EEG and TMS-EEG studies on the cortical excitability and plasticity associated with human motor control and learning

Motor adaptation relies on error-based learning for accurate movements in changing environments. However, the neurophysiological mechanisms driving individual differences in performance are unclear. Transcranial magnetic stimulation (TMS)-evoked potential can provide a direct measure of cortical excitability. To investigate cortical excitability as a predictor of motor learning and motor adaptation in a robot-mediated forcefield. A group of 15 right-handed healthy participants (mean age 23 years) performed a robot-mediated forcefield perturbation task. There were two conditions: unperturbed non-adaptation and perturbed adaptation. TMS was applied in the resting state at baseline and following motor adaptation over the contralateral primary motor cortex (left M1). Electroencephalographic (EEG) activity was continuously recorded, and cortical excitability was measured by TMS-evoked potential (TEP). Motor learning was quantified by the motor learning index. Larger error-related negativity (ERN) in fronto-central regions was associated with improved motor performance as measured by a reduction in trajectory errors. Baseline TEP N100 peak amplitude predicted motor learning (P=0.005), which was significantly attenuated relative to baseline (P=0.0018) following motor adaptation. ERN reflected the formation of a predictive internal model adapted to the forcefield perturbation. Attenuation in TEP N100 amplitude reflected an increase in cortical excitability with motor adaptation reflecting neuroplastic changes in the sensorimotor cortex. TEP N100 is a potential biomarker for predicting the outcome in robot-mediated therapy and a mechanism to investigate psychomotor abnormalities in depression.

Disruption of a cortical region can paradoxically improve behavior. After unilateral damage to the primary motor cortex (M1), increased excitability of the unaffected M1 has been shown. The M1 plays a critical role in motor performance and also early aspects of motor skill learning. Repetitive transcranial magnetic stimulation (rTMS) of one motor cortex can lead a temporary reduction in cortical excitability. We hypothesize that unilateral suppression of one M1 by rTMS may increase excitability of the unaffected motor cortex and thus improve motor performance and motor skill learning with the ipsilateral hand by releasing the contralateral motor cortex from transcallosal inhibition. Forty healthy volunteers participated in our study; 16 for the experiment I and 24 for the experiment II. In the experiment I, after practicing a sequential simple key-pressing task with the index finger, their motor performance was monitored before and after slow-frequency (1Hz) rTMS, applied on the M1 ipsilateral or contralateral to the hand, ipsilateral premotor area or vertex (Cz). In the experiment II, participants were randomly divided into three stimulation groups: i) ipsilateral M1; ii) contralateral M1; and iii) Cz. rTMS was applied before the initiation of practice and learning of a simple motor skill. Mean execution time and error rate were recorded in 4 sessions distributed over 2 days. In experiment I: rTMS of M1 shortened execution time of the motor task with the ipsilateral hand, without affecting performance with the contralateral hand. This effect outlasted rTMS by at least 10 min, and was most prominent for M1 stimulation. In experiment II, disruption of M1 with rTMS slowed down skill acquisition with the contralateral hand, but paradoxically accelerated learning with the ipsilateral hand. This effect was evident during the first of 2 days of practice in the group with rTMS over the ipsilateral M1 compared to the other two groups (Cz and contralateral M1). Our results support the notion of an interhemispheric competition, and demonstrate the utility of rTMS to explore the functional facilitation of the un-stimulated counterpart M1 with effects on motor execution and learning, which may have implications for neurorehabilitation.

The Ipsilateral Human Motor Cortex Can Functionally Compensate for Acute Contralateral Motor Cortex Dysfunction

Co-activation of homo- and heterotopic representations in the primary motor cortex (M1) ipsilateral to a unilateral motor task has been observed in neuroimaging studies. Further analysis showed that the ipsilateral M1 is involved in motor execution along with the contralateral M1 in humans. Additionally, transcranial magnetic stimulation (TMS) studies have revealed that the size of the co-activation in the ipsilateral M1 has a muscle-dominant effect in the upper limbs, with a prominent decline of inhibition within the ipsilateral M1 occurring when a homologous muscle contracts. However, the homologous muscle-dominant effect in the ipsilateral M1 is less clear in the lower limbs. The present study investigates the response of corticospinal output and intracortical inhibition in the leg representation of the ipsilateral M1 during a unilateral motor task, with homo- or heterogeneous muscles. We assessed functional changes within the ipsilateral M1 and in corticospinal outputs associated with different contracting muscles in 15 right-handed healthy subjects. Motor tasks were performed with the right-side limb, including movements of the upper and lower limbs. TMS paradigms were measured, consisting of short-interval intracortical inhibition (SICI) and recruitment curves (RCs) of motor evoked potentials (MEPs) in the right M1, and responses were recorded from the left rectus femoris (RF) and left tibialis anterior (TA) muscles. TMS results showed that significant declines in SICI and prominent increases in MEPs of the left TA and left RF during unilateral movements. Cortical activations were associated with the muscles contracting during the movements. The present data demonstrate that activation of the ipsilateral M1 on leg representation could be increased during unilateral movement. However, no homologous muscle-dominant effect was evident in the leg muscles. The results may reflect that functional coupling of bilateral leg muscles is a reciprocal movement.

P 81. Effects of motor cortical quadripulse transcranial magnetic stimulation (QPS) on the contralateral primary motor cortex

Functional imaging and behavioral studies suggest involvement of the ipsilateral hemisphere in hand movements, particularly of the left hand. If this is so, transient disturbance of the motor cortex (M1) with repetitive transcranial magnetic stimulation (rTMS) may affect ipsilateral motor sequences, and the effects may differ on the two sides. We studied 15 right-handed subjects who played a simple and a complex piano sequence for 8 seconds each. Two seconds after the beginning of each sequence, rTMS was delivered to the ipsilateral or contralateral M1, or directed away from the head (control trial). Ipsilateral M1 stimulation on either side induced timing errors in both sequences, and with the complex sequence induced more timing errors in the left hand than in the right hand. Errors of the right hand with both sequences occurred in the stimulation period only, but errors of the left hand with the complex sequence occurred in both the stimulation and poststimulation periods. We conclude that the ipsilateral M1 is involved in fine finger movements. The left hemisphere plays a greater role in timing ipsilateral complex sequences than the right hemisphere and may be more involved in the processing of complex motor programs.

The main aim of this thesis was to explore the neural and behavioural responses underpinning upper-limb motor control in a novel (force-field) robot-mediated reaching task using a non-invasive brain stimulation method known as transcranial magnetic stimulation (TMS). A new TMS-based network mapping technique was used to target different regions of the motor circuit (i.e. network nodes) using a ‘virtual disruption’ approach. Seven cortical regions including the left and right primary motor cortex (M1), the supplementary motor area (SMA), the left and right posterior parietal cortex (PPC) and the left and right dorsal pre-motor cortex (PMC) were targeted with TMS at nine different time points during the preparation phase of upper-limb reaching towards a north-west target (i.e. reaching away from the body). Both neural mechanisms (corticospinal excitability with left M1 stimulation) and kinematic (behavioural) responses such as, movement onset, movement offset, maximum velocity, movement duration, summed error (reaching errors quantified by the calculating the difference between the subject’s reaching trajectory and the ideal reaching trajectory) and maximum force were explored offline. When exploring the impact of TMS on each cortical region individually, the results demonstrated a behavioural effect on reaching responses because 1) TMS caused a significant disruption in reaching trajectories during motor adaptation compared to normal reaching (no force-field) at most time points and 2) TMS caused a significant delay in movement onset, particularly during motor adaptation. As well as exploring the effect of TMS on each region separately, it was important to determine the network of regions that may play a more functional role in novel reaching. Therefore a comparative analysis was performed between all stimulated regions for each kinematic parameter. The comparative analysis revealed a region specific relative influence on summed error. More specifically, the left M1 and left PPC were the principle structures that were involved in novel reaching because TMS to these structures resulted in significantly greater reaching trajectory errors. Based on this finding, it can be concluded that the left M1 and left PPC play a pivotal role in the preparation phase of upper-limb novel reaching compared to other regions in the motor network, including the right M1, SMA, left and right dPMC and right PPC. Overall, the findings from this project can not only help 1) refine our understanding of the mechanistic elements that operate during reaching and 2) gain an insight into the functional role of the different regions that are involved in novel reaching, but they also have a wide range of applications, ranging from brain machine interfaces (BMI) to neurocomputational models where data-based virtual lesions have been introduced into models of stroke patients.

The authors applied transcranial magnetic stimulation (TMS) to investigate the causal role of the primary motor cortex (M1) for the contextual-interference effect in motor learning. Previous work using a nonfocal TMS coil suggested a casual role for M1 during high-interference practice conditions, but this hypothesis has not yet been proven. In the 1st experiment, participants practiced 3 rapid elbow flexion–extension tasks in either a blocked or random order, with learning assessed by a delayed retention test. TMS was delivered immediately after feedback during practice using a circular coil, centered over the contralateral M1. Each participant practiced with 1 of 3 TMS conditions: no TMS, real TMS, or sham TMS. Although no significant differences were observed between groups during acquisition, retention of the random group was better than the blocked group. The learning benefits of random practice were attenuated in the real-TMS condition, but not in the sham-TMS or no-TMS conditions. In the 2nd experiment, the authors studied the effects of suprathreshold TMS and subthreshold TMS over M1, lateral premotor cortex, and peripheral arm stimulation using a focal figure-8 coil on motor learning under random practice conditions. The authors found that only suprathreshold TMS on M1 produced significant disruption of retention compared to the other stimulation conditions. Results suggest that a high-threshold neuronal population within M1 is causally important for enhanced retention following random, but not block, practice. Results also support the early intertrial interval as a critical period of M1 activity during practice. Overall, these results suggest neural circuits within M1 contribute to motor learning processing that depends on learners’ training experience. Results contribute to knowledge of the critical and specific role that M1 plays in generating a learning advantage following high-interference practice conditions.

BackgroundNon-invasive neuromodulation is an emerging therapy for children with early brain injury but is difficult to apply to preschoolers when windows of developmental plasticity are optimal. Transcranial static magnetic field stimulation (tSMS) decreases primary motor cortex (M1) excitability in adults but effects on the developing brain are unstudied.Objective/HypothesisWe aimed to determine the effects of tSMS on cortical excitability and motor learning in healthy children. We hypothesized that tSMS over right M1 would reduce cortical excitability and inhibit contralateral motor learning.MethodsThis randomized, sham-controlled, double-blinded, three-arm, cross-over trial enrolled 24 healthy children aged 10–18 years. Transcranial Magnetic Stimulation (TMS) assessed cortical excitability via motor-evoked potential (MEP) amplitude and paired pulse measures. Motor learning was assessed via the Purdue Pegboard Test (PPT). A tSMS magnet (677 Newtons) or sham was held over left or right M1 for 30 min while participants trained the non-dominant hand. A linear mixed effect model was used to examine intervention effects.ResultsAll 72 tSMS sessions were well tolerated without serious adverse effects. Neither cortical excitability as measured by MEPs nor paired-pulse intracortical neurophysiology was altered by tSMS. Possible behavioral effects included contralateral tSMS inhibiting early motor learning (p < 0.01) and ipsilateral tSMS facilitating later stages of motor learning (p < 0.01) in the trained non-dominant hand.ConclusiontSMS is feasible in pediatric populations. Unlike adults, tSMS did not produce measurable changes in MEP amplitude. Possible effects of M1 tSMS on motor learning require further study. Our findings support further exploration of tSMS neuromodulation in young children with cerebral palsy.

BackgroundRepeated transcranial magnetic stimulation (rTMS) could induce alterations in cortical excitability and promote neuroplasticity. To precisely quantify these effects, functional near-infrared spectroscopy (fNIRS), an optical neuroimaging modality adept at detecting changes in cortical hemodynamic responses, has been employed concurrently alongside rTMS to measure and tailor the impact of diverse rTMS protocols on the brain cortex.ObjectiveThis systematic review and meta-analysis aimed to elucidate the effects of rTMS on cortical hemodynamic responses over the primary motor cortex (M1) as detected by fNIRS.MethodsOriginal articles that utilized rTMS to stimulate the M1 cortex in combination with fNIRS for the assessment of cortical activity were systematically searched across the PubMed, Embase, and Scopus databases. The search encompassed records from the inception of these databases up until April, 2024. The assessment for risk of bias was also conducted. A meta-analysis was also conducted in studies with extractable raw data.ResultsAmong 312 studies, 14 articles were eligible for qualitative review. 7 studies were eligible for meta-analysis. A variety of rTMS protocols was employed on M1 cortex. In inhibitory rTMS, multiple studies observed a reduction in the concentration of oxygenated hemoglobin [HbO] at the ipsilateral M1, contrasted by an elevation at the contralateral M1. Meta-analysis also corroborated this consistent trend. Nevertheless, certain investigations unveiled diminished [HbO] in bilateral M1. Several studies also depicted intricate inhibitory or excitatory interplay among distinct cortical regions.ConclusionDiverse rTMS protocols led to varied patterns of cortical activity detected by fNIRS. Meta-analysis revealed a trend of increasing [HbO] in the contralateral cortices and decreasing [HbO] in the ipsilateral cortices following low frequency inhibitory rTMS. However, due to the heterogeneity between studies, further research is necessary to comprehensively understand rTMS-induced alterations in brain activity.

Ipsilateral M1 transcranial direct current stimulation increases excitability of the contralateral M1 during an active motor task: Implications for stroke rehabilitation

BackgroundRecently, it was shown that the highly variable after-effect of continuous theta-burst stimulation (cTBS) of the primary motor cortex (M1) can be predicted by the latency of motor-evoked potentials (MEPs) recorded before cTBS. This suggests that at least part of this inter-individual variability is driven by differences in the neuronal populations preferentially activated by transcranial magnetic stimulation (TMS).MethodsHere, we recorded MEPs, TMS-evoked brain potentials (TEPs) and somatosensory-evoked potentials (SEPs) to investigate the effects of cTBS delivered over the primary sensorimotor cortex on both the ipsilateral and contralateral M1, and the ipsilateral and contralateral primary somatosensory cortex (S1).ResultsWe confirm that the after-effects of cTBS can be predicted by the latency of MEPs recorded before cTBS. Over the hemisphere onto which cTBS was delivered, short-latency MEPs at baseline were associated with an increase of MEP magnitude (i.e. an excitatory effect of cTBS) whereas late-latency MEPs were associated with reduced MEPs (i.e. an inhibitory effect of cTBS). This relationship was reversed over the contralateral hemisphere, indicating opposite effects of cTBS on the responsiveness of the ipsilateral and contralateral M1. Baseline MEP latencies also predicted changes in the magnitude of the N100 wave of TEPs elicited by stimulation of the ipsilateral and contralateral hemisphere, indicating that this TEP component is specifically dependent on the state of M1. Finally, there was a reverse relationship between MEP latency and the effects of cTBS on the SEP waveforms (50–130 ms), indicating that after-effects of cTBS on S1 are opposite to those on M1.ConclusionTaken together, our results confirm that the variable after-effects of cTBS can be explained by differences in the neuronal populations activated by TMS. Furthermore, our results show that this variability also determines remote effects of cTBS in S1 and the contralateral hemisphere, compatible with inter-hemispheric and sensorimotor interactions.

Transcranial magnetic stimulation

Cerebro-muscular and cerebro-cerebral coherence in patients with pre- and perinatally acquired unilateral brain lesions

Background. Training-related improvements in motor function are associated with changes in movement representation of the primary motor cortex (M1). In healthy individuals, transcranial magnetic stimulation (TMS) of M1 delivered in a strict temporal relationship (Hebbian-type stimulation) during execution of movements enhances these effects and is superior to random stimulation. Objective. The authors tested whether training combined with Hebbian-type M1 stimulation enhances M1 reorganization in patients with stroke. Methods. Six patients with chronic stroke participated in the study. Patients executed robot-assisted wrist extension movements at 0.2 Hz frequency while subthreshold repetitive TMS was applied over M1 in a strict temporal relationship to the training movements. TMS was applied to either the affected hemisphere (contralateral M1) or the nonaffected hemisphere (ipsilateral M1) at 0.1 Hz. Intervention-related changes in motor maps and intracortical excitability were measured using TMS. Results. Training alone or combined Hebbian-type stimulation of either M1 resulted in differential effects on motor maps and intracortical inhibition. Shifts in motor maps were associated with increases in intracortical excitability. In contrast to previous results for healthy participants, the inhibitory effect of ipsilateral M1 Hebbian-type stimulation was not present, and the facilitatory effect of contralateral M1 stimulation was more subtle. Conclusions. Hebbian-type stimulation is feasible in patients poststroke and induces map reorganization and associated decreases in GABAergic inhibition. However, because TMS protocols have a different effect on motor reorganization in the injured brain and may depend on location of the lesion, protocols need to be tailored to the patient’s pathology.