Corticospinal Integrity Research Articles

Identifying biomarkers related to motor function in chronic stroke: A fNIRS and TMS study.

Upper limb motor impairment commonly occurs after stroke, impairing quality of life. Brain network reorganization likely differs between subgroups with differing impairment severity. This study explored differences in functional connectivity (FC) and corticospinal tract (CST) integrity between patients with mild/moderate versus severe hemiplegia poststroke to clarify the neural correlates underlying motor deficits. Sixty chronic stroke patients with upper limb motor impairment were categorized into mild/moderate and severe groups based on Fugl-Meyer scores. Resting-state FC was assessed using functional near-infrared spectroscopy (fNIRS) to compare connectivity patterns between groups across motor regions. CST integrity was evaluated by inducing motor evoked potentials (MEP) via transcranial magnetic stimulation. Compared to the mild/moderate group, the severe group exhibited heightened premotor cortex-primary motor cortex (PMC-M1) connectivity (t = 4.56, p < 0.01). Absence of MEP was also more frequent in the severe group (χ2 = 12.31, p = 0.01). Bayesian models effectively distinguished subgroups and identified the PMC-M1 connection as highly contributory (accuracy = 91.30%, area under the receiver operating characteristic curve [AUC] = 0.86). Distinct patterns of connectivity and corticospinal integrity exist between stroke subgroups with differing impairments. Strengthened connectivity potentially indicates recruitment of additional motor resources to compensate for damage. These findings elucidate the neural correlates underlying motor deficits poststroke and could guide personalized, network-based therapies targeting predictive biomarkers to improve rehabilitation outcomes.

From Molecule to Patient Rehabilitation: The Impact of Transcranial Direct Current Stimulation and Magnetic Stimulation on Stroke-A Narrative Review.

Stroke is a major health problem worldwide, with numerous health, social, and economic implications for survivors and their families. One simple answer to this problem would be to ensure the best rehabilitation with full social reintegration. As such, a plethora of rehabilitation programs was developed and used by healthcare professionals. Among them, modern techniques such as transcranial magnetic stimulation and transcranial direct current stimulation are being used and seem to bring improvements to poststroke rehabilitation. This success is attributed to their capacity to enhance cellular neuromodulation. This modulation includes the reduction of the inflammatory response, autophagy suppression, antiapoptotic effects, angiogenesis enhancement, alterations in the blood-brain barrier permeability, attenuation of oxidative stress, influence on neurotransmitter metabolism, neurogenesis, and enhanced structural neuroplasticity. The favorable effects have been demonstrated at the cellular level in animal models and are supported by clinical studies. Thus, these methods proved to reduce infarct volumes and to improve motor performance, deglutition, functional independence, and high-order cerebral functions (i.e., aphasia and heminegligence). However, as with every therapeutic method, these techniques can also have limitations. Their regimen of administration, the phase of the stroke at which they are applied, and the patients' characteristics (i.e., genotype and corticospinal integrity) seem to influence the outcome. Thus, no response or even worsening effects were obtained under certain circumstances both in animal stroke model studies and in clinical trials. Overall, weighing up risks and benefits, the new transcranial electrical and magnetic stimulation techniques can represent effective tools with which to improve the patients' recovery after stroke, with minimal to no adverse effects. Here, we discuss their effects and the molecular and cellular events underlying their effects as well as their clinical implications.

Multiple sclerosis-related heat sensitivity linked to absence of DMT prescription and subjective hand impairment but not autonomic or corticospinal dysfunction.

Heat sensitivity (HS) describes a temporary worsening of multiple sclerosis (MS) symptoms with increased body temperature. The pathophysiology may relate to central nervous system conduction deficits and autonomic dysfunction. We conducted deep clinical phenotyping of a cohort of persons with MS to identify predictors of HS. We recruited 59 MS participants with HS or No HS. Participants self-reported symptom severity (Hospital Anxiety and Depression Scale, Multiple Sclerosis Impact Scale, and fatigue visual analog scale) and underwent maximal exercise and transcranial magnetic stimulation testing to characterize autonomic and corticospinal function. We examined associations with HS using binomial logistic regression. People with HS (36/59) had significantly greater disability, depression, fatigue, and physical and psychological functional effects of MS. They also had significantly lower corticospinal excitability but not conduction. After controlling for disease-modifying therapy (DMT), disability, and disease type, self-reported difficulty using hands in everyday tasks was significantly associated with a large increase in the odds of HS. Autonomic and corticospinal dysfunction were not associated with HS. Lack of DMT use alone was also associated with a large increase in the odds of HS. Following a comprehensive assessment of plausible contributors to HS, HS was most strongly associated with lack of a DMT prescription and self-reported hand dysfunction. Surprisingly, objective measurement of autonomic and corticospinal integrity did not contribute to HS.

Recovery of walking in nonambulatory children with chronic spinal cord injuries: Case series.

The immature central nervous system is recognized as having substantial neuroplastic capacity. In this study, we explored the hypothesis that rehabilitation can exploit that potential and elicit reciprocal walking in nonambulatory children with chronic, severe (i.e., lower extremity motor score < 10/50) spinal cord injuries (SCIs). Seven male subjects (3-12 years of age) who were at least 1-year post-SCI and incapable of discrete leg movements believed to be required for walking, enrolled in activity-based locomotor training (ABLT; clinicaltrials.gov NCT00488280). Six children completed the study. Following a minimum of 49 sessions of ABLT, three of the six children achieved walking with reverse rolling walkers. Stepping development, however, was not accompanied by improvement in discrete leg movements as underscored by the persistence of synergistic movements and little change in lower extremity motor scores. Interestingly, acoustic startle responses exhibited by the three responding children suggested preserved reticulospinal inputs to circuitry below the level of injury capable of mediating leg movements. On the other hand, no indication of corticospinal integrity was obtained with transcranial magnetic stimulation evoked responses in the same individuals. These findings suggest some children who are not predicted to improve motor and locomotor function may have a reserve of adaptive plasticity that can emerge in response to rehabilitative strategies such as ABLT. Further studies are warranted to determine whether a critical need exists to re-examine rehabilitation approaches for pediatric SCI with poor prognosis for any ambulatory recovery.

Blood pressure changes impact corticospinal integrity and downstream gait and balance control

Blood pressure (BP) plays an important role in white matter integrity. We sought to determine the role of intra-individual BP changes on white matter and evaluate the impact on gait speed and imbalance by sex. We identified 990 eligible participants in the population-based Mayo Clinic Study of Aging and analyzed fractional anisotropy (FA) in white matter regions. Using structural equation models (SEM), we assessed the effect of BP slope on corticospinal tract (CST) FA and downstream effects on gait speed and imbalance after age and sex effects. Of 990 participants, 438 (44%) were female with mean age of 76 years. In linear models predicting CST FA, a greater change in BP slope (0.0004; p = 0.026) and female sex (0.017; p < 0.001) were significant predictors of lower CST FA. SEMs showed that older age, female sex, and higher BP slope predicted lower CST FA, and lower CST FA predicted worse downstream motor control. Therefore, intra-individual BP slope and variability impact corticospinal tract microstructural properties of white matter with females having increased susceptibility to damage.

Effect of a tailored upper extremity strength training intervention combined with direct current stimulation in chronic stroke survivors: A Randomized Controlled Trial.

Strengthening exercises are recommended for managing persisting upper limb (UL) weakness following a stroke. Yet, strengthening exercises often lead to variable gains because of their generic nature. For this randomized controlled trial (RCT), we aimed to determine whether tailoring strengthening exercises using a biomarker of corticospinal integrity, as reflected in the amplitude of motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS), could optimize training effects in the affected UL. A secondary aim was to determine whether applying anodal transcranial direct current stimulation (tDCS) could enhance exercise-induced training effects. For this multisite RCT, 90 adults at the chronic stage after stroke (>6 months) were recruited. Before training, participants underwent TMS to detect the presence of MEPs in the affected hand. The MEP amplitude was used to stratify participants into three training groups: (1) low-intensity, MEP <50 μV, (2) moderate-intensity, 50 μV < MEP < 120 μV, and (3) high-intensity, MEP>120 μV. Each group trained at a specific intensity based on the one-repetition maximum (1 RM): low-intensity, 35–50% 1RM; moderate-intensity, 50–65% 1RM; high-intensity, 70–85% 1RM. The strength training targeted the affected UL and was delivered 3X/week for four consecutive weeks. In each training group, participants were randomly assigned to receive either real or sham anodal tDCS (2 mA, 20 min) over the primary motor area of the affected hemisphere. Pre-/post-intervention, participants underwent a clinical evaluation of their UL to evaluate motor impairments (Fugl-Meyer Assessment), manual dexterity (Box and Blocks test) and grip strength. Post-intervention, all groups exhibited similar gains in terms of reduced impairments, improved dexterity, and grip strength, which was confirmed by multivariate and univariate analyses. However, no effect of interaction was found for tDCS or training group, indicating that tDCS had no significant impact on outcomes post-intervention. Collectively, these results indicate that adjusting training intensity based on the size of MEPs in the affected extremity provides a useful approach to optimize responses to strengthening exercises in chronic stroke survivors. Also, the lack of add-on effects of tDCS applied to the lesioned hemisphere on exercise-induced improvements in the affected UL raises questions about the relevance of combining such interventions in stroke.Clinical trial registry numberNCT02915185. https://www.clinicaltrials.gov/ct2/show/NCT02915185.

The role of Neuroradiology in Neuroplasticity: New advancements

Neuroplasticity, the brain’s capacity to adapt to internal and external environmental changes, occurs physiologically throughout growth and in reaction to damage. Many MRI studies of neuroplasticity have shown strong evidence that the brain changes quickly and extensively when people have new experiences. · In this paper, we review the most advancement in the role of neuroradiology in neuroplasticity and using biomarkers. o Detecting neuroplasticity in global brain circuits in vivo is critical for understanding various processes such as memory, learning, and injury healing. o MRI-biomarkers can be used to check for corticospinal integrity and how well motor resources are used. White matter neuroplasticity is studied via MRI. It has been used to study structural changes using diffusion tensor imaging (DTI) o The ultrafast fMRI (ufMRI) technique allows for high spatiotemporal sensitivity and resolution in dispersed brain circuits to detect fMRI signals more connected with the underlying neural dynamics. White matter hemodynamics may change over time, explaining functional neuroplasticity in this tissue.

Impaired phase synchronization of motor-evoked potentials reflects the degree of motor dysfunction in the lesioned human brain.

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.

Dual transcranial direct current stimulation for subacute stroke patients with compromised corticospinal integrity: a randomized, double-blind, sham-controlled study

Dual transcranial direct current stimulation for subacute stroke patients with compromised corticospinal integrity: a randomized, double-blind, sham-controlled study

Time-Frequency Representation of Motor Evoked Potentials in Brain Tumor Patients.

Background: The integrity of the motor system can be examined by applying navigated transcranial magnetic stimulation (nTMS) to the cortex. The corresponding motor-evoked potentials (MEPs) in the target muscles are mirroring the status of the human motor system, far beyond corticospinal integrity. Commonly used time domain features of MEPs (e.g., peak-to-peak amplitudes and onset latencies) exert a high inter-subject and intra-subject variability. Frequency domain analysis might help to resolve or quantify disease-related MEP changes, e.g., in brain tumor patients. The aim of the present study was to describe the time-frequency representation of MEPs in brain tumor patients, its relation to clinical and imaging findings, and the differences to healthy subject.Methods: This prospective study compared 12 healthy subjects with 12 consecutive brain tumor patients (with and without a paresis) applying nTMS mapping. Resulting MEPs were evaluated in the time series domain (i.e., amplitudes and latencies). After transformation into the frequency domain using a Morlet wavelet approach, event-related spectral perturbation (ERSP), and inter-trial coherence (ITC) were calculated and compared to diffusion tensor imaging (DTI) results.Results: There were no significant differences in the time series characteristics between groups. MEPs were projecting to a frequency band between 30 and 300 Hz with a local maximum around 100 Hz for both healthy subjects and patients. However, there was ERSP reduction for higher frequencies (>100 Hz) in patients in contrast to healthy subjects. This deceleration was mirrored in an increase of the inter-peak MEP latencies. Patients with a paresis showed an additional disturbance in ITC in these frequencies. There was no correlation between the CST integrity (as measured by DTI) and the MEP parameters.Conclusion: Time-frequency analysis may provide additional information above and beyond classical MEP time domain features and the status of the corticospinal system in brain tumor patients. This first evaluation indicates that brain tumors might affect cortical physiology and the responsiveness of the cortex to TMS resulting in a temporal dispersion of the corticospinal transmission.

Targeted Walking in Incomplete Spinal Cord Injury: Role of Corticospinal Control.

Locomotor recovery after incomplete spinal cord injury (iSCI) is influenced by spinal and supraspinal networks. Conventional clinical gait analysis fails to differentiate between these components. There is evidence that corticospinal control is enhanced during targeted walking, where each foot must be continuously placed on visual targets in randomized order. This study investigates the potential of targeted walking in the functional assessment of corticospinal integrity. Twenty-one controls and 16 individuals with chronic iSCI performed normal and targeted walking on a treadmill while electromyograms (EMGs) and kinematics were recorded. Precision (% of accurate foot placements) in targeted walking was significantly lower in individuals with iSCI (82.9 ± 14.7%, controls: 94.9 ± 4.0%). Although the overall kinematic pattern was comparable between walking conditions, controls showed significantly higher semitendinosus (ST) activity before heel-strike during targeted walking. This was accompanied by a shift of relative EMG intensity from 90-120 Hz to lower frequencies of 20-60 Hz, previously associated with corticospinal control of muscle activity. Targeted walking in individuals with iSCI evoked smaller EMG changes, suggesting that the switch to more corticospinal control is impaired. Accordingly, mildly impaired iSCI individuals revealed higher adaptations to the targeted walking task than more-impaired individuals. Recording of EMGs during targeted walking holds potential as a research tool to reveal further insights into the neuromuscular control of locomotion. It also complements findings of pre-clinical studies and is a promising novel surrogate marker of integrity of corticospinal control in individuals with iSCI and other neurological impairments. Future studies should investigate its potential for diagnosis or tracking recovery during rehabilitation.

Impact of Corticospinal Integrity on the Effects of tDCS

To determine if cathodal and anodal tDCS would yield differential effects depending on presence or absence of motor evoked potentials (MEP +, MEP-), measured with transcranial magnetic stimulation at baseline.

Clinical improvement with intensive robot-assisted arm training in chronic stroke is unchanged by supplementary tDCS.

Intensive robot-assisted arm training in the chronic phase of stroke recovery can lead to clinical improvement. Combinatorial therapeutic approaches are sought to further optimize stroke recovery. Transcranial direct current stimulation (tDCS) is one candidate to combine with robotic training, as transient increases in excitability and improvements in motor behavior have separately been reported. To determine whether tDCS, delivered prior to robotic training, could augment clinical improvement. We conducted a dual-site, randomized controlled trial in 82 chronic ischemic stroke patients (inclusion > 6 m post-injury, dominant hemisphere, first stroke; residual hemiparesis) who were split into two groups to receive tDCS (M1-SO montage, anode ipsilesional, 5×7 cm electrodes, 2 mA, 20 mins) or sham tDCS, prior to robotic upper-limb training (12 weeks; 36 sessions; shoulder-elbow robot or wrist robot on alternating sessions). The primary end-point was taken after 12 weeks of training, and assessed with the Upper Extremity Fugl-Meyer impairment scale (FM). Corticomotor conduction was assessed with transcranial magnetic stimulation (TMS). For the combined group (n = 82; post-training) robotic training increased the FM by 7.36 points compared to baseline (p < 0.0001). There was no difference in the FM increase between the tDCS and sham groups (6.97 and 7.73 respectively, p = 0.46). In both groups, clinically meaningful improvement (≥5 points) from baseline was evident in the majority of patients (56/77), was sustained six months later (54/72), and could be attained in severe, moderate and mild baseline hemiparesis. Clinical improvement was associated with increased excitability in the affected hemisphere as assessed by resting motor threshold (pre-post p = 0.029; pre-post 6 months p = 0.029), but not with threshold-adjusted assessment of MEP amplitude (pre-post p = 0.09; pre-post 6 months p = 0.15). Participants with motor evoked potentials were more likely to improve clinically than those without (17/18, 94%, versus 39/59, 66%, p = 0.018). Our study confirms the benefit of intensive robot-assisted training in stroke recovery, and indicates that conventional tDCS does not confer further advantage to robotic training. We also showed that corticospinal integrity, as assessed by TMS, is a predictor of clinically meaningful response to intensive arm therapy in chronic stroke.

A population-based atlas of the human pyramidal tract in 410 healthy participants.

With the advances in diffusion MRI and tractography, numerous atlases of the human pyramidal tract (PyT) have been proposed, but the inherent limitation of tractography to resolve crossing bundles within the centrum semiovale has so far prevented the complete description of the most lateral PyT projections. Here, we combined a precise manual positioning of individual subcortical regions of interest along the descending pathway of the PyT with a new bundle-specific tractography algorithm. This later is based on anatomical priors to improve streamlines tracking in crossing areas. We then extracted both left and right PyT in a large cohort of 410 healthy participants and built a population-based atlas of the whole-fanning PyT with a complete description of its most corticolateral projections. Clinical applications are envisaged, the whole-fanning PyT atlas being likely a better marker of corticospinal integrity metrics than those currently used within the frame of prediction of poststroke motor recovery. The present population-based PyT, freely available, provides an interesting tool for clinical applications to locate specific PyT damage and its impact to the short- and long-term motor recovery after stroke.

Noninvasive neuromodulation for rehabilitation of sensorimotor function and reduction of chronic pain

Objectives People with motor disorders or chronic pain demonstrate plateaued improvements despite compliance with therapy and willing to improve daily life quality. This limitation may result from brain maladaptive plasticity (pathways, maps). Therefore, noninvasive neuromodulation, via painless repetitive magnetic stimulation of brain or muscles, is tested in research to influence brain mechanisms that favor recovery. But no consensus yet is proposed about the most efficient protocols. The talk focuses on the need to individualize the approach, i.e., to adapt neurostimulation protocols owing to individual factors (e.g., lesion or pain severity and side, balance of hemispheric activity, pathways integrity). Methods The research breakthroughs in collaboration with clinicians are illustrated by data in chronic stroke, cerebral palsy, traumatic brain injury, immobilization (learned non-use), Parkinson's disease, chronic low back pain, complex regional pain syndrome. The respective influence of brain and peripheral neurostimulation on clinical outcomes has been related to brain plasticity (markers of the primary motor cortex (M1) function: M1 excitability, structural reserve, factors predictive of success). Results Studies suggest that protocols of neurostimulation should be case-specific and adapted to the intertwined influences of M1 excitability imbalance, corticospinal integrity (M1 structural reserve for rehabilitation) and lesion or pain side (dominant, non-dominant). Neurostimulation systematically improved responsiveness to subsequent therapy and the persistence of changes has been related to sessions repetition, combination with therapy, and cognitive integrity. Conclusion Further efforts are warranted to adapt neuromodulation/neurostimulation protocols per patient owing to neuroplastic changes that favor vs. hinder improvement of function. A sole solution for all cases is not suggested. An individualized approach relying on biomarkers and clinical outcomes should ease the implementation in clinical practice of noninvasive neuromodulation as an innovative therapeutic option to speed-up recovery towards gains beyond those already reached, thus to further improve the quality of life.

PREP2: A biomarker-based algorithm for predicting upper limb function after stroke.

ObjectiveRecovery of motor function is important for regaining independence after stroke, but difficult to predict for individual patients. Our aim was to develop an efficient, accurate, and accessible algorithm for use in clinical settings. Clinical, neurophysiological, and neuroimaging biomarkers of corticospinal integrity obtained within days of stroke were combined to predict likely upper limb motor outcomes 3 months after stroke.MethodsData from 207 patients recruited within 3 days of stroke [103 females (50%), median age 72 (range 18–98) years] were included in a Classification and Regression Tree analysis to predict upper limb function 3 months poststroke.ResultsThe analysis produced an algorithm that sequentially combined a measure of upper limb impairment; age; the presence or absence of upper limb motor evoked potentials elicited with transcranial magnetic stimulation; and stroke lesion load obtained from MRI or stroke severity assessed with the NIHSS score. The algorithm makes correct predictions for 75% of patients. A key biomarker obtained with transcranial magnetic stimulation is required for one third of patients. This biomarker combined with NIHSS score can be used in place of more costly magnetic resonance imaging, with no loss of prediction accuracy.InterpretationThe new algorithm is more accurate, efficient, and accessible than its predecessors, which may support its use in clinical practice. While further work is needed to potentially incorporate sensory and cognitive factors, the algorithm can be used within days of stroke to provide accurate predictions of upper limb functional outcomes at 3 months after stroke. www.presto.auckland.ac.nz

Spontaneous brain activity in the sensorimotor cortex in amyotrophic lateral sclerosis can be negatively regulated by corticospinal fiber integrity

Previous studies failed to detect reduced value of the amplitude of low frequency fluctuation (ALFF) derived from resting state functional magnetic resonance imaging in the primary motor cortex in amyotrophic lateral sclerosis (ALS) though primary motor cortex was mainly affected with ALS. We aimed to investigate the cause of masking the abnormality in the primary motor cortex in ALS and usefulness of ALFF for differential diagnosis among diseases showing muscle weakness. We enrolled ten patients with ALS and eleven disease controls showing muscle weakness. Voxel-wise analysis revealed that significant reduction of ALFF value was present in the right sensorimotor cortex in ALS. There was a significant negative correlation between ALFF value in the right sensorimotor cortex and fractional anisotropy (FA) value in the posterior limbs of the internal capsule (PLIC). For a diagnostic tool, the area under receiver operating characteristic curve improved if the ALS patients with disease duration >1year were excluded. The present findings raised the possibility of usefulness of ALFF value in the sensorimotor cortex for differential diagnosis of ALS, and supported the notion that adjustment for FA value in the PLIC could improve accuracy.

MRI Biomarkers for Hand-Motor Outcome Prediction and Therapy Monitoring following Stroke.

Several biomarkers have been identified which enable a considerable prediction of hand-motor outcome after cerebral damage already in the subacute stage after stroke. We here review the value of MRI biomarkers in the evaluation of corticospinal integrity and functional recruitment of motor resources. Many of the functional imaging parameters are not feasible early after stroke or for patients with high impairment and low compliance. Whereas functional connectivity parameters have demonstrated varying results on their predictive value for hand-motor outcome, corticospinal integrity evaluation using structural imaging showed robust and high predictive power for patients with different levels of impairment. Although this is indicative of an overall higher value of structural imaging for prediction, we suggest that this variation be explained by structure and function relationships. To gain more insight into the recovering brain, not only one biomarker is needed. We rather argue for a combination of different measures in an algorithm to classify fine-graded subgroups of patients. Approaches to determining biomarkers have to take into account the established markers to provide further information on certain subgroups. Assessing the best therapy approaches for individual patients will become more feasible as these subgroups become specified in more detail. This procedure will help to considerably save resources and optimize neurorehabilitative therapy.

Noninvasive neurostimulation in chronic stroke: a double-blind randomized sham-controlled testing of clinical and corticomotor effects

Background:Repetitive peripheral magnetic stimulation (RPMS) is a painless and noninvasive method to produce afferents via the depolarization of the peripheral nervous system. A few studies tested RPMS after-effects on cerebral plasticity and motor recovery in stroke individuals, but evidences remain limited.Objectives:This study aimed to explore whether RPMS could mediate improvements in corticomotor and clinical outcomes associated with ankle impairments in chronic stroke.Methods:Eighteen subjects with chronic stroke were randomly allocated to RPMS or sham group and compared to 14 healthy subjects. Stimulation was applied over the paretic tibialis anterior (TA). Ankle impairments on the paretic side and ipsilesional TA cortical motor representation were tested clinically and by transcranial magnetic stimulation (TMS), respectively.Results:In the RPMS group, ankle dorsiflexion mobility and maximal isometric strength increased and resistance to plantar flexor stretch decreased. The magnitude of change seemed to be related to cortical and corticospinal integrity. Sham stimulation yielded no effect. Changes in TMS outcome and their relationships with clinical improvements were limited.Conclusions:RPMS improved ankle impairments in chronic stroke likely by a dynamic influence of sensory inputs on synaptic plasticity. The neurophysiological mechanisms potentially underlying the clinical effects are unclear. More studies are warranted to test the spinal and hemispheric changes responsible for the clinical improvements with emphasis on circuits spared by the lesion.

Corticospinal Integrity and Motor Impairment Predict Outcomes After Excitatory Repetitive Transcranial Magnetic Stimulation: A Preliminary Study

ObjectiveTo identify the effective predictors for therapeutic outcomes based on intermittent theta-burst stimulation (iTBS). DesignA sham-controlled, double-blind parallel study design. SettingA tertiary hospital. ParticipantsPeople with stroke (N=72) who presented with unilateral hemiplegia. InterventionsTen consecutive sessions of real or sham iTBS were implemented with the aim of enhancing hand function. Patients were categorized into 4 groups according to the presence (MEP+) or absence (MEP−) of motor-evoked potentials (MEPs) and grip strength according to the Medical Research Council (MRC) scale. Main Outcome MeasuresCortical excitability, Wolf Motor Function Test (WMFT), finger-tapping task (FT), and simple reaction time were performed before and after the sessions. ResultsMEPs and the MRC scale were predictive of iTBS therapeutic outcomes. Group A (MEP+, MRC>1) exhibited the greatest WMFT change (7.6±2.3, P<.001), followed by group B (MEP−, MRC>1; 5.2±2.2 score change) and group C (MEP−, MRC=0; 2.3±1.5 score change). These improvements were correlated significantly with baseline motor function and ipsilesional maximum MEP amplitude. ConclusionsThe effectiveness of iTBS modulation for poststroke motor enhancement depends on baseline hand grip strength and the presence of MEPs. Our findings indicate that establishing neurostimulation strategies based on the proposed electrophysiological and clinical criteria can allow iTBS to be executed with substantial precision. Effective neuromodulatory strategies can be formulated by using electrophysiological features and clinical presentation information as guidelines.