Greater and More Natural Use of the Upper Limbs During Everyday Life by Former Amputees Versus Prosthesis Users

Hand loss profoundly impacts daily functioning. Reversal of amputation through hand replantation or transplantation offers an alternative to prosthetics for some. Whether recipients exhibit more extensive and natural limb use during everyday life than prosthesis users is, however, unknown. We asked unilateral, below-elbow amputees (N = 22), hand graft recipients (transplants N = 4; replants N = 2), and healthy matched controls (N = 20) to wear wireless accelerometers distally on their forearms/prostheses and proximally on their upper arms. These units captured limb activity over 3 days within participants’ natural environments. Graft recipients exhibited heavier reliance on their affected hands compared to amputees’ reliance on their prostheses, P < .001. Likewise, reliance on the injured side upper arm was also greater for hand graft recipients than amputees, regardless of whether they were wearing their prostheses, P < .05 in both cases. Hand graft recipients, like healthy controls, also relied more on forearm vs upper arm movements when controlling their limbs, P < .001. Compared with conventional prosthesis users, graft recipients exhibited more extensive and natural functioning of the upper limbs during everyday activities. This information is an important addition to other considerations when evaluating risk-benefit of these treatment alternatives.

Multimodal Imaging Biomarker-Based Model Using Stratification Strategies for Predicting Upper Extremity Motor Recovery in Severe Stroke Patients

Background. Various prognostic biomarkers for upper extremity (UE) motor recovery after stroke have been reported. However, most have relatively low predictive accuracy in severe stroke patients. Objective. This study suggests an imaging biomarker-based model for effectively predicting UE recovery in severe stroke patients. Methods. Of 104 ischemic stroke patients screened, 42 with severe motor impairment were included. All patients underwent structural, diffusion, and functional magnetic resonance imaging at 2 weeks and underwent motor function assessments at 2 weeks and 3 months after stroke onset. According to motor function recovery at 3 months, patients were divided into good and poor subgroups. The value of multimodal imaging biomarkers of lesion load, lesion volume, white matter integrity, and cortical functional connectivity for motor recovery prediction was investigated in each subgroup. Results. Imaging biomarkers varied depending on recovery pattern. The integrity of the cerebellar tract ( P = .005, R 2 = .432) was the primary biomarker in the good recovery group. In contrast, the sensory-related corpus callosum tract ( P = .026, R 2 = .332) and sensory-related functional connectivity ( P = .001, R 2 = .531) were primary biomarkers in the poor recovery group. A prediction model was proposed by applying each biomarker in the subgroup to patients with different motor evoked potential responses ( P < .001, R 2 = .853, root mean square error = 5.28). Conclusions. Our results suggest an optimized imaging biomarker model for predicting UE motor recovery after stroke. This model can contribute to individualized management of severe stroke in a clinical setting.

Neurorehabilitation in Adults With Traumatic Upper Extremity Amputation: A Scoping Review

Background Most of the current literature around amputation focuses on lower extremity amputation or engineering aspects of prosthetic devices. There is a need to more clearly understand neurobehavioral mechanisms related to upper extremity amputation and how such mechanisms might influence recovery and utilization of prostheses. Objective This scoping review aims to identify and summarize the current literature on adult traumatic upper limb amputation in regard to recovery and functional outcomes and how neuroplasticity might influence these findings. Methods We identified appropriate articles using Academic Search Complete EBSCO, OVID Medline, and Cochrane databases. The resulting articles were then exported, screened, and reviewed based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews (PRISMA-ScR) guidelines. Results Eleven (11) studies met the study criteria. Of these studies, 7 focused on sensory involvement, 3 focused on neuroplastic changes post-amputation related to functional impact, and 1 study focused on motor control and learning post-amputation. Overall, these studies revealed an incomplete understanding of the neural mechanisms involved in motor rehabilitation in the central and peripheral nervous systems, while also demonstrating the value of an individualized approach to neurorehabilitation in upper limb loss. Conclusions There is a gap in our understanding of the role of neurorehabilitation following amputation. Overall, focused rehabilitation parameters, demographic information, and clarity around central and peripheral neural mechanisms are needed in future research to address neurobehavioral mechanisms to promote functional recovery following traumatic upper extremity amputation.

Functional Connectivity and Speech Entrainment Speech Entrainment Improves Connectivity Between Anterior and Posterior Cortical Speech Areas in Non-fluent Aphasia

Background Speech entrainment (SE), the online mimicking of an audio-visual speech model, has been shown to increase speech fluency in individuals with non-fluent aphasia. One theory that may explain why SE improves speech output is that it synchronizes functional connectivity between anterior and posterior language regions to be more similar to that of neurotypical speakers. Objectives The present study tested this by measuring functional connectivity between 2 regions shown to be necessary for speech production, and their right hemisphere homologues, in 24 persons with aphasia compared to 20 controls during both free (spontaneous) speech and SE. Methods Regional functional connectivity in participants with aphasia were normalized to the control data. Two analyses were then carried out: (1) normalized functional connectivity was compared between persons with aphasia and controls during free speech and SE and (2) stepwise linear models with leave-one-out cross-validation including normed functional connectivity during both tasks and proportion damage to the left hemisphere as independent variables were created for each language score. Results Left anterior–posterior functional connectivity and left posterior to right anterior functional connectivity were significantly more similar to connectivity of the control group during SE compared to free speech. Additionally, connectivity during free speech was more associated with language measures than connectivity during SE. Conclusions Overall, these results suggest that SE promotes normalization of functional connectivity (i.e., return to patterns observed in neurotypical controls), which may explain why individuals with non-fluent aphasia produce more fluent speech during SE compared to spontaneous speech.

Brain–Computer Interface Training Based on Brain Activity Can Induce Motor Recovery in Patients With Stroke: A Meta-Analysis

Background Brain–computer interface (BCI) is a procedure involving brain activity in which neural status is provided to the participants for self-regulation. The current review aims to evaluate the effect sizes of clinical studies investigating the use of BCI-based rehabilitation interventions in restoring upper extremity function and effective methods to detect brain activity for motor recovery. Methods A computerized search of MEDLINE, CENTRAL, Web of Science, and PEDro was performed to identify relevant articles. We selected clinical trials that used BCI-based training for post-stroke patients and provided motor assessment scores before and after the intervention. The pooled standardized mean differences of BCI-based training were calculated using the random-effects model. Results We initially identified 655 potentially relevant articles; finally, 16 articles fulfilled the inclusion criteria, involving 382 participants. A significant effect of neurofeedback intervention for the paretic upper limb was observed (standardized mean difference = .48, [.16-.80], P = .006). However, the effect estimates were moderately heterogeneous among the studies ( I2 = 45%, P = .03). Subgroup analysis of the method of measurement of brain activity indicated the effectiveness of the algorithm focusing on sensorimotor rhythm. Conclusion This meta-analysis suggested that BCI-based training was superior to conventional interventions for motor recovery of the upper limbs in patients with stroke. However, the results are not conclusive because of a high risk of bias and a large degree of heterogeneity due to the differences in the BCI interventions and the participants; therefore, further studies involving larger cohorts are required to confirm these results.

Corticospinal Tract Lesion Load Originating From Both Ventral Premotor and Primary Motor Cortices Are Associated With Post-stroke Motor Severity

Lesion load of the corticospinal tract (CST-LL), a measure of overlap between a stroke lesion and the CST, is one of the strongest predictors of motor outcomes following stroke. CST-LL is typically calculated by using a probabilistic map of the CST originating from the primary motor cortex (M1). However, higher order motor areas also have projections that contribute to the CST and motor control. In this retrospective study, we examined whether evaluating CST-LL from additional motor origins is more strongly associated with post-stroke motor severity than using CST-LL originating from M1 only. We found that lesion load to both the ventral premotor (PMv) cortex and M1 were more strongly related to stroke motor severity indexed by Fugl-Meyer Assessment cut-off scores than CST-LL of M1 alone, suggesting that higher order motor regions add clinical relevance to motor impairment.

Step Number and Aerobic Minute Exercise Prescription and Progression in Stroke: A Roadmap

Background While higher therapeutic intensity improves motor recovery after stroke, translating findings from successful studies is challenging without clear exercise intensity targets. We show in the DOSE trial 1 more than double the steps and aerobic minutes within a session can be achieved compared with usual care and translates to improved long-term walking outcomes. Objective We modeled data from this successful higher intensity multi-site RCT to develop targets for prescribing and progressing exercise for varying levels of walking impairment after stroke. Methods In twenty-five individuals in inpatient rehabilitation, twenty sessions were monitored for a total of 500 one-hour physical therapy sessions. For the 500 sessions, step number and aerobic minute progression were modeled using linear mixed effects regression. Using formulas from the linear mixed effects regression, targets were calculated. Results The model for step number included session number and baseline walking speed, and for aerobic minutes, session number and age. For steps, there was an increase of 73 steps per session. With baseline walking speed, for every 0.1 m/s increase, a corresponding increase of 302 steps was predicted. For aerobic minutes, there was an increase of .56 minutes of aerobic activity (ie, 34 seconds) per session. For every year increase in age, a decrease of .39 minutes (ie, 23 seconds) was predicted. Conclusions Using data associated with better walking outcomes, we provide step number and aerobic minute targets that future studies can cross-validate. As walking speed and age are collected at admission, these models allow for uptake of routine measurement of therapeutic intensity. Registration: www.clinicaltrials.gov ; NCT01915368.

Resting-state Functional Connectivity After Occipital Stroke

Background Resting-state functional magnetic resonance imaging (rsfMRI) reflects spontaneous activation of cortical networks. After stroke, these networks reorganize, both due to structural lesion and reorganization of functional connectivity (FC). Objective We studied FC in chronic phase occipital stroke patients with homonymous visual field defects before and after repetitive transorbital alternating current stimulation (rtACS). Methods This spin-off study, embedded in the randomized, sham-controlled REVIS trial, comprised 16 chronic occipital stroke patients with visual field defect and 12 healthy control subjects. The patients underwent rsfMRI at baseline, after two weeks of rtACS or sham treatment, and after two months of treatment-free follow-up, whereas the control subjects were measured once. We used a multivariate regression connectivity model to determine mutual prediction accuracy between 74 cortical regions of interest. Additionally, the model parameters were included into a graph to analyze average path length, centrality eigenvector, centrality degree, and clustering of the network. The patients and controls at baseline and the two treatment groups were compared with multilevel modeling. Results Before treatment, the patients and controls had similar whole-network prediction accuracy and network parameters, whereas centrality eigenvector differed in perilesional regions, indicating local modification in connectivity. In line with behavioral results, neither prediction accuracy nor any network parameter changed systematically as a result of rtACS rehabilitation compared to sham. Conclusions Whole-network FC showed no difference between occipital stroke patients and healthy population, congruent with the peripheral location of the visual network in relation to the high-density cortical core. rtACS treatment in the given setting did not affect FC.

Reward During Arm Training Improves Impairment and Activity After Stroke: A Randomized Controlled Trial

Background Learning and learning-related neuroplasticity in motor cortex are potential mechanisms mediating recovery of movement abilities after stroke. These mechanisms depend on dopaminergic projections from midbrain that may encode reward information. Likewise, therapist experience confirms the role of feedback/reward for training efficacy after stroke. Objective To test the hypothesis that rehabilitative training can be enhanced by adding performance feedback and monetary rewards. Methods This multicentric, assessor-blinded, randomized controlled trial used the ArmeoSenso virtual reality rehabilitation system to train 37 first-ever subacute stroke patients in arm-reaching to moving targets. The rewarded group (n = 19) trained with performance feedback (gameplay) and contingent monetary reward. The control group (n = 18) used the same system without monetary reward and with graphically minimized performance feedback. Primary outcome was the change in the two-dimensional reaching space until the end of the intervention period. Secondary clinical assessments were performed at baseline, after 3 weeks of training (15 1-hour sessions), and at 3 month follow-up. Duration and intensity of the interventions as well as concomitant therapy were comparable between groups. Results The two-dimensional reaching space showed an overall improvement but no difference between groups. The rewarded group, however, showed significantly greater improvements from baseline in secondary outcomes assessing arm activity (Box and Block Test at post-training: 6.03±2.95, P = .046 and 3 months: 9.66±3.11, P = .003; Wolf Motor Function Test [Score] at 3 months: .63±.22, P = .007) and arm impairment (Fugl-Meyer Upper Extremity at 3 months: 8.22±3.11, P = .011). Conclusions Although neutral in its primary outcome, the trial signals a potential facilitating effect of reward on training-mediated improvement of arm paresis. Trial registration ClinicalTrials.gov (ID: NCT02257125).

Cerebellar Dysfunction in Multiple Sclerosis: Considerations for Research and Rehabilitation Therapy

Introduction. Cerebellar pathology is common among persons with multiple sclerosis (PwMS). The cerebellum is well recognized for its role in motor control and motor learning and cerebellar pathology in multiple sclerosis is associated with enhanced motor impairment and disability progression. The Problem. To mitigate motor disability progression, PwMS are commonly prescribed exercise and task-specific rehabilitation training. Yet, whether cerebellar dysfunction differentially affects rehabilitation outcomes in this population remains unknown. Furthermore, we lack rehabilitation interventions targeting cerebellar dysfunction. The Solution. Here, we summarize the current understanding of the impact of cerebellar dysfunction on motor control, motor training, and rehabilitation in persons with multiple sclerosis. Recommendations. Additionally, we highlight critical knowledge gaps and propose that these guide future research studying cerebellar dysfunction in persons with multiple sclerosis.