Neurorehabilitation and Neural Repair

Background. The mirror neuron network provides a neural mechanism to prime the motor system through action observation in stroke survivors. Objective. To examine whether action observation training with immediate physical practice improves upper-limb function in chronic stroke. Methods. In a within-subject design, 14 chronic stroke survivors were assessed at baseline, then participated in 2 weeks of relaxation-sham plus physical practice (control) and reassessed. Thereafter, they participated in 2 weeks of action observation training coupled with immediate physical practice (intervention), followed by a final assessment. Duration of each action observation video sequence (priming exposure) was 30 s followed immediately by practice of the observed motor skill. Results. There were significant improvements in control and intervention phases on primary outcome measures—Upper Extremity Fugl-Meyer Motor Assessment (FMA) and Functional Test of the Hemiparetic Upper Extremity (FTHUE)—as well as secondary outcome measures of self-perceptions of arm use. Gains in the primary outcomes were greater during the intervention phase (action observation + physical practice; FMA, 10.64; FTHUE level, 0.79, and tasks, 1.57) than during the control phase (relaxation-sham plus physical practice; FMA, 6.64; FTHUE level, 0.43, and tasks, 1.00). Interviews with participants highlighted the added value of watching an actor perform the movement before physically attempting to perform the action. Conclusions. This study provides preliminary evidence of the additive value of action observation plus physical practice over relaxation-sham plus physical practice. There appears to be capacity for further recovery of upper-limb function in chronic stroke that persists at least in the short term.

Background and objective. Patient-led therapy has the potential to increase the amount of therapy patients undertake during stroke rehabilitation and to enhance recovery. Our objective was to assess the feasibility and acceptability of 2 patient-led therapies during the acute stages of stroke care: mirror therapy for the upper limb and lower-limb exercises for the lower limb. Methods. This was a blind assessed, multicenter, pragmatic randomized controlled trial of patient-led upper-limb mirror therapy and patient-led lower leg exercises. Stroke survivors with upper and lower limb limitations, undergoing inpatient rehabilitation and able to consent were recruited at least 1 week poststroke. Results. Both interventions proved feasible, with >90% retention. No serious adverse events were reported. Both groups did less therapy than recommended; typically 5 to 15 minutes for 7 days or less. Participants receiving mirror therapy (n = 63) tended to do less practice than those doing lower-limb exercises (n = 31). Those with neglect did 69% less mirror therapy than those without (P = .02), which was not observed in the exercise group. Observed between-group differences were modest but neglect, upper-limb strength, and dexterity showed some improvement in the mirror therapy group. No changes were seen in the lower-limb group. Conclusions. Both patient-led mirror therapy and lower-limb exercises during inpatient stroke care are safe, feasible, and acceptable and warrant further investigation. Practice for 5 to 15 minutes for 7 days is a realistic prescription unless strategies to enhance adherence are included.

Background. Highly challenging exercises have been suggested to induce neuroplasticity in individuals with Parkinson’s disease (PD); however, its effect on clinical outcomes remains largely unknown. Objective. To evaluate the short-term effects of the HiBalance program, a highly challenging balance-training regimen that incorporates both dual-tasking and PD-specific balance components, compared with usual care in elderly with mild to moderate PD. Methods. Participants with PD (n = 100) were randomized, either to the 10-week HiBalance program (n = 51) or to the control group (n = 49). Participants were evaluated before and after the intervention. The main outcomes were balance performance (Mini-BESTest), gait velocity (during normal and dual-task gait), and concerns about falling (Falls Efficacy Scale–International). Performance of a cognitive task while walking, physical activity level (average steps per day), and activities of daily living were secondary outcomes. Results. A total of 91 participants completed the study. After the intervention, the between group comparison showed significantly improved balance and gait performance in the training group. Moreover, although no significant between group difference was observed regarding gait performance during dual-tasking; the participants in the training group improved their performance of the cognitive task while walking, as compared with the control group. Regarding physical activity levels and activities of daily living, in comparison to the control group, favorable results were found for the training group. No group differences were found for concerns about falling. Conclusions. The HiBalance program significantly benefited balance and gait abilities when compared with usual care and showed promising transfer effects to everyday living. Long-term follow-up assessments will further explore these effects.

Background. Tinnitus is the phantom perception of sound and can have negative effect on the quality of life. Transcranial direct current stimulation (tDCS) is a noninvasive neuromodulation technique, which can increase or decrease the cortical excitability in the brain region to which it is applied. tDCS has been used for tinnitus research since 2006. Objective. To investigate whether tDCS affects tinnitus perception, related emotion, or both, and the potential implications for tinnitus management. Methods. A scoping review was undertaken using the methods proposed by Arksey and O’Malley. After initial consideration of title relevance and reading abstracts, 15 studies were included in this review. The data from these studies were charted to investigate the impact of tDCS on tinnitus perception and emotions. Results. tDCS results in transient suppression of tinnitus loudness and annoyance; however, it does not lead to long-term impact on tinnitus related emotion. Local stimulation of different sites of stimulation (left temporoparietal area, dorsolateral prefrontal cortex, and auditory cortex) might modulate tinnitus perception (loudness) and emotions differently; however, further research is needed to explore this hypothesis. This review has identified aspects of methodologies that require attention in upcoming tinnitus and tDCS trials to offer better insights. Conclusions. tDCS is an effective research tool for transient tinnitus neuromodulation. However, efforts should be invested in designing clinical trials using local and multiple sites of stimulation, optimized parameters, and objective outcome measures before it can be translated in to a clinical tool for tinnitus management.

Background. Regaining independent ambulation is important to those with stroke. Increased walking practice during “down time” in rehabilitation could improve walking function for individuals with stroke. Objective. To determine the effect of providing physiotherapists with accelerometer-based feedback on patient activity and walking-related goals during inpatient stroke rehabilitation. Methods. Participants with stroke wore accelerometers around both ankles every weekday during inpatient rehabilitation. Participants were randomly assigned to receive daily feedback about walking activity via their physiotherapists (n = 29) or to receive no feedback (n = 28). Changes in measures of daily walking (walking time, number of steps, average cadence, longest bout duration, and number of “long” walking bouts) and changes in gait control and function assessed in-laboratory were compared between groups. Results. There was no significant increase in walking time, number of steps, longest bout duration, or number of long walking bouts for the feedback group compared with the control group (P values > .20). However, individuals who received feedback significantly increased cadence of daily walking more than the control group (P = .013). From the in-laboratory gait assessment, individuals who received feedback had a greater increase in walking speed and decrease in step time variability than the control group (P values < .030). Conclusion. Feedback did not increase the amount of walking completed by individuals with stroke. However, there was a significant increase in cadence, indicating that intensity of daily walking was greater for those who received feedback than the control group. Additionally, more intense daily walking activity appeared to translate to greater improvements in walking speed.

Background. Crossed cerebellar diaschisis is the disruption of functional connectivity between cerebrum and cerebellum after hemispheric unilateral brain lesions. In adults and to a lesser extent in children, crossed cerebellar diaschisis has been largely investigated by functional connectivity and demonstrated to influence paretic hand function. Objective. We aim to demonstrate a disruption in structural corticopontocerebellar (CPC) connectivity in children with congenital brain lesions and examine its correlation with paretic hand motor function. Methods. Thirty-six children (Manual Ability Classification System: I, n = 21; II, n = 15) with unilateral brain lesions and 18 controls were analyzed in a case-control study, and diffusion magnetic resonance imaging data were acquired at 3T. High angular resolution diffusion imaging probabilistic tractography was employed for the region of interest–based reconstruction of CPC tracts. To identify statistical differences in structural cerebrocerebellar connectivity between case and control groups, an asymmetry index based on the number of streamlines of CPC tracts was used. In the case group, the correlation between asymmetry index and hand function measures was also determined. Results. Projections through the middle cerebellar peduncle to the contralateral cerebral cortex showed greater asymmetry in children with congenital unilateral brain lesion compared to controls (P = .03), thus indicating a disruption of structural cerebrocerebellar connectivity. The degree of asymmetry index showed a correlation (P < .03; r = −0.31) with impaired hand abilities in bimanual tasks. Conclusions. Disruption of structural cerebrocerebellar connectivity is present in patients with congenital unilateral brain injury and might be related to impaired hand function in bimanual skills, with potential implication in tailoring early intervention strategies.

Background. Several novel drug- and cell-based potential therapies for spinal cord injury (SCI) have either been applied or will be considered for future clinical trials. Limitations on the number of eligible patients require trials be undertaken in a highly efficient and effective manner. However, this is particularly challenging when people living with incomplete SCI (iSCI) represent a very heterogeneous population in terms of recovery patterns and can improve spontaneously over the first year after injury. Objective. The current study addresses 2 requirements for designing SCI trials: first, enrollment of as many eligible participants as possible; second, refined stratification of participants into homogeneous cohorts from a heterogeneous iSCI population. Methods. This is a retrospective, longitudinal analysis of prospectively collected SCI data from the European Multicenter study about Spinal Cord Injury (EMSCI). We applied conditional inference trees to provide a prediction-based stratification algorithm that could be used to generate decision rules for the appropriate inclusion of iSCI participants to a trial. Results. Based on baseline clinical assessments and a defined subsequent clinical endpoint, conditional inference trees partitioned iSCI participants into more homogeneous groups with regard to the illustrative endpoint, upper extremity motor score. Assuming a continuous endpoint, the conditional inference tree was validated both internally as well as externally, providing stable and generalizable results. Conclusion. The application of conditional inference trees is feasible for iSCI participants and provides easily implementable, prediction-based decision rules for inclusion and stratification. This algorithm could be utilized to model various trial endpoints and outcome thresholds.

Background. Parkinson’s disease (PD) is associated with stooped postural alignment, increased postural sway, and reduced mobility. The Alexander Technique (AT) is a mindfulness-based approach to improving posture and mobility by reducing muscular interference while maintaining upward intentions. Evidence suggests that AT can reduce disability associated with PD, but a mechanism for this effect has not yet been established. Objective. We investigated whether AT-based instructions reduce axial rigidity and increase upright postural alignment, and whether these instructions have different effects on postural alignment, axial rigidity, postural sway, and mobility than effort-based instructions regarding posture. Method. Twenty subjects with PD practiced 2 sets of instructions and then attempted to implement both approaches (as well as a relaxed control condition) during quiet standing and step initiation. The “Lighten Up” instructions relied on AT principles of reducing excess tension while encouraging length. The “Pull Up” instructions relied on popular concepts of effortful posture correction. We measured kinematics, resistance to axial rotation, and ground reaction forces. Results. Both sets of experimental instructions led to increases in upright postural alignment relative to the control condition. Only the Lighten Up instructions led to reduced postural sway, reduced axial postural tone, greater modifiability of tone, and a smoother center of pressure trajectory during step initiation, possibly indicating greater movement efficiency. Conclusion. Mindful movement approaches such as AT may benefit balance and mobility in subjects with PD by acutely facilitating increased upright postural alignment while decreasing rigidity.

Background. Weakness is reported in Parkinson’s but always unadjusted for recognized factors that influence muscle strength such as participants’ age, gender, and body size. This may obscure the true association of Parkinson’s with muscle strength. Objective. To evaluate the relationship between grip strength, Parkinson’s severity, and duration adjusting for these factors. Methods. Age, gender, height, weight, grip strength, Unified Parkinson’s Disease Rating Score (UPDRS) motor score, Hoehn and Yahr (H&Y) stage, disease duration, number of comorbidities and medications, Barthel score, Mini Mental State Examination (MMSE) score, and Malnutrition Universal Screening Tool (MUST) score were recorded. Results. Fifty-seven of 79 (72%) people with Parkinson’s resident in one town were recruited. Age, gender, height, and Parkinson’s severity were the most significant determinants of grip strength. Each unit increase in UPDRS motor score and H&Y stage was associated with lower grip strength in univariate linear regression analyses adjusted for gender: −0.3 kg strength (95% confidence interval = −0.51, −0.09), P = .006 for each additional UPDRS point, and −3.87 kg strength (95% confidence interval = −6.54, −1.21), P = .005 for each additional H&Y stage. Disease duration was not associated with grip strength. In multivariate regression, Parkinson’s severity remained strongly associated with grip strength (UPDRS score P = .09; H&Y stage P = .04). Conclusions. This is the first demonstration that increasing severity of Parkinson’s was associated with weaker grip after adjustment for known influences on muscle strength. Participants’ age, gender, and body size also had a significant impact on strength. Adjustment of reported values for all these factors is essential to allow accurate reporting of grip strength values in intervention trials and comparison between different groups.

Previous work demonstrates that spatial (explicit) and nonspatial (implicit) elements of place learning in the Morris water maze (MWM) task can be dissociated and examined in the context of experimental traumatic brain injury (TBI). Providing nonspatial cognitive training (CT) after injury can improve place learning compared with untrained controls. In the present study, we hypothesized that brief exposure to extra-maze cues, in conjunction with CT, may further improve MWM performance and extra-maze cue utilization compared with CT alone. Adult male Sprague-Dawley rats (n = 66) received controlled cortical impact (CCI) injury or sham surgery. Beginning day 8 postsurgery, CCI and sham rats received 6 days of no training (NT) or CT with/without brief, noncontextualized exposure to extra-maze cues (BE and CT, respectively). Acquisition (days 14-18), visible platform (VP; day 19), carryover (CO; days 20-26), and periodic probe trials were performed. Platform latencies, peripheral and target zone time allocation, and search strategies were assessed. CCI/BE rats had shorter acquisition trial latencies than CCI/NT (P < .001) and tended to have shorter latencies than CCI/CT rats (P < .10). Both BE and CT reduced peripheral zone swimming for CCI rats versus CCI/NT. CCI/BE animals increased spatial swim strategies from day 14 to day 18 relative to CCI/CT and showed similar swim strategy selection to the Sham/NT group. These data suggest that visual priming improves initial place learning in the MWM. These results support the visual priming response as another clinically relevant experimental rehabilitation construct, to use when assessing injury and treatment effects of behavioral and pharmacological therapies on cognition after TBI.