Neurorehabilitation and Neural Repair

There is ample agreement in the scientific literature, across diverse areas of study, that suggests that language and movement are interrelated. In particular, it is widely held that the upper limb and hand play a key role in language use. Aphasia, a common, disabling language disorder frequently associated with stroke, requires new restorative methods. A combinatorial hand-arm-language paradigm that capitalizes on shared neural networks may therefore prove beneficial for aphasia recovery in stroke patients and requires further exploration.

Introduction. The effects of long-term stretching (>6 months) in hemiparesis are unknown. This prospective, randomized, single-blind controlled trial compared changes in architectural and clinical parameters in plantar flexors of individuals with chronic hemiparesis following a 1-year guided self-stretch program, compared with conventional rehabilitation alone. Methods. Adults with chronic stroke-induced hemiparesis (time since lesion >1 year) were randomized into 1 of 2, 1-year rehabilitation programs: conventional therapy (CONV) supplemented with the Guided Self-rehabilitation Contract (GSC) program, or CONV alone. In the GSC group, specific lower limb muscles, including plantar flexors, were identified for a diary-based treatment utilizing daily, high-load, home self-stretching. Blinded assessments included (1) ultrasonographic measurements of soleus and medial gastrocnemius (MG) fascicle length and thickness, with change in soleus fascicle length as primary outcome; (2) maximum passive muscle extensibility (X_V1, Tardieu Scale); (3) 10-m maximal barefoot ambulation speed. Results. In all, 23 individuals (10 women; mean age [SD], 56 [±12] years; time since lesion, 9 [±8] years) were randomized into either the CONV (n = 11) or GSC (n = 12) group. After 1 year, all significant between-group differences favored the GSC group: soleus fascicle length, +18.1mm [9.3; 29.9]; MG fascicle length, +6.3mm [3.5; 9.1]; soleus thickness, +4.8mm [3.0; 7.7]; X_V1 soleus, +4.1° [3.1; 7.2]; X_V1 gastrocnemius, +7.0° [2.1; 11.9]; and ambulation speed, +0.07m/s [+0.02; +0.16]. Conclusions. In chronic hemiparesis, daily self-stretch of the soleus and gastrocnemius over 1 year using GSC combined with conventional rehabilitation increased muscle fascicle length, extensibility, and ambulation speed more than conventional rehabilitation alone.

Background. Physical rehabilitation programs can lead to improvements in mobility in people with multiple sclerosis (PwMS). Objective. To identify which rehabilitation program elements are employed in real life and how they might affect mobility improvement in PwMS. Methods. Participants were divided into improved and nonimproved mobility groups based on changes observed in the Multiple Sclerosis Walking Scale–12 following multimodal physical rehabilitation programs. Analyses were performed at group and subgroup (mild and moderate-severe disability) levels. Rehabilitation program elements included setting, number of weeks, number of sessions, total duration, therapy format (individual, group, autonomous), therapy goals, and therapeutic approaches. Results. The study comprised 279 PwMS from 17 European centers. PwMS in the improved group received more sessions of individual therapy in both subgroups. In the mildly disabled group, 60.9% of the improved received resistance training, whereas, 68.5% of the nonimproved received self-stretching. In the moderately-severely disabled group, 31.4% of the improved, received aerobic training, while 50.4% of the nonimproved received passive mobilization/stretching. Conclusions. We believe that our findings are an important step in opening the black-box of physical rehabilitation, imparting guidance, and assisting future research in defining characteristics of effective physical rehabilitation.

Background. Growing evidences suggest that brain-derived neurotrophic factor/tropomyosin receptor kinase B (BDNF/TrkB) plays a key role in the regulation of hippocampal synaptic plasticity in a prenatal stress (PNS) rat model. Repetitive transcranial magnetic stimulation (rTMS) is currently being acknowledged to affect attention and memory in both preclinical and clinical studies, although the mechanism is still unclear. Objective. The current study aimed to explore whether a whole brain rTMS (5 Hz, 14 days) could ameliorate cognitive dysfunction–induced PNS in male offspring, and examine if the positive effect of rTMS was associated with the BDNF/TrkB signaling in the hippocampus. Methods. The rats were randomly divided into 5 groups: CON, PNS, PNS + rTMS, PNS + rTMS + DMSO (dimethyl sulfoxide), and PNS + rTMS + K252a. Spatial cognition was evaluated by using Morris water maze test. Following behavioral assessment, both paired-pulse facilitation and long-term potentiation were recorded from Schaffer collaterals to CA1 region in the hippocampus. Synaptic, apoptotic, and BDNF/TrkB signaling proteins were measured by Western blot. Results. PNS-exposed offspring exhibited cognitive deficits, long-term potentiation inhibition in the hippocampus, the decrease of synaptic and BDNF/TrkB signaling proteins expression, apoptosis, and reduced number of cells in the CA1 region. Five-hertz rTMS significantly alleviated the PNS-induced abnormalities. However, the effect of rTMS was antagonized by intracerebroventricular infusion of K252a (a TrkB inhibitor). Conclusions. The findings suggest that 5-Hz rTMS significantly improves the impairment of spatial cognition and hippocampal synaptic plasticity, which is possibly associated with the activation of BDNF/TrkB signaling.

Background. Abnormal muscle co-activation contributes to impairment after stroke. We developed a myoelectric computer interface (MyoCI) training paradigm to reduce abnormal co-activation. MyoCI provides intuitive feedback about muscle activation patterns, enabling decoupling of these muscles. Objective. To investigate tolerability and effects of MyoCI training of 3 muscle pairs on arm motor recovery after stroke, including effects of training dose and isometric versus movement-based training. Methods. We randomized chronic stroke survivors with moderate-to-severe arm impairment to 3 groups. Two groups tested different doses of isometric MyoCI (60 vs 90 minutes), and one group tested MyoCI without arm restraint (90 minutes), over 6 weeks. Primary outcome was arm impairment (Fugl-Meyer Assessment). Secondary outcomes included function, spasticity, and elbow range-of-motion at weeks 6 and 10. Results. Over all 32 subjects, MyoCI training of 3 muscle pairs significantly reduced impairment (Fugl-Meyer Assessment) by 3.3 ± 0.6 and 3.1 ± 0.7 (P < 10⁻⁴) at weeks 6 and 10, respectively. Each group improved significantly from baseline; no significant differences were seen between groups. Participants’ lab-based and home-based function also improved at weeks 6 and 10 (P ≤ .01). Spasticity also decreased over all subjects, and elbow range-of-motion improved. Both moderately and severely impaired patients showed significant improvement. No participants had training-related adverse events. MyoCI reduced abnormal co-activation, which appeared to transfer to reaching in the movement group. Conclusions. MyoCI is a well-tolerated, novel rehabilitation tool that enables stroke survivors to reduce abnormal co-activation. It may reduce impairment and spasticity and improve arm function, even in severely impaired patients.

Background. Cognitive impairment is common in long-term survivors of out-of-hospital cardiac arrest (OHCA) but corresponding neuroimaging data are lacking. Objectives. This study explored the relationship among the cortical brain structure, cognitive performance, and clinical variables after OHCA. Methods. Three months after resuscitation, 13 OHCA survivors who had recovered from a coma to living independently and 19 healthy controls were assessed by cerebral magnetic resonance imaging and neuropsychological tests quantifying memory, fine-motor coordination, and attention/executive functions. Cortical thickness (Cth) and surface area (SA) were compared between groups and analyzed for relationships with cognitive performance as well as the clinical variables of coma duration and the time to return of spontaneous circulation (ROSC). All analyses were controlled for age and sex. Results. Analyses of SA revealed no significant differences. Compared with controls, survivors had significantly reduced memory and fine-motor coordination and significantly thinner cortex in large clusters in the frontal, parietal, and inferior temporal cortices, with additional regions in the left occipital lobe and the left temporal lobe. Widespread thinner cortical regions were significantly associated with decreased memory performance in survivors when compared with those in controls and were significantly associated with an increased time to ROSC and increased coma duration in the OHCA group. Increased coma duration, but not increased time to ROSC, was significantly correlated with cognitive test performance. Conclusions. The results suggest that widespread Cth reductions correspond to the cognitive impairments observed after OHCA. Neuroimaging studies of long-term OHCA survivors are warranted to guide the development of diagnostics and treatment options.

Background. Camera technique–based mirror visual feedback (MVF) is an optimal interface for mirror therapy. However, its efficiency for stroke rehabilitation and the underlying neural mechanisms remain unclear. Objective. To investigate the possible treatment benefits of camera-based MVF (camMVF) for priming prior to hand function exercise in subacute stroke patients, and to reveal topological reorganization of brain network in response to the intervention. Methods. Twenty subacute stroke patients were assigned randomly to the camMVF group (MG, N = 10) or a conventional group (CG, N = 10). Before, and after 2 and 4 weeks of intervention, the Fugl-Meyer Assessment Upper Limb subscale (FMA_UL), the Functional Independence Measure (FIM), the modified Ashworth Scale (MAS), manual muscle testing (MMT), and the Berg Balance Scale (BBS) were measured. Resting-state electroencephalography (EEG) signals were recorded before and after 4-week intervention. Results. The MG showed more improvements in the FMA_UL, the FMA_WH (wrist and hand), and the FIM than the CG. The clustering coefficient (CC) of the resting EEG network in the alpha band was increased globally in the MG after intervention but not in the CG. Nodal CC analyses revealed that the CC in the MG tended to increase in the ipsilesional occipital and temporal areas, and the bilateral central and parietal areas, suggesting improved local efficiency of communication in the visual, somatosensory, and motor areas. The changes of nodal CC at TP8 and PO8 were significantly positively correlated with the motor recovery. Conclusions. The camMVF-based priming could improve the motor recovery, daily function, and brain network segregation in subacute stroke patients.

Background: Persistent deficits in arm function are common after stroke. An improved understanding of the factors that contribute to the performance of skilled arm movements is needed. One such factor may be self-efficacy (SE). Objective: To determine the level of SE for skilled, goal-directed reach actions in individuals with mild motor impairment after stroke and whether SE for reach performance correlated with actual reach performance. Methods: A total of 20 individuals with chronic stroke (months poststroke: mean 58.1 ± 38.8) and mild motor impairment (upper-extremity Fugl-Meyer [FM] motor score: mean 53.2, range 39 to 66) and 6 age-matched controls reached to targets presented in 2 directions (ipsilateral, contralateral). Prior to each block (24 reach trials), individuals rated their confidence on reaching to targets accurately and quickly on a scale that ranged from 0 (not very confident) to 10 (very confident). Results: Overall reach performance was slower and less accurate in the more-affected arm compared with both the less-affected arm and controls. SE for both reach speed and reach accuracy was lower for the more-affected arm compared with the less-affected arm. For reaches with the more-affected arm, SE for reach speed and age significantly predicted movement time to ipsilateral targets (R² = 0.352), whereas SE for reach accuracy and FM motor score significantly predicted end point error to contralateral targets (R² = 0.291). Conclusions: SE relates to measures of reach control and may serve as a target for interventions to improve proximal arm control after stroke.