Neurorehabilitation and Neural Repair

Background. Elucidation of the relative importance of commonly targeted biomechanical variables to poststroke long-distance walking function would facilitate optimal intervention design. Objectives. To determine the relative contribution of variables from 3 biomechanical constructs to poststroke long-distance walking function and identify the biomechanical changes underlying posttraining improvements in long-distance walking function. Methods. Forty-four individuals >6 months after stroke participated in this study. A subset of these subjects (n = 31) underwent 12 weeks of high-intensity locomotor training. Cross-sectional (pretraining) and longitudinal (posttraining change) regression quantified the relationships between poststroke long-distance walking function, as measured via the 6-Minute Walk Test (6MWT), and walking biomechanics. Biomechanical variables were organized into stance phase (paretic propulsion and trailing limb angle), swing phase (paretic ankle dorsiflexion and knee flexion), and symmetry (step length and swing time) constructs. Results. Pretraining, all variables correlated with 6MWT distance (rs = .39 to .75, Ps < .05); however, only propulsion (Prop) and trailing limb angle (TLA) independently predicted 6MWT distance, R² = .655, F(6, 36) = 11.38, P < .001. Interestingly, only ΔProp predicted Δ6MWT; however, pretraining Prop, pretraining TLA, and ΔTLA moderated this relationship (moderation model R²s = .383, .468, .289, respectively). Conclusions. The paretic limb’s ability to generate propulsion during walking is a critical determinant of long-distance walking function after stroke. This finding supports the development of poststroke interventions that target deficits in propulsion and trailing limb angle.

Background. Mirror therapy is a priming technique to improve motor function of the affected arm after stroke. Objective. To investigate whether a mirror therapy–based action observation (AO) protocol contributes to motor learning of the affected arm after stroke. Methods. A total of 37 participants in the chronic stage after stroke were randomly allocated to the AO or control observation (CO) group. Participants were instructed to perform an upper-arm reaching task as fast and as fluently as possible. All participants trained the upper-arm reaching task with their affected arm alternated with either AO or CO. Participants in the AO group observed mirrored video tapes of reaching movements performed by their unaffected arm, whereas participants in the CO group observed static photographs of landscapes. The experimental condition effect was investigated by evaluating the primary outcome measure: movement time (in seconds) of the reaching movement, measured by accelerometry. Results. Movement time decreased significantly in both groups: 18.3% in the AO and 9.1% in the CO group. Decrease in movement time was significantly more in the AO compared with the CO group (mean difference = 0.14 s; 95% confidence interval = 0.02, 0.26; P = .026). Conclusion. The present study showed that a mirror therapy–based AO protocol contributes to motor learning after stroke.

Background. There is limited evidence for the effects of constraint-induced movement therapy (CIMT) in the early stages of stroke recovery. Objective. To evaluate the effect of a modified CIMT within 4 weeks poststroke. Methods. This single-blinded randomized multisite trial investigated the effects of CIMT in 47 individuals who had experienced a stroke in the preceding 26 days. Patients were allocated to a CIMT or a usual care (control) group. The CIMT program was 3 h/d over 10 consecutive working days, with mitt use on the unaffected arm for up to 90% of waking hours. The follow-up time was 6 months. The primary outcome was the Wolf Motor Function test (WMFT) score. Secondary outcomes were the Fugl-Meyer upper-extremity motor score, Nine-Hole Peg test (NHPT) score, the arm use ratio, and the Stroke Impact Scale. Analyses of covariance with adjustment for baseline values were used to assess differences between the groups. Results. After treatment, the mean timed WMFT score was significantly better in the CIMT group compared with the control group. Moreover, posttreatment dexterity, as tested with the NHPT, was significantly better in the CIMT group, whereas the other test results were similar in both the groups. At the 6-month follow-up, the 2 groups showed no significant difference in arm impairment, function, or use in daily activities. Conclusions. Despite a favorable effect of CIMT on timed movement measures immediately after treatment, significant effects were not found after 6 months.

Purpose. The purpose of this study was to estimate the effect of the Cognitive Orientation to daily Occupational Performance (CO-OP) approach compared with usual outpatient rehabilitation on activity and participation in people <3 months poststroke. Methods. An exploratory, single-blind, randomized controlled trial, with a usual-care control arm, was conducted. Participants referred to 2 stroke rehabilitation outpatient programs were randomized to receive either usual care or CO-OP. The primary outcome was actual performance of trained and untrained self-selected activities, measured using the Performance Quality Rating Scale (PQRS). Additional outcomes included the Canadian Occupational Performance Measure (COPM), the Stroke Impact Scale Participation Domain, the Community Participation Index, and the Self-Efficacy Gauge. Results. A total of 35 eligible participants were randomized; 26 completed the intervention. Post intervention, PQRS change scores demonstrated that CO-OP had a medium effect over usual care on trained self-selected activities (d = 0.5) and a large effect on untrained activities (d = 1.2). At a 3-month follow-up, PQRS change scores indicated a large effect of CO-OP on both trained (d = 1.6) and untrained activities (d = 1.1). CO-OP had a small effect on COPM and a medium effect on the Community Participation Index perceived control and on the Self-Efficacy Gauge. Conclusion. CO-OP was associated with a large treatment effect on follow-up performances of self-selected activities and demonstrated transfer to untrained activities. A larger trial is warranted.

Background. Sensory stimulation is often provided to persons incurring severe traumatic brain injury (TBI), but therapeutic effects are unclear. Objective. This preliminary study investigated neurobehavioral and neurophysiological effects related to sensory stimulation on global neurobehavioral functioning, arousal, and awareness. Methods. A double-blind randomized placebo-controlled trial where 15 participants in states of disordered consciousness (DOC), an average of 70 days after TBI, were provided either the Familiar Auditory Sensory Training (FAST) or Placebo of silence. Global neurobehavioral functioning was measured with the Disorders of Consciousness Scale (DOCS). Arousal and awareness were measured with the Coma-Near-Coma (CNC) scale. Neurophysiological effect was measured using functional magnetic resonance imaging (fMRI). Results. FAST (n = 8) and Placebo (n = 7) groups each showed neurobehavioral improvement. Mean DOCS change (FAST = 13.5, SD = 8.2; Placebo = 18.9, SD = 15.6) was not different, but FAST patients had significantly (P = .049; 95% confidence interval [CI] = −1.51, −.005) more CNC gains (FAST = 1.01, SD = 0.60; Placebo = 0.25, SD = 0.70). Mixed-effects models confirm CNC findings (P = .002). Treatment effect, based on CNC, is large (d = 1.88, 95% CI = 0.77, 3.00). Number needed to treat is 2. FAST patients had more fMRI activation in language regions and whole brain (P values <.05) resembling healthy controls’ activation. Conclusions. For persons with DOC 29 to 170 days after TBI, FAST resulted in CNC gains and increased neural responsivity to vocal stimuli in language regions. Clinicians should consider providing the FAST to support patient engagement in neurorehabilitation.

Studies indicate that motor functions in patients with traumatic brain injury (TBI) can be improved with action observation. It has been hypothesized that this clinical practice relies on modulation of motor cortical excitability elicited by passive action observation in patients with TBI, a phenomenon shown thus far only in normal controls. The purpose of this work was to test this hypothesis and characterize the modulation of motor cortex excitability during passive action observation in patients with subacute moderate to severe TBI. We measured motor evoked potentials induced by single-pulse transcranial magnetic stimulation to the left primary motor cortex and recorded from the contralateral first dorsal interosseus while 20 participants observed videos of static and moving right index finger. Results were compared with those of 20 age-and gender-matched healthy controls. As expected, greater excitability was elicited during moving than static stimuli in healthy subjects. However, this was not observed in patients with TBI. Modulation of motor excitability during action observation is impaired in patients with TBI depending on motor dysfunction, lesion site, and number of days postinjury. These preliminary results suggest a strategy to identify patients in whom action observation might be a valuable neurorehabilitative strategy.

Background. Resting brain activity can be modulated by motor tasks to adapt to function. In multiple sclerosis (MS) patients, altered resting-state functional connectivity (RS-FC) has been reported and associated with impaired function and disability; little is known on how RS-FC is modulated by a simple repetitive motor task. Objective. To assess changes in RS-FC in early relapsing-remitting MS (RRMS) patients associated with repetitive thumb flexions (RTFs). Methods. A total of 20 right-handed patients with early RRMS and 14 healthy controls underwent a resting functional magnetic resonance imaging (fMRI) scan, before and after 25 minutes of alternate 30-s blocks of right RTF and rest. Dual-regression analysis of resting fMRI data followed the independent component analysis. Individual spatial maps of coherence between brain areas for 2 networks of interest, sensorimotor and cerebellar, were compared at the group level and correlated with measures of both clinical impairment and brain damage. Results. Significant RTF-induced differences in RS-FC were observed between groups in the cerebellar network because of increased RS-FC in patients but not in controls. In the sensorimotor network, the RS-FC after RTF increased in both groups, with no significant between-group differences. The sensorimotor and the cerebellar RS-FC were intercorrelated only in patients and only after the RTF. The sensorimotor RS-FC increase in patients correlated with structural MRI alterations. Conclusions. Our study unmasked RS-FC changes of motor-related networks occurring after a simple repetitive motor task in early RRMS patients only. Evaluation of altered RSN dynamics might prove useful for anticipating neuroplasticity and for MRI-informed neurorehabilitation.

Background. Spinal cord injury (SCI) results in impaired function, and ankle joint spasticity is a common secondary complication. Different interventions have been trialed with variable results. Objective. We investigated the effects of pharmacological and physical (locomotor training) interventions on function in people living with incomplete motor function loss caused by SCI and used different analytical techniques to understand whether functional levels affect recovery with different interventions. Methods. Participants with an incomplete SCI were assigned to 3 groups: no intervention, Lokomat, or tizanidine. Outcome measures were the 10-m walk test, 6-minute walk test, and the Timed Up and Go. Participants were classified in 2 ways: (1) based on achieving an improvement above the minimally important difference (MID) and (2) using growth mixture modeling (GMM). Functional levels of participants who achieved the MID were compared and random coefficient regression (RCR) was used to assess recovery in GMM classes. Results. Overall, walking speed and endurance improved, with no difference between interventions. Only a small number of participants achieved the MID. Both MID and GMM-RCR analyses revealed that tizanidine improved endurance in high-functioning participants. GMM-RCR classification also showed that speed and mobility improved after locomotor training. Conclusions. Improvements in function were achieved in a limited number of people with SCI. Using the MID and GMM techniques, differences in responses to interventions between high-and low-functioning participants could be identified. These techniques may, therefore, have potential to be used for characterizing therapeutic effects resulting from different interventions.

Physical exercise is a cornerstone in the management of many neurodegenerative disorders, such as Parkinson’s disease, dementia, and stroke. However, much of its beneficial effects on improving motor functions and cognition as well as decreasing neurodegeneration and neuroinflammation are not yet well understood. The obvious limitations of studying the protective mechanisms behind exercise, for example, brain plasticity and neurodegeneration, could be overcome by generating novel animal models of neurodegenerative disorders. In this narrative review, we discuss the beneficial effects of exercise performed in animal models of neurodegenerative disorders and how the results from animal studies can be used in clinical settings. From preclinical studies, the positive effects of exercise have been related to increased levels of neurotrophic factors, elevated expression of anti-inflammatory cytokines, and reduced levels of pro-inflammatory cytokines and activated microglia. It is clear that parameters influencing the effect of exercise, such as intensity, still remain to be investigated in animal studies in order to find the optimal program that can be translated into exercise interventions for patients with neurodegenerative diseases.

Background. Motor rehabilitative training improves behavioral functionality and promotes beneficial neural reorganization following stroke but is often insufficient to normalize function. Rodent studies have relied on skilled reaching tasks to model motor rehabilitation and explore factors contributing to its efficacy. It has been found that greater training intensity (sessions/day) and duration (training days) facilitates motor skill learning in intact animals. Whether rehabilitative training efficacy varies with intensity following stroke is unclear. Methods. Mice were trained preoperatively on a skilled reaching task. Following focal ischemic lesions, mice received rehabilitative training either twice daily (high intensity [HI]), once daily (low intensity [LI]), or not at all (control) to determine the effects of rehabilitative training intensity on skilled motor performance. Results. Within 7 days, the HI-trained mice achieved preischemic levels of performance. Mice receiving LI training eventually reached similar performance levels but required a greater quantity of training. Training intensity did not consistently affect the maintenance of performance gains, which were partially lost over time in both groups. Discussion. These data indicate that increased training intensity increases the rate of functional improvements per time and per training session following ischemic insult. Thus, training intensity is an important variable to consider in efforts to optimize rehabilitation efficacy.