior temporal, left supramarginal, left postcentral, and occipital regions (P values were between <.001 and .03 after clusterwise correction). Although IQ increased similarly in patients with schizophrenia and control participants, changes in IQ were negatively correlated with changes in lateral ventricular volume (P = .05) and positively correlated with changes in cortical volume (P = .007) and thickness (P = .004) only in patients with schizophrenia. Positive correlations between changes in IQ and cortical volume and thickness were found globally and in widespread regions across frontal, temporal, and parietal cortices (P values were between <.001 and .03 after clusterwise correction). These findings were independent of symptom severity at follow-up, cannabis use, and the use of cumulative antipsychotic medications during the 3 years of follow-up. Progressive brain tissue loss in schizophrenia is related to relative cognitive decline during the early course of illness.

Transcranial current stimulation focality using disc and ring electrode configurations: FEM analysis

NASA Astrophysics Data System (ADS)

Datta, Abhishek; Elwassif, Maged; Battaglia, Fortunato; Bikson, Marom

2008-06-01

We calculated the electric fields induced in the brain during transcranial current stimulation (TCS) using a finite-element concentric spheres human head model. A range of disc electrode configurations were simulated: (1) distant-bipolar; (2) adjacent-bipolar; (3) tripolar; and three ring designs, (4) belt, (5) concentric ring, and (6) double concentric ring. We compared the focality of each configuration targeting cortical structures oriented normal to the surface ('surface-radial' and 'cross-section radial'), cortical structures oriented along the brain surface ('surface-tangential' and 'cross-section tangential') and non-oriented cortical surface structures ('surface-magnitude' and 'cross-section magnitude'). For surface-radial fields, we further considered the 'polarity' of modulation (e.g. superficial cortical neuron soma hyper/depolarizing). The distant-bipolar configuration, which is comparable with commonly used TCS protocols, resulted in diffuse (un-focal) modulation with bi-directional radial modulation under each electrode and tangential modulation between electrodes. Increasing the proximity of the two electrodes (adjacent-bipolar electrode configuration) increased focality, at the cost of more surface current. At similar electrode distances, the tripolar-electrodes configuration produced comparable peak focality, but reduced radial bi-directionality. The concentric-ring configuration resulted in the highest spatial focality and uni-directional radial modulation, at the expense of increased total surface current. Changing ring dimensions, or use of two concentric rings, allow titration of this balance. The concentric-ring design may thus provide an optimized configuration for targeted modulation of superficial cortical neurons.

Evoked effective connectivity of the human neocortex.

PubMed

Entz, László; Tóth, Emília; Keller, Corey J; Bickel, Stephan; Groppe, David M; Fabó, Dániel; Kozák, Lajos R; Erőss, Loránd; Ulbert, István; Mehta, Ashesh D

2014-12-01

The role of cortical connectivity in brain function and pathology is increasingly being recognized. While in vivo magnetic resonance imaging studies have provided important insights into anatomical and functional connectivity, these methodologies are limited in their ability to detect electrophysiological activity and the causal relationships that underlie effective connectivity. Here, we describe results of cortico-cortical evoked potential (CCEP) mapping using single pulse electrical stimulation in 25 patients undergoing seizure monitoring with subdural electrode arrays. Mapping was performed by stimulating adjacent electrode pairs and recording CCEPs from the remainder of the electrode array. CCEPs reliably revealed functional networks and showed an inverse relationship to distance between sites. Coregistration to Brodmann areas (BA) permitted group analysis. Connections were frequently directional with 43% of early responses and 50% of late responses of connections reflecting relative dominance of incoming or outgoing connections. The most consistent connections were seen as outgoing from motor cortex, BA6-BA9, somatosensory (SS) cortex, anterior cingulate cortex, and Broca's area. Network topology revealed motor, SS, and premotor cortices along with BA9 and BA10 and language areas to serve as hubs for cortical connections. BA20 and BA39 demonstrated the most consistent dominance of outdegree connections, while BA5, BA7, auditory cortex, and anterior cingulum demonstrated relatively greater indegree. This multicenter, large-scale, directional study of local and long-range cortical connectivity using direct recordings from awake, humans will aid the interpretation of noninvasive functional connectome studies. © 2014 Wiley Periodicals, Inc.

Spontaneous cortical activity alternates between motifs defined by regional axonal projections

PubMed Central

Mohajerani, Majid H.; Chan, Allen W.; Mohsenvand, Mostafa; LeDue, Jeffrey; Liu, Rui; McVea, David A.; Boyd, Jamie D.; Wang, Yu Tian; Reimers, Mark; Murphy, Timothy H.

2014-01-01

In lightly anaesthetized or awake adult mice using millisecond timescale voltage sensitive dye imaging, we show that a palette of sensory-evoked and hemisphere-wide activity motifs are represented in spontaneous activity. These motifs can reflect multiple modes of sensory processing including vision, audition, and touch. Similar cortical networks were found with direct cortical activation using channelrhodopsin-2. Regional analysis of activity spread indicated modality specific sources such as primary sensory areas, and a common posterior-medial cortical sink where sensory activity was extinguished within the parietal association area, and a secondary anterior medial sink within the cingulate/secondary motor cortices for visual stimuli. Correlation analysis between functional circuits and intracortical axonal projections indicated a common framework corresponding to long-range mono-synaptic connections between cortical regions. Maps of intracortical mono-synaptic structural connections predicted hemisphere-wide patterns of spontaneous and sensory-evoked depolarization. We suggest that an intracortical monosynaptic connectome shapes the ebb and flow of spontaneous cortical activity. PMID:23974708

Intra-operative multi-site stimulation: Expanding methodology for cortical brain mapping of language functions

PubMed Central

Korn, Akiva; Kirschner, Adi; Perry, Daniella; Hendler, Talma; Ram, Zvi

2017-01-01

Direct cortical stimulation (DCS) is considered the gold-standard for functional cortical mapping during awake surgery for brain tumor resection. DCS is performed by stimulating one local cortical area at a time. We present a feasibility study using an intra-operative technique aimed at improving our ability to map brain functions which rely on activity in distributed cortical regions. Following standard DCS, Multi-Site Stimulation (MSS) was performed in 15 patients by applying simultaneous cortical stimulations at multiple locations. Language functioning was chosen as a case-cognitive domain due to its relatively well-known cortical organization. MSS, performed at sites that did not produce disruption when applied in a single stimulation point, revealed additional language dysfunction in 73% of the patients. Functional regions identified by this technique were presumed to be significant to language circuitry and were spared during surgery. No new neurological deficits were observed in any of the patients following surgery. Though the neuro-electrical effects of MSS need further investigation, this feasibility study may provide a first step towards sophistication of intra-operative cortical mapping. PMID:28700619

Intra-operative multi-site stimulation: Expanding methodology for cortical brain mapping of language functions.

PubMed

Gonen, Tal; Gazit, Tomer; Korn, Akiva; Kirschner, Adi; Perry, Daniella; Hendler, Talma; Ram, Zvi

2017-01-01

Direct cortical stimulation (DCS) is considered the gold-standard for functional cortical mapping during awake surgery for brain tumor resection. DCS is performed by stimulating one local cortical area at a time. We present a feasibility study using an intra-operative technique aimed at improving our ability to map brain functions which rely on activity in distributed cortical regions. Following standard DCS, Multi-Site Stimulation (MSS) was performed in 15 patients by applying simultaneous cortical stimulations at multiple locations. Language functioning was chosen as a case-cognitive domain due to its relatively well-known cortical organization. MSS, performed at sites that did not produce disruption when applied in a single stimulation point, revealed additional language dysfunction in 73% of the patients. Functional regions identified by this technique were presumed to be significant to language circuitry and were spared during surgery. No new neurological deficits were observed in any of the patients following surgery. Though the neuro-electrical effects of MSS need further investigation, this feasibility study may provide a first step towards sophistication of intra-operative cortical mapping.

Cone-beam computed tomography evaluation of the association of cortical plate proximity and apical root resorption after orthodontic treatment.

PubMed

Nakada, Tomoo; Motoyoshi, Mitsuru; Horinuki, Eri; Shimizu, Noriyoshi

2016-01-01

We investigated the effects of proximity of the root apex to the maxillary labial cortical plate, palatal cortical plate, and incisive canal cortical plate on apical root resorption. Cone-beam computed tomography was used to measure the amount of root resorption and root apex movement around maxillary right and left central incisors in 30 adults who underwent four-bicuspid extraction followed by treatment with multibracket appliances. The patients were divided into three groups on the basis of the direction of root apex movement, after which the correlation between the amount of root resorption and root apex movement was determined. Mean apical root resorption was 1.80 ± 0.82 mm (range, 0.18-3.96 mm). The amount of root apex movement was positively correlated with the amount of root resorption on the side of pressure. Root apex proximity to the maxillary labial cortical plate, palatal cortical plate, and incisive canal cortical plate was associated with apical root resorption. Orthodontic treatment plans should carefully consider root proximity to the maxillary cortical plate. (J Oral Sci 58, 231-236, 2016).

Cortical thickness abnormalities in trichotillomania: international multi-site analysis.

PubMed

Chamberlain, Samuel R; Harries, Michael; Redden, Sarah A; Keuthen, Nancy J; Stein, Dan J; Lochner, Christine; Grant, Jon E

2018-06-01

Trichotillomania is a prevalent but often hidden psychiatric condition, characterized by repetitive hair pulling. The aim of this study was to confirm or refute structural brain abnormalities in trichotillomania by pooling all available global data. De-identified MRI scans were pooled by contacting authors of previous studies. Cortical thickness and sub-cortical volumes were compared between patients and controls. Patients (n = 76) and controls (n = 41) were well-matched in terms of demographic characteristics. Trichotillomania patients showed excess cortical thickness in a cluster maximal at right inferior frontal gyrus, unrelated to symptom severity. No significant sub-cortical volume differences were detected in the regions of interest. Morphometric changes in the right inferior frontal gyrus appear to play a central role in the pathophysiology of trichotillomania, and to be trait in nature. The findings are distinct from other impulsive-compulsive disorders (OCD, ADHD, gambling disorder), which have typically been associated with reduced, rather than increased, cortical thickness. Future work should examine sub-cortical and cerebellar morphology using analytic approaches designed for this purpose, and should also characterize grey matter densities/volumes.

Cortical gray and subcortical white matter associations in Parkinson's disease.

PubMed

Sterling, Nicholas W; Du, Guangwei; Lewis, Mechelle M; Swavely, Steven; Kong, Lan; Styner, Martin; Huang, Xuemei

2017-01-01

Cortical atrophy has been documented in both Parkinson's disease (PD) and healthy aging, but its relationship to changes in subcortical white matter is unknown. This was investigated by obtaining T1- and diffusion-weighted images from 76 PD and 70 controls at baseline and 18 and 36 months, from which cortical volumes and underlying subcortical white matter axial diffusivity (AD), radial diffusivity (RD), and fractional anisotropy (FA) were determined. Twelve of 69 cortical subregions had significant group differences, and for these, underlying subcortical white matter was explored. At baseline, higher cortical volumes were significantly correlated with lower underlying subcortical white matter AD, RD, and higher FA (ps ≤ 0.017) in PD. Longitudinally, higher rates of cortical atrophy in PD were associated with increased rates of change in AD RD, and FA values (ps ≤ 0.0013) in 2 subregions explored. The significant gray-white matter associations were not found in controls. Thus, unlike healthy aging, cortical atrophy and subcortical white matter changes may not be independent events in PD. Copyright © 2016 Elsevier Inc. All rights reserved.

Onsite-effects of dual-hemisphere versus conventional single-hemisphere transcranial direct current stimulation: A functional MRI study.

PubMed

Kwon, Yong Hyun; Jang, Sung Ho

2012-08-25

We performed functional MRI examinations in six right-handed healthy subjects. During functional MRI scanning, transcranial direct current stimulation was delivered with the anode over the right primary sensorimotor cortex and the cathode over the left primary sensorimotor cortex using dual-hemispheric transcranial direct current stimulation. This was compared to a cathode over the left supraorbital area using conventional single-hemispheric transcranial direct current stimulation. Voxel counts and blood oxygenation level-dependent signal intensities in the right primary sensorimotor cortex regions were estimated and compared between the two transcranial direct current stimulation conditions. Our results showed that dual-hemispheric transcranial direct current stimulation induced greater cortical activities than single-hemispheric transcranial direct current stimulation. These findings suggest that dual-hemispheric transcranial direct current stimulation may provide more effective cortical stimulation than single-hemispheric transcranial direct current stimulation.

Onsite-effects of dual-hemisphere versus conventional single-hemisphere transcranial direct current stimulation

PubMed Central

Kwon, Yong Hyun; Jang, Sung Ho

2012-01-01

We performed functional MRI examinations in six right-handed healthy subjects. During functional MRI scanning, transcranial direct current stimulation was delivered with the anode over the right primary sensorimotor cortex and the cathode over the left primary sensorimotor cortex using dual-hemispheric transcranial direct current stimulation. This was compared to a cathode over the left supraorbital area using conventional single-hemispheric transcranial direct current stimulation. Voxel counts and blood oxygenation level-dependent signal intensities in the right primary sensorimotor cortex regions were estimated and compared between the two transcranial direct current stimulation conditions. Our results showed that dual-hemispheric transcranial direct current stimulation induced greater cortical activities than single-hemispheric transcranial direct current stimulation. These findings suggest that dual-hemispheric transcranial direct current stimulation may provide more effective cortical stimulation than single-hemispheric transcranial direct current stimulation. PMID:25624815

Cortical Thickness Change in Autism during Early Childhood

PubMed Central

Smith, Elizabeth; Thurm, Audrey; Greenstein, Deanna; Farmer, Cristan; Swedo, Susan; Giedd, Jay; Raznahan, Armin

2016-01-01

Structural magnetic resonance imaging (MRI) scans at high spatial resolution can detect potential foci of early brain dysmaturation in children with autism spectrum disorders (ASD). In addition, comparison between MRI and behavior measures over time can identify patterns of brain change accompanying specific outcomes. We report structural MRI data from two time points for a total of 84 scans in children with ASD and 30 scans in typical controls (mean age time one=4.1 years, mean age at time two=6.6 years). Surface-based cortical morphometry and linear mixed effects models were used to link changes in cortical anatomy to both diagnostic status and individual differences in changes in language and autism severity. Compared to controls, children with ASD showed accelerated gray matter volume gain with age, which was driven by a lack of typical age-related cortical thickness (CT) decrease within ten cortical regions involved in language, social cognition and behavioral control. Greater expressive communication gains with age in children with ASD were associated with greater CT gains in a set of right hemisphere homologues to dominant language cortices, potentially identifying a compensatory system for closer translational study. PMID:27061356

Grey matter abnormalities in social anxiety disorder: a pilot study.

PubMed

Syal, Supriya; Hattingh, Coenraad J; Fouché, Jean-Paul; Spottiswoode, Bruce; Carey, Paul D; Lochner, Christine; Stein, Dan J

2012-09-01

While a number of studies have explored the functional neuroanatomy of social anxiety disorder (SAD), data on grey matter integrity are lacking. We conducted structural MRI scans to examine the cortical thickness of grey matter in individuals with SAD. 13 unmedicated adult patients with a primary diagnosis of generalized social anxiety disorder and 13 demographically (age, gender and education) matched healthy controls underwent 3T structural magnetic resonance imaging. Cortical thickness and subcortical volumes were estimated using an automated algorithm (Freesurfer Version 4.5). Compared to controls, social anxiety disorder patients showed significant bilateral cortical thinning in the fusiform and post central regions. Additionally, right hemisphere specific thinning was found in the frontal, temporal, parietal and insular cortices of individuals with social anxiety disorder. Although uncorrected cortical grey matter volumes were significantly lower in individuals with SAD, we did not detect volumetric differences in corrected amygdala, hippocampal or cortical grey matter volumes across study groups. Structural differences in grey matter thickness between SAD patients and controls highlight the diffuse neuroanatomical networks involved in both social anxiety and social behavior. Additional work is needed to investigate the causal mechanisms involved in such structural abnormalities in SAD.

Definitions of state variables and state space for brain-computer interface : Part 2. Extraction and classification of feature vectors.

PubMed

Freeman, Walter J

2007-06-01

The hypothesis is proposed that the central dynamics of the action-perception cycle has five steps: emergence from an existing macroscopic brain state of a pattern that predicts a future goal state; selection of a mesoscopic frame for action control; execution of a limb trajectory by microscopic spike activity; modification of microscopic cortical spike activity by sensory inputs; construction of mesoscopic perceptual patterns; and integration of a new macroscopic brain state. The basis is the circular causality between microscopic entities (neurons) and the mesoscopic and macroscopic entities (populations) self-organized by axosynaptic interactions. Self-organization of neural activity is bidirectional in all cortices. Upwardly the organization of mesoscopic percepts from microscopic spike input predominates in primary sensory areas. Downwardly the organization of spike outputs that direct specific limb movements is by mesoscopic fields constituting plans to achieve predicted goals. The mesoscopic fields in sensory and motor cortices emerge as frames within macroscopic activity. Part 1 describes the action-perception cycle and its derivative reflex arc qualitatively. Part 2 describes the perceptual limb of the arc from microscopic MSA to mesoscopic wave packets, and from these to macroscopic EEG and global ECoG fields that express experience-dependent knowledge in successive states. These macroscopic states are conceived to embed and control mesoscopic frames in premotor and motor cortices that are observed in local ECoG and LFP of frontoparietal areas. The fields sampled by ECoG and LFP are conceived as local patterns of neural activity in which trajectories of multiple spike activities (MSA) emerge that control limb movements. Mesoscopic frames are located by use of the analytic signal from the Hilbert transform after band pass filtering. The state variables in frames are measured to construct feature vectors by which to describe and classify frame patterns. Evidence is cited to justify use of linear analysis. The aim of the review is to enable researchers to conceive and identify goal-oriented states in brain activity for use as commands, in order to relegate the details of execution to adaptive control devices outside the brain.

Jealousy increased by induced relative left frontal cortical activity.

PubMed

Kelley, Nicholas J; Eastwick, Paul W; Harmon-Jones, Eddie; Schmeichel, Brandon J

2015-10-01

Asymmetric frontal cortical activity may be one key to the process linking social exclusion to jealous feelings. The current research examined the causal role of asymmetric frontal brain activity in modulating jealousy in response to social exclusion. Transcranial direct-current stimulation (tDCS) over the frontal cortex to manipulate asymmetric frontal cortical activity was combined with a modified version of the Cyberball paradigm designed to induce jealousy. After receiving 15 min of tDCS, participants were excluded by a desired partner and reported how jealous they felt. Among individuals who were excluded, tDCS to increase relative left frontal cortical activity caused greater levels of self-reported jealousy compared to tDCS to increase relative right frontal cortical activity or sham stimulation. Limitations concerning the specificity of this effect and implications for the role of the asymmetric prefrontal cortical activity in motivated behaviors are discussed. (c) 2015 APA, all rights reserved).

Prefrontal-limbic connectivity during worry in older adults with generalized anxiety disorder.

PubMed

Mohlman, Jan; Eldreth, Dana A; Price, Rebecca B; Staples, Alison M; Hanson, Catherine

2017-04-01

Although generalized anxiety disorder (GAD) is one of the most prevalent anxiety disorders in older adults, very little is known about the neurobiology of worry, the hallmark symptom of GAD in adults over the age of 60. This study investigated the neurobiology and neural circuitry of worry in older GAD patients and controls. Twenty older GAD patients and 16 age-matched controls (mean age = 67.88) were compared on clinical measures and neural activity during worry using functional magnetic resonance imaging. As expected, worry elicited activation in frontal regions, amygdala, and insula within the GAD group, with a similar but less prominent frontal pattern was observed in controls. Effective connectivity analyses revealed a positive directional circuit in the GAD group extending from ventromedial through dorsolateral prefrontal cortices, converging on the amygdala. A less complex circuit was observed in controls with only dorsolateral prefrontal regions converging on the amygdala; however, a separate circuit passing through the orbitofrontal cortex converged on the insula. Results elucidate a different neurobiology of pathological versus normal worry in later life. A limited resource model is implicated wherein worry in GAD competes for the same neural resources (e.g. prefrontal cortical areas) that are involved in the adaptive regulation of emotion through cognitive and behavioral strategies.

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

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

PubMed

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

2016-04-13

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

Pronounced prefronto-temporal cortical thinning in schizophrenia: Neuroanatomical correlate of suicidal behavior?

PubMed

Besteher, Bianca; Wagner, Gerd; Koch, Kathrin; Schachtzabel, Claudia; Reichenbach, Jürgen R; Schlösser, Ralf; Sauer, Heinrich; Schultz, C Christoph

2016-10-01

Schizophrenia is characterized by increased mortality for which suicidality is the decisive factor. An analysis of cortical thickness and folding to further elucidate neuroanatomical correlates of suicidality in schizophrenia has not yet been performed. We searched for relevant brain regions with such differences between patients with suicide-attempts, patients without any suicidal thoughts and healthy controls. 37 schizophrenia patients (14 suicide-attempters and 23 non-suicidal) and 50 age- and gender-matched healthy controls were included. Suicidality was documented through clinical interview and chart review. All participants underwent T1-weighted MRI scans. Whole brain node-by-node cortical thickness and folding were estimated (FreeSurfer Software) and compared. Additionally a three group comparison for prefrontal regions-of-interest was performed in SPSS using a multifactorial GLM. Compared with the healthy controls patients showed a typical pattern of cortical thinning in prefronto-temporal regions and altered cortical folding in the right medial temporal cortex. Patients with suicidal behavior compared with non-suicidal patients demonstrated pronounced (p<0.05) cortical thinning in the right DLPFC and the superior temporal cortex. Comparing cortical thickness in suicidal patients with non-suicidal patients significant (p<0.05) cortical thinning was additionally found in the right superior and middle temporal, temporopolar and insular cortex. Our findings extend the evidence for neuroanatomical underpinnings of suicidal behaviour in schizophrenia. We identified cortical thinning in a network strongly involved in regulation of impulsivity, emotions and planning of behaviour in suicide attempters, which might lead to neuronal dysregulation in this network and consequently to a higher risk of suicidal behavior. Copyright © 2016 Elsevier B.V. All rights reserved.

Reduced Cortical Thickness and Increased Surface Area in Antisocial Personality Disorder

PubMed Central

Jiang, Weixiong; Li, Gang; Liu, Huasheng; Shi, Feng; Wang, Tao; Shen, Celina; Shen, Hui; Hu, Dewen; Wang, Wei; Shen, Dinggang

2016-01-01

Antisocial Personality Disorder (ASPD), one of whose characteristics is high impulsivity, is of great interest in the field of brain structure and function. However, little is known about possible impairments in the cortical anatomy in ASPD, in terms of cortical thickness and surface area, as well as their possible relationship with impulsivity. In this neuroimaging study, we first investigated the changes of cortical thickness and surface area in ASPD patients, in comparison to those of healthy controls, and then performed correlation analyses between these measures and the ability of impulse control. We found that ASPD patients showed thinner cortex while larger surface area in several specific brain regions, i.e., bilateral superior frontal gyrus, orbitofrontal and triangularis, insula cortex, precuneus, middle frontal gyrus, middle temporal gyrus, and left bank of superior temporal sulcus. In addition, we also found that the ability of impulse control was positively correlated with cortical thickness in the superior frontal gyrus, middle frontal gyrus, orbitofrontal cortex, pars triangularis, superior temporal gyrus, and insula cortex. To our knowledge, this study is the first to reveal simultaneous changes in cortical thickness and surface area in ASPD, as well as their relationship with impulsivity. These cortical structural changes may introduce uncontrolled and callous behavioral characteristic in ASPD patients, and these potential biomarkers may be very helpful in understanding the pathomechanism of ASPD. PMID:27600947

Prefrontal, posterior parietal and sensorimotor network activity underlying speed control during walking

PubMed Central

Bulea, Thomas C.; Kim, Jonghyun; Damiano, Diane L.; Stanley, Christopher J.; Park, Hyung-Soon

2015-01-01

Accumulating evidence suggests cortical circuits may contribute to control of human locomotion. Here, noninvasive electroencephalography (EEG) recorded from able-bodied volunteers during a novel treadmill walking paradigm was used to assess neural correlates of walking. A systematic processing method, including a recently developed subspace reconstruction algorithm, reduced movement-related EEG artifact prior to independent component analysis and dipole source localization. We quantified cortical activity while participants tracked slow and fast target speeds across two treadmill conditions: an active mode that adjusted belt speed based on user movements and a passive mode reflecting a typical treadmill. Our results reveal frequency specific, multi-focal task related changes in cortical oscillations elicited by active walking. Low γ band power, localized to the prefrontal and posterior parietal cortices, was significantly increased during double support and early swing phases, critical points in the gait cycle since the active controller adjusted speed based on pelvis position and swing foot velocity. These phasic γ band synchronizations provide evidence that prefrontal and posterior parietal networks, previously implicated in visuo-spatial and somotosensory integration, are engaged to enhance lower limb control during gait. Sustained μ and β band desynchronization within sensorimotor cortex, a neural correlate for movement, was observed during walking thereby validating our methods for isolating cortical activity. Our results also demonstrate the utility of EEG recorded during locomotion for probing the multi-regional cortical networks which underpin its execution. For example, the cortical network engagement elicited by the active treadmill suggests that it may enhance neuroplasticity for more effective motor training. PMID:26029077

Cholinesterase inhibitors affect brain potentials in amnestic mild cognitive impairment

PubMed Central

Irimajiri, Rie; Michalewski, Henry J; Golob, Edward J; Starr, Arnold

2007-01-01

Amnestic mild cognitive impairment (MCI) is an isolated episodic memory disorder that has a high likelihood of progressing to Alzheimer’s disease. Auditory sensory cortical responses (P50, N100) have been shown to be increased in amplitude in MCI compared to older controls. We tested whether (1) cortical potentials to other sensory modalities (somatosensory and visual) were also affected in MCI and (2) cholinesterase inhibitors (ChEIs), one of the therapies used in this disorder, modulated sensory cortical potentials in MCI. Somatosensory cortical potentials to median nerve stimulation and visual cortical potentials to reversing checkerboard stimulation were recorded from 15 older controls and 15 amnestic MCI subjects (single domain). Results were analyzed as a function of diagnosis (Control, MCI) and ChEIs treatment (Treated MCI, Untreated MCI). Somatosensory and visual potentials did not differ significantly in amplitude in MCI subjects compared to controls. When ChEIs use was considered, somatosensory potentials (N20, P50) but not visual potentials (N70, P100, N150) were of larger amplitude in untreated MCI subjects compared to treated MCI subjects. Three individual MCI subjects showed increased N20 amplitude while off ChEIs compared to while on ChEIs. An enhancement of N20 somatosensory cortical activity occurs in amnestic single domain MCI and is sensitive to modulation by ChEIs. PMID:17320833

Longitudinal Changes in Cortical Thickness in Children after Traumatic Brain Injury and their Relation to Behavioral Regulation and Emotional Control

PubMed Central

Wilde, Elisabeth A.; Merkley, Tricia L.; Bigler, Erin D.; Max, Jeffrey E.; Schmidt, Adam T.; Ayoub, Kareem W.; McCauley, Stephen R.; Hunter, Jill V.; Hanten, Gerri; Li, Xiaoqi; Chu, Zili D.; Levin, Harvey S.

2012-01-01

The purpose of this study was to assess patterns of cortical development over time in children who had sustained traumatic brain injury (TBI) as compared to children with orthopedic injury (OI), and to examine how these patterns related to emotional control and behavioral dysregulation, two common post-TBI symptoms. Cortical thickness was measured at approximately 3 and 18 months post-injury in 20 children aged 8.2 to 17.5 years who had sustained moderate-to-severe closed head injury and 21 children aged 7.4 to 16.7 years who had sustained OI. At approximately 3 months post-injury, the TBI group evidenced decreased cortical thickness bilaterally in aspects of the superior frontal, dorsolateral frontal, orbital frontal, and anterior cingulate regions compared to the control cohort, areas of anticipated vulnerability to TBI-induced change. At 18 months post-injury, some of the regions previously evident at 3 months post-injury remained significantly decreased in the TBI group, including bilateral frontal, fusiform, and lingual regions. Additional regions of significant cortical thinning emerged at this time interval (bilateral frontal regions and fusiform gyrus and left parietal regions). However, differences in other regions appeared attenuated (no longer areas of significant cortical thinning) by 18 months post-injury including large bilateral regions of the medial aspects of the frontal lobes and anterior cingulate. Cortical thinning within the OI group was evident over time in dorsolateral frontal and temporal regions bilaterally and aspects of the left medial frontal and precuneus, and right inferior parietal regions. Longitudinal analyses within the TBI group revealed decreases in cortical thickness over time in numerous aspects throughout the right and left cortical surface, but with notable “sparing” of the right and left frontal and temporal poles, the medial aspects of both the frontal lobes, the left fusiform gyrus, and the cingulate bilaterally. An analysis of longitudinal changes in cortical thickness over time (18 months – 3 months) in the TBI versus OI group demonstrated regions of relative cortical thinning in the TBI group in bilateral superior parietal and right paracentral regions, but relative cortical thickness increases in aspects of the medial orbital frontal lobes and bilateral cingulate and in the right lateral orbital frontal lobe. Finally, findings from analyses correlating the longitudinal cortical thickness changes in TBI with symptom report on the Emotional Control subscale of the Behavior Rating Inventory of Executive Function (BRIEF) demonstrated a region of significant correlation in the right medial frontal and right anterior cingulate gyrus. A region of significant correlation between the longitudinal cortical thickness changes in the TBI group and symptom report on the Behavioral Regulation Index was also seen in the medial aspect of the left frontal lobe. Longitudinal analyses of cortical thickness highlight an important deviation from the expected pattern of developmental change in children and adolescents with TBI, particularly in the medial frontal lobes, where typical patterns of thinning fail to occur over time. Regions which fail to undergo expected cortical thinning in the medial aspects of the frontal lobes correlate with difficulties in emotional control and behavioral regulation, common problems for youth with TBI. Examination of post-TBI brain development in children may be critical to identification of children that may be at risk for persistent problems with executive functioning deficits and the development of interventions to address these issues. PMID:22266409

Characteristics of lesional and extra-lesional cortical grey matter in relapsing-remitting and secondary progressive multiple sclerosis: A magnetisation transfer and diffusion tensor imaging study.

PubMed

Yaldizli, Özgür; Pardini, Matteo; Sethi, Varun; Muhlert, Nils; Liu, Zheng; Tozer, Daniel J; Samson, Rebecca S; Wheeler-Kingshott, Claudia Am; Yousry, Tarek A; Miller, David H; Chard, Declan T

2016-02-01

In multiple sclerosis (MS), diffusion tensor and magnetisation transfer imaging are both abnormal in lesional and extra-lesional cortical grey matter, but differences between clinical subtypes and associations with clinical outcomes have only been partly assessed. To compare mean diffusivity, fractional anisotropy and magnetisation transfer ratio (MTR) in cortical grey matter lesions (detected using phase-sensitive inversion recovery (PSIR) imaging) and extra-lesional cortical grey matter, and assess associations with disability in relapse-onset MS. Seventy-two people with MS (46 relapsing-remitting (RR), 26 secondary progressive (SP)) and 36 healthy controls were included in this study. MTR, mean diffusivity and fractional anisotropy were measured in lesional and extra-lesional cortical grey matter. Mean fractional anisotropy was higher and MTR lower in lesional compared with extra-lesional cortical grey matter. In extra-lesional cortical grey matter mean fractional anisotropy and MTR were lower, and mean diffusivity was higher in the MS group compared with controls. Mean MTR was lower and mean diffusivity was higher in lesional and extra-lesional cortical grey matter in SPMS when compared with RRMS. These differences were independent of disease duration. In multivariate analyses, MTR in extra-lesional more so than lesional cortical grey matter was associated with disability. Magnetic resonance abnormalities in lesional and extra-lesional cortical grey matter are greater in SPMS than RRMS. Changes in extra-lesional compared with lesional cortical grey matter are more consistently associated with disability. © The Author(s), 2015.

An Implantable Neural Sensing Microsystem with Fiber-Optic Data Transmission and Power Delivery

PubMed Central

Park, Sunmee; Borton, David A.; Kang, Mingyu; Nurmikko, Arto V.; Song, Yoon-Kyu

2013-01-01

We have developed a prototype cortical neural sensing microsystem for brain implantable neuroengineering applications. Its key feature is that both the transmission of broadband, multichannel neural data and power required for the embedded microelectronics are provided by optical fiber access. The fiber-optic system is aimed at enabling neural recording from rodents and primates by converting cortical signals to a digital stream of infrared light pulses. In the full microsystem whose performance is summarized in this paper, an analog-to-digital converter and a low power digital controller IC have been integrated with a low threshold, semiconductor laser to extract the digitized neural signals optically from the implantable unit. The microsystem also acquires electrical power and synchronization clocks via optical fibers from an external laser by using a highly efficient photovoltaic cell on board. The implantable unit employs a flexible polymer substrate to integrate analog and digital microelectronics and on-chip optoelectronic components, while adapting to the anatomical and physiological constraints of the environment. A low power analog CMOS chip, which includes preamplifier and multiplexing circuitry, is directly flip-chip bonded to the microelectrode array to form the cortical neurosensor device. PMID:23666130

An Approximation of the Error Backpropagation Algorithm in a Predictive Coding Network with Local Hebbian Synaptic Plasticity

PubMed Central

Whittington, James C. R.; Bogacz, Rafal

2017-01-01

To efficiently learn from feedback, cortical networks need to update synaptic weights on multiple levels of cortical hierarchy. An effective and well-known algorithm for computing such changes in synaptic weights is the error backpropagation algorithm. However, in this algorithm, the change in synaptic weights is a complex function of weights and activities of neurons not directly connected with the synapse being modified, whereas the changes in biological synapses are determined only by the activity of presynaptic and postsynaptic neurons. Several models have been proposed that approximate the backpropagation algorithm with local synaptic plasticity, but these models require complex external control over the network or relatively complex plasticity rules. Here we show that a network developed in the predictive coding framework can efficiently perform supervised learning fully autonomously, employing only simple local Hebbian plasticity. Furthermore, for certain parameters, the weight change in the predictive coding model converges to that of the backpropagation algorithm. This suggests that it is possible for cortical networks with simple Hebbian synaptic plasticity to implement efficient learning algorithms in which synapses in areas on multiple levels of hierarchy are modified to minimize the error on the output. PMID:28333583

Corticospinal activation confounds cerebellar effects of posterior fossa stimuli.

PubMed

Fisher, Karen M; Lai, H Ming; Baker, Mark R; Baker, Stuart N

2009-12-01

To investigate the efficacy of magnetic stimulation over the posterior fossa (PF) as a non-invasive assessment of cerebellar function in man. We replicated a previously reported conditioning-test paradigm in 11 healthy subjects. Transcranial magnetic stimulation (TMS) at varying intensities was applied to the PF and motor cortex with a 3, 5 or 7 ms interstimulus interval (ISI), chosen randomly for each trial. Surface electromyogram (EMG) activity was recorded from two intrinsic hand muscles and two forearm muscles. Responses were averaged and rectified, and MEP amplitudes were compared to assess whether suppression of the motor output occurred as a result of the PF conditioning pulse. Cortical MEPs were suppressed following conditioning-test ISIs of 5 or 7 ms. No suppression occurred with an ISI of 3 ms. PF stimuli alone also produced EMG responses, suggesting direct activation of the corticospinal tract (CST). CST collaterals are known to contact cortical inhibitory interneurones; antidromic CST activation could therefore contribute to the observed suppression of cortical MEPs. PF stimulation probably activates multiple pathways; even at low intensities it should not be regarded as a selective assessment of cerebellar function unless stringent controls can confirm the absence of confounding activity in other pathways.

Organization of cortical microtubules in graviresponding maize roots

NASA Technical Reports Server (NTRS)

Blancaflor, E. B.; Hasenstein, K. H.

1993-01-01

Immunofluorescence labeling of cortical microtubules (MTs) was used to investigate the relationship between MT arrangement and changes in growth rate of the upper and lower sides of horizontally placed roots of maize (Zea mays L. cv. Merit). Cap cells and cells of the elongation zone of roots grown vertically in light or darkness showed MT arrangements that were transverse (perpendicular) to the growth direction. Microtubules of cells basal to the elongation zone typically showed oblique orientation. Two hours after horizontal reorientation, cap cells of gravicompetent, light-grown and curving roots contained MTs parallel to the gravity vector. The MT arrangement on the upper side of the elongation zone remained transverse but the MTs of the outer four to five layers of cortical cells along the lower side of the elongation zone showed reorientation parallel to the axis of the root. The MTs of the lower epidermis retained their transverse orientation. Dark-grown roots did not curve and did not show reorientation of MTs in cells of the root cap or elongation zone. The data indicate that MT depolymerization and reorientation is correlated with reduction in growth rate, and that MT reorientation is one of the steps of growth control of graviresponding roots.

An Approximation of the Error Backpropagation Algorithm in a Predictive Coding Network with Local Hebbian Synaptic Plasticity.

PubMed

Whittington, James C R; Bogacz, Rafal

2017-05-01

To efficiently learn from feedback, cortical networks need to update synaptic weights on multiple levels of cortical hierarchy. An effective and well-known algorithm for computing such changes in synaptic weights is the error backpropagation algorithm. However, in this algorithm, the change in synaptic weights is a complex function of weights and activities of neurons not directly connected with the synapse being modified, whereas the changes in biological synapses are determined only by the activity of presynaptic and postsynaptic neurons. Several models have been proposed that approximate the backpropagation algorithm with local synaptic plasticity, but these models require complex external control over the network or relatively complex plasticity rules. Here we show that a network developed in the predictive coding framework can efficiently perform supervised learning fully autonomously, employing only simple local Hebbian plasticity. Furthermore, for certain parameters, the weight change in the predictive coding model converges to that of the backpropagation algorithm. This suggests that it is possible for cortical networks with simple Hebbian synaptic plasticity to implement efficient learning algorithms in which synapses in areas on multiple levels of hierarchy are modified to minimize the error on the output.

Auditory cortical activity during cochlear implant-mediated perception of spoken language, melody, and rhythm.

PubMed

Limb, Charles J; Molloy, Anne T; Jiradejvong, Patpong; Braun, Allen R

2010-03-01

Despite the significant advances in language perception for cochlear implant (CI) recipients, music perception continues to be a major challenge for implant-mediated listening. Our understanding of the neural mechanisms that underlie successful implant listening remains limited. To our knowledge, this study represents the first neuroimaging investigation of music perception in CI users, with the hypothesis that CI subjects would demonstrate greater auditory cortical activation than normal hearing controls. H(2) (15)O positron emission tomography (PET) was used here to assess auditory cortical activation patterns in ten postlingually deafened CI patients and ten normal hearing control subjects. Subjects were presented with language, melody, and rhythm tasks during scanning. Our results show significant auditory cortical activation in implant subjects in comparison to control subjects for language, melody, and rhythm. The greatest activity in CI users compared to controls was seen for language tasks, which is thought to reflect both implant and neural specializations for language processing. For musical stimuli, PET scanning revealed significantly greater activation during rhythm perception in CI subjects (compared to control subjects), and the least activation during melody perception, which was the most difficult task for CI users. These results may suggest a possible relationship between auditory performance and degree of auditory cortical activation in implant recipients that deserves further study.

Cortical activation changes underlying stimulation-induced behavioural gains in chronic stroke

PubMed Central

Bachtiar, Velicia; O'Shea, Jacinta; Allman, Claire; Bosnell, Rosemary Ann; Kischka, Udo; Matthews, Paul McMahan; Johansen-Berg, Heidi

2012-01-01

Transcranial direct current stimulation, a form of non-invasive brain stimulation, is showing increasing promise as an adjunct therapy in rehabilitation following stroke. However, although significant behavioural improvements have been reported in proof-of-principle studies, the underlying mechanisms are poorly understood. The rationale for transcranial direct current stimulation as therapy for stroke is that therapeutic stimulation paradigms increase activity in ipsilesional motor cortical areas, but this has not previously been directly tested for conventional electrode placements. This study was performed to test directly whether increases in ipsilesional cortical activation with transcranial direct current stimulation are associated with behavioural improvements in chronic stroke patients. Patients at least 6 months post-first stroke participated in a behavioural experiment (n = 13) or a functional magnetic resonance imaging experiment (n = 11), each investigating the effects of three stimulation conditions in separate sessions: anodal stimulation to the ipsilesional hemisphere; cathodal stimulation to the contralesional hemisphere; and sham stimulation. Anodal (facilitatory) stimulation to the ipsilesional hemisphere led to significant improvements (5–10%) in response times with the affected hand in both experiments. This improvement was associated with an increase in movement-related cortical activity in the stimulated primary motor cortex and functionally interconnected regions. Cathodal (inhibitory) stimulation to the contralesional hemisphere led to a functional improvement only when compared with sham stimulation. We show for the first time that the significant behavioural improvements produced by anodal stimulation to the ipsilesional hemisphere are associated with a functionally relevant increase in activity within the ipsilesional primary motor cortex in patients with a wide range of disabilities following stroke. PMID:22155982

The effects of whole body vibration combined computerized postural control training on the lower extremity muscle activity and cerebral cortex activity in stroke patients.

PubMed

Uhm, Yo-Han; Yang, Dae-Jung

2018-02-01

[Purpose] The purpose of this study was to examine the effect of computerized postural control training using whole body vibration on lower limb muscle activity and cerebral cortical activation in acute stroke patients. [Subjects and Methods] Thirty stroke patients participated and were divided into groups of 10, a group of the computerized postural control training using whole body vibration (Group I), the computerized postural control training combined with aero step (Group II) and computerized postural control training (Group III). MP100 was used to measure lower limb muscle activity, and QEEG-8 was used to measure cerebral cortical activation. [Results] Comparison of muscle activity and cerebral cortical activation before and after intervention between groups showed that Group I had significant differences in lower limb muscle activity and cerebral cortical activation compared to Groups II and III. [Conclusion] This study showed that whole body vibration combined computerized postural control training is effective for improving muscle activity and cerebral cortex activity in stroke patients.

Speech Sound Processing Deficits and Training-Induced Neural Plasticity in Rats with Dyslexia Gene Knockdown

PubMed Central

Centanni, Tracy M.; Chen, Fuyi; Booker, Anne M.; Engineer, Crystal T.; Sloan, Andrew M.; Rennaker, Robert L.; LoTurco, Joseph J.; Kilgard, Michael P.

2014-01-01

In utero RNAi of the dyslexia-associated gene Kiaa0319 in rats (KIA-) degrades cortical responses to speech sounds and increases trial-by-trial variability in onset latency. We tested the hypothesis that KIA- rats would be impaired at speech sound discrimination. KIA- rats needed twice as much training in quiet conditions to perform at control levels and remained impaired at several speech tasks. Focused training using truncated speech sounds was able to normalize speech discrimination in quiet and background noise conditions. Training also normalized trial-by-trial neural variability and temporal phase locking. Cortical activity from speech trained KIA- rats was sufficient to accurately discriminate between similar consonant sounds. These results provide the first direct evidence that assumed reduced expression of the dyslexia-associated gene KIAA0319 can cause phoneme processing impairments similar to those seen in dyslexia and that intensive behavioral therapy can eliminate these impairments. PMID:24871331

Auditory and visual cortex of primates: a comparison of two sensory systems

PubMed Central

Rauschecker, Josef P.

2014-01-01

A comparative view of the brain, comparing related functions across species and sensory systems, offers a number of advantages. In particular, it allows separating the formal purpose of a model structure from its implementation in specific brains. Models of auditory cortical processing can be conceived by analogy to the visual cortex, incorporating neural mechanisms that are found in both the visual and auditory systems. Examples of such canonical features on the columnar level are direction selectivity, size/bandwidth selectivity, as well as receptive fields with segregated versus overlapping on- and off-sub-regions. On a larger scale, parallel processing pathways have been envisioned that represent the two main facets of sensory perception: 1) identification of objects and 2) processing of space. Expanding this model in terms of sensorimotor integration and control offers an overarching view of cortical function independent of sensory modality. PMID:25728177

Cortical Spatio-Temporal Dynamics Underlying Phonological Target Detection in Humans

ERIC Educational Resources Information Center

Chang, Edward F.; Edwards, Erik; Nagarajan, Srikantan S.; Fogelson, Noa; Dalal, Sarang S.; Canolty, Ryan T.; Kirsch, Heidi E.; Barbaro, Nicholas M.; Knight, Robert T.

2011-01-01

Selective processing of task-relevant stimuli is critical for goal-directed behavior. We used electrocorticography to assess the spatio-temporal dynamics of cortical activation during a simple phonological target detection task, in which subjects press a button when a prespecified target syllable sound is heard. Simultaneous surface potential…

Task-dependent and distinct roles of the temporoparietal junction and inferior frontal cortex in the control of imitation

PubMed Central

Obhi, Sukhvinder S.; Banissy, Michael J.; Santiesteban, Idalmis; Press, Clare; Catmur, Caroline; Bird, Geoffrey

2015-01-01

The control of neurological networks supporting social cognition is crucially important for social interaction. In particular, the control of imitation is directly linked to interaction quality, with impairments associated with disorders characterized by social difficulties. Previous work suggests inferior frontal cortex (IFC) and the temporoparietal junction (TPJ) are involved in controlling imitation, but the functional roles of these areas remain unclear. Here, transcranial direct current stimulation (tDCS) was used to enhance cortical excitability at IFC and the TPJ prior to the completion of three tasks: (i) a naturalistic social interaction during which increased imitation is known to improve rapport, (ii) a choice reaction time task in which imitation needs to be inhibited for successful performance and (iii) a non-imitative control task. Relative to sham stimulation, stimulating IFC improved the context-dependent control of imitation—participants imitated more during the social interaction and less during the imitation inhibition task. In contrast, stimulating the TPJ reduced imitation in the inhibition task without affecting imitation during social interaction. Neither stimulation site affected the non-imitative control task. These data support a model in which IFC modulates imitation directly according to task demands, whereas TPJ controls task-appropriate shifts in attention toward representation of the self or the other, indirectly impacting upon imitation. PMID:25481003

Weibull analysis of fracture test data on bovine cortical bone: influence of orientation.

PubMed

Khandaker, Morshed; Ekwaro-Osire, Stephen

2013-01-01

The fracture toughness, K IC, of a cortical bone has been experimentally determined by several researchers. The variation of K IC values occurs from the variation of specimen orientation, shape, and size during the experiment. The fracture toughness of a cortical bone is governed by the severest flaw and, hence, may be analyzed using Weibull statistics. To the best of the authors' knowledge, however, no studies of this aspect have been published. The motivation of the study is the evaluation of Weibull parameters at the circumferential-longitudinal (CL) and longitudinal-circumferential (LC) directions. We hypothesized that Weibull parameters vary depending on the bone microstructure. In the present work, a two-parameter Weibull statistical model was applied to calculate the plane-strain fracture toughness of bovine femoral cortical bone obtained using specimens extracted from CL and LC directions of the bone. It was found that the Weibull modulus of fracture toughness was larger for CL specimens compared to LC specimens, but the opposite trend was seen for the characteristic fracture toughness. The reason for these trends is the microstructural and extrinsic toughening mechanism differences between CL and LC directions bone. The Weibull parameters found in this study can be applied to develop a damage-mechanics model for bone.

Which is the best method of sterilization of tumour bone for reimplantation? a biomechanical and histopathological study

PubMed Central

2010-01-01

Introduction Sterilization and re-usage of tumour bone for reconstruction after tumour resection is now gaining popularity in the East. This recycle tumour bone needs to be sterilized in order to eradicate the tumour cells before re-implantation for limb salvage procedures. The effect of some of these treatments on the integrity and sterility of the bone after treatment has been published but there has yet been a direct comparison between the various methods of sterilization to determine the one method that gives the best tumour kill without compromising the bone's structural integrity. Method This study was performed to evaluate the effect of several sterilization methods on the mechanical behavior of human cortical bone graft and histopathology evaluation of tumour bone samples after being processed with 4 different methods of sterilization. Fresh human cortical tumour bone is harvested from the diaphyseal region of the tumour bone were sterilized by autoclave (n =10); boiling (n =10); pasteurization (n =10); and irradiation (n =10). There were also 10 control specimens that did not receive any form of sterilization treatment. The biomechanical test conducted were stress to failure, modulus and strain to failure, which were determined from axial compression testing. Statistical analysis (ANOVA) was performed on these results. Significance level (α) and power (β) were set to 0.05 and 0.90, respectively. Results ANOVA analysis of 'failure stress', 'modulus' and 'strain to failure' demonstrated significant differences (p < 0.05) between treated cortical bone and untreated specimens under mechanical loading. 'Stress to failure' was significantly reduced in boiled, autoclaved and irradiated cortical bone samples (p < 0.05). 'Modulus' detected significant differences in the boiled, autoclaved and pasteurization specimens compared to controls (p < 0.05). 'Strain to failure' was reduced by irradiation (p < 0.05) but not by the other three methods of treatments. Histopathology study revealed no viable tumour cell in any of four types of treatment group compared to the untreated control group. Conclusions Sterilization of cortical bone sample by pasteurization and to a lesser extent, irradiation does not significantly alter the mechanical properties when compared with untreated samples. Mechanical properties degrade with the use of high temperature for sterilization (boiling). All methods of sterilization gave rise to 100 percent tumour kill. PMID:20831801

Whole-brain MRI phenotyping in dysplasia-related frontal lobe epilepsy.

PubMed

Hong, Seok-Jun; Bernhardt, Boris C; Schrader, Dewi S; Bernasconi, Neda; Bernasconi, Andrea

2016-02-16

To perform whole-brain morphometry in patients with frontal lobe epilepsy and evaluate the utility of group-level patterns for individualized diagnosis and prognosis. We compared MRI-based cortical thickness and folding complexity between 2 frontal lobe epilepsy cohorts with histologically verified focal cortical dysplasia (FCD) (13 type I; 28 type II) and 41 closely matched controls. Pattern learning algorithms evaluated the utility of group-level findings to predict histologic FCD subtype, the side of the seizure focus, and postsurgical seizure outcome in single individuals. Relative to controls, FCD type I displayed multilobar cortical thinning that was most marked in ipsilateral frontal cortices. Conversely, type II showed thickening in temporal and postcentral cortices. Cortical folding also diverged, with increased complexity in prefrontal cortices in type I and decreases in type II. Group-level findings successfully guided automated FCD subtype classification (type I: 100%; type II: 96%), seizure focus lateralization (type I: 92%; type II: 86%), and outcome prediction (type I: 92%; type II: 82%). FCD subtypes relate to diverse whole-brain structural phenotypes. While cortical thickening in type II may indicate delayed pruning, a thin cortex in type I likely results from combined effects of seizure excitotoxicity and the primary malformation. Group-level patterns have a high translational value in guiding individualized diagnostics. © 2016 American Academy of Neurology.

Somatosensory cortex functional connectivity abnormalities in autism show opposite trends, depending on direction and spatial scale

PubMed Central

Khan, Sheraz; Michmizos, Konstantinos; Tommerdahl, Mark; Ganesan, Santosh; Kitzbichler, Manfred G.; Zetino, Manuel; Garel, Keri-Lee A.; Herbert, Martha R.; Hämäläinen, Matti S.

2015-01-01

Functional connectivity is abnormal in autism, but the nature of these abnormalities remains elusive. Different studies, mostly using functional magnetic resonance imaging, have found increased, decreased, or even mixed pattern functional connectivity abnormalities in autism, but no unifying framework has emerged to date. We measured functional connectivity in individuals with autism and in controls using magnetoencephalography, which allowed us to resolve both the directionality (feedforward versus feedback) and spatial scale (local or long-range) of functional connectivity. Specifically, we measured the cortical response and functional connectivity during a passive 25-Hz vibrotactile stimulation in the somatosensory cortex of 20 typically developing individuals and 15 individuals with autism, all males and right-handed, aged 8–18, and the mu-rhythm during resting state in a subset of these participants (12 per group, same age range). Two major significant group differences emerged in the response to the vibrotactile stimulus. First, the 50-Hz phase locking component of the cortical response, generated locally in the primary (S1) and secondary (S2) somatosensory cortex, was reduced in the autism group (P < 0.003, corrected). Second, feedforward functional connectivity between S1 and S2 was increased in the autism group (P < 0.004, corrected). During resting state, there was no group difference in the mu-α rhythm. In contrast, the mu-β rhythm, which has been associated with feedback connectivity, was significantly reduced in the autism group (P < 0.04, corrected). Furthermore, the strength of the mu-β was correlated to the relative strength of 50 Hz component of the response to the vibrotactile stimulus (r = 0.78, P < 0.00005), indicating a shared aetiology for these seemingly unrelated abnormalities. These magnetoencephalography-derived measures were correlated with two different behavioural sensory processing scores (P < 0.01 and P < 0.02 for the autism group, P < 0.01 and P < 0.0001 for the typical group), with autism severity (P < 0.03), and with diagnosis (89% accuracy). A biophysically realistic computational model using data driven feedforward and feedback parameters replicated the magnetoencephalography data faithfully. The direct observation of both abnormally increased and abnormally decreased functional connectivity in autism occurring simultaneously in different functional connectivity streams, offers a potential unifying framework for the unexplained discrepancies in current findings. Given that cortical feedback, whether local or long-range, is intrinsically non-linear, while cortical feedforward is generally linear relative to the stimulus, the present results suggest decreased non-linearity alongside an increased veridical component of the cortical response in autism. PMID:25765326

Effects of transcranial direct current stimulation on the control of finger force during dexterous manipulation in healthy older adults.

PubMed

Parikh, Pranav J; Cole, Kelly J

2015-01-01

The contribution of poor finger force control to age-related decline in manual dexterity is above and beyond ubiquitous behavioral slowing. Altered control of the finger forces can impart unwanted torque on the object affecting its orientation, thus impairing manual performance. Anodal transcranial direct current stimulation (tDCS) over primary motor cortex (M1) has been shown to improve the performance speed on manual tasks in older adults. However, the effects of anodal tDCS over M1 on the finger force control during object manipulation in older adults remain to be fully explored. Here we determined the effects of anodal tDCS over M1 on the control of grip force in older adults while they manipulated an object with an uncertain mechanical property. Eight healthy older adults were instructed to grip and lift an object whose contact surfaces were unexpectedly made more or less slippery across trials using acetate and sandpaper surfaces, respectively. Subjects performed this task before and after receiving anodal or sham tDCS over M1 on two separate sessions using a cross-over design. We found that older adults used significantly lower grip force following anodal tDCS compared to sham tDCS. Friction measured at the finger-object interface remained invariant after anodal and sham tDCS. These findings suggest that anodal tDCS over M1 improved the control of grip force during object manipulation in healthy older adults. Although the cortical networks for representing objects and manipulative actions are complex, the reduction in grip force following anodal tDCS over M1 might be due to a cortical excitation yielding improved processing of object-specific sensory information and its integration with the motor commands for production of manipulative forces. Our findings indicate that tDCS has a potential to improve the control of finger force during dexterous manipulation in older adults.

High-resolution 2-deoxyglucose mapping of functional cortical columns in mouse barrel cortex.

PubMed

McCasland, J S; Woolsey, T A

1988-12-22

Cortical columns associated with barrels in layer IV of the somatosensory cortex were characterized by high-resolution 2-deoxy-D-glucose (2DG) autoradiography in freely behaving mice. The method demonstrates a more exact match between columnar labeling and cytoarchitectonic barrel boundaries than previously reported. The pattern of cortical activation seen with stimulation of a single whisker (third whisker in the middle row of large hairs--C3) was compared with the patterns from two control conditions--normal animals with all whiskers present ("positive control")--and with all large whiskers clipped ("negative control"). Two types of measurements were made from 2DG autoradiograms of tangential cortical sections: 1) labeled cells were identified by eye and tabulated with a computer, and 2) grain densities were obtained automatically with a computer-controlled microscope and image processor. We studied the fine-grained patterns of 2DG labeling in a nine-barrel grid with the C3 barrel in the center. From the analysis we draw five major conclusions. 1. Approximately 30-40% of the total number of neurons in the C3 barrel column are activated when only the C3 whisker is stimulated. This is about twice the number of neurons labeled in the C3 column when all whiskers are stimulated and about ten times the number of neurons labeled when all large whiskers are clipped. 2. There is evidence for a vertical functional organization within a barrel-related whisker column which has smaller dimensions in the tangential direction than a barrel. There are densely labeled patches within a barrel which are unique to an individual cortex. The same patchy pattern is found in the appropriate regions of sections above and below the barrels through the full thickness of the cortex. This functional arrangement could be considered to be a "minicolumn" or more likely a group of "minicolumns" (Mountcastle: In G.M. Edelman and U.B. Mountcastle (eds): The Material Brain: Cortical Organization and the Group-Selective Theory of Higher Brain Function. Cambridge: MIT Press, '78). 3. Within the stereotyped geometry of the barrel field, there is considerable individual variation in the radial labeling distribution in corresponding (homotypical) columns of different cerebral hemispheres. This result is consistent with the hypothesis that dynamic processes operate to determine the connection strengths between neural elements in somatosensory cortex. It provides a basis for testing various "connectionist" and "group selection" theories of neural organization and development.(ABSTRACT TRUNCATED AT 400 WORDS)

Autonomic and brain responses associated with empathy deficits in autism spectrum disorder

PubMed Central

Eilam‐Stock, Tehila; Zhou, Thomas; Anagnostou, Evdokia; Kolevzon, Alexander; Soorya, Latha; Hof, Patrick R.; Friston, Karl J.

2015-01-01

Abstract Accumulating evidence suggests that autonomic signals and their cortical representations are closely linked to emotional processes, and that related abnormalities could lead to social deficits. Although socio‐emotional impairments are a defining feature of autism spectrum disorder (ASD), empirical evidence directly supporting the link between autonomic, cortical, and socio‐emotional abnormalities in ASD is still lacking. In this study, we examined autonomic arousal indexed by skin conductance responses (SCR), concurrent cortical responses measured by functional magnetic resonance imaging, and effective brain connectivity estimated by dynamic causal modeling in seventeen unmedicated high‐functioning adults with ASD and seventeen matched controls while they performed an empathy‐for‐pain task. Compared to controls, adults with ASD showed enhanced SCR related to empathetic pain, along with increased neural activity in the anterior insular cortex, although their behavioral empathetic pain discriminability was reduced and overall SCR was decreased. ASD individuals also showed enhanced correlation between SCR and neural activities in the anterior insular cortex. Importantly, significant group differences in effective brain connectivity were limited to greater reduction in the negative intrinsic connectivity of the anterior insular cortex in the ASD group, indicating a failure in attenuating anterior insular responses to empathetic pain. These results suggest that aberrant interoceptive precision, as indexed by abnormalities in autonomic activity and its central representations, may underlie empathy deficits in ASD. Hum Brain Mapp 36:3323–3338, 2015. © 2015 The Authors Human Brain Mapping Published byWiley Periodicals, Inc. PMID:25995134

Differences in Early Stages of Tactile ERP Temporal Sequence (P100) in Cortical Organization during Passive Tactile Stimulation in Children with Blindness and Controls.

PubMed

Ortiz Alonso, Tomás; Santos, Juan Matías; Ortiz Terán, Laura; Borrego Hernández, Mayelin; Poch Broto, Joaquín; de Erausquin, Gabriel Alejandro

2015-01-01

Compared to their seeing counterparts, people with blindness have a greater tactile capacity. Differences in the physiology of object recognition between people with blindness and seeing people have been well documented, but not when tactile stimuli require semantic processing. We used a passive vibrotactile device to focus on the differences in spatial brain processing evaluated with event related potentials (ERP) in children with blindness (n = 12) vs. normally seeing children (n = 12), when learning a simple spatial task (lines with different orientations) or a task involving recognition of letters, to describe the early stages of its temporal sequence (from 80 to 220 msec) and to search for evidence of multi-modal cortical organization. We analysed the P100 of the ERP. Children with blindness showed earlier latencies for cognitive (perceptual) event related potentials, shorter reaction times, and (paradoxically) worse ability to identify the spatial direction of the stimulus. On the other hand, they are equally proficient in recognizing stimuli with semantic content (letters). The last observation is consistent with the role of P100 on somatosensory-based recognition of complex forms. The cortical differences between seeing control and blind groups, during spatial tactile discrimination, are associated with activation in visual pathway (occipital) and task-related association (temporal and frontal) areas. The present results show that early processing of tactile stimulation conveying cross modal information differs in children with blindness or with normal vision.

Cadherin-8 expression, synaptic localization, and molecular control of neuronal form in prefrontal corticostriatal circuits.

PubMed

Friedman, Lauren G; Riemslagh, Fréderike W; Sullivan, Josefa M; Mesias, Roxana; Williams, Frances M; Huntley, George W; Benson, Deanna L

2015-01-01

Neocortical interactions with the dorsal striatum support many motor and executive functions, and such underlying functional networks are particularly vulnerable to a variety of developmental, neurological, and psychiatric brain disorders, including autism spectrum disorders, Parkinson's disease, and Huntington's disease. Relatively little is known about the development of functional corticostriatal interactions, and in particular, virtually nothing is known of the molecular mechanisms that control generation of prefrontal cortex-striatal circuits. Here, we used regional and cellular in situ hybridization techniques coupled with neuronal tract tracing to show that Cadherin-8 (Cdh8), a homophilic adhesion protein encoded by a gene associated with autism spectrum disorders and learning disability susceptibility, is enriched within striatal projection neurons in the medial prefrontal cortex and in striatal medium spiny neurons forming the direct or indirect pathways. Developmental analysis of quantitative real-time polymerase chain reaction and western blot data show that Cdh8 expression peaks in the prefrontal cortex and striatum at P10, when cortical projections start to form synapses in the striatum. High-resolution immunoelectron microscopy shows that Cdh8 is concentrated at excitatory synapses in the dorsal striatum, and Cdh8 knockdown in cortical neurons impairs dendritic arborization and dendrite self-avoidance. Taken together, our findings indicate that Cdh8 delineates developing corticostriatal circuits where it is a strong candidate for regulating the generation of normal cortical projections, neuronal morphology, and corticostriatal synapses. © 2014 Wiley Periodicals, Inc.

Differences in Early Stages of Tactile ERP Temporal Sequence (P100) in Cortical Organization during Passive Tactile Stimulation in Children with Blindness and Controls

PubMed Central

Ortiz Alonso, Tomás; Santos, Juan Matías; Ortiz Terán, Laura; Borrego Hernández, Mayelin; Poch Broto, Joaquín; de Erausquin, Gabriel Alejandro

2015-01-01

Compared to their seeing counterparts, people with blindness have a greater tactile capacity. Differences in the physiology of object recognition between people with blindness and seeing people have been well documented, but not when tactile stimuli require semantic processing. We used a passive vibrotactile device to focus on the differences in spatial brain processing evaluated with event related potentials (ERP) in children with blindness (n = 12) vs. normally seeing children (n = 12), when learning a simple spatial task (lines with different orientations) or a task involving recognition of letters, to describe the early stages of its temporal sequence (from 80 to 220 msec) and to search for evidence of multi-modal cortical organization. We analysed the P100 of the ERP. Children with blindness showed earlier latencies for cognitive (perceptual) event related potentials, shorter reaction times, and (paradoxically) worse ability to identify the spatial direction of the stimulus. On the other hand, they are equally proficient in recognizing stimuli with semantic content (letters). The last observation is consistent with the role of P100 on somatosensory-based recognition of complex forms. The cortical differences between seeing control and blind groups, during spatial tactile discrimination, are associated with activation in visual pathway (occipital) and task-related association (temporal and frontal) areas. The present results show that early processing of tactile stimulation conveying cross modal information differs in children with blindness or with normal vision. PMID:26225827

Dissociable effects of prefrontal and anterior temporal cortical lesions on stereotypical gender attitudes.

PubMed

Gozzi, Marta; Raymont, Vanessa; Solomon, Jeffrey; Koenigs, Michael; Grafman, Jordan

2009-08-01

Clinical observations of patients with ventral frontal and anterior temporal cortical lesions reveal marked abnormalities in social attitudes. A previous study in seven patients with ventral prefrontal lesions provided the first direct experimental evidence for abnormalities in social attitudes using a well-established measure of gender stereotypes, the Implicit Association Test (IAT). Here, we were able to test whether these first findings could be reproduced in a larger sample of 154 patients with penetrating head injuries, and to determine the differential effects of ventromedial prefrontal (vmPFC) and ventrolateral prefrontal (vlPFC) cortical lesions on IAT performance. In addition, we investigated the role of the superior anterior temporal lobe (aTL), recently shown to represent conceptual social knowledge. First, we used a linear regression model to identify the role of each of the three regions, while controlling for the extent of damage to other regions. We found that larger lesions in either the vmPFC or the superior aTL were associated with increased stereotypical attitudes, whereas larger lesions in the vlPFC were associated with decreased stereotypical attitudes. Second, in a confirmatory analysis, we grouped patients by lesion location and compared their performance on the IAT with that of healthy volunteers. Compared to controls, patients with lesions in either the vmPFC or the superior aTL showed increased stereotypical attitudes, whereas patients with lesions in the vlPFC showed decreased stereotypical attitudes. The functional contributions of these regions in social attitudes are discussed.

Different Neuroplasticity for Task Targets and Distractors

PubMed Central

Spingath, Elsie Y.; Kang, Hyun Sug; Plummer, Thane; Blake, David T.

2011-01-01

Adult learning-induced sensory cortex plasticity results in enhanced action potential rates in neurons that have the most relevant information for the task, or those that respond strongly to one sensory stimulus but weakly to its comparison stimulus. Current theories suggest this plasticity is caused when target stimulus evoked activity is enhanced by reward signals from neuromodulatory nuclei. Prior work has found evidence suggestive of nonselective enhancement of neural responses, and suppression of responses to task distractors, but the differences in these effects between detection and discrimination have not been directly tested. Using cortical implants, we defined physiological responses in macaque somatosensory cortex during serial, matched, detection and discrimination tasks. Nonselective increases in neural responsiveness were observed during detection learning. Suppression of responses to task distractors was observed during discrimination learning, and this suppression was specific to cortical locations that sampled responses to the task distractor before learning. Changes in receptive field size were measured as the area of skin that had a significant response to a constant magnitude stimulus, and these areal changes paralleled changes in responsiveness. From before detection learning until after discrimination learning, the enduring changes were selective suppression of cortical locations responsive to task distractors, and nonselective enhancement of responsiveness at cortical locations selective for target and control skin sites. A comparison of observations in prior studies with the observed plasticity effects suggests that the non-selective response enhancement and selective suppression suffice to explain known plasticity phenomena in simple spatial tasks. This work suggests that differential responsiveness to task targets and distractors in primary sensory cortex for a simple spatial detection and discrimination task arise from nonselective increases in response over a broad cortical locus that includes the representation of the task target, and selective suppression of responses to the task distractor within this locus. PMID:21297962

Neuropeptide Y as a possible homeostatic element for changes in cortical excitability induced by repetitive transcranial magnetic stimulation.

PubMed

Jazmati, Danny; Neubacher, Ute; Funke, Klaus

2018-02-24

Repetitive transcranial magnetic stimulation (rTMS) is able to modify cortical excitability. Rat rTMS studies revealed a modulation of inhibitory systems, in particular that of the parvalbumin-expressing (PV+) interneurons, when using intermittent theta-burst stimulation (iTBS). The potential disinhibitory action of iTBS raises the questions of how neocortical circuits stabilize excitatory-inhibitory balance within a physiological range. Neuropeptide Y (NPY) appears to be one candidate. Analysis of cortical expression of PV, NPY and vesicular glutamate transporter type 1 (vGluT1) by immunohistochemical means at the level of cell counts, mean neuropil expression and single cell pre-/postsynaptic expression, with and without intraventricular NPY-injection. Our results show that iTBS not only reduced the number of neurons with high-PV expression in a dose-dependent fashion, but also increased the cortical expression of NPY, discussed to reduce glutamatergic transmission, and this was further associated with a reduced vGluT1 expression, an indicator of glutamateric presynaptic activity. Interneurons showing a low-PV expression exhibit less presynaptic vGluT1 expression compared to those with a high-PV expression. Intraventricular application of NPY prior to iTBS prevented the iTBS-induced reduction in the number of high-PV neurons, the reduction in tissue vGluT1 level and that presynaptic to high-PV cells. We conclude that NPY, possibly via a global but also slow homeostatic control of glutamatergic transmission, modulates the strength and direction of the iTBS effects, likely preventing pathological imbalance of excitatory and inhibitory cortical activity but still allowing enough disinhibition beneficial for plastic changes as during learning. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Differential alterations of cortical glutamatergic binding sites in senile dementia of the Alzheimer type

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chalmers, D.T.; Dewar, D.; Graham, D.I.

1990-02-01

Involvement of cortical glutamatergic mechanisms in senile dementia of the Alzheimer type (SDAT) has been investigated with quantitative ligand-binding autoradiography. The distribution and density of Na(+)-dependent glutamate uptake sites and glutamate receptor subtypes--kainate, quisqualate, and N-methyl-D-aspartate--were measured in adjacent sections of frontal cortex obtained postmortem from six patients with SDAT and six age-matched controls. The number of senile plaques was determined in the same brain region. Binding of D-(3H)aspartate to Na(+)-dependent uptake sites was reduced by approximately 40% throughout SDAT frontal cortex relative to controls, indicating a general loss of glutamatergic presynaptic terminals. (3H)Kainate receptor binding was significantly increased bymore » approximately 70% in deep layers of SDAT frontal cortex compared with controls, whereas this binding was unaltered in superficial laminae. There was a positive correlation (r = 0.914) between kainate binding and senile plaque number in deep cortical layers. Quisqualate receptors, as assessed by 2-amino-3-hydroxy-5-(3H)methylisoxazole-4-propionic acid binding, were unaltered in SDAT frontal cortex compared with controls. There was a small reduction (25%) in N-methyl-D-aspartate-sensitive (3H)glutamate binding only in superficial cortical layers of SDAT brains relative to control subjects. (3H)Glutamate binding in SDAT subjects was unrelated to senile plaque number in superficial cortical layers (r = 0.104). These results indicate that in the presence of cortical glutamatergic terminal loss in SDAT plastic alterations occur in some glutamate receptor subtypes but not in others.« less

Using Individualized Brain Network for Analyzing Structural Covariance of the Cerebral Cortex in Alzheimer's Patients.

PubMed

Kim, Hee-Jong; Shin, Jeong-Hyeon; Han, Cheol E; Kim, Hee Jin; Na, Duk L; Seo, Sang Won; Seong, Joon-Kyung

2016-01-01

Cortical thinning patterns in Alzheimer's disease (AD) have been widely reported through conventional regional analysis. In addition, the coordinated variance of cortical thickness in different brain regions has been investigated both at the individual and group network levels. In this study, we aim to investigate network architectural characteristics of a structural covariance network (SCN) in AD, and further to show that the structural covariance connectivity becomes disorganized across the brain regions in AD, while the normal control (NC) subjects maintain more clustered and consistent coordination in cortical atrophy variations. We generated SCNs directly from T1-weighted MR images of individual patients using surface-based cortical thickness data, with structural connectivity defined as similarity in cortical thickness within different brain regions. Individual SCNs were constructed using morphometric data from the Samsung Medical Center (SMC) dataset. The structural covariance connectivity showed higher clustering than randomly generated networks, as well as similar minimum path lengths, indicating that the SCNs are "small world." There were significant difference between NC and AD group in characteristic path lengths (z = -2.97, p < 0.01) and small-worldness values (z = 4.05, p < 0.01). Clustering coefficients in AD was smaller than that of NC but there was no significant difference (z = 1.81, not significant). We further observed that the AD patients had significantly disrupted structural connectivity. We also show that the coordinated variance of cortical thickness is distributed more randomly from one region to other regions in AD patients when compared to NC subjects. Our proposed SCN may provide surface-based measures for understanding interaction between two brain regions with co-atrophy of the cerebral cortex due to normal aging or AD. We applied our method to the AD Neuroimaging Initiative (ADNI) data to show consistency in results with the SMC dataset.

Early visual cortical structural changes in diabetic patients without diabetic retinopathy.

PubMed

Ferreira, Fábio S; Pereira, João M S; Reis, Aldina; Sanches, Mafalda; Duarte, João V; Gomes, Leonor; Moreno, Carolina; Castelo-Branco, Miguel

2017-11-01

It is known that diabetic patients have changes in cortical morphometry as compared to controls, but it remains to be clarified whether the visual cortex is a disease target, even when diabetes complications such as retinopathy are absent. Therefore, we compared type 2 diabetes patients without diabetic retinopathy with control subjects using magnetic resonance imaging to assess visual cortical changes when retinal damage is not yet present. We performed T1-weighted imaging in 24 type 2 diabetes patients without diabetic retinopathy and 27 age- and gender-matched controls to compare gray matter changes in the occipital cortex between groups using voxel based morphometry. Patients without diabetic retinopathy showed reduced gray matter volume in the occipital lobe when compared with controls. Reduced gray matter volume in the occipital cortex was found in diabetic patients without retinal damage. We conclude that cortical early visual processing regions may be affected in diabetic patients even before retinal damage occurs.

Adaptations of young adult rat cortical bone to 14 days of spaceflight

NASA Technical Reports Server (NTRS)

Vailas, A. C.; Vanderby, R., Jr.; Martinez, D. A.; Ashman, R. B.; Ulm, M. J.; Grindeland, R. E.; Durnova, G. N.; Kaplanskii, A.

1992-01-01

To determine whether mature humeral cortical bone would be modified significantly by an acute exposure to weightlessness, adult rats (110 days old) were subjected to 14 days of microgravity on the COSMOS 2044 biosatellite. There were no significant changes in peak force, stiffness, energy to failure, and displacement at failure in the flight rats compared with ground-based controls. Concentrations and contents of hydroxyproline, calcium, and mature stable hydroxylysylpyridinoline and lysylpyridinoline collagen cross-links remained unchanged after spaceflight. Bone lengths, cortical and endosteal areas, and regionl thicknesses showed no significant differences between flight animals and ground controls. The findings suggest that responsiveness of cortical bone to microgravity is less pronounced in adult rats than in previous spaceflight experiments in which young growing animals were used. It is hypothesized that 14 days of spaceflight may not be sufficient to impact the biochemical and biomechanical properties of cortical bone in the mature rat skeleton.

Absence of beta-amyloid in cortical cataracts of donors with and without Alzheimer's disease.

PubMed

Michael, Ralph; Rosandić, Jurja; Montenegro, Gustavo A; Lobato, Elvira; Tresserra, Francisco; Barraquer, Rafael I; Vrensen, Gijs F J M

2013-01-01

Eye lenses from human donors with and without Alzheimer's disease (AD) were studied to evaluate the presence of amyloid in cortical cataract. We obtained 39 lenses from 21 postmortem donors with AD and 15 lenses from age-matched controls provided by the Banco de Ojos para Tratamientos de la Ceguera (Barcelona, Spain). For 17 donors, AD was clinically diagnosed by general physicians and for 4 donors the AD diagnosis was neuropathologically confirmed. Of the 21 donors with AD, 6 had pronounced bilateral cortical lens opacities and 15 only minor or no cortical opacities. As controls, 7 donors with pronounced cortical opacities and 8 donors with almost transparent lenses were selected. All lenses were photographed in a dark field stereomicroscope. Histological sections were analyzed using a standard and a more sensitive Congo red protocol, thioflavin staining and beta-amyloid immunohistochemistry. Brain tissue from two donors, one with cerebral amyloid angiopathy and another with advanced AD-related changes and one cornea with lattice dystrophy were used as positive controls for the staining techniques. Thioflavin, standard and modified Congo red staining were positive in the control brain tissues and in the dystrophic cornea. Beta-amyloid immunohistochemistry was positive in the brain tissues but not in the cornea sample. Lenses from control and AD donors were, without exception, negative after Congo red, thioflavin, and beta-amyloid immunohistochemical staining. The results of the positive control tissues correspond well with known observations in AD, amyloid angiopathy and corneas with lattice dystrophy. The absence of staining in AD and control lenses with the techniques employed lead us to conclude that there is no beta-amyloid in lenses from donors with AD or in control cortical cataracts. The inconsistency with previous studies of Goldstein et al. (2003) and Moncaster et al. (2010), both of which demonstrated positive Congo red, thioflavin, and beta-amyloid immunohistochemical staining in AD and Down syndrome lenses, is discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

The Unique Brain Anatomy of Meditation Practitioners: Alterations in Cortical Gyrification

PubMed Central

Luders, Eileen; Kurth, Florian; Mayer, Emeran A.; Toga, Arthur W.; Narr, Katherine L.; Gaser, Christian

2012-01-01

Several cortical regions are reported to vary in meditation practitioners. However, prior analyses have focused primarily on examining gray matter or cortical thickness. Thus, additional effects with respect to other cortical features might have remained undetected. Gyrification (the pattern and degree of cortical folding) is an important cerebral characteristic related to the geometry of the brain’s surface. Thus, exploring cortical gyrification in long-term meditators may provide additional clues with respect to the underlying anatomical correlates of meditation. This study examined cortical gyrification in a large sample (n = 100) of meditators and controls, carefully matched for sex and age. Cortical gyrification was established by calculating mean curvature across thousands of vertices on individual cortical surface models. Pronounced group differences indicating larger gyrification in meditators were evident within the left precentral gyrus, right fusiform gyrus, right cuneus, as well as left and right anterior dorsal insula (the latter representing the global significance maximum). Positive correlations between gyrification and the number of meditation years were similarly pronounced in the right anterior dorsal insula. Although the exact functional implications of larger cortical gyrification remain to be established, these findings suggest the insula to be a key structure involved in aspects of meditation. For example, variations in insular complexity could affect the regulation of well-known distractions in the process of meditation, such as daydreaming, mind-wandering, and projections into past or future. Moreover, given that meditators are masters in introspection, awareness, and emotional control, increased insular gyrification may reflect an integration of autonomic, affective, and cognitive processes. Due to the cross-sectional nature of this study, further research is necessary to determine the relative contribution of nature and nurture to links between cortical gyrification and meditation. PMID:22393318

Dlx1&2-Dependent Expression of Zfhx1b (Sip1, Zeb2) Regulates the Fate Switch Between Cortical and Striatal Interneurons

PubMed Central

McKinsey, Gabriel L.; Lindtner, Susan; Trzcinski, Brett; Visel, Axel; Pennacchio, Len A.; Huylebroeck, Danny; Higashi, Yujiro; Rubenstein, John L. R.

2013-01-01

Summary Mammalian pallial (cortical and hippocampal) and striatal interneurons are both generated in the embryonic subpallium, including the medial ganglionic eminence (MGE). Herein we demonstrate that the Zfhx1b (Sip1, Zeb2) zinc finger homeobox gene is required in the MGE, directly downstream of Dlx1&2, to generate cortical interneurons that express Cxcr7, MafB and cMaf. In its absence, Nkx2-1 expression is not repressed, and cells that ordinarily would become cortical interneurons appear to transform towards a subtype of GABAeric striatal interneurons. These results show that Zfhx1b is required to generate cortical interneurons, and suggest a mechanism for the epilepsy observed in humans with Zfhx1b mutations (Mowat-Wilson syndrome). PMID:23312518

Reduced modulation of scanpaths in response to task demands in posterior cortical atrophy.

PubMed

Shakespeare, Timothy J; Pertzov, Yoni; Yong, Keir X X; Nicholas, Jennifer; Crutch, Sebastian J

2015-02-01

A difficulty in perceiving visual scenes is one of the most striking impairments experienced by patients with the clinico-radiological syndrome posterior cortical atrophy (PCA). However whilst a number of studies have investigated perception of relatively simple experimental stimuli in these individuals, little is known about multiple object and complex scene perception and the role of eye movements in posterior cortical atrophy. We embrace the distinction between high-level (top-down) and low-level (bottom-up) influences upon scanning eye movements when looking at scenes. This distinction was inspired by Yarbus (1967), who demonstrated how the location of our fixations is affected by task instructions and not only the stimulus' low level properties. We therefore examined how scanning patterns are influenced by task instructions and low-level visual properties in 7 patients with posterior cortical atrophy, 8 patients with typical Alzheimer's disease, and 19 healthy age-matched controls. Each participant viewed 10 scenes under four task conditions (encoding, recognition, search and description) whilst eye movements were recorded. The results reveal significant differences between groups in the impact of test instructions upon scanpaths. Across tasks without a search component, posterior cortical atrophy patients were significantly less consistent than typical Alzheimer's disease patients and controls in where they were looking. By contrast, when comparing search and non-search tasks, it was controls who exhibited lowest between-task similarity ratings, suggesting they were better able than posterior cortical atrophy or typical Alzheimer's disease patients to respond appropriately to high-level needs by looking at task-relevant regions of a scene. Posterior cortical atrophy patients had a significant tendency to fixate upon more low-level salient parts of the scenes than controls irrespective of the viewing task. The study provides a detailed characterisation of scene perception abilities in posterior cortical atrophy and offers insights into the mechanisms by which high-level cognitive schemes interact with low-level perception. Copyright © 2015 Elsevier Ltd. All rights reserved.

APC sets the Wnt tone necessary for cerebral cortical progenitor development

PubMed Central

Nakagawa, Naoki; Li, Jingjun; Yabuno-Nakagawa, Keiko; Eom, Tae-Yeon; Cowles, Martis; Mapp, Tavien; Taylor, Robin; Anton, E.S.

2017-01-01

Adenomatous polyposis coli (APC) regulates the activity of β-catenin, an integral component of Wnt signaling. However, the selective role of the APC–β-catenin pathway in cerebral cortical development is unknown. Here we genetically dissected the relative contributions of APC-regulated β-catenin signaling in cortical progenitor development, a necessary early step in cerebral cortical formation. Radial progenitor-specific inactivation of the APC–β-catenin pathway indicates that the maintenance of appropriate β-catenin-mediated Wnt tone is necessary for the orderly differentiation of cortical progenitors and the resultant formation of the cerebral cortex. APC deletion deregulates β-catenin, leads to high Wnt tone, and disrupts Notch1 signaling and primary cilium maintenance necessary for radial progenitor functions. β-Catenin deregulation directly disrupts cilium maintenance and signaling via Tulp3, essential for intraflagellar transport of ciliary signaling receptors. Surprisingly, deletion of β-catenin or inhibition of β-catenin activity in APC-null progenitors rescues the APC-null phenotype. These results reveal that APC-regulated β-catenin activity in cortical progenitors sets the appropriate Wnt tone necessary for normal cerebral cortical development. PMID:28916710

Abnormalities of fixation, saccade and pursuit in posterior cortical atrophy

PubMed Central

Kaski, Diego; Yong, Keir X. X.; Paterson, Ross W.; Slattery, Catherine F.; Ryan, Natalie S.; Schott, Jonathan M.; Crutch, Sebastian J.

2015-01-01

The clinico-neuroradiological syndrome posterior cortical atrophy is the cardinal ‘visual dementia’ and most common atypical Alzheimer’s disease phenotype, offering insights into mechanisms underlying clinical heterogeneity, pathological propagation and basic visual phenomena (e.g. visual crowding). Given the extensive attention paid to patients’ (higher order) perceptual function, it is surprising that there have been no systematic analyses of basic oculomotor function in this population. Here 20 patients with posterior cortical atrophy, 17 patients with typical Alzheimer’s disease and 22 healthy controls completed tests of fixation, saccade (including fixation/target gap and overlap conditions) and smooth pursuit eye movements using an infrared pupil-tracking system. Participants underwent detailed neuropsychological and neurological examinations, with a proportion also undertaking brain imaging and analysis of molecular pathology. In contrast to informal clinical evaluations of oculomotor dysfunction frequency (previous studies: 38%, current clinical examination: 33%), detailed eyetracking investigations revealed eye movement abnormalities in 80% of patients with posterior cortical atrophy (compared to 17% typical Alzheimer’s disease, 5% controls). The greatest differences between posterior cortical atrophy and typical Alzheimer’s disease were seen in saccadic performance. Patients with posterior cortical atrophy made significantly shorter saccades especially for distant targets. They also exhibited a significant exacerbation of the normal gap/overlap effect, consistent with ‘sticky fixation’. Time to reach saccadic targets was significantly associated with parietal and occipital cortical thickness measures. On fixation stability tasks, patients with typical Alzheimer’s disease showed more square wave jerks whose frequency was associated with lower cerebellar grey matter volume, while patients with posterior cortical atrophy showed large saccadic intrusions whose frequency correlated significantly with generalized reductions in cortical thickness. Patients with both posterior cortical atrophy and typical Alzheimer’s disease showed lower gain in smooth pursuit compared to controls. The current study establishes that eye movement abnormalities are near-ubiquitous in posterior cortical atrophy, and highlights multiple aspects of saccadic performance which distinguish posterior cortical atrophy from typical Alzheimer’s disease. We suggest the posterior cortical atrophy oculomotor profile (e.g. exacerbation of the saccadic gap/overlap effect, preserved saccadic velocity) reflects weak input from degraded occipito-parietal spatial representations of stimulus location into a superior collicular spatial map for eye movement regulation. This may indicate greater impairment of identification of oculomotor targets rather than generation of oculomotor movements. The results highlight the critical role of spatial attention and object identification but also precise stimulus localization in explaining the complex real world perception deficits observed in posterior cortical atrophy and many other patients with dementia-related visual impairment. PMID:25895507

Cortical influences drive amyotrophic lateral sclerosis.

PubMed

Eisen, Andrew; Braak, Heiko; Del Tredici, Kelly; Lemon, Roger; Ludolph, Albert C; Kiernan, Matthew C

2017-11-01

The early motor manifestations of sporadic amyotrophic lateral sclerosis (ALS), while rarely documented, reflect failure of adaptive complex motor skills. The development of these skills correlates with progressive evolution of a direct corticomotoneuronal system that is unique to primates and markedly enhanced in humans. The failure of this system in ALS may translate into the split hand presentation, gait disturbance, split leg syndrome and bulbar symptomatology related to vocalisation and breathing, and possibly diffuse fasciculation, characteristic of ALS. Clinical neurophysiology of the brain employing transcranial magnetic stimulation has convincingly demonstrated a presymptomatic reduction or absence of short interval intracortical inhibition, accompanied by increased intracortical facilitation, indicating cortical hyperexcitability. The hallmark of the TDP-43 pathological signature of sporadic ALS is restricted to cortical areas as well as to subcortical nuclei that are under the direct control of corticofugal projections. This provides anatomical support that the origins of the TDP-43 pathology reside in the cerebral cortex itself, secondarily in corticofugal fibres and the subcortical targets with which they make monosynaptic connections. The latter feature explains the multisystem degeneration that characterises ALS. Consideration of ALS as a primary neurodegenerative disorder of the human brain may incorporate concepts of prion-like spread at synaptic terminals of corticofugal axons. Further, such a concept could explain the recognised widespread imaging abnormalities of the ALS neocortex and the accepted relationship between ALS and frontotemporal dementia. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Cortical thinning in former professional soccer players.

PubMed

Koerte, Inga K; Mayinger, Michael; Muehlmann, Marc; Kaufmann, David; Lin, Alexander P; Steffinger, Denise; Fisch, Barbara; Rauchmann, Boris-Stephan; Immler, Stefanie; Karch, Susanne; Heinen, Florian R; Ertl-Wagner, Birgit; Reiser, Maximilian; Stern, Robert A; Zafonte, Ross; Shenton, Martha E

2016-09-01

Soccer is the most popular sport in the world. Soccer players are at high risk for repetitive subconcussive head impact when heading the ball. Whether this leads to long-term alterations of the brain's structure associated with cognitive decline remains unknown. The aim of this study was to evaluate cortical thickness in former professional soccer players using high-resolution structural MR imaging. Fifteen former male professional soccer players (mean age 49.3 [SD 5.1] years) underwent high-resolution structural 3 T MR imaging, as well as cognitive testing. Fifteen male, age-matched former professional non-contact sport athletes (mean age 49.6 [SD 6.4] years) served as controls. Group analyses of cortical thickness were performed using voxel-based statistics. Soccer players demonstrated greater cortical thinning with increasing age compared to controls in the right inferolateral-parietal, temporal, and occipital cortex. Cortical thinning was associated with lower cognitive performance as well as with estimated exposure to repetitive subconcussive head impact. Neurocognitive evaluation revealed decreased memory performance in the soccer players compared to controls. The association of cortical thinning and decreased cognitive performance, as well as exposure to repetitive subconcussive head impact, further supports the hypothesis that repetitive subconcussive head impact may play a role in early cognitive decline in soccer players. Future studies are needed to elucidate the time course of changes in cortical thickness as well as their association with impaired cognitive function and possible underlying neurodegenerative process.

EEG source space analysis of the supervised factor analytic approach for the classification of multi-directional arm movement

NASA Astrophysics Data System (ADS)

Shenoy Handiru, Vikram; Vinod, A. P.; Guan, Cuntai

2017-08-01

Objective. In electroencephalography (EEG)-based brain-computer interface (BCI) systems for motor control tasks the conventional practice is to decode motor intentions by using scalp EEG. However, scalp EEG only reveals certain limited information about the complex tasks of movement with a higher degree of freedom. Therefore, our objective is to investigate the effectiveness of source-space EEG in extracting relevant features that discriminate arm movement in multiple directions. Approach. We have proposed a novel feature extraction algorithm based on supervised factor analysis that models the data from source-space EEG. To this end, we computed the features from the source dipoles confined to Brodmann areas of interest (BA4a, BA4p and BA6). Further, we embedded class-wise labels of multi-direction (multi-class) source-space EEG to an unsupervised factor analysis to make it into a supervised learning method. Main Results. Our approach provided an average decoding accuracy of 71% for the classification of hand movement in four orthogonal directions, that is significantly higher (>10%) than the classification accuracy obtained using state-of-the-art spatial pattern features in sensor space. Also, the group analysis on the spectral characteristics of source-space EEG indicates that the slow cortical potentials from a set of cortical source dipoles reveal discriminative information regarding the movement parameter, direction. Significance. This study presents evidence that low-frequency components in the source space play an important role in movement kinematics, and thus it may lead to new strategies for BCI-based neurorehabilitation.

Toward a Proprioceptive Neural Interface That Mimics Natural Cortical Activity

PubMed Central

Tomlinson, Tucker

2017-01-01

The dramatic advances in efferent neural interfaces over the past decade are remarkable, with cortical signals used to allow paralyzed patients to control the movement of a prosthetic limb or even their own hand. However, this success has thrown into relief, the relative lack of progress in our ability to restore somatosensation to these same patients. Somatosensation, including proprioception, the sense of limb position and movement, plays a crucial role in even basic motor tasks like reaching and walking. Its loss results in crippling deficits. Historical work dating back decades and even centuries has demonstrated that modality-specific sensations can be elicited by activating the central nervous system electrically. Recent work has focused on the challenge of refining these sensations by stimulating the somatosensory cortex (S1) directly. Animals are able to detect particular patterns of stimulation and even associate those patterns with particular sensory cues. Most of this work has involved areas of the somatosensory cortex that mediate the sense of touch. Very little corresponding work has been done for proprioception. Here we describe the effort to develop afferent neural interfaces through spatiotemporally precise intracortical microstimulation (ICMS). We review what is known of the cortical representation of proprioception, and describe recent work in our lab that demonstrates for the first time, that sensations like those of natural proprioception may be evoked by ICMS in S1. These preliminary findings are an important first step to the development of an afferent cortical interface to restore proprioception. PMID:28035576

Toward a Proprioceptive Neural Interface that Mimics Natural Cortical Activity.

PubMed

Tomlinson, Tucker; Miller, Lee E

2016-01-01

The dramatic advances in efferent neural interfaces over the past decade are remarkable, with cortical signals used to allow paralyzed patients to control the movement of a prosthetic limb or even their own hand. However, this success has thrown into relief, the relative lack of progress in our ability to restore somatosensation to these same patients. Somatosensation, including proprioception, the sense of limb position and movement, plays a crucial role in even basic motor tasks like reaching and walking. Its loss results in crippling deficits. Historical work dating back decades and even centuries has demonstrated that modality-specific sensations can be elicited by activating the central nervous system electrically. Recent work has focused on the challenge of refining these sensations by stimulating the somatosensory cortex (S1) directly. Animals are able to detect particular patterns of stimulation and even associate those patterns with particular sensory cues. Most of this work has involved areas of the somatosensory cortex that mediate the sense of touch. Very little corresponding work has been done for proprioception. Here we describe the effort to develop afferent neural interfaces through spatiotemporally precise intracortical microstimulation (ICMS). We review what is known of the cortical representation of proprioception, and describe recent work in our lab that demonstrates for the first time, that sensations like those of natural proprioception may be evoked by ICMS in S1. These preliminary findings are an important first step to the development of an afferent cortical interface to restore proprioception.

Cognitive Control Signals in Posterior Cingulate Cortex

PubMed Central

Hayden, Benjamin Y.; Smith, David V.; Platt, Michael L.

2010-01-01

Efficiently shifting between tasks is a central function of cognitive control. The role of the default network – a constellation of areas with high baseline activity that declines during task performance – in cognitive control remains poorly understood. We hypothesized that task switching demands cognitive control to shift the balance of processing toward the external world, and therefore predicted that switching between the two tasks would require suppression of activity of neurons within the posterior cingulate cortex (CGp). To test this idea, we recorded the activity of single neurons in CGp, a central node in the default network, in monkeys performing two interleaved tasks. As predicted, we found that basal levels of neuronal activity were reduced following a switch from one task to another and gradually returned to pre-switch baseline on subsequent trials. We failed to observe these effects in lateral intraparietal cortex, part of the dorsal fronto-parietal cortical attention network directly connected to CGp. These findings indicate that suppression of neuronal activity in CGp facilitates cognitive control, and suggest that activity in the default network reflects processes that directly compete with control processes elsewhere in the brain. PMID:21160560

Brain-Machine Interface Enables Bimanual Arm Movements in Monkeys

PubMed Central

Ifft, Peter J.; Shokur, Solaiman; Li, Zheng; Lebedev, Mikhail A.; Nicolelis, Miguel A. L.

2014-01-01

Brain-machine interfaces (BMIs) are artificial systems that aim to restore sensation and movement to severely paralyzed patients. However, previous BMIs enabled only single arm functionality, and control of bimanual movements was a major challenge. Here, we developed and tested a bimanual BMI that enabled rhesus monkeys to control two avatar arms simultaneously. The bimanual BMI was based on the extracellular activity of 374–497 neurons recorded from several frontal and parietal cortical areas of both cerebral hemispheres. Cortical activity was transformed into movements of the two arms with a decoding algorithm called a 5th order unscented Kalman filter (UKF). The UKF is well-suited for BMI decoding because it accounts for both characteristics of reaching movements and their representation by cortical neurons. The UKF was trained either during a manual task performed with two joysticks or by having the monkeys passively observe the movements of avatar arms. Most cortical neurons changed their modulation patterns when both arms were engaged simultaneously. Representing the two arms jointly in a single UKF decoder resulted in improved decoding performance compared with using separate decoders for each arm. As the animals’ performance in bimanual BMI control improved over time, we observed widespread plasticity in frontal and parietal cortical areas. Neuronal representation of the avatar and reach targets was enhanced with learning, whereas pairwise correlations between neurons initially increased and then decreased. These results suggest that cortical networks may assimilate the two avatar arms through BMI control. PMID:24197735

Intracortical signal processing of periodontal ligament sensations in rat.

PubMed

Minoda, Aoi; Mizoguchi, Naoko; Kobayashi, Masayuki; Suda, Naoto; Muramoto, Kazuyo

2017-07-04

The somatosensory information from the orofacial region, including the periodontal ligament (PDL), is processed in a manner that differs from that used for other body somatosensory information in the related cortices. It was reported that electrical stimulation to rat PDL elicited activation of the insular oral region (IOR) and the primary (S1) and secondary (S2) somatosensory cortices. However, the physiological relationship between S1 and S2/IOR is not well understood. To address this issue, we performed in vivo optical imaging using a voltage-sensitive dye. Our results demonstrated that the electrical stimulation to the PDL of the mandibular incisor evoked the simultaneous activation of S1 and the S2/IOR. The stimulation to the initial response area of the S1 evoked responses in the S2/IOR, and vice versa. An injection of tetrodotoxin (TTX) to the cortical region between S1 and S2/IOR attenuated such elicited responses only in the non-stimulated cortical partner site. The cortico-cortical interaction between S1 and S2/IOR was suppressed by the application of TTX, indicating that these two cortical regions bi-directionally communicate the signal processing of PDL sensations. An injection of FluoroGold™ (FG) to the initial response area in S1 or the S2/IOR showed that FG-positive cells were scattered in the non-injected cortical counterpart. This morphological result demonstrated the presence of a bi-directional intracortical connection between the initial response areas in S1 and the S2/IOR. These findings suggest the presence of a mutual connection between S1 and the S2/IOR as an intracortical signal processing network for orofacial nociception. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Using an Artificial Neural Bypass to Restore Cortical Control of Rhythmic Movements in a Human with Quadriplegia

NASA Astrophysics Data System (ADS)

Sharma, Gaurav; Friedenberg, David A.; Annetta, Nicholas; Glenn, Bradley; Bockbrader, Marcie; Majstorovic, Connor; Domas, Stephanie; Mysiw, W. Jerry; Rezai, Ali; Bouton, Chad

2016-09-01

Neuroprosthetic technology has been used to restore cortical control of discrete (non-rhythmic) hand movements in a paralyzed person. However, cortical control of rhythmic movements which originate in the brain but are coordinated by Central Pattern Generator (CPG) neural networks in the spinal cord has not been demonstrated previously. Here we show a demonstration of an artificial neural bypass technology that decodes cortical activity and emulates spinal cord CPG function allowing volitional rhythmic hand movement. The technology uses a combination of signals recorded from the brain, machine-learning algorithms to decode the signals, a numerical model of CPG network, and a neuromuscular electrical stimulation system to evoke rhythmic movements. Using the neural bypass, a quadriplegic participant was able to initiate, sustain, and switch between rhythmic and discrete finger movements, using his thoughts alone. These results have implications in advancing neuroprosthetic technology to restore complex movements in people living with paralysis.

Adaptive training of cortical feature maps for a robot sensorimotor controller.

PubMed

Adams, Samantha V; Wennekers, Thomas; Denham, Sue; Culverhouse, Phil F

2013-08-01

This work investigates self-organising cortical feature maps (SOFMs) based upon the Kohonen Self-Organising Map (SOM) but implemented with spiking neural networks. In future work, the feature maps are intended as the basis for a sensorimotor controller for an autonomous humanoid robot. Traditional SOM methods require some modifications to be useful for autonomous robotic applications. Ideally the map training process should be self-regulating and not require predefined training files or the usual SOM parameter reduction schedules. It would also be desirable if the organised map had some flexibility to accommodate new information whilst preserving previous learnt patterns. Here methods are described which have been used to develop a cortical motor map training system which goes some way towards addressing these issues. The work is presented under the general term 'Adaptive Plasticity' and the main contribution is the development of a 'plasticity resource' (PR) which is modelled as a global parameter which expresses the rate of map development and is related directly to learning on the afferent (input) connections. The PR is used to control map training in place of a traditional learning rate parameter. In conjunction with the PR, random generation of inputs from a set of exemplar patterns is used rather than predefined datasets and enables maps to be trained without deciding in advance how much data is required. An added benefit of the PR is that, unlike a traditional learning rate, it can increase as well as decrease in response to the demands of the input and so allows the map to accommodate new information when the inputs are changed during training. Copyright © 2013 Elsevier Ltd. All rights reserved.

Mapping the stability of human brain asymmetry across five sex-chromosome aneuploidies.

PubMed

Lin, Amy; Clasen, Liv; Lee, Nancy Raitano; Wallace, Gregory L; Lalonde, Francois; Blumenthal, Jonathan; Giedd, Jay N; Raznahan, Armin

2015-01-07

The human brain displays stereotyped and early emerging patterns of cortical asymmetry in health. It is unclear if these asymmetries are highly sensitive to genetic and environmental variation or fundamental features of the brain that can survive severe developmental perturbations. To address this question, we mapped cortical thickness (CT) asymmetry in a group of genetically defined disorders known to impact CT development. Participants included 137 youth with one of five sex-chromosome aneuploidies [SCAs; XXX (n = 28), XXY (n = 58), XYY (n = 26), XXYY (n = 20), and XXXXY (n = 5)], and 169 age-matched typically developing controls (80 female). In controls, we replicated previously reported rightward inferior frontal and leftward lateral parietal CT asymmetry. These opposing frontoparietal CT asymmetries were broadly preserved in all five SCA groups. However, we also detected foci of shifting CT asymmetry with aneuploidy, which fell almost exclusively within regions of significant CT asymmetry in controls. Specifically, X-chromosome aneuploidy accentuated normative rightward inferior frontal asymmetries, while Y-chromosome aneuploidy reversed normative rightward medial prefrontal and lateral temporal asymmetries. These findings indicate that (1) the stereotyped normative pattern of opposing frontoparietal CT asymmetry arises from developmental mechanisms that can withstand gross chromosomal aneuploidy and (2) X and Y chromosomes can exert focal, nonoverlapping and directionally opposed influences on CT asymmetry within cortical regions of significant asymmetry in health. Our study attests to the resilience of developmental mechanisms that support the global patterning of CT asymmetry in humans, and motivates future research into the molecular bases and functional consequences of sex chromosome dosage effects on CT asymmetry. Copyright © 2015 the authors 0270-6474/15/350140-06$15.00/0.

Altered cortical processing of motor inhibition in schizophrenia.

PubMed

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

2016-12-01

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

The role of asymmetric frontal cortical activity in emotion-related phenomena: a review and update.

PubMed

Harmon-Jones, Eddie; Gable, Philip A; Peterson, Carly K

2010-07-01

Conceptual and empirical approaches to the study of the role of asymmetric frontal cortical activity in emotional processes are reviewed. Although early research suggested that greater left than right frontal cortical activity was associated with positive affect, more recent research, primarily on anger, suggests that greater left than right frontal cortical activity is associated with approach motivation, which can be positive (e.g., enthusiasm) or negative in valence (e.g., anger). In addition to reviewing this research on anger, research on guilt, bipolar disorder, and various types of positive affect is reviewed with relation to their association with asymmetric frontal cortical activity. The reviewed research not only contributes to a more complete understanding of the emotive functions of asymmetric frontal cortical activity, but it also points to the importance of considering motivational direction as separate from affective valence in psychological models of emotional space. Copyright © 2009 Elsevier B.V. All rights reserved.

SU90. The Relationship Between Changes in Cortical Thickness and Cognitive Empathy in Individuals With Schizophrenia

PubMed Central

Petersen, Julie; Cobia, Derin

2017-01-01

Abstract Background: Prior studies suggest the thickness of the medial prefrontal cortex (mPFC), inferior frontal gyrus (IFG), anterior mid-cingulate (aMCC), insula (INS), supplementary motor area (SMA), temporo-parietal junction (TPJ), and precuneus (PREC) are associated with cognitive empathy, which is impaired in schizophrenia. The current study examines the relationship between cognitive empathy performance at baseline and changes in cortical thickness in both healthy controls and individuals with schizophrenia. Methods: Thirty clinically stable community-dwelling individuals with schizophrenia and 26 healthy controls group-matched on demographic variables completed a cognitive empathy task and structural magnetic resonance imaging at 2 time points approximately 24 months apart. Difference scores representing change in cortical thickness were calculated as: follow-up − baseline = difference score. Repeated-measures ANOVAs evaluated changes in cortical thickness between groups. OLS regressions were computed to determine the effect of cognitive empathy performance on change in cortical thickness. Results: Change in cortical thickness in individuals with schizophrenia differed from controls in the mPFC, IFG, INS, SMA, TPJ, and PREC 
(all P < .05) between baseline and 2-year follow-up. Among individuals with schizophrenia, we found that baseline cognitive empathy performance predicted changes in cortical thickness in the left (b = 0.346, t(28) = 3.752, P < .001) and right precuneus (b = 0.399, t(28) = 3.649, P < .001), and left (b = 0.319, t(28) = 3.141, P = .004) and right TPJ (b = 0.294, t(28) = 2.7, P = .012). We did not observe a relationship between baseline cognitive empathy performance and changes in cortical thickness of the empathy circuit in controls. Conclusion: Consistent with prior studies, we observed that individuals with schizophrenia had greater thinning in cortical regions, which were specific to the empathy circuit. Also, we observed that baseline cognitive empathy performance predicted greater cortical thinning among individuals with schizophrenia. It is possible that individuals with schizophrenia who have greater cognitive empathy are more likely to engage in social activities, which might be neuroprotective. Future research is needed to evaluate these relationships.

Fatigue of immature baboon cortical bone.

PubMed

Keller, T S; Lovin, J D; Spengler, D M; Carter, D R

1985-01-01

Strain-controlled uniaxial fatigue and monotonic tensile tests were conducted on turned femoral cortical bone specimens obtained from baboons at various ages of maturity. Fatigue loading produced a progressive loss in stiffness and an increase in hysteresis prior to failure, indicating that immature primate cortical bone responds to repeated loading in a fashion similar to that previously observed for adult human cortical bone. Bone fatigue resistance under this strain controlled testing decreased during maturation. Maturation was also associated with an increase in bone dry density, ash fraction and elastic modulus. The higher elastic modulus of more mature bone meant that these specimens were subjected to higher stress levels during testing than more immature bone specimens. Anatomical regions along the femoral shaft exhibited differences in strength and fatigue resistance.

Effects of smoking marijuana on focal attention and brain blood flow.

PubMed

O'Leary, Daniel S; Block, Robert I; Koeppel, Julie A; Schultz, Susan K; Magnotta, Vincent A; Ponto, Laura Boles; Watkins, G Leonard; Hichwa, Richard D

2007-04-01

Using an attention task to control cognitive state, we previously found that smoking marijuana changes regional cerebral blood flow (rCBF). The present study measured rCBF during tasks requiring attention to left and right ears in different conditions. Twelve occasional marijuana users (mean age 23.5 years) were imaged with PET using [15O]water after smoking marijuana or placebo cigarettes as they performed a reaction time (RT) baseline task, and a dichotic listening task with attend-right- and attend-left-ear instructions. Smoking marijuana, but not placebo, resulted in increased normalized rCBF in orbital frontal cortex, anterior cingulate, temporal pole, insula, and cerebellum. RCBF was reduced in visual and auditory cortices. These changes occurred in all three tasks and replicated our earlier studies. They appear to reflect the direct effects of marijuana on the brain. Smoking marijuana lowered rCBF in auditory cortices compared to placebo but did not alter the normal pattern of attention-related rCBF asymmetry (i.e., greater rCBF in the temporal lobe contralateral to the direction of attention) that was also observed after placebo. These data indicate that marijuana has dramatic direct effects on rCBF, but causes relatively little change in the normal pattern of task-related rCBF on this auditory focused attention task. Copyright 2007 John Wiley & Sons, Ltd.

Cortical Thinning in Network-Associated Regions in Cognitively Normal and Below-Normal Range Schizophrenia

PubMed Central

Pinnock, Farena; Parlar, Melissa; Hawco, Colin; Hanford, Lindsay; Hall, Geoffrey B.

2017-01-01

This study assessed whether cortical thickness across the brain and regionally in terms of the default mode, salience, and central executive networks differentiates schizophrenia patients and healthy controls with normal range or below-normal range cognitive performance. Cognitive normality was defined using the MATRICS Consensus Cognitive Battery (MCCB) composite score (T = 50 ± 10) and structural magnetic resonance imaging was used to generate cortical thickness data. Whole brain analysis revealed that cognitively normal range controls (n = 39) had greater cortical thickness than both cognitively normal (n = 17) and below-normal range (n = 49) patients. Cognitively normal controls also demonstrated greater thickness than patients in regions associated with the default mode and salience, but not central executive networks. No differences on any thickness measure were found between cognitively normal range and below-normal range controls (n = 24) or between cognitively normal and below-normal range patients. In addition, structural covariance between network regions was high and similar across subgroups. Positive and negative symptom severity did not correlate with thickness values. Cortical thinning across the brain and regionally in relation to the default and salience networks may index shared aspects of the psychotic psychopathology that defines schizophrenia with no relation to cognitive impairment. PMID:28348889

Cortical bone thickening in Type A posterior atlas arch defects: experimental report.

PubMed

Sanchis-Gimeno, Juan A; Llido, Susanna; Guede, David; Martinez-Soriano, Francisco; Ramon Caeiro, Jose; Blanco-Perez, Esther

2017-03-01

To date, no information about the cortical bone microstructural properties in atlas vertebrae with posterior arch defects has been reported. To test if there is an increased cortical bone thickening in atlases with Type A posterior atlas arch defects in an experimental model. Micro-computed tomography (CT) study on cadaveric atlas vertebrae. We analyzed the cortical bone thickness, the cortical volume, and the medullary volume (SkyScan 1172 Bruker micro-CT NV, Kontich, Belgium) in cadaveric dry vertebrae with a Type A atlas arch defect and normal control vertebrae. The micro-CT study revealed significant differences in cortical bone thickness (p=.005), cortical volume (p=.003), and medullary volume (p=.009) values between the normal and the Type A vertebrae. Type A congenital atlas arch defects present a cortical bone thickening that may play a protective role against atlas fractures. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Cortical Bone Morphological and Trabecular Bone Microarchitectural Changes in the Mandible and Femoral Neck of Ovariectomized Rats

PubMed Central

Hsu, Pei-Yu; Tsai, Ming-Tzu; Wang, Shun-Ping; Chen, Ying-Ju; Wu, Jay; Hsu, Jui-Ting

2016-01-01

Objective This study used microcomputed tomography (micro-CT) to evaluate the effects of ovariectomy on the trabecular bone microarchitecture and cortical bone morphology in the femoral neck and mandible of female rats. Materials and Methods Twelve female Wister rats were divided into two groups: the control and ovariectomized groups. The rats in the ovariectomized group received ovariectomy at 8 weeks of age; all the rats were sacrificed at 20 weeks of age, and their mandibles and femurs were removed and scanned using micro-CT. Four microstructural trabecular bone parameters were measured for the region below the first mandibular molar and the femoral neck region: bone volume fraction (BV/TV), trabecular thickness (TbTh), trabecular separation (TbSp), and trabecular number (TbN). In addition, four cortical bone parameters were measured for the femoral neck region: total cross-sectional area (TtAr), cortical area (CtAr), cortical bone area fraction (CtAr/TtAr), and cortical thickness (CtTh). The CtTh at the masseteric ridge was used to assess the cortical bone morphology in the mandible. The trabecular bone microarchitecture and cortical bone morphology in the femoral necks and mandibles of the control group were compared with those of the ovariectomized group. Furthermore, Spearman’s correlation (rs) was conducted to analyze the correlation between the osteoporosis conditions of the mandible and femoral neck. Results Regarding the trabecular bone microarchitectural parameters, the BV/TV of the trabecular bone microarchitecture in the femoral necks of the control group (61.199±11.288%, median ± interquartile range) was significantly greater than that of the ovariectomized group (40.329±5.153%). Similarly, the BV/TV of the trabecular bone microarchitecture in the mandibles of the control group (51.704±6.253%) was significantly greater than that of the ovariectomized group (38.486±9.111%). Furthermore, the TbSp of the femoral necks in the ovariectomized group (0.185±0.066 mm) was significantly greater than that in the control group (0.130±0.026mm). Similarly, the TbSp of the mandibles in the ovariectomized group (0.322±0.047mm) was significantly greater than that in the control group (0.285±0.041mm). However, the TbTh and TbN trends for the mandibles and femoral necks were inconsistent between the control and ovariectomized groups. Regarding the cortical bone morphology parameters, the TtAr of the femoral necks in the ovariectomized group was significantly smaller than that in the control group. There was no significant difference in the TtAr, CtAr, or CtTh of the femoral necks between the control and ovariectomized groups, and no significant difference in the CtTh of the mandibles between the control and ovariectomized groups. Moreover, the BV/TV and TbSp of the mandibles were highly correlated with those of the femurs (rs = 0.874 and rs = 0.755 for BV/TV and TbSp, respectively). Nevertheless, the TbTh, TbN, and CtTh of the mandibles were not correlated with those of the femoral necks. Conclusion After the rats were ovariectomized, osteoporosis of the trabecular bone microarchitecture occurred in their femurs and mandibles; however, ovariectomy did not influence the cortical bone morphology. In addition, the parametric values of the trabecular bone microarchitecture in the femoral necks were highly correlated with those of the trabecular bone microarchitecture in the mandibles. PMID:27127909

Control of Chaos: New Perspectives in Experimental and Theoretical Science. International Journal of Bifurcation and Chaos in Applied Sciences and Engineering. Theme Issue. Part 2, Volume 8, Number 9, September 1998.

DTIC Science & Technology

1998-09-01

discharges in the Onchidium pacemaker neu- "Episodic multiregional cortical coherence at multiple ron," J. Theor. Biol. 156, 269-291. frequencies during...with delay: A model of synchronization of Sepulchre, J. A. & Babloyantz, A. [1993] "Controlling cortical tissue," Neural Comput. 6, 1141-1154...generating circuit of different 363, 411 417. networks," Nature 351, 60-63. Singer, W. [1993] "Synchronization of cortical activity Mpitsos, G. J., Burton, R

Modulation of Specific Sensory Cortical Areas by Segregated Basal Forebrain Cholinergic Neurons Demonstrated by Neuronal Tracing and Optogenetic Stimulation in Mice

PubMed Central

Chaves-Coira, Irene; Barros-Zulaica, Natali; Rodrigo-Angulo, Margarita; Núñez, Ángel

2016-01-01

Neocortical cholinergic activity plays a fundamental role in sensory processing and cognitive functions. Previous results have suggested a refined anatomical and functional topographical organization of basal forebrain (BF) projections that may control cortical sensory processing in a specific manner. We have used retrograde anatomical procedures to demonstrate the existence of specific neuronal groups in the BF involved in the control of specific sensory cortices. Fluoro-Gold (FlGo) and Fast Blue (FB) fluorescent retrograde tracers were deposited into the primary somatosensory (S1) and primary auditory (A1) cortices in mice. Our results revealed that the BF is a heterogeneous area in which neurons projecting to different cortical areas are segregated into different neuronal groups. Most of the neurons located in the horizontal limb of the diagonal band of Broca (HDB) projected to the S1 cortex, indicating that this area is specialized in the sensory processing of tactile stimuli. However, the nucleus basalis magnocellularis (B) nucleus shows a similar number of cells projecting to the S1 as to the A1 cortices. In addition, we analyzed the cholinergic effects on the S1 and A1 cortical sensory responses by optogenetic stimulation of the BF neurons in urethane-anesthetized transgenic mice. We used transgenic mice expressing the light-activated cation channel, channelrhodopsin-2, tagged with a fluorescent protein (ChR2-YFP) under the control of the choline-acetyl transferase promoter (ChAT). Cortical evoked potentials were induced by whisker deflections or by auditory clicks. According to the anatomical results, optogenetic HDB stimulation induced more extensive facilitation of tactile evoked potentials in S1 than auditory evoked potentials in A1, while optogenetic stimulation of the B nucleus facilitated either tactile or auditory evoked potentials equally. Consequently, our results suggest that cholinergic projections to the cortex are organized into segregated pools of neurons that may modulate specific cortical areas. PMID:27147975

Modulation of Specific Sensory Cortical Areas by Segregated Basal Forebrain Cholinergic Neurons Demonstrated by Neuronal Tracing and Optogenetic Stimulation in Mice.

PubMed

Chaves-Coira, Irene; Barros-Zulaica, Natali; Rodrigo-Angulo, Margarita; Núñez, Ángel

2016-01-01

Neocortical cholinergic activity plays a fundamental role in sensory processing and cognitive functions. Previous results have suggested a refined anatomical and functional topographical organization of basal forebrain (BF) projections that may control cortical sensory processing in a specific manner. We have used retrograde anatomical procedures to demonstrate the existence of specific neuronal groups in the BF involved in the control of specific sensory cortices. Fluoro-Gold (FlGo) and Fast Blue (FB) fluorescent retrograde tracers were deposited into the primary somatosensory (S1) and primary auditory (A1) cortices in mice. Our results revealed that the BF is a heterogeneous area in which neurons projecting to different cortical areas are segregated into different neuronal groups. Most of the neurons located in the horizontal limb of the diagonal band of Broca (HDB) projected to the S1 cortex, indicating that this area is specialized in the sensory processing of tactile stimuli. However, the nucleus basalis magnocellularis (B) nucleus shows a similar number of cells projecting to the S1 as to the A1 cortices. In addition, we analyzed the cholinergic effects on the S1 and A1 cortical sensory responses by optogenetic stimulation of the BF neurons in urethane-anesthetized transgenic mice. We used transgenic mice expressing the light-activated cation channel, channelrhodopsin-2, tagged with a fluorescent protein (ChR2-YFP) under the control of the choline-acetyl transferase promoter (ChAT). Cortical evoked potentials were induced by whisker deflections or by auditory clicks. According to the anatomical results, optogenetic HDB stimulation induced more extensive facilitation of tactile evoked potentials in S1 than auditory evoked potentials in A1, while optogenetic stimulation of the B nucleus facilitated either tactile or auditory evoked potentials equally. Consequently, our results suggest that cholinergic projections to the cortex are organized into segregated pools of neurons that may modulate specific cortical areas.

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

Biomechanics of the Proximal Radius Following Drilling of the Bicipital Tuberosity to Mimic Cortical Button Distal Biceps Repair Technique.

PubMed

Oak, Nikhil R; Lien, John R; Brunfeldt, Alexander; Lawton, Jeffrey N

2018-05-01

A fracture through the proximal radius is a theoretical concern after cortical button distal biceps fixation in an active patient. The permanent, nonossified cortical defect and medullary tunnel is at risk during a fall eliciting rotational and compressive forces. We hypothesized that during simulated torsion and compression, in comparison with unaltered specimens, the cortical button distal biceps repair model would have decreased torsional and compressive strength and would fracture in the vicinity of the bicipital tuberosity bone tunnel. Sixteen fourth-generation composite radius Sawbones models were used in this controlled laboratory study. A bone tunnel was created through the bicipital tuberosity to mimic the exact bone tunnel, 8 mm near cortex and 3.2 mm far cortex, made for the BicepsButton distal biceps tendon repair. The radius was then prepared and mounted on either a torsional or compression testing device and compared with undrilled control specimens. Compression tests resulted in average failure loads of 9015.2 N in controls versus 8253.25 N in drilled specimens ( P = .074). Torsional testing resulted in an average failure torque of 27.3 Nm in controls and 19.3 Nm in drilled specimens ( P = .024). Average fracture angle was 35.1° in controls versus 21.1° in drilled. Gross fracture patterns were similar in compression testing; however, in torsional testing all fractures occurred through the bone tunnel in the drilled group. There are weaknesses in the vicinity of the bone tunnel in the proximal radius during biomechanical stress testing which may not be clinically relevant in nature. In cortical button fixation, distal biceps repairs creates a permanent, nonossified cortical defect with tendon interposed in the bone tunnel, which can alter the biomechanical properties of the proximal radius during compressive and torsional loading.

Linking Major Depression and The Neural Substrates of Associative Processing

PubMed Central

Harel, Eiran Vadim; Tennyson, Robert Langley; Fava, Maurizio; Bar, Moshe

2016-01-01

It has been proposed that mood correlates with the breadth of associative thinking. Here we set to test this hypothesis in healthy and depressed individuals. Generating contextual associations engages a network of cortical regions including the parahippocampal cortex (PHC), retrosplenial complex, and medial prefrontal cortex. The link between mood, associative processing, and its underlying cortical infrastructure provides a promising avenue for elucidating the mechanisms underlying cognitive impairments in Major Depressive Disorder (MDD). Participants included fifteen non-medicated individuals with acute Major Depressive Episode and fifteen healthy matched controls. In an fMRI experiment, participants viewed images of objects that are either strongly or weakly associated with a specific context (e.g., a beach chair vs. a water bottle), while rating the commonality of each object. Analyses were performed to examine brain activation and structural differences between groups. Consistent with our hypothesis, controls showed greater activation of the contextual associations network compared with depressed participants. In addition, PHC structural volume was correlated with ruminative tendency and, volumes of the hippocampal subfields were significantly smaller in depressed participants. Surprisingly, depressed participants showed increased activity in the entorhinal cortex (ERC) compared with controls. We integrate these findings within a mechanistic account linking mood and associative thinking, and suggest directions for the future. PMID:27553369

Cortical Plasticity Induction by Pairing Subthalamic Nucleus Deep-Brain Stimulation and Primary Motor Cortical Transcranial Magnetic Stimulation in Parkinson's Disease.

PubMed

Udupa, Kaviraja; Bahl, Nina; Ni, Zhen; Gunraj, Carolyn; Mazzella, Filomena; Moro, Elena; Hodaie, Mojgan; Lozano, Andres M; Lang, Anthony E; Chen, Robert

2016-01-13

Noninvasive brain stimulation studies have shown abnormal motor cortical plasticity in Parkinson's disease (PD). These studies used peripheral nerve stimulation paired with transcranial magnetic stimulation (TMS) to primary motor cortex (M1) at specific intervals to induce plasticity. Induction of cortical plasticity through stimulation of the basal ganglia (BG)-M1 connections has not been studied. In the present study, we used a novel technique of plasticity induction by repeated pairing of deep-brain stimulation (DBS) of the BG with M1 stimulation using TMS. We hypothesize that repeated pairing of subthalamic nucleus (STN)-DBS and M1-TMS at specific time intervals will lead to plasticity in the M1. Ten PD human patients with STN-DBS were studied in the on-medication state with DBS set to 3 Hz. The interstimulus intervals (ISIs) between STN-DBS and TMS that produced cortical facilitation were determined individually for each patient. Three plasticity induction conditions with repeated pairings (180 times) at specific ISIs (∼ 3 and ∼ 23 ms) that produced cortical facilitation and a control ISI of 167 ms were tested in random order. Repeated pairing of STN-DBS and M1-TMS at short (∼ 3 ms) and medium (∼ 23 ms) latencies increased M1 excitability that lasted for at least 45 min, whereas the control condition (fixed ISI of 167 ms) had no effect. There were no specific changes in motor thresholds, intracortical circuits, or recruitment curves. Our results indicate that paired-associative cortical plasticity can be induced by repeated STN and M1 stimulation at specific intervals. These results show that STN-DBS can modulate cortical plasticity. We introduced a new experimental paradigm to test the hypothesis that pairing subthalamic nucleus deep-brain stimulation (STN-DBS) with motor cortical transcranial magnetic stimulation (M1-TMS) at specific times can induce cortical plasticity in patients with Parkinson's disease (PD). We found that repeated pairing of STN-DBS with TMS at short (∼ 3 ms) and medium (∼ 23 ms) intervals increased cortical excitability that lasted for up to 45 min, whereas the control condition (fixed latency of 167 ms) had no effects on cortical excitability. This is the first demonstration of associative plasticity in the STN-M1 circuits in PD patients using this novel technique. The potential therapeutic effects of combining DBS and noninvasive cortical stimulation should be investigated further. Copyright © 2016 the authors 0270-6474/16/360397-09$15.00/0.

Directed Interaction Between Monkey Premotor and Posterior Parietal Cortex During Motor-Goal Retrieval from Working Memory

PubMed Central

Martínez-Vázquez, Pablo; Gail, Alexander

2018-01-01

Abstract Goal-directed behavior requires cognitive control of action, putatively by means of frontal-lobe impact on posterior brain areas. We investigated frontoparietal directed interaction (DI) in monkeys during memory-guided rule-based reaches, to test if DI supports motor-goal selection or working memory (WM) processes. We computed DI between the parietal reach region (PRR) and dorsal premotor cortex (PMd) with a Granger-causality measure of intracortical local field potentials (LFP). LFP mostly in the beta (12–32 Hz) and low-frequency (f≤10Hz) ranges contributed to DI. During movement withholding, beta-band activity in PRR had a Granger-causal effect on PMd independent of WM content. Complementary, low-frequency PMd activity had a transient Granger-causing effect on PRR specifically during WM retrieval of spatial motor goals, while no DI was associated with preliminary motor-goal selection. Our results support the idea that premotor and posterior parietal cortices interact functionally to achieve cognitive control during goal-directed behavior, in particular, that frontal-to-parietal interaction occurs during retrieval of motor-goal information from spatial WM. PMID:29481586

Directed Interaction Between Monkey Premotor and Posterior Parietal Cortex During Motor-Goal Retrieval from Working Memory.

PubMed

Martínez-Vázquez, Pablo; Gail, Alexander

2018-05-01

Goal-directed behavior requires cognitive control of action, putatively by means of frontal-lobe impact on posterior brain areas. We investigated frontoparietal directed interaction (DI) in monkeys during memory-guided rule-based reaches, to test if DI supports motor-goal selection or working memory (WM) processes. We computed DI between the parietal reach region (PRR) and dorsal premotor cortex (PMd) with a Granger-causality measure of intracortical local field potentials (LFP). LFP mostly in the beta (12-32 Hz) and low-frequency (f≤10Hz) ranges contributed to DI. During movement withholding, beta-band activity in PRR had a Granger-causal effect on PMd independent of WM content. Complementary, low-frequency PMd activity had a transient Granger-causing effect on PRR specifically during WM retrieval of spatial motor goals, while no DI was associated with preliminary motor-goal selection. Our results support the idea that premotor and posterior parietal cortices interact functionally to achieve cognitive control during goal-directed behavior, in particular, that frontal-to-parietal interaction occurs during retrieval of motor-goal information from spatial WM.

Imaging of amyloid deposition in human brain using positron emission tomography and [18F]FACT: comparison with [11C]PIB.

PubMed

Ito, Hiroshi; Shinotoh, Hitoshi; Shimada, Hitoshi; Miyoshi, Michie; Yanai, Kazuhiko; Okamura, Nobuyuki; Takano, Harumasa; Takahashi, Hidehiko; Arakawa, Ryosuke; Kodaka, Fumitoshi; Ono, Maiko; Eguchi, Yoko; Higuchi, Makoto; Fukumura, Toshimitsu; Suhara, Tetsuya

2014-04-01

The characteristic neuropathological changes in Alzheimer's disease (AD) are deposition of amyloid senile plaques and neurofibrillary tangles. The (18)F-labeled amyloid tracer, [(18)F]2-[(2-{(E)-2-[2-(dimethylamino)-1,3-thiazol-5-yl]vinyl}-1,3-benzoxazol-6-yl)oxy]-3-fluoropropan-1-ol (FACT), one of the benzoxazole derivatives, was recently developed. In the present study, deposition of amyloid senile plaques was measured by positron emission tomography (PET) with both [(11)C]Pittsburgh compound B (PIB) and [(18)F]FACT in the same subjects, and the regional uptakes of both radiotracers were directly compared. Two PET scans, one of each with [(11)C]PIB and [(18)F]FACT, were performed sequentially on six normal control subjects, two mild cognitive impairment (MCI) patients, and six AD patients. The standardized uptake value ratio of brain regions to the cerebellum was calculated with partial volume correction using magnetic resonance (MR) images to remove the effects of white matter accumulation. No significant differences in the cerebral cortical uptake were observed between normal control subjects and AD patients in [(18)F]FACT studies without partial volume correction, while significant differences were observed in [(11)C]PIB. After partial volume correction, the cerebral cortical uptake was significantly larger in AD patients than in normal control subjects for [(18)F]FACT studies as well as [(11)C]PIB. Relatively lower uptakes of [(11)C]PIB in distribution were observed in the medial side of the temporal cortex and in the occipital cortex as compared with [(18)F]FACT. Relatively higher uptake of [(11)C]PIB in distribution was observed in the frontal and parietal cortices. Since [(18)F]FACT might bind more preferentially to dense-cored amyloid deposition, regional differences in cerebral cortical uptake between [(11)C]PIB and [(18)F]FACT might be due to differences in regional distribution between diffuse and dense-cored amyloid plaque shown in the autoradiographic and histochemical assays of postmortem AD brain sections.

Behavioral approach and orbitofrontal cortical activity during decision-making in substance dependence.

PubMed

Yamamoto, Dorothy J; Banich, Marie T; Regner, Michael F; Sakai, Joseph T; Tanabe, Jody

2017-11-01

Behavioral approach, defined as behavior directed toward a reward or novel stimulus, when elevated, may increase one's vulnerability to substance use disorder. Behavioral approach has been associated with relatively greater left compared to right frontal activity; behavioral inhibition may be associated with relatively greater right compared to left frontal brain activity. We hypothesized that substance dependent individuals (SDI) would have higher behavioral approach than controls and greater prefrontal cortical activity during decision-making involving reward. We hypothesized that behavioral approach would correlate with left frontal activity during decision-making and that the correlation would be stronger in SDI than controls. 31 SDI and 21 controls completed the Behavioral Inhibition System/Behavioral Approach System (BIS/BAS) scales and performed a decision-making task during fMRI. Orbitofrontal (OFC) and dorsolateral prefrontal activity were correlated with BIS and BAS scores. Compared to controls, SDI had higher BAS Fun Seeking scores (p<0.001) and worse decision-making performance (p=0.004). BAS Fun Seeking correlated with left OFC activity during decision-making across group (r=0.444, p<0.003). The correlation did not differ by group. There was no correlation between BIS and right frontal activity. Left OFC may play a role in reward-related decision-making in substance use disorder especially in individuals with high behavioral approach. Copyright © 2017 Elsevier B.V. All rights reserved.

Cortical thickness of the dorsolateral prefrontal cortex predicts strategic choices in economic games.

PubMed

Yamagishi, Toshio; Takagishi, Haruto; Fermin, Alan de Souza Rodrigues; Kanai, Ryota; Li, Yang; Matsumoto, Yoshie

2016-05-17

Human prosociality has been traditionally explained in the social sciences in terms of internalized social norms. Recent neuroscientific studies extended this traditional view of human prosociality by providing evidence that prosocial choices in economic games require cognitive control of the impulsive pursuit of self-interest. However, this view is challenged by an intuitive prosociality view emphasizing the spontaneous and heuristic basis of prosocial choices in economic games. We assessed the brain structure of 411 players of an ultimatum game (UG) and a dictator game (DG) and measured the strategic reasoning ability of 386. According to the reflective norm-enforcement view of prosociality, only those capable of strategically controlling their selfish impulses give a fair share in the UG, but cognitive control capability should not affect behavior in the DG. Conversely, we support the intuitive prosociality view by showing for the first time, to our knowledge, that strategic reasoning and cortical thickness of the dorsolateral prefrontal cortex were not related to giving in the UG but were negatively related to giving in the DG. This implies that the uncontrolled choice in the DG is prosocial rather than selfish, and those who have a thicker dorsolateral prefrontal cortex and are capable of strategic reasoning (goal-directed use of the theory of mind) control this intuitive drive for prosociality as a means to maximize reward when there are no future implications of choices.

Cortical thickness of the dorsolateral prefrontal cortex predicts strategic choices in economic games

PubMed Central

Yamagishi, Toshio; Takagishi, Haruto; Fermin, Alan de Souza Rodrigues; Kanai, Ryota; Li, Yang; Matsumoto, Yoshie

2016-01-01

Human prosociality has been traditionally explained in the social sciences in terms of internalized social norms. Recent neuroscientific studies extended this traditional view of human prosociality by providing evidence that prosocial choices in economic games require cognitive control of the impulsive pursuit of self-interest. However, this view is challenged by an intuitive prosociality view emphasizing the spontaneous and heuristic basis of prosocial choices in economic games. We assessed the brain structure of 411 players of an ultimatum game (UG) and a dictator game (DG) and measured the strategic reasoning ability of 386. According to the reflective norm-enforcement view of prosociality, only those capable of strategically controlling their selfish impulses give a fair share in the UG, but cognitive control capability should not affect behavior in the DG. Conversely, we support the intuitive prosociality view by showing for the first time, to our knowledge, that strategic reasoning and cortical thickness of the dorsolateral prefrontal cortex were not related to giving in the UG but were negatively related to giving in the DG. This implies that the uncontrolled choice in the DG is prosocial rather than selfish, and those who have a thicker dorsolateral prefrontal cortex and are capable of strategic reasoning (goal-directed use of the theory of mind) control this intuitive drive for prosociality as a means to maximize reward when there are no future implications of choices. PMID:27140622

Cortical Correlates of Fitts’ Law

PubMed Central

Ifft, Peter J.; Lebedev, Mikhail A.; Nicolelis, Miguel A. L.

2011-01-01

Fitts’ law describes the fundamental trade-off between movement accuracy and speed: it states that the duration of reaching movements is a function of target size (TS) and distance. While Fitts’ law has been extensively studied in ergonomics and has guided the design of human–computer interfaces, there have been few studies on its neuronal correlates. To elucidate sensorimotor cortical activity underlying Fitts’ law, we implanted two monkeys with multielectrode arrays in the primary motor (M1) and primary somatosensory (S1) cortices. The monkeys performed reaches with a joystick-controlled cursor toward targets of different size. The reaction time (RT), movement time, and movement velocity changed with TS, and M1 and S1 activity reflected these changes. Moreover, modifications of cortical activity could not be explained by changes of movement parameters alone, but required TS as an additional parameter. Neuronal representation of TS was especially prominent during the early RT period where it influenced the slope of the firing rate rise preceding movement initiation. During the movement period, cortical activity was correlated with movement velocity. Neural decoders were applied to simultaneously decode TS and motor parameters from cortical modulations. We suggest that sensorimotor cortex activity reflects the characteristics of both the movement and the target. Classifiers that extract these parameters from cortical ensembles could improve neuroprosthetic control. PMID:22275888

Cortical asymmetries in unaffected siblings of patients with obsessive-compulsive disorder.

PubMed

Peng, Ziwen; Li, Gang; Shi, Feng; Shi, Changzheng; Yang, Qiong; Chan, Raymond C K; Shen, Dinggang

2015-12-30

Obsessive-compulsive disorder (OCD) is considered to be associated with atypical brain asymmetry. However, no study has examined the asymmetry in OCD from the perspective of cortical morphometry. This study is aimed to describe the characteristics of cortical asymmetry in OCD patients, and to investigate whether these features exist in their unaffected siblings - a vital step in identifying putative endophenotypes for OCD. A total of 48 subjects (16 OCD patients, 16 unaffected siblings, and 16 matched controls) were recruited who had complete magnetic resonance imaging scans. Left-right hemispheric asymmetries of cortical thickness were measured using a surface-based threshold-free cluster enhancement method. OCD patients and siblings both showed leftward asymmetries of cortical thickness in the anterior cingulate cortex (ACC), which showed a significant positive correlation with compulsive subscale scores. In addition, siblings and healthy controls showed significantly decreased leftward asymmetries in the orbitofrontal cortex (OFC), and the decreased leftward bias in the OFC was accompanied by lower scales on the Yale-Brown Obsessive-Compulsive Scale. To sum up, leftward asymmetries of cortical thickness in the ACC may represent an endophenotype of increased hereditary risk for OCD, while decreased leftward asymmetries of cortical thickness in the OFC may represent a protective factor. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Deafferentation in thalamic and pontine areas in severe traumatic brain injury.

PubMed

Laouchedi, M; Galanaud, D; Delmaire, C; Fernandez-Vidal, S; Messé, A; Mesmoudi, S; Oulebsir Boumghar, F; Pélégrini-Issac, M; Puybasset, L; Benali, H; Perlbarg, V

2015-07-01

Severe traumatic brain injury (TBI) is characterized mainly by diffuse axonal injuries (DAI). The cortico-subcortical disconnections induced by such fiber disruption play a central role in consciousness recovery. We hypothesized that these cortico-subcortical deafferentations inferred from diffusion MRI data could differentiate between TBI patients with favorable or unfavorable (death, vegetative state, or minimally conscious state) outcome one year after injury. Cortico-subcortical fiber density maps were derived by using probabilistic tractography from diffusion tensor imaging data acquired in 24 severe TBI patients and 9 healthy controls. These maps were compared between patients and controls as well as between patients with favorable (FO) and unfavorable (UFO) 1-year outcome to identify the thalamo-cortical and ponto-thalamo-cortical pathways involved in the maintenance of consciousness. Thalamo-cortical and ponto-thalamo-cortical fiber density was significantly lower in TBI patients than in healthy controls. Comparing FO and UFO TBI patients showed thalamo-cortical deafferentation associated with unfavorable outcome for projections from ventral posterior and intermediate thalamic nuclei to the associative frontal, sensorimotor and associative temporal cortices. Specific ponto-thalamic deafferentation in projections from the upper dorsal pons (including the reticular formation) was also associated with unfavorable outcome. Fiber density of cortico-subcortical pathways as measured from diffusion MRI tractography is a relevant candidate biomarker for early prediction of one-year favorable outcome in severe TBI. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Functional Connectivity in Multiple Cortical Networks Is Associated with Performance Across Cognitive Domains in Older Adults.

PubMed

Shaw, Emily E; Schultz, Aaron P; Sperling, Reisa A; Hedden, Trey

2015-10-01

Intrinsic functional connectivity MRI has become a widely used tool for measuring integrity in large-scale cortical networks. This study examined multiple cortical networks using Template-Based Rotation (TBR), a method that applies a priori network and nuisance component templates defined from an independent dataset to test datasets of interest. A priori templates were applied to a test dataset of 276 older adults (ages 65-90) from the Harvard Aging Brain Study to examine the relationship between multiple large-scale cortical networks and cognition. Factor scores derived from neuropsychological tests represented processing speed, executive function, and episodic memory. Resting-state BOLD data were acquired in two 6-min acquisitions on a 3-Tesla scanner and processed with TBR to extract individual-level metrics of network connectivity in multiple cortical networks. All results controlled for data quality metrics, including motion. Connectivity in multiple large-scale cortical networks was positively related to all cognitive domains, with a composite measure of general connectivity positively associated with general cognitive performance. Controlling for the correlations between networks, the frontoparietal control network (FPCN) and executive function demonstrated the only significant association, suggesting specificity in this relationship. Further analyses found that the FPCN mediated the relationships of the other networks with cognition, suggesting that this network may play a central role in understanding individual variation in cognition during aging.

Altered cortical excitability in anorexia nervosa.

PubMed

Khedr, E M; El Fetoh, N A; El Bieh, E; Ali, A M; Karim, A A

2014-09-01

Recent EEG and positron emission tomography (PET) studies have reported hyperactivation of the right hemisphere in anorexia nervosa (AN). The aim of the present study was to test this notion by examining cortical excitability in subjects with AN using transcranial magnetic stimulation (TMS). We investigated thirteen patients meeting the DSM IV diagnostic criteria for AN and 14 controls age and sex matched. Each subject was assessed clinically using the Eating Disorder Inventory (EDI), the Eating Attitude Test (EAT) and Beck's Depression Inventory (BDI-II). TMS measures involved resting and active motor thresholds (RMT, AMT) as well as motor evoked potentials (MEP), cortical silent period duration (CSP), transcallosal inhibition (TCI), and short latency intracortical inhibition (SICI) of the first dorsal interosseous muscle (FDI) were assessed. Cortical esophageal MEP latencies (CL) were also recorded. The RMT and MEP onset latency of the FDI and the esophagus as well as duration of the TCI were significantly reduced in anorexic patients compared to the control group. There were no significant differences neither in AMT nor CSP between patients and controls. Moreover, we found significant negative correlations between the EAT scores and RMT, and TCI duration. Although anorexic patients had significantly higher BDI score, there was no correlation between it and cortical excitability. Anorexic individuals are characterized by pathologically increased motor and esophageal cortical excitability that significantly correlates with clinical symptoms of anorexia nervosa. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Probabilistic map of critical functional regions of the human cerebral cortex: Broca's area revisited.

PubMed

Tate, Matthew C; Herbet, Guillaume; Moritz-Gasser, Sylvie; Tate, Joseph E; Duffau, Hugues

2014-10-01

The organization of basic functions of the human brain, particularly in the right hemisphere, remains poorly understood. Recent advances in functional neuroimaging have improved our understanding of cortical organization but do not allow for direct interrogation or determination of essential (versus participatory) cortical regions. Direct cortical stimulation represents a unique opportunity to provide novel insights into the functional distribution of critical epicentres. Direct cortical stimulation (bipolar, 60 Hz, 1-ms pulse) was performed in 165 consecutive patients undergoing awake mapping for resection of low-grade gliomas. Tasks included motor, sensory, counting, and picture naming. Stimulation sites eliciting positive (sensory/motor) or negative (speech arrest, dysarthria, anomia, phonological and semantic paraphasias) findings were recorded and mapped onto a standard Montreal Neurological Institute brain atlas. Montreal Neurological Institute-space functional data were subjected to cluster analysis algorithms (K-means, partition around medioids, hierarchical Ward) to elucidate crucial network epicentres. Sensorimotor function was observed in the pre/post-central gyri as expected. Articulation epicentres were also found within the pre/post-central gyri. However, speech arrest localized to ventral premotor cortex, not the classical Broca's area. Anomia/paraphasia data demonstrated foci not only within classical Wernicke's area but also within the middle and inferior frontal gyri. We report the first bilateral probabilistic map for crucial cortical epicentres of human brain functions in the right and left hemispheres, including sensory, motor, and language (speech, articulation, phonology and semantics). These data challenge classical theories of brain organization (e.g. Broca's area as speech output region) and provide a distributed framework for future studies of neural networks. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Pharmacological modulation of cortical excitability shifts induced by transcranial direct current stimulation in humans.

PubMed

Nitsche, M A; Fricke, K; Henschke, U; Schlitterlau, A; Liebetanz, D; Lang, N; Henning, S; Tergau, F; Paulus, W

2003-11-15

Transcranial direct current stimulation (tDCS) of the human motor cortex results in polarity-specific shifts of cortical excitability during and after stimulation. Anodal tDCS enhances and cathodal stimulation reduces excitability. Animal experiments have demonstrated that the effect of anodal tDCS is caused by neuronal depolarisation, while cathodal tDCS hyperpolarises cortical neurones. However, not much is known about the ion channels and receptors involved in these effects. Thus, the impact of the sodium channel blocker carbamazepine, the calcium channel blocker flunarizine and the NMDA receptor antagonist dextromethorphane on tDCS-elicited motor cortical excitability changes of healthy human subjects were tested. tDCS-protocols inducing excitability alterations (1) only during tDCS and (2) eliciting long-lasting after-effects were applied after drug administration. Carbamazepine selectively eliminated the excitability enhancement induced by anodal stimulation during and after tDCS. Flunarizine resulted in similar changes. Antagonising NMDA receptors did not alter current-generated excitability changes during a short stimulation, which elicits no after-effects, but prevented the induction of long-lasting after-effects independent of their direction. These results suggest that, like in other animals, cortical excitability shifts induced during tDCS in humans also depend on membrane polarisation, thus modulating the conductance of sodium and calcium channels. Moreover, they suggest that the after-effects may be NMDA receptor dependent. Since NMDA receptors are involved in neuroplastic changes, the results suggest a possible application of tDCS in the modulation or induction of these processes in a clinical setting. The selective elimination of tDCS-driven excitability enhancements by carbamazepine proposes a role for this drug in focussing the effects of cathodal tDCS, which may have important future clinical applications.

Pharmacological modulation of cortical excitability shifts induced by transcranial direct current stimulation in humans

PubMed Central

Nitsche, M A; Fricke, K; Henschke, U; Schlitterlau, A; Liebetanz, D; Lang, N; Henning, S; Tergau, F; Paulus, W

2003-01-01

Transcranial direct current stimulation (tDCS) of the human motor cortex results in polarity-specific shifts of cortical excitability during and after stimulation. Anodal tDCS enhances and cathodal stimulation reduces excitability. Animal experiments have demonstrated that the effect of anodal tDCS is caused by neuronal depolarisation, while cathodal tDCS hyperpolarises cortical neurones. However, not much is known about the ion channels and receptors involved in these effects. Thus, the impact of the sodium channel blocker carbamazepine, the calcium channel blocker flunarizine and the NMDA receptor antagonist dextromethorphane on tDCS-elicited motor cortical excitability changes of healthy human subjects were tested. tDCS-protocols inducing excitability alterations (1) only during tDCS and (2) eliciting long-lasting after-effects were applied after drug administration. Carbamazepine selectively eliminated the excitability enhancement induced by anodal stimulation during and after tDCS. Flunarizine resulted in similar changes. Antagonising NMDA receptors did not alter current-generated excitability changes during a short stimulation, which elicits no after-effects, but prevented the induction of long-lasting after-effects independent of their direction. These results suggest that, like in other animals, cortical excitability shifts induced during tDCS in humans also depend on membrane polarisation, thus modulating the conductance of sodium and calcium channels. Moreover, they suggest that the after-effects may be NMDA receptor dependent. Since NMDA receptors are involved in neuroplastic changes, the results suggest a possible application of tDCS in the modulation or induction of these processes in a clinical setting. The selective elimination of tDCS-driven excitability enhancements by carbamazepine proposes a role for this drug in focussing the effects of cathodal tDCS, which may have important future clinical applications. PMID:12949224

Cortical fibers orientation mapping using in-vivo whole brain 7 T diffusion MRI.

PubMed

Gulban, Omer F; De Martino, Federico; Vu, An T; Yacoub, Essa; Uğurbil, Kamil; Lenglet, Christophe

2018-05-10

Diffusion MRI of the cortical gray matter is challenging because the micro-environment probed by water molecules is much more complex than within the white matter. High spatial and angular resolutions are therefore necessary to uncover anisotropic diffusion patterns and laminar structures, which provide complementary (e.g. to anatomical and functional MRI) microstructural information about the cortex architectonic. Several ex-vivo and in-vivo MRI studies have recently addressed this question, however predominantly with an emphasis on specific cortical areas. There is currently no whole brain in-vivo data leveraging multi-shell diffusion MRI acquisition at high spatial resolution, and depth dependent analysis, to characterize the complex organization of cortical fibers. Here, we present unique in-vivo human 7T diffusion MRI data, and a dedicated cortical depth dependent analysis pipeline. We leverage the high spatial (1.05 mm isotropic) and angular (198 diffusion gradient directions) resolution of this whole brain dataset to improve cortical fiber orientations mapping, and study neurites (axons and/or dendrites) trajectories across cortical depths. Tangential fibers in superficial cortical depths and crossing fiber configurations in deep cortical depths are identified. Fibers gradually inserting into the gyral walls are visualized, which contributes to mitigating the gyral bias effect. Quantitative radiality maps and histograms in individual subjects and cortex-based aligned datasets further support our results. Copyright © 2018 Elsevier Inc. All rights reserved.

Proximal femoral anatomy and collared stems in hip arthroplasty: is a single collar size sufficient?

PubMed

Bonin, Nicolas; Gedouin, Jean-Emmanuel; Pibarot, Vincent; Bejui-Hughues, Jacques; Bothorel, Hugo; Saffarini, Mo; Batailler, Cécile

2017-10-03

Even if the benefits of collars are unclear, they remain widely used, in several femoral stem designs. This study aimed to determine whether collar size should be proportional to hip dimensions and morphology. The hypothesis was that the collar should be larger for greater stem sizes and for varus femoral necks. Computed Tomography scans of 204 healthy hips were digitally analysed and manually templated to determine principle dimensions, appropriate stem size and model, as well as cortical distance at the femoral calcar (ideal collar size). Univariable analysis revealed that cortical distance was moderately correlated with mediolateral offset (r = 0.572; p < 0.0001) and stem model (r = 0.520; p < 0.0001). Cortical distance was weakly correlated with head diameter (r = 0.399; p < 0.0001), stem size (r = 0.200; p = 0.017), and patient gender (r = 0.361; p < 0.0001). Multivariable analysis confirmed that stem model (p < 0.0001) and head diameter (p = 0.0162) are directly correlated to cortical distance. We found that cortical distance along the femoral calcar is directly correlated with the model of the stem implanted ('standard' or 'varus') and with the head diameter. This cortical distance indicates optimal collar size, which would grant maximum calcar coverage without prosthetic overhang. Collar size should be proportional to the size of the operated hip, and should be larger for 'varus' stem models than for 'standard' stem models.

Effects of Long-term Diving Training on Cortical Gyrification.

PubMed

Zhang, Yuanchao; Zhao, Lu; Bi, Wenwei; Wang, Yue; Wei, Gaoxia; Evans, Alan; Jiang, Tianzi

2016-06-20

During human brain development, cortical gyrification, which is believed to facilitate compact wiring of neural circuits, has been shown to follow an inverted U-shaped curve, coinciding with the two-stage neurodevelopmental process of initial synaptic overproduction with subsequent pruning. This trajectory allows postnatal experiences to refine the wiring, which may manifest as endophenotypic changes in cortical gyrification. Diving experts, typical elite athletes who commence intensive motor training at a very young age in their early childhood, serve ideal models for examining the gyrification changes related to long-term intensive diving training. Using local gyrification index (LGI), we compared the cortical gyrification between 12 diving experts and 12 controls. Compared with controls, diving experts showed widespread LGI reductions in regions relevant to diving performance. Negative correlations between LGIs and years of diving training were also observed in diving experts. Further exploratory network efficiency analysis of structural cortical networks, inferred from interregional correlation of LGIs, revealed comparable global and local efficiency in diving experts relative to controls. These findings suggest that gyrification reductions in diving experts may be the result of long-term diving training which could refine the neural circuitry (via synaptic pruning) and might be the anatomical substrate underlying their extraordinary diving performance.

PAR-2, LGL-1 and the CDC-42 GAP CHIN-1 act in distinct pathways to maintain polarity in the C. elegans embryo

PubMed Central

Beatty, Alexander; Morton, Diane G.; Kemphues, Kenneth

2013-01-01

In the one-cell C. elegans embryo, polarity is maintained by mutual antagonism between the anterior cortical proteins PAR-3, PKC-3, PAR-6 and CDC-42, and the posterior cortical proteins PAR-2 and LGL-1 on the posterior cortex. The mechanisms by which these proteins interact to maintain polarity are incompletely understood. In this study, we investigate the interplay among PAR-2, LGL-1, myosin, the anterior PAR proteins and CDC-42. We find that PAR-2 and LGL-1 affect cortical myosin accumulation by different mechanisms. LGL-1 does not directly antagonize the accumulation of cortical myosin and instead plays a role in regulating PAR-6 levels. By contrast, PAR-2 likely has separate roles in regulating cortical myosin accumulation and preventing the expansion of the anterior cortical domain. We also provide evidence that asymmetry of active CDC-42 can be maintained independently of LGL-1 and PAR-2 by a redundant pathway that includes the CDC-42 GAP CHIN-1. Finally, we show that, in addition to its primary role in regulating the size of the anterior cortical domain via its binding to PAR-6, CDC-42 has a secondary role in regulating cortical myosin that is not dependent on PAR-6. PMID:23536568

Influences of brain development and ageing on cortical interactive networks.

PubMed

Zhu, Chengyu; Guo, Xiaoli; Jin, Zheng; Sun, Junfeng; Qiu, Yihong; Zhu, Yisheng; Tong, Shanbao

2011-02-01

To study the effect of brain development and ageing on the pattern of cortical interactive networks. By causality analysis of multichannel electroencephalograph (EEG) with partial directed coherence (PDC), we investigated the different neural networks involved in the whole cortex as well as the anterior and posterior areas in three age groups, i.e., children (0-10 years), mid-aged adults (26-38 years) and the elderly (56-80 years). By comparing the cortical interactive networks in different age groups, the following findings were concluded: (1) the cortical interactive network in the right hemisphere develops earlier than its left counterpart in the development stage; (2) the cortical interactive network of anterior cortex, especially at C3 and F3, is demonstrated to undergo far more extensive changes, compared with the posterior area during brain development and ageing; (3) the asymmetry of the cortical interactive networks declines during ageing with more loss of connectivity in the left frontal and central areas. The age-related variation of cortical interactive networks from resting EEG provides new insights into brain development and ageing. Our findings demonstrated that the PDC analysis of EEG is a powerful approach for characterizing the cortical functional connectivity during brain development and ageing. Copyright © 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Cortical network reorganization guided by sensory input features.

PubMed

Kilgard, Michael P; Pandya, Pritesh K; Engineer, Navzer D; Moucha, Raluca

2002-12-01

Sensory experience alters the functional organization of cortical networks. Previous studies using behavioral training motivated by aversive or rewarding stimuli have demonstrated that cortical plasticity is specific to salient inputs in the sensory environment. Sensory experience associated with electrical activation of the basal forebrain (BasF) generates similar input specific plasticity. By directly engaging plasticity mechanisms and avoiding extensive behavioral training, BasF stimulation makes it possible to efficiently explore how specific sensory features contribute to cortical plasticity. This review summarizes our observations that cortical networks employ a variety of strategies to improve the representation of the sensory environment. Different combinations of receptive-field, temporal, and spectrotemporal plasticity were generated in primary auditory cortex neurons depending on the pitch, modulation rate, and order of sounds paired with BasF stimulation. Simple tones led to map expansion, while modulated tones altered the maximum cortical following rate. Exposure to complex acoustic sequences led to the development of combination-sensitive responses. This remodeling of cortical response characteristics may reflect changes in intrinsic cellular mechanisms, synaptic efficacy, and local neuronal connectivity. The intricate relationship between the pattern of sensory activation and cortical plasticity suggests that network-level rules alter the functional organization of the cortex to generate the most behaviorally useful representation of the sensory environment.

PAR-2, LGL-1 and the CDC-42 GAP CHIN-1 act in distinct pathways to maintain polarity in the C. elegans embryo.

PubMed

Beatty, Alexander; Morton, Diane G; Kemphues, Kenneth

2013-05-01

In the one-cell C. elegans embryo, polarity is maintained by mutual antagonism between the anterior cortical proteins PAR-3, PKC-3, PAR-6 and CDC-42, and the posterior cortical proteins PAR-2 and LGL-1 on the posterior cortex. The mechanisms by which these proteins interact to maintain polarity are incompletely understood. In this study, we investigate the interplay among PAR-2, LGL-1, myosin, the anterior PAR proteins and CDC-42. We find that PAR-2 and LGL-1 affect cortical myosin accumulation by different mechanisms. LGL-1 does not directly antagonize the accumulation of cortical myosin and instead plays a role in regulating PAR-6 levels. By contrast, PAR-2 likely has separate roles in regulating cortical myosin accumulation and preventing the expansion of the anterior cortical domain. We also provide evidence that asymmetry of active CDC-42 can be maintained independently of LGL-1 and PAR-2 by a redundant pathway that includes the CDC-42 GAP CHIN-1. Finally, we show that, in addition to its primary role in regulating the size of the anterior cortical domain via its binding to PAR-6, CDC-42 has a secondary role in regulating cortical myosin that is not dependent on PAR-6.

A Mechanistic Link from GABA to Cortical Architecture and Perception.

PubMed

Kolasinski, James; Logan, John P; Hinson, Emily L; Manners, Daniel; Divanbeighi Zand, Amir P; Makin, Tamar R; Emir, Uzay E; Stagg, Charlotte J

2017-06-05

Understanding both the organization of the human cortex and its relation to the performance of distinct functions is fundamental in neuroscience. The primary sensory cortices display topographic organization, whereby receptive fields follow a characteristic pattern, from tonotopy to retinotopy to somatotopy [1]. GABAergic signaling is vital to the maintenance of cortical receptive fields [2]; however, it is unclear how this fine-grain inhibition relates to measurable patterns of perception [3, 4]. Based on perceptual changes following perturbation of the GABAergic system, it is conceivable that the resting level of cortical GABAergic tone directly relates to the spatial specificity of activation in response to a given input [5-7]. The specificity of cortical activation can be considered in terms of cortical tuning: greater cortical tuning yields more localized recruitment of cortical territory in response to a given input. We applied a combination of fMRI, MR spectroscopy, and psychophysics to substantiate the link between the cortical neurochemical milieu, the tuning of cortical activity, and variability in perceptual acuity, using human somatosensory cortex as a model. We provide data that explain human perceptual acuity in terms of both the underlying cellular and metabolic processes. Specifically, higher concentrations of sensorimotor GABA are associated with more selective cortical tuning, which in turn is associated with enhanced perception. These results show anatomical and neurochemical specificity and are replicated in an independent cohort. The mechanistic link from neurochemistry to perception provides a vital step in understanding population variability in sensory behavior, informing metabolic therapeutic interventions to restore perceptual abilities clinically. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Revealing unobserved factors underlying cortical activity with a rectified latent variable model applied to neural population recordings.

PubMed

Whiteway, Matthew R; Butts, Daniel A

2017-03-01

The activity of sensory cortical neurons is not only driven by external stimuli but also shaped by other sources of input to the cortex. Unlike external stimuli, these other sources of input are challenging to experimentally control, or even observe, and as a result contribute to variability of neural responses to sensory stimuli. However, such sources of input are likely not "noise" and may play an integral role in sensory cortex function. Here we introduce the rectified latent variable model (RLVM) in order to identify these sources of input using simultaneously recorded cortical neuron populations. The RLVM is novel in that it employs nonnegative (rectified) latent variables and is much less restrictive in the mathematical constraints on solutions because of the use of an autoencoder neural network to initialize model parameters. We show that the RLVM outperforms principal component analysis, factor analysis, and independent component analysis, using simulated data across a range of conditions. We then apply this model to two-photon imaging of hundreds of simultaneously recorded neurons in mouse primary somatosensory cortex during a tactile discrimination task. Across many experiments, the RLVM identifies latent variables related to both the tactile stimulation as well as nonstimulus aspects of the behavioral task, with a majority of activity explained by the latter. These results suggest that properly identifying such latent variables is necessary for a full understanding of sensory cortical function and demonstrate novel methods for leveraging large population recordings to this end. NEW & NOTEWORTHY The rapid development of neural recording technologies presents new opportunities for understanding patterns of activity across neural populations. Here we show how a latent variable model with appropriate nonlinear form can be used to identify sources of input to a neural population and infer their time courses. Furthermore, we demonstrate how these sources are related to behavioral contexts outside of direct experimental control. Copyright © 2017 the American Physiological Society.

The effect of surface demineralization of cortical bone allograft on the properties of recombinant adeno-associated virus coatings.

PubMed

Yazici, Cemal; Yanoso, Laura; Xie, Chao; Reynolds, David G; Samulski, R Jude; Samulski, Jade; Yannariello-Brown, Judith; Gertzman, Arthur A; Zhang, Xinping; Awad, Hani A; Schwarz, Edward M

2008-10-01

Freeze-dried recombinant adeno-associated virus (rAAV) coated structural allografts have emerged as an approach to engender necrotic cortical bone with host factors that will persist for weeks following surgery to facilitate revascularization, osteointegration, and remodeling. However, one major limitation is the nonporous cortical surface that prohibits uniform distribution of the rAAV coating prior to freeze-drying. To overcome this we have developed a demineralization method to increase surface absorbance while retaining the structural integrity of the allograft. Demineralized bone wafers (DBW) made from human femoral allograft rings demonstrated a significant 21.1% (73.6+/-3.9% versus 52.5+/-2.6%; p<0.001) increase in percent surface area coating versus mineralized controls. Co-incubation of rAAV-luciferase (rAAV-Luc) coated DBW with a monolayer of C3H10T1/2 cells in culture led to peak luciferase levels that were not significantly different from soluble rAAV-Luc controls (p>0.05), although the peaks occurred at 60h and 12h, respectively. To assess the transduction efficiency of rAAV-Luc coated DBW in vivo, we first performed a dose response with allografts containing 10(7), 10(9) or 10(10) particles that were surgically implanted into the quadriceps of mice, and assayed by in vivo bioluminescence imaging (BLI) on days 1, 3, 5, 7, 10, 14, and 21. The results demonstrated a dose response in which the DBW coated with 10(10) rAAV-Luc particles achieved peak gene expression levels on day 3, which persisted until day 21, and was significantly greater than the 10(7) dose throughout this time period (p<0.01). A direct comparison of mineralized versus DBW coated with 10(10) rAAV-Luc particles failed to demonstrate any significant differences in transduction kinetics or efficiency in vivo. Thus, surface demineralization of human cortical bone allograft increases its absorbance for uniform rAAV coating, without affecting vector transduction efficiency.

Prenatal Exposure to Autism-Specific Maternal Autoantibodies Alters Proliferation of Cortical Neural Precursor Cells, Enlarges Brain, and Increases Neuronal Size in Adult Animals.

PubMed

Martínez-Cerdeño, Verónica; Camacho, Jasmin; Fox, Elizabeth; Miller, Elaine; Ariza, Jeanelle; Kienzle, Devon; Plank, Kaela; Noctor, Stephen C; Van de Water, Judy

2016-01-01

Autism spectrum disorders (ASDs) affect up to 1 in 68 children. Autism-specific autoantibodies directed against fetal brain proteins have been found exclusively in a subpopulation of mothers whose children were diagnosed with ASD or maternal autoantibody-related autism. We tested the impact of autoantibodies on brain development in mice by transferring human antigen-specific IgG directly into the cerebral ventricles of embryonic mice during cortical neurogenesis. We show that autoantibodies recognize radial glial cells during development. We also show that prenatal exposure to autism-specific maternal autoantibodies increased stem cell proliferation in the subventricular zone (SVZ) of the embryonic neocortex, increased adult brain size and weight, and increased the size of adult cortical neurons. We propose that prenatal exposure to autism-specific maternal autoantibodies directly affects radial glial cell development and presents a viable pathologic mechanism for the maternal autoantibody-related prenatal ASD risk factor. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Relationship between brainstem, cortical and behavioral measures relevant to pitch salience in humans.

PubMed

Krishnan, Ananthanarayan; Bidelman, Gavin M; Smalt, Christopher J; Ananthakrishnan, Saradha; Gandour, Jackson T

2012-10-01

Neural representation of pitch-relevant information at both the brainstem and cortical levels of processing is influenced by language or music experience. However, the functional roles of brainstem and cortical neural mechanisms in the hierarchical network for language processing, and how they drive and maintain experience-dependent reorganization are not known. In an effort to evaluate the possible interplay between these two levels of pitch processing, we introduce a novel electrophysiological approach to evaluate pitch-relevant neural activity at the brainstem and auditory cortex concurrently. Brainstem frequency-following responses and cortical pitch responses were recorded from participants in response to iterated rippled noise stimuli that varied in stimulus periodicity (pitch salience). A control condition using iterated rippled noise devoid of pitch was employed to ensure pitch specificity of the cortical pitch response. Neural data were compared with behavioral pitch discrimination thresholds. Results showed that magnitudes of neural responses increase systematically and that behavioral pitch discrimination improves with increasing stimulus periodicity, indicating more robust encoding for salient pitch. Absence of cortical pitch response in the control condition confirms that the cortical pitch response is specific to pitch. Behavioral pitch discrimination was better predicted by brainstem and cortical responses together as compared to each separately. The close correspondence between neural and behavioral data suggest that neural correlates of pitch salience that emerge in early, preattentive stages of processing in the brainstem may drive and maintain with high fidelity the early cortical representations of pitch. These neural representations together contain adequate information for the development of perceptual pitch salience. Copyright © 2012 Elsevier Ltd. All rights reserved.

Differences in hemispherical thalamo-cortical causality analysis during resting-state fMRI.

PubMed

Anwar, Abdul Rauf; Muthalib, Makii; Perrey, Stephane; Wolff, Stephan; Deuschl, Guunther; Heute, Ulrich; Muthuraman, Muthuraman

2014-01-01

Thalamus is a very important part of the human brain. It has been reported to act as a relay for the messaging taking place between the cortical and sub-cortical regions of the brain. In the present study, we analyze the functional network between both hemispheres of the brain with the focus on thalamus. We used conditional Granger causality (CGC) and time-resolved partial directed coherence (tPDC) to investigate the functional connectivity. Results of CGC analysis revealed the asymmetry between connection strengths of the bilateral thalamus. Upon testing the functional connectivity of the default-mode network (DMN) at low-frequency fluctuations (LFF) and comparing coherence vectors using Spearman's rank correlation, we found that thalamus is a better source for the signals directed towards the contralateral regions of the brain, however, when thalamus acts as sink, it is a better sink for signals generated from ipsilateral regions of the brain.

Thalamo-Cortical Disruption Contributes to Short-Term Memory Deficits in Patients with Medial Temporal Lobe Damage.

PubMed

Voets, Natalie L; Menke, Ricarda A L; Jbabdi, Saad; Husain, Masud; Stacey, Richard; Carpenter, Katherine; Adcock, Jane E

2015-11-01

Short-term (STM) and long-term memory (LTM) have largely been considered as separate brain systems reflecting fronto-parietal and medial temporal lobe (MTL) functions, respectively. This functional dichotomy has been called into question by evidence of deficits on aspects of working memory in patients with MTL damage, suggesting a potentially direct hippocampal contribution to STM. As the hippocampus has direct anatomical connections with the thalamus, we tested the hypothesis that damage to thalamic nuclei regulating cortico-cortical interactions may contribute to STM deficits in patients with hippocampal dysfunction. We used diffusion-weighted magnetic resonance imaging-based tractography to identify anatomical subdivisions in patients with MTL epilepsy. From these, we measured resting-state functional connectivity with detailed cortical divisions of the frontal, temporal, and parietal lobes. Whereas thalamo-temporal functional connectivity reflected LTM performance, thalamo-prefrontal functional connectivity specifically predicted STM performance. Notably, patients with hippocampal volume loss showed thalamic volume loss, most prominent in the pulvinar region, not detected in patients with normal hippocampal volumes. Aberrant thalamo-cortical connectivity in the epileptic hemisphere was mirrored in a loss of behavioral association with STM performance specifically in patients with hippocampal atrophy. These findings identify thalamo-cortical disruption as a potential mechanism contributing to STM deficits in the context of MTL damage. © The Author 2015. Published by Oxford University Press.

Divergent Human Cortical Regions for Processing Distinct Acoustic-Semantic Categories of Natural Sounds: Animal Action Sounds vs. Vocalizations

PubMed Central

Webster, Paula J.; Skipper-Kallal, Laura M.; Frum, Chris A.; Still, Hayley N.; Ward, B. Douglas; Lewis, James W.

2017-01-01

A major gap in our understanding of natural sound processing is knowledge of where or how in a cortical hierarchy differential processing leads to categorical perception at a semantic level. Here, using functional magnetic resonance imaging (fMRI) we sought to determine if and where cortical pathways in humans might diverge for processing action sounds vs. vocalizations as distinct acoustic-semantic categories of real-world sound when matched for duration and intensity. This was tested by using relatively less semantically complex natural sounds produced by non-conspecific animals rather than humans. Our results revealed a striking double-dissociation of activated networks bilaterally. This included a previously well described pathway preferential for processing vocalization signals directed laterally from functionally defined primary auditory cortices to the anterior superior temporal gyri, and a less well-described pathway preferential for processing animal action sounds directed medially to the posterior insulae. We additionally found that some of these regions and associated cortical networks showed parametric sensitivity to high-order quantifiable acoustic signal attributes and/or to perceptual features of the natural stimuli, such as the degree of perceived recognition or intentional understanding. Overall, these results supported a neurobiological theoretical framework for how the mammalian brain may be fundamentally organized to process acoustically and acoustic-semantically distinct categories of ethologically valid, real-world sounds. PMID:28111538

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

PubMed

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

2018-04-25

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

Research on acupuncture points and cortical functional activation position in cats by infrared imaging detection

NASA Astrophysics Data System (ADS)

Chen, Shuwang; Sha, Zhanyou; Wang, Shuhai; Wen, Huanming

2007-12-01

The research of the brain cognition is mainly to find out the activation position in brain according to the stimulation at present in the world. The research regards the animals as the experimental objects and explores the stimulation response on the cerebral cortex of acupuncture. It provides a new method, which can detect the activation position on the creatural cerebral cortex directly by middle-far infrared imaging. According to the theory of local temperature situation, the difference of cortical temperature maybe associate with the excitement of cortical nerve cells, the metabolism of local tissue and the local hemal circulation. Direct naked detection of temperature variety on cerebral cortex is applied by middle and far infrared imaging technology. So the activation position is ascertained. The effect of stimulation response is superior to other indirect methods. After removing the skulls on the head, full of cerebral cortex of a cat are exposed. By observing the infrared images and measuring the temperatures of the visual cerebral cortex during the process of acupuncturing, the points are used to judge the activation position. The variety in the cortical functional sections is corresponding to the result of the acupuncture points in terms of infrared images and temperatures. According to experimental results, we know that the variety of a cortical functional section is corresponding to a special acupuncture point exactly.

Abnormalities of fixation, saccade and pursuit in posterior cortical atrophy.

PubMed

Shakespeare, Timothy J; Kaski, Diego; Yong, Keir X X; Paterson, Ross W; Slattery, Catherine F; Ryan, Natalie S; Schott, Jonathan M; Crutch, Sebastian J

2015-07-01

The clinico-neuroradiological syndrome posterior cortical atrophy is the cardinal 'visual dementia' and most common atypical Alzheimer's disease phenotype, offering insights into mechanisms underlying clinical heterogeneity, pathological propagation and basic visual phenomena (e.g. visual crowding). Given the extensive attention paid to patients' (higher order) perceptual function, it is surprising that there have been no systematic analyses of basic oculomotor function in this population. Here 20 patients with posterior cortical atrophy, 17 patients with typical Alzheimer's disease and 22 healthy controls completed tests of fixation, saccade (including fixation/target gap and overlap conditions) and smooth pursuit eye movements using an infrared pupil-tracking system. Participants underwent detailed neuropsychological and neurological examinations, with a proportion also undertaking brain imaging and analysis of molecular pathology. In contrast to informal clinical evaluations of oculomotor dysfunction frequency (previous studies: 38%, current clinical examination: 33%), detailed eyetracking investigations revealed eye movement abnormalities in 80% of patients with posterior cortical atrophy (compared to 17% typical Alzheimer's disease, 5% controls). The greatest differences between posterior cortical atrophy and typical Alzheimer's disease were seen in saccadic performance. Patients with posterior cortical atrophy made significantly shorter saccades especially for distant targets. They also exhibited a significant exacerbation of the normal gap/overlap effect, consistent with 'sticky fixation'. Time to reach saccadic targets was significantly associated with parietal and occipital cortical thickness measures. On fixation stability tasks, patients with typical Alzheimer's disease showed more square wave jerks whose frequency was associated with lower cerebellar grey matter volume, while patients with posterior cortical atrophy showed large saccadic intrusions whose frequency correlated significantly with generalized reductions in cortical thickness. Patients with both posterior cortical atrophy and typical Alzheimer's disease showed lower gain in smooth pursuit compared to controls. The current study establishes that eye movement abnormalities are near-ubiquitous in posterior cortical atrophy, and highlights multiple aspects of saccadic performance which distinguish posterior cortical atrophy from typical Alzheimer's disease. We suggest the posterior cortical atrophy oculomotor profile (e.g. exacerbation of the saccadic gap/overlap effect, preserved saccadic velocity) reflects weak input from degraded occipito-parietal spatial representations of stimulus location into a superior collicular spatial map for eye movement regulation. This may indicate greater impairment of identification of oculomotor targets rather than generation of oculomotor movements. The results highlight the critical role of spatial attention and object identification but also precise stimulus localization in explaining the complex real world perception deficits observed in posterior cortical atrophy and many other patients with dementia-related visual impairment. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.

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

Multimodal Approach for Radical Excision of Focal Cortical Dysplasia by Combining Advanced Magnetic Resonance Imaging Data to Intraoperative Ultrasound, Electrocorticography, and Cortical Stimulation: A Preliminary Experience.

PubMed

Tringali, Giovanni; Bono, Beatrice; Dones, Ivano; Cordella, Roberto; Didato, Giuseppe; Villani, Flavio; Prada, Francesco

2018-05-01

Type II focal cortical dysplasia is the most common malformation of cortical development associated with drug resistant epilepsy and susceptible to surgical resection. Although, at present, advanced imaging modalities are capable of detecting most cortical disorders, it is still a challenge for the surgeon to visualize them intraoperatively. The lack of direct identification between normal brain and subtle dysplastic tissue may explain the poor results in terms of being seizure-free versus other forms of epilepsy. The aim of this study is to compare magnetic resonance imaging (MRI) and intraoperative ultrasound-guided neuronavigation, along with cortical stimulation and acute electrocorticography, as a multimodal surgical approach to cortical dysplasia's tailored resection. Six consecutive patients with type II cortical dysplasia underwent epilepsy surgery by means of MRI/intraoperative ultrasound-guided neuronavigation. Intraoperative cortical stimulation of sensory/motor cortex was performed to localize cortical eloquent areas. Acute electrocorticography was used to identify epileptogenic tissue. These findings were correlated to real-time ultrasound imaging to establish the extent of the resection. Intraoperative ultrasound depicted cortical dysplasias at a higher resolution and accuracy than MRI. Therefore it maximized the extent of the resection. Both postoperative MRIs and pathology documented the extent of the resection in all patients. Seizure-freedom was achieved in 5 cases (Engel class IA), and in 1 patient it was classified as Engel class IB. No postoperative neurological deficits were observed. These results strongly suggest feasibility of ultrasound-guided resection of focal cortical dysplasia. Providing high resolution and accuracy, it allows an easy, real-time discrimination between normal and dysplastic brain. Copyright © 2018 Elsevier Inc. All rights reserved.

Technical Note: Cortical thickness and density estimation from clinical CT using a prior thickness-density relationship

DOE Office of Scientific and Technical Information (OSTI.GOV)

Humbert, Ludovic, E-mail: ludohumberto@gmail.com; Hazrati Marangalou, Javad; Rietbergen, Bert van

Purpose: Cortical thickness and density are critical components in determining the strength of bony structures. Computed tomography (CT) is one possible modality for analyzing the cortex in 3D. In this paper, a model-based approach for measuring the cortical bone thickness and density from clinical CT images is proposed. Methods: Density variations across the cortex were modeled as a function of the cortical thickness and density, location of the cortex, density of surrounding tissues, and imaging blur. High resolution micro-CT data of cadaver proximal femurs were analyzed to determine a relationship between cortical thickness and density. This thickness-density relationship was usedmore » as prior information to be incorporated in the model to obtain accurate measurements of cortical thickness and density from clinical CT volumes. The method was validated using micro-CT scans of 23 cadaver proximal femurs. Simulated clinical CT images with different voxel sizes were generated from the micro-CT data. Cortical thickness and density were estimated from the simulated images using the proposed method and compared with measurements obtained using the micro-CT images to evaluate the effect of voxel size on the accuracy of the method. Then, 19 of the 23 specimens were imaged using a clinical CT scanner. Cortical thickness and density were estimated from the clinical CT images using the proposed method and compared with the micro-CT measurements. Finally, a case-control study including 20 patients with osteoporosis and 20 age-matched controls with normal bone density was performed to evaluate the proposed method in a clinical context. Results: Cortical thickness (density) estimation errors were 0.07 ± 0.19 mm (−18 ± 92 mg/cm{sup 3}) using the simulated clinical CT volumes with the smallest voxel size (0.33 × 0.33 × 0.5 mm{sup 3}), and 0.10 ± 0.24 mm (−10 ± 115 mg/cm{sup 3}) using the volumes with the largest voxel size (1.0 × 1.0 × 3.0 mm{sup 3}). A trend for the cortical thickness and density estimation errors to increase with voxel size was observed and was more pronounced for thin cortices. Using clinical CT data for 19 of the 23 samples, mean errors of 0.18 ± 0.24 mm for the cortical thickness and 15 ± 106 mg/cm{sup 3} for the density were found. The case-control study showed that osteoporotic patients had a thinner cortex and a lower cortical density, with average differences of −0.8 mm and −58.6 mg/cm{sup 3} at the proximal femur in comparison with age-matched controls (p-value < 0.001). Conclusions: This method might be a promising approach for the quantification of cortical bone thickness and density using clinical routine imaging techniques. Future work will concentrate on investigating how this approach can improve the estimation of mechanical strength of bony structures, the prevention of fracture, and the management of osteoporosis.« less

Cortical surface shift estimation using stereovision and optical flow motion tracking via projection image registration

PubMed Central

Ji, Songbai; Fan, Xiaoyao; Roberts, David W.; Hartov, Alex; Paulsen, Keith D.

2014-01-01

Stereovision is an important intraoperative imaging technique that captures the exposed parenchymal surface noninvasively during open cranial surgery. Estimating cortical surface shift efficiently and accurately is critical to compensate for brain deformation in the operating room (OR). In this study, we present an automatic and robust registration technique based on optical flow (OF) motion tracking to compensate for cortical surface displacement throughout surgery. Stereo images of the cortical surface were acquired at multiple time points after dural opening to reconstruct three-dimensional (3D) texture intensity-encoded cortical surfaces. A local coordinate system was established with its z-axis parallel to the average surface normal direction of the reconstructed cortical surface immediately after dural opening in order to produce two-dimensional (2D) projection images. A dense displacement field between the two projection images was determined directly from OF motion tracking without the need for feature identification or tracking. The starting and end points of the displacement vectors on the two cortical surfaces were then obtained following spatial mapping inversion to produce the full 3D displacement of the exposed cortical surface. We evaluated the technique with images obtained from digital phantoms and 18 surgical cases – 10 of which involved independent measurements of feature locations acquired with a tracked stylus for accuracy comparisons, and 8 others of which 4 involved stereo image acquisitions at three or more time points during surgery to illustrate utility throughout a procedure. Results from the digital phantom images were very accurate (0.05 pixels). In the 10 surgical cases with independently digitized point locations, the average agreement between feature coordinates derived from the cortical surface reconstructions was 1.7–2.1 mm relative to those determined with the tracked stylus probe. The agreement in feature displacement tracking was also comparable to tracked probe data (difference in displacement magnitude was <1 mm on average). The average magnitude of cortical surface displacement was 7.9 ± 5.7 mm (range 0.3–24.4 mm) in all patient cases with the displacement components along gravity being 5.2 ± 6.0 mm relative to the lateral movement of 2.4 ± 1.6 mm. Thus, our technique appears to be sufficiently accurate and computationally efficiency (typically ~15 s), for applications in the OR. PMID:25077845

Task-dependent and distinct roles of the temporoparietal junction and inferior frontal cortex in the control of imitation.

PubMed

Hogeveen, Jeremy; Obhi, Sukhvinder S; Banissy, Michael J; Santiesteban, Idalmis; Press, Clare; Catmur, Caroline; Bird, Geoffrey

2015-07-01

The control of neurological networks supporting social cognition is crucially important for social interaction. In particular, the control of imitation is directly linked to interaction quality, with impairments associated with disorders characterized by social difficulties. Previous work suggests inferior frontal cortex (IFC) and the temporoparietal junction (TPJ) are involved in controlling imitation, but the functional roles of these areas remain unclear. Here, transcranial direct current stimulation (tDCS) was used to enhance cortical excitability at IFC and the TPJ prior to the completion of three tasks: (i) a naturalistic social interaction during which increased imitation is known to improve rapport, (ii) a choice reaction time task in which imitation needs to be inhibited for successful performance and (iii) a non-imitative control task. Relative to sham stimulation, stimulating IFC improved the context-dependent control of imitation-participants imitated more during the social interaction and less during the imitation inhibition task. In contrast, stimulating the TPJ reduced imitation in the inhibition task without affecting imitation during social interaction. Neither stimulation site affected the non-imitative control task. These data support a model in which IFC modulates imitation directly according to task demands, whereas TPJ controls task-appropriate shifts in attention toward representation of the self or the other, indirectly impacting upon imitation. © The Author (2014). Published by Oxford University Press.

Behavioral and neuroimaging evidence for overreliance on habit learning in alcohol-dependent patients

PubMed Central

Sjoerds, Z; de Wit, S; van den Brink, W; Robbins, T W; Beekman, A T F; Penninx, B W J H; Veltman, D J

2013-01-01

Substance dependence is characterized by compulsive drug-taking despite negative consequences. Animal research suggests an underlying imbalance between goal-directed and habitual action control with chronic drug use. However, this imbalance, and its associated neurophysiological mechanisms, has not yet been experimentally investigated in human drug abusers. The aim of the present study therefore was to assess the balance between goal-directed and habit-based learning and its neural correlates in abstinent alcohol-dependent (AD) patients. A total of 31 AD patients and 19 age, gender and education matched healthy controls (HC) underwent functional magnetic resonance imaging (fMRI) during completion of an instrumental learning task designed to study the balance between goal-directed and habit learning. Task performance and task-related blood oxygen level-dependent activations in the brain were compared between AD patients and healthy matched controls. Findings were additionally associated with duration and severity of alcohol dependence. The results of this study provide evidence for an overreliance on stimulus-response habit learning in AD compared with HC, which was accompanied by decreased engagement of brain areas implicated in goal-directed action (ventromedial prefrontal cortex and anterior putamen) and increased recruitment of brain areas implicated in habit learning (posterior putamen) in AD patients. In conclusion, this is the first human study to provide experimental evidence for a disturbed balance between goal-directed and habitual control by use of an instrumental learning task, and to directly implicate cortical dysfunction to overreliance on inflexible habits in AD patients. PMID:24346135

Behavioral and neuroimaging evidence for overreliance on habit learning in alcohol-dependent patients.

PubMed

Sjoerds, Z; de Wit, S; van den Brink, W; Robbins, T W; Beekman, A T F; Penninx, B W J H; Veltman, D J

2013-12-17

Substance dependence is characterized by compulsive drug-taking despite negative consequences. Animal research suggests an underlying imbalance between goal-directed and habitual action control with chronic drug use. However, this imbalance, and its associated neurophysiological mechanisms, has not yet been experimentally investigated in human drug abusers. The aim of the present study therefore was to assess the balance between goal-directed and habit-based learning and its neural correlates in abstinent alcohol-dependent (AD) patients. A total of 31 AD patients and 19 age, gender and education matched healthy controls (HC) underwent functional magnetic resonance imaging (fMRI) during completion of an instrumental learning task designed to study the balance between goal-directed and habit learning. Task performance and task-related blood oxygen level-dependent activations in the brain were compared between AD patients and healthy matched controls. Findings were additionally associated with duration and severity of alcohol dependence. The results of this study provide evidence for an overreliance on stimulus-response habit learning in AD compared with HC, which was accompanied by decreased engagement of brain areas implicated in goal-directed action (ventromedial prefrontal cortex and anterior putamen) and increased recruitment of brain areas implicated in habit learning (posterior putamen) in AD patients. In conclusion, this is the first human study to provide experimental evidence for a disturbed balance between goal-directed and habitual control by use of an instrumental learning task, and to directly implicate cortical dysfunction to overreliance on inflexible habits in AD patients.

Gamma-Aminobutyric Acid Concentration is Reduced in Visual Cortex in Schizophrenia and Correlates with Orientation-Specific Surround Suppression

PubMed Central

Yoon, Jong H.; Maddock, Richard J.; Rokem, Ariel; Silver, Michael A.; Minzenberg, Michael J.; Ragland, J. Daniel; Carter, Cameron S.

2010-01-01

The neural mechanisms underlying cognitive deficits in schizophrenia remain largely unknown. The gamma-aminobutyric acid (GABA) hypothesis proposes that reduced neuronal GABA concentration and neurotransmission results in cognitive impairments in schizophrenia. However, few in vivo studies have directly examined this hypothesis. We employed magnetic resonance spectroscopy (MRS) at high field to measure visual cortical GABA levels in 13 subjects with schizophrenia and 13 demographically matched healthy control subjects. We found that the schizophrenia group had an approximately 10% reduction in GABA concentration. We further tested the GABA hypothesis by examining the relationship between visual cortical GABA levels and orientation-specific surround suppression (OSSS), a behavioral measure of visual inhibition thought to be dependent on GABAergic synaptic transmission. Previous work has shown that subjects with schizophrenia exhibit reduced OSSS of contrast discrimination (Yoon et al., 2009). For subjects with both MRS and OSSS data (n=16), we found a highly significant positive correlation (r=0.76) between these variables. GABA concentration was not correlated with overall contrast discrimination performance for stimuli without a surround (r=-0.10). These results suggest that a neocortical GABA deficit in subjects with schizophrenia leads to impaired cortical inhibition and that GABAergic synaptic transmission in visual cortex plays a critical role in OSSS. PMID:20220012

GABA concentration is reduced in visual cortex in schizophrenia and correlates with orientation-specific surround suppression.

PubMed

Yoon, Jong H; Maddock, Richard J; Rokem, Ariel; Silver, Michael A; Minzenberg, Michael J; Ragland, J Daniel; Carter, Cameron S

2010-03-10

The neural mechanisms underlying cognitive deficits in schizophrenia remain essentially unknown. The GABA hypothesis proposes that reduced neuronal GABA concentration and neurotransmission results in cognitive impairments in schizophrenia. However, few in vivo studies have directly examined this hypothesis. We used magnetic resonance spectroscopy (MRS) at high field to measure visual cortical GABA levels in 13 subjects with schizophrenia and 13 demographically matched healthy control subjects. We found that the schizophrenia group had an approximately 10% reduction in GABA concentration. We further tested the GABA hypothesis by examining the relationship between visual cortical GABA levels and orientation-specific surround suppression (OSSS), a behavioral measure of visual inhibition thought to be dependent on GABAergic synaptic transmission. Previous work has shown that subjects with schizophrenia exhibit reduced OSSS of contrast discrimination (Yoon et al., 2009). For subjects with both MRS and OSSS data (n = 16), we found a highly significant positive correlation (r = 0.76) between these variables. GABA concentration was not correlated with overall contrast discrimination performance for stimuli without a surround (r = -0.10). These results suggest that a neocortical GABA deficit in subjects with schizophrenia leads to impaired cortical inhibition and that GABAergic synaptic transmission in visual cortex plays a critical role in OSSS.

APC sets the Wnt tone necessary for cerebral cortical progenitor development.

PubMed

Nakagawa, Naoki; Li, Jingjun; Yabuno-Nakagawa, Keiko; Eom, Tae-Yeon; Cowles, Martis; Mapp, Tavien; Taylor, Robin; Anton, E S

2017-08-15

Adenomatous polyposis coli (APC) regulates the activity of β-catenin, an integral component of Wnt signaling. However, the selective role of the APC-β-catenin pathway in cerebral cortical development is unknown. Here we genetically dissected the relative contributions of APC-regulated β-catenin signaling in cortical progenitor development, a necessary early step in cerebral cortical formation. Radial progenitor-specific inactivation of the APC-β-catenin pathway indicates that the maintenance of appropriate β-catenin-mediated Wnt tone is necessary for the orderly differentiation of cortical progenitors and the resultant formation of the cerebral cortex. APC deletion deregulates β-catenin, leads to high Wnt tone, and disrupts Notch1 signaling and primary cilium maintenance necessary for radial progenitor functions. β-Catenin deregulation directly disrupts cilium maintenance and signaling via Tulp3, essential for intraflagellar transport of ciliary signaling receptors. Surprisingly, deletion of β-catenin or inhibition of β-catenin activity in APC-null progenitors rescues the APC-null phenotype. These results reveal that APC-regulated β-catenin activity in cortical progenitors sets the appropriate Wnt tone necessary for normal cerebral cortical development. © 2017 Nakagawa et al.; Published by Cold Spring Harbor Laboratory Press.

Cortical gyrification in autistic and Asperger disorders: a preliminary magnetic resonance imaging study.

PubMed

Jou, Roger J; Minshew, Nancy J; Keshavan, Matcheri S; Hardan, Antonio Y

2010-12-01

The validity of Asperger disorder as a distinct syndrome from autism is unclear partly because of the paucity of differentiating neurobiological evidence. Frontal lobe cortical folding between these disorders was compared using the gyrification index. Twenty-three boys underwent structural magnetic resonance imaging: 6 with high-functioning autism, 9 with Asperger disorder, and 8 controls. Using the first coronal slice anterior to the corpus callosum, total and outer cortical contours were traced to calculate the gyrification index. This index was also calculated for superior and inferior regions to examine dorsolateral prefrontal and orbitofrontal cortices, respectively. Analysis of variance revealed differences in the left inferior gyrification index, which was higher in the autism group compared with Asperger and control groups. There were no differences in age, intelligence quotient, and brain volume. These preliminary findings suggest that cortical folding may be abnormally high in the frontal lobe in autism but not Asperger disorder, suggesting distinct frontal lobe neuropathology.

Central Nervous System Control of Voice and Swallowing

PubMed Central

Ludlow, Christy L.

2015-01-01

This review of the central nervous control systems for voice and swallowing has suggested that the traditional concepts of a separation between cortical and limbic and brain stem control should be refined and more integrative. For voice production, a separation of the non-human vocalization system from the human learned voice production system has been posited based primarily on studies of non-human primates. However, recent humans studies of emotionally based vocalizations and human volitional voice production has shown more integration between these two systems than previously proposed. Recent human studies have shown that reflexive vocalization as well as learned voice production not involving speech, involve a common integrative system. On the other hand, recent studies of non-human primates have provided evidence of some cortical activity during vocalization and cortical changes with training during vocal behavior. For swallowing, evidence from the macaque and functional brain imaging in humans indicates that the control for the pharyngeal phase of swallowing is not primarily under brain stem mechanisms as previously proposed. Studies suggest that the initiation and patterning of swallowing for the pharyngeal phase is also under active cortical control for both spontaneous as well as volitional swallowing in awake humans and non-human primates. PMID:26241238

A brain-machine interface enables bimanual arm movements in monkeys.

PubMed

Ifft, Peter J; Shokur, Solaiman; Li, Zheng; Lebedev, Mikhail A; Nicolelis, Miguel A L

2013-11-06

Brain-machine interfaces (BMIs) are artificial systems that aim to restore sensation and movement to paralyzed patients. So far, BMIs have enabled only one arm to be moved at a time. Control of bimanual arm movements remains a major challenge. We have developed and tested a bimanual BMI that enables rhesus monkeys to control two avatar arms simultaneously. The bimanual BMI was based on the extracellular activity of 374 to 497 neurons recorded from several frontal and parietal cortical areas of both cerebral hemispheres. Cortical activity was transformed into movements of the two arms with a decoding algorithm called a fifth-order unscented Kalman filter (UKF). The UKF was trained either during a manual task performed with two joysticks or by having the monkeys passively observe the movements of avatar arms. Most cortical neurons changed their modulation patterns when both arms were engaged simultaneously. Representing the two arms jointly in a single UKF decoder resulted in improved decoding performance compared with using separate decoders for each arm. As the animals' performance in bimanual BMI control improved over time, we observed widespread plasticity in frontal and parietal cortical areas. Neuronal representation of the avatar and reach targets was enhanced with learning, whereas pairwise correlations between neurons initially increased and then decreased. These results suggest that cortical networks may assimilate the two avatar arms through BMI control. These findings should help in the design of more sophisticated BMIs capable of enabling bimanual motor control in human patients.

Altering Effort Costs in Parkinson's Disease with Noninvasive Cortical Stimulation

PubMed Central

Salimpour, Yousef; Mari, Zoltan K.

2015-01-01

In Parkinson's disease (PD), the human brain is capable of producing motor commands, but appears to require greater than normal subjective effort, particularly for the more-affected side. What is the nature of this subjective effort and can it be altered? We used an isometric task in which patients produced a goal force by engaging both arms, but were free to assign any fraction of that force to each arm. The patients preferred their less-affected arm, but only in some directions. This preference was correlated with lateralization of signal-dependent noise: the direction of force for which the brain was less willing to assign effort to an arm was generally the direction for which that arm exhibited greater noise. Therefore, the direction-dependent noise in each arm acted as an implicit cost that discouraged use of that arm. To check for a causal relationship between noise and motor cost, we used bilateral transcranial direct current stimulation of the motor cortex, placing the cathode on the more-affected side and the anode on the less-affected side. This stimulation not only reduced the noise on the more-affected arm, it also increased the willingness of the patients to assign force to that arm. In a 3 d double-blind study and in a 10 d repeated stimulation study, bilateral stimulation of the two motor cortices with cathode on the more-affected side reduced noise and increased the willingness of the patients to exert effort. This stimulation also improved the clinical motor symptoms of the disease. SIGNIFICANCE STATEMENT In Parkinson's disease, patients are less willing to assign force to their affected arm. Here, we find that this pattern is direction dependent: directions for which the arm is noisier coincide with directions for which the brain is less willing to assign force. We hypothesized that if we could reduce the noise on the affected arm, then we may increase the willingness for the brain to assign force to that arm. We found a way to do this via noninvasive cortical stimulation. In addition to reducing effort costs associated with the affected arm, the cortical stimulation also improved clinical motor symptoms of the disease. PMID:26338339

The Neural Circuits that Generate Tics in Gilles de la Tourette Syndrome

PubMed Central

Wang, Zhishun; Maia, Tiago V.; Marsh, Rachel; Colibazzi, Tiziano; Gerber, Andrew; Peterson, Bradley S.

2014-01-01

Objective To study neural activity and connectivity within cortico-striato-thalamo-cortical circuits and to reveal circuit-based neural mechanisms that govern tic generation in Tourette syndrome. Method We acquired fMRI data from 13 participants with Tourette syndrome and 21 controls during spontaneous or simulated tics. We used independent component analysis with hierarchical partner matching to isolate neural activity within functionally distinct regions of cortico-striato-thalamo-cortical circuits. We used Granger causality to investigate causal interactions among these regions. Results We found that the Tourette group exhibited stronger neural activity and interregional causality than controls throughout all portions of the motor pathway including sensorimotor cortex, putamen, pallidum, and substania nigra. Activity in these areas correlated positively with the severity of tic symptoms. Activity within the Tourette group was stronger during spontaneous tics than during voluntary tics in somatosensory and posterior parietal cortices, putamen, and amygdala/hippocampus complex, suggesting that activity in these regions may represent features of the premonitory urges that generate spontaneous tic behaviors. In contrast, activity was weaker in the Tourette group than in controls within portions of cortico-striato-thalamo-cortical circuits that exert top-down control over motor pathways (caudate and anterior cingulate cortex), and progressively less activity in these regions accompanied more severe tic symptoms, suggesting that faulty activity in these circuits may fail to control tic behaviors or the premonitory urges that generate them. Conclusions Our findings taken together suggest that tics are caused by the combined effects of excessive activity in motor pathways and reduced activation in control portions of cortico-striato-thalamo-cortical circuits. PMID:21955933

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.

The evolution of the neocortex in mammals: intrinsic and extrinsic contributions to the cortical phenotype.

PubMed

Karlen, Sarah J; Krubitzer, Leah

2006-01-01

The neocortex is that portion of the brain that is involved in volitional motor control, perception, cognition and a number of other complex behaviours exhibited by mammals, including humans. Indeed, the increase in the size of the cortical sheet and cortical field number is one of the hallmarks of human brain evolution. Fossil records and comparative studies of the neocortex indicate that early mammalian neocortices were composed of only a few parts or cortical fields, and that in some lineages such as primates, the neocortex expanded dramatically. More significantly, the number of cortical fields increased and the connectivity between cortical fields became more complex. While we do not know the exact transformation between this type of increase in cortical field number and connectivity; and the emergence of complex behaviours like those mentioned above, we know that species that have large neocorticies with multiple parts generally have more complex behaviours, both overt and covert. Although a number of inroads have been made into understanding how neurons in the neocortex respond to a variety of stimuli, the micro and macro circuitry of particular neocortical fields, and the molecular developmental events that construct current organization, very little is known about how more cortical fields are added in evolution. In particular, we do not know the rules of change, nor the constraints imposed on evolving nervous systems that dictate the particular phenotype that will ultimately emerge. One reason why these issues are unresolved is that the brain is a compromise between existing genetic constraints and the need to adapt. Thus, the functions that the brain generates are absolutely imperfect, although functionally optimized. This makes it very difficult to determine the rules of construction, to generate viable computational models of brain evolution, and to predict the direction of changes that may occur over time. Despite these obstacles, it is still possible to study the evolution of the neocortex. One way is to study the products of the evolutionary process--extant mammal brains-and to make inferences about the process. The second way to study brain evolution is to examine the developmental mechanisms that give rise to complex brains. We have begun to test our theories regarding cortical evolution, generated from comparative studies, by 'tweaking' in a developing nervous system what we believe is naturally being modified in evolution. Our goals are to identify the constraints imposed on the evolving neocortex, to disentangle the genetic and activity dependent mechanisms that give rise to complex brains, and ultimately to produce a cortical phenotype that is consistent with what would naturally occur in evolution.

(Con)text-specific effects of visual dysfunction on reading in posterior cortical atrophy.

PubMed

Yong, Keir X X; Shakespeare, Timothy J; Cash, Dave; Henley, Susie M D; Warren, Jason D; Crutch, Sebastian J

2014-08-01

Reading deficits are a common early feature of the degenerative syndrome posterior cortical atrophy (PCA) but are poorly understood even at the single word level. The current study evaluated the reading accuracy and speed of 26 PCA patients, 17 typical Alzheimer's disease (tAD) patients and 14 healthy controls on a corpus of 192 single words in which the following perceptual properties were manipulated systematically: inter-letter spacing, font size, length, font type, case and confusability. PCA reading was significantly less accurate and slower than tAD patients and controls, with performance significantly adversely affected by increased letter spacing, size, length and font (cursive < non-cursive), and characterised by visual errors (69% of all error responses). By contrast, tAD and control accuracy rates were at or near ceiling, letter spacing was the only perceptual factor to influence reading speed in the same direction as controls, and, in contrast to PCA patients, control reading was faster for larger font sizes. The inverse size effect in PCA (less accurate reading of large than small font size print) was associated with lower grey matter volume in the right superior parietal lobule. Reading accuracy was associated with impairments of early visual (especially crowding), visuoperceptual and visuospatial processes. However, these deficits were not causally related to a universal impairment of reading as some patients showed preserved reading for small, unspaced words despite grave visual deficits. Rather, the impact of specific types of visual dysfunction on reading was found to be (con)text specific, being particularly evident for large, spaced, lengthy words. These findings improve the characterisation of dyslexia in PCA, shed light on the causative and associative factors, and provide clear direction for the development of reading aids and strategies to maximise and sustain reading ability in the early stages of disease. Copyright © 2014. Published by Elsevier Ltd.

(Con)text-specific effects of visual dysfunction on reading in posterior cortical atrophy

PubMed Central

Yong, Keir X.X.; Shakespeare, Timothy J.; Cash, Dave; Henley, Susie M.D.; Warren, Jason D.; Crutch, Sebastian J.

2014-01-01

Reading deficits are a common early feature of the degenerative syndrome posterior cortical atrophy (PCA) but are poorly understood even at the single word level. The current study evaluated the reading accuracy and speed of 26 PCA patients, 17 typical Alzheimer's disease (tAD) patients and 14 healthy controls on a corpus of 192 single words in which the following perceptual properties were manipulated systematically: inter-letter spacing, font size, length, font type, case and confusability. PCA reading was significantly less accurate and slower than tAD patients and controls, with performance significantly adversely affected by increased letter spacing, size, length and font (cursive < non-cursive), and characterised by visual errors (69% of all error responses). By contrast, tAD and control accuracy rates were at or near ceiling, letter spacing was the only perceptual factor to influence reading speed in the same direction as controls, and, in contrast to PCA patients, control reading was faster for larger font sizes. The inverse size effect in PCA (less accurate reading of large than small font size print) was associated with lower grey matter volume in the right superior parietal lobule. Reading accuracy was associated with impairments of early visual (especially crowding), visuoperceptual and visuospatial processes. However, these deficits were not causally related to a universal impairment of reading as some patients showed preserved reading for small, unspaced words despite grave visual deficits. Rather, the impact of specific types of visual dysfunction on reading was found to be (con)text specific, being particularly evident for large, spaced, lengthy words. These findings improve the characterisation of dyslexia in PCA, shed light on the causative and associative factors, and provide clear direction for the development of reading aids and strategies to maximise and sustain reading ability in the early stages of disease. PMID:24841985

Initial cognitive decline is associated with cortical thinning in early Parkinson disease

PubMed Central

Svenningsson, Per; Weintraub, Daniel; Brønnick, Kolbjørn; Lebedev, Alexander; Westman, Eric; Aarsland, Dag

2014-01-01

Objectives: Our aim was to assess cortical thickness in a large multicenter cohort of drug-naive patients with early Parkinson disease (PD), with and without mild cognitive impairment (MCI), and explore the cognitive correlates of regional cortical thinning. Methods: One hundred twenty-three newly diagnosed patients with PD and 56 healthy controls with 3-tesla structural MRI scans and complete neuropsychological assessment from the Parkinson's Progression Markers Initiative were included. Modified Movement Disorders Society Task Force level II criteria were applied to diagnose MCI in PD. FreeSurfer image processing and analysis software was used to measure cortical thickness across groups and the association with cognitive domains and tests. Results: In patients with MCI, atrophy was found in temporal, parietal, frontal, and occipital areas compared with controls. Specific regional thinning in the right inferior temporal cortex was also found in cognitively normal patients. Memory, executive, and visuospatial performance was associated with temporoparietal and superior frontal thinning, suggesting a relationship between cognitive impairment and both anterior and posterior cortical atrophy in the whole patient sample. Conclusions: These findings confirm that MCI is associated with widespread cortical atrophy. In addition, they suggest that regional cortical thinning is already present at the time of diagnosis in patients with early, untreated PD who do not meet the criteria for MCI. Together, the results indicate that cortical thinning can serve as a marker for initial cognitive decline in early PD. PMID:24808018

Closing the loop of deep brain stimulation

PubMed Central

Carron, Romain; Chaillet, Antoine; Filipchuk, Anton; Pasillas-Lépine, William; Hammond, Constance

2013-01-01

High-frequency deep brain stimulation is used to treat a wide range of brain disorders, like Parkinson's disease. The stimulated networks usually share common electrophysiological signatures, including hyperactivity and/or dysrhythmia. From a clinical perspective, HFS is expected to alleviate clinical signs without generating adverse effects. Here, we consider whether the classical open-loop HFS fulfills these criteria and outline current experimental or theoretical research on the different types of closed-loop DBS that could provide better clinical outcomes. In the first part of the review, the two routes followed by HFS-evoked axonal spikes are explored. In one direction, orthodromic spikes functionally de-afferent the stimulated nucleus from its downstream target networks. In the opposite direction, antidromic spikes prevent this nucleus from being influenced by its afferent networks. As a result, the pathological synchronized activity no longer propagates from the cortical networks to the stimulated nucleus. The overall result can be described as a reversible functional de-afferentation of the stimulated nucleus from its upstream and downstream nuclei. In the second part of the review, the latest advances in closed-loop DBS are considered. Some of the proposed approaches are based on mathematical models, which emphasize different aspects of the parkinsonian basal ganglia: excessive synchronization, abnormal firing-rate rhythms, and a deficient thalamo-cortical relay. The stimulation strategies are classified depending on the control-theory techniques on which they are based: adaptive and on-demand stimulation schemes, delayed and multi-site approaches, stimulations based on proportional and/or derivative control actions, optimal control strategies. Some of these strategies have been validated experimentally, but there is still a large reservoir of theoretical work that may point to ways of improving practical treatment. PMID:24391555

Closing the loop of deep brain stimulation.

PubMed

Carron, Romain; Chaillet, Antoine; Filipchuk, Anton; Pasillas-Lépine, William; Hammond, Constance

2013-12-20

High-frequency deep brain stimulation is used to treat a wide range of brain disorders, like Parkinson's disease. The stimulated networks usually share common electrophysiological signatures, including hyperactivity and/or dysrhythmia. From a clinical perspective, HFS is expected to alleviate clinical signs without generating adverse effects. Here, we consider whether the classical open-loop HFS fulfills these criteria and outline current experimental or theoretical research on the different types of closed-loop DBS that could provide better clinical outcomes. In the first part of the review, the two routes followed by HFS-evoked axonal spikes are explored. In one direction, orthodromic spikes functionally de-afferent the stimulated nucleus from its downstream target networks. In the opposite direction, antidromic spikes prevent this nucleus from being influenced by its afferent networks. As a result, the pathological synchronized activity no longer propagates from the cortical networks to the stimulated nucleus. The overall result can be described as a reversible functional de-afferentation of the stimulated nucleus from its upstream and downstream nuclei. In the second part of the review, the latest advances in closed-loop DBS are considered. Some of the proposed approaches are based on mathematical models, which emphasize different aspects of the parkinsonian basal ganglia: excessive synchronization, abnormal firing-rate rhythms, and a deficient thalamo-cortical relay. The stimulation strategies are classified depending on the control-theory techniques on which they are based: adaptive and on-demand stimulation schemes, delayed and multi-site approaches, stimulations based on proportional and/or derivative control actions, optimal control strategies. Some of these strategies have been validated experimentally, but there is still a large reservoir of theoretical work that may point to ways of improving practical treatment.

Association of Higher Cortical Amyloid Burden With Loneliness in Cognitively Normal Older Adults.

PubMed

Donovan, Nancy J; Okereke, Olivia I; Vannini, Patrizia; Amariglio, Rebecca E; Rentz, Dorene M; Marshall, Gad A; Johnson, Keith A; Sperling, Reisa A

2016-12-01

Emotional and behavioral symptoms in cognitively normal older people may be direct manifestations of Alzheimer disease (AD) pathophysiology at the preclinical stage, prior to the onset of mild cognitive impairment. Loneliness is a perceived state of social and emotional isolation that has been associated with cognitive and functional decline and an increased risk of incident AD dementia. We hypothesized that loneliness might occur in association with elevated cortical amyloid burden, an in vivo research biomarker of AD. To determine whether cortical amyloid burden is associated with greater loneliness in cognitively normal older adults. Cross-sectional analyses using data from the Harvard Aging Brain Study of 79 cognitively normal, community-dwelling participants. A continuous, aggregate measure of cortical amyloid burden, determined by Pittsburgh Compound B-positron emission tomography (PiB-PET), was examined in association with loneliness in linear regression models adjusting for age, sex, apolipoprotein E ε4 (APOEε4), socioeconomic status, depression, anxiety, and social network (without and with the interaction of amyloid and APOEε4). We also quantified the association of high amyloid burden (amyloid-positive group) to loneliness (lonely group) using logistic regression, controlling for the same covariates, with the amyloid-positive group and the lonely group, each composing 32% of the sample (n = 25). Loneliness, as determined by the 3-item UCLA Loneliness Scale (possible range, 3-12, with higher score indicating greater loneliness). The 79 participants included 43 women and 36 men with a mean (SD) age of 76.4 (6.2) years. Mean (SD) cortical amyloid burden via PiB-PET was 1.230 (0.209), and the mean (SD) UCLA-3 loneliness score was 5.3 (1.8). Twenty-two (28%) had positive APOEε4 carrier status, and 25 (32%) were in the amyloid-positive group with cortical PiB distribution volume ratio greater than 1.2. Controlling for age, sex, APOEε4, socioeconomic status, depression, anxiety, and social network, we found that higher amyloid burden was significantly associated with greater loneliness: compared with individuals in the amyloid-negative group, those in the amyloid-positive group were 7.5-fold (95% CI, 1.7-fold to 34.0-fold) more likely to be classified as lonely than nonlonely (β = 3.3, partial r = 0.4, P = .002). Furthermore, the association of high amyloid burden and loneliness was stronger in APOEε4 carriers than in noncarriers. We report a novel association of loneliness with cortical amyloid burden in cognitively normal older adults, suggesting that loneliness is a neuropsychiatric symptom relevant to preclinical AD. This work will inform new research into the neural underpinnings and disease mechanisms involved in loneliness and may enhance early detection and intervention research in AD.

Sensorineural hearing loss degrades behavioral and physiological measures of human spatial selective auditory attention

PubMed Central

Dai, Lengshi; Best, Virginia; Shinn-Cunningham, Barbara G.

2018-01-01

Listeners with sensorineural hearing loss often have trouble understanding speech amid other voices. While poor spatial hearing is often implicated, direct evidence is weak; moreover, studies suggest that reduced audibility and degraded spectrotemporal coding may explain such problems. We hypothesized that poor spatial acuity leads to difficulty deploying selective attention, which normally filters out distracting sounds. In listeners with normal hearing, selective attention causes changes in the neural responses evoked by competing sounds, which can be used to quantify the effectiveness of attentional control. Here, we used behavior and electroencephalography to explore whether control of selective auditory attention is degraded in hearing-impaired (HI) listeners. Normal-hearing (NH) and HI listeners identified a simple melody presented simultaneously with two competing melodies, each simulated from different lateral angles. We quantified performance and attentional modulation of cortical responses evoked by these competing streams. Compared with NH listeners, HI listeners had poorer sensitivity to spatial cues, performed more poorly on the selective attention task, and showed less robust attentional modulation of cortical responses. Moreover, across NH and HI individuals, these measures were correlated. While both groups showed cortical suppression of distracting streams, this modulation was weaker in HI listeners, especially when attending to a target at midline, surrounded by competing streams. These findings suggest that hearing loss interferes with the ability to filter out sound sources based on location, contributing to communication difficulties in social situations. These findings also have implications for technologies aiming to use neural signals to guide hearing aid processing. PMID:29555752

Major Superficial White Matter Abnormalities in Huntington's Disease

PubMed Central

Phillips, Owen R.; Joshi, Shantanu H.; Squitieri, Ferdinando; Sanchez-Castaneda, Cristina; Narr, Katherine; Shattuck, David W.; Caltagirone, Carlo; Sabatini, Umberto; Di Paola, Margherita

2016-01-01

Background: The late myelinating superficial white matter at the juncture of the cortical gray and white matter comprising the intracortical myelin and short-range association fibers has not received attention in Huntington's disease. It is an area of the brain that is late myelinating and is sensitive to both normal aging and neurodegenerative disease effects. Therefore, it may be sensitive to Huntington's disease processes. Methods: Structural MRI data from 25 Pre-symptomatic subjects, 24 Huntington's disease patients and 49 healthy controls was run through a cortical pattern-matching program. The surface corresponding to the white matter directly below the cortical gray matter was then extracted. Individual subject's Diffusion Tensor Imaging (DTI) data was aligned to their structural MRI data. Diffusivity values along the white matter surface were then sampled at each vertex point. DTI measures with high spatial resolution across the superficial white matter surface were then analyzed with the General Linear Model to test for the effects of disease. Results: There was an overall increase in the axial and radial diffusivity across much of the superficial white matter (p < 0.001) in Pre-symptomatic subjects compared to controls. In Huntington's disease patients increased diffusivity covered essentially the whole brain (p < 0.001). Changes are correlated with genotype (CAG repeat number) and disease burden (p < 0.001). Conclusions: This study showed broad abnormalities in superficial white matter even before symptoms are present in Huntington's disease. Since, the superficial white matter has a unique microstructure and function these abnormalities suggest it plays an important role in the disease. PMID:27242403

Using an Artificial Neural Bypass to Restore Cortical Control of Rhythmic Movements in a Human with Quadriplegia

PubMed Central

Sharma, Gaurav; Friedenberg, David A.; Annetta, Nicholas; Glenn, Bradley; Bockbrader, Marcie; Majstorovic, Connor; Domas, Stephanie; Mysiw, W. Jerry; Rezai, Ali; Bouton, Chad

2016-01-01

Neuroprosthetic technology has been used to restore cortical control of discrete (non-rhythmic) hand movements in a paralyzed person. However, cortical control of rhythmic movements which originate in the brain but are coordinated by Central Pattern Generator (CPG) neural networks in the spinal cord has not been demonstrated previously. Here we show a demonstration of an artificial neural bypass technology that decodes cortical activity and emulates spinal cord CPG function allowing volitional rhythmic hand movement. The technology uses a combination of signals recorded from the brain, machine-learning algorithms to decode the signals, a numerical model of CPG network, and a neuromuscular electrical stimulation system to evoke rhythmic movements. Using the neural bypass, a quadriplegic participant was able to initiate, sustain, and switch between rhythmic and discrete finger movements, using his thoughts alone. These results have implications in advancing neuroprosthetic technology to restore complex movements in people living with paralysis. PMID:27658585

Meninges control tangential migration of hem-derived Cajal-Retzius cells via CXCL12/CXCR4 signaling.

PubMed

Borrell, Víctor; Marín, Oscar

2006-10-01

Cajal-Retzius cells are critical in the development of the cerebral cortex, but little is known about the mechanisms controlling their development. Three focal sources of Cajal-Retzius cells have been identified in mice-the cortical hem, the ventral pallium and the septum-from where they migrate tangentially to populate the cortical surface. Using a variety of tissue culture assays and in vivo manipulations, we demonstrate that the tangential migration of cortical hem-derived Cajal-Retzius cells is controlled by the meninges. We show that the meningeal membranes are a necessary and sufficient substrate for the tangential migration of Cajal-Retzius cells. We also show that the chemokine CXCL12 secreted by the meninges enhances the dispersion of Cajal-Retzius cells along the cortical surface, while retaining them within the marginal zone in a CXCR4-dependent manner. Thus, the meningeal membranes are fundamental in the development of Cajal-Retzius cells and, hence, in the normal development of the cerebral cortex.

Sniffin' Sticks and olfactory system imaging in patients with Kallmann syndrome.

PubMed

Ottaviano, Giancarlo; Cantone, Elena; D'Errico, Arianna; Salvalaggio, Alessandro; Citton, Valentina; Scarpa, Bruno; Favaro, Angela; Sinisi, Antonio Agostino; Liuzzi, Raffaele; Bonanni, Guglielmo; Di Salle, Francesco; Elefante, Andrea; Manara, Renzo; Staffieri, Alberto; Martini, Alessandro; Brunetti, Arturo

2015-09-01

The relationship between olfactory function, rhinencephalon and forebrain changes in Kallmann syndrome (KS) have not been adequately investigated. We evaluated a large cohort of male KS patients using Sniffin' Sticks and MRI in order to study olfactory bulb (OB) volume, olfactory sulcus (OS) depth, cortical thickness close to the OS, and olfactory phenotype. Olfaction was assessed administering Sniffin' Sticks®, in 38 KS patients and 17 controls (by means of Screening 12 test®). All subjects underwent magnetic resonance imaging (MRI) to study OB volume, sulcus depth, and cortical thickness. Compared to controls, KS patients showed smaller OB volume (p<0.0001), reduced sulcus depth (p<0.0001), and thicker cortex in the region close to the OS (p<0.0001). Anosmic KS patients had smaller OB than controls and hyposmic KS patients; there was no difference between hyposmic KS patients and controls. OB volume correlated with Sniffin' Sticks score (r = 0.64; p < 0.001), OS depth (p<0.0001) and, inversely, with cortical thickness changes (p<0.0001). Sniffin' Sticks showed an inverse correlation with cortical thickness (r = -0.5; p<0.0001) and a trend toward a statistically significant correlation with OS depth. The present study provides further evidence of the strict relationship between olfaction and OB volume. The strong correlation between OB volume and the overlying cortical changes highlights the key role of rhinencephalon in forebrain embryogenesis. © 2015 ARS-AAOA, LLC.

The sexually dimorphic impact of maltreatment on cortical thickness, surface area and gyrification.

PubMed

Kelly, Philip A; Viding, Essi; Puetz, Vanessa B; Palmer, Amy L; Samuel, Sophie; McCrory, Eamon J

2016-09-01

An extensive literature has detailed how maltreatment experience impacts brain structure in children and adolescents. However, there is a dearth of studies on the influence of maltreatment on surface based indices, and to date no study has investigated how sex influences the impact of maltreatment on cortical thickness, surface area and local gyrification. We investigated sex differences in these measures of cortical structure in a large community sample of children aged 10-14 years (n = 122) comprising 62 children with verified maltreatment experience and 60 matched non-maltreated controls. The maltreated group relative to the controls presented with a pattern of decreased cortical thickness within a region of right anterior cingulate, orbitofrontal cortex and superior frontal gyrus; decreased surface area within the right inferior parietal cortex; and increased local gyrification within left superior parietal cortex. This atypical pattern of cortical structure was similar across males and females. An interaction between maltreatment exposure and sex was found only in local gyrification, within two clusters: the right tempo-parietal junction and the left precentral gyrus. These findings suggest that maltreatment impacts cortical structure in brain areas associated with emotional regulation and theory of mind, with few differences between the sexes.

Dynamics of place, boundary and object encoding in rat anterior claustrum

PubMed Central

Jankowski, Maciej M.; O’Mara, Shane M.

2015-01-01

Discrete populations of brain cells signal differing types of spatial information. These “spatial cells” are largely confined to a closely-connected network of sites. We describe here, for the first time, cells in the anterior claustrum of the freely-moving rat encoding place, boundary and object information. This novel claustral spatial signal potentially directly modulates a wide variety of anterior cortical regions. We hypothesize that one of the functions of the claustrum is to provide information about body position, boundaries and landmark information, enabling dynamic control of behavior. PMID:26557060

Slow-oscillatory Transcranial Direct Current Stimulation Modulates Memory in Temporal Lobe Epilepsy by Altering Sleep Spindle Generators: A Possible Rehabilitation Tool.

PubMed

Del Felice, Alessandra; Magalini, Alessandra; Masiero, Stefano

2015-01-01

Temporal lobe epilepsy (TLE) is often associated with memory deficits. Given the putative role for sleep spindles memory consolidation, spindle generators skewed toward the affected lobe in TLE subjects may be a neurophysiological marker of defective memory. Slow-oscillatory transcranial direct current stimulation (sotDCS) during slow waves sleep (SWS) has previously been shown to enhance sleep-dependent memory consolidation by increasing slow-wave sleep and modulating sleep spindles. To test if anodal sotDCS over the affected TL prior to a nap affects sleep spindles and whether this improves memory consolidation. Randomized controlled cross-over study. 12 people with TLE underwent sotDCS (0.75 Hz; 0-250 μV, 30 min) or sham before daytime nap. Declarative verbal and visuospatial learning were tested. Fast and slow spindle signals were recorded by 256-channel EEG during sleep. In both study arms, electrical source imaging (ESI) localized cortical generators. Neuropsychological data were analyzed with general linear model statistics or the Kruskal-Wallis test (P or Z < 0.05), and neurophysiological data tested with the Mann-Whitney t test and binomial distribution test (P or Z < 0.05). An improvement in declarative (P = 0.05) and visuospatial memory performance (P = 0.048) emerged after sotDCS. SotDCS increased slow spindle generators current density (Z = 0.001), with a shift to the anterior cortical areas. Anodal sotDCS over the affected temporal lobe improves declarative and visuospatial memory performance by modulating slow sleep spindles cortical source generators. SotDCS appears a promising tool for memory rehabilitation in people with TLE. Copyright © 2015 Elsevier Inc. All rights reserved.

Graphical Neuroimaging Informatics: Application to Alzheimer’s Disease

PubMed Central

Bowman, Ian; Joshi, Shantanu H.; Greer, Vaughan

2013-01-01

The Informatics Visualization for Neuroimaging (INVIZIAN) framework allows one to graphically display image and meta-data information from sizeable collections of neuroimaging data as a whole using a dynamic and compelling user interface. Users can fluidly interact with an entire collection of cortical surfaces using only their mouse. In addition, users can cluster and group brains according in multiple ways for subsequent comparison using graphical data mining tools. In this article, we illustrate the utility of INVIZIAN for simultaneous exploration and mining a large collection of extracted cortical surface data arising in clinical neuroimaging studies of patients with Alzheimer’s Disease, mild cognitive impairment, as well as healthy control subjects. Alzheimer’s Disease is particularly interesting due to the wide-spread effects on cortical architecture and alterations of volume in specific brain areas associated with memory. We demonstrate INVIZIAN’s ability to render multiple brain surfaces from multiple diagnostic groups of subjects, showcase the interactivity of the system, and showcase how INVIZIAN can be employed to generate hypotheses about the collection of data which would be suitable for direct access to the underlying raw data and subsequent formal statistical analysis. Specifically, we use INVIZIAN show how cortical thickness and hippocampal volume differences between group are evident even in the absence of more formal hypothesis testing. In the context of neurological diseases linked to brain aging such as AD, INVIZIAN provides a unique means for considering the entirety of whole brain datasets, look for interesting relationships among them, and thereby derive new ideas for further research and study. PMID:24203652

Chronic intraventricular administration of lysergic acid diethylamide (LSD) affects the sensitivity of cortical cells to monocular deprivation.

PubMed

McCall, M A; Tieman, D G; Hirsch, H V

1982-11-04

In kittens, but not in adult cats, depriving one eye of pattern vision by suturing the lids shut (monocular deprivation or MD) for one week reduces the proportion of binocular units in the visual cortex. A sensitivity of cortical units in adult cats to MD can be produced by infusing exogenous monoamines into the visual cortex. Since LSD interacts with monoamines, we have examined the effects of chronic administration of LSD on the sensitivity to MD for cortical cells in adult cats. Cats were assigned randomly to one of four conditions: MD/LSD, MD/No-LSD, No-MD/LSD, No-MD/No-LSD. An osmotic minipump delivered either LSD or the vehicle solution alone during a one-week period of MD. The animals showed no obvious anomalies during the administration of the drug. After one week the response properties of single units in area 17 of the visual cortex were studied without knowledge of the contents of the individual minipumps. With the exception of ocular dominance, the response properties of units recorded in all animals did not differ from normal. In the control animals (MD/No-LSD, No-MD/LSD, No-MD/No-LSD) the average proportion of binocular cells was 78%; similar to that observed for normal adult cats. However, in the experimental animals, which received LSD during the period of MD, only 52% of the cells were binocular. Our results suggest that chronic intraventricular administration of LSD affects either directly or indirectly the sensitivity of cortical neurons to MD.

Automatic cortical thickness analysis on rodent brain

NASA Astrophysics Data System (ADS)

Lee, Joohwi; Ehlers, Cindy; Crews, Fulton; Niethammer, Marc; Budin, Francois; Paniagua, Beatriz; Sulik, Kathy; Johns, Josephine; Styner, Martin; Oguz, Ipek

2011-03-01

Localized difference in the cortex is one of the most useful morphometric traits in human and animal brain studies. There are many tools and methods already developed to automatically measure and analyze cortical thickness for the human brain. However, these tools cannot be directly applied to rodent brains due to the different scales; even adult rodent brains are 50 to 100 times smaller than humans. This paper describes an algorithm for automatically measuring the cortical thickness of mouse and rat brains. The algorithm consists of three steps: segmentation, thickness measurement, and statistical analysis among experimental groups. The segmentation step provides the neocortex separation from other brain structures and thus is a preprocessing step for the thickness measurement. In the thickness measurement step, the thickness is computed by solving a Laplacian PDE and a transport equation. The Laplacian PDE first creates streamlines as an analogy of cortical columns; the transport equation computes the length of the streamlines. The result is stored as a thickness map over the neocortex surface. For the statistical analysis, it is important to sample thickness at corresponding points. This is achieved by the particle correspondence algorithm which minimizes entropy between dynamically moving sample points called particles. Since the computational cost of the correspondence algorithm may limit the number of corresponding points, we use thin-plate spline based interpolation to increase the number of corresponding sample points. As a driving application, we measured the thickness difference to assess the effects of adolescent intermittent ethanol exposure that persist into adulthood and performed t-test between the control and exposed rat groups. We found significantly differing regions in both hemispheres.

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

Structural and Diffusion Property Alterations in Unaffected Siblings of Patients with Obsessive-Compulsive Disorder

PubMed Central

Shi, Changzheng; Miao, Guodong; Yang, Qiong; Gao, Wei; Wolff, Jason J.; Chan, Raymond C. K.; Shen, Dinggang

2014-01-01

Disrupted white matter integrity and abnormal cortical thickness are widely reported in the pathophysiology of obsessive-compulsive disorder (OCD). However, the relationship between alterations in white matter connectivity and cortical thickness in OCD is unclear. In addition, the heritability of this relationship is poorly understood. To investigate the relationship of white matter microstructure with cortical thickness, we measure fractional anisotropy (FA) of white matter in 30 OCD patients, 19 unaffected siblings and 30 matched healthy controls. Then, we take those regions of significantly altered FA in OCD patients compared with healthy controls to perform fiber tracking. Next, we calculate the fiber quantity in the same tracts. Lastly, we compare cortical thickness in the target regions of those tracts. Patients with OCD exhibited decreased FA in cingulum, arcuate fibers near the superior parietal lobule, inferior longitudinal fasciculus near the right superior temporal gyrus and uncinate fasciculus. Siblings showed reduced FA in arcuate fibers near the superior parietal lobule and anterior limb of internal capsule. Significant reductions in both fiber quantities and cortical thickness in OCD patients and their unaffected siblings were also observed in the projected brain areas when using the arcuate fibers near the left superior parietal lobule as the starting points. Reduced FA in the left superior parietal lobule was observed not only in patients with OCD but also in their unaffected siblings. Originated from the superior parietal lobule, the number of fibers was also found to be decreased and the corresponding cortical regions were thinner relative to controls. The linkage between disrupted white matter integrity and the abnormal cortical thickness may be a vulnerability marker for OCD. PMID:24489665

Mean cortical curvature reflects cytoarchitecture restructuring in mild traumatic brain injury

PubMed Central

King, Jace B.; Lopez-Larson, Melissa P.; Yurgelun-Todd, Deborah A.

2016-01-01

In the United States alone, the number of persons living with the enduring consequences of traumatic brain injuries is estimated to be between 3.2 and 5 million. This number does not include individuals serving in the United States military or seeking care at Veterans Affairs hospitals. The importance of understanding the neurobiological consequences of mild traumatic brain injury (mTBI) has increased with the return of veterans from conflicts overseas, many of who have suffered this type of brain injury. However, identifying the neuroanatomical regions most affected by mTBI continues to prove challenging. The aim of this study was to assess the use of mean cortical curvature as a potential indicator of progressive tissue loss in a cross-sectional sample of 54 veterans with mTBI compared to 31 controls evaluated with MRI. It was hypothesized that mean cortical curvature would be increased in veterans with mTBI, relative to controls, due in part to cortical restructuring related to tissue volume loss. Mean cortical curvature was assessed in 60 bilateral regions (31 sulcal, 29 gyral). Of the 120 regions investigated, nearly 50% demonstrated significantly increased mean cortical curvature in mTBI relative to controls with 25% remaining significant following multiple comparison correction (all, pFDR < .05). These differences were most prominent in deep gray matter regions of the cortex. Additionally, significant relationships were found between mean cortical curvature and gray and white matter volumes (all, p < .05). These findings suggest potentially unique patterns of atrophy by region and indicate that changes in brain microstructure due to mTBI are sensitive to measures of mean curvature. PMID:26909332

Mean cortical curvature reflects cytoarchitecture restructuring in mild traumatic brain injury.

PubMed

King, Jace B; Lopez-Larson, Melissa P; Yurgelun-Todd, Deborah A

2016-01-01

In the United States alone, the number of persons living with the enduring consequences of traumatic brain injuries is estimated to be between 3.2 and 5 million. This number does not include individuals serving in the United States military or seeking care at Veterans Affairs hospitals. The importance of understanding the neurobiological consequences of mild traumatic brain injury (mTBI) has increased with the return of veterans from conflicts overseas, many of who have suffered this type of brain injury. However, identifying the neuroanatomical regions most affected by mTBI continues to prove challenging. The aim of this study was to assess the use of mean cortical curvature as a potential indicator of progressive tissue loss in a cross-sectional sample of 54 veterans with mTBI compared to 31 controls evaluated with MRI. It was hypothesized that mean cortical curvature would be increased in veterans with mTBI, relative to controls, due in part to cortical restructuring related to tissue volume loss. Mean cortical curvature was assessed in 60 bilateral regions (31 sulcal, 29 gyral). Of the 120 regions investigated, nearly 50% demonstrated significantly increased mean cortical curvature in mTBI relative to controls with 25% remaining significant following multiple comparison correction (all, pFDR < .05). These differences were most prominent in deep gray matter regions of the cortex. Additionally, significant relationships were found between mean cortical curvature and gray and white matter volumes (all, p < .05). These findings suggest potentially unique patterns of atrophy by region and indicate that changes in brain microstructure due to mTBI are sensitive to measures of mean curvature.

Complement is activated in progressive multiple sclerosis cortical grey matter lesions.

PubMed

Watkins, Lewis M; Neal, James W; Loveless, Sam; Michailidou, Iliana; Ramaglia, Valeria; Rees, Mark I; Reynolds, Richard; Robertson, Neil P; Morgan, B Paul; Howell, Owain W

2016-06-22

The symptoms of multiple sclerosis (MS) are caused by damage to myelin and nerve cells in the brain and spinal cord. Inflammation is tightly linked with neurodegeneration, and it is the accumulation of neurodegeneration that underlies increasing neurological disability in progressive MS. Determining pathological mechanisms at play in MS grey matter is therefore a key to our understanding of disease progression. We analysed complement expression and activation by immunocytochemistry and in situ hybridisation in frozen or formalin-fixed paraffin-embedded post-mortem tissue blocks from 22 progressive MS cases and made comparisons to inflammatory central nervous system disease and non-neurological disease controls. Expression of the transcript for C1qA was noted in neurons and the activation fragment and opsonin C3b-labelled neurons and glia in the MS cortical and deep grey matter. The density of immunostained cells positive for the classical complement pathway protein C1q and the alternative complement pathway activation fragment Bb was significantly increased in cortical grey matter lesions in comparison to control grey matter. The number of cells immunostained for the membrane attack complex was elevated in cortical lesions, indicating complement activation to completion. The numbers of classical (C1-inhibitor) and alternative (factor H) pathway regulator-positive cells were unchanged between MS and controls, whilst complement anaphylatoxin receptor-bearing microglia in the MS cortex were found closely apposed to cortical neurons. Complement immunopositive neurons displayed an altered nuclear morphology, indicative of cell stress/damage, supporting our finding of significant neurodegeneration in cortical grey matter lesions. Complement is activated in the MS cortical grey matter lesions in areas of elevated numbers of complement receptor-positive microglia and suggests that complement over-activation may contribute to the worsening pathology that underlies the irreversible progression of MS.

Cortical bone is more sensitive to alcohol dose effects than trabecular bone in the rat.

PubMed

Maurel, Delphine B; Boisseau, Nathalie; Benhamou, Claude-Laurent; Jaffré, Christelle

2012-10-01

While chronic alcohol consumption is known to decrease bone mineral content (BMC), bone mineral density (BMD), and negatively modify trabecular bone microarchitecture, the impact of alcohol on cortical microarchitecture is still unclear. The aim of this study was to investigate the effects of various doses of alcohol on bone density, trabecular and cortical parameters and bone strength in rats. Forty-eight male Wistar rats were divided into four groups: control (C), alcohol 25% v/v (A25), alcohol 30% v/v (A30) and alcohol 35% v/v (A35). Rats in the alcohol groups were fed a solution composed of ethanol and water for 17 weeks while the control group drank only water. Bone quality and quantity were evaluated through the analysis of density, trabecular and cortical bone microarchitectural parameters, osteocalcin and N-Telopeptide concentrations and a 3-point bending test. Bone density along with trabecular and cortical thickness were lower in alcohol groups compared to C. BMD was lower in A35 vs. A30 and cortical thickness was lower in A35 vs. A25 and A30. Pore number was increased by alcohol and the porosity was greater in A35 compared to C. N-Telopeptide concentration was decreased in alcohol groups compared to control whereas no differences were observed in osteocalcin concentrations. Maximal energy to failure was lower in A25 and A35 compared to C. Chronic ethanol consumption increases cortical bone damage in rats and may have detrimental effects on bone strength. These effects were dose-dependent, with greater negative effects proportionate to greater alcohol doses. Copyright © 2011 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Reduced Current Spread by Concentric Electrodes in Transcranial Electrical Stimulation (tES).

PubMed

Bortoletto, M; Rodella, C; Salvador, R; Miranda, P C; Miniussi, C

2016-01-01

We propose the use of a new montage for transcranial direct current stimulation (tDCS), called concentric electrodes tDCS (CE-tDCS), involving two concentric round electrodes that may improve stimulation focality. To test efficacy and focality of CE-tDCS, we modelled the current distribution and tested physiological effects on cortical excitability. Motor evoked potentials (MEPs) from first dorsal interosseous (FDI) and abductor digiti minimi (ADM) were recorded before and after the delivery of anodal, cathodal and sham stimulation on the FDI hotspot for 10 minutes. MEP amplitude of FDI increased after anodal-tDCS and decreased after cathodal-tDCS, supporting the efficacy of CE-tDCS in modulating cortical excitability. Moreover, modelled current distribution and no significant effects of stimulation on MEP amplitude of ADM suggest high focality of CE-tDCS. CE-tDCS may allow a better control of current distribution and may represent a novel tool for applying tDCS and other transcranial current stimulation approaches. Copyright © 2016 Elsevier Inc. All rights reserved.

Feature-Selective Attentional Modulations in Human Frontoparietal Cortex.

PubMed

Ester, Edward F; Sutterer, David W; Serences, John T; Awh, Edward

2016-08-03

Control over visual selection has long been framed in terms of a dichotomy between "source" and "site," where top-down feedback signals originating in frontoparietal cortical areas modulate or bias sensory processing in posterior visual areas. This distinction is motivated in part by observations that frontoparietal cortical areas encode task-level variables (e.g., what stimulus is currently relevant or what motor outputs are appropriate), while posterior sensory areas encode continuous or analog feature representations. Here, we present evidence that challenges this distinction. We used fMRI, a roving searchlight analysis, and an inverted encoding model to examine representations of an elementary feature property (orientation) across the entire human cortical sheet while participants attended either the orientation or luminance of a peripheral grating. Orientation-selective representations were present in a multitude of visual, parietal, and prefrontal cortical areas, including portions of the medial occipital cortex, the lateral parietal cortex, and the superior precentral sulcus (thought to contain the human homolog of the macaque frontal eye fields). Additionally, representations in many-but not all-of these regions were stronger when participants were instructed to attend orientation relative to luminance. Collectively, these findings challenge models that posit a strict segregation between sources and sites of attentional control on the basis of representational properties by demonstrating that simple feature values are encoded by cortical regions throughout the visual processing hierarchy, and that representations in many of these areas are modulated by attention. Influential models of visual attention posit a distinction between top-down control and bottom-up sensory processing networks. These models are motivated in part by demonstrations showing that frontoparietal cortical areas associated with top-down control represent abstract or categorical stimulus information, while visual areas encode parametric feature information. Here, we show that multivariate activity in human visual, parietal, and frontal cortical areas encode representations of a simple feature property (orientation). Moreover, representations in several (though not all) of these areas were modulated by feature-based attention in a similar fashion. These results provide an important challenge to models that posit dissociable top-down control and sensory processing networks on the basis of representational properties. Copyright © 2016 the authors 0270-6474/16/368188-12$15.00/0.

Cortical Reorganisation during a 30-Week Tinnitus Treatment Program

PubMed Central

McMahon, Catherine M.; Ibrahim, Ronny K.; Mathur, Ankit

2016-01-01

Subjective tinnitus is characterised by the conscious perception of a phantom sound. Previous studies have shown that individuals with chronic tinnitus have disrupted sound-evoked cortical tonotopic maps, time-shifted evoked auditory responses, and altered oscillatory cortical activity. The main objectives of this study were to: (i) compare sound-evoked brain responses and cortical tonotopic maps in individuals with bilateral tinnitus and those without tinnitus; and (ii) investigate whether changes in these sound-evoked responses occur with amelioration of the tinnitus percept during a 30-week tinnitus treatment program. Magnetoencephalography (MEG) recordings of 12 bilateral tinnitus participants and 10 control normal-hearing subjects reporting no tinnitus were recorded at baseline, using 500 Hz, 1000 Hz, 2000 Hz, and 4000 Hz tones presented monaurally at 70 dBSPL through insert tube phones. For the tinnitus participants, MEG recordings were obtained at 5-, 10-, 20- and 30- week time points during tinnitus treatment. Results for the 500 Hz and 1000 Hz sources (where hearing thresholds were within normal limits for all participants) showed that the tinnitus participants had a significantly larger and more anteriorly located source strengths when compared to the non-tinnitus participants. During the 30-week tinnitus treatment, the participants’ 500 Hz and 1000 Hz source strengths remained higher than the non-tinnitus participants; however, the source locations shifted towards the direction recorded from the non-tinnitus control group. Further, in the left hemisphere, there was a time-shifted association between the trajectory of change of the individual’s objective (source strength and anterior-posterior source location) and subjective measures (using tinnitus reaction questionnaire, TRQ). The differences in source strength between the two groups suggest that individuals with tinnitus have enhanced central gain which is not significantly influenced by the tinnitus treatment, and may result from the hearing loss per se. On the other hand, the shifts in the tonotopic map towards the non-tinnitus participants’ source location suggests that the tinnitus treatment might reduce the disruptions in the map, presumably produced by the tinnitus percept directly or indirectly. Further, the similarity in the trajectory of change across the objective and subjective parameters after time-shifting the perceptual changes by 5 weeks suggests that during or following treatment, perceptual changes in the tinnitus percept may precede neurophysiological changes. Subgroup analyses conducted by magnitude of hearing loss suggest that there were no differences in the 500 Hz and 1000 Hz source strength amplitudes for the mild-moderate compared with the mild-severe hearing loss subgroup, although the mean source strength was consistently higher for the mild-severe subgroup. Further, the mild-severe subgroup had 500 Hz and 1000 Hz source locations located more anteriorly (i.e., more disrupted compared to the control group) compared to the mild-moderate group, although this was trending towards significance only for the 500Hz left hemisphere source. While the small numbers of participants within the subgroup analyses reduce the statistical power, this study suggests that those with greater magnitudes of hearing loss show greater cortical disruptions with tinnitus and that tinnitus treatment appears to reduce the tonotopic map disruptions but not the source strength (or central gain). PMID:26901425

Toward more versatile and intuitive cortical brain-machine interfaces.

PubMed

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

2014-09-22

Brain-machine interfaces have great potential for the development of neuroprosthetic applications to assist patients suffering from brain injury or neurodegenerative disease. One type of brain-machine interface 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: recordings from cortical areas outside motor cortex; local field potentials as a source of recorded signals; somatosensory feedback for more dexterous control of robotics; and new decoding methods that work in concert to form an ecology of decode algorithms. These new advances promise to greatly accelerate the applicability and ease of operation of motor prosthetics. Copyright © 2014 Elsevier Ltd. All rights reserved.

Brain activation associated with eccentric movement: A narrative review of the literature.

PubMed

Perrey, Stéphane

2018-02-01

The movement occurring when a muscle exerts tension while lengthening is known as eccentric muscle action. Literature contains limited evidence on how our brain controls eccentric movement. However, how the cortical regions in the motor network are activated during eccentric muscle actions may be critical for understanding the underlying control mechanism of eccentric movements encountered in daily tasks. This is a novel topic that has only recently begun to be investigated through advancements in neuroimaging methods (electroencephalography, EEG; functional magnetic resonance imaging, fMRI). This review summarizes a selection of seven studies indicating mainly: longer time and higher cortical signal amplitude (EEG) for eccentric movement preparation and execution, greater magnitude of cortical signals with wider activated brain area (EEG, fMRI), and weaker brain functional connectivity (fMRI) between primary motor cortex (M1) and other cortical areas involved in the motor network during eccentric muscle actions. Only some differences among studies due to the forms of movement with overload were observed in the contralateral (to the active hand) M1 activity during eccentric movement. Altogether, the findings indicate an important challenge to the brain for controlling the eccentric movement. However, our understanding remains limited regarding the acute effects of eccentric exercise on cortical regions and their cooperation as functional networks that support motor functions. Further analysis and standardized protocols will provide deeper insights into how different cortical regions of the underlying motor network interplay with each other in increasingly demanding muscle exertions in eccentric mode.

In vivo high-resolution 7 Tesla MRI shows early and diffuse cortical alterations in CADASIL.

PubMed

De Guio, François; Reyes, Sonia; Vignaud, Alexandre; Duering, Marco; Ropele, Stefan; Duchesnay, Edouard; Chabriat, Hugues; Jouvent, Eric

2014-01-01

Recent data suggest that early symptoms may be related to cortex alterations in CADASIL (Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy), a monogenic model of cerebral small vessel disease (SVD). The aim of this study was to investigate cortical alterations using both high-resolution T2* acquisitions obtained with 7 Tesla MRI and structural T1 images with 3 Tesla MRI in CADASIL patients with no or only mild symptomatology (modified Rankin's scale ≤1 and Mini Mental State Examination (MMSE) ≥24). Complete reconstructions of the cortex using 7 Tesla T2* acquisitions with 0.7 mm isotropic resolution were obtained in 11 patients (52.1±13.2 years, 36% male) and 24 controls (54.8±11.0 years, 42% male). Seven Tesla T2* within the cortex and cortical thickness and morphology obtained from 3 Tesla images were compared between CADASIL and control subjects using general linear models. MMSE, brain volume, cortical thickness and global sulcal morphology did not differ between groups. By contrast, T2* measured by 7 Tesla MRI was significantly increased in frontal, parietal, occipital and cingulate cortices in patients after correction for multiple testing. These changes were not related to white matter lesions, lacunes or microhemorrhages in patients having no brain atrophy compared to controls. Seven Tesla MRI, by contrast to state of the art post-processing of 3 Tesla acquisitions, shows diffuse T2* alterations within the cortical mantle in CADASIL whose origin remains to be determined.

Normalization of Cortical Gray Matter Deficits in Nonpsychotic Siblings of Patients With Childhood-Onset Schizophrenia

PubMed Central

Mattai, Anand A.; Weisinger, Brian; Greenstein, Deanna; Stidd, Reva; Clasen, Liv; Miller, Rachel; Tossell, Julia W.; Rapoport, Judith L.; Gogtay, Nitin

2012-01-01

Objective Cortical gray matter (GM) abnormalities in patients with childhood-onset schizophrenia (COS) progress during adolescence ultimately localizing to prefrontal and temporal cortices by early adult age. A previous study of 52 nonpsychotic siblings of COS probands had significant prefrontal and temporal GM deficits that appeared to “normalize” by age 17 years. Here we present a replication with nonoverlapping groups of healthy full siblings and healthy controls. Method Using an automated measure and prospectively acquired anatomical brain magnetic resonance images, we mapped cortical GM thickness in nonpsychotic full siblings (n = 43, 68 scans; ages 5 through 26 years) of patients with COS, contrasting them with age-, gender-, and scan interval–matched healthy controls (n = 86, 136 scans). The false-discovery rate procedure was used to control for type I errors due to multiple comparisons. Results As in our previous study, young nonpsychotic siblings (<17 years) showed significant GM deficits in bilateral prefrontal and left temporal cortices and, in addition, smaller deficits in the parietal and right inferior temporal cortices. These deficits in nonpsychotic siblings normalized with age with minimal abnormalities remaining by age 17. Conclusions Our results support previous findings showing nonpsychotic siblings of COS probands to have early GM deficits that ameliorate with time. At early ages, prefrontal and/or temporal loss may serve as a familial/trait marker for COS. Late adolescence appears to be a critical period for greatest localization of deficits in probands or normalization in nonpsychotic siblings. PMID:21703497

Throwing enhances humeral shaft cortical bone properties in pre-pubertal baseball players: a 12-month longitudinal pilot study.

PubMed

Weatherholt, Alyssa M; Warden, Stuart J

2018-06-01

To explore throwing athletes as a prospective, within-subject controlled model for studying the response of the skeleton to exercise. Male pre-pubertal throwing athletes (n=12; age=10.3±0.6 yrs) had distal humerus cortical volumetric bone mineral density (Ct.vBMD), cortical bone mineral content (Ct.BMC), total area (Tt.Ar), cortical area (Ct.Ar), medullary area (Me.Ar), cortical thickness (Ct.Th) and polar moment of inertia (IP) assessed within their throwing (exercised) and nonthrowing (control) arms by peripheral quantitative computed tomography at baseline and 12 months. Throwing-to-nonthrowing arm percent differences (i.e. bilateral asymmetry) were compared over time. Over 12 months, the throwing arm gained 4.3% (95% Cl=1.1% to 7.5%), 2.9% (95% Cl=0.3% to 5.4%), 3.9% (95% Cl=0.7% to 7.0%), and 8.2% (95% Cl=2.0% to 6.8%) more Ct.BMC, Ct.Ar, Tt.Ar, and I P than the nonthrowing arm, respectively (all p<0.05). There was no significant effect of throwing on Ct.vBMD, Ct.Th and Me.Ar (all p=0.18-0.82). Throwing induced surface-specific cortical bone adaptation at the distal humeral diaphysis that contributed to a gain in estimated strength. These longitudinal pilot data support the utility of throwing athletes as a within-subject controlled model to explore factors influencing exercise-induced bone adaptation during the critical growing years.

Influence of basis images and skull position on evaluation of cortical bone thickness in cone beam computed tomography.

PubMed

Nascimento, Monikelly do Carmo Chagas; Boscolo, Solange Maria de Almeida; Haiter-Neto, Francisco; Santos, Emanuela Carla Dos; Lambrichts, Ivo; Pauwels, Ruben; Jacobs, Reinhilde

2017-06-01

The aim of this study was to assess the influence of the number of basis images and the orientation of the skull on the evaluation of cortical alveolar bone in cone beam computed tomography (CBCT). Eleven skulls with a total of 59 anterior teeth were selected. CBCT images were acquired by using 4 protocols, by varying the rotation of the tube-detector arm and the orientation of the skull (protocol 1: 360°/0°; protocol 2: 180°/0°; protocol 3: 180°/90°; protocol 4: 180°/180°). Observers evaluated cortical bone as absent, thin, or thick. Direct observation of the skulls was used as the gold standard. Intra- and interobserver agreement, as well as agreement of scoring between the 3 bone thickness classifications, were calculated by using the κ statistic. The Wilcoxon signed-rank test was used to compare the 4 protocols. For lingual cortical bone, protocol 1 showed no statistical difference from the gold standard. Higher reliability was found in protocol 3 for absent (κ = 0.80) and thin (κ = 0.47) cortices, whereas for thick cortical bone, protocol 2 was more consistent (κ = 0.60). In buccal cortical bone, protocol 1 obtained the highest agreement for absent cortices (κ = 0.61), whereas protocol 4 was better for thin cortical plates (κ = 0.38) and protocol 2 for thick cortical plates (κ = 0.40). No consistent effect of the number of basis images or head orientation for visual detection of alveolar bone was detected, except for lingual cortical bone, for which full rotation scanning showed improved visualization. Copyright © 2017 Elsevier Inc. All rights reserved.

Atrophy and structural covariance of the cholinergic basal forebrain in primary progressive aphasia.

PubMed

Teipel, Stefan; Raiser, Theresa; Riedl, Lina; Riederer, Isabelle; Schroeter, Matthias L; Bisenius, Sandrine; Schneider, Anja; Kornhuber, Johannes; Fliessbach, Klaus; Spottke, Annika; Grothe, Michel J; Prudlo, Johannes; Kassubek, Jan; Ludolph, Albert; Landwehrmeyer, Bernhard; Straub, Sarah; Otto, Markus; Danek, Adrian

2016-10-01

Primary progressive aphasia (PPA) is characterized by profound destruction of cortical language areas. Anatomical studies suggest an involvement of cholinergic basal forebrain (BF) in PPA syndromes, particularly in the area of the nucleus subputaminalis (NSP). Here we aimed to determine the pattern of atrophy and structural covariance as a proxy of structural connectivity of BF nuclei in PPA variants. We studied 62 prospectively recruited cases with the clinical diagnosis of PPA and 31 healthy older control participants from the cohort study of the German consortium for frontotemporal lobar degeneration (FTLD). We determined cortical and BF atrophy based on high-resolution magnetic resonance imaging (MRI) scans. Patterns of structural covariance of BF with cortical regions were determined using voxel-based partial least square analysis. We found significant atrophy of total BF and BF subregions in PPA patients compared with controls [F(1, 82) = 20.2, p < .001]. Atrophy was most pronounced in the NSP and the posterior BF, and most severe in the semantic variant and the nonfluent variant of PPA. Structural covariance analysis in healthy controls revealed associations of the BF nuclei, particularly the NSP, with left hemispheric predominant prefrontal, lateral temporal, and parietal cortical areas, including Broca's speech area (p < .001, permutation test). In contrast, the PPA patients showed preserved structural covariance of the BF nuclei mostly with right but not with left hemispheric cortical areas (p < .001, permutation test). Our findings agree with the neuroanatomically proposed involvement of the cholinergic BF, particularly the NSP, in PPA syndromes. We found a shift from a structural covariance of the BF with left hemispheric cortical areas in healthy aging towards right hemispheric cortical areas in PPA, possibly reflecting a consequence of the profound and early destruction of cortical language areas in PPA. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Impaired decision-making and selective cortical frontal thinning in Cushing's syndrome.

PubMed

Crespo, Iris; Esther, Granell-Moreno; Santos, Alicia; Valassi, Elena; Yolanda, Vives-Gilabert; De Juan-Delago, Manel; Webb, Susan M; Gómez-Ansón, Beatriz; Resmini, Eugenia

2014-12-01

Cushing's syndrome (CS) is caused by a glucocorticoid excess. This hypercortisolism can damage the prefrontal cortex, known to be important in decision-making. Our aim was to evaluate decision-making in CS and to explore cortical thickness. Thirty-five patients with CS (27 cured, eight medically treated) and thirty-five matched controls were evaluated using Iowa gambling task (IGT) and 3 Tesla magnetic resonance imaging (MRI) to assess cortical thickness. The IGT evaluates decision-making, including strategy and learning during the test. Cortical thickness was determined on MRI using freesurfer software tools, including a whole-brain analysis. There were no differences between medically treated and cured CS patients. They presented an altered decision-making strategy compared to controls, choosing a lower number of the safer cards (P < 0·05). They showed more difficulties than controls to learn the correct profiles of wins and losses for each card group (P < 0·05). In whole-brain analysis, patients with CS showed decreased cortical thickness in the left superior frontal cortex, left precentral cortex, left insular cortex, left and right rostral anterior cingulate cortex, and right caudal middle frontal cortex compared to controls (P < 0·001). Patients with CS failed to learn advantageous strategies and their behaviour was driven by short-term reward and long-term punishment, indicating learning problems because they did not use previous experience as a feedback factor to regulate their choices. These alterations in decision-making and the decreased cortical thickness in frontal areas suggest that chronic hypercortisolism promotes brain changes which are not completely reversible after endocrine remission. © 2014 John Wiley & Sons Ltd.

Cortical abnormalities in adults and adolescents with major depression based on brain scans from 20 cohorts worldwide in the ENIGMA Major Depressive Disorder Working Group

PubMed Central

Schmaal, L; Hibar, D P; Sämann, P G; Hall, G B; Baune, B T; Jahanshad, N; Cheung, J W; van Erp, T G M; Bos, D; Ikram, M A; Vernooij, M W; Niessen, W J; Tiemeier, H; Hofman, A; Wittfeld, K; Grabe, H J; Janowitz, D; Bülow, R; Selonke, M; Völzke, H; Grotegerd, D; Dannlowski, U; Arolt, V; Opel, N; Heindel, W; Kugel, H; Hoehn, D; Czisch, M; Couvy-Duchesne, B; Rentería, M E; Strike, L T; Wright, M J; Mills, N T; de Zubicaray, G I; McMahon, K L; Medland, S E; Martin, N G; Gillespie, N A; Goya-Maldonado, R; Gruber, O; Krämer, B; Hatton, S N; Lagopoulos, J; Hickie, I B; Frodl, T; Carballedo, A; Frey, E M; van Velzen, L S; Penninx, B W J H; van Tol, M-J; van der Wee, N J; Davey, C G; Harrison, B J; Mwangi, B; Cao, B; Soares, J C; Veer, I M; Walter, H; Schoepf, D; Zurowski, B; Konrad, C; Schramm, E; Normann, C; Schnell, K; Sacchet, M D; Gotlib, I H; MacQueen, G M; Godlewska, B R; Nickson, T; McIntosh, A M; Papmeyer, M; Whalley, H C; Hall, J; Sussmann, J E; Li, M; Walter, M; Aftanas, L; Brack, I; Bokhan, N A; Thompson, P M; Veltman, D J

2017-01-01

The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen's d effect sizes: −0.10 to −0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: −0.26 to −0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life. PMID:27137745

Cortical Spiking Network Interfaced with Virtual Musculoskeletal Arm and Robotic Arm.

PubMed

Dura-Bernal, Salvador; Zhou, Xianlian; Neymotin, Samuel A; Przekwas, Andrzej; Francis, Joseph T; Lytton, William W

2015-01-01

Embedding computational models in the physical world is a critical step towards constraining their behavior and building practical applications. Here we aim to drive a realistic musculoskeletal arm model using a biomimetic cortical spiking model, and make a robot arm reproduce the same trajectories in real time. Our cortical model consisted of a 3-layered cortex, composed of several hundred spiking model-neurons, which display physiologically realistic dynamics. We interconnected the cortical model to a two-joint musculoskeletal model of a human arm, with realistic anatomical and biomechanical properties. The virtual arm received muscle excitations from the neuronal model, and fed back proprioceptive information, forming a closed-loop system. The cortical model was trained using spike timing-dependent reinforcement learning to drive the virtual arm in a 2D reaching task. Limb position was used to simultaneously control a robot arm using an improved network interface. Virtual arm muscle activations responded to motoneuron firing rates, with virtual arm muscles lengths encoded via population coding in the proprioceptive population. After training, the virtual arm performed reaching movements which were smoother and more realistic than those obtained using a simplistic arm model. This system provided access to both spiking network properties and to arm biophysical properties, including muscle forces. The use of a musculoskeletal virtual arm and the improved control system allowed the robot arm to perform movements which were smoother than those reported in our previous paper using a simplistic arm. This work provides a novel approach consisting of bidirectionally connecting a cortical model to a realistic virtual arm, and using the system output to drive a robotic arm in real time. Our techniques are applicable to the future development of brain neuroprosthetic control systems, and may enable enhanced brain-machine interfaces with the possibility for finer control of limb prosthetics.

Cortical abnormalities in adults and adolescents with major depression based on brain scans from 20 cohorts worldwide in the ENIGMA Major Depressive Disorder Working Group.

PubMed

Schmaal, L; Hibar, D P; Sämann, P G; Hall, G B; Baune, B T; Jahanshad, N; Cheung, J W; van Erp, T G M; Bos, D; Ikram, M A; Vernooij, M W; Niessen, W J; Tiemeier, H; Hofman, A; Wittfeld, K; Grabe, H J; Janowitz, D; Bülow, R; Selonke, M; Völzke, H; Grotegerd, D; Dannlowski, U; Arolt, V; Opel, N; Heindel, W; Kugel, H; Hoehn, D; Czisch, M; Couvy-Duchesne, B; Rentería, M E; Strike, L T; Wright, M J; Mills, N T; de Zubicaray, G I; McMahon, K L; Medland, S E; Martin, N G; Gillespie, N A; Goya-Maldonado, R; Gruber, O; Krämer, B; Hatton, S N; Lagopoulos, J; Hickie, I B; Frodl, T; Carballedo, A; Frey, E M; van Velzen, L S; Penninx, B W J H; van Tol, M-J; van der Wee, N J; Davey, C G; Harrison, B J; Mwangi, B; Cao, B; Soares, J C; Veer, I M; Walter, H; Schoepf, D; Zurowski, B; Konrad, C; Schramm, E; Normann, C; Schnell, K; Sacchet, M D; Gotlib, I H; MacQueen, G M; Godlewska, B R; Nickson, T; McIntosh, A M; Papmeyer, M; Whalley, H C; Hall, J; Sussmann, J E; Li, M; Walter, M; Aftanas, L; Brack, I; Bokhan, N A; Thompson, P M; Veltman, D J

2017-06-01

The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen's d effect sizes: -0.10 to -0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: -0.26 to -0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life.

Vestibulo-cortical Hemispheric Dominance: the link between Anxiety and the Vestibular System?

PubMed

Bednarczuk, Nadja F; Casanovas Ortega, Marta; Fluri, Anne-Sophie; Arshad, Qadeer

2018-05-16

Vestibular processing and anxiety networks are functionally intertwined, as demonstrated by reports of reciprocal influences upon each other. Yet whether there is an underlying link between these two systems remains unknown Previous findings have highlighted the involvement of hemispheric lateralisation in processing of both anxiety and vestibular signals. Accordingly, we explored the interaction between vestibular cortical processing and anxiety by assessing the relationship between anxiety levels and the degree of hemispheric lateralisation of vestibulo-cortical processing in 64 right-handed, healthy individuals. Vestibulo-cortical hemispheric lateralisation was determined by gaging the degree of caloric-induced nystagmus suppression following modulation of cortical excitability using trans-cranial direct current stimulation targeted over the posterior parietal cortex, an area implicated in the processing of vestibular signals. The degree of nystagmus suppression yields an objective biomarker, allowing the quantification of the degree of right vestibulo-cortical hemisphere dominance. Anxiety levels were quantified using the Trait component of the Spielberger State-Trait Anxiety Questionnaire. Our findings demonstrate that the degree of an individual's vestibulo-cortical hemispheric dominance correlates with their anxiety levels. That is, those individuals with greater right hemispheric vestibulo-cortical dominance exhibited lower levels of anxiety. By extension, our results support the notion that hemispheric lateralisation determines an individual's emotional processing, thereby linking cortical circuits involved in processing anxiety and vestibular signals respectively. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Amygdala lesions do not compromise the cortical network for false-belief reasoning.

PubMed

Spunt, Robert P; Elison, Jed T; Dufour, Nicholas; Hurlemann, René; Saxe, Rebecca; Adolphs, Ralph

2015-04-14

The amygdala plays an integral role in human social cognition and behavior, with clear links to emotion recognition, trust judgments, anthropomorphization, and psychiatric disorders ranging from social phobia to autism. A central feature of human social cognition is a theory-of-mind (ToM) that enables the representation other people's mental states as distinct from one's own. Numerous neuroimaging studies of the best studied use of ToM--false-belief reasoning--suggest that it relies on a specific cortical network; moreover, the amygdala is structurally and functionally connected with many components of this cortical network. It remains unknown whether the cortical implementation of any form of ToM depends on amygdala function. Here we investigated this question directly by conducting functional MRI on two patients with rare bilateral amygdala lesions while they performed a neuroimaging protocol standardized for measuring cortical activity associated with false-belief reasoning. We compared patient responses with those of two healthy comparison groups that included 480 adults. Based on both univariate and multivariate comparisons, neither patient showed any evidence of atypical cortical activity or any evidence of atypical behavioral performance; moreover, this pattern of typical cortical and behavioral response was replicated for both patients in a follow-up session. These findings argue that the amygdala is not necessary for the cortical implementation of ToM in adulthood and suggest a reevaluation of the role of the amygdala and its cortical interactions in human social cognition.

Amygdala lesions do not compromise the cortical network for false-belief reasoning

PubMed Central

Elison, Jed T.; Dufour, Nicholas; Hurlemann, René; Saxe, Rebecca; Adolphs, Ralph

2015-01-01

The amygdala plays an integral role in human social cognition and behavior, with clear links to emotion recognition, trust judgments, anthropomorphization, and psychiatric disorders ranging from social phobia to autism. A central feature of human social cognition is a theory-of-mind (ToM) that enables the representation other people's mental states as distinct from one's own. Numerous neuroimaging studies of the best studied use of ToM—false-belief reasoning—suggest that it relies on a specific cortical network; moreover, the amygdala is structurally and functionally connected with many components of this cortical network. It remains unknown whether the cortical implementation of any form of ToM depends on amygdala function. Here we investigated this question directly by conducting functional MRI on two patients with rare bilateral amygdala lesions while they performed a neuroimaging protocol standardized for measuring cortical activity associated with false-belief reasoning. We compared patient responses with those of two healthy comparison groups that included 480 adults. Based on both univariate and multivariate comparisons, neither patient showed any evidence of atypical cortical activity or any evidence of atypical behavioral performance; moreover, this pattern of typical cortical and behavioral response was replicated for both patients in a follow-up session. These findings argue that the amygdala is not necessary for the cortical implementation of ToM in adulthood and suggest a reevaluation of the role of the amygdala and its cortical interactions in human social cognition. PMID:25825732

PSD-95 uncoupling from NMDA receptors by Tat- N-dimer ameliorates neuronal depolarization in cortical spreading depression.

PubMed

Kucharz, Krzysztof; Søndergaard Rasmussen, Ida; Bach, Anders; Strømgaard, Kristian; Lauritzen, Martin

2017-05-01

Cortical spreading depression is associated with activation of NMDA receptors, which interact with the postsynaptic density protein 95 (PSD-95) that binds to nitric oxide synthase (nNOS). Here, we tested whether inhibition of the nNOS/PSD-95/NMDA receptor complex formation by anti-ischemic compound, UCCB01-144 (Tat- N-dimer) ameliorates the persistent effects of cortical spreading depression on cortical function. Using in vivo two-photon microscopy in somatosensory cortex in mice, we show that fluorescently labelled Tat- N-dimer readily crosses blood-brain barrier and accumulates in nerve cells during the first hour after i.v. injection. The Tat- N-dimer suppressed stimulation-evoked synaptic activity by 2-20%, while cortical blood flow and cerebral oxygen metabolic (CMRO 2 ) responses were preserved. During cortical spreading depression, the Tat- N-dimer reduced the average amplitude of the negative shift in direct current potential by 33% (4.1 mV). Furthermore, the compound diminished the average depression of spontaneous electrocorticographic activity by 11% during first 40 min of post-cortical spreading depression recovery, but did not mitigate the suppressing effect of cortical spreading depression on cortical blood flow and CMRO 2 . We suggest that uncoupling of PSD-95 from NMDA receptors reduces overall neuronal excitability and the amplitude of the spreading depolarization wave. These findings may be of interest for understanding the neuroprotective effects of the nNOS/PSD-95 uncoupling in stroke.

Restoration of Central Programmed Movement Pattern by Temporal Electrical Stimulation-Assisted Training in Patients with Spinal Cerebellar Atrophy.

PubMed

Huang, Ying-Zu; Chang, Yao-Shun; Hsu, Miao-Ju; Wong, Alice M K; Chang, Ya-Ju

2015-01-01

Disrupted triphasic electromyography (EMG) patterns of agonist and antagonist muscle pairs during fast goal-directed movements have been found in patients with hypermetria. Since peripheral electrical stimulation (ES) and motor training may modulate motor cortical excitability through plasticity mechanisms, we aimed to investigate whether temporal ES-assisted movement training could influence premovement cortical excitability and alleviate hypermetria in patients with spinal cerebellar ataxia (SCA). The EMG of the agonist extensor carpi radialis muscle and antagonist flexor carpi radialis muscle, premovement motor evoked potentials (MEPs) of the flexor carpi radialis muscle, and the constant and variable errors of movements were assessed before and after 4 weeks of ES-assisted fast goal-directed wrist extension training in the training group and of general health education in the control group. After training, the premovement MEPs of the antagonist muscle were facilitated at 50 ms before the onset of movement. In addition, the EMG onset latency of the antagonist muscle shifted earlier and the constant error decreased significantly. In summary, temporal ES-assisted training alleviated hypermetria by restoring antagonist premovement and temporal triphasic EMG patterns in SCA patients. This technique may be applied to treat hypermetria in cerebellar disorders. (This trial is registered with NCT01983670.).

Nanoindentation analysis of the micromechanical anisotropy in mouse cortical bone

PubMed Central

Balmelli, Anna; Carnelli, Davide; Courty, Diana; Müller, Ralph

2017-01-01

Studies investigating micromechanical properties in mouse cortical bone often solely focus on the mechanical behaviour along the long axis of the bone. Therefore, data on the anisotropy of mouse cortical bone is scarce. The aim of this study is the first-time evaluation of the anisotropy ratio between the longitudinal and transverse directions of reduced modulus and hardness in mouse femurs by using the nanoindentation technique. For this purpose, nine 22-week-old mice (C57BL/6) were sacrificed and all femurs extracted. A total of 648 indentations were performed with a Berkovich tip in the proximal (P), central (C) and distal (D) regions of the femoral shaft in the longitudinal and transverse directions. Higher values for reduced modulus are obtained for indentations in the longitudinal direction, with anisotropy ratios of 1.72 ± 0.40 (P), 1.75 ± 0.69 (C) and 1.34 ± 0.30 (D). Hardness is also higher in the longitudinal direction, with anisotropic ratios of 1.35 ± 0.27 (P), 1.35 ± 0.47 (C) and 1.17 ± 0.19 (D). We observed a significant anisotropy in the micromechanical properties of the mouse femur, but the correlation for reduced modulus and hardness between the two directions is low (r2 < 0.3) and not significant. Therefore, we highly recommend performing independent indentation testing in both the longitudinal and transverse directions when knowledge of the tissue mechanical behaviour along multiple directions is required. PMID:28386450

Edentulation alters material properties of cortical bone in the human craniofacial skeleton: functional implications for craniofacial structure in primate evolution

PubMed Central

Dechow, Paul C.; Wang, Qian; Peterson, Jill

2011-01-01

Skeletal adaptations to reduced function are an important source of skeletal variation and may be indicative of environmental pressures that lead to evolutionary changes. Humans serve as a model animal to investigate the effects of loss of craniofacial function through edentulation. In the human maxilla, it is known that edentulation leads to significant changes in skeletal structure such as residual ridge resorption and loss of cortical thickness. However, little is known about changes in bone tissue structure and material properties, which are also important for understanding skeletal mechanics but are often ignored. The aims of this study were to determine cortical material properties in edentulous crania and to evaluate differences with dentate crania and thus examine the effects of loss of function on craniofacial structure. Cortical bone samples from fifteen edentulous human skulls were measured for thickness and density. Elastic properties and directions of maximum stiffness were determined by using ultrasonic techniques. These data were compared to those from dentate crania reported in a previous investigation. Cortical bone from all regions of the facial skeleton of edentulous individuals is thinner than in dentate skulls. Elastic and shear moduli, and density are similar or greater in the zygoma and cranial vault of edentulous individuals, while these properties are less in the maxilla. Most cortical bone, especially in edentulous maxillae, has reduced directional orientation. The loss of significant occlusal loads following edentulation may contribute to the change in material properties and the loss of orientation over time during the normal process of bone remodeling. These results suggest that area-specific cortical microstructural changes accompany bone resorption following edentulation. They also suggest that functional forces are important for maintaining bone mass throughout the craniofacial skeleton, even in areas such as the browridges, which have been thought to be little affected by function, because of low in vivo strains found there in several primate studies. PMID:20235319

Tracking the time-varying cortical connectivity patterns by adaptive multivariate estimators.

PubMed

Astolfi, L; Cincotti, F; Mattia, D; De Vico Fallani, F; Tocci, A; Colosimo, A; Salinari, S; Marciani, M G; Hesse, W; Witte, H; Ursino, M; Zavaglia, M; Babiloni, F

2008-03-01

The directed transfer function (DTF) and the partial directed coherence (PDC) are frequency-domain estimators that are able to describe interactions between cortical areas in terms of the concept of Granger causality. However, the classical estimation of these methods is based on the multivariate autoregressive modelling (MVAR) of time series, which requires the stationarity of the signals. In this way, transient pathways of information transfer remains hidden. The objective of this study is to test a time-varying multivariate method for the estimation of rapidly changing connectivity relationships between cortical areas of the human brain, based on DTF/PDC and on the use of adaptive MVAR modelling (AMVAR) and to apply it to a set of real high resolution EEG data. This approach will allow the observation of rapidly changing influences between the cortical areas during the execution of a task. The simulation results indicated that time-varying DTF and PDC are able to estimate correctly the imposed connectivity patterns under reasonable operative conditions of signal-to-noise ratio (SNR) ad number of trials. An SNR of five and a number of trials of at least 20 provide a good accuracy in the estimation. After testing the method by the simulation study, we provide an application to the cortical estimations obtained from high resolution EEG data recorded from a group of healthy subject during a combined foot-lips movement and present the time-varying connectivity patterns resulting from the application of both DTF and PDC. Two different cortical networks were detected with the proposed methods, one constant across the task and the other evolving during the preparation of the joint movement.

EEG neural correlates of goal-directed movement intention.

PubMed

Pereira, Joana; Ofner, Patrick; Schwarz, Andreas; Sburlea, Andreea Ioana; Müller-Putz, Gernot R

2017-04-01

Using low-frequency time-domain electroencephalographic (EEG) signals we show, for the same type of upper limb movement, that goal-directed movements have different neural correlates than movements without a particular goal. In a reach-and-touch task, we explored the differences in the movement-related cortical potentials (MRCPs) between goal-directed and non-goal-directed movements. We evaluated if the detection of movement intention was influenced by the goal-directedness of the movement. In a single-trial classification procedure we found that classification accuracies are enhanced if there is a goal-directed movement in mind. Furthermore, by using the classifier patterns and estimating the corresponding brain sources, we show the importance of motor areas and the additional involvement of the posterior parietal lobule in the discrimination between goal-directed movements and non-goal-directed movements. We discuss next the potential contribution of our results on goal-directed movements to a more reliable brain-computer interface (BCI) control that facilitates recovery in spinal-cord injured or stroke end-users. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Broca’s Area as a Pre-articulatory Phonetic Encoder: Gating the Motor Program

PubMed Central

Ferpozzi, Valentina; Fornia, Luca; Montagna, Marcella; Siodambro, Chiara; Castellano, Antonella; Borroni, Paola; Riva, Marco; Rossi, Marco; Pessina, Federico; Bello, Lorenzo; Cerri, Gabriella

2018-01-01

The exact nature of the role of Broca’s area in control of speech and whether it is exerted at the cognitive or at the motor level is still debated. Intraoperative evidence of a lack of motor responses to direct electrical stimulation (DES) of Broca’s area and the observation that its stimulation induces a “speech arrest” without an apparent effect on the ongoing activity of phono-articulatory muscles, raises the argument. Essentially, attribution of direct involvement of Broca’s area in motor control of speech, requires evidence of a functional connection of this area with the phono-articulatory muscles’ motoneurons. With a quantitative approach we investigated, in 20 patients undergoing surgery for brain tumors, whether DES delivered on Broca’s area affects the recruitment of the phono-articulatory muscles’ motor units. The electromyography (EMG) of the muscles active during two speech tasks (object picture naming and counting) was recorded during and in absence of DES on Broca’s area. Offline, the EMG of each muscle was analyzed in frequency (power spectrum, PS) and time domain (root mean square, RMS) and the two conditions compared. Results show that DES on Broca’s area induces an intensity-dependent “speech arrest.” The intensity of DES needed to induce “speech arrest” when applied on Broca’s area was higher when compared to the intensity effective on the neighboring pre-motor/motor cortices. Notably, PS and RMS measured on the EMG recorded during “speech arrest” were superimposable to those recorded at baseline. Partial interruptions of speech were not observed. Speech arrest was an “all-or-none” effect: muscle activation started only by removing DES, as if DES prevented speech onset. The same effect was observed when stimulating directly the subcortical fibers running below Broca’s area. Intraoperative data point to Broca’s area as a functional gate authorizing the phonetic translation to be executed by the motor areas. Given the absence of a direct effect on motor units recruitment, a direct control of Broca’s area on the phono-articulatory apparatus seems unlikely. Moreover, the strict correlation between DES-intensity and speech prevention, might attribute this effect to the inactivation of the subcortical fibers rather than to Broca’s cortical neurons. PMID:29520225

Disease-specific molecular events in cortical multiple sclerosis lesions

PubMed Central

Wimmer, Isabella; Höftberger, Romana; Gerlach, Susanna; Haider, Lukas; Zrzavy, Tobias; Hametner, Simon; Mahad, Don; Binder, Christoph J.; Krumbholz, Markus; Bauer, Jan; Bradl, Monika

2013-01-01

Cortical lesions constitute an important part of multiple sclerosis pathology. Although inflammation appears to play a role in their formation, the mechanisms leading to demyelination and neurodegeneration are poorly understood. We aimed to identify some of these mechanisms by combining gene expression studies with neuropathological analysis. In our study, we showed that the combination of inflammation, plaque-like primary demyelination and neurodegeneration in the cortex is specific for multiple sclerosis and is not seen in other chronic inflammatory diseases mediated by CD8-positive T cells (Rasmussen’s encephalitis), B cells (B cell lymphoma) or complex chronic inflammation (tuberculous meningitis, luetic meningitis or chronic purulent meningitis). In addition, we performed genome-wide microarray analysis comparing micro-dissected active cortical multiple sclerosis lesions with those of tuberculous meningitis (inflammatory control), Alzheimer’s disease (neurodegenerative control) and with cortices of age-matched controls. More than 80% of the identified multiple sclerosis-specific genes were related to T cell-mediated inflammation, microglia activation, oxidative injury, DNA damage and repair, remyelination and regenerative processes. Finally, we confirmed by immunohistochemistry that oxidative damage in cortical multiple sclerosis lesions is associated with oligodendrocyte and neuronal injury, the latter also affecting axons and dendrites. Our study provides new insights into the complex mechanisms of neurodegeneration and regeneration in the cortex of patients with multiple sclerosis. PMID:23687122

Neural basis for brain responses to TV commercials: a high-resolution EEG study.

PubMed

Astolfi, Laura; De Vico Fallani, F; Cincotti, F; Mattia, D; Bianchi, L; Marciani, M G; Salinari, S; Colosimo, A; Tocci, A; Soranzo, R; Babiloni, F

2008-12-01

We investigated brain activity during the observation of TV commercials by tracking the cortical activity and the functional connectivity changes in normal subjects. The aim was to elucidate if the TV commercials that were remembered by the subjects several days after their first observation elicited particular brain activity and connectivity compared with those generated during the observation of TV commercials that were quickly forgotten. High-resolution electroencephalogram (EEG) recordings were performed in a group of healthy subjects and the cortical activity during the observation of TV commercials was evaluated in several regions of interest coincident with the Brodmann areas (BAs). The patterns of cortical connectivity were obtained in the four principal frequency bands, Theta (3-7 Hz), Alpha (8-12 Hz), Beta (13-30 Hz), Gamma (30-40 Hz) and the directed influences between any given pair of the estimated cortical signals were evaluated by use of a multivariate spectral technique known as partial directed coherence. The topology of the cortical networks has been identified with tools derived from graph theory. Results suggest that the cortical activity and connectivity elicited by the viewing of the TV commercials that were remembered by the experimental subjects are markedly different from the brain activity elicited during the observation of the TV commercials that were forgotten. In particular, during the observation of the TV commercials that were remembered, the amount of cortical spectral activity from the frontal areas (BA 8 and 9) and from the parietal areas (BA 5, 7, and 40) is higher compared with the activity elicited by the observation of TV commercials that were forgotten. In addition, network analysis suggests a clear role of the parietal areas as a target of the incoming flow of information from all the other parts of the cortex during the observation of TV commercials that have been remembered. The techniques presented here shed new light on all the cortical networks and their behavior during the memorization of TV commercials. Such techniques could also be relevant in neuroeconomics and neuromarketing for the investigation of the neural substrates subserving other decision-making and recognition tasks.

Evidence for Neuroplastic Compensation in the Cerebral Cortex of Persons with Depressive Illness

PubMed Central

Bansal, Ravi; Hellerstein, David J.; Peterson, Bradley S.

2017-01-01

We yoked anatomical brain Magnetic Resonance Imaging to a randomized, double-blind, placebo-controlled trial (RCT) of antidepressant medication for 10-week’s duration in patients with dysthymia. The RCT study design mitigated ascertainment bias by randomizing patients to receive either duloxetine or placebo, and it supported true causal inferences about treatment effects on the brain by controlling treatment assignment experimentally. We acquired 121 anatomical scans: at baseline and endpoint in 41 patients, and once in 39 healthy controls. At baseline, patients had diffusely thicker cortices than did healthy participants, and patients who had thicker cortices had proportionately less severe symptoms. During the trial, symptoms improved significantly more in medication- compared with placebo-treated patients; concurrently, thicknesses in medication-treated patients declined toward values in healthy controls, but they increased slightly, away from control values, in placebo-treated patients. Changes in symptom severity during the trial mediated the association of treatment assignment with the change in thickness, suggesting that the beneficial effects of medication on symptom severity were at least partially responsible for normalizing cortical thickness. Together our findings suggest that baseline cortical hypertrophy in medication-free patients likely represented a compensatory, neuroplastic response that attenuated symptom severity. Medication then reduced symptoms and lessened the need for compensation, thereby normalizing thickness. This is to the best of our knowledge the first study to report within an RCT a differential change in cortical morphology during medication treatment for depressive illness and the first to provide within an RCT in vivo evidence for the presence of neuroanatomical plasticity in humans. PMID:28265119

Alzheimer's disease: a correlative study.

PubMed Central

Neary, D; Snowden, J S; Mann, D M; Bowen, D M; Sims, N R; Northen, B; Yates, P O; Davison, A N

1986-01-01

In a study of 17 patients with histologically proven Alzheimer's disease the relationship between psychological, pathological and chemical measures of disorder was examined. Severity of dementia, determined by mental test performance, correlated highly with pathological change in large cortical neurons (cell loss and reduction in nuclear and nucleolar volume and cytoplasmic RNA content), to a lesser extent with cortical senile plaque and neurofibrillary tangle frequency and reduction in acetylcholine (ACh) synthesis, and not with reduction in choline acetyltransferase (CAT) activity. A strongly significant relationship was demonstrated between cell loss and reductions in nuclear and nucleolar volume and cytoplasmic RNA content. Reduction in CAT activity and senile plaque frequency were significantly correlated, thereby linking changes in the sub-cortical projection system of the nucleus basalis with the cortical pathology. The pattern of correlations suggests that the dementia of Alzheimer's disease is largely a reflection of the state of large cortical neurons, and it is argued that abnormalities in the latter may not be directly related to primary loss of cholinergic neurons in the subcortex. PMID:2420941

Intra-Subject Consistency and Reliability of Response Following 2 mA Transcranial Direct Current Stimulation.

PubMed

Dyke, Katherine; Kim, Soyoung; Jackson, Georgina M; Jackson, Stephen R

Transcranial direct current stimulation (tDCS) is a popular non-invasive brain stimulation technique that has been shown to influence cortical excitability. While polarity specific effects have often been reported, this is not always the case, and variability in both the magnitude and direction of the effects have been observed. We aimed to explore the consistency and reliability of the effects of tDCS by investigating changes in cortical excitability across multiple testing sessions in the same individuals. A within subjects design was used to investigate the effects of anodal and cathodal tDCS applied to the motor cortex. Four experimental sessions were tested for each polarity in addition to two sham sessions. Transcranial magnetic stimulation (TMS) was used to measure cortical excitability (TMS recruitment curves). Changes in excitability were measured by comparing baseline measures and those taken immediately following 20 minutes of 2 mA stimulation or sham stimulation. Anodal tDCS significantly increased cortical excitability at a group level, whereas cathodal tDCS failed to have any significant effects. The sham condition also failed to show any significant changes. Analysis of intra-subject responses to anodal stimulation across four sessions suggest that the amount of change in excitability across sessions was only weakly associated, and was found to have poor reliability across sessions (ICC = 0.276). The effects of cathodal stimulation show even poorer reliability across sessions (ICC = 0.137). In contrast ICC analysis for the two sessions of sham stimulation reflect a moderate level of reliability (ICC = .424). Our findings indicate that although 2 mA anodal tDCS is effective at increasing cortical excitability at group level, the effects are unreliable across repeated testing sessions within individual participants. Our results suggest that 2 mA cathodal tDCS does not significantly alter cortical excitability immediately following stimulation and that there is poor reliability of the effect within the same individual across different testing sessions. Copyright © 2016. Published by Elsevier Inc.

Regional Neuroplastic Brain Changes in Patients with Chronic Inflammatory and Non-Inflammatory Visceral Pain

PubMed Central

Hong, Jui-Yang; Labus, Jennifer S.; Jiang, Zhiguo; Ashe-Mcnalley, Cody; Dinov, Ivo; Gupta, Arpana; Shi, Yonggang; Stains, Jean; Heendeniya, Nuwanthi; Smith, Suzanne R.; Tillisch, Kirsten; Mayer, Emeran A.

2014-01-01

Regional cortical thickness alterations have been reported in many chronic inflammatory and painful conditions, including inflammatory bowel diseases (IBD) and irritable bowel syndrome (IBS), even though the mechanisms underlying such neuroplastic changes remain poorly understood. In order to better understand the mechanisms contributing to grey matter changes, the current study sought to identify the differences in regional alterations in cortical thickness between healthy controls and two chronic visceral pain syndromes, with and without chronic gut inflammation. 41 healthy controls, 11 IBS subjects with diarrhea, and 16 subjects with ulcerative colitis (UC) underwent high-resolution T1-weighted magnetization-prepared rapid acquisition gradient echo scans. Structural image preprocessing and cortical thickness analysis within the region of interests were performed by using the Laboratory of Neuroimaging Pipeline. Group differences were determined using the general linear model and linear contrast analysis. The two disease groups differed significantly in several cortical regions. UC subjects showed greater cortical thickness in anterior cingulate cortical subregions, and in primary somatosensory cortex compared with both IBS and healthy subjects. Compared with healthy subjects, UC subjects showed lower cortical thickness in orbitofrontal cortex and in mid and posterior insula, while IBS subjects showed lower cortical thickness in the anterior insula. Large effects of correlations between symptom duration and thickness in the orbitofrontal cortex and postcentral gyrus were only observed in UC subjects. The findings suggest that the mechanisms underlying the observed gray matter changes in UC subjects represent a consequence of peripheral inflammation, while in IBS subjects central mechanisms may play a primary role. PMID:24416245

Longitudinal course of cortical thickness decline in amyotrophic lateral sclerosis.

PubMed

Schuster, Christina; Kasper, Elisabeth; Machts, Judith; Bittner, Daniel; Kaufmann, Jörn; Benecke, Reiner; Teipel, Stefan; Vielhaber, Stefan; Prudlo, Johannes

2014-10-01

To determine longitudinal rates of cortical atrophy in classical Amyotrophic lateral sclerosis (ALS) and ALS variants. Rates of cortical thinning were determined between 2 scans, 3-15 months apart, in 77 ALS patients: 51 classical, 12 upper motor neuron (UMN), and 14 lower motor neuron (LMN) ALS variants. Cortical thickness at the first assessment was compared with 60 healthy controls matched by age and gender. Atrophy rates were compared between patient sub-groups and correlated with disease duration, progression, and severity. Using a cross-sectional analysis, we found a significant difference in cortical thickness between ALS patients and controls in the motor and extra-motor areas (left medial orbito frontal gyrus, left inferior parietal gyrus, bilateral insular cortex, right fusiform gyrus, bilateral precuneus). Using a longitudinal analysis, we found a significant decline of cortical thickness in frontal, temporal, and parietal regions over the course of the study in ALS patients. Effects were independent of the clinical subtype, with exception of the precentral gyrus (p < 0.001). The LMN ALS variants demonstrated the highest rates of cortical thinning in the precentral gyrus, the UMN-dominant subjects exhibited intermediate rates of atrophy, and the classical ALS patients exhibited no such change. Atrophy of the precentral gyrus in classical ALS indicates a floor effect at the first assessment, resulting in a lack of further atrophy over time. Structural loss of the precentral gyrus appears to be an early sign of classical ALS. Over time, patterns of cortical thinning in extra-motor areas can be identified in ALS, regardless of the phenotype.

Spatio-Temporal Progression of Cortical Activity Related to Continuous Overt and Covert Speech Production in a Reading Task.

PubMed

Brumberg, Jonathan S; Krusienski, Dean J; Chakrabarti, Shreya; Gunduz, Aysegul; Brunner, Peter; Ritaccio, Anthony L; Schalk, Gerwin

2016-01-01

How the human brain plans, executes, and monitors continuous and fluent speech has remained largely elusive. For example, previous research has defined the cortical locations most important for different aspects of speech function, but has not yet yielded a definition of the temporal progression of involvement of those locations as speech progresses either overtly or covertly. In this paper, we uncovered the spatio-temporal evolution of neuronal population-level activity related to continuous overt speech, and identified those locations that shared activity characteristics across overt and covert speech. Specifically, we asked subjects to repeat continuous sentences aloud or silently while we recorded electrical signals directly from the surface of the brain (electrocorticography (ECoG)). We then determined the relationship between cortical activity and speech output across different areas of cortex and at sub-second timescales. The results highlight a spatio-temporal progression of cortical involvement in the continuous speech process that initiates utterances in frontal-motor areas and ends with the monitoring of auditory feedback in superior temporal gyrus. Direct comparison of cortical activity related to overt versus covert conditions revealed a common network of brain regions involved in speech that may implement orthographic and phonological processing. Our results provide one of the first characterizations of the spatiotemporal electrophysiological representations of the continuous speech process, and also highlight the common neural substrate of overt and covert speech. These results thereby contribute to a refined understanding of speech functions in the human brain.

Properties of slow oscillation during slow-wave sleep and anesthesia in cats.

PubMed

Chauvette, Sylvain; Crochet, Sylvain; Volgushev, Maxim; Timofeev, Igor

2011-10-19

Deep anesthesia is commonly used as a model of slow-wave sleep (SWS). Ketamine-xylazine anesthesia reproduces the main features of sleep slow oscillation: slow, large-amplitude waves in field potential, which are generated by the alternation of hyperpolarized and depolarized states of cortical neurons. However, direct quantitative comparison of field potential and membrane potential fluctuations during natural sleep and anesthesia is lacking, so it remains unclear how well the properties of sleep slow oscillation are reproduced by the ketamine-xylazine anesthesia model. Here, we used field potential and intracellular recordings in different cortical areas in the cat to directly compare properties of slow oscillation during natural sleep and ketamine-xylazine anesthesia. During SWS cortical activity showed higher power in the slow/delta (0.1-4 Hz) and spindle (8-14 Hz) frequency range, whereas under anesthesia the power in the gamma band (30-100 Hz) was higher. During anesthesia, slow waves were more rhythmic and more synchronous across the cortex. Intracellular recordings revealed that silent states were longer and the amplitude of membrane potential around transition between active and silent states was bigger under anesthesia. Slow waves were mostly uniform across cortical areas under anesthesia, but in SWS, they were most pronounced in associative and visual areas but smaller and less regular in somatosensory and motor cortices. We conclude that, although the main features of the slow oscillation in sleep and anesthesia appear similar, multiple cellular and network features are differently expressed during natural SWS compared with ketamine-xylazine anesthesia.

Rapid Long-Range Disynaptic Inhibition Explains the Formation of Cortical Orientation Maps

PubMed Central

Antolík, Ján

2017-01-01

Competitive interactions are believed to underlie many types of cortical processing, ranging from memory formation, attention and development of cortical functional organization (e.g., development of orientation maps in primary visual cortex). In the latter case, the competitive interactions happen along the cortical surface, with local populations of neurons reinforcing each other, while competing with those displaced more distally. This specific configuration of lateral interactions is however in stark contrast with the known properties of the anatomical substrate, i.e., excitatory connections (mediating reinforcement) having longer reach than inhibitory ones (mediating competition). No satisfactory biologically plausible resolution of this conflict between anatomical measures, and assumed cortical function has been proposed. Recently a specific pattern of delays between different types of neurons in cat cortex has been discovered, where direct mono-synaptic excitation has approximately the same delay, as the combined delays of the disynaptic inhibitory interactions between excitatory neurons (i.e., the sum of delays from excitatory to inhibitory and from inhibitory to excitatory neurons). Here we show that this specific pattern of delays represents a biologically plausible explanation for how short-range inhibition can support competitive interactions that underlie the development of orientation maps in primary visual cortex. We demonstrate this statement analytically under simplifying conditions, and subsequently show using network simulations that development of orientation maps is preserved when long-range excitation, direct inhibitory to inhibitory interactions, and moderate inequality in the delays between excitatory and inhibitory pathways is added. PMID:28408869

Spatio-Temporal Progression of Cortical Activity Related to Continuous Overt and Covert Speech Production in a Reading Task

PubMed Central

Brumberg, Jonathan S.; Krusienski, Dean J.; Chakrabarti, Shreya; Gunduz, Aysegul; Brunner, Peter; Ritaccio, Anthony L.; Schalk, Gerwin

2016-01-01

How the human brain plans, executes, and monitors continuous and fluent speech has remained largely elusive. For example, previous research has defined the cortical locations most important for different aspects of speech function, but has not yet yielded a definition of the temporal progression of involvement of those locations as speech progresses either overtly or covertly. In this paper, we uncovered the spatio-temporal evolution of neuronal population-level activity related to continuous overt speech, and identified those locations that shared activity characteristics across overt and covert speech. Specifically, we asked subjects to repeat continuous sentences aloud or silently while we recorded electrical signals directly from the surface of the brain (electrocorticography (ECoG)). We then determined the relationship between cortical activity and speech output across different areas of cortex and at sub-second timescales. The results highlight a spatio-temporal progression of cortical involvement in the continuous speech process that initiates utterances in frontal-motor areas and ends with the monitoring of auditory feedback in superior temporal gyrus. Direct comparison of cortical activity related to overt versus covert conditions revealed a common network of brain regions involved in speech that may implement orthographic and phonological processing. Our results provide one of the first characterizations of the spatiotemporal electrophysiological representations of the continuous speech process, and also highlight the common neural substrate of overt and covert speech. These results thereby contribute to a refined understanding of speech functions in the human brain. PMID:27875590

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

PubMed

Kubis, Nathalie

2016-01-01

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

Investigation into mechanical properties of bone and its main constituents

NASA Astrophysics Data System (ADS)

Evdokimenko, Ekaterina

Bone is a hierarchically structured natural composite material, consisting of organic phase (type-I collagen), inorganic phase (hydroxyapatite), and water. Studies of the two main bone constituents, utilizing controlled demineralization and deproteinization, can shed light on mineral-collagen interaction which makes bone such a unique biological material. This knowledge is necessary for computational analysis of bone structure to identify preferential sites in the collagen matrix and mineral network that degrade more easily. The main goal of this work is to develop a comprehensive picture of mechanical properties of bone and its main constituents. Following the Introduction, Chapter 2 presents an investigation of microstructure and compressive mechanical properties of bovine femur cortical bone carried out on completely demineralized, completely deproteinized, and untreated bone samples in three anatomical directions. Anisotropic nature of bone was clearly identified in all cases. Extra levels of porosity along with microstructural differences for the three directions were found to be the main sources of the anisotropy. In Chapter 3, a new theoretical model of cortical and trabecular bone as composite materials with hierarchical structure spanning from nanometer (collagen-mineral) level to millimeter (bone) level was developed. Compression testing was performed on untreated, demineralized, and deproteinized cortical and trabecular bovine femur bone samples to verify the model. The experimental data were compared with theoretical predictions; excellent agreement was found between the theory and experiments for all bone phases. Optical microscopy, scanning electron microscopy, and micro-computed tomography techniques were applied to characterize the structure of the samples at multiple length scales and provide further inputs for the modeling. Chapter 4 presents a comparative study of mechanical properties, microstructure, and porosity of mature and young bovine femur cortical bone. It was found that the amount of porosity decreases, while the microhardness increases with maturation. Osteoporotic degradation of trabecular bone elasticity, described in Chapter 5, was modeled using a cellular mechanics approach. Evolution equations for elastic modulus of bone in terms of those of mineral and protein trabeculae and in terms of demineralized and deproteinized bones were formulated and verified by the analysis of compressive properties of bovine femur trabecular bone.

Non-Invasive Brain Stimulation to Enhance Post-Stroke Recovery

PubMed Central

Kubis, Nathalie

2016-01-01

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

Transient synchronization of hippocampo-striato-thalamo-cortical networks during sleep spindle oscillations induces motor memory consolidation.

PubMed

Boutin, Arnaud; Pinsard, Basile; Boré, Arnaud; Carrier, Julie; Fogel, Stuart M; Doyon, Julien

2018-04-01

Sleep benefits motor memory consolidation. This mnemonic process is thought to be mediated by thalamo-cortical spindle activity during NREM-stage2 sleep episodes as well as changes in striatal and hippocampal activity. However, direct experimental evidence supporting the contribution of such sleep-dependent physiological mechanisms to motor memory consolidation in humans is lacking. In the present study, we combined EEG and fMRI sleep recordings following practice of a motor sequence learning (MSL) task to determine whether spindle oscillations support sleep-dependent motor memory consolidation by transiently synchronizing and coordinating specialized cortical and subcortical networks. To that end, we conducted EEG source reconstruction on spindle epochs in both cortical and subcortical regions using novel deep-source localization techniques. Coherence-based metrics were adopted to estimate functional connectivity between cortical and subcortical structures over specific frequency bands. Our findings not only confirm the critical and functional role of NREM-stage2 sleep spindles in motor skill consolidation, but provide first-time evidence that spindle oscillations [11-17 Hz] may be involved in sleep-dependent motor memory consolidation by locally reactivating and functionally binding specific task-relevant cortical and subcortical regions within networks including the hippocampus, putamen, thalamus and motor-related cortical regions. Copyright © 2018 Elsevier Inc. All rights reserved.

Perspectives on How Human Simultaneous Multi-Modal Imaging Adds Directionality to Spread Models of Alzheimer’s Disease

PubMed Central

Neitzel, Julia; Nuttall, Rachel; Sorg, Christian

2018-01-01

Previous animal research suggests that the spread of pathological agents in Alzheimer’s disease (AD) follows the direction of signaling pathways. Specifically, tau pathology has been suggested to propagate in an infection-like mode along axons, from transentorhinal cortices to medial temporal lobe cortices and consequently to other cortical regions, while amyloid-beta (Aβ) pathology seems to spread in an activity-dependent manner among and from isocortical regions into limbic and then subcortical regions. These directed connectivity-based spread models, however, have not been tested directly in AD patients due to the lack of an in vivo method to identify directed connectivity in humans. Recently, a new method—metabolic connectivity mapping (MCM)—has been developed and validated in healthy participants that uses simultaneous FDG-PET and resting-state fMRI data acquisition to identify directed intrinsic effective connectivity (EC). To this end, postsynaptic energy consumption (FDG-PET) is used to identify regions with afferent input from other functionally connected brain regions (resting-state fMRI). Here, we discuss how this multi-modal imaging approach allows quantitative, whole-brain mapping of signaling direction in AD patients, thereby pointing out some of the advantages it offers compared to other EC methods (i.e., Granger causality, dynamic causal modeling, Bayesian networks). Most importantly, MCM provides the basis on which models of pathology spread, derived from animal studies, can be tested in AD patients. In particular, future work should investigate whether tau and Aβ in humans propagate along the trajectories of directed connectivity in order to advance our understanding of the neuropathological mechanisms causing disease progression. PMID:29434570

Interhemispheric Effective and Functional Cortical Connectivity Signatures of Spina Bifida Are Consistent with Callosal Anomaly

PubMed Central

Malekpour, Sheida; Li, Zhimin; Cheung, Bing Leung Patrick; Castillo, Eduardo M.; Papanicolaou, Andrew C.; Kramer, Larry A.; Fletcher, Jack M.

2012-01-01

Abstract The impact of the posterior callosal anomalies associated with spina bifida on interhemispheric cortical connectivity is studied using a method for estimating cortical multivariable autoregressive models from scalp magnetoencephalography data. Interhemispheric effective and functional connectivity, measured using conditional Granger causality and coherence, respectively, is determined for the anterior and posterior cortical regions in a population of five spina bifida and five control subjects during a resting eyes-closed state. The estimated connectivity is shown to be consistent over the randomly selected subsets of the data for each subject. The posterior interhemispheric effective and functional connectivity and cortical power are significantly lower in the spina bifida group, a result that is consistent with posterior callosal anomalies. The anterior interhemispheric effective and functional connectivity are elevated in the spina bifida group, a result that may reflect compensatory mechanisms. In contrast, the intrahemispheric effective connectivity is comparable in the two groups. The differences between the spina bifida and control groups are most significant in the θ and α bands. PMID:22571349

Cortical and subcortical mechanisms of brain-machine interfaces.

PubMed

Marchesotti, Silvia; Martuzzi, Roberto; Schurger, Aaron; Blefari, Maria Laura; Del Millán, José R; Bleuler, Hannes; Blanke, Olaf

2017-06-01

Technical advances in the field of Brain-Machine Interfaces (BMIs) enable users to control a variety of external devices such as robotic arms, wheelchairs, virtual entities and communication systems through the decoding of brain signals in real time. Most BMI systems sample activity from restricted brain regions, typically the motor and premotor cortex, with limited spatial resolution. Despite the growing number of applications, the cortical and subcortical systems involved in BMI control are currently unknown at the whole-brain level. Here, we provide a comprehensive and detailed report of the areas active during on-line BMI control. We recorded functional magnetic resonance imaging (fMRI) data while participants controlled an EEG-based BMI inside the scanner. We identified the regions activated during BMI control and how they overlap with those involved in motor imagery (without any BMI control). In addition, we investigated which regions reflect the subjective sense of controlling a BMI, the sense of agency for BMI-actions. Our data revealed an extended cortical-subcortical network involved in operating a motor-imagery BMI. This includes not only sensorimotor regions but also the posterior parietal cortex, the insula and the lateral occipital cortex. Interestingly, the basal ganglia and the anterior cingulate cortex were involved in the subjective sense of controlling the BMI. These results inform basic neuroscience by showing that the mechanisms of BMI control extend beyond sensorimotor cortices. This knowledge may be useful for the development of BMIs that offer a more natural and embodied feeling of control for the user. Hum Brain Mapp 38:2971-2989, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

A Causal Role for the Cortical Frontal Eye Fields in Microsaccade Deployment

PubMed Central

Dash, Suryadeep; Lomber, Stephen G.

2016-01-01

Microsaccades aid vision by helping to strategically sample visual scenes. Despite the importance of these small eye movements, no cortical area has ever been implicated in their generation. Here, we used unilateral and bilateral reversible inactivation of the frontal eye fields (FEF) to identify a cortical drive for microsaccades. Unexpectedly, FEF inactivation altered microsaccade metrics and kinematics. Such inactivation also impaired microsaccade deployment following peripheral cue onset, regardless of cue side or inactivation configuration. Our results demonstrate that the FEF provides critical top-down drive for microsaccade generation, particularly during the recovery of microsaccades after disruption by sensory transients. Our results constitute the first direct evidence, to our knowledge, for the contribution of any cortical area to microsaccade generation, and they provide a possible substrate for how cognitive processes can influence the strategic deployment of microsaccades. PMID:27509130

A Causal Role for the Cortical Frontal Eye Fields in Microsaccade Deployment.

PubMed

Peel, Tyler R; Hafed, Ziad M; Dash, Suryadeep; Lomber, Stephen G; Corneil, Brian D

2016-08-01

Microsaccades aid vision by helping to strategically sample visual scenes. Despite the importance of these small eye movements, no cortical area has ever been implicated in their generation. Here, we used unilateral and bilateral reversible inactivation of the frontal eye fields (FEF) to identify a cortical drive for microsaccades. Unexpectedly, FEF inactivation altered microsaccade metrics and kinematics. Such inactivation also impaired microsaccade deployment following peripheral cue onset, regardless of cue side or inactivation configuration. Our results demonstrate that the FEF provides critical top-down drive for microsaccade generation, particularly during the recovery of microsaccades after disruption by sensory transients. Our results constitute the first direct evidence, to our knowledge, for the contribution of any cortical area to microsaccade generation, and they provide a possible substrate for how cognitive processes can influence the strategic deployment of microsaccades.

Bipolar disorder type I and II show distinct relationships between cortical thickness and executive function.

PubMed

Abé, C; Rolstad, S; Petrovic, P; Ekman, C-J; Sparding, T; Ingvar, M; Landén, M

2018-06-15

Frontal cortical abnormalities and executive function impairment co-occur in bipolar disorder. Recent studies have shown that bipolar subtypes differ in the degree of structural and functional impairments. The relationships between cognitive performance and cortical integrity have not been clarified and might differ across patients with bipolar disorder type I, II, and healthy subjects. Using a vertex-wise whole-brain analysis, we investigated how cortical integrity, as measured by cortical thickness, correlates with executive performance in patients with bipolar disorder type I, II, and controls (N = 160). We found focal associations between executive function and cortical thickness in the medial prefrontal cortex in bipolar II patients and controls, but not in bipolar I disorder. In bipolar II patients, we observed additional correlations in lateral prefrontal and occipital regions. Our findings suggest that bipolar disorder patients show altered structure-function relationships, and importantly that those relationships may differ between bipolar subtypes. The findings are line with studies suggesting subtype-specific neurobiological and cognitive profiles. This study contributes to a better understanding of brain structure-function relationships in bipolar disorder and gives important insights into the neuropathophysiology of diagnostic subtypes. © 2018 The Authors Acta Psychiatrica Scandinavica Published by John Wiley & Sons Ltd.

Altered white matter and cortical structure in neonates with antenatally diagnosed isolated ventriculomegaly.

PubMed

Lockwood Estrin, G; Kyriakopoulou, V; Makropoulos, A; Ball, G; Kuhendran, L; Chew, A; Hagberg, B; Martinez-Biarge, M; Allsop, J; Fox, M; Counsell, S J; Rutherford, M A

2016-01-01

Ventriculomegaly (VM) is the most common central nervous system abnormality diagnosed antenatally, and is associated with developmental delay in childhood. We tested the hypothesis that antenatally diagnosed isolated VM represents a biological marker for altered white matter (WM) and cortical grey matter (GM) development in neonates. 25 controls and 21 neonates with antenatally diagnosed isolated VM had magnetic resonance imaging at 41.97(± 2.94) and 45.34(± 2.14) weeks respectively. T2-weighted scans were segmented for volumetric analyses of the lateral ventricles, WM and cortical GM. Diffusion tensor imaging (DTI) measures were assessed using voxel-wise methods in WM and cortical GM; comparisons were made between cohorts. Ventricular and cortical GM volumes were increased, and WM relative volume was reduced in the VM group. Regional decreases in fractional anisotropy (FA) and increases in mean diffusivity (MD) were demonstrated in WM of the VM group compared to controls. No differences in cortical DTI metrics were observed. At 2 years, neurodevelopmental delays, especially in language, were observed in 6/12 cases in the VM cohort. WM alterations in isolated VM cases may be consistent with abnormal development of WM tracts involved in language and cognition. Alterations in WM FA and MD may represent neural correlates for later neurodevelopmental deficits.

Mandibular Inferior Cortical Bone Thickness on Panoramic Radiographs in Patients using Bisphosphonates

PubMed Central

Torres, Sandra R.; Chen, Curtis S. K.; Leroux, Brian G.; Lee, Peggy P.; Hollender, Lars G.; Lloid, Michelle; Drew, Shane Patrick; Schubert, Mark M.

2015-01-01

Objective To detect dimensional changes in the mandibular cortical bone associated with bisphosphonate (BP) use and to correlate the measurements of the cortical bone with the cumulative dose of BP therapy. Methods Mandibular inferior cortical bone thickness (MICBT) was measured under the mental foramen from panoramic radiographs of subjects using BP with and without bisphosphonate related osteonecrosis of the jaws (BRONJ) and controls. Results The highest mean MICBT was observed in BRONJ subjects 6.81 (± 1.35 mm), when compared to subjects using BP 5.44 (± 1.09 mm) and controls 4.79 (± 0.85 mm; p<0.01). The mean MICBT of BRONJ subjects was significantly higher than that of subjects using BP without BRONJ. There was a correlation between MICBT and cumulative dose of zolendronate. Conclusion The MICBT on panoramic radiograph is a potentially useful tool for the detection of dimensional changes associated with BP therapy. PMID:25864820

Thalamic amplification of cortical connectivity sustains attentional control

PubMed Central

Schmitt, L. Ian; Wimmer, Ralf D.; Nakajima, Miho; Happ, Michael; Mofakham, Sima; Halassa, Michael M.

2017-01-01

While interactions between the thalamus and cortex are critical for cognitive function1–3, the exact contribution of the thalamus to these interactions is often unclear. Recent studies have shown diverse connectivity patterns across the thalamus 4,5, but whether this diversity translates to thalamic functions beyond relaying information to or between cortical regions6 is unknown. Here, by investigating prefrontal cortical (PFC) representation of two rules used to guide attention, we find that the mediodorsal thalamus (MD) sustains these representations without relaying categorical information. Specifically, MD input amplifies local PFC connectivity, enabling rule-specific neural sequences to emerge and thereby maintain rule representations. Consistent with this notion, broadly enhancing PFC excitability diminishes rule specificity and behavioral performance, while enhancing MD excitability improves both. Overall, our results define a previously unknown principle in neuroscience; thalamic control of functional cortical connectivity. This function indicates that the thalamus plays much more central roles in cognition than previously thought. PMID:28467827

Unique cortical physiology associated with ipsilateral hand movements and neuroprosthetic implications.

PubMed

Wisneski, Kimberly J; Anderson, Nicholas; Schalk, Gerwin; Smyth, Matt; Moran, Daniel; Leuthardt, Eric C

2008-12-01

Brain computer interfaces (BCIs) offer little direct benefit to patients with hemispheric stroke because current platforms rely on signals derived from the contralateral motor cortex (the same region injured by the stroke). For BCIs to assist hemiparetic patients, the implant must use unaffected cortex ipsilateral to the affected limb. This requires the identification of distinct electrophysiological features from the motor cortex associated with ipsilateral hand movements. In this study we studied 6 patients undergoing temporary placement of intracranial electrode arrays. Electrocorticographic (ECoG) signals were recorded while the subjects engaged in specific ipsilateral or contralateral hand motor tasks. Spectral changes were identified with regards to frequency, location, and timing. Ipsilateral hand movements were associated with electrophysiological changes that occur in lower frequency spectra, at distinct anatomic locations, and earlier than changes associated with contralateral hand movements. In a subset of 3 patients, features specific to ipsilateral and contralateral hand movements were used to control a cursor on a screen in real time. In ipsilateral derived control this was optimal with lower frequency spectra. There are distinctive cortical electrophysiological features associated with ipsilateral movements which can be used for device control. These findings have implications for patients with hemispheric stroke because they offer a potential methodology for which a single hemisphere can be used to enhance the function of a stroke induced hemiparesis.

Increased Executive Functioning, Attention, and Cortical Thickness in White-Collar Criminals

PubMed Central

Raine, Adrian; Laufer, William S.; Yang, Yaling; Narr, Katherine L.; Thompson, Paul; Toga, Arthur W.

2011-01-01

Very little is known on white collar crime and how it differs to other forms of offending. This study tests the hypothesis that white collar criminals have better executive functioning, enhanced information processing, and structural brain superiorities compared to offender controls. Using a case-control design, executive functioning, orienting, and cortical thickness was assessed in 21 white collar criminals matched with 21 controls on age, gender, ethnicity, and general level of criminal offending. White collar criminals had significantly better executive functioning, increased electrodermal orienting, increased arousal, and increased cortical gray matter thickness in the ventromedial prefrontal cortex, inferior frontal gyrus, somatosensory cortex, and the temporal-parietal junction compared to controls. Results, while initial, constitute the first findings on neurobiological characteristics of white-collar criminals It is hypothesized that white collar criminals have information-processing and brain superiorities that give them an advantage in perpetrating criminal offenses in occupational settings. PMID:22002326

Increased executive functioning, attention, and cortical thickness in white-collar criminals.

PubMed

Raine, Adrian; Laufer, William S; Yang, Yaling; Narr, Katherine L; Thompson, Paul; Toga, Arthur W

2012-12-01

Very little is known on white-collar crime and how it differs to other forms of offending. This study tests the hypothesis that white-collar criminals have better executive functioning, enhanced information processing, and structural brain superiorities compared with offender controls. Using a case-control design, executive functioning, orienting, and cortical thickness was assessed in 21 white-collar criminals matched with 21 controls on age, gender, ethnicity, and general level of criminal offending. White-collar criminals had significantly better executive functioning, increased electrodermal orienting, increased arousal, and increased cortical gray matter thickness in the ventromedial prefrontal cortex, inferior frontal gyrus, somatosensory cortex, and the temporal-parietal junction compared with controls. Results, while initial, constitute the first findings on neurobiological characteristics of white-collar criminals. It is hypothesized that white-collar criminals have information-processing and brain superiorities that give them an advantage in perpetrating criminal offenses in occupational settings. Copyright © 2011 Wiley Periodicals, Inc.

Remapping cortical modulation for electrocorticographic brain-computer interfaces: a somatotopy-based approach in individuals with upper-limb paralysis

NASA Astrophysics Data System (ADS)

Degenhart, Alan D.; Hiremath, Shivayogi V.; Yang, Ying; Foldes, Stephen; Collinger, Jennifer L.; Boninger, Michael; Tyler-Kabara, Elizabeth C.; Wang, Wei

2018-04-01

Objective. Brain-computer interface (BCI) technology aims to provide individuals with paralysis a means to restore function. Electrocorticography (ECoG) uses disc electrodes placed on either the surface of the dura or the cortex to record field potential activity. ECoG has been proposed as a viable neural recording modality for BCI systems, potentially providing stable, long-term recordings of cortical activity with high spatial and temporal resolution. Previously we have demonstrated that a subject with spinal cord injury (SCI) could control an ECoG-based BCI system with up to three degrees of freedom (Wang et al 2013 PLoS One). Here, we expand upon these findings by including brain-control results from two additional subjects with upper-limb paralysis due to amyotrophic lateral sclerosis and brachial plexus injury, and investigate the potential of motor and somatosensory cortical areas to enable BCI control. Approach. Individuals were implanted with high-density ECoG electrode grids over sensorimotor cortical areas for less than 30 d. Subjects were trained to control a BCI by employing a somatotopic control strategy where high-gamma activity from attempted arm and hand movements drove the velocity of a cursor. Main results. Participants were capable of generating robust cortical modulation that was differentiable across attempted arm and hand movements of their paralyzed limb. Furthermore, all subjects were capable of voluntarily modulating this activity to control movement of a computer cursor with up to three degrees of freedom using the somatotopic control strategy. Additionally, for those subjects with electrode coverage of somatosensory cortex, we found that somatosensory cortex was capable of supporting ECoG-based BCI control. Significance. These results demonstrate the feasibility of ECoG-based BCI systems for individuals with paralysis as well as highlight some of the key challenges that must be overcome before such systems are translated to the clinical realm. ClinicalTrials.gov Identifier: NCT01393444.

Lateral prefrontal cortex: architectonic and functional organization

PubMed Central

Petrides, Michael

2005-01-01

A comparison of the architecture of the human prefrontal cortex with that of the macaque monkey showed a very similar architectonic organization in these two primate species. There is no doubt that the prefrontal cortical areas of the human brain have undergone considerable development, but it is equally clear that the basic architectonic organization is the same in the two species. Thus, a comparative approach to the study of the functional organization of the primate prefrontal cortex is more likely to reveal the essential aspects of the various complex control processes that are the domain of frontal function. The lateral frontal cortex appears to be functionally organized along both a rostral–caudal axis and a dorsal–ventral axis. The most caudal frontal region, the motor region on the precentral gyrus, is involved in fine motor control and direct sensorimotor mappings, whereas the caudal lateral prefrontal region is involved in higher order control processes that regulate the selection among multiple competing responses and stimuli based on conditional operations. Further rostrally, the mid-lateral prefrontal region plays an even more abstract role in cognitive control. The mid-lateral prefrontal region is itself organized along a dorsal–ventral axis of organization, with the mid-dorsolateral prefrontal cortex being involved in the monitoring of information in working memory and the mid-ventrolateral prefrontal region being involved in active judgments on information held in posterior cortical association regions that are necessary for active retrieval and encoding of information. PMID:15937012

Spatial organization of xylem cell walls by ROP GTPases and microtubule-associated proteins.

PubMed

Oda, Yoshihisa; Fukuda, Hiroo

2013-12-01

Proper patterning of cellulosic cell walls is critical for cell shaping and differentiation of plant cells. Cortical microtubule arrays regulate the deposition patterns of cellulose microfibrils by controlling the targeting and trajectory of cellulose synthase complexes. Although some microtubule-associated proteins (MAPs) regulate the arrangement of cortical microtubules, knowledge about the overall mechanism governing the spacing of cortical microtubules is still limited. Recent studies reveal that ROP GTPases and MAPs spatially regulate the assembly and disassembly of cortical microtubules in developing xylem cells, in which localized secondary cell walls are deposited. Here, we review recent insights into the regulation of xylem cell wall patterning by cortical microtubules, ROP GTPases, and MAPs. Copyright © 2013 Elsevier Ltd. All rights reserved.

Disconnection syndromes of basal ganglia, thalamus, and cerebrocerebellar systems.

PubMed

Schmahmann, Jeremy D; Pandya, Deepak N

2008-09-01

Disconnection syndromes were originally conceptualized as a disruption of communication between different cerebral cortical areas. Two developments mandate a re-evaluation of this notion. First, we present a synopsis of our anatomical studies in monkey elucidating principles of organization of cerebral cortex. Efferent fibers emanate from every cortical area, and are directed with topographic precision via association fibers to ipsilateral cortical areas, commissural fibers to contralateral cerebral regions, striatal fibers to basal ganglia, and projection subcortical bundles to thalamus, brainstem and/or pontocerebellar system. We note that cortical areas can be defined by their patterns of subcortical and cortical connections. Second, we consider motor, cognitive and neuropsychiatric disorders in patients with lesions restricted to basal ganglia, thalamus, or cerebellum, and recognize that these lesions mimic deficits resulting from cortical lesions, with qualitative differences between the manifestations of lesions in functionally related areas of cortical and subcortical nodes. We consider these findings on the basis of anatomical observations from tract tracing studies in monkey, viewing them as disconnection syndromes reflecting loss of the contribution of subcortical nodes to the distributed neural circuits. We introduce a new theoretical framework for the distributed neural circuits, based on general, and specific, principles of anatomical organization, and on the architecture of the nodes that comprise these systems. We propose that neural architecture determines function, i.e., each architectonically distinct cortical and subcortical area contributes a unique transform, or computation, to information processing; anatomically precise and segregated connections between nodes define behavior; and association fiber tracts that link cerebral cortical areas with each other enable the cross-modal integration required for evolved complex behaviors. This model enables the formulation and testing of future hypotheses in investigations using evolving magnetic resonance imaging techniques in humans, and in clinical studies in patients with cortical and subcortical lesions.

Intelligence and cortical thickness in children with complex partial seizures.

PubMed

Tosun, Duygu; Caplan, Rochelle; Siddarth, Prabha; Seidenberg, Michael; Gurbani, Suresh; Toga, Arthur W; Hermann, Bruce

2011-07-15

Prior studies on healthy children have demonstrated regional variations and a complex and dynamic relationship between intelligence and cerebral tissue. Yet, there is little information regarding the neuroanatomical correlates of general intelligence in children with epilepsy compared to healthy controls. In vivo imaging techniques, combined with methods for advanced image processing and analysis, offer the potential to examine quantitative mapping of brain development and its abnormalities in childhood epilepsy. A surface-based, computational high resolution 3-D magnetic resonance image analytic technique was used to compare the relationship of cortical thickness with age and intelligence quotient (IQ) in 65 children and adolescents with complex partial seizures (CPS) and 58 healthy controls, aged 6-18 years. Children were grouped according to health status (epilepsy; controls) and IQ level (average and above; below average) and compared on age-related patterns of cortical thickness. Our cross-sectional findings suggest that disruption in normal age-related cortical thickness expression is associated with intelligence in pediatric CPS patients both with average and below average IQ scores. Copyright © 2011 Elsevier Inc. All rights reserved.

Hypothesis-driven methods to augment human cognition by optimizing cortical oscillations

PubMed Central

Horschig, Jörn M.; Zumer, Johanna M.; Bahramisharif, Ali

2014-01-01

Cortical oscillations have been shown to represent fundamental functions of a working brain, e.g., communication, stimulus binding, error monitoring, and inhibition, and are directly linked to behavior. Recent studies intervening with these oscillations have demonstrated effective modulation of both the oscillations and behavior. In this review, we collect evidence in favor of how hypothesis-driven methods can be used to augment cognition by optimizing cortical oscillations. We elaborate their potential usefulness for three target groups: healthy elderly, patients with attention deficit/hyperactivity disorder, and healthy young adults. We discuss the relevance of neuronal oscillations in each group and show how each of them can benefit from the manipulation of functionally-related oscillations. Further, we describe methods for manipulation of neuronal oscillations including direct brain stimulation as well as indirect task alterations. We also discuss practical considerations about the proposed techniques. In conclusion, we propose that insights from neuroscience should guide techniques to augment human cognition, which in turn can provide a better understanding of how the human brain works. PMID:25018706

Anodal transcranial direct current stimulation of the motor cortex increases cortical voluntary activation and neural plasticity.

PubMed

Frazer, Ashlyn; Williams, Jacqueline; Spittles, Michael; Rantalainen, Timo; Kidgell, Dawson

2016-11-01

We examined the cumulative effect of 4 consecutive bouts of noninvasive brain stimulation on corticospinal plasticity and motor performance, and whether these responses were influenced by the brain-derived neurotrophic factor (BDNF) polymorphism. In a randomized double-blinded cross-over design, changes in strength and indices of corticospinal plasticity were analyzed in 14 adults who were exposed to 4 consecutive sessions of anodal and sham transcranial direct current stimulation (tDCS). Participants also undertook a blood sample for BDNF genotyping (N = 13). We observed a significant increase in isometric wrist flexor strength with transcranial magnetic stimulation revealing increased corticospinal excitability, decreased silent period duration, and increased cortical voluntary activation compared with sham tDCS. The results show that 4 consecutive sessions of anodal tDCS increased cortical voluntary activation manifested as an improvement in strength. Induction of corticospinal plasticity appears to be influenced by the BDNF polymorphism. Muscle Nerve 54: 903-913, 2016. © 2016 Wiley Periodicals, Inc.

Sharpened cortical tuning and enhanced cortico-cortical communication contribute to the long-term neural mechanisms of visual motion perceptual learning.

PubMed

Chen, Nihong; Bi, Taiyong; Zhou, Tiangang; Li, Sheng; Liu, Zili; Fang, Fang

2015-07-15

Much has been debated about whether the neural plasticity mediating perceptual learning takes place at the sensory or decision-making stage in the brain. To investigate this, we trained human subjects in a visual motion direction discrimination task. Behavioral performance and BOLD signals were measured before, immediately after, and two weeks after training. Parallel to subjects' long-lasting behavioral improvement, the neural selectivity in V3A and the effective connectivity from V3A to IPS (intraparietal sulcus, a motion decision-making area) exhibited a persistent increase for the trained direction. Moreover, the improvement was well explained by a linear combination of the selectivity and connectivity increases. These findings suggest that the long-term neural mechanisms of motion perceptual learning are implemented by sharpening cortical tuning to trained stimuli at the sensory processing stage, as well as by optimizing the connections between sensory and decision-making areas in the brain. Copyright © 2015 Elsevier Inc. All rights reserved.

Correlation of fingertip shear force direction with somatosensory cortical activity in monkey

PubMed Central

Fortier-Poisson, Pascal; Langlais, Jean-Sébastien

2015-01-01

To examine the activity of somatosensory cortex (S1) neurons to self-generated shear forces on the index and thumb, two monkeys were trained to grasp a stationary metal tab with a key grip and exert forces without the fingers slipping in one of four orthogonal directions for 1 s. A majority (∼85%) of slowly adapting and rapidly adapting (RA) S1 neurons had activity modulated with shear force direction. The cells were recorded mainly in areas 1 and 2 of the S1, although some area 3b neurons also responded to shear direction or magnitude. The preferred shear vectors were distributed in every direction, with tuning arcs varying from 50° to 170°. Some RA neurons sensitive to dynamic shear force direction also responded to static shear force but within a narrower range, suggesting that the direction of the shear force may influence the adaptation rate. Other neurons were modulated with shear forces in diametrically opposite directions. The directional sensitivity of S1 cortical neurons is consistent with recordings from cutaneous afferents showing that shear direction, even without slip, is a powerful stimulus to S1 neurons. PMID:26467520

Trait- and state-dependent cortical inhibitory deficits in bipolar disorder.

PubMed

Ruiz-Veguilla, Miguel; Martín-Rodríguez, Juan Francisco; Palomar, Francisco J; Porcacchia, Paolo; Álvarez de Toledo, Paloma; Perona-Garcelán, Salvador; Rodríguez-Testal, Juan Francisco; Huertas-Fernández, Ismael; Mir, Pablo

2016-05-01

Euthymic patients with bipolar disorder (BD) have deficits in cortical inhibition. However, whether cortical inhibitory deficits are trait- or state-dependent impairments is not yet known and their relationship with psychiatric symptoms is not yet understood. In the present study, we examined trait- and state-dependent cortical inhibitory deficits and evaluated the potential clinical significance of these deficits. Nineteen patients with bipolar I disorder were evaluated using the paired-pulse transcranial stimulation protocol, which assessed cortical inhibition during an acute manic episode. Cortical inhibition measures were compared with those obtained in 28 demographically matched healthy controls. A follow-up assessment was performed in 15 of these patients three months later, when there was remission from their mood and psychotic symptoms. The association between cortical inhibitory measures and severity of psychiatric symptoms was also studied. During mania, patients showed decreased short-interval intracortical and transcallosal inhibition, as well as a normal cortical silent period and long-interval cortical inhibition. These findings were the same during euthymia. Symptoms associated with motor hyperactivity were correlated negatively with the degree of cortical inhibition. These correlations were not significant when a Bonferroni correction was applied. The present longitudinal study showed cortical inhibitory deficits in patients with BD, and supports the hypothesis that cortical inhibitory deficits in BD are trait dependent. Further research is necessary to confirm the clinical significance of these deficits. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Female Mice Lacking Estrogen Receptor-α in Hypothalamic Proopiomelanocortin (POMC) Neurons Display Enhanced Estrogenic Response on Cortical Bone Mass.

PubMed

Farman, H H; Windahl, S H; Westberg, L; Isaksson, H; Egecioglu, E; Schele, E; Ryberg, H; Jansson, J O; Tuukkanen, J; Koskela, A; Xie, S K; Hahner, L; Zehr, J; Clegg, D J; Lagerquist, M K; Ohlsson, C

2016-08-01

Estrogens are important regulators of bone mass and their effects are mainly mediated via estrogen receptor (ER)α. Central ERα exerts an inhibitory role on bone mass. ERα is highly expressed in the arcuate (ARC) and the ventromedial (VMN) nuclei in the hypothalamus. To test whether ERα in proopiomelanocortin (POMC) neurons, located in ARC, is involved in the regulation of bone mass, we used mice lacking ERα expression specifically in POMC neurons (POMC-ERα(-/-)). Female POMC-ERα(-/-) and control mice were ovariectomized (OVX) and treated with vehicle or estradiol (0.5 μg/d) for 6 weeks. As expected, estradiol treatment increased the cortical bone thickness in femur, the cortical bone mechanical strength in tibia and the trabecular bone volume fraction in both femur and vertebrae in OVX control mice. Importantly, the estrogenic responses were substantially increased in OVX POMC-ERα(-/-) mice compared with the estrogenic responses in OVX control mice for cortical bone thickness (+126 ± 34%, P < .01) and mechanical strength (+193 ± 38%, P < .01). To test whether ERα in VMN is involved in the regulation of bone mass, ERα was silenced using an adeno-associated viral vector. Silencing of ERα in hypothalamic VMN resulted in unchanged bone mass. In conclusion, mice lacking ERα in POMC neurons display enhanced estrogenic response on cortical bone mass and mechanical strength. We propose that the balance between inhibitory effects of central ERα activity in hypothalamic POMC neurons in ARC and stimulatory peripheral ERα-mediated effects in bone determines cortical bone mass in female mice.

Functional reorganization during cognitive function tasks in patients with amyotrophic lateral sclerosis.

PubMed

Keller, Jürgen; Böhm, Sarah; Aho-Özhan, Helena E A; Loose, Markus; Gorges, Martin; Kassubek, Jan; Uttner, Ingo; Abrahams, Sharon; Ludolph, Albert C; Lulé, Dorothée

2018-06-01

Cognitive deficits, especially in the domains of social cognition and executive function including verbal fluency, are common in amyotrophic lateral sclerosis (ALS) patients. There is yet sparse understanding of pathogenesis of the underlying, possibly adaptive, cortical patterns. To address this issue, 65 patients with ALS and 33 age-, gender- and education-matched healthy controls were tested on cognitive and behavioral deficits with the Edinburgh Cognitive and Behavioural ALS Screen (ECAS). Using functional magnetic resonance imaging (fMRI), cortical activity during social cognition and executive function tasks (theory of mind, verbal fluency, alternation) adapted from the ECAS was determined in a 3 Tesla scanner. Compared to healthy controls, ALS patients performed worse in the ECAS overall (p < 0.001) and in all of its subdomains (p < 0.02), except memory. Imaging revealed altered cortical activation during all tasks, with patients consistently showing a hyperactivation in relevant brain areas compared to healthy controls. Additionally, cognitively high performing ALS patients consistently exhibited more activation in frontal brain areas than low performing patients and behaviorally unimpaired patients presented with more neuronal activity in orbitofrontal areas than behaviorally impaired patients. In conclusion, hyperactivation in fMRI cognitive tasks seems to represent an early adaptive process to overcome neuronal cell loss in relevant brain areas. The hereby presented cortical pattern change might suggest that, once this loss passes a critical threshold and no cortical buffering is possible, clinical representation of cognitive and behavioral impairment evolves. Future studies might shed light on the pattern of cortical pattern change in the course of ALS.

Prenatal Cannabis and Tobacco Exposure in Relation to Brain Morphology: A Prospective Neuroimaging Study in Young Children.

PubMed

El Marroun, Hanan; Tiemeier, Henning; Franken, Ingmar H A; Jaddoe, Vincent W V; van der Lugt, Aad; Verhulst, Frank C; Lahey, Benjamin B; White, Tonya

2016-06-15

Cannabis use during pregnancy has been associated with negative behavioral outcomes and psychopathology in offspring. However, there has been little research evaluating alterations in brain structure as a result of maternal cannabis use. In this prospective study, we investigated the association between prenatal cannabis exposure and brain morphology in young children. We matched 96 children prenatally exposed to tobacco only (without cannabis) with 113 unexposed control subjects on the basis of age and gender and subsequently selected 54 children exposed to prenatal cannabis (mostly combined with tobacco exposure). These children (aged 6 to 8 years) were part of a population-based study in the Netherlands, the Generation R Study, and were followed from pregnancy onward. We assessed brain volumetric measures and cortical thickness in magnetic resonance imaging scans using FreeSurfer. We performed vertexwise analyses in FreeSurfer and linear regression analyses adjusting for relevant covariates using Statistical Package for the Social Sciences. Prenatal cannabis exposure was not associated with global brain volumes, such as total brain volume, gray matter volume, or white matter volume. However, prenatal cannabis exposure was associated with differences in cortical thickness: compared with nonexposed control subjects, cannabis-exposed children had thicker frontal cortices. Prenatal tobacco exposure compared with nonexposed control subjects was associated with cortical thinning, primarily in the superior frontal and superior parietal cortices. Our findings suggest an association between prenatal cannabis exposure and cortical thickness in children. Further research is needed to explore the causal nature of this association. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

In Vivo High-Resolution 7 Tesla MRI Shows Early and Diffuse Cortical Alterations in CADASIL

PubMed Central

De Guio, François; Reyes, Sonia; Vignaud, Alexandre; Duering, Marco; Ropele, Stefan; Duchesnay, Edouard; Chabriat, Hugues; Jouvent, Eric

2014-01-01

Background and Purpose Recent data suggest that early symptoms may be related to cortex alterations in CADASIL (Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy), a monogenic model of cerebral small vessel disease (SVD). The aim of this study was to investigate cortical alterations using both high-resolution T2* acquisitions obtained with 7 Tesla MRI and structural T1 images with 3 Tesla MRI in CADASIL patients with no or only mild symptomatology (modified Rankin’s scale ≤1 and Mini Mental State Examination (MMSE) ≥24). Methods Complete reconstructions of the cortex using 7 Tesla T2* acquisitions with 0.7 mm isotropic resolution were obtained in 11 patients (52.1±13.2 years, 36% male) and 24 controls (54.8±11.0 years, 42% male). Seven Tesla T2* within the cortex and cortical thickness and morphology obtained from 3 Tesla images were compared between CADASIL and control subjects using general linear models. Results MMSE, brain volume, cortical thickness and global sulcal morphology did not differ between groups. By contrast, T2* measured by 7 Tesla MRI was significantly increased in frontal, parietal, occipital and cingulate cortices in patients after correction for multiple testing. These changes were not related to white matter lesions, lacunes or microhemorrhages in patients having no brain atrophy compared to controls. Conclusions Seven Tesla MRI, by contrast to state of the art post-processing of 3 Tesla acquisitions, shows diffuse T2* alterations within the cortical mantle in CADASIL whose origin remains to be determined. PMID:25165824