Neurorehabilitation and Neural Repair

Background and Objective. Rodent models of stroke impairment should capture translatable features of behavioral injury. This study characterized poststroke impairment of motor precision separately from strength in an automated behavioral assay. Methods. We measured skilled distal forelimb reach-and-grasp motions within a target force range requiring moderate-strength. We assessed whether deficits reflected an increase in errors on only one or both sides of the target force range after photothrombotic cortical stroke. Results. Pull accuracy was impaired for 6 weeks after stroke, with errors redistributing to both sides of the target range. No decrease in maximum force was measured. Conclusions. This automated reach task measures sustained loss of motor precision following cortical stroke in mice.

Background. Priming results in a type of implicit memory that prepares the brain for a more plastic response, thereby changing behavior. New evidence in neurorehabilitation points to the use of priming interventions to optimize functional gains of the upper extremity in poststroke individuals. Objective. To determine the effects of priming on task-oriented training on upper extremity outcomes (body function and activity) in chronic stroke. Methods. The PubMed, CINAHL, Web of Science, EMBASE, and PEDro databases were searched in October 2019. Outcome data were pooled into categories of measures considering the International Classification Functional (ICF) classifications of body function and activity. Means and standard deviations for each group were used to determine group effect sizes by calculating mean differences (MDs) and 95% confidence intervals via a fixed effects model. Heterogeneity among the included studies for each factor evaluated was measured using the I² statistic. Results. Thirty-six studies with 814 patients undergoing various types of task-oriented training were included in the analysis. Of these studies, 17 were associated with stimulation priming, 12 with sensory priming, 4 with movement priming, and 3 with action observation priming. Stimulation priming showed moderate-quality evidence of body function. Only the Wolf Motor Function Test (time) in the activity domain showed low-quality evidence. However, gains in motor function and in use of extremity members were measured by the Fugl-Meyer Assessment (UE-FMA). Regarding sensory priming, we found moderate-quality evidence and effect size for UE-FMA, corresponding to the body function domain (MD 4.77, 95% CI 3.25-6.29, Z = 6.15, P < .0001), and for the Action Research Arm Test, corresponding to the activity domain (MD 7.47, 95% CI 4.52-10.42, Z = 4.96, P < .0001). Despite the low-quality evidence, we found an effect size (MD 8.64, 95% CI 10.85-16.43, Z = 2.17, P = .003) in movement priming. Evidence for action observation priming was inconclusive. Conclusion. Combining priming and task-oriented training for the upper extremities of chronic stroke patients can be a promising intervention strategy. Studies that identify which priming techniques combined with task-oriented training for upper extremity function in chronic stroke yield effective outcomes in each ICF domain are needed and may be beneficial for the recovery of upper extremities poststroke.

Background. Fatigue is a debilitating symptom in multiple sclerosis (MS) that may be associated with reduced physical activity and increased sedentary behavior. Objective. This study examined the associations among fatigue and device-measured physical activity and sedentary behavior in people with MS. Methods. The participants (n = 252) completed the Patient Determined Disease Steps (PDDS) and Fatigue Severity Scale (FSS) and wore a waist-mounted accelerometer for 7 days. Participants were divided into 2 groups based on fatigue severity as measured by the FSS scale. We compared percentage of wear time spent in sedentary, light physical activity (LPA), and moderate to vigorous physical activity (MVPA) between the 2 groups. Results. Persons in the fatigued group (FSS score ≥ 4) spent a greater percentage of time in sedentary behavior (P = .004) and a lower percentage of time in LPA (P = .035). Persons in the fatigued group further spent a lower percentage of time in nontransformed MVPA (P < .001) and square-root-transformed MVPA (P < .001) than persons in the nonfatigued group. When controlling for PDDS scores and years of education, there were no longer significant differences between groups in sedentary behavior, LPA, or transformed MVPA values; the difference in nontransformed MVPA was still statistically significant but likely the result of nonnormally distributed data. Conclusion. The present study suggests that factors other than fatigue might be associated with physical activity and sedentary behavior in MS, and this group might benefit from focal behavioral interventions that take into account mobility status in persons with MS who have fatigue.

Background. Nonuse (NU) after stroke is characterized by failure to use the contralesional arm despite adequate capacity. It has been suggested that NU is a consequence of the greater effort and/or attention required to use the affected limb, but such accounts have not been directly tested, and we have poor understanding of the predictors of NU. Objective. We aimed to provide preliminary evidence regarding demographic, neuropsychological (ie, apraxia, attention/arousal, neglect), and psychological (ie, self-efficacy) factors that may influence NU in chronic stroke. Methods. Twenty chronic stroke survivors with mild to moderate sensory-motor impairment characterized by the Upper-Extremity Fugl-Meyer (UEFM) were assessed for NU with a modified version of the Actual Amount of Use Test (AAUT), which measures the disparity between amount of use in spontaneous versus forced conditions. Participants were also assessed with measures of limb apraxia, spatial neglect, attention/arousal, and self-efficacy. Using stepwise multiple regression, we determined which variables predicted AAUT NU scores. Results. Scores on the UEFM as well as attention/arousal predicted the degree of NU (P < .05). Attention/arousal predicted NU above and beyond UEFM (P < .05). Conclusions. The results are consistent with the importance of attention and engagement necessary to fully incorporate the paretic limb into daily activities. Larger-scale studies that include additional behavioral (eg, sensation, proprioception, spasticity, pain, mental health, motivation) and neuroanatomical measures (eg, lesion volume and white matter connectivity) will be important for future investigations.

Background. Fatigue is one of the most frequent symptoms in persons with multiple sclerosis (MS). Distinction is made between subjective perceptions of fatigue and objective measures of fatigability. Fatigability can be measured by different protocols. Yet no studies have compared isometric and concentric contraction protocols of the lower extremities head-to-head. Therefore, the purpose of the present study was to (1) compare 2 such protocols head-to-head and (2) to investigate the association between fatigability evoked by the 2 protocols and measures of fatigue and walking. Methods. A total of 45 patients with MS had their walking capacity measured objectively by the 6-minute walk test (6MWT) and subjectively by the 12-item Multiple Sclerosis Walking Scale (MSWS-12). Fatigue was measured by the Modified Fatigue Impact Scale (MFIS) and fatigability by 2 knee extension protocols: sustained isometric and concentric. Results. The sustained isometric protocol induced a higher degree of fatigability than the concentric protocol (P < .01). Regression analyses revealed that sustained isometric fatigability was not associated with either measures of fatigue or walking (all r² = 0.00; P = .85-.99), whereas the concentric protocol was significantly associated with fatigue (r² = 0.20; P < .01), 6MWT (r² = 0.09; P < .05), and MSWS-12 (r² = 0.16; P < .01). Furthermore, after adjusting for maximal strength and sex, concentric fatigability remained a strong and significant predictor of fatigue (β = 0.49) and walking (6MWT: β = −0.26; MSWS: β = 0.37). Conclusion. This study provides the first evidence that a lower-extremity concentric fatigability protocol provides superior reflection of both fatigue and walking when compared with a sustained isometric protocol. We suggest that concentric protocols should be the focus of future studies investigating fatigability.

Background. In children with unilateral cerebral palsy (UCP), the fibers of the corticospinal tract (CST) emerging from the lesioned hemisphere are damaged following the initial brain injury. The extent to which the integrity of these fibers is restorable with training is unknown. Objective. To assess changes in CST integrity in children with UCP following Hand-and-Arm-Bimanual-Intensive-Therapy-Including-Lower-Extremity (HABIT-ILE) compared to a control group. Methods. Forty-four children with UCP participated in this study. Integrity of the CSTs was measured using diffusion tensor imaging before and after 2 weeks of HABIT-ILE (treatment group, n = 23) or 2 weeks apart without intensive treatment (control group, n = 18). Fractional anisotropy (FA) and mean diffusivity (MD) were the endpoints for assessing the integrity of CST. Results. As highlighted in our whole tract analysis, the FA of the CST originating from the nonlesioned and lesioned hemispheres increased significantly after therapy in the treatment group compared to the control group (group * test session interaction: P < .001 and P = .049, respectively). A decrease in MD was also observed in the CST emerging from the nonlesioned and lesioned hemispheres (group * time interaction: both P < .001). In addition, changes in manual ability correlated with changes in FA in both CSTs (r = 0.463, P = .024; r = 0.643, P < .001) and changes in MD in CST emerging from nonlesioned hemisphere (r = −0.662, P < .001). Conclusions. HABIT-ILE improves FA/MD in the CST and hand function of children with UCP, suggesting that CST fibers retain a capacity for functional restoration. This finding supports the application of intensive motor skill training in clinical practice for the benefit of numerous patients.

Background. Resting state functional connectivity (RSFC) is a developmental priority for stroke recovery. Objective. To determine whether (1) RSFC differs between stroke survivors based on integrity of descending motor pathways; (2) RSFC is associated with upper-limb behavior in chronic stroke; and (3) the relationship between interhemispheric RSFC and upper-limb behavior differs based on descending motor pathway integrity. Methods. A total of 36 people with stroke (aged 64.4 ± 11.1 years, time since stroke 4.0 ± 2.8 years) and 25 healthy adults (aged 67.3 ± 6.7 years) participated in this study. RSFC was estimated from electroencephalography (EEG) recordings. Integrity of descending motor pathways was ascertained using transcranial magnetic stimulation to determine motor-evoked potential (MEP) status and magnetic resonance imaging to determine lesion overlap and fractional anisotropy of the corticospinal tract (CST). For stroke participants, upper-limb motor behavior was assessed using the Fugl-Meyer test, Action Research Arm Test and grip strength. Results. β-Frequency interhemispheric sensorimotor RSFC was greater for MEP+ stroke participants compared with MEP− (P = .020). There was a significant positive correlation between β RSFC and upper-limb behavior (P = .004) that appeared to be primarily driven by the MEP+ group. A hierarchical regression identified that the addition of β RSFC to measures of CST integrity explained greater variance in upper-limb behavior (R² change = 0.13; P = .01). Conclusions. This study provides insight to understand the role of EEG-based measures of interhemispheric network activity in chronic stroke. Resting state interhemispheric connectivity was positively associated with upper-limb behavior for stroke survivors where residual integrity of descending motor pathways was maintained.

Background. Brain injury often causes severe motor dysfunction, leading to difficulties with living a self-reliant social life. Injured neural circuits must be reconstructed to restore functions, but the adult brain is limited in its ability to restore neuronal connections. The combination of molecular targeting, which enhances neural plasticity, and rehabilitative motor exercise is an important therapeutic approach to promote neuronal rewiring in the spared circuits and motor recovery. Objective. We tested whether genetic reduction of Src homology 2-containing phosphatase-1 (SHP-1), an inhibitor of brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) signaling, has synergistic effects with rehabilitative training to promote reorganization of motor circuits and functional recovery in a mouse model of brain injury. Methods. Rewiring of the corticospinal circuit was examined using neuronal tracers following unilateral cortical injury in control mice and in Shp-1 mutant mice subjected to voluntary exercise. Recovery of motor functions was assessed using motor behavior tests. Results. We found that rehabilitative exercise decreased SHP-1 and increased BDNF and TrkB expression in the contralesional motor cortex after the injury. Genetic reduction of SHP-1 and voluntary exercise significantly increased sprouting of corticospinal tract axons and enhanced motor recovery in the impaired forelimb. Conclusions. Our data demonstrate that combining voluntary exercise and SHP-1 suppression promotes motor recovery and neural circuit reorganization after brain injury.