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A vast body of research suggests that the primary motor cortex is involved in motor imagery. This raises the issue of inhibition: how is it possible for motor imagery not to lead to motor execution? Bach et al. (Psychol Res Psychol Forschung. 10.1007/s00426-022-01773-w, 2022, this issue) suggest that the motor execution threshold may be "upregulated" during motor imagery to prevent execution. Alternatively, it has been proposed that, in parallel to excitatory mechanisms, inhibitory mechanisms may be actively suppressing motor output during motor imagery. These theories are verbal in nature, with well-known limitations. Here, we describe a toy-model of the inhibitory mechanisms thought to be at play during motor imagery to start disentangling predictions from competing hypotheses., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Swiftly halting ongoing motor actions is essential to react to unforeseen and potentially perilous circumstances. However, the neural bases subtending the complex interplay between emotions and motor control have been scarcely investigated. Here, we used an emotional stop signal task (SST) to investigate whether specific neural circuits engaged by action suppression are differently modulated by emotional signals with respect to neutral ones. Participants performed an SST before and after the administration of one session of repetitive transcranial magnetic stimulation (rTMS) over the pre-supplementary motor cortex (pre-SMA), the right inferior frontal gyrus (rIFG), and the left primary motor cortex (lM1). Results show that rTMS over the pre-SMA improved the ability to inhibit prepotent action (i.e., better action control) when emotional stimuli were presented. In contrast, action control in a neutral context was fostered by rTMS over the rIFG. No changes were observed after lM1 stimulation. Intriguingly, individuals with higher impulsivity traits exhibited enhanced motor control when facing neutral stimuli following rIFG stimulation. These results further our understanding of the interplay between emotions and motor functions, shedding light on the selective modulation of neural pathways underpinning these processes., (© 2024 The Author(s). Annals of the New York Academy of Sciences published by Wiley Periodicals LLC on behalf of The New York Academy of Sciences.)

Transcranial magnetic stimulation (TMS) is a non-invasive method to assess neurophysiology of the primary motor cortex in humans. Dystonia is a poorly understood neurological movement disorder, often presenting in an idiopathic, isolated form across different parts of the body. The neurophysiological profile of isolated dystonia compared to healthy adults remains unclear. We conducted a systematic review with meta-analysis of neurophysiologic TMS measures in people with isolated dystonia to provide a synthesized understanding of cortical neurophysiology associated with isolated dystonia. We performed a systematic database search and data were extracted independently by the two authors. Separate meta-analyses were performed for TMS measures of: motor threshold, corticomotor excitability, short interval intracortical inhibition, cortical silent period, intracortical facilitation and afferent-induced inhibition. Standardized mean differences were calculated using a random effects model to determine overall effect sizes and confidence intervals. Heterogeneity was explored using dystonia type subgroup analysis. The search resulted in 78 studies meeting inclusion criteria, of these 57 studies reported data in participants with focal hand dystonia, cervical dystonia, blepharospasm or spasmodic dysphonia, and were included in at least one meta-analysis. The cortical silent period, short-interval intracortical inhibition and afferent-induced inhibition was found to be reduced in isolated dystonia compared to controls. Reduced GABAergic-mediated inhibition in the primary motor cortex in idiopathic isolated dystonia's suggest interventions targeted to aberrant cortical disinhibition could provide a novel treatment. Future meta-analyses require neurophysiology studies to use homogeneous cohorts of isolated dystonia participants, publish raw data values, and record electromyographic responses from dystonic musculature where possible., (© 2020 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Huntington's disease (HD) mouse models suggest that cardiovascular exercise may enhance neuroplasticity and delay disease signs, however, the effects of exercise on neuroplasticity in people with HD are unknown. Using a repeated-measures experimental design, we compared the effects of a single bout of high-intensity exercise, moderate-intensity exercise, or rest, on motor cortex synaptic plasticity in 14 HD CAG-expanded participants (9 premanifest and 5 early manifest) and 20 CAG-healthy control participants, using transcranial magnetic stimulation. Measures of cortico-motor excitability, short-interval intracortical inhibition and intracortical facilitation were obtained before and after a 20-min bout of either high-intensity interval exercise, moderate-intensity continuous exercise, or rest, and again after intermittent theta burst stimulation (iTBS). HD participants showed less inhibition at baseline compared to controls. Whereas the control group showed increased excitability and facilitation following high-intensity exercise and iTBS, the HD group showed no differences in neuroplasticity responses following either exercise intensity or rest, with follow-up Bayesian analyses providing consistent evidence that these effects were absent in the HD group. These findings indicate that exercise-induced synaptic plasticity mechanisms in response to acute exercise may be attenuated in HD, and demonstrate the need for future research to further investigate exercise and plasticity mechanisms in people with HD., (© 2022. The Author(s).)

Neuroplasticity underpins motor learning, with abnormal neuroplasticity related to age-associated motor declines. Bilateral transfer of motor learning, through rehabilitation, may mitigate these declines; however, the magnitude of transfer may be reduced in older populations. This study investigated excitatory and inhibitory pathways in the trained and untrained hemispheres following unilateral training of a complex finger-tapping task across ageing. Fifteen young (26.2 ± 3.8 years) and 11 older adults (63.7 ± 15.4 years) received transcranial magnetic stimulation, although surface electromyography was recorded from the extensor digitorum communis (EDC) and abductor pollicis brevis (APB), before and after practicing a complex finger-tapping task with the dominant hand. Excitability, inhibition (expressed as percent change scores from pre- to post-training), motor task performance and bilateral transfer were assessed between groups. Investigation of hemispheric differences within each group was completed for measures that significantly differed between groups. There were no between-group differences in task performance or bilateral transfer, with task performance improving post-training irrespective of group for both hands (p < 0.05). Pre- to post-inhibition change scores of the untrained EDC muscle increased (p = 0.034) in older compared with younger adults, indicating reduced inhibition in older adults. Inhibition change scores significantly differed between hemispheres for the young group only (p = 0.037). Only the younger group presented with hemispheric lateralisation, providing some support for the Hemispheric Asymmetry Reduction in OLDer adults (HAROLD) hypothesis. Whether this reduction is evidence of de-differentiation or compensation will need to be confirmed with additional measures., (© 2021 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

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.

Key Points: We explored the large variability in motor skill acquisition-related effects on the primary and sensory cortices. Namely, we tested whether this variability depends on interindividual variance or the type of motor task investigated. We compared different motor-learning tasks, i.e. model-free vs. model-based learning tasks, and their possible differential effects on the primary motor and sensory cortices by using transcranial magnetic stimulation techniques. The model-free learning task induced an increase in corticospinal excitability and a reduction in the amplitude of somatosensory-evoked potentials. Conversely, the model-based learning tasks induced a decrease in intracortical inhibition. No correlations were found between neurophysiological changes and motor performance, indicating that this differential modulation may be secondary to the motor skill acquisition. The study results suggest differential motor skill acquisition-related effects on cortical parameters, possibly due to the engagement of specific neurophysiological substrates., Abstract: A large variability in learning-related neurophysiological changes in the primary motor and sensory cortices has been observed. It is unclear whether these differential effects are due to the different tasks investigated or to interindividual variance. Only a few studies have assessed different motor-learning tasks and their effects on neurophysiological features within the same group of participants, and several issues are unclear. Here, we compared the effects of different tasks within each individual. We investigated the effects on motor and sensory cortex parameters after a model-free learning task, i.e. a ballistic motor task, compared with model-based learning tasks, i.e. visuomotor-learning tasks. Motor- and sensory-evoked potentials, intracortical excitability as assessed by short-interval intracortical inhibition, and sensorimotor interaction, i.e. short-latency afferent inhibition, were recorded from 15 healthy subjects before and after the tasks. The ballistic motor task induced an increase in corticospinal excitability but did not change motor cortex intracortical inhibition or sensorimotor integration. In addition, it decreased the amplitude of cortical components of the somatosensory-evoked potentials. The visuomotor-learning tasks induced a reduction in motor cortex intracortical inhibition but did not modulate corticospinal and sensory cortex excitability or sensorimotor integration. This differential modulation is likely to be secondary to the motor skill acquisition, since no correlation was observed between neurophysiological changes and motor performance. Our results demonstrate differential motor skill acquisition-related effects on cortical parameters, possibly reflecting the engagement of specific neurophysiological substrates, and contribute in-depth knowledge of the mechanisms involved in different types of motor skill acquisition in humans., (© 2020 The Authors. The Journal of Physiology © 2020 The Physiological Society.)

Because compensatory changes in brain activity underlie functional recovery after brain damage, monitoring of these changes will help to improve rehabilitation effectiveness. Functional near-infrared spectroscopy (fNIRS) has the potential to measure brain activity in freely moving subjects. We recently established a macaque model of internal capsule infarcts and an fNIRS system for use in the monkey brain. Here, we used these systems to study motor recovery in two macaques, for which focal infarcts of different sizes were induced in the posterior limb of the internal capsule. Immediately after the injection, flaccid paralysis was observed in the hand contralateral to the injected hemisphere. Thereafter, dexterous hand movements gradually recovered over months. After movement recovery, task-evoked hemodynamic responses increased in the ventral premotor cortex (PMv). The response in the PMv of the infarcted (i.e., ipsilesional) hemisphere increased in the monkey that had received less damage. In contrast, the PMv of the non-infarcted (contralesional) hemisphere was recruited in the monkey with more damage. A pharmacological inactivation experiment with muscimol suggested the involvement of these areas in dexterous hand movements during recovery. These results indicate that fNIRS can be used to evaluate brain activity changes crucial for functional recovery after brain damage.

Motor function after hemispheric lesions has been associated with the structural integrity of either the pyramidal tract (PT) or alternate motor fibers (aMF). In this study, we aimed to differentially characterize the roles of PT and aMF in motor compensation by relating diffusion-tensor-imaging-derived parameters of white matter microstructure to measures of proximal and distal motor function in patients after hemispherotomy. Twenty-five patients (13 women; mean age: 21.1 years) after hemispherotomy (at mean age: 12.4 years) underwent Diffusion Tensor Imaging and evaluation of motor function using the Fugl-Meyer Assessment and the index finger tapping test. Regression analyses revealed that fractional anisotropy of the PT explained (p = 0.050) distal motor function including finger tapping rate (p = 0.027), whereas fractional anisotropy of aMF originating in the contralesional cortex and crossing to the ipsilesional hemisphere in the pons explained proximal motor function (p = 0.001). Age at surgery was found to be the only clinical variable to explain motor function (p < 0.001). Our results are indicative of complementary roles of the PT and of aMF in motor compensation of hemispherotomy mediating distal and proximal motor compensation of the upper limb, respectively.

Structural disconnectome analyses have provided valuable insights into how a stroke lesion results in widespread network disturbances and how these relate to deficits, recovery patterns, and outcomes. Previous analyses have primarily focused on patients with relatively mild to moderate deficits. However, outcomes vary among survivors of severe strokes, and the mechanisms of recovery remain poorly understood. This study assesses the association between lesion‐induced network disconnection and outcome after severe stroke. Thirty‐eight ischaemic stroke patients underwent MRI brain imaging early after stroke and longitudinal clinical follow‐up. Lesion information was integrated with normative connectome data to infer individual disconnectome profiles on a localized regional and region‐to‐region pathway level. Ordinal logistic regressions were computed to link disconnectome information to the modified Rankin Scale after 3–6 months. Disconnections of ipsilesional frontal, parietal, and temporal cortical brain areas were significantly associated with a worse motor outcome after a severe stroke, adjusted for the initial deficit, lesion volume, and age. The analysis of the underlying pathways mediating this association revealed location‐specific results: For frontal, prefrontal, and temporal brain areas, the association was primarily driven by relatively sparse intrahemispheric disconnections. In contrast, the ipsilesional primary motor cortex, the dorsal premotor cortex, and various parietal brain regions showed a remarkable involvement of either frontoparietal intrahemispheric or additionally interhemispheric disconnections. These results indicate that localized disconnection of multiple regions embedded in the structural frontoparietal network correlates with worse outcomes after severe stroke. Specifically, primary motor and parietal cortices might gain particular importance as they structurally link frontoparietal networks of both hemispheres. These data shed novel light on the significance of distinct brain networks for recovery after a severe stroke. [ABSTRACT FROM AUTHOR]

Anodal transcranial direct current stimulation (tDCS) promotes neuromodulation and neuroplasticity in the brain. The aim of this study was to determine the long‐term effects of the anodal tDCS on postural and trunk stability, physical performance, anticipatory postural adjustment and quality of life in sub‐acute stroke patients. Thirty‐six participants with sub‐acute stroke were divided into experimental and control groups using sealed envelope randomization. Outcome measures comprised the Postural Assessment Scale for Stroke, Trunk Impairment Scale, Time Up and Go Test, Functional Reach Test, and Stroke‐Specific Quality of Life Scale. Assessments were conducted at 0, 3, 6, 9, and 12 weeks. Within‐group analysis revealed significant improvement in both the experimental (p‐value < 0.05) and control groups (p‐value < 0.005). Notably, significant effects were observed in postural stability after intervention, and during one of the detraining assessments, the experimental group showed superior results compared to the control group in subacute stroke. Anodal tDCS yield significant short‐ and long‐term effects on postural stability, while short term effects on trunk stability. Additionally, long term effects were observed on the physical performance and anticipatory postural adjustments while no effects at quality of life either short or long term basis among the subacute stroke patients. [ABSTRACT FROM AUTHOR]

Upper limb actions require intersegmental coordination of the scapula, shoulders, elbows, forearms, wrists, and hand muscles. Stroke hemiparesis, presenting as an impairment of an intersegmentally coordinated voluntary movement, is associated with altered integrity of corticospinal tract (CST) transmission from the motor cortex (M1) to muscles. Motor evoked potentials (MEPs) elicited by M1 transcranial magnetic stimulation (TMS) of "at rest" muscles, or as a backup, during muscle contraction have been used to identify CST integrity and predict the outcome after hemiparesis, under the implicit assumption that MEPs present in only one or two muscles are manifest surrogates of CST integrity for other muscles of the upper limbs. This study presents a method for applying TMS during motor tasks that involve proximal and distal muscles. It focuses on evaluating multi-muscle electromyography (EMG) and MEPs across all task-relevant limb segments. Protocols are presented for assessing voluntary motor behavior in individuals with hemiparetic stroke using isometric, unimanual, bimanual, and "REST" conditions that broaden the concept of the degree of CST integrity in order to inform clinical prescription for neurorehabilitation and distinguish its potential as a prognostic tool. Data describing the recordings of multi-muscle transcranial magnetic stimulation induced motor evoked potentials (TMS-MEP) will be presented in a case of subacute hemiparetic stroke to elucidate our perspective. [ABSTRACT FROM AUTHOR]

Introduction: Previous studies found that post-stroke motor impairments are associated with damage to the lesioned corticospinal tract (CST) and hyperexcitability of the contralesional cortico-reticulospinal tract (CRST). This proof-of-concept study aims to develop a non-invasive brain stimulation protocol that facilitates the lesioned CST and inhibits the contralesional CRST to improve upper extremity rehabilitation in individuals with moderate-to-severe motor impairments post-stroke. Methods: Fourteen individuals (minimum 3 months post ischemic stroke) consented. Physician decision of the participants baseline assessment qualified eight to continue in a randomized, double-blind cross-over pilot trial (ClinicalTrials. gov Identifier: NCT05174949) with: (1) anodal high-definition transcranial direct stimulation (HD-tDCS) over the ipsilesional primary motor cortex (M1), (2) cathodal HD-tDCS over contralesional dorsal premotor cortex (PMd), (3) sham stimulation, with a two-week washout period in-between. Subject-specific MR images and computer simulation were used to guide HD-tDCS and verified by Transcranial Magnetic Stimulation (TMS) induced Motor Evoked Potential (MEP). The motor behavior outcome was evaluated by an Fugl-Meyer Upper Extremity score (primary outcome measure) and the excitability of the ipslesoinal CST and contralesional CRST was determined by the change of MEP latencies and amplitude (secondary outcome measures). Results: The baseline ipsilesional M1 MEP latency and amplitude were correlated with FM-UE. FM-UE scores were improved post HD-tDCS, in comparison to sham stimulation. Both anodal and cathodal HD-tDCS reduced the latency of the ipsilesional M1 MEP. The contralesional PMd MEP disappeared/delayed after HD-tDCS. Discussion: These results suggest that HD-tDCS could improve the function of the lesioned corticospinal tract and reduce the excitability of the contralesional cortico-reticulospinal tract, thus, improving motor function of the upper extremity in more severely impaired individuals. [ABSTRACT FROM AUTHOR]

Short-interval intracortical inhibition (SICI) is a common paired-pulse transcranial magnetic stimulation (TMS) measure used to assess primary motor cortex (M1) interneuron activity in healthy populations and in neurological disorders. Many of the parameters of TMS stimulation to most accurately measure SICI have been determined. However, one TMS parameter that has not been investigated is the time between SICI trials (termed inter-trial interval; ITI). This is despite a series of single-pulse TMS studies which have reported that motor evoked potential (MEP) amplitude were suppressed for short, but not long ITIs in approximately the initial ten trials of a TMS block of 20–30 trials. The primary purpose was to examine the effects of ITI on the quantification of SICI at rest. A total of 23 healthy adults completed an experimental session that included four SICI trial blocks. Each block utilized a different ITI (4, 6, 8, and 10 s) and was comprised of a total of 26 SICI trials divided into three epochs. ANOVA revealed that the main effects for ITI and epoch as well as their interaction were all non-statistically significant for SICI. We conclude that the shorter (4–6 s) ITIs used in studies investigating SICI should not alter the interpretation of M1 activity, while having the advantages of being more comfortable to participants and reducing the experimental time needed to evaluate perform single and paired-pulse TMS experiments. [ABSTRACT FROM AUTHOR]

Transcranial direct current stimulation (tDCS) exerts beneficial effects on motor recovery after stroke, presumably by enhancement of adaptive neural plasticity. However, patients with extensive damage may experience null or deleterious effects with the predominant application mode of anodal (excitatory) stimulation of the damaged hemisphere. In such cases, excitatory stimulation of the non-damaged hemisphere might be considered. Here we asked whether tDCS exerts a measurable effect on movement quality of the hemiparetic upper limb, following just a single treatment session. Such effect may inform on the hemisphere that should be excited. Using a single-blinded crossover experimental design, stroke patients and healthy control subjects were assessed before and after anodal, cathodal and sham tDCS, each provided during a single session of reaching training (repeated point-to-point hand movement on an electronic tablet). Group comparisons of endpoint kinematics at baseline—number of peaks in the speed profile (NoP; smoothness), hand-path deviations from the straight line (SLD; accuracy) and movement time (MT; speed)—disclosed greater NoP, larger SLD and longer MT in the stroke group. NoP and MT revealed an advantage for anodal compared to sham stimulation of the lesioned hemisphere. NoP and MT improvements under anodal stimulation of the non-lesioned hemisphere correlated positively with the severity of hemiparesis. Damage to specific cortical regions and white-matter tracts was associated with lower kinematic gains from tDCS. The study shows that simple descriptors of movement kinematics of the hemiparetic upper limb are sensitive enough to demonstrate gain from neuromodulation by tDCS, following just a single session of reaching training. Moreover, the results show that tDCS-related gain is affected by the severity of baseline motor impairment, and by lesion topography. [ABSTRACT FROM AUTHOR]

Background: Balance and mobility impairments are prevalent post-stroke and a large number of survivors require walking assistance at 6 months post-stroke which diminishes their overall quality of life. Personalized interventions for gait and balance rehabilitation are crucial. Recent evidence indicates that stroke lesions in primary motor pathways, such as corticoreticular pathways (CRP) and corticospinal tract (CST), may lead to reliance on alternate motor pathways as compensation, but the current evidence lacks comprehensive knowledge about the underlying neural mechanisms. Methods: In this study, we investigate the functional connectivity (FC) changes within the motor network derived from an individualized cortical parcellation approach in 33 participants with chronic stroke compared to 17 healthy controls. The correlations between altered motor FC and gait deficits (i.e., walking speed and walking balance) were then estimated in the stroke population to understand the compensation mechanism of the motor network in motor function rehabilitation post-stroke. Results: Our results demonstrated significant FC increases between ipsilesional medial supplementary motor area (SMA) and premotor in stroke compared to healthy controls. Furthermore, we also revealed a negative correlation between ipsilesional SMA-premotor FC and self-selected walking speed, as well as the Functional Gait Assessment (FGA) scores. Conclusion: The increased FC between the ipsilesional SMA and premotor regions could be a compensatory mechanism within the motor network following a stroke when the individual can presumably no longer rely on the more precise CST modulation of movements to produce a healthy walking pattern. These findings enhance our understanding of individualized motor network FC changes and their connection to gait and walking balance impairments post-stroke, improving stroke rehabilitation interventions. [ABSTRACT FROM AUTHOR]

Measurement of the input–output (IO) curves of motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) can be used to assess corticospinal excitability and motor recruitment. While IO curves have been used to study disease and pharmacology, few studies have compared the IO curves across the body. This study sought to characterize IO curve parameters across the dominant and non-dominant sides of upper and lower limbs in healthy participants. Laterality preferences were assessed in eight healthy participants and IO curves were measured bilaterally for the first dorsal interosseous (FDI), biceps brachii (BB), and tibialis anterior (TA) muscles. Results show that FDI has lower motor threshold than BB which is, in turn, lower than TA. In addition, both BB and TA have markedly shallower logarithmic IO curve slopes from small to large MEP responses than FDI. After normalizing these slopes by their midpoints to account for differences in motor thresholds, which could result from geometric factors such as the target depth, large differences in logarithmic slopes remain present between all three muscles. The differences in slopes between the muscles could not be explained by differences in normalized IO curve spreads, which relate to the extent of the cortical representation and were comparable across the muscles. The IO curve differences therefore suggest muscle-dependent variations in TMS-evoked recruitment across the primary motor cortex, which should be considered when utilizing TMS-evoked MEPs to study disease states and treatment effects. [ABSTRACT FROM AUTHOR]

Diagnoses in patients with disorders of consciousness are prone to misdiagnosis; thus, research has sought approaches to increase reliability, for instance, with functional MRI. By applying a motor imagery task, patients showing covert command following despite the absence of behavioural signs of awareness can be identified as being in a cognitive motor dissociation. This study seeks to determine the proportion of patients, with unresponsive wakefulness syndrome and minimally conscious state, who display covert command following. Moreover, the prognostic value of the improved diagnosis and different methodical approaches to analyse the functional MRI data were evaluated. 73 disorder of consciousness patients (35 unresponsive, 35 minimally conscious, and three already recovered) underwent weekly standardized behavioural assessments with the coma-recovery scale—revised and one functional MRI examination comparing their brain activations in the supplementary motor area between phases of imaging playing tennis and rest. 27 healthy controls served as a control group. The data was evaluated using different region-of-interest analyses (one- and two-tailed small-volume correction and region-of-interest exploration approaches) and a whole-brain analysis. Based on the one-tailed small volume correction data, seven patients, all of nontraumatic aetiology, showed covert command following. The one-tailed region-of-interest exploration identified three additional responders. 10 patients showed significantly more activation during rest than during the imagery paradigm (negative responders). 40% of patients (minimally conscious patients being three times more likely) showed significant activations in the whole brain analysis. Besides, no significant further associations were found between covert command following and clinical parameters. The analyses showed that the tennis paradigm could identify patients with cognitive motor dissociation with a nontraumatic aetiology, but our data failed to show any short-term prognostic validity. The relevance of negative responders and activated regions outside of the region of interest should be further investigated. [ABSTRACT FROM AUTHOR]

Intracortical facilitation (ICF) is a paired-pulse transcranial magnetic stimulation (TMS) measurement used to quantify interneuron activity in the primary motor cortex (M1) in healthy populations and motor disorders. Due to the prevalence of the technique, most of the stimulation parameters to optimize ICF quantification have been established. However, the underappreciated methodological issue of the time between ICF trials (inter-trial interval; ITI) has been unstandardized, and different ITIs have never been compared in a paired-pulse TMS study. This is important because single-pulse TMS studies have found motor evoked potential (MEP) amplitude reductions over time during TMS trial blocks for short, but not long ITIs. The primary purpose was to determine the influence of different ITIs on the measurement of ICF. Twenty adults completed one experimental session that involved 4 separate ICF trial blocks with each utilizing a different ITI (4, 6, 8, and 10 s). Two-way ANOVAs indicated no significant ITI main effects for test MEP amplitudes, condition-test MEP amplitudes, and therefore ICF. Accordingly, all ITIs studied provided nearly identical ICF values when averaged over entire trial blocks. Therefore, it is recommended that ITIs of 4–6 s be utilized for ICF quantification to optimize participant comfort and experiment time efficiency. [ABSTRACT FROM AUTHOR]

Aim: To compare transcranial magnetic stimulation (TMS)‐derived measures of primary motor cortex (M1) physiology between children with and without Tourette syndrome, and to dimensionally analyze TMS measures with Tourette syndrome‐related symptom severity. Method: We used a cross‐sectional experimental design. Sixty 8‐ to 12‐year‐old children participated (30 with Tourette syndrome: three females, mean age 10 years 10 months, standard deviation [SD] 1 year 3 months; 30 typically developing children: seven females, mean age 10 years 7 months, SD 1 year 3 months). In the group with Tourette syndrome, 15 (one female, mean age 10 years 11 months, SD 1 year 3 months) had comorbid attention‐deficit/hyperactivity disorder (ADHD), rated with the Conners, Third Edition and the parent‐reported ADHD rating scales. Tic severity was rated with the Yale Global Tic Severity Scale and urge severity with the Individualized Premonitory Urge for Tics Scale. M1 short‐interval cortical inhibition (SICI) and intracortical facilitation were compared between diagnostic groups and, within the group with Tourette syndrome, correlated with symptom severity using linear mixed‐effects models for repeated measures. Results: Accounting for ADHD, we found no difference in SICI or intracortical facilitation in those with Tourette syndrome versus typically developing children (p > 0.1). In the group with Tourette syndrome, reduced M1 SICI predicted greater total (p = 0.012) and global (p = 0.002) tic severity. There were no associations with urge severity (p > 0.5). Interpretation: Reduced M1 SICI is robustly associated with increased tic, but not urge, severity. What this paper adds: Increased tic severity is associated with reduced motor cortex short‐interval cortical inhibition (SICI).Children with Tourette syndrome with increased urge severity also show increased tic severity.However, reduced motor cortex SICI is associated with tic, but not urge, severity. [ABSTRACT FROM AUTHOR]

Objective: To investigate changes in interhemispheric imbalance of cortical excitability during motor recovery after stroke and to clarify the relationship between motor function recovery and alterations in interhemispheric imbalance, with the aim to establish more effective neuromodulation strategies. Methods: Thirty-one patients underwent assessments of resting motor threshold (RMT) using transcranial magnetic stimulation (TMS); the cortical activity of the primary motor cortex (M1), premotor cortex (PMC), and supplementary motor area (SMA) using functional near-infrared spectroscopy (fNIRS); as well as motor function using upper extremity Fugl-Meyer (FMA-UE). The laterality index (LI) of RMT and fNIRS were also calculated. All indicators were measured at baseline(T1) and 1 month later(T2). Correlations between motor function outcome and TMS and fNIRS metrics at baseline were analyzed using bivariate correlation. Results: All the motor function (FMA-UE1, FMA-UE2, FMA-d2) and LI-RMT (LI-RMT1 and LI-RMT2) had a moderate negative correlation. The higher the corticospinal excitability of the affected hemisphere, the better the motor outcome of the upper extremity, especially in the distal upper extremity (r  = −0.366, p  =  0.043; r  = −0.393, p  =  0.029). The greater the activation of the SMA of the unaffected hemisphere, the better the motor outcome, especially in the distal upper extremity (r  = −0.356, p  =  0.049; r  = −0.367, p  =  0.042). There was a significant moderate positive correlation observed between LI-RMT2 and LI-SMA1 (r  =  0.422, p  =  0.018). The improvement in motor function was most significant when both LI-RMT1 and LI-SMA1 were lower. Besides, in patients dominated by unaffected hemisphere corticospinal excitability during motor recovery, LI-(M1  +  SMA  +  PMC)2 exhibited a significant moderate positive association with the proximal upper extremity function 1 month later (r  =  0.642, p  =  0.007). Conclusion: The combination of both TMS and fNIRS can infer the prognosis of motor function to some extent. Which can infer the role of both hemispheres in recovery and may contribute to the development of effective individualized neuromodulation strategies. [ABSTRACT FROM AUTHOR]

Cross‐education, a phenomenon where unilateral strength (or skill) training enhances strength (or skill) in the contralateral untrained limb, has been well studied in able‐bodied individuals. Cross‐education effect accompanies bilateral changes of corticomotor activity in the motor cortex (M1). Recent reports demonstrated greater cross‐education effect in stroke survivors compared to healthy individuals, however, corticomotor responses to cross‐education in stroke remains unclear. This study aimed to determine the effects of non‐paretic leg movements on corticomotor excitability (CME) and reaction time of the paretic leg in severely impaired stroke survivors. Seventeen post stroke individuals with severe leg motor impairment (Fugl‐Meyer lower extremity score less than 21 and absence of motor evoked potential in the paretic leg) performed three 20‐min motor trainings using their non‐paretic ankle: skill (targeted dynamic movements), strength (isometric resistance) and sham (sub‐threshold electrical nerve stimulation). During training, verbal instructions were given to the participants to limit their movement to the non‐paretic leg and this was confirmed with visual observation of the paretic leg. Transcranial magnetic stimulation measured CME of the contralateral pathways from the non‐lesioned M1 to the non‐paretic tibialis anterior (TA) muscle, ipsilateral pathways to the paretic TA and transcallosal inhibition (TCI) from the non‐lesioned to lesioned M1. Paretic ankle reaction time was measured using a reaction time paradigm. All outcomes were measured before, immediately post, 30‐min post and 60‐min post priming. CME of the non‐paretic TA increased after skill (.08 ±.10 mV) and strength (.06 ±.05 mV) training (p <.01). Ipsilateral CME of the paretic TA (.02 ±.01 mV) and TCI (.01 ±.01 s, ipsilateral silent period; more inhibition to the lesioned M1) increased after skill (p <.05) but not strength training. Reaction time of the paretic ankle improved after skill and strength training (−.11 ±.2 and −.13 ±.20 s, respectively; p <.05) and was sustained at 60 min. No changes were observed during the sham condition. Our findings may inform future studies for using non‐paretic leg movements as a priming modality, especially for those who are contraindicated to other priming paradigms (e.g., brain stimulation) or unable to perform paretic leg movements. Conclusion: Non‐paretic leg movements can be used as a priming modality, especially for those who are contraindicated to other priming paradigms (e.g., brain stimulation) or unable to perform paretic leg movements. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) is a non‐invasive technique that is increasingly used to study the human brain. One of the principal outcome measures is the motor‐evoked potential (MEP) elicited in a muscle following TMS over the primary motor cortex (M1), where it is used to estimate changes in corticospinal excitability. However, multiple elements play a role in MEP generation, so even apparently simple measures such as peak‐to‐peak amplitude have a complex interpretation. Here, we summarize what is currently known regarding the neural pathways and circuits that contribute to the MEP and discuss the factors that should be considered when interpreting MEP amplitude measured at rest in the context of motor processing and patients with neurological conditions. In the last part of this work, we also discuss how emerging technological approaches can be combined with TMS to improve our understanding of neural substrates that can influence MEPs. Overall, this review aims to highlight the capabilities and limitations of TMS that are important to recognize when attempting to disentangle sources that contribute to the physiological state‐related changes in corticomotor excitability. [ABSTRACT FROM AUTHOR]

Objectives: The integrity of cortical motor networks and their descending effector pathway (the corticospinal tract [CST]) is a major determinant motor recovery after stroke. However, this view neglects the importance of ascending tracts and their modulatory effects on cortical physiology. Here, we explore the role of such a tract that connects dopaminergic ventral tegmental midbrain nuclei to the motor cortex (the VTMC tract) for post‐stroke recovery. Methods: Lesion data and diffusivity parameters (fractional anisotropy) of the ipsi‐ and contralesional VTMC tract and CST were obtained from 133 patients (63.9 ± 13.4 years, 45 women) during the acute and chronic stage after the first ever ischemic stroke in the middle cerebral artery territory. Degeneration of VTMC tract and CST was quantified and related to clinical outcome parameters (National Institute of Health Stroke Scale with motor and cortical symptom subscores; modified Fugl‐Meyer upper extremity score; modified Ranking Scale [mRS]). Results: A significant post‐stroke degeneration occurred in both tracts, but only VTMC degeneration was associated with lesion size. Using multiple regression models, we dissected the impact of particular tracts on recovery: Changes in VTMC tract integrity were stronger associated with independence in daily activities (mRS), upper limb motor impairment (modified Fugl‐Meyer upper extremity score) and cortical symptoms (aphasia, neglect) captured by National Institute of Health Stroke Scale compared to CST. Changes in CST integrity merely were associated with the degree of hemiparesis (National Institute of Health Stroke Scale motor subscale). Interpretation: Post‐stroke outcome is influenced by ascending (VTMC) and descending (CST) fiber tracts. Favorable outcome regarding independence (modified Ranking Scale), upper limb motor function (modified Fugl‐Meyer upper extremity score), and cortical symptoms (aphasia, neglect) was more strongly related to the ascending than descending tract. ANN NEUROL 2023;93:922–933 [ABSTRACT FROM AUTHOR]

BACKGROUND: Repetitive Transcranial Magnetic Stimulation (rTMS) over the primary motor cortex (M1) has been used to treat stroke motor sequelae regulating cortical excitability. Early interventions are widely recommended, but there is also evidence showing interventions in subacute or chronic phases are still useful. OBJECTIVE: To synthetize the evidence of rTMS protocols to improve upper limb motor function in people with subacute and/or chronic stroke. METHODS: Four databases were searched in July 2022. Clinical trials investigating the effectiveness of different rTMS protocols on upper limb motor function in subacute or chronic phases post-stroke were included. PRISMA guidelines and PEDro scale were used. RESULTS: Thirty-two studies representing 1137 participants were included. Positive effects of all types of rTMS protocols on upper limb motor function were found. These effects were heterogeneous and not always clinically relevant or related to neurophysiological changes but produced evident changes if evaluated with functional tests. CONCLUSION: rTMS interventions over M1 are effective for improving upper limb motor function in people with subacute and chronic stroke. When rTMS protocols were priming physical rehabilitation better effects were achieved. Studies considering minimal clinical differences and different dosing will help to generalize the use of these protocols in clinical practice. [ABSTRACT FROM AUTHOR]

Background and objective: Transcranial magnetic stimulation and peripheral repetitive magnetic stimulation (rPMS), as non-invasive neuromodulation techniques, can promote functional recovery in patients with post-stroke spasticity (PSS), but the effects of transcranial magnetic stimulation combined with peripheral magnetic stimulation on PSS remain largely unknown. Therefore, we examined the effects of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) combined with rPMS on PSS patients and its potential neural correlates to behavioral improvements. Methods: Forty-nine PSS patients were divided randomly into three groups: a combined group (n D 20), a LF-rTMS group (n D 15), and a control group (n D 14). The combined group received LF-rTMS and rPMS treatment, the rTMS group received LF-rTMS treatment, and the control group received only routine rehabilitation. All patients underwent Ashworth Spasm Scale (MAS), upper extremity Fugl-Meyer (FMA-UE), and modified Barthel Index (MBI) assessments before and after intervention. In addition, resting-state functional magnetic resonance imaging data were collected pre- and post-treatment to observe changes in the amplitude of low-frequency fluctuation (ALFF). Results: The MAS score was decreased, FMA-UE score and MBI scores were increased in the three groups after therapy than before therapy (all P < 0.05). In particular, the combined group showed significant effect on improved motor function and relieved spasticity in PSS (P < 0.01). Moreover, the combined treatment increased ALFF values mainly in the right supplementary motor area, right middle frontal gyrus, and right cerebellum, while reduced ALFF values mainly in the right post-central gyrus compared with pre-treatment. Compared with the LF-rTMS and control groups, the combined treatment increased ALFF values in the right cerebellum and reduced ALFF values mainly in the frontoparietal cortex. Improvements in the MAS score were positively correlated with the change in ALFF values in the right cerebellum (r D 0.698, P D 0.001) and the right supplementary motor area (r D 0.700, P D 0.001) after combined treatment. Conclusion: Transcranial combined with peripheral repetitive magnetic stimulation could improve spastic state and motor function in PSS patients, and this effect may be associated with altered cerebellar and frontoparietal cortical activity. [ABSTRACT FROM AUTHOR]

Understanding the impact of variation in lesion topography on the expression of functional impairments following stroke is important, as it may pave the way to modeling structure–function relations in statistical terms while pointing to constraints for adaptive remapping and functional recovery. Multi‐perturbation Shapley‐value analysis (MSA) is a relatively novel game‐theoretical approach for multivariate lesion‐symptom mapping. In this methodological paper, we provide a comprehensive explanation of MSA. We use synthetic data to assess the method's accuracy and perform parameter optimization. We then demonstrate its application using a cohort of 107 first‐event subacute stroke patients, assessed for upper limb (UL) motor impairment (Fugl‐Meyer Assessment scale). Under the conditions tested, MSA could correctly detect simulated ground‐truth lesion‐symptom relationships with a sensitivity of 75% and specificity of ~90%. For real behavioral data, MSA disclosed a strong hemispheric effect in the relative contribution of specific regions‐of‐interest (ROIs): poststroke UL motor function was mostly contributed by damage to ROIs associated with movement planning (supplementary motor cortex and superior frontal gyrus) following left‐hemispheric damage (LHD) and by ROIs associated with movement execution (primary motor and somatosensory cortices and the ventral brainstem) following right‐hemispheric damage (RHD). Residual UL motor ability following LHD was found to depend on a wider array of brain structures compared to the residual motor ability of RHD patients. The results demonstrate that MSA can provide a unique insight into the relative importance of different hubs in neural networks, which is difficult to obtain using standard univariate methods. [ABSTRACT FROM AUTHOR]

L‐dopa variably influences transcranial magnetic stimulation (TMS) parameters of motor cortex (M1) excitability and plasticity in Parkinson's disease (PD). In patients OFF dopaminergic medication, impaired M1 plasticity and defective GABA‐A‐ergic inhibition can be restored by boosting gamma (γ) oscillations via transcranial alternating current stimulation (tACS) during intermittent theta‐burst stimulation (iTBS). However, it is unknown whether L‐dopa modifies the beneficial effects of iTBS‐γ‐tACS on M1 in PD. In this study, a PD patients group underwent combined iTBS‐γ‐tACS and iTBS‐sham‐tACS, each performed both OFF and ON dopaminergic therapy (four sessions in total). Motor evoked potentials (MEPs) elicited by single TMS pulses and short‐interval intracortical inhibition (SICI) were assessed before and after iTBS‐tACS. We also evaluated possible SICI changes during γ‐tACS delivered alone in OFF and ON conditions. The amplitude of MEP elicited by single TMS pulses and the degree of SICI inhibition significantly increased after iTBS‐γ‐tACS. The amount of change produced by iTBS‐γ‐tACS was similar in patients OFF and ON therapy. Finally, γ‐tACS (delivered alone) modulated SICI during stimulation and this effect did not depend on the dopaminergic condition of patients. In conclusion, boosting cortical γ oscillatory activity via tACS during iTBS improved M1 plasticity and enhanced GABA‐A‐ergic transmission in PD patients to the same extent regardless of dopaminergic state. These results suggest a lack of interaction between L‐dopa and γ‐tACS effects at the M1 level. The possible neural substrate underlying iTBS‐γ tACS effects, that is, γ‐resonant GABA‐A‐ergic interneurons activity, may explain our findings. [ABSTRACT FROM AUTHOR]

Motor imagery (MI) refers to the mental simulation of an action without overt movement. While numerous transcranial magnetic stimulation (TMS) studies provided evidence for a modulation of corticospinal excitability and intracortical inhibition during MI, the neural signature within the primary motor cortex is not clearly established. In the current study, we used directional TMS to probe the modulation of the excitability of early and late indirect waves (I‐waves) generating pathways during MI. Corticospinal responses evoked by TMS with posterior–anterior (PA) and anterior–posterior (AP) current flow within the primary motor cortex evoke preferentially early and late I‐waves, respectively. Seventeen participants were instructed to stay at rest or to imagine maximal isometric contractions of the right flexor carpi radialis. We demonstrated that the increase of corticospinal excitability during MI is greater with PA than AP orientation. By using paired‐pulse stimulations, we confirmed that short‐interval intracortical inhibition (SICI) increased during MI in comparison to rest with PA orientation, whereas we found that it decreased with AP orientation. Overall, these results indicate that the pathways recruited by PA and AP orientations that generate early and late I‐waves are differentially modulated by MI. [ABSTRACT FROM AUTHOR]

Introduction: Improved understanding of the relationship between post-stroke rehabilitation interventions and functionalmotor outcomes could result in improvements in the effcacy of post-stroke physical rehabilitation. The laterality of motor cortex activity (M1-LAT) during paretic upper-extremity movement has been documented as a useful biomarker of post-stroke motor recovery. However, the expensive, labor intensive, and laboratory-based equipment required to takemeasurements of M1-LAT limit its potential clinical utility in improving post-stroke physical rehabilitation. The present study tested the ability of a mobile functional near-infrared spectroscopy (fNIRS) system (designed to enable independentmeasurement by stroke survivors) tomeasure cerebral hemodynamics at the motor cortex in the homes of chronic stroke survivors. Methods: Eleven chronic stroke survivors, ranging widely in their level of upper-extremity motor deficit, used their stroke-affected upper-extremity to performa simple unilateralmovement protocol in their homes while a wireless prototype fNIRS headband took measurements at the motor cortex. Measures of participants' upper-extremity impairment and function were taken. Results: Participants demonstrated either a typically lateralized response, with an increase in contralateral relative oxyhemoglobin (1HbO), or response showing a bilateral pattern of increase in 1HbO during the motor task. During the simple unilateral task, M1-LAT correlated significantly with measures of both upper-extremity impairment and function, indicating that participants withmore severemotor deficits hadmore amore atypical (i.e., bilateral) pattern of lateralization. Discussion: These results indicate it is feasible to gain M1-LAT measures from stroke survivors in their homes using fNIRS. These findings represent a preliminary step toward the goals of using ergonomic functional neuroimaging to improve post-stroke rehabilitative care, via the capture of neural biomarkers of post-stroke motor recovery, and/or via use as part of an accessible rehabilitation brain-computer-interface. [ABSTRACT FROM AUTHOR]

While mentally simulated actions activate similar neural structures to overt movement, the role of the primary motor cortex (PMC) in motor imagery remains disputed. The aim of the study was to use continuous theta burst stimulation (cTBS) to modulate corticospinal activity to investigate the putative role of the PMC in implicit motor imagery in young adults with typical and atypical motor ability. A randomized, double blind, sham‐controlled, crossover, offline cTBS protocol was applied to 35 young adults. During three separate sessions, adults with typical and low motor ability (developmental coordination disorder [DCD]), received active cTBS to the PMC and supplementary motor area (SMA), and sham stimulation to either the PMC or SMA. Following stimulation, participants completed measures of motor imagery (i.e., hand rotation task) and visual imagery (i.e., letter number rotation task). Although active cTBS significantly reduced corticospinal excitability in adults with typical motor ability, neither task performance was altered following active cTBS to the PMC or SMA, compared to performance after sham cTBS. These results did not differ across motor status (i.e., typical motor ability and DCD). These findings are not consistent with our hypothesis that the PMC (and SMA) is directly involved in motor imagery. Instead, previous motor cortical activation observed during motor imagery may be an epiphenomenon of other neurophysiological processes and/or activity within brain regions involved in motor imagery. This study highlights the need to consider multi‐session theta burst stimulation application and its neural effects when probing the putative role of motor cortices in motor imagery. A controlled continuous theta burst stimulation protocol was adopted to examine the role of the primary motor cortex in motor imagery. While corticospinal excitability was suppressed in individuals with typical motor ability, no changes in imagery performance were detected after applying active stimulation to the motor regions. This suggests that motor regions may not be causally implicated in motor imagery and/or that multiple stimulation sessions may be required when inducing cognitive‐behavioral changes. [ABSTRACT FROM AUTHOR]

Mental imagery is a powerful capability that engages similar neurophysiological processes that underlie real sensory and motor experiences. Previous studies show that motor cortical excitability can increase during mental imagery of actions. In this study, we focused on possible inhibitory effects of mental imagery on motor functions. We assessed whether imagined arm paralysis modulates motor cortical excitability in healthy participants, as measured by motor evoked potentials (MEPs) of the hand induced by near‐threshold transcranial magnetic stimulation (TMS) over the primary motor cortex hand area. We found lower MEP amplitudes during imagined arm paralysis when compared to imagined leg paralysis or baseline stimulation without paralysis imagery. These results show that purely imagined bodily constraints can selectively inhibit basic motor corticospinal functions. The results are discussed in the context of motoric embodiment/disembodiment. In this study we investigated whether imagining a specific motor impairment has a physiological effect on motor corticospinal function in healthy participants. We found that imagined hand (but not leg) paralysis reduced TMS induced MEPs of the hand muscle. While previous research mainly focused on excitatory effects of mental imagery, our results point to possible inhibitory effects on motor functions. The results may have relevance in the context of (dis)embodiment research and physiological rehabilitation. [ABSTRACT FROM AUTHOR]

The heterogeneity of transcranial direct current stimulation (tDCS) protocols and clinical profiles may explain variable results in modulating excitability in the motor cortex after stroke. However, the cortical electrical effects induced by different tDCS protocols remain unclear. Here, we aimed to compare rhythm changes in electroencephalography (EEG) induced by three tDCS position protocols and the association between tDCS effects and clinical factors in stroke. Nineteen patients with chronic ischemic stroke underwent four experimental sessions with three tDCS protocols [anodal (atDCS), cathodal (ctDCS), and bilateral (bi-tDCS)] and a sham protocol, according to a single-blind randomized crossover design. Resting-state EEG was acquired before and after each protocol. First, a paired-sample t-test was used to examine the difference in spectral power between pre- and post-stimulation. Then, linear and quadratic regression models were used separately to describe the association between the clinical factors of stroke and changes in spectral power which was significantly different between pre- and post-tDCS. Finally, repeated measures analysis of variance with lesion hemisphere, stimulation protocol, and the location was performed to investigate the effects of tDCS over time. The induced effect of tDCS was mainly reflected in the alpha rhythms. The alpha power was increased by atDCS, especially low-alpha (8-10 Hz), in localized areas of the central and distant areas of the frontal and parietal lobes. Bi-tDCS also affected alpha power but in a smaller area that mainly focused on high-alpha rhythms (10-13 Hz). However, ctDCS and sham had no significant effects on any EEG rhythm. The clinical factors of time since stroke and motor impairment level were related to the change in high-alpha induced by atDCS and bi-tDCS following quadratic regression models. The above-mentioned modulation effect lasted for 20 min without attenuation. In conclusion, our findings provide evidence that the alpha rhythm of EEG is modulated differently by different tDCS protocols and that high alpha is affected by clinical characteristics such as post-stroke time and motor deficits, which is of great significance for understanding the modulation effect of different tDCS protocols on stroke and the guidance of protocols to promote motor recovery following stroke. [ABSTRACT FROM AUTHOR]

The functional corticospinal integrity (CSI) can be indexed by motor‐evoked potentials (MEP) following transcranial magnetic stimulation of the motor cortex. Glial brain tumors in motor‐eloquent areas are frequently disturbing CSI resulting in different degrees of motor dysfunction. However, this is unreliably mirrored by MEP characteristics. In 59 consecutive patients with diffuse glial tumors and 21 healthy controls (CTRL), we investigated the conventional MEP features, that is, resting motor threshold (RMT), amplitudes and latencies. In addition, frequency‐domain MEP features were analyzed to estimate the event‐related spectral perturbation (ERSP), and the induced phase synchronization by intertrial coherence (ITC). The clinical motor status was captured including the Medical Research Council Scale (MRCS), the Grooved Pegboard Test (GPT), and the intake of antiepileptic drugs (AED). Motor function was classified according to MRCS and GPT as no motor deficit (NMD), fine motor deficits (FMD) and gross motor deficits (GMD). CSI was assessed by diffusion‐tensor imaging (DTI). Motor competent subjects (CTRL and NMD) had similar ERSP and ITC values. The presence of a motor deficit (FMD and GMD) was associated with an impairment of high‐frequency ITC (150–300 Hz). GMD and damage to the CSI demonstrated an additional reduction of high‐frequency ERSP (150–300 Hz). GABAergic AED increased ERSP but not ITC. Notably, groups were indistinguishable based on conventional MEP features. Estimating MEP phase synchronization provides information about the corticospinal transmission after transcranial magnetic stimulation and reflects the degree of motor impairment that is not captured by conventional measures. [ABSTRACT FROM AUTHOR]

Purpose: To explore the changes of cerebral blood flow (CBF) and fractional anisotropy (FA) in stroke patients with motor dysfunction after repetitive transcranial magnetic stimulation (rTMS) treatment, and to better understand the role of rTMS on motor rehabilitation of subcortical stroke patients from the perfusion and structural level. Materials and Methods: In total, 23 first-episode acute ischemic stroke patients and sixteen healthy controls (HCs) were included. The patients were divided into the rTMS and sham group. The rehabilitation assessments and examination of perfusion and structural MRI were performed before and after rTMS therapy for each patient. Voxel-based analysis was used to detect the difference in CBF and FA among all three groups. The Pearson correlation analysis was conducted to evaluate the relationship between the CBF/FA value and the motor scales. Results: After rTMS, significantly increased CBF was found in the ipsilesional supplementary motor area, postcentral gyrus, precentral gyrus, pons, medulla oblongata, contralesional midbrain, superior cerebellar peduncle, and middle cerebellar peduncle compared to that during the prestimulation and in the sham group, these fasciculi comprise the cortex-pontine-cerebellum-cortex (CPC) loop. Besides, altered CBF in the ipsilesional precentral gyrus, postcentral gyrus, and pons was positively associated with the improved Fugl-Meyer assessment (FMA) scores. Significantly decreased FA was found in the contralesional precentral gyrus, increased FA was found in the ipsilesional postcentral gyrus, precentral gyrus, contralesional supplementary motor area, and bilateral cerebellum, these fasciculi comprise the corticospinal tract (CST). The change of FMA score was positively correlated with altered FA value in the ipsilesional postcentral gyrus and negatively correlated with altered FA value in the contralesional precentral gyrus. Conclusion: Our results suggested that rTMS could facilitate the motor recovery of stroke patients. High frequency could promote the improvement of functional activity of ipsilesional CPC loop and the recovery of the microstructure of CST. [ABSTRACT FROM AUTHOR]

Brain plasticity and functional reorganization are mechanisms behind functional motor recovery of patients after an ischemic stroke. The study of resting-state motor network functional connectivity by means of EEG proved to be useful in investigating changes occurring in the information flow and find correlation with motor function recovery. In the literature, most studies applying EEG to post-stroke patients investigated the undirected functional connectivity of interacting brain regions. Quite recently, works started to investigate the directionality of the connections and many approaches or features have been proposed, each of them being more suitable to describe different aspects, e.g., direct or indirect information flow between network nodes, the coupling strength or its characteristic oscillation frequency. Each work chose one specific measure, despite in literature there is not an agreed consensus, and the selection of the most appropriate measure is still an open issue. In an attempt to shed light on this methodological aspect, we propose here to combine the information of direct and indirect coupling provided by two frequency-domain measures based on Granger's causality, i.e., the directed coherence (DC) and the generalized partial directed coherence (gPDC), to investigate the longitudinal changes of resting-state directed connectivity associated with sensorimotor rhythms α and β, occurring in 18 sub-acute ischemic stroke patients who followed a rehabilitation treatment. Our results showed a relevant role of the information flow through the pre-motor regions in the reorganization of the motor network after the rehabilitation in the sub-acute stage. In particular, DC highlighted an increase in intra-hemispheric coupling strength between pre-motor and primary motor areas, especially in ipsi-lesional hemisphere in both α and β frequency bands, whereas gPDC was more sensitive in the detection of those connection whose variation was mostly represented within the population. A decreased causal flow from contra-lesional premotor cortex towards supplementary motor area was detected in both α and β frequency bands and a significant reinforced inter-hemispheric connection from ipsi to contra-lesional pre-motor cortex was observed in β frequency. Interestingly, the connection from contra towards ipsilesional pre-motor area correlated with upper limb motor recovery in α band. The usage of two different measures of directed connectivity allowed a better comprehension of those coupling changes between brain motor regions, either direct or mediated, which mostly were influenced by the rehabilitation, revealing a particular involvement of the pre-motor areas in the cerebral functional reorganization. [ABSTRACT FROM AUTHOR]

Background: Blood flow restriction exercise (BFR-E) could be a useful training adjunct for patients with weakness after stroke to augment the effects of exercise on muscle activity. We aimed to examine neurophysiological changes (primary aim) and assess patient perceptions (secondary aim) following BFR-E. Methods: Fourteen participants with stroke performed BFR-E (1 session) and exercise without blood flow restrictsion (Exercise only) (1 session), on two days, ≈7 days apart. In each session, two sets of tibialis anterior (TA) contractions were performed and electromyography (EMG) was recorded. Eight participants underwent transcranial magnetic stimulation (single-pulse stimulation, short interval intracortical inhibition (SICI), intracortical facilitation (ICF)) and peripheral electrical stimulation (maximal peak-to-peak M-wave (M-max)) of the TA before, immediately-after, 10-min-after and 20-min-after BFR-E and Exercise only. Numerical rating scores (NRS) for pain, discomfort, fatigue, safety, focus and difficulty were collected for all subjects (n = 14). Paired comparisons and linear mixed models assessed the effects of BFR-E and Exercise only. Results: No adverse events due to exercise were reported. There was no contraction-number × condition interaction for EMG amplitude during exercise (p = 0.15), or time × condition interaction for single-pulse stmulation, SICI, ICF or M-max amplitude (p = 0.34 to p = 0.97). There was no difference between BFR-E and Exercise only in NRS scores (p = 0.10 to p = 0.50). Conclusion: Using our training paradigm, neurophysiological parameters, feasibility, tolerability and perceptions of safety were not different between BFR-E and Exercise only. As participants were generally well-functioning, our results are not generalizable to lower functioning people with stroke, different (more intense) exercise protocols or longer term training over weeks or months. [ABSTRACT FROM AUTHOR]

Dopaminergic signaling is a prerequisite for motor learning. Delayed degeneration of dopaminergic neurons after stroke is linked to motor learning deficits impairing motor rehabilitation. This study investigates safety and efficacy of substance P (SP) treatment on post-stroke rehabilitation, as this neuropeptide combines neuroprotective and plasticity-promoting properties. Male Sprague Dawley rats received a photothrombotic stroke within the primary motor cortex (M1) after which a previously acquired skilled reaching task was rehabilitated. Rats were treated with intraperitoneal saline (control group, n = 7) or SP-injections (250 µg/kg) 30 min before (SP-pre; n = 7) or 16 h (SP-post; n = 6) after rehabilitation training. Dopaminergic neurodegeneration, microglial activation and substance P-immunoreactivity (IR) were analyzed immunohistochemically. Systemic SP significantly facilitated motor rehabilitation. This effect was more pronounced in SP-pre compared to SP-post animals. SP prevented dopaminergic cell loss after stroke, particularly in the SP-pre condition. Despite its proinflammatory propensity, SP administration did not increase stroke volumes, post-stroke deficits or activation of microglia in the midbrain. Finally, SP administration prevented ipsilesional hypertrophy of striatal SPergic innervation, particularly in the SP-post condition. Mechanistically, SP-pre likely involved plasticity-promoting effects in the early phase of rehabilitation, whereas preservation of dopaminergic signaling may have ameliorated rehabilitative success in both SP groups during later stages of training. Our results demonstrate the facilitating effect of SP treatment on motor rehabilitation after stroke, especially if administered prior to training. SP furthermore prevented delayed dopaminergic degeneration and preserved physiological endogenous SPergic innervation. [ABSTRACT FROM AUTHOR]

Objective: Intermittent theta burst stimulation (iTBS) has been widely used as a neural modulation approach in stroke rehabilitation. Concurrent use of transcranial magnetic stimulation and electroencephalography (TMS-EEG) offers a chance to directly measure cortical reactivity and oscillatory dynamics and allows for investigating neural effects induced by iTBS in all stroke survivors including individuals without recordable MEPs. Here, we used TMS-EEG to investigate aftereffects of iTBS following stroke. Methods: We studied 22 stroke survivors (age: 65.2 ± 11.4 years; chronicity: 4.1 ± 3.5 months) with upper limb motor deficits. Upper-extremity component of Fugl-Meyer motor function assessment and action research arm test were used to measure motor function of stroke survivors. Stroke survivors were randomly divided into two groups receiving either Active or Sham iTBS applied over the ipsilesional primary motor cortex. TMS-EEG recordings were performed at baseline and immediately after Active or Sham iTBS. Time and time-frequency domain analyses were performed for quantifying TMS-evoked EEG responses. Results: At baseline, natural frequency was slower in the ipsilesional compared with the contralesional hemisphere (P = 0.006). Baseline natural frequency in the ipsilesional hemisphere was positively correlated with upper limb motor function following stroke (P = 0.007). After iTBS, natural frequency in the ipsilesional hemisphere was significantly increased (P < 0.001). Conclusions: This is the first study to investigate the acute neural adaptations after iTBS in stroke survivors using TMS-EEG. Our results revealed that natural frequency is altered following stroke which is related to motor impairments. iTBS increases natural frequency in the ipsilesional motor cortex in stroke survivors. Our findings implicate that iTBS holds the potential to normalize natural frequency in stroke survivors, which can be utilized in stroke rehabilitation. [ABSTRACT FROM AUTHOR]

Background and Purpose: Motor deficits are the most common disability after stroke, and early prediction of motor outcomes is critical for guiding the choice of early interventions. Two main factors that may impact the response to rehabilitation are variations in the microstructure of the affected corticospinal tract (CST) and genetic polymorphisms in brain-derived neurotrophic factor (BDNF). The purpose of this article was to review the role of these factors in stroke recovery, which will be useful for constructing a predictive model of rehabilitation outcomes. Summary of Review: We review the microstructure of the CST, including its origins in the primary motor area (M1), primary sensory area (S1), premotor cortex (PMC), and supplementary motor area (SMA). Damage to these fibers is disease-causing and can directly affect rehabilitation after subcortical stroke. BDNF polymorphisms are not disease-causing but can indirectly affect neuroplasticity and thus motor recovery. Both factors are known to be correlated with motor recovery. Further work is needed using large longitudinal patient samples and animal experiments to better establish the role of these two factors in stroke rehabilitation. Conclusions: Microstructure and genetic polymorphisms should be considered possible predictors or covariates in studies investigating motor recovery after subcortical stroke. Future predictive models of stroke recovery will likely include a combination of structural and genetic factors to allow precise individualization of stroke rehabilitation strategies. [ABSTRACT FROM AUTHOR]

Neural oscillations may contain important information pertaining to stroke rehabilitation. This study examined the predictive performance of electroencephalography‐derived neural oscillations following stroke using a data‐driven approach. Individuals with stroke admitted to an inpatient rehabilitation facility completed a resting‐state electroencephalography recording and structural neuroimaging around the time of admission and motor testing at admission and discharge. Using a lasso regression model with cross‐validation, we determined the extent of motor recovery (admission to discharge change in Functional Independence Measurement motor subscale score) prediction from electroencephalography, baseline motor status, and corticospinal tract injury. In 27 participants, coherence in a 1–30 Hz band between leads overlying ipsilesional primary motor cortex and 16 leads over bilateral hemispheres predicted 61.8% of the variance in motor recovery. High beta (20–30 Hz) and alpha (8–12 Hz) frequencies contributed most to the model demonstrating both positive and negative associations with motor recovery, including high beta leads in supplementary motor areas and ipsilesional ventral premotor and parietal regions and alpha leads overlying contralesional temporal–parietal and ipsilesional parietal regions. Electroencephalography power, baseline motor status, and corticospinal tract injury did not significantly predict motor recovery during hospitalization (R2 = 0–6.2%). Findings underscore the relevance of oscillatory synchronization in early stroke rehabilitation while highlighting contributions from beta and alpha frequency bands and frontal, parietal, and temporal–parietal regions overlooked by traditional hypothesis‐driven prediction models. [ABSTRACT FROM AUTHOR]

Background: Although dopaminergic medication has been the foundation of Parkinson's disease (PD) therapy for decades, sensitive and specific therapeutic response biomarkers that allow for better treatment optimization are lacking. Objective: We tested whether the features of Transcranial Magnetic Stimulation-based neurophysiological measures taken off-medication are associated with dopaminergic medication-induced clinical effects. Method: Motor cortex excitability [short-latency intracortical inhibition (SICI), intracortical facilitation (ICF), short-latency afferent inhibition (SAI), and input-output (IO) curve], and plasticity [paired associative stimulation (PAS) protocol] neurophysiological measures were examined in 23 PD patients off-medication. Clinical features were quantified by the motor section of the Unified Parkinson's Disease Scale (total score and lateralized total, bradykinesia, and rigidity sub-scores), and the differences between measures off-medication and on-medication (following the usual morning dose), were determined. Total daily dopaminergic medication dose (expressed as levodopa equivalent daily dose-LEDD), was also determined. Results: SICI significantly correlated with changes in lateralized UPDRS motor and bradykinesia sub-scores, suggesting that patients with stronger basal intracortical inhibition benefit more from dopaminergic treatment than patients with weaker intracortical inhibition. Also, ICF significantly negatively correlated with LEDD, suggesting that patients with stronger intracortical facilitation require less dopaminergic medication to achieve optimal therapeutic benefit. Both associations were independent of disease severity and duration. Conclusions: The results suggest variability of (patho) physiological phenotypes related to intracortical inhibitory and facilitatory mechanisms determining clinical response to dopaminergic medication in PD. Measures of intracortical excitability may help predict patients' response to dopaminergic therapy, thus potentially providing a background for developing personalized therapy in PD. [ABSTRACT FROM AUTHOR]

Executing voluntary motor actions in the upper extremities after a stroke is frequently challenging and frustrating. Although spontaneous motor recovery can occur, reorganizing the activation of the primary motor cortex and supplementary motor area takes a considerable amount of time involving effective rehabilitation interventions. Based on motor control theory and experience-dependent neural plasticity, stroke protocols centered on bimanual movement coordination are generating considerable evidence in overcoming dysfunctional movements. Looking backward and forward in this comprehensive review, we discuss noteworthy upper extremity improvements reported in bimanual movement coordination studies including force generation. Importantly, the effectiveness of chronic stroke rehabilitation approaches that involve voluntary interlimb coordination principles look promising. [ABSTRACT FROM AUTHOR]

Acupuncture is widely recognized as a potentially effective treatment for stroke rehabilitation. Researchers in this area are actively investigating its therapeutic mechanisms. Magnetic resonance imaging (MRI), as a noninvasive, high anatomical resolution technique, has been employed to investigate neuroplasticity on acupuncture in stroke patients from a system level. However, there is no review on the mechanism of acupuncture treatment for stroke based on MRI. Therefore, we aim to summarize the current evidence about this aspect and provide useful information for future research. After searching PubMed, Web of Science, and Embase databases, 24 human and five animal studies were identified. This review focuses on the evidence on the possible mechanisms underlying mechanisms of acupuncture therapy in treating stroke by regulating brain plasticity. We found that acupuncture reorganizes not only motor-related network, including primary motor cortex (M1), premotor cortex, supplementary motor area (SMA), frontoparietal network (LFPN and RFPN), and sensorimotor network (SMN), as well as default mode network (aDMN and pDMN), but also language-related brain areas including inferior frontal gyrus frontal, temporal, parietal, and occipital lobes, as well as cognition-related brain regions. In addition, acupuncture therapy can modulate the function and structural plasticity of post-stroke, which may be linked to the mechanism effect of acupuncture. [ABSTRACT FROM AUTHOR]

Inhibitory control is the ability to suppress inappropriate movements and unwanted actions, allowing to regulate impulses and responses. This ability can be measured via the Stop Signal Task, which provides a temporal index of response inhibition, namely the stop signal reaction time (SSRT). At the neural level, Transcranial Magnetic Stimulation (TMS) allows to investigate motor inhibition within the primary motor cortex (M1), such as the cortical silent period (CSP) which is an index of GABAB-mediated intracortical inhibition within M1. Although there is strong evidence that intracortical inhibition varies during action stopping, it is still not clear whether differences in the neurophysiological markers of intracortical inhibition contribute to behavioral differences in actual inhibitory capacities. Hence, here we explored the relationship between intracortical inhibition within M1 and behavioral response inhibition. GABABergic-mediated inhibition in M1 was determined by the duration of CSP, while behavioral inhibition was assessed by the SSRT. We found a significant positive correlation between CSP's duration and SSRT, namely that individuals with greater levels of GABABergic-mediated inhibition seem to perform overall worse in inhibiting behavioral responses. These results support the assumption that individual differences in intracortical inhibition are mirrored by individual differences in action stopping abilities. [ABSTRACT FROM AUTHOR]

Magnetic resonance spectroscopy (MRS) measures cerebral metabolite concentrations, which can inform our understanding of the neurobiological processes associated with stroke recovery. Here, we investigated whether metabolite concentrations in primary motor and somatosensory cortices (sensorimotor cortex) are impacted by stroke and relate to upper‐extremity motor impairment in 45 individuals with chronic stroke. Cerebral metabolite estimates were adjusted for cerebrospinal fluid and brain tissue composition in the MRS voxel. Upper‐extremity motor impairment was indexed with the Fugl‐Meyer (FM) scale. N‐acetylaspartate (NAA) concentration was reduced bilaterally in stroke participants with right hemisphere lesions (n = 23), relative to right‐handed healthy older adults (n = 15; p =.006). Within the entire stroke sample (n = 45) NAA and glutamate/glutamine (GLX) were lower in the ipsilesional sensorimotor cortex, relative to the contralesional cortex (NAA: p <.001; GLX: p =.003). Lower ipsilesional NAA was related to greater extent of corticospinal tract (CST) injury, quantified by a weighted CST lesion load (p =.006). Cortical NAA and GLX concentrations did not relate to the severity of chronic upper‐extremity impairment (p >.05), including after a sensitivity analysis imputing missing metabolite data for individuals with large cortical lesions (n = 5). Our results suggest that NAA, a marker of neuronal integrity, is sensitive to stroke‐related cortical damage and may provide mechanistic insights into cellular processes of cortical adaptation to stroke. However, cortical MRS metabolites may have limited clinical utility as prospective biomarkers of upper‐extremity outcomes in chronic stroke. [ABSTRACT FROM AUTHOR]

The spatial accuracy of transcranial magnetic stimulation (TMS) may be as small as a few millimeters. Despite such great potential, navigated TMS (nTMS) mapping is still underused for the assessment of motor plasticity, particularly in clinical settings. Here, we investigate the within‐limb somatotopy gradient as well as absolute and relative reliability of three hand muscle cortical representations (MCRs) using a comprehensive grid‐based sulcus‐informed nTMS motor mapping. We enrolled 22 young healthy male volunteers. Two nTMS mapping sessions were separated by 5–10 days. Motor evoked potentials were obtained from abductor pollicis brevis (APB), abductor digiti minimi, and extensor digitorum communis. In addition to individual MRI‐based analysis, we studied normalized MNI MCRs. For the reliability assessment, we calculated intraclass correlation and the smallest detectable change. Our results revealed a somatotopy gradient reflected by APB MCR having the most lateral location. Reliability analysis showed that the commonly used metrics of MCRs, such as areas, volumes, centers of gravity (COGs), and hotspots had a high relative and low absolute reliability for all three muscles. For within‐limb TMS somatotopy, the most common metrics such as the shifts between MCR COGs and hotspots had poor relative reliability. However, overlaps between different muscle MCRs were highly reliable. We, thus, provide novel evidence that inter‐muscle MCR interaction can be reliably traced using MCR overlaps while shifts between the COGs and hotspots of different MCRs are not suitable for this purpose. Our results have implications for the interpretation of nTMS motor mapping results in healthy subjects and patients with neurological conditions. [ABSTRACT FROM AUTHOR]

Bimanual coordination is essential for the performance of many everyday tasks. There are several types of bimanually coordinated movements, classified according to whether the arms are acting to achieve a single goal (cooperative) or separate goals (independent), and whether the arms are moving symmetrically or asymmetrically. Symmetric bimanual movements are thought to facilitate corticomotor excitability (CME), while asymmetric bimanual movements are thought to recruit interhemispheric inhibition to reduce functional coupling between the motor cortices. The influences of movement symmetry and goal conceptualisation on interhemispheric interactions have not been studied together, and not during bimanually active dynamic tasks. The present study used transcranial magnetic stimulation (TMS) to investigate the modulation of CME and short- and long-latency interhemispheric inhibition (SIHI and LIHI, respectively) during bimanually active dynamic tasks requiring different types of bimanual coordination. Twenty healthy right-handed adults performed four bimanual tasks in which they held a dumbbell in each hand (independent) or a custom device between both hands (cooperative) while rhythmically flexing and extending their wrists symmetrically or asymmetrically. Motor-evoked potentials were recorded from the right extensor carpi ulnaris. We found CME was greater during asymmetric tasks than symmetric tasks, and movement symmetry did not modulate SIHI or LIHI. There was no effect of goal conceptualisation nor any interaction with movement symmetry for CME, SIHI or LIHI. Based on these results, movement symmetry and goal conceptualisation may not modulate interhemispheric inhibition during dynamic bimanual tasks. These findings contradict prevailing thinking about the roles of CME and interhemispheric inhibition in bimanual coordination. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate whether oxygenated hemoglobin (oxy-Hb) generated during a motor imagery (MI) task is associated with the motor learning level of the task. Methods: We included 16 right-handed healthy participants who were trained to perform a ball rotation (BR) task. Hemodynamic brain activity was measured using near-infrared spectroscopy to monitor changes in oxy-Hb concentration during the BR MI task. The experimental protocol used a block design, and measurements were performed three times before and after the initial training of the BR task as well as after the final training. The BR count during training was also measured. Furthermore, subjective vividness of MI was evaluated three times after NIRS measurement using the Visual Analog Scale (VAS). Results: The results showed that the number of BRs increased significantly with training (P < 0.001). VAS scores also improved with training (P < 0.001). Furthermore, oxy-Hb concentration and the region of interest (ROI) showed a main effect (P = 0.001). An interaction was confirmed (P < 0.001), and it was ascertained that the change in oxy-Hb concentrations due to training was different for each ROI. The most significant predictor of subjective MI vividness was supplementary motor area (SMA) oxy-Hb concentration (coefficient = 0.365). Discussion: Hemodynamic brain activity during MI tasks may be correlated with task motor learning levels, since significant changes in oxy-Hb concentrations were observed following initial and final training in the SMA. In particular, hemodynamic brain activity in the SMA was suggested to reflect the MI vividness of participants. [ABSTRACT FROM AUTHOR]

Introduction: Previous transcranial magnetic stimulation (TMS) studies have revealed that the activity of the primary motor cortex ipsilateral to an active hand (ipsi-M1) plays an important role in motor control. The aim of this study was to investigate whether the ipsi-M1 excitability would be influenced by goal-directed movement and laterality during unilateral finger movements. Method: Ten healthy right-handed subjects performed four finger tapping tasks with the index finger: (1) simple tapping (Tap) task, (2) Real-word task, (3) Pseudoword task, and (4) Visually guided tapping (VT) task. In the Tap task, the subject performed self-paced simple tapping on a touch screen. In the real-word task, the subject tapped letters displayed on the screen one by one to create a Real-word (e.g., apple). Because the action had a specific purpose (i.e., creating a word), this task was considered to be goal-directed as compared to the Tap task. In the Pseudoword task, the subject tapped the letters to create a pseudoword (e.g., gdiok) in the same manner as in the Real-word task; however, the word was less meaningful. In the VT task, the subject was required to touch a series of illuminated buttons. This task was considered to be less goal-directed than the Pseudoword task. The tasks were performed with the right and left hand, and a rest condition was added as control. Single- and paired-pulse TMS were applied to the ipsi-M1 to measure corticospinal excitability and short- and long-interval intracortical inhibition (SICI and LICI) in the resting first dorsal interosseous (FDI) muscle. Results: We found the smaller SICI in the ipsi-M1 during the VT task compared with the resting condition. Further, both SICI and LICI were smaller in the right than in the left M1, regardless of the task conditions. Discussion: We found that SICI in the ipsi-M1 is smaller during visual illumination-guided finger movement than during the resting condition. Our finding provides basic data for designing a rehabilitation program that modulates the M1 ipsilateral to the moving limb, for example, for post-stroke patients with severe hemiparesis. [ABSTRACT FROM AUTHOR]