Primary Motor Cortex

Non-technical summary Calcium ions play crucial roles in many forms of synaptic plasticity at central nervous system level. We studied the effects of chronic and acute hypercalcaemia on synaptic plasticity in patients with primary hyperparathyroidism and healthy controls by applying over the primary motor cortex a non-invasive neurophysiological technique named repetitive transcranial magnetic stimulation (rTMS). Our results showed that conditions of hypercalcaemia decreased synaptic plasticity as tested by rTMS. Our results may help to understand the mechanisms underlying neuronal dysfunctions during hypercalcaemia and to evaluate asymptomatic patients.

Previous research suggests that meaning-laden gestures, even when produced in the absence of language (i.e., pantomimed gestures), influence lexical retrieval. Yet, little is known about the neural mechanisms that underlie this process. Based on embodied cognition theories, many studies have demonstrated motor cortex involvement in the representation of action verbs and in the understanding of actions. The present study aimed to investigate whether the motor system plays a critical role in the behavioral influence of pantomimed gestures on action naming. Continuous theta burst stimulation (cTBS) was applied over the hand area of the left primary motor cortex and to a control site (occipital cortex). An action-picture naming task followed cTBS. In the naming task, participants named action pictures that were preceded by videos of congruent pantomimed gestures, unrelated pantomimed gestures or a control video with no movement (as a neutral, non-gestural condition). In addition to behavioral measures of performance, cTBS-induced changes in corticospinal activity were assessed. We replicated previous finding that exposure to congruent pantomimed gestures facilitates word production, compared to unrelated or neutral primes. However, we found no evidence that the left primary motor area is crucially involved in the mechanism underlying behavioral facilitation effects of gesture on verb production. Although, at the group level, cTBS induced motor cortex suppression, at the individual level we found remarkable variability of cTBS effects on the motor cortex. We found cTBS induction of both inhibition of corticospinal activity (with slower behavioral of responses) and enhancement (with faster behavioral responses). Our findings cast doubt on assumptions that the motor cortex is causally involved in the impact of gestures on action-word processing. Our results also highlight the importance of careful consideration of interindividual variability for the interpretation of cTBS effects.

OBJECTIVE-To determine how inter-hemispheric balance in stroke, measured using transcranial magnetic stimulation (TMS), relates to balance defined using neuroimaging (functional magnetic resonance (fMRI) and diffusion tensor imaging (DTI)), and how these metrics of balance are associated with clinical measures of upper limb function and disability. PARTICIPANTS-Ten chronic stroke patients (63±9 years) in a population based sample with unilateral upper-limb paresis.

To determine how inter-hemispheric balance in stroke, measured using transcranial magnetic stimulation (TMS), relates to balance defined using neuroimaging (functional magnetic resonance (fMRI) and diffusion tensor imaging (DTI)), and how these metrics of balance are associated with clinical measures of upper limb function and disability. Cross-Sectional SETTING: Clinical Research Laboratory PARTICIPANTS: Ten chronic stroke patients (63±9 years) in a population based sample with unilateral upper-limb paresis. Not applicable MAIN OUTCOME MEASURES: Inter-hemispheric balance was measured with TMS, fMRI and DTI. TMS defined inter-hemispheric differences in recruitment of corticospinal output, the size of the corticomotor output maps and the degree of mutual transcallosal inhibition they exerted upon one another. fMRI studied whether cortical activation during the movement of the paretic hand was lateralized to the ipsilesional or to the contralesional primary motor (M1), premotor (PMC) ...

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

Previous brain imaging studies suggest that stroke alters functional connectivity in motor execution networks. Moreover, current understanding of brain plasticity has led to new approaches in stroke rehabilitation. Recent studies showed a significant role of effective coupling of neuronal activity in the SMA (supplementary motor area) and M1 (primary motor cortex) network for motor outcome in patients after stroke. After a subcortical stroke, functional magnetic resonance imaging (fMRI) during movement reveals cortical reorganization that is associated with the recovery of function. The aim of the present study was to explore connectivity alterations within the motor-related areas combining motor fMRI with a novel MR-compatible hand-induced robotic device (MR_CHIROD) training. Patients completed training at home and underwent serial MR evaluation at baseline and after 8 weeks of training. Training at home consisted of squeezing a gel exercise ball with the paretic hand at ~75% of maximum strength for 1 h/day, 3 days/week. The fMRI analysis revealed alterations in M1, SMA, PMC (premotor cortex) and Cer (cerebellum) in both stroke patients and healthy controls after the training. Findings of the present study suggest that enhancement of SMA activity could benefit M1 dysfunction in stroke survivors. These results also indicate that connectivity alterations between motor areas might assist the counterbalance of a functionally abnormal M1 in chronic stroke survivors and possibly other patients with motor dysfunction.

The current work addresses the development of cognitive abilities in artificial organisms, a topic that has attracted many research efforts recently. In our approach, neural network- based agent structures are employed to represent distinct brain areas. We introduce a Hierarchical Collaborative CoEvolutionary (HCCE) approach to design autonomous, yet cooperating agents. Thus, partial brain models consisting of many substructures can be designed. Replication of lesion studies is used as a means to increase reliability of brain model, highlighting the distinct roles of agents. The HCCE is appropriately designed to support systematic modelling of brain structures, able to reproduce biological lesion data. The proposed approach designs cooperating agents properly, by considering the desired pre-and post-lesion performance of the model. The effectiveness of the proposed approach is illustrated on the design of a computational model of Primary Motor cortex and Premotor cortex interactions in the mammalian brain. The model is successfully tested in driving a simulated robot, with different pre-and post-lesion performance.

Accurate presurgical mapping of motor, speech, and language cortices, while crucial for neurosurgical planning and minimizing post-operative functional deficits, is challenging in young children with neurological disease. In such children, both invasive (cortical stimulation mapping) and non-invasive functional mapping imaging methods (MEG, fMRI) have limited success, often leading to delayed surgery or adverse post-surgical outcomes. We therefore examined the clinical utility of transcranial magnetic stimulation (TMS) in young children who require functional mapping. In a retrospective chart review of TMS studies performed on children with refractory epilepsy or a brain tumor, at our institution, we identified 47 mapping sessions in 36 children 3 years of age or younger, in whom upper and lower extremity motor mapping was attempted; and 13 children 5–6 years old in whom language mapping, using a naming paradigm, was attempted. The primary hand motor cortex was identified in at leas...

Objectives We investigated sex differences and the influence of brain-derived neurotrophic factor (BDNF) in the descending pain modulatory system (DPMS), as measured by change on the numerical pain scale (NPS; 0–10) during conditioned pain modulation (CPM task; primary outcome) and by function of the corticospinal motor pathway and heat pain thresholds (HPTs; secondary outcomes). Methods This cross-sectional study included healthy volunteers ranging in age from 18 to 45 years (32 male and 24 female). Assessment included serum BDNF, HPT, change on the NPS (0–10) during the CPM task, and motor-evoked potential (MEP) using transcranial magnetic stimulation (TMS). Results The MEP (Mv) amplitude was larger in male participants compared with female participants (mean [SE] = 1.55 [0.34] vs mean [SE] = 1.27 [0.27], respectively, P = 0.001). The mean NPS (0–10) during CPM task changed more substantially for female compared with male participants (mean [SE] = −3.25 [2.01] vs mean [SE] = −2.29...

Amputees can move their phantom limb at will. These 'movements without movements' have generally been considered as motor imagery rather than motor execution, but amputees can in fact perform both executed and imagined movements with their phantom and they report distinct perceptions during each task. Behavioural evidence for this dual ability comes from the fact that executed movements are associated with stump muscle contractions whereas imagined movements are not, and that phantom executed movements are slower than intact hand executed movements whereas the speed of imagined movements is identical for both hands. Since neither execution nor imagination produces any visible movement, we hypothesized that the perceptual difference between these two motor tasks relies on the activation of distinct cerebral networks. Using functional magnetic resonance imaging and changes in functional connectivity (dynamic causal modelling), we examined the activity associated with imagined and executed movements of the intact and phantom hands of 14 upper-limb amputees. Distinct but partially overlapping cerebral networks were active during both executed and imagined phantom limb movements (both performed at the same speed). A region of interest analysis revealed a 'switch' between execution and imagination; during execution there was more activity in the primary somatosensory cortex, the primary motor cortex and the anterior lobe of the cerebellum, while during imagination there was more activity in the parietal and occipital lobes, and the posterior lobe of the cerebellum. In overlapping areas, task-related differences were detected in the location of activation peaks. The dynamic causal modelling analysis further confirmed the presence of a clear neurophysiological distinction between imagination and execution, as motor imagery and motor execution had opposite effects on the supplementary motor area-primary motor cortex network. This is the first imaging evidence that the neurophysiological network activated during phantom limb movements is similar to that of executed movements of intact limbs and differs from the phantom limb imagination network. The dual ability of amputees to execute and imagine movements of their phantom limb and the fact that these two tasks activate distinct

Transcranial direct current stimulation (tDCS) is a form of non-invasive brain stimulation that safely modulates brain excitability and has therapeutic potential for many conditions. Several studies have shown that anodal tDCS of the primary motor cortex (M1) facilitates motor learning and plasticity, but there is little information about the underlying mechanisms. Using magnetic resonance spectroscopy (MRS), it has been shown that tDCS can affect local levels of γ-aminobutyric acid (GABA) and Glx (a measure of glutamate and glutamine combined) in adults, both of which are known to be associated with skill acquisition and plasticity; however this has yet to be studied in children and adolescents. This study examined GABA and Glx in response to conventional anodal tDCS (a-tDCS) and high definition tDCS (HD-tDCS) targeting the M1 in a pediatric population. Twenty-four typically developing, right-handed children ages 12-18 years participated in five consecutive days of tDCS interventio...

Short interval intracortical inhibition (SICI) is a biomarker for altered motor inhibition in schizophrenia, but the manner in which distant sites influence the inhibitory cortical-effector response remains elusive. Our study investigated local and long-distance resting state functional connectivity (rsFC) markers of SICI in a sample of N = 23 patients with schizophrenia and N = 29 controls. Local functional connectivity was quantified using regional homogeneity (ReHo) analysis and long-range connectivity was estimated using seed-based rsFC analysis. Direct and indirect effects of connectivity measures on SICI were modeled using mediation analysis. Higher SICI ratios (indicating reduced inhibition) in patients were associated with lower ReHo in the right insula. Follow-up rsFC analyses showed that higher SICI scores (indicating reduced inhibition) were associated with reduced connectivity between right insula and hubs of the corticospinal pathway: sensorimotor cortex and basal ganglia. Mediation analysis supported a model in which the direct effect of local insular connectivity strength on SICI is mediated by the interhemispheric connectivity between insula and left sensorimotor cortex. The broader clinical implications of these findings are discussed with emphasis on how these preliminary findings might inform novel interventions designed to restore or improve SICI in schizophrenia and deepen our understanding of motor inhibitory control and impact of abnormal signaling in motor-inhibitory pathways in schizophrenia.

Introduction. Earlier studies have shown that brain stimulation by means of repetitive Transcranial Magnetic Stimulation (rTMS) over the primary motor cortex can decrease the motor impairments in Parkinson's disease (PD). The present study focused on the clinical relevance of rTMS in the treatment of PD. Method. Thirteen PD patients received a minimum of 10 sessions of 2,000 pulses 5 Hz rTMS over the hand and leg area over the primary motor cortex, with a stimulation intensity of 120% of the motor threshold. In our analysis an effect could be considered as clinically relevant if the quality of life (QoL) improved with 30% or more. Results. Paired-sample t-tests revealed a significant improvement of Unified Parkinson's Disease Rating Scale score, walking speed, and mood. A minority of the patients (38%) who underwent rTMS showed an improvement in QoL of greater than 30%. The improvements on QoL correlated significantly to scores of motor improvements on the Unified Parkinson's Disease Rating Scale but not to improvements in mood as assessed by the Geriatric Depression Scale. The use of rTMS did not demonstrate any effects on tremor, freezing of gait, and activities of daily life, and rTMS had no effect on the stage of disease. It mainly improved rigidity, finger and hand movements, and leg agility. Conclusion. This study shows that although there can be significant group effects of rTMS on PD symptoms, these significant effects do not automatically imply that these are clinically relevant. Therefore we advise that future studies in the field of neuromodulation (rTMS, neurofeedback, etc.) also focus more on the clinical relevance of the treatment under investigation rather than only report ''significant group differences.''

A peripherally generated afferent volley that arrives at the peak negative (PN) phase during the movement related cortical potential (MRCP) induces significant plasticity at the cortical level in healthy individuals and chronic stroke patients. Transferring this type of associative brain-computer interface (BCI) intervention into the clinical setting requires that the proprioceptive input is comparable to the techniques implemented during the rehabilitation process. These consist mainly of functional electrical stimulation (FES) and passive movement induced by an actuated orthosis. In this study, we compared these two interventions (BCI FES and BCI passive ) where the afferent input was timed to arrive at the motor cortex during the PN of the MRCP. Twelve healthy participants attended two experimental sessions. They were asked to perform 30 dorsiflexion movements timed to a cue while continuous electroencephalographic (EEG) data were collected from FP1, Fz, FC1, FC2, C3, Cz, C4, CP1, CP2, and Pz, according to the standard international 10-20 system. MRCPs were extracted and the PN time calculated. Next, participants were asked to imagine the same movement 30 times while either FES (frequency: 20 Hz, intensity: 8-35 mAmp) or a passive ankle movement (amplitude and velocity matched to a normal gait cycle) was applied such that the first afferent inflow would coincide with the PN of the MRCP. The change in the output of the primary motor cortex (M1) was quantified by applying single transcranial magnetic stimuli to the area of M1 controlling the tibialis anterior (TA) muscle and measuring the motor evoked potential (MEP). Spinal changes were assessed pre and post by eliciting the TA stretch reflex. Both BCI FES and BCI passive led to significant increases in the excitability of the cortical projections to TA (F (2,22) = 4.44, p = 0.024) without any concomitant changes at the spinal level. These effects were still present 30 minutes after the cessation of both interventions. There was no significant main effect of intervention, F (1,11) = 0.38, p = 0.550, indicating that the changes in MEP occurred independently of the type of afferent inflow. An afferent volley generated from a passive movement or an electrical stimulus arrives at the somatosensory cortex at similar times. It is thus likely that the similar effects observed here are strictly due to the tight coupling in time between the afferent inflow and the PN of the MRCP. This provides further support to the associative nature of the proposed BCI system.

A peripherally generated afferent volley that arrives at the peak negative (PN) phase during the movement related cortical potential (MRCP) induces significant plasticity at the cortical level in healthy individuals and chronic stroke patients. Transferring this type of associative brain-computer interface (BCI) intervention into the clinical setting requires that the proprioceptive input is comparable to the techniques implemented during the rehabilitation process. These consist mainly of functional electrical stimulation (FES) and passive movement induced by an actuated orthosis. In this study, we compared these two interventions (BCI FES and BCI passive ) where the afferent input was timed to arrive at the motor cortex during the PN of the MRCP. Twelve healthy participants attended two experimental sessions. They were asked to perform 30 dorsiflexion movements timed to a cue while continuous electroencephalographic (EEG) data were collected from FP1, Fz, FC1, FC2, C3, Cz, C4, CP1, CP2, and Pz, according to the standard international 10-20 system. MRCPs were extracted and the PN time calculated. Next, participants were asked to imagine the same movement 30 times while either FES (frequency: 20 Hz, intensity: 8-35 mAmp) or a passive ankle movement (amplitude and velocity matched to a normal gait cycle) was applied such that the first afferent inflow would coincide with the PN of the MRCP. The change in the output of the primary motor cortex (M1) was quantified by applying single transcranial magnetic stimuli to the area of M1 controlling the tibialis anterior (TA) muscle and measuring the motor evoked potential (MEP). Spinal changes were assessed pre and post by eliciting the TA stretch reflex. Both BCI FES and BCI passive led to significant increases in the excitability of the cortical projections to TA (F (2,22) = 4.44, p = 0.024) without any concomitant changes at the spinal level. These effects were still present 30 minutes after the cessation of both interventions. There was no significant main effect of intervention, F (1,11) = 0.38, p = 0.550, indicating that the changes in MEP occurred independently of the type of afferent inflow. An afferent volley generated from a passive movement or an electrical stimulus arrives at the somatosensory cortex at similar times. It is thus likely that the similar effects observed here are strictly due to the tight coupling in time between the afferent inflow and the PN of the MRCP. This provides further support to the associative nature of the proposed BCI system.

The paper argues for an embodied and enactive view of linguistic concepts as a solution to the „scaling up” problem, namely the transition from embodied experience to symbolic and abstract thought. Drawing on phenomenology, neurobiology, conceptual metaphor theory and enactivism, it aims to demonstrate the constitutive role of the body and intersubjectivity in concept formation. Concrete con¬cepts (“chair”, “table”, etc.) emerge from sensorimotor interactions with the environment which are transformed into simulated actions, while abstract concepts—such as “space”, “time”, “truth”, and others—arise both through metaphorical extensions of bodily experience and participatory sense-making in social contexts. Neurobiological findings support this view, showing strong connections between language processing, sensorimotor and social brain systems, and tracing language evolution to exaptation or reuse of motor coordination areas.

Phenomenological analysis then highlights how bodily or operative intentionality underlies grammatical structures, and how concepts retain their roots in action and interaction even when ab¬stracted. As examples, the study explores container schemas as the embodied basis of categoriza¬tion and analyzes the bodily origins of space, time, causality, and moral concepts. In sum, concepts are not free-floating symbols but remain anchored in corporeal and intersubjective experience, thus integrating embodiment, language, and culture. Human reason proves to be not disembodied, but fundamentally rooted in embodied interaction and intersubjective practice.

Research investigating age-related differences in intracortical inhibition acting within the primary motor cortex (M1) reports inconsistent results. Age-related changes in the balance of inhibition and facilitation acting within M1 might underlie the inconsistent findings. Here, paired-pulse TMS was used to examine the balance between short-interval intracortical inhibition (SICI) and short-interval intracortical facilitation (SICF) in younger (n=26) and older (n=21) adults. First, the inter-stimulus intervals (ISIs) that produced maximal and minimal SICF at the first peak and trough were identified for each individual. Second, SICI stimulus-response functions (conditioning stimulus (CS): 50-110% resting motor threshold) were determined at ISIs that produced maximal and minimal facilitation for each individual. When SICI was measured with the ISI that produced maximal facilitation, the shift from net inhibition to net facilitation occurred at a lower CS intensity in older than younger adults. When SICI was measured with the ISI that produced minimal facilitation, older adults showed a persistent net inhibition at the highest CS intensity, whereas younger adults showed a shift from net inhibition to net facilitation at high CS intensities. Relationships between SICI and SICF and manual dexterity were evident across all measures of the inhibitionfacilitation balance, whereby a balance favouring inhibition is associated with better manual dexterity and a balance favouring facilitation is associated with poorer manual dexterity. These findings contribute to our understanding of age-related differences in intracortical inhibitory and facilitatory processes, as well as highlight the importance of considering the balance between inhibitory and facilitatory processes when measuring SICI and SICF.

Static magnetic fields (SMFs) are known to alter neural activity, but evidence of their ability to modify learning-related neuroplasticity is lacking. The present study tested the hypothesis that application of static magnetic stimulation (SMS), an SMF applied transcranially via a neodymium magnet, over the primary motor cortex (M1) would alter learning of a serial reaction time task (SRTT). Thirty-nine participants took part in two experimental sessions separated by 24 h where they had to learn the SRTT with their right hand. During the first session, two groups received SMS either over contralateral (i.e., left) or ipsilateral (i.e., right) M1 while a third group received sham stimulation. SMS was not applied during the second session. Results of the first session showed that application of SMS over contralateral M1 impaired online learning as compared to both ipsilateral and sham groups, which did not differ. Results further revealed that application of SMS did not impair offline...

Upon exposure to a new sensorimotor relationship, motor behaviors iteratively change early in adaptation but eventually stabilize as adaptation proceeds. Behavioral work suggests that motor memory consolidation is initiated upon the attainment of asymptotic levels of performance. Separate lines of evidence point to a critical role of the primary motor cortex (M1) in consolidation. However, a causal relationship between M1 activity during asymptote and consolidation has yet to be demonstrated. The present study investigated this issue in male and female participants using single-pulse transcranial magnetic stimulation (TMS) to interfere with postmovement activity in M1 in two behavioral phases of a ramp-and-hold visuomotor adaptation paradigm. TMS was either provided after each trial of the ramp phase of adaptation when a gradual increase in the visuomotor rotation caused movements to be changing, or after each trial of the hold phase of adaptation when the rotation was held constant and movements tended to stabilize. Consolidation was assessed by measuring performance on the same task 24 h later. Results revealed that TMS did not influence adaptation to the new visuomotor relationship in either condition. Critically, however, TMS disruption of M1 activity selectively impaired consolidation of motor memories when it was provided during the hold phase of adaptation. This effect did not take place when TMS was delivered over adjacent dorsal premotor cortex or when motor behaviors in late adaptation were prevented from plateauing. Together, these data suggest that the impaired consolidation stemmed from interference with mechanisms of repetition-dependent plasticity in M1.

: The present thesis seeks to provide insights into the contribution of the two major learning mechanisms driving motor memory consolidation in the primary motor cortex (M1): repetition-dependent and reward-based learning mechanisms. However, because evidence remains scarce on this last learning mechanism, the study of the neural manifestation of reward processing in motor areas was investigated. More specifically, the first scientific contribution presented in this thesis sought to address the contribution of repetition-dependent mechanisms to motor memory consolidation in M1. As such, the first project used single-pulse transcranial magnetic stimulation (TMS) to interfere with M1 activity as participants executed newly learned motor behaviors during a performance asymptote. Results revealed that motor memory formation in M1 was initiated when behaviors were repeating, suggesting that repetition-dependent mechanisms contributed to retention in M1. The second scientific contribution...

Upon exposure to a new sensorimotor relationship, motor behaviors iteratively change early in adaptation but eventually stabilize as adaptation proceeds. Behavioral work suggests that motor memory consolidation is initiated upon the attainment of asymptotic levels of performance. Separate lines of evidence point to a critical role of the primary motor cortex (M1) in consolidation. However, a causal relationship between M1 activity during asymptote and consolidation has yet to be demonstrated. The present study investigated this issue in male and female participants using single-pulse transcranial magnetic stimulation (TMS) to interfere with postmovement activity in M1 in two behavioral phases of a ramp-and-hold visuomotor adaptation paradigm. TMS was either provided after each trial of the ramp phase of adaptation when a gradual increase in the visuomotor rotation caused movements to be changing, or after each trial of the hold phase of adaptation when the rotation was held constant...

Static magnetic fields (SMFs) are known to alter neural activity, but evidence of their ability to modify learning-related neuroplasticity is lacking. The present study tested the hypothesis that application of static magnetic stimulation (SMS), an SMF applied transcranially via a neodymium magnet, over the primary motor cortex (M1) would alter learning of a serial reaction time task (SRTT). Thirty-nine participants took part in two experimental sessions separated by 24 h where they had to learn the SRTT with their right hand. During the first session, two groups received SMS either over contralateral (i.e., left) or ipsilateral (i.e., right) M1 while a third group received sham stimulation. SMS was not applied during the second session. Results of the first session showed that application of SMS over contralateral M1 impaired online learning as compared to both ipsilateral and sham groups, which did not differ. Results further revealed that application of SMS did not impair offline...

Introduction: Epileptic conditions are characterized by impaired cortical excitation/inhibition balance and interneuronal disinhibition. Transcranial magnetic stimulation (TMS) is a neurophysiological method that assesses brain excitation/inhibition. Area covered: This review was written after a detailed search in PubMed, EMBASE, ISI web of science, SciELO, Scopus, and Cochrane Controlled Trials databases from 1990 to 2020. It summarizes TMS applications for diagnostic and therapeutic purposes in epilepsy. TMS studies help to distinguish different epilepsy conditions and explore the antiepileptic drugs' (AEDs') effects on neuronal microcircuits and plasticity mechanisms. Repetitive TMS studies showed that low-frequency rTMS (0.33-1 Hz) can reduce seizures' frequency in refractory epilepsy or pause ongoing seizures; however, there is no current approval for its use in such patients as adjunctive treatment to AEDs. Expert opinion: There are variable and conflicting TMS results which reflect the distinct pathogenic mechanisms of each epilepsy condition, the dynamic epileptogenic process over the long disease course resulting in the development of recurrent spontaneous seizures and/or progression of epilepsy after it is established, and the differential effect of AEDs on cortical excitability. Future epilepsy research should focus on combined TMS/functional connectivity studies that explore the complex cortical excitability circuits and networks using different TMS parameters and techniques.

Objective: To evaluate therapeutic potential of different montages of transcranial direct current stimulation (tDCS) in Parkinson\ue2\u80\u99s Disease (PD) patients with asymmetric motor symptoms. Materials and Methods: Fourteen patients with asymmetric PD underwent, while on treatment, seven separate sessions including electrophysiological and clinical evaluation at baseline and after anodal, cathodal and sham tDCS of the primary motor cortex (M1) of the two hemispheres. Changes in motor cortical excitability were evaluated by transcranial magnetic stimulation (TMS). Effects on motor symptoms were assessed by testing finger tapping (FT) and upper limb bradykinesia, and by using the Italian validated Movement Disorder Society revision of the Unified PD Rating Scale (MDS-UPDRS). Results: Only anodal tDCS of the more-affected M1 (contralateral to the more-affected body side) and cathodal tDCS of the less-affected M1 (contralateral to the less-affected body side) were able to induce si...

ABSTRACTTheta burst stimulation (TBS) is a form of repetitive transcranial magnetic stimulation designed to induce changes of cortical excitability that outlast the period of TBS application. In this study, we explored the effects of continuous TBS (cTBS) and intermittent TBS (iTBS) versus sham TBS stimulation, applied to the primary motor cortex, on modulation of resting state electroencephalography (rsEEG) power. We first conducted hypothesis-driven region-of-interest (ROI) analyses examining changes in alpha (8-12 Hz) and beta (13-21 Hz) bands over the left and right motor cortex. Additionally, we performed data-driven whole-brain analyses across a wide range of frequencies (1-50 Hz) and all electrodes. Finally, we assessed the reliability of TBS effects across two sessions approximately 1 month apart. None of the protocols produced significant group-level effects in the ROI. Whole-brain analysis revealed that cTBS significantly enhanced relative power between 19-43 Hz over multi...

In chronic obstructive pulmonary disease (COPD), the diaphragm may contribute to respiratory decompensation. The aim of this study was to investigate the function of central neural diaphragmatic pathways in mild and moderate grades of COPD (Gold I/II) and its related factors. This study included 20 COPD patients (mean age: 52.80±3.30 years) and 20 matched healthy subjects. All were tested by applying transcranial magnetic stimulation (TMS) of the diaphragmatic motor cortex area and cervical magnetic stimulation (CMS) of the phrenic nerve roots in the neck. Diaphragmatic resting motor threshold (DRMT), cortical motor evoked potential latency (CMEPL), cortical MEP amplitude (CMEPA), peripheral motor evoked potential latency (PMEPL) and amplitude (PMEPA), were recorded from both sides. Central motor conduction time (CMCT) was estimated as follow: CMCT = CMEPL-PMEPL. Compared to controls, patients had increase in CMEPL and CMCT (P<0.0001), while DRMT was decreased (P<0.0001). Among patients, 9 (45%) had delayed CMEPL, 6 (30%) had lower CMEPA, 3 (15%) had delayed PMEPL, 5 (25%) had lower PMEPA, 9 (75%) had prolonged CMCT and 11 (55%) had reduced DRMT. Significant correlations were identified between CMEPA and FVC% (r=0.326,P<0.038), FEV 1 % (r=0.563,P<0.0001) and FEV 1 %/FVC% (r=0.710,P<0.0001); between CMEPL and FEV 1 % (r=-0.368,P<0.020), FEV 1 %/FVC% (r =-0.463,P<0.003) and between CMCT and FVC% (r=-0.316,P<0.047), FEV 1 % (r=-0.397,P<0.011), FVV 1 /FVC % (r=-0.395, P<0.012) and between DRMT and CMCT (r =-0.337,P<0.034). This study indicates that central impairment (corticospinal dysfunction) occurs early in stable COPD.

Objective: We determined whether the primary motor hand area was most frequently located in the precentral gyrus in young patients with intractable focal seizures. Methods: Sixty-five patients with focal seizures aged between 5 months and 20 years who underwent a two-stage epilepsy surgery using chronic subdural-EEG monitoring were studied. Pairs of subdural electrodes were electrically stimulated, and the brain region with contralateral hand movement induced by the lowest-intense stimulus was defined as the primary motor hand area. Results: Contralateral hand movement was induced without afterdischarges in 50 children but not in the remaining 15 children. The unpaired t-test revealed that failure to induce contralateral hand motor movement was associated with younger age of subjects. Among the 50 patients with a positive motor response, the primary motor hand area was confined to the precentral gyrus in 9 patients, confined to the postcentral gyrus in 24, and located in both the pre-and post-central gyri in the remaining 17. The McNemar's test revealed that the observed frequency of 24 patients showing the primary motor hand area confined to the postcentral gyrus was larger than chance frequency. Logistic regression analysis failed to demonstrate that the observation of the primary motor hand area confined to the postcentral gyrus was associated with the age, the presence of dysplastic lesion or the seizure onset involving the frontal lobe. Our study failed to support the traditionally-accepted notion that the primary motor hand area is most frequently located in the precentral gyrus but rather demonstrated that a substantial proportion of young patients had the primary motor hand area in the postcentral gyrus.

Disruption of the function of the primary motor cortex (M1) is thought to play a critical role in motor dysfunction in Parkinson’s disease (PD). Detailed information regarding the specific aspects of M1 circuits that become abnormal is lacking. We recorded single units and local field potentials (LFPs) of M1 neurons in unilateral 6-hydroxydopamine (6-OHDA) lesion rats and control rats to assess the impact of dopamine (DA) cell loss during rest and a forelimb reaching task. Our results indicated that M1 neurons can be classified into two groups (putative pyramidal neurons and putative interneurons) and that 6-OHDA could modify the activity of different M1 subpopulations to a large extent. Reduced activation of putative pyramidal neurons during inattentive rest and reaching was observed. In addition, 6-OHDA intoxication was associated with an increase in certain LFP frequencies, especially those in the beta range (broadly defined here as any frequency between 12 and 35 Hz), which beco...

Introduction: Epileptic conditions are characterized by impaired cortical excitation/inhibition balance and interneuronal disinhibition. Transcranial magnetic stimulation (TMS) is a neurophysiological method that assesses brain excitation/inhibition. Area covered: This review was written after a detailed search in PubMed, EMBASE, ISI web of science, SciELO, Scopus, and Cochrane Controlled Trials databases from 1990 to 2020. It summarizes TMS applications for diagnostic and therapeutic purposes in epilepsy. TMS studies help to distinguish different epilepsy conditions and explore the antiepileptic drugs' (AEDs') effects on neuronal microcircuits and plasticity mechanisms. Repetitive TMS studies showed that low-frequency rTMS (0.33-1 Hz) can reduce seizures' frequency in refractory epilepsy or pause ongoing seizures; however, there is no current approval for its use in such patients as adjunctive treatment to AEDs. Expert opinion: There are variable and conflicting TMS results which reflect the distinct pathogenic mechanisms of each epilepsy condition, the dynamic epileptogenic process over the long disease course resulting in the development of recurrent spontaneous seizures and/or progression of epilepsy after it is established, and the differential effect of AEDs on cortical excitability. Future epilepsy research should focus on combined TMS/functional connectivity studies that explore the complex cortical excitability circuits and networks using different TMS parameters and techniques.

The present topical review deals with the motor control of facial expressions in humans. Facial expressions are a central part of human communication. Emotional face expressions have a crucial role in human non-verbal behavior, allowing a rapid transfer of information between individuals. Facial expressions can be both voluntarily or emotionally controlled. Recent studies in non-human primates and humans revealed that the motor control of facial expressions has a distributed neural representation. At least 5 cortical regions on the medial and lateral aspects of each hemisphere are involved: the primary motor cortex, the ventral lateral premotor cortex, the supplementary motor area on the medial wall, and, finally, the rostral and caudal cingulate cortex. The results of studies in humans and non-human primates suggest that the innervation of the face is bilaterally controlled for the upper part, and mainly contralaterally controlled for the lower part. Furthermore, the primary motor cortex, the ventral lateral premotor cortex, and the supplementary motor area are essential for the voluntary control of facial expressions. In contrast, the cingulate cortical areas are important for emotional expression, since they receive input from different structures of the limbic system.

ABSTRACTThe present Review deals with the motor control of facial expressions in humans. Facial expressions are a central part of human communication. Emotional face expressions have a crucial role in human nonverbal behavior, allowing a rapid transfer of information between individuals. Facial expressions can be either voluntarily or emotionally controlled. Recent studies in nonhuman primates and humans have revealed that the motor control of facial expressions has a distributed neural representation. At least five cortical regions on the medial and lateral aspects of each hemisphere are involved: the primary motor cortex, the ventral lateral premotor cortex, the supplementary motor area on the medial wall, and the rostral and caudal cingulate cortex. The results of studies in humans and nonhuman primates suggest that the innervation of the face is bilaterally controlled for the upper part and mainly contralaterally controlled for the lower part. Furthermore, the primary motor cort...

Regional brain glucose utilisation was investigated with positron emission tomography (PET) and fluorodeoxyglucose (FDG) in four siblings with neuronal ceroid-lipofuscinosis. A consistent pattern was found, namely a decrease of glucose utilisation in all grey structures but more marked at the level of the thalamus and posterior association cortex. The severity of metabolic anomalies was correlated with the degree of clinical impairment and with disease duration; they were the most severe in the oldest patient, who was also the most affected clinically, intermediate in two others, and minimal in the subject with the shortest period of development of the disease. These observations suggest that PET is useful for the definition of anatomical targets of metabolic diseases and for the investigation of their pathophysiology.

Summary Upper-limb movements are often composed of regular submovements, and neural correlates of submovement frequencies between 1 and 4 Hz have been found in the motor cortex. The temporal profile of movements is usually assumed to be determined by extrinsic factors such as limb biomechanics and feedback delays, but another possibility is that an intrinsic rhythmicity contributes to low frequencies in behavior. We used multielectrode recordings in monkeys performing an isometric movement task to reveal cyclic activity in primary motor cortex locked to submovements, and a distinct oscillation in premotor cortex. During ketamine sedation and natural sleep, cortical activity traversed similar cycles and became synchronized across areas. Because the same cortical dynamics are coupled to submovements and also observed in the absence of behavior, we conclude that the motor networks controlling the upper limb exhibit an intrinsic periodicity at submovement frequencies that is reflected i...

Every movement ends in a period of stillness. In current models of reaching, the commands that hold the arm still at a target, depend on the spatial location of the target, but not on the reach commands that moved the arm to the target. Contrary to this assumption, in a series of tasks in humans and non-human primates, we find that the commands that hold the arm still have a consistent mathematical relationship to the reach commands that moved the arm. With damage to the corticospinal tract, reach commands become impaired as expected, but remarkably, the mathematical dependence of hold commands upon the now imperfect reach commands remains intact. Therefore, we find that the brain uses a design principle in which its holding controller is not driven by the spatial location of the target. Rather, holding is obtained via mathematical integration of moving, potentially through a subcortical structure.

High-resolution functional magnetic resonance imaging of healthy volunteers was used to study the functional anatomy of the human primary motor (M1) and somatosensory (S1) cortical hand representations during simple movements of thumb, little finger and wrist and a sequential movement of the middle three fingers. Rest served as a control state. The results demonstrated an orderly somatotopy in both M1 and S1, even though the cortical areas active with individual movements significantly overlapped. Moreover, the activation patterns in M1 and S1 differed in three aspects: (i) S1 activation was distributed into significantly more clusters than M1 and the primary cluster was smaller; (ii) the overlaps of areas active with different movements were significantly larger in M1 than in S1; (iii) the difference between the three-finger sequential movement and the single-finger movements was more pronounced in S1 than in M1. The sequence-activated S1 cortex was distributed into significantly m...

Restoration of motor function following stroke involves reorganization of motor output through intact pathways, with compensatory brain activity likely variable by task. One class of motor tasks, those involved in self-care, is particularly important in stroke rehabilitation. Identifying the brain areas that are engaged in self-care and how they reorganize after stroke may enable development of more effective rehabilitation strategies. We piloted a paradigm for functional MRI assessment of self-care activity. In two groups, young adults and older adults, two self-care tasks (buttoning and zipping) produce activation similar to a bimanual tapping task, with bilateral activation of primary and secondary motor cortices, primary sensory cortex, and cerebellum. Quantitative differences include more activation of sensorimotor cortex and cerebellum in buttoning than bimanual tapping. Pilot subjects with stroke showed greater superior parietal activity across tasks than controls, potentiall...

Background: Motor function impairment occurs in approximately two-thirds of patients with subcortical stroke. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique for modulating cortical excitability. Objectives: The present study was designed for assessing the efficacy of highfrequency rTMS (5 Hz) on ipsilesional primary motor cortex in patients with subcortical stroke. Materials and Methods: Thirty participants who had subcortical stroke in the previous four weeks to four months were enrolled in this randomized double blinded clinical trial. Participants were divided into experimental and control groups and their motor ability of both upper and lower extremities were assessed using Fugl-Meyer assessment of motor recovery after stroke (FMA) before and after intervention. The study intervention rTMS (5 Hz) was administered in six 10-minute sessions on the ipsilesional primary motor cortex in the experimental group and on the vertex in the control group. Results: Mean change in FMA score after rTMS sessions was significantly higher in the experimental group than in the control group (p = 0.00). Mean time interval between the stroke and rTMS intervention had a weak and insignificant (ρ = 0.097; p = 0.61) correlation with changes of FMA score. Conclusions: High-frequency (5 Hz) rTMS effectively improved motor function in patients with subcortical stroke.

To understand how the information derived from different motor cortical areas representing different body parts is organized in the basal ganglia, we examined the neuronal responses in the subthalamic nucleus (STN), and the external (GPe) and internal (GPi) segments of the globus pallidus (input, relay and output nuclei, respectively) to stimulation of the orofacial, forelimb and hindlimb regions of the primary motor cortex (MI) and supplementary motor area (SMA) in macaque monkeys under the awake state. Most STN and GPe/GPi neurons responded exclusively to stimulation of either the MI or SMA, and one-fourth to one-third of neurons responded to both. STN neurons responding to the hindlimb, forelimb and orofacial regions of the MI were located along the medial-lateral axis in the posterolateral STN, while neurons responding to the orofacial region of the SMA were located more medially than the others in the anteromedial STN. GPe/GPi neurons responding to the hindlimb, forelimb and orofacial regions of the MI were found along the dorsal-ventral axis in the posterolateral GPe/GPi, and neurons responding to the corresponding regions of the SMA were similarly but less clearly distributed in more anteromedial regions. Moreover, neurons responding to the distal and proximal forelimb MI regions were found along the lateral-medial axis in the STN and the ventral-dorsal axis in the GPe/GPi. Most STN and GPe/GPi neurons showed kinaesthetic responses with similar somatotopic maps. These observations suggest that the somatotopically organized inputs from the MI and SMA are well preserved in the STN and GPe/GPi with partial convergence.

The subthalamic nucleus (STN) is an effective neurosurgical target to improve motor symptoms in Parkinson's Disease (PD) patients. MR-guided Focused Ultrasound (MRgFUS) subthalamotomy is being explored as a therapeutic alternative to Deep Brain Stimulation (DBS) of the STN. The hyperdirect pathway provides a direct connection between the cortex and the STN and is likely to play a key role in the therapeutic effects of MRgFUS intervention in PD patients.This study aims to investigate the topography and somatotopy of hyperdirect pathway projections from the primary motor cortex (M1).We used advanced multi-fiber tractography and high-resolution diffusion MRI data acquired on five subjects of the Human Connectome Project (HCP) to reconstruct hyperdirect pathway projections from M1. Two neuroanatomy experts reviewed the anatomical accuracy of the tracts. We extracted the fascicles arising from the trunk, arm, hand, face and tongue area from the reconstructed pathways. We assessed the var...

Inhibitory transcranial magnetic stimulation, of which continuous theta burst stimulation (cTBS) is a common form, has been used to inhibit cortical areas during investigations of their function. cTBS applied to the primary motor area (M1) depresses motor output excitability via a local effect and impairs procedural motor learning. This could be due to an effect on M1 itself and/or to changes in its connectivity with other nodes in the learning network. To investigate this issue, we used functional magnetic resonance imaging to measure changes in brain activation and connectivity during implicit procedural learning after real and sham cTBS of M1. Compared to sham, real cTBS impaired motor sequence learning, but caused no local or distant changes in brain activation. Rather, it reduced functional connectivity between motor (M1, dorsal premotor & supplementary motor areas) and visual (superior & inferior occipital gyri) areas. It also increased connectivity between frontal associative (superior & inferior frontal gyri), cingulate (dorsal & middle cingulate), and temporal areas. This potentially compensatory shift in coupling, from a motor-based learning network to an associative learning network accounts for the behavioral effects of cTBS of M1. The findings suggest that the inhibitory transcranial magnetic stimulation

Handwriting is an advanced motor skill and one of the key developments in human culture. Here we show that handwriting can be decoded-offline and onlinefrom electromyographic (EMG) signals recorded from multiple hand and forearm muscles. We convert EMGs into continuous handwriting traces and into discretely decoded font characters. For this purpose, we use Wiener and Kalman filters, and machine learning algorithms. Our approach is applicable to clinical neural prostheses for restoration of dexterous hand movements, and to medical diagnostics of neural disorders that affect handwriting. We also propose that handwriting could be decoded from cortical activity, such as the activity recorded with electrocorticography (ECoG). The development of bioelectric interfaces holds significant promise for both clinical and consumer applications . Although handwriting is one of the essential motor skills, it has received relatively little attention from the developers of both brain-computer and myoelectric interfaces. This is because the major focus of the