Cortico-spinal excitability and hand motor recovery in stroke: a longitudinal study

Objective

To describe the relationship between changes of cortico-spinal excitability and motor recovery of the affected hand after stroke.

Methods

Eighteen hemiparetic stroke patients with a severe-to-mild upper limb motor impairment were randomized. Cortico-spinal excitability measures (resting motor thresholds and motor evoked potentials) obtained from a distal (abductor pollicis brevis) and proximal (biceps brachii) upper limb muscle were assessed for both hemispheres. Motor function of the affected hand was tested by the Wolf Motor Function and Action Research Arm tests. The evaluations were performed at baseline and weekly over 7 weeks of in-patient neurological rehabilitation.

Results

Severe hand dysfunction was associated with a strong suppression of ipsilesional cortico-spinal excitability and a shift of excitability towards the contralesional hemisphere. Mild hand impairment was associated with a shift of cortico-spinal excitability towards the ipsilesional hemisphere. Favorable motor recovery correlated with an increase of ipsilesional cortico-spinal excitability.

     

Proactive Motor Functional Recovery Following Immersive Virtual Reality–Based Limb Mirroring Therapy in Patients with Subacute Stroke

Virtual reality (VR) is considered to be a promising therapeutic technology for the rehabilitation of upper extremities (UEs) post-stroke. Recently, we designed and then implemented a neuroscientifically grounded VR protocol for the rehabilitation of patients with stroke. The system provides unilateral and bilateral limb mirroring exercises in a fully immersive virtual environment that may stimulate and activate the mirror neuron system in the brain to help patients for their rehabilitation. Twelve patients with subacute stroke underwent the newly implemented VR treatment in addition to conventional rehabilitation for 8 consecutive weekdays. The treatment effect on brain reorganization and motor function was investigated using resting-state fMRI (rs-fMRI) and the Fugl-Meyer assessment for Upper Extremity (FM-UE), respectively. Fifteen healthy controls (HCs) also underwent rs-fMRI scanning one time. The study finally obtained usable data from 8 patients and 13 HCs. After the intervention, patients demonstrated significant improvement in their FM-UE scores (p values < 0.042). Voxel-wise functional connectivity (FC) analysis based on the rs-fMRI data found that HCs showed widespread bilateral FC patterns associated with the dominant hemispheric primary motor cortex (M1). However, the FC patterns in patients revealed intra-hemispheric association with the ipsilesional M1 seed and this association became visible in the contra-hemisphere after the intervention. Moreover, the change of FC values between the bilateral M1 was significantly correlated with the changes in FM-UE scores (p values < 0.037). We conclude that unilateral and bilateral limb mirroring exercise in an immersive virtual environment may enhance cortical reorganization and lead to improved motor function.Electronic supplementary materialThe online version of this article (10.1007/s13311-020-00882-x) contains supplementary material, which is available to authorized users.Key Words: Virtual reality, limb mirroring therapy, mirror neuron system, stroke rehabilitation, resting-state fMRI, upper extremity     

BOLD fMRI signal in stroke patients and its importance for prognosis in the subacute disease period – Preliminary report

Functional magnetic resonance imaging (fMRI) allows for the assessment of neuronal activity through the blood-level-dependent signal. The purpose of study was to evaluate the pattern of brain activity in fMRI in patients with ischemic stroke and to assess the potential relationship between the activity pattern and the neurological/functional status.

Neurofunctional changes after a single mirror therapy intervention in chronic ischemic stroke

Background: Mirror therapy (MT) is becoming an alternative rehabilitation strategy for various conditions, including stroke. Although recent studies suggest the positive benefit of MT in chronic stroke motor recovery, little is known about its neural mechanisms.

Purpose: To identify functional brain changes induced by a single MT intervention in ischemic stroke survivors, assessed by both transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI).

Materials and methods: TMS and fMRI were used to investigate 15 stroke survivors immediately before and after a single 30-min MT session.

Results: We found statistically significant increase in post-MT motor evoked potential (MEP) amplitude (increased excitability) from the affected primary motor cortex (M1), when compared to pre-MT MEP. Post-MT fMRI maps were associated with a more organized and constrained pattern, with a more focal M1 activity within the affected hemisphere after MT, limited to the cortical area of hand representation. Furthermore, we find a change in the balance of M1 activity toward the affected hemisphere. In addition, significant correlation was found between decreased fMRI β-values and increased MEP amplitude post-MT, in the affected hemisphere.

Conclusion: Our study suggests that a single MT intervention in stroke survivors is related to increased MEP of the affected limb, and a more constrained activity of the affected M1, as if activity had become more constrained and limited to the affected hemisphere.     

Degeneration of corpus callosum and recovery of motor function after stroke: A multimodal magnetic resonance imaging study

Animal models of stroke demonstrated that white matter ischemia may cause both axonal damage and myelin degradation distant from the core lesion, thereby impacting on behavior and functional outcome after stroke. We here used parameters derived from diffusion magnetic resonance imaging (MRI) to investigate the effect of focal white matter ischemia on functional reorganization within the motor system. Patients (n = 18) suffering from hand motor deficits in the subacute or chronic stage after subcortical stroke and healthy controls (n = 12) were scanned with both diffusion MRI and functional MRI while performing a motor task with the left or right hand. A laterality index was employed on activated voxels to assess functional reorganization across hemispheres. Regression analyses revealed that diffusion MRI parameters of both the ipsilesional corticospinal tract (CST) and corpus callosum (CC) predicted increased activation of the unaffected hemisphere during movements of the stroke‐affected hand. Changes in diffusion MRI parameters possibly reflecting axonal damage and/or destruction of myelin sheath correlated with a stronger bilateral recruitment of motor areas and poorer motor performance. Probabilistic fiber tracking analyses revealed that the region in the CC correlating with the fMRI laterality index and motor deficits connected to sensorimotor cortex, supplementary motor area, ventral premotor cortex, superior parietal lobule, and temporoparietal junction. The results suggest that degeneration of transcallosal fibers connecting higher order sensorimotor regions constitute a relevant factor influencing cortical reorganization and motor outcome after subcortical stroke. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.     

Altered intra‐ and inter‐network functional coupling of resting‐state networks associated with motor dysfunction in stroke

Motor functions are supported through functional integration across the extended motor system network. Individuals following stroke often show deficits on motor performance requiring coordination of multiple brain networks; however, the assessment of connectivity patterns after stroke was still unclear. This study aimed to investigate the changes in intra‐ and inter‐network functional connectivity (FC) of multiple networks following stroke and further correlate FC with motor performance. Thirty‐three left subcortical chronic stroke patients and 34 healthy controls underwent resting‐state functional magnetic resonance imaging. Eleven resting‐state networks were identified via independent component analysis (ICA). Compared with healthy controls, the stroke group showed abnormal FC within the motor network (MN), visual network (VN), dorsal attention network (DAN), and executive control network (ECN). Additionally, the FC values of the ipsilesional inferior parietal lobule (IPL) within the ECN were negatively correlated with the Fugl‐Meyer Assessment (FMA) scores (hand + wrist). With respect to inter‐network interactions, the ipsilesional frontoparietal network (FPN) decreased FC with the MN and DAN; the contralesional FPN decreased FC with the ECN, but it increased FC with the default mode network (DMN); and the posterior DMN decreased FC with the VN. In sum, this study demonstrated the coexistence of intra‐ and inter‐network alterations associated with motor‐visual attention and high‐order cognitive control function in chronic stroke, which might provide insights into brain network plasticity following stroke.     

Behavioral and neurophysiological mechanisms underlying motor skill learning in patients with post-stroke hemiparesis

Objective

Given the presence of execution deficits after stroke, it is difficult to determine if patients with stroke have deficits in motor skill learning with the paretic arm. Here, we controlled for execution deficits while testing practice effects of the paretic arm on motor skill learning, long-term retention, and corticospinal excitability.

Long‐term effects of cognitive rehabilitation on brain,functional outcome and cognition in Parkinson's disease

Background and purpose

Cognitive rehabilitation has demonstrated efficacy in producing short‐term cognitive and brain changes in patients with Parkinson's disease (PD). To date, no study has assessed the long‐term effects of cognitive rehabilitation using neuroimaging techniques in PD. The aim was to assess the longitudinal effects of a 3‐month cognitive rehabilitation programme evaluating the cognitive, behavioural and neuroimaging changes after 18 months.

Methods

Fifteen patients with PD underwent a cognitive, behavioural and neuroimaging assessment at pre‐treatment (T₀), post‐treatment (T₁) and after 18 months (T₂). This study examined the long‐term effects (from T₀ to T₂) and the maintenance of the changes (from T₁ to T₂). T1‐weighted, diffusion‐weighted, functional magnetic resonance imaging during both a resting‐state and a memory paradigm were acquired. Voxel‐based morphometry and tract‐based spatial statistics were used for grey and white matter analyses. A region‐of‐interest‐to‐region‐of‐interest approach was used for resting‐state functional connectivity (FC) and a model‐based approach was used for brain activation during the memory paradigm.

Results

Patients with PD showed increased cognitive performance, decreased functional disability, increased brain FC and activation at T₂ compared with T₀ (P < 0.05, FDR). Moreover, patients showed maintenance of the improvements in cognition and functionality, and maintenance of the increased brain FC and activation at T₂ compared with T₁. However, significant grey matter reduction and alterations of white matter integrity were found at T₂ (P < 0.05, FWE).

Conclusions

Findings suggest that the improved cognitive performance and increased brain FC and activation after cognitive rehabilitation were significantly maintained after 18 months in patients with PD, despite the structural brain changes, consistent with a progression of neurodegenerative processes.     

Stroke causes a transient imbalance of interhemispheric information flow in EEG during non-REM sleep

Objective

Large-scale connectivity, especially interhemispheric connections, plays a crucial role for recovery after stroke. Here we used methods from information theory to characterize interhemispheric information flow in wake- and sleep-EEG after cerebral ischemia.

Periinfarct rewiring supports recovery after primary motor cortex stroke

After stroke restricted to the primary motor cortex (M1), it is uncertain whether network reorganization associated with recovery involves the periinfarct or more remote regions. We studied 16 patients with focal M1 stroke and hand paresis. Motor function and resting-state MRI functional connectivity (FC) were assessed at three time points: acute (<10 days), early subacute (3 weeks), and late subacute (3 months). FC correlates of recovery were investigated at three spatial scales, (i) ipsilesional non-infarcted M1, (ii) core motor network (M1, premotor cortex (PMC), supplementary motor area (SMA), and primary somatosensory cortex), and (iii) extended motor network including all regions structurally connected to the upper limb representation of M1. Hand dexterity was impaired only in the acute phase (P = 0.036). At a small spatial scale, clinical recovery was more frequently associated with connections involving ipsilesional non-infarcted M1 (Odds Ratio = 6.29; P = 0.036). At a larger scale, recovery correlated with increased FC strength in the core network compared to the extended motor network (rho = 0.71;P = 0.006). These results suggest that FC changes associated with motor improvement involve the perilesional M1 and do not extend beyond the core motor network. Core motor regions, and more specifically ipsilesional non-infarcted M1, could hence become primary targets for restorative therapies.     

Early motor network connectivity after stroke: An interplay of general reorganization and state‐specific compensation

Motor recovery after stroke relies on functional reorganization of the motor network, which is commonly assessed via functional magnetic resonance imaging (fMRI)‐based resting‐state functional connectivity (rsFC) or task‐related effective connectivity (trEC). Measures of either connectivity mode have been shown to successfully explain motor impairment post‐stroke, posing the question whether motor impairment is more closely reflected by rsFC or trEC. Moreover, highly similar changes in ipsilesional and interhemispheric motor network connectivity have been reported for both rsFC and trEC after stroke, suggesting that altered rsFC and trEC may capture similar aspects of information integration in the motor network reflecting principle, state‐independent mechanisms of network reorganization rather than state‐specific compensation strategies. To address this question, we conducted the first direct comparison of rsFC and trEC in a sample of early subacute stroke patients (n = 26, included on average 7.3 days post‐stroke). We found that both rsFC and trEC explained motor impairment across patients, stressing the clinical potential of fMRI‐based connectivity. Importantly, intrahemispheric connectivity between ipsilesional M1 and premotor areas depended on the activation state, whereas interhemispheric connectivity between homologs was state‐independent. From a mechanistic perspective, our results may thus arise from two distinct aspects of motor network plasticity: task‐specific compensation within the ipsilesional hemisphere and a more fundamental form of reorganization between hemispheres.     

Functional MRI and motor behavioral changes obtained with constraint‐induced movement therapy in chronic stroke

Background: The clinical benefits of intensive stroke rehabilitation vary individually. We used multimodal functional imaging to assess the relationship of clinical gain and imaging changes in patients with chronic stroke whose voluntary motor control improved after constraint‐induced movement therapy (CIMT). Methods: Eleven patients (37.6 ± 36.8 months from stroke) were studied by functional MRI (fMRI), transcranial magnetic stimulation (TMS), and behavioral assessment of hand motor control (Wolf Motor Function Test) before and after 2 weeks of CIMT. Individual and group‐level changes in imaging and behavioral parameters were investigated. Results: Increase in fMRI activation in the sensorimotor areas was greater amongst those subjects who had poor hand motor behavior before therapy and/or whose motor behavior improved notably because of therapy than amongst subjects with relatively good motor behavior already before therapy. The magnitude of CIMT‐induced changes in task‐related fMRI activation differed between lesioned and non‐lesioned hemispheres, and the fMRI laterality index was different for paretic and non‐paretic hand tasks. The corticospinal conduction time in TMS was significantly decreased after CIM therapy. Conclusions: Alterations in sensorimotor cortical activations (fMRI) and corticospinal conductivity (TMS) were observed after intensive rehabilitation in patients with chronic stroke. Activation and functional changes in fMRI and TMS correlated significantly with the degree of clinical improvement in hand motor behavior. The present data advance the understanding of the functional underpinnings of motor recovery, which may be obtained even years after the stroke.     

Effects of motor rehabilitation on mobility and brain plasticity in multiple sclerosis: a structural and functional MRI study

Background

Rehabilitation seems to promote brain plasticity, but objective measures of efficacy are lacking and there is a limited understanding of the mechanisms underlying functional recovery.

Objective

To study functional and structural brain changes induced by gait rehabilitation.

Methods

We enrolled MS inpatients (EDSS 4.5–6.5) undergoing a 4-week neurorehabilitation. Several clinical measures were obtained, including: 2-min walk test (2MWT), dynamic gait index (DGI), Berg balance scale (BBS). Furthermore, motor-task functional MRI (fMRI) of plantar dorsiflexion, resting state fMRI, and regional diffusion tensor imaging (DTI) metrics were obtained. All the assessments were performed at baseline (T0), after the end of the rehabilitation period (T1) and 3 months later (T2).

Results

Twenty-nine patients were enrolled at T0, 26 at T1, and 16 completed all timepoints. At T1, there was a significant improvement of 2MWT, DGI, and BBS scores, along with a reduced extent of the widespread activation related to the motor task at the fMRI and an increased functional connectivity in the precentral and post-central gyrus, bilaterally. None of these changes were maintained at T2.

Conclusions

Our findings show a short-term beneficial effect of motor rehabilitation on gait performances in MS, accompanied by brain functional reorganization in the sensory-motor network.

     

Outcome Evaluation with Signal Activation of Functional MRI in Spinal Cord Injury

Objective

The authors investigated the changes of cortical sensorimotor activity in functional MRI (fMRI) and functional recovery in spinal cord injury (SCI) patients who had been treated by bone marrow cell transplantation.

Methods

Nineteen patients with SCI were included in this study; ten patients with clinical improvement and nine without. The cortical sensorimotor activations were studied using the proprioceptive stimulation during the fMRI.

Results

Diagnostic accuracy of fMRI with neurological improvement was 70.0% and 44.4% for sensitivity and specificity, respectively. Signal activation in the ipsilateral motor cortex in fMRI was commonly observed in the clinically neurological improved group (p-value=0.002). Signal activation in the contralateral temporal lobe and basal ganglia was more commonly found in the neurological unimproved group (p-value<0.001). Signal activation in other locations was not statistically different.

Conclusion

In patients with SCI, activation patterns of fMRI between patients with neurologic recovery and those without varied. Such plasticity should be considered in evaluating SCI interventions based on behavioral and neurological measurements.     

Effectiveness of home rehabilitation program for ischemic stroke upon disability and quality of life: a randomized controlled trial

Background

To develop and examine the effectiveness of individual 6-month home rehabilitation program in ischemic stroke patients upon disability and quality of life at 2 years.

Methods

This is a prospective randomized controlled trial (RCT) in 60 patients with recent ischemic stroke. They were randomly assigned to receive either home rehabilitation program once a month for 6 months with audiovisual materials (intervention group) or usual care (control group). We collected outcome data after discharge from the hospital until 2 years. The Barthel index (BI), the modified Rankin Scale (mRS) and utility index (EQ-5D) were measured for function, disability and quality of life respectively.

Results

At 2 years, the BI was significantly improved in the intervention group more than the control group: 97.2 ± 2.8 vs. 76.4 ± 9.4, p < 0.001. The good outcome, defined as BI 95–100, or mRS 0 or 1. For BI, there were 29 patients (96.7%) in intervention group vs 12 patients (42.9%) in usual care group (95% CI, 42.0, 85.0, p = 0.03). For mRS, there were 28 patients (93.3%) in intervention group vs 9 patients (32.1%) in usual care group (95% CI, 38.2, 87.0, p = 0.02). Number needed to treat for good outcome in mRS was 2.0 (95% CI: 1.0, 1.3). The mean (SD) of utility index in intervention group and control group were 0.9 ± 0.02 and 0.7 ± 0.04 respectively (p = 0.03). There was no significant interaction in baseline characteristics and treatment outcome.

Conclusions

Early home rehabilitation program in the first 6 months period after ischemic stroke leads to more rapid improvement in function, reducing disability and increase quality of life than usual care.     

Cortical activation changes associated with motor recovery in patients with precentral knob infarct

We investigated the cortical activation changes associated with motor recovery in six hemiparetic patients with precentral knob infarct. fMRI at 1.5 T with finger movements at a fixed rate was performed twice in each patient, 1 and 6 months after stroke onset. From the images obtained, the LI (laterality index) for the primary sensorimotor cortex (SM1) was calculated to measure the degree of the cortical activity concentration in the contralateral hemisphere. Our results showed that a greater improvement in motor function scores was significantly correlated with a greater increment in LI induced by affected finger movements (p < 0.05). Motor recovery after precentral knob infarct was found to be positively related with the concentration of SM1 activity in the ipsilesional hemisphere. This finding may imply motor recovery through cortical reorganization after precentral knob infarct in the human brain.     

Temporal evolution of event-related desynchronization in acute stroke: A pilot study

ObjectiveAssessment of event-related desynchronization (ERD) may assist in predicting recovery from stroke and rehabilitation, for instance in BCI applications. Here, we explore the temporal evolution of ERD during stroke recovery.MethodsTen stroke patients and eleven healthy controls were recruited to participate in a hand movement task while EEG was being recorded. Four measurements were conducted in eight patients within four months. We quantified changes of ERD using a modulation strength measure, S_m, which represents an area and amplitude of ERD.Results7/8 patients showed good recovery. Absence-or-reduction of ipsilesional modulation was initially found in stroke patients but not in the healthy controls. In the patient group, two evolutions were found in 6/8 patients: a significant increase in ipsilesional S_m; and a decreasing trend in contralesional S_m. In the only non-recovery patient, absence of ipsilesional modulation was observed, while his contralesional S_m increased with time after stroke.ConclusionThe two evolutions presumably reflect the reorganization of brain networks and functional recovery after acute stroke. The significant increase of ipsilesional S_m in patients with a good recovery suggests an important role of this hemisphere during recovery.SignificanceImproved understanding of ERD in acute stroke may assist in prognostication and rehabilitation.     

The effects of electromyography-controlled functional electrical stimulation on upper extremity function and cortical perfusion in stroke patients

Objective

The relation was investigated between hemiparetic arm function improvement and brain cortical perfusion (BCP) change during voluntary muscle contraction (VOL), EMG-controlled FES (EMG-FES) and simple electrical muscle stimulation (ES) before and after EMG-FES therapy in chronic stroke patients.

Methods

Sixteen chronic stroke patients with moderate residual hemiparesis underwent 5 months of task-orientated EMG-FES therapy of the paretic arm once or twice a week. Before and after treatment, arm function was clinically evaluated and BCP during VOL, ES and EMG-FES were assessed using multi-channel near-infrared spectroscopy.

Results

BCP in the ipsilesional sensory-motor cortex (SMC) was greater during EMG-FES than during VOL or ES; therefore, EMG-FES caused a shift in the dominant BCP from the contralesional to ipsilesional SMC. After EMG-FES therapy, arm function improved in most patients, with some individual variability, and there was significant improvement in Fugl–Meyer (FM) score and maximal grip strength (GS). Clinical improvement was accompanied by an increase in ipsilesional SMC activation during VOL and EMG-FES condition.

Conclusion

The EMG-FES may have more influence on ipsilesional BCP than VOL or ES alone.

Significance

The sensory motor integration during EMG-FES therapy might facilitate BCP of the ipsilesional SMC and result in functional improvement of hemiparetic upper extremity.     

Task-modulated neural activation patterns in chronic stroke patients with aphasia

Background: Neuroimaging research on language recovery in patients with aphasia due to left hemisphere damage has generated some intriguing results. However, it is still not clear what role the right hemisphere plays in supporting recovered language functions in the chronic phase for patients with different site and size of lesion when different tasks are used.

Aims: The present study aimed at exploring the role of perilesional, ipsilesional, and contralesional activation in participants with aphasia with different site and size of lesion using two different language tasks. All participants were in the chronic stage with well- recovered or significant improvements in language functions.

Methods & Procedures: Functional magnetic resonance imaging (fMRI) was used to characterise brain activations in eight stroke patients and eight age/gender-matched controls during semantic judgement and oral picture naming. An event-related design using jittered interstimulus intervals (ISIs) was employed to present the stimuli.

Outcomes & Results: The fMRI scans of both language tasks in patients revealed differences in activation pattern relative to the normal control participants. The nature of this difference was task specific. During the semantic judgement task patients without lesions involving the left frontal region activated the left inferior frontal gyrus similar to observations in the normal control participants. Participants with left frontal lesions activated contralesional regions in addition to perilesional left frontal regions. During the picture-naming task all participants activated bilateral brain regions irrespective of the site or size of lesion, consistent with other published studies utilising this task. Subsequent regions of interest analysis and laterality index analysis revealed that patients with large lesions produced greater right hemisphere activation than patients with small lesions.

Conclusions: The results of this study demonstrate that recovery is task, lesion site, and size specific. Further, the results also indicate a role for both activation of homologous contralesional cortex and activity of left hemisphere regions (perilesional and ipsilesional) as efficient mechanisms for supporting language functions in chronic stroke patients.