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Objective: Hepatic encephalopathy (HE) is a potentially reversible brain dysfunction caused by liver failure. Altered synaptic plasticity is supposed to play a major role in the pathophysiology of HE. Here, we used paired associative stimulation with an inter-stimulus interval of 25 ms (PAS25), a transcranial magnetic stimulation (TMS) protocol, to test synaptic plasticity of the motor cortex in patients with manifest HE., Methods: 23 HE-patients and 23 healthy controls were enrolled in the study. Motor evoked potential (MEP) amplitudes were assessed as measure for cortical excitability. Time courses of MEP amplitude changes after the PAS25 intervention were compared between both groups., Results: MEP-amplitudes increased after PAS25 in the control group, indicating PAS25-induced synaptic plasticity in healthy controls, as expected. In contrast, MEP-amplitudes within the HE group did not change and were lower than in the control group, indicating no induction of plasticity., Conclusions: Our study revealed reduced synaptic plasticity of the primary motor cortex in HE., Significance: Reduced synaptic plasticity in HE provides a link between pathological changes on the molecular level and early clinical symptoms of the disease. This decrease may be caused by disturbances in the glutamatergic neurotransmission due to the known hyperammonemia in HE patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Pathological oscillations including elevated beta activity in the subthalamic nucleus (STN) and between STN and cortical areas are a hallmark of neural activity in Parkinson's disease (PD). Oscillations also play an important role in normal physiological processes and serve distinct functional roles at different points in time. We characterised the effect of dopaminergic medication on oscillatory whole-brain networks in PD in a time-resolved manner by employing a hidden Markov model on combined STN local field potentials and magnetoencephalography (MEG) recordings from 17 PD patients. Dopaminergic medication led to coherence within the medial and orbitofrontal cortex in the delta/theta frequency range. This is in line with known side effects of dopamine treatment such as deteriorated executive functions in PD. In addition, dopamine caused the beta band activity to switch from an STN-mediated motor network to a frontoparietal-mediated one. In contrast, dopamine did not modify local STN-STN coherence in PD. STN-STN synchrony emerged both on and off medication. By providing electrophysiological evidence for the differential effects of dopaminergic medication on the discovered networks, our findings open further avenues for electrical and pharmacological interventions in PD., Competing Interests: AS, DV, JV, EF No competing interests declared, AS has been serving as a consultant for Medtronic Inc, Boston Scientific, St. Jude Medical, Grünenthal, and has received lecture fees from Abbvie, Boston Scientific, St. Jude Medical, Medtronic Inc, UCB., (© 2021, Sharma et al.)

Conditioning transcranial magnetic stimulation (TMS) with subthreshold conditioning stimulus followed by supra-threshold test stimulus at inter-stimulus intervals (ISI) of 1-5 ms results in inhibition (SICI), while ISI at 10-15 ms results in facilitation (ICF). One concerning issue, applying ICF/SICI protocols on patients is the substantial protocol variability. Here, we hypothesized that increasing the number of CS could result in more robust ICF/SICI protocols. Twenty healthy subjects participated in the study. Motor-evoked potentials (MEP) were obtained from conditioning TMS with a varying number of conditioning stimuli in 3, 4, 10, and 15 ms ISI over the primary motor cortex. MEP amplitudes were then compared to examine excitability. TMS with 3, 5, and 7 conditioning stimuli but not with one conditioning stimulus induced ICF. Moreover, 10 ms ISI produced stronger ICF than 15 ms ISI. Significant SICI was only induced with one conditioning stimulus. Besides, 3 ms ISI resulted in stronger SICI than 4 ms ISI. Only a train of conditioning stimuli induced stable ICF and may be more advantageous than the classical paired pulse ICF paradigm.

Understanding action-related language recruits the brain's motor system and can interact with motor behaviour. The current study shows MEG oscillatory patterns during verb-motor priming. Hand and foot verbs were followed by hand or foot responses, with faster reaction times for congruent conditions. In ROIs placed in the hand/arm and foot/leg portions of the sensorimotor cortex, this behavioural priming effect was accompanied by modulations in MEG oscillatory patterns preceding the responses. Power suppression in the alpha/beta frequency bands was reduced in congruent conditions in the body-part-specific ROIs. These results imply that the verb-motor priming effect may be a direct consequence of motor cortex contributions to action word processing.

Background: Tics are the core symptom of patients with Gilles de la Tourette syndrome, yet the spatial-temporal dynamics of neural activity causing a tic remains to be determined., Objective: Identification of cortical events preceding tic onset., Methods: In twelve patients with Tourette syndrome we performed magnetoencephalography to trace the time course of beta oscillations (15-30 Hz) in motor cortical areas before tic onset., Results: Patients showed a biphasic modulation of cortical beta activity during the second before tic onset. We observed an initial increase of beta power over the left-hemispheric channels overlying the motor cortex. This increase was subsequently replaced by a decrease in beta power. The beta decrease close to tic onset resembled the typical pattern accompanying preparation of voluntary movements. Only the initial increase in beta power positively correlated with the intensity of motor urges preceding tics., Conclusions: The spatial-temporal dynamics of cortical activity suggests a voluntary component of tics that might be triggered by a failure of compensatory motor inhibitory mechanisms., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: The GABA hypothesis of hepatic encephalopathy (HE) proposes an increased cerebral GABA-ergic tone in HE but has not been investigated in vivo in HE-patients yet. Cortical GABA-ergic and glutamatergic neurotransmission in HE-patients were evaluated using transcranial magnetic stimulation., Methods: Twenty-one patients with HE grade 1 and 2 and age matched controls participated in the study. GABA-ergic (short- and long-interval intracortical inhibition (SICI and LICI)) and glutamatergic (intracortical and short-interval intracortical facilitation (ICF and SICF)) excitability of the primary motor cortex (M1) and global corticospinal excitability (motor threshold, motor evoked potential recruitment curve (MEP-RC) were compared between the groups. SICI and ICF were correlated to the critical flicker frequency (CFF) as measure for disease severity., Results: In HE-patients, the slope of MEP-RC was significantly shallower compared to healthy controls. SICI was significantly reduced in patients with HE grade 2 compared to healthy controls. In HE-patients, SICI and ICF was significantly correlated to CFF., Conclusion: Although global corticospinal excitability was reduced in HE-patients, GABA-ergic inhibition was reduced in M1 depending on HE severity. Moreover CFF related alteration of GABAergic and glutamatergic neurotransmission in patients with HE could support the notion of a severity dependent alteration of cortical excitability., Significance: The decrease of cortical GABA-ergic tone challenges the classical GABA hypothesis in HE., (Copyright © 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Akinesia, a cardinal symptom of Parkinson's disease, has been linked to abnormal activation in putamen and posterior medial frontal cortex (pMFC). However, little is known whether clinical severity of akinesia is linked to dysfunctional connectivity of these regions. Using a seed-based approach, we here investigated resting-state functional connectivity (RSFC) of putamen, pMFC and primary motor cortex (M1) in 60 patients with Parkinson's disease on regular medication and 72 healthy controls. We found that in patients putamen featured decreases of connectivity for a number of cortical and subcortical areas engaged in sensorimotor and cognitive processing. In contrast, the pMFC showed reduced connectivity with a more focal cortical network involved in higher-level motor-cognition. Finally, M1 featured a selective disruption of connectivity in a network specifically connected with M1. Correlating clinical impairment with connectivity changes revealed a relationship between akinesia and reduced RSFC between pMFC and left intraparietal lobule (IPL). Together, the present study demonstrated RSFC decreases in networks for motor initiation and execution in Parkinson's disease. Moreover, results suggest a relationship between pMFC-IPL decoupling and the manifestation of akinetic symptoms.

Background: Inhibitory oscillatory mechanisms subserving tic compensation have been put forward in Tourette syndrome. Modulation of the beta rhythm (15-25 Hz) as the well-established oscillatory movement execution-inhibition indicator was tested during a cognitive-motor task in patients with Tourette syndrome., Methods: Performing a Go/NoGo task, 12 patients with Tourette syndrome and 12 matched controls were recorded using whole-head magnetoencephalography., Results: Compared to healthy participants, patients showed less beta suppression in the sensorimotor area and enhanced beta power in parieto-occipital brain regions contralaterally to the response hand. Average beta power and power gain correlated negatively with tic severity., Conclusions: Increased motor inhibitory as well as visuomotor attentional processes are likely to subserve tic compensation. Correlational results suggest that stronger inhibitory compensation accompanies less tic severity., (© 2016 International Parkinson and Movement Disorder Society.)

Several studies have shown activation of the mirror neuron system (MNS), comprising the temporal, posterior parietal, and sensorimotor areas when observing plausible actions, but far less is known on how these cortical areas interact during the recognition of a plausible action. Here, we recorded neural activity with magnetoencephalography while subjects viewed point-light displays of biologically plausible and scrambled versions of actions. We were interested in modulations of oscillatory activity and, specifically, in coupling of oscillatory activity between visual and motor areas. Both plausible and scrambled actions elicited modulations of θ (5-7 Hz), α (7-13 Hz), β (13-35 Hz), and γ (55-100 Hz) power within visual and motor areas. When comparing between the two actions, we observed sequential and spatially distinct increases of γ (∼65 Hz), β (∼25 Hz), and α (∼11 Hz) power between 0.5 and 1.3 s in parieto-occipital, sensorimotor, and left temporal areas. In addition, significant clusters of γ (∼65 Hz) and α/β (∼15 Hz) power decrease were observed in right temporal and parieto-occipital areas between 1.3 and 2.0 s. We found β-power in sensorimotor areas to be positively correlated on a trial-by-trial basis with parieto-occipital γ and left temporal α-power for the plausible but not for the scrambled condition. These results provide new insights in the neuronal oscillatory activity of the areas involved in the recognition of plausible action movements and their interaction. The power correlations between specific areas underscore the importance of interactions between visual and motor areas of the MNS during the recognition of a plausible action., (Copyright © 2012 Wiley Periodicals, Inc.)

Gilles de la Tourette syndrome is a neuropsychiatric disorder characterized by an impaired ability to inhibit unwanted behaviour. Although the presence of chronic motor and vocal tics defines Tourette's syndrome, other distinctive behavioural features like echo- and coprophenomena, and non-obscene socially inappropriate behaviour are also core features. We investigated neuronal activation during stimulus-driven execution and inhibition of prepared movements in Tourette's syndrome. To this end, we performed event-related functional magnetic resonance imaging and structural diffusion tensor imaging in 15 moderately affected uncomplicated patients with 'pure' Tourette's syndrome and 15 healthy control participants matched for age and gender. Subjects underwent functional magnetic resonance imaging during a Go/NoGo reaction time task. They had to withhold a prepared finger movement for a variable time until a stimulus instructed them to either execute (Go) or inhibit it (NoGo). Tics were monitored throughout the experiments, combining surface electromyogram, video recording, and clinical assessment in the scanner. Patients with Tourette's syndrome had longer reaction times than healthy controls in Go trials and made more errors in total. Their functional brain activation was decreased in left primary motor cortex and secondary motor areas during movement execution (Go trials) but not during response inhibition (NoGo trials) compared with healthy control subjects. Volume of interest analysis demonstrated less task-related activation in patients with Tourette's syndrome in primary and secondary motor cortex bilaterally, but not in the basal ganglia and cortical non-motor areas. They showed reduced co-activation between the left primary sensory-motor hand area and a network of contralateral sensory-motor areas and ipsilateral cerebellar regions. There were no between-group differences in structural connectivity of the left primary sensory-motor cortex as measured by diffusion tensor imaging-based probabilistic tractography. Our results link reduced sensory-motor cortical activation during movement execution to a decreased co-activation between the sensory-motor cortex and other brain areas involved in motor processing. These functional changes in patients with Tourette's syndrome might result from adaptive reorganization in fronto-parietal brain networks engaged in motor and behavioural control, possibly triggered by abnormal processing and presumably overactivity in cortico-striato-cortical circuits. This might enable patients with Tourette's syndrome to better suppress unwanted movements but comes at a price of behavioural deficits in other domains.

Parkinson's disease (PD) is a common neurodegenerative disorder owing to loss of dopaminergic cells. Akinesia - one of the core symptoms of PD - is associated with exaggerated oscillations at beta frequency (13-30 Hz) within the subthalamic nucleus (STN). Thus, enhanced oscillations below 30 Hz are assumed to represent a pathophysiological marker of PD. However, recent data suggest that OFF medication exaggerated beta oscillations within basal ganglia (BG) cortical networks may serve for the compensation of BG dysfunctions. The STN is functionally connected to mesial prefrontal areas like the supplementary motor area (SMA). But, it is still not fully understood how enhanced beta oscillations within the BG exert dominance over the primary motor cortex (M1) thereby yielding motor impairment. The present study, therefore, investigates the effect of dopaminergic state on SMA-M1 functional connectivity using Magnetoencephalography (MEG). MEG data were recorded in 7 patients suffering from PD with preponderance of akinesia during isometric contraction of the right forearm and during rest. Coherence as a measure of functional connectivity between M1 and SMA was calculated OFF and ON medication and correlated with the motor part of the Unified Parkinson's Disease Rating Scale (UPDRS III) and with disease duration. During rest a significant positive correlation between disease duration and SMA-M1 coherence was found ON but not OFF medication. Conversely, during isometric contraction SMA-M1 coherence and UPDRS III were inversely correlated OFF but not ON medication explaining more than 80% of variance. The results favor the hypothesis that OFF medication exaggerated cortical coherence at beta frequency represents a compensatory mechanism rather than a pathophysiological marker per se., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Apart from tics, echopraxia or echophenomena (EP), i.e., automatic imitation of observed movements, are common in patients with Gilles de la Tourette syndrome (TS). The supplementary motor area (SMA) has been shown to be overactive before the onset of tics in these patients, and it is possible that this area might also play a key role in the generation of echopraxia. We wondered whether EP can also be evoked in healthy controls (HC) by modifying neural activity of this cortical region. To this end, we modulated activity of the SMA in 30 HC by repetitive transcranial magnetic stimulation (rTMS) in an attempt to induce EP. We used both 5 Hz (which can temporarily increase neural activity) and 1 Hz (which disrupts or reduces cortical activity) rTMS. Video clips were presented to 30 HC before and after stimulation. Each clip showed one single movement, either a tic of a TS patient or a spontaneous movement of a HC. During the whole presentation, participants were videotaped in order to detect EP. Video films of participants' responses were rated by two independent raters with respect to EP frequency. Our results reveal an increase of EP following 5 Hz stimulation but no effect following 1 Hz stimulation. This finding implies that the SMA is a relay mediating EP., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Cortico-muscular coherence (CMC) at beta frequency (13-30 Hz) occurs particularly during weak to moderate isometric contraction. It is a well-established measure of communication between the primary motor cortex (M1) and corresponding muscles revealing information about the integrity of the pyramidal system. Although the slowing of brain and muscle dynamics during healthy aging has been evidenced, functional communication as determined by CMC has not been investigated so far. Since decline of motor functions at higher age is likely to be associated with CMC changes, the present study aims at shedding light on the functionality of the motor system from a functional interaction perspective. To this end, CMC was investigated in 27 healthy subjects aging between 22 and 77 years during isometric contraction of their right forearm. Neuromagnetic activity was measured using whole-head magnetoencephalography (MEG). Muscle activity was measured by means of surface electromyography (EMG) of the right extensor digitorum communis (EDC) muscle. Additionally, MEG-EMG phase lags were calculated in order to estimate conducting time. The analysis revealed CMC and M1 power amplitudes to be increased with age accompanied by slowing of M1, EMG, and CMC. Frequency changes were particularly found in subjects aged above 40 years suggesting that at this middle age, neurophysiological changes occur, possibly reflecting an early neurophysiological marker of seniority. Since MEG-EMG phase lags did not vary with age, changes cannot be explained by alterations of nerve conduction. We argue that the M1 power amplitude increase and the shift towards lower frequencies might represent a neurophysiological marker of healthy aging which is possibly compensated by increased CMC amplitude.

Background: In Gilles de la Tourette syndrome (GTS) increased activation of the primary motor cortex (M1) before and during movement execution followed by increased inhibition after movement termination was reported. The present study aimed at investigating, whether this activation pattern is due to altered functional interaction between motor cortical areas., Methodology/principal Findings: 10 GTS-patients and 10 control subjects performed a self-paced finger movement task while neuromagnetic brain activity was recorded using Magnetoencephalography (MEG). Cerebro-cerebral coherence as a measure of functional interaction was calculated. During movement preparation and execution coherence between contralateral M1 and supplementary motor area (SMA) was significantly increased at beta-frequency in GTS-patients. After movement termination no significant differences between groups were evident., Conclusions/significance: The present data suggest that increased M1 activation in GTS-patients might be due to increased functional interaction between SMA and M1 most likely reflecting a pathophysiological marker of GTS. The data extend previous findings of motor-cortical alterations in GTS by showing that local activation changes are associated with alterations of functional networks between premotor and primary motor areas. Interestingly enough, alterations were evident during preparation and execution of voluntary movements, which implies a general theme of increased motor-cortical interaction in GTS.

Brain imaging has shown altered corpus callosum (CC) morphology in patients with Gilles de la Tourette syndrome (GTS). Yet it is unclear whether these morphological changes are associated with altered interhemispheric interactions. Here, we combined transcranial magnetic stimulation (TMS) with diffusion tensor magnetic resonance imaging (DTI) to explore functional and structural interhemispheric connections between the left and right motor hand areas. We studied 14 unmedicated GTS patients without psychiatric comorbidity (2 women, mean age 35.5 years) and 15 healthy volunteers (3 women, mean age 35 years). Left-to-right and right-to-left interhemispheric inhibitions (IHIs) were measured in hand muscles with TMS. In 13 GTS patients and all healthy controls, we measured fractional anisotropy (FA) with DTI to examine the relation between functional measures of interhemispheric connectivity as derived by TMS and structural properties of the CC region that carries fibers interconnecting both motor cortices. In GTS patients, left-to-right IHI was weaker than right-to-left IHI. Left-to-right IHI in GTS patients was also reduced compared with healthy controls. Voxel-based morphometric analysis revealed that FA in the motor region of the CC did not differ between groups. However, there was a significant interaction between groups and the relation between regional FA and left-to-right IHI in the motor region of the CC. A negative linear relation between FA and left-to-right IHI was present in control subjects but not in patients. Our combined TMS-DTI approach demonstrates abnormal functional interhemispheric connectivity in GTS accompanied by an altered structure-function relationship in the motor CC., (© 2010 Movement Disorder Society.)

In patients with Gilles de la Tourette syndrome (GTS) alterations of motor cortex (M1) excitability at rest have been evidenced. In contrast, there has so far been little research into changes of motor cortical reactivity during the time course of voluntary movements in GTS patients. The present study investigates neuromagnetic event-related desynchronization (ERD) and event-related synchronization (ERS) of bilateral M1 in 11 GTS patients and 11 healthy control subjects. ERD represents motor cortical activation, whereas ERS most likely indicates its inhibition. Subjects performed a self-paced finger movement task while magnetoencephalography was used to record neuromagnetic activity. In GTS patients, ERD at beta frequency was significantly increased in the contralateral hemisphere before and during movements, whereas ERS following movement termination was increased in M1 ipsilateral. Ipsilateral ERS was inversely correlated with tic severity as determined by the Yale Global Tic Severity Rating Scale. The data of the present study support the hypothesis that during voluntary movements, motor cortical reactivity is pathologically altered in GTS patients. The observed pattern of increased activation (ERD) prior to and during movement execution followed by increased inhibition (ERS) after movement termination at beta frequency suggests abnormally increased motor cortical activation, possibly driving stronger inhibition. The stronger this inhibition is, the better symptoms appear to be controlled., (© 2010 Movement Disorder Society.)

Movement execution strongly relies on precise sensorimotor synchronization. In a finger-tapping task that requires subjects to synchronize their finger taps to regular pacing signal synchronization accuracy varies with respect to pacing signal's modality. This study aimed at elucidating functional brain dynamics associated with modality specific behavioral synchronization accuracy. To this end, 10 right-handed subjects performed a finger-tapping task with respect to regular auditory and visual pacing, respectively, whereas neuromagnetic activity was recorded using a 122-channel whole-head neuromagnetometer. Visual pacing was associated with significantly reduced tap-to-pacer asynchrony and increased intertap variability as compared to auditory pacing. The brain dynamics associated with task execution were analyzed using the frequency domain beamformer approach dynamic imaging of coherent sources (DICS). Both tasks were shown to be associated with comparable networks. However, during visual pacing involvement of the ventral premotor cortex (PMv) was shown, whereas during auditory pacing the dorsal premotor cortex (PMd) was concerned with task execution. Synchronization with respect to visual pacing was associated with significantly increased functional interaction between thalamus and PMv at beta frequency as compared to functional interplay between thalamus and PMd during auditory pacing. Auditory synchronization was associated with increased functional interaction between left superior temporal gyrus and PMd at alpha frequency. Furthermore, functional interaction between thalamus and premotor cortex at beta frequency was significantly correlated with synchronization accuracy. All in all the present data suggest that modality specific synchronization differences are associated with frequency and connectivity specific changes of functional interaction in distinct brain networks., ((c) 2009 Wiley-Liss, Inc.)

It has been suggested that the left dorsolateral premotor cortex (dPMC) controls timing abilities of either hand. To further clarify its functional significance for movement timing, low-frequency repetitive transcranial magnetic stimulation (rTMS) was applied over the left and right dPMC, respectively, while subjects performed an auditorily paced finger-tapping task with each hand. rTMS over the left dPMC decreased tapping accuracy of both hands, whereas no behavioural effects occurred following right dPMC stimulation. To elucidate the time window in which left dPMC TMS disturbs synchronization abilities, pairs of TMS pulses were applied over the left dPMC and the left anterior parietal cortex serving as control condition. TMS pulses were applied randomly at 40 ms, 80 ms, 120 ms, 160 ms, 200 ms and 240 ms before pacer onset, as taps precede the pacing signal for about 20-60 ms. Again, the analysis revealed that TMS over the left dPMC disturbed synchronization abilities of either hand; however, this effect was shown at different times suggesting that the left dPMC affects the right M1 via at least one additional relay station. The present data support the hypothesis that the left dPMC is crucial for accurate timing of either hand. Additionally, they reveal a piece of evidence that the left dPMC affects the left hand not via a direct left dPMC-right M1 connection.

Human brain functions are heavily contingent on neural interactions both at the single neuron and the neural population or system level. Accumulating evidence from neurophysiological studies strongly suggests that coupling of oscillatory neural activity provides an important mechanism to establish neural interactions. With the availability of whole-head magnetoencephalography (MEG) macroscopic oscillatory activity can be measured non-invasively from the human brain with high temporal and spatial resolution. To localise, quantify and map oscillatory activity and interactions onto individual brain anatomy we have developed the 'dynamic imaging of coherent sources' (DICS) method which allows to identify and analyse cerebral oscillatory networks from MEG recordings. Using this approach we have characterized physiological and pathological oscillatory networks in the human sensorimotor system. Coherent 8 Hz oscillations emerge from a cerebello-thalamo-premotor-motor cortical network and exert an 8 Hz oscillatory drive on the spinal motor neurons which can be observed as a physiological tremulousness of the movement termed movement discontinuities. This network represents the neurophysiological substrate of a discrete mode of motor control. In parkinsonian resting tremor we have identified an extensive cerebral network consisting of primary motor and lateral premotor cortex, supplementary motor cortex, thalamus/basal ganglia, posterior parietal cortex and secondary somatosensory cortex, which are entrained in the tremor or twice the tremor rhythm. This low frequency entrapment of motor areas likely plays an important role in the pathophysiology of parkinsonian motor symptoms. Finally, studies on patients with postural tremor in hepatic encephalopathy revealed that this type of tremor results from a pathologically slow thalamocortical and cortico-muscular coupling during isometric hold tasks. In conclusion, the analysis of oscillatory cerebral networks provides new insights into physiological mechanisms of motor control and pathophysiological mechanisms of tremor disorders.

Background: Following an ischemic brain lesion, the affected cortex undergoes structural and functional changes that may lead to increased cortical excitability or decreased inhibitory neuronal activity, resulting in the occurrence of poststroke epileptic seizures in 6 to 10% of patients with stroke., Methods: To assess motor cortical excitability, transcranial magnetic stimulation (TMS) was used to determine the silent period (SP) duration in 84 consecutive patients with ischemic stroke., Results: In a subpopulation of six patients (38 to 72 years old) a significant decrease of the SP duration (mean 116 +/- 14 msec) was detected in either the arm or the leg on the affected side as compared to the corresponding unaffected limb (mean 231 +/- 32 msec). This electrophysiologic abnormality was clinically associated with focal motor seizures in five of the six patients, whereas none of the other 76 patients with normal or prolonged SP durations developed seizures or epilepsy., Conclusions: Silent period shortening in this group reflects decreased inhibitory activity that may partly be related to functional or structural impairment of GABAergic interneurons. TMS may be of value for determining patients with stroke at risk for developing poststroke seizures.

Hepatic encephalopathy (HE) is a common neurological manifestation of liver cirrhosis and is characterized by an increase of ammonia in the brain accompanied by a disrupted neurotransmitter balance, including the GABAergic and glutamatergic systems. The aim of this study is to investigate metabolic abnormalities in the cerebello-thalamo-cortical system of HE patients using GABA-edited MRS and links between metabolite levels, disease severity, critical flicker frequency (CFF), motor performance scores, and blood ammonia levels. GABA-edited MRS was performed in 35 participants (16 controls, 19 HE patients) on a clinical 3 T MRI system. MRS voxels were placed in the right cerebellum, left thalamus, and left motor cortex. Levels of GABA+ and of other metabolites of interest (glutamine, glutamate, myo-inositol, glutathione, total choline, total NAA, and total creatine) were assessed. Group differences in metabolite levels and associations with clinical metrics were tested. GABA+ levels were significantly increased in the cerebellum of patients with HE. GABA+ levels in the motor cortex were significantly decreased in HE patients, and correlated with the CFF (r = 0.73; p <.05) and motor performance scores (r = -0.65; p <.05). Well-established HE-typical metabolite patterns (increased glutamine, decreased myo-inositol and total choline) were confirmed in all three regions and were closely linked to clinical metrics. In summary, our findings provide further evidence for alterations in the GABAergic system in the cerebellum and motor cortex in HE. These changes were accompanied by characteristic patterns of osmolytes and oxidative stress markers in the cerebello-thalamo-cortical system. These metabolic disturbances are a likely contributor to HE motor symptoms in HE. In patients with hepatic encephalopathy, GABA+ levels in the cerebello-thalamo-cortical loop are significantly increased in the cerebellum and significantly decreased in the motor cortex. GABA+ levels in the motor cortex strongly correlate with critical flicker frequency (CFF) and motor performance score (pegboard test tPEG), but not blood ammonia levels (NH3). [ABSTRACT FROM AUTHOR]

Cortical facilitation assessed with triad conditioning transcranial magnetic stimulation has been termed triad-conditioned facilitation (TCF). TCF has been supposed to reflect increased intracortical facilitation (ICF) at short interstimulus intervals (ISI) around 10 ms and an intrinsic rhythm of the motor cortex at longer ISI around 25 ms. To gain further insight into the pathophysiological mechanism of TCF, we systematically studied the effect of suprathreshold conditioning stimulus (CS) and test stimulus (TS) intensity on TCF. Various CS intensities and TS intensities were used in a triad-conditioning paradigm that was applied to 11 healthy subjects. ISI between pulses were studied between 5 and 200 ms. TCF at 10 ms ISI enhanced with increasing CS intensity but decreased with increasing TS intensity. The duration of facilitation was longer with higher CS intensity. However, TCF at 25 ms ISI could not be elicited with none of the CS and TS intensities addressed here. Our results are consistent with the notion of TCF at short ISI reflecting ICF. The enhanced and prolonged facilitation with increase of CS without additional isolated facilitation at longer ISI suggest a prolongation of ICF. [ABSTRACT FROM AUTHOR]

The grounded cognition framework proposes that sensorimotor brain areas, which are typically involved in perception and action, also play a role in linguistic processing. We assessed oscillatory modulation during visual presentation of single verbs and localized cortical motor regions by means of isometric contraction of hand and foot muscles. Analogously to oscillatory activation patterns accompanying voluntary movements, we expected a somatotopically distributed suppression of beta and alpha frequencies in the motor cortex during processing of body-related action verbs. Magnetoencephalographic data were collected during presentation of verbs that express actions performed using the hands (H) or feet (F). Verbs denoting no bodily movement (N) were used as a control. Between 150 and 500 msec after visual word onset, beta rhythms were suppressed in H and F in comparison with N in the left hemisphere. Similarly, alpha oscillations showed left-lateralized power suppression in the H-N contrast, although at a later stage. The cortical oscillatory activity that typically occurs during voluntary movements is therefore found to somatotopically accompany the processing of body-related verbs. The combination of a localizer task with the oscillatory investigation applied to verb reading as in the present study provides further methodological possibilities of tracking language processing in the brain. [ABSTRACT FROM AUTHOR]

Gilles de la Tourette syndrome is a neuropsychiatric disorder characterized by an impaired ability to inhibit unwanted behaviour. Although the presence of chronic motor and vocal tics defines Tourette’s syndrome, other distinctive behavioural features like echo- and coprophenomena, and non-obscene socially inappropriate behaviour are also core features. We investigated neuronal activation during stimulus-driven execution and inhibition of prepared movements in Tourette’s syndrome. To this end, we performed event-related functional magnetic resonance imaging and structural diffusion tensor imaging in 15 moderately affected uncomplicated patients with ‘pure’ Tourette’s syndrome and 15 healthy control participants matched for age and gender. Subjects underwent functional magnetic resonance imaging during a Go/NoGo reaction time task. They had to withhold a prepared finger movement for a variable time until a stimulus instructed them to either execute (Go) or inhibit it (NoGo). Tics were monitored throughout the experiments, combining surface electromyogram, video recording, and clinical assessment in the scanner. Patients with Tourette’s syndrome had longer reaction times than healthy controls in Go trials and made more errors in total. Their functional brain activation was decreased in left primary motor cortex and secondary motor areas during movement execution (Go trials) but not during response inhibition (NoGo trials) compared with healthy control subjects. Volume of interest analysis demonstrated less task-related activation in patients with Tourette’s syndrome in primary and secondary motor cortex bilaterally, but not in the basal ganglia and cortical non-motor areas. They showed reduced co-activation between the left primary sensory-motor hand area and a network of contralateral sensory-motor areas and ipsilateral cerebellar regions. There were no between-group differences in structural connectivity of the left primary sensory-motor cortex as measured by diffusion tensor imaging-based probabilistic tractography. Our results link reduced sensory-motor cortical activation during movement execution to a decreased co-activation between the sensory-motor cortex and other brain areas involved in motor processing. These functional changes in patients with Tourette’s syndrome might result from adaptive reorganization in fronto-parietal brain networks engaged in motor and behavioural control, possibly triggered by abnormal processing and presumably overactivity in cortico-striato-cortical circuits. This might enable patients with Tourette’s syndrome to better suppress unwanted movements but comes at a price of behavioural deficits in other domains. [ABSTRACT FROM PUBLISHER]

Parkinson's disease (PD) is associated with pathologically altered oscillatory activity. While synchronized oscillations between 13 and 30 Hz are increased within a cortico-subcortical network, cortico-muscular coupling (CMC) is decreased. The present study aims at investigating the effect of non-invasive transcranial alternating current stimulation (tACS) of the primary motor cortex (M1) on motor symptoms and motor-cortical oscillations in PD. In 10 PD patients and 10 healthy control subjects, static isometric contraction, dynamic fast finger tapping, and diadochokinesia of the more severely affected hand were investigated prior to and shortly after tACS of the contralateral M1 at 10 Hz vs. 20 Hz vs. sham. During isometric contraction, neuromagnetic activity was recorded using magnetoencephalography. 20 Hz tACS attenuated beta band CMC during isometric contraction and amplitude variability during finger tapping in PD patients but not in healthy control subjects. 10 Hz tACS yielded no significant after-effects. The present data suggest that PD is associated with pathophysiological alterations which abet a higher responsiveness toward frequency-specific tACS - possibly due to pathologically altered motor-cortical oscillatory synchronization at frequencies between 13 and 30 Hz. [ABSTRACT FROM AUTHOR]

Synchronous oscillatory activity at alpha (8-12Hz), beta (13-30 Hz), and gamma (30-90 Hz) frequencies is assumed to play a key role for motor control. Corticomuscular coherence (CMC) represents an established measure of the pyramidal system's integrity. Transcranial alternating current stimulation (tACS) offers the possibility to modulate ongoing oscillatory activity. Behaviorally, 20Hz tACS in healthy subjects has been shown to result in movement slowing. However, the neurophysiological changes underlying these effects are not entirely understood yet. The present study aimed at ascertaining the effects of tACS at 10 and 20Hz in healthy subjects on CMC and local power of the primary sensorimotor cortex. Neuromagnetic activity was recorded during isometric contraction before and at two time points (2-10min and 30-38 min) after tACS of the left primary motor cortex (M1), using a 306 channel whole head magnetoencephalography (MEG) system. Additionally, electromyography (EMG) of the right extensor digitorum communis (EDC) muscle was measured. TACS was applied at 10 and 20 Hz, respectively, for 10 min at 1 mA. Sham stimulation served as control condition. The data suggest that 10Hz tACS significantly reduced low gamma band CMC during isometric contraction. This implies that tACS does not necessarily cause effects at stimulation frequency. Rather, the findings suggest cross-frequency interplay between alpha and low gamma band activity modulating functional interaction between motor cortex and muscle. [ABSTRACT FROM AUTHOR]

It has been suggested that a simple auditorily paced finger tapping task is associated with three tap-related neuromagnetic sources in the primary sensorimotor cortex contralateral to the tapping hand. Since a first source peaking at ~100 ms before tap-onset most likely represents activation of the primary motor cortex (M1) due to the motor command, a second source localized in the primary somatosensory cortex (S1) peaking around tap-onset could be due to kinesthetic feedback of the finger movement. A third source peaking at ~100 ms after tap-onset is also localized in the primary somatosensory cortex but inferior to the first S1 source (S1 inferior). The functional meaning of this source is still under debate. On the one hand it has been argued that S1 inferior represents the neuromagnetic correlate of tactile-kinesthetic feedback due to finger-taps and movements. On the other hand the functional meaning of this source could go beyond the sole processing of somatosensory feedback monitoring the temporal distance between tap and pacer (click) to keep the subject in time with the external event. This hypothesis is based on the observation that (1) S1 inferior seems to be coupled equally well to tap and click and (2) that this source might be triggered by the last event (i.show $132#e. tap or click). In the present study we re-examined this hypothesis by using a 122-channel whole-head neuromagnetometer. Eight healthy subjects synchronized their right index finger taps to an auditory pacing signal presented with a constant interstimulus interval of 800 ms. To test the hypothesis that the last event triggers S1 inferior we compared neuromagnetic activity following the tap as the first and the last event. In the auditorily paced finger tapping task usually the tap leads over the click (negative asynchrony). Therefore, the tap usually occurs as the first event. Since it has been shown that delivering additional feedback at the time of tap-onset results in a reduced negative asynchrony, in a second run auditory feedback was presented at tap-onset to enhance the number of positive asynchronies (i.show $132#e. the tap is the last event). Since no latency differences of S1 inferior associated with positive and negative asynchronies were found, results from the present study do not support the assumption that S1 inferior is triggered by the last event. Moreover, the amplitude of S1 inferior is significantly reduced following positive asynchronies as compared to negative asynchronies. Additionally, tap duration (i.show $132#e. the time between tap-onset and tap-offset) is significantly reduced while subjects produce positive asynchronies. Therefore, the amplitude of S1 inferior seems to be modulated by movement kinematics. This observation agrees well with the idea that activation of S1 is solely associated with the processing of somatosensory information. To conclude, our data contradict the hypothesis of an evaluation process localized in the primary somatosensory cortex and substantiate the idea that S1 inferior exclusively represents the processing of somatosensory feedback information. [ABSTRACT FROM AUTHOR]

Deep brain stimulation (DBS) is an established therapy to treat motor symptoms in movement disorders such as Parkinson's disease (PD). The mechanisms leading to the high therapeutic effectiveness of DBS are poorly understood so far, but modulation of oscillatory activity is likely to play an important role. Thus, investigating the effect of DBS on cortical oscillatory activity can help clarifying the neurophysiological mechanisms of DBS. Here, we aimed at scrutinizing changes of cortical oscillatory activity by DBS at different frequencies using magnetoencephalography (MEG). MEG data from 17 PD patients were acquired during DBS of the subthalamic nucleus (STN) the day after electrode implantation and before implanting the pulse generator. We stimulated the STN unilaterally at two different stimulation frequencies, 130 Hz and 340 Hz using an external stimulator. Data from six patients had to be discarded due to strong artefacts and two other datasets were excluded since these patients were not able to finalize the paradigm. After DBS artefact removal, power spectral density (PSD) values of MEG were calculated for each individual patient and averaged over the group. DBS at both 130 Hz and 340 Hz led to a widespread suppression of cortical alpha/beta band activity (8–22 Hz) specifically over bilateral sensorimotor cortices. No significant differences were observed between the two stimulation frequencies. Our finding of a widespread suppression of cortical alpha/beta band activity is particularly interesting as PD is associated with pathologically increased levels of beta band activity in the basal ganglia-thalamo-cortical circuit. Therefore, suppression of such oscillatory activity might be an essential effect of DBS for relieving motor symptoms in PD and can be achieved at different stimulation frequencies above 100 Hz. [ABSTRACT FROM AUTHOR]

The interaction of action-related language processing with actual movement is an indicator of the functional role of motor cortical involvement in language understanding. This paper describes two experiments using single action verb stimuli. Motor responses were performed with the hand or the foot. To test the double dissociation of language-motor facilitation effects within subjects, Experiments 1 and 2 used a priming procedure where both hand and foot reactions had to be performed in response to different geometrical shapes, which were preceded by action verbs. In Experiment 1, the semantics of the verbs could be ignored whereas Experiment 2 included semantic decisions. Only Experiment 2 revealed a clear double dissociation in reaction times: reactions were facilitated when preceded by verbs describing actions with the matching effector. In Experiment 1, by contrast, there was an interaction between verb-response congruence and a semantic variable related to motor features of the verbs. Thus, the double dissociation paradigm of semantic motor priming was effective, corroborating the role of the motor system in action-related language processing. Importantly, this effect was body part specific. [ABSTRACT FROM AUTHOR]