Neurorehabilitation and Neural Repair

Background. Few therapeutic options exist for the millions of persons living with severe arm impairment after stroke to increase their dose of arm rehabilitation. This study compared self-guided, high-repetition home therapy with a mechanical device (the resonating arm exerciser [RAE]) to conventional therapy in patients with chronic stroke and explored RAE use for patients with subacute stroke. Methods. A total of 16 participants with severe upper-extremity impairment (mean Fugl-Meyer [FM] score = 21.4 ± 8.8 out of 66) >6 months poststroke were randomized to 3 weeks of exercise with the RAE or conventional exercises. The primary outcome measure was FM score 1 month posttherapy. Secondary outcome measures included Motor Activity Log, Visual Analog Pain Scale, and Ashworth Spasticity Scale. After a 1-month break, individuals in the conventional group also received a 3-week course of RAE therapy. Results. The change in FM score was significant in both the RAE and conventional groups after training (2.6 ± 1.4 and 3.4 ± 2.4, P = .008 and .016, respectively). These improvements were not significant at 1 month. Exercise with the RAE led to significantly greater improvements in distal FM score than conventional therapy at the 1-month follow-up (P = .02). In a separate cohort of patients with subacute stroke, the RAE was found feasible for exercise. Discussion. In those with severe arm impairment after chronic stroke, home-based training with the RAE was feasible and significantly reduced impairment without increasing pain or spasticity. Gains with the RAE were comparable to those found with conventional training and also included distal arm improvement.

Background. Walking-related disability is the most frequent reason for inpatient stroke rehabilitation. Task-related practice is a critical component for improving patient outcomes. Objective. To test the feasibility of providing quantitative feedback about daily walking performance and motivating greater skills practice via remote sensing. Methods. In this phase III randomized, single blind clinical trial, patients participated in conventional therapies while wearing wireless sensors (triaxial accelerometers) at both ankles. Activity-recognition algorithms calculated the speed, distance, and duration of walking bouts. Three times a week, therapists provided either feedback about performance on a 10-meter walk (speed only) or walking speed feedback plus a review of walking activity recorded by the sensors (augmented). Primary outcomes at discharge included total daily walking time, derived from the sensors, and a timed 15-meter walk. Results. Sixteen rehabilitation centers in 11 countries enrolled 135 participants over 15 months. Sensors recorded more than 1800 days of therapy, 37 000 individual walking bouts, and 2.5 million steps. No significant differences were found between the 2 feedback groups in daily walking time (15.1 ± 13.1 vs 16.6 ± 14.3 minutes, P = .54) or 15-meter walking speed (0.93 ± 0.47 vs 0.91 ± 0.53 m/s, P = .96). Remarkably, 30% of participants decreased their total daily walking time over their rehabilitation stay. Conclusions. In this first trial of remote monitoring of inpatient stroke rehabilitation, augmented feedback beyond speed alone did not increase the time spent practicing or improve walking outcomes. Remarkably modest time was spent walking. Wireless sensing, however, allowed clinicians to audit skills practice and provided ground truth regarding changes in clinically important, mobility-related activities.

Background. A higher energy cost of walking poststroke has been linked to reduced walking performance and reduced participation in the community. Objective. To determine the contribution of postintervention improvements in walking speed and spatiotemporal gait asymmetry to the reduction in the energy cost of walking after stroke. Methods. In all, 42 individuals with chronic hemiparesis (>6 months poststroke) were recruited to participate in 12 weeks of walking rehabilitation. The energy cost of walking, walking speed, and step length, swing time, and stance time asymmetries were calculated pretraining and posttraining. Sequential regression analyses tested the cross-sectional (ie, pretraining) and longitudinal (ie, posttraining changes) relationships between the energy cost of walking versus speed and each measure of asymmetry. Results. Pretraining walking speed (β = −.506) and swing time asymmetry (β = .403) predicted pretraining energy costs: _adjR² = 0.713; F(3, 37) = 34.05; P < .001. In contrast, change in walking speed (β = .340) and change in step length asymmetry (β = .934) predicted change in energy costs with a significant interaction between these independent predictors: _adjR² = 0.699; F(4, 31) = 21.326; P < .001. Moderation by the direction or the magnitude of pretraining asymmetry was not found. Conclusions. For persons in the chronic phase of stroke recovery, faster and more symmetric walking after intervention appears to be more energetically advantageous than merely walking faster or more symmetrically. This finding has important functional implications, given the relationship between the energy cost of walking and community walking participation.

Background. Multiple sclerosis (MS) can be accompanied by motor, cognitive, and sensory impairments. Additionally, MS patients often report fatigue as one of their most debilitating symptoms. It is, therefore, expected that MS patients will have difficulties in performing cognitive-motor dual tasks (DTs), especially in a fatiguing condition. Objective. To determine whether MS patients are more challenged by a DT than controls in a fatiguing and less-fatiguing condition and whether DT performance is associated with perceived fatigue. Methods. A group of 19 MS patients and 19 age-, sex-, and education-matched controls performed a cognitive task (2-choice reaction time task) separately or concurrent with a low-force or a high-force motor task (index finger abduction at 10% or 30% maximal voluntary contraction). Results. MS patients performed less well on a cognitive task than controls. Cognitive task performance under DT conditions decreased more for MS patients. Moreover, under high-force DT conditions, cognitive performance declined in both groups but to a larger degree for MS patients. Besides a decline in cognitive task performance, MS patients also showed a stronger decrease in motor performance under high-force DT conditions. DT costs were positively related to perceived fatigue as measured by questionnaires. Conclusions. Compared with controls, MS patients performed less well on DTs as demonstrated by a reduction in both cognitive and motor performances. This performance decrease was stronger under fatiguing conditions and was related to the sense of fatigue of MS patients. These data illustrate problems that MS patients may encounter in daily life because of their fatigue.

Background. One important objective for clinical trialists in rehabilitation is determining efficacy of interventions to enhance motor behavior. In part, limitation in the precision of measurement presents a challenge. The few valid, low-cost observational tools available to assess motor behavior cannot escape the variability inherent in test administration and scoring. This is especially true when there are multiple evaluators and raters, as in the case of multisite randomized controlled trials (RCTs). One way to enhance reliability and reduce variability is to implement rigorous quality control (QC) procedures. Objective. This article describes a systematic QC process used to refine the administration and scoring procedures for the Wolf Motor Function Test (WMFT)–Functional Ability Scale (FAS). Methods. The QC process, a systematic focus-group collaboration, was developed and used for a phase III RCT, which enlisted multiple evaluators and an experienced WMFT-FAS rater panel. Results. After 3 staged refinements to the administration and scoring instructions, we achieved a sufficiently high interrater reliability (weighted κ = 0.8). Conclusions and Implications. A systematic focus-group process was shown to be an effective method to improve reliability of observational assessment tools for motor behavior in neurorehabilitation. A reduction in noise-related variability in performance assessments will increase power and potentially lower the number needed to treat. Improved precision of measurement can lead to more cost-effective and efficient clinical trials. Finally, we suggest that improved precision in measures of motor behavior may provide more insight into recovery mechanisms than a single measure of movement time alone.

Background and Objective. Mirror therapy is a new form of stroke rehabilitation that uses the mirror reflection of the unaffected hand in place of the affected hand to augment movement training. The mechanism of mirror therapy is not known but is thought to involve changes in cerebral organization. We used magnetoencephalography (MEG) to measure changes in cortical activity during mirror training after stroke. In particular, we examined movement-related changes in the power of cortical oscillations in the beta (15-30 Hz) frequency range, known to be involved in movement. Methods. Ten stroke patients with upper limb paresis and 13 healthy controls were recorded using MEG while performing bimanual hand movements in 2 different conditions. In one, subjects looked directly at their affected hand (or dominant hand in controls), and in the other, they looked at a mirror reflection of their unaffected hand in place of their affected hand. The movement-related beta desynchronization was calculated in both primary motor cortices. Results. Movement-related beta desynchronization was symmetrical during bilateral movement and unaltered by the mirror condition in controls. In the patients, movement-related beta desynchronization was generally smaller than in controls, but greater in contralesional compared to ipsilesional motor cortex. This initial asymmetry in movement-related beta desynchronization between hemispheres was made more symmetrical by the presence of the mirror. Conclusions. Mirror therapy could potentially aid stroke rehabilitation by normalizing an asymmetrical pattern of movement-related beta desynchronization in primary motor cortices during bilateral movement.

Objective. To evaluate the effectiveness of a home-based cognitive rehabilitation (CR) program based on the video game Dr Kawashima’s Brain Training (DKBT; Nintendo, Japan), in improving attention, processing speed, and working memory of patients with multiple sclerosis (MS). Methods. This was a randomized, wait-list control study. Patients with MS and failure in at least one between Stroop Test (ST), Paced Auditory Serial Addition Test (PASAT), and Symbol Digit Modalities Test (SDMT) were submitted to an 8-week home-based CR program playing DKBT. Patients were evaluated at baseline and after DKBT by the aforementioned tests, by the Modified Fatigue Impact Scale (MFIS) and by the MS Quality of Life-54 questionnaire (MSQoL-54). Results. Fifty-two 52 patients were screened for eligibility; 35 (mean [standard deviation] age of 43.9 [8.4] years, median Expanded Disability Status Scale score of 2.0 (range = 2.0-6.0) were randomly assigned to the intervention group (n = 18) or wait-list control group (n = 17). ANCOVA analysis showed a significant effect of DKBT on ST (F = 5.027; P = .034; F² = 0.210), SDMT (F = 4.240; P = .049; F² = 0.177), and on some subscales of MSQoL-54. The PASAT and cognitive subscale of MFIS also showed an improvement, but this was just not significant (F = 4.104, P = .054, F² = 0.171, and F = 4.226, P = .054, F² = 0.237, respectively). Conclusion. We suggest that a home-based DKBT program may improve cognitive functions, some aspects of QoL, and cognitive fatigue in patients with MS.

A goal of brain–computer interface research is to develop fast and reliable means of communication for individuals with paralysis and anarthria. We evaluated the ability of an individual with incomplete locked-in syndrome enrolled in the BrainGate Neural Interface System pilot clinical trial to communicate using neural point-and-click control. A general-purpose interface was developed to provide control of a computer cursor in tandem with one of two on-screen virtual keyboards. The novel BrainGate Radial Keyboard was compared to a standard QWERTY keyboard in a balanced copy-spelling task. The Radial Keyboard yielded a significant improvement in typing accuracy and speed—enabling typing rates over 10 correct characters per minute. The participant used this interface to communicate face-to-face with research staff by using text-to-speech conversion, and remotely using an internet chat application. This study demonstrates the first use of an intracortical brain–computer interface for neural point-and-click communication by an individual with incomplete locked-in syndrome.

Background. In preclinical stroke models, improvement in motor performance is associated with reorganization of cortical motor maps. However, the temporal relationship between performance gains and map plasticity is not clear. Objective. This study was designed to assess the effects of rehabilitative training on the temporal dynamics of behavioral and neurophysiological endpoints in a rat model of focal cortical infarct. Methods. Eight days after an ischemic infarct in primary motor cortex, adult rats received either rehabilitative training or were allowed to recover spontaneously. Motor performance and movement quality of the paretic forelimb was assessed on a skilled reach task. Intracortical microstimulation mapping procedures were conducted to assess the topography of spared forelimb representations either at the end of training (post-lesion day 18) or at the end of a 3-week follow-up period (post-lesion day 38). Results. Rats receiving rehabilitative training demonstrated more rapid improvement in motor performance and movement quality during the training period that persisted through the follow-up period. Motor maps in both groups were unusually small on post-lesion day 18. On post-lesion day 38, forelimb motor maps in the rehabilitative training group were significantly enlarged compared with the no-rehab group, and within the range of normal maps. Conclusions. Postinfarct rehabilitative training rapidly improves motor performance and movement quality after an ischemic infarct in motor cortex. However, training-induced motor improvements are not reflected in spared motor maps until substantially later, suggesting that early motor training after stroke can help shape the evolving poststroke neural network.

Background. Following traumatic brain injury (TBI), clinical cognitive training paradigms harness implicit and explicit learning and memory systems to improve function; however, these systems are differentially affected by TBI, highlighting the need for an experimental TBI model that can test efficacy of cognitive training approaches. Objectives. To develop a clinically relevant experimental cognitive training model using the Morris water maze (MWM) wherein training on implicitly learned task components was provided to improve behavioral performance post-TBI. Methods. Eighty-one adult male rats were divided by injury status (controlled cortical impact [CCI]/Sham), non-spatial cognitive training (CogTrained/No-CogTrained), and extra-maze cues (Cued/Non-Cued) during MWM testing. Platform latencies, thigmotaxis, and search strategies were assessed during MWM trials. Results. Cognitive training was associated with improved platform latencies, reduced thigmotaxis, and more effective search strategy use for Sham and CCI rats. In the Cued and Non-Cued MWM paradigm, there were no differences between CCI/CogTrained and Sham/No-CogTrained groups. During novel testing conditions, CogTrained groups applied implicitly learned knowledge/skills; however, sham-cued CogTrained/rats better incorporated extramaze cues into their search strategy than the CCI-Cued group. Cognitive training had no effects on contusion size or hippocampal cell survival. Conclusions. The results provide evidence that CCI-CogTrained rats that learned the nonspatial components of the MWM task applied these skills during multiple conditions of the place-learning task, thereby mitigating cognitive deficits typically associated with this injury model. The results show that a systematic application of clinically relevant constructs associated with cognitive training paradigms can be used with experimental TBI to affect place learning.