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Finding an optimal rehabilitation paradigm after stroke: enhancing fiber growth and training of the brain at the right moment.

ABSTRACT: After stroke the central nervous system reveals a spectrum of intrinsic capacities to react as a highly dynamic system which can change the properties of its circuits, form new contacts, erase others, and remap related cortical and spinal cord regions. This plasticity can lead to a surprising degree of spontaneous recovery. It includes the activation of neuronal molecular mechanisms of growth and of extrinsic growth promoting factors and guidance signals in the tissue. Rehabilitative training and pharmacological interventions may modify and boost these neuronal processes, but almost nothing is known on the optimal timing of the different processes and therapeutic interventions and on their detailed interactions. Finding optimal rehabilitation paradigms requires an optimal orchestration of the internal processes of re-organization and the therapeutic interventions in accordance with defined plastic time windows. In this review we summarize the mechanisms of spontaneous plasticity after stroke and experimental interventions to enhance growth and plasticity, with an emphasis on anti-Nogo-A immunotherapy. We highlight critical time windows of growth and of rehabilitative training and consider different approaches of combinatorial rehabilitative schedules. Finally, we discuss potential future strategies for designing repair and rehabilitation paradigms by introducing a "3 step model": determination of the metabolic and plastic status of the brain, pharmacological enhancement of its plastic mechanisms, and stabilization of newly formed functional connections by rehabilitative training.

SUBMITTER: Wahl AS

PROVIDER: S-EPMC4072965 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Finding an optimal rehabilitation paradigm after stroke: enhancing fiber growth and training of the brain at the right moment.

Wahl Anna-Sophia AS Schwab Martin E ME

Frontiers in human neuroscience 20140627

After stroke the central nervous system reveals a spectrum of intrinsic capacities to react as a highly dynamic system which can change the properties of its circuits, form new contacts, erase others, and remap related cortical and spinal cord regions. This plasticity can lead to a surprising degree of spontaneous recovery. It includes the activation of neuronal molecular mechanisms of growth and of extrinsic growth promoting factors and guidance signals in the tissue. Rehabilitative training an ...[more]

PMID: 25018717

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Project description:Introduction: Robot-assisted therapy for upper extremity (UE) impairments post-stroke has yielded modest gains in motor capacity and little evidence of improved UE performance during activities of daily living. A paradigm shift that embodies principles of motor learning and exercise dependent neuroplasticity may improve robot therapy outcomes by incorporating active problem solving, salience of trained tasks, and strategies to facilitate the transfer of acquired motor skills to use of the paretic arm and hand during everyday activities. Objective: To pilot and test the feasibility of a novel therapy protocol, the Active Learning Program for Stroke (ALPS), designed to complement repetitive, robot-assisted therapy for the paretic UE. Key ALPS ingredients included training in the use of cognitive strategies (e.g., STOP, THINK, DO, CHECK) and a goal-directed home action plan (HAP) to facilitate UE self-management and skill transfer. Methods: Ten participants with moderate impairments in UE function >6 months after stroke received eighteen 1-h treatment sessions 2-3/x week over 6-8 weeks. In addition to ALPS training, individuals were randomly assigned to either robot-assisted therapy (RT) or robot therapy and task-oriented training (RT-TOT) to trial whether the inclusion of TOT reinforced participants' understanding and implementation of ALPS strategies. Results: Statistically significant group differences were found for the upper limb subtest of the Fugl-Meyer Assessment (FMA-UE) at discharge and one-month follow-up favoring the RT group. Analyses to examine overall effects of the ALPS protocol in addition to RT and RT-TOT showed significant and moderate to large effects on the FMA-UE, Motor Activity Log, Wolf Motor Function Test, and hand portion of the Stroke Impact Scale. Conclusion: The ALPS protocol was the first to extend cognitive strategy training to robot-assisted therapy. The intervention in this development of concept pilot trial was feasible and well-tolerated, with good potential to optimize paretic UE performance following robot-assisted therapy.

Project description:Proprioception has a crucial role in promoting or hindering motor learning. In particular, an intact position sense strongly correlates with the chances of recovery after stroke. A great majority of neurological patients present both motor dysfunctions and impairments in kinesthesia, but traditional robot and virtual reality training techniques focus either in recovering motor functions or in assessing proprioceptive deficits. An open challenge is to implement effective and reliable tests and training protocols for proprioception that go beyond the mere position sense evaluation and exploit the intrinsic bidirectionality of the kinesthetic sense, which refers to both sense of position and sense of movement. Modulated haptic interaction has a leading role in promoting sensorimotor integration, and it is a natural way to enhance volitional effort. Therefore, we designed a preliminary clinical study to test a new proprioception-based motor training technique for augmenting kinesthetic awareness via haptic feedback. The feedback was provided by a robotic manipulandum and the test involved seven chronic hemiparetic subjects over 3?weeks. The protocol included evaluation sessions that consisted of a psychometric estimate of the subject's kinesthetic sensation, and training sessions, in which the subject executed planar reaching movements in the absence of vision and under a minimally assistive haptic guidance made by sequences of graded force pulses. The bidirectional haptic interaction between the subject and the robot was optimally adapted to each participant in order to achieve a uniform task difficulty over the workspace. All the subjects consistently improved in the perceptual scores as a consequence of training. Moreover, they could minimize the level of haptic guidance in time. Results suggest that the proposed method is effective in enhancing kinesthetic acuity, but the level of impairment may affect the ability of subjects to retain their improvement in time.

Project description:BACKGROUND: Loss of fluency is a significant source of functional impairment in many individuals with aphasia. Repetitive transcranial magnetic stimulation (rTMS) administered to the right inferior frontal gyrus (IFG) has been shown to facilitate naming in persons with chronic left hemisphere stroke and non-fluent aphasia. However, changes in fluency in aphasic subjects receiving rTMS have not been adequately explored. AIMS: To determine whether rTMS improves fluency in individuals with chronic nonfluent aphasia, and to identify aspects of fluency that are modulated in persons who respond to rTMS. METHODS #ENTITYSTARTX00026; PROCEDURES: Ten individuals with left hemisphere MCA strokes and mild to moderate non-fluent aphasia participated in the study. Before treatment, subjects were asked to describe the Cookie Theft picture in three separate sessions. During treatment, all subjects received 1200 pulses of 1 Hz rTMS daily in 10 sessions over two weeks at a site that had previously been shown to improve naming. Subjects repeated the Cookie Theft description two months after treatment. Five subjects initially received sham stimulation instead of real TMS. Two months after sham treatment, these individuals received real rTMS. Performance both at baseline and after stimulation was coded using Quantitative Production Analysis (Saffran, Berndt & Schwartz, 1989) and Correct Information Unit (Nicholas & Brookshire, 1993) analysis. OUTCOMES #ENTITYSTARTX00026; RESULTS: Across all subjects (n=10), real rTMS treatment resulted in a significant increase in multiple measures of discourse productivity compared to baseline performance. There was no significant increase in measures of sentence productivity or grammatical accuracy. There was no significant increase from baseline in the sham condition (n=5) on any study measures. CONCLUSIONS: Stimulation of the right IFG in patients with chronic non-fluent aphasia facilitates discourse production. We posit that this effect may be attributable to improved lexical-semantic access.

Project description:Background and Purpose- Therapeutic strategies that capitalize on the intrinsic capacity for neurological recovery early poststroke to improve locomotion are uncertain. Emerging data suggest that task-specific stepping practice provided at higher cardiovascular intensities may be critical dosage parameters that could maximize locomotor recovery. The purpose of this investigation was to determine the comparative effectiveness of providing high-intensity training on locomotor capacity early poststroke as compared with usual care. Methods- A quasi-experimental design was used to compare changes in stepping activity (StepWatch), walking, and balance outcomes during usual care (n=56) versus high-intensity stepping intervention (n=54) in inpatient stroke patients. Primary outcomes assessed weekly included self-selected and fastest gait speed, 6-minute walk test, and the Berg Balance Scale, with secondary outcomes of Swedish Postural Assessment Scale for Stroke-Norwegian version, Functional Ambulation Category, 30-s sit-to-stand, strength (average manual muscle testing), and Barthel Index. Regression analyses identified relationships between demographics, baseline function, and training activities (steps per day; duration achieved, 70%-85% maximum heart rates) and primary outcomes at discharge. Results- Following implementation of high-intensity stepping, average steps per day (5777±2784) were significantly greater than during usual care (3917±2656; P<0.001). Statistically different and clinically meaningful changes in self-selected speed (0.39±0.28 versus 0.16±0.26 m/s) and fastest gait speed (0.47±0.41 versus 0.17±0.38 m/s; both P<0.001) were observed following high-intensity interventions versus usual care and at every assessment throughout the length of stay. Changes in Berg Balance Scale and 6-minute walk test were also statistically and clinically different between groups, while secondary measures of Functional Ambulation Category and strength were also different at discharge. Primary predictors of improved walking capacity were steps per day, baseline impairments, and age. Conclusions- Provision of high-intensity stepping training applied during inpatient rehabilitation resulted in significantly greater walking and balance outcomes. This training paradigm should be further tested in other contexts to determine the generalizability to real-world and community settings.

Project description:Traditional rehabilitation strategies become difficult in the chronic phase stage of stroke prognosis. Brain-computer interface (BCI) combined with external devices may improve motor function in chronic stroke patients, but it lacks comprehensive assessments of neurological changes regarding functional rehabilitation. This study aimed to comprehensively and quantitatively investigate the changes in brain activity induced by BCI-FES training in patients with chronic stroke. We analyzed the EEG of two groups of patients with chronic stroke, one group received functional electrical stimulation (FES) rehabilitation training (FES group) and the other group received BCI combined with FES training (BCI-FES group). We constructed functional networks in both groups of patients based on direct directed transfer function (dDTF) and assessed the changes in brain activity using graph theory analysis. The results of this study can be summarized as follows: (i) after rehabilitation training, the Fugl-Meyer assessment scale (FMA) score was significantly improved in the BCI-FES group (p < 0.05), and there was no significant difference in the FES group. (ii) Both the global and local graph theory measures of the brain network of patients with chronic stroke in the BCI-FES group were improved after rehabilitation training. (iii) The node strength in the contralesional hemisphere and central region of patients in the BCI-FES group was significantly higher than that in the FES group after the intervention (p < 0.05), and a significant increase in the node strength of C4 in the contralesional sensorimotor cortex region could be observed in the BCI-FES group (p < 0.05). These results suggest that BCI-FES rehabilitation training can induce clinically significant improvements in motor function of patients with chronic stroke. It can improve the functional integration and functional separation of brain networks and boost compensatory activity in the contralesional hemisphere to a certain extent. The findings of our study may provide new insights into understanding the plastic changes of brain activity in patients with chronic stroke induced by BCI-FES rehabilitation training.

Project description:INTRODUCTION:The Rehabilitation Training (ReTrain) intervention aims to improve functional mobility, adherence to poststroke exercise guidelines and quality of life for people after stroke. A definitive randomised controlled trial (RCT) is required to assess the clinical and cost-effectiveness of ReTrain, which is based on Action for Rehabilitation from Neurological Injury (ARNI). The purpose of this pilot study is to assess the feasibility of such a definitive trial and inform its design. METHODS AND ANALYSIS:A 2-group, assessor-blinded, randomised controlled external pilot trial with parallel mixed-methods process evaluation and economic evaluation. 48 participants discharged from clinical rehabilitation despite residual physical disability will be individually randomised 1:1 to ReTrain (25 sessions) or control (exercise advice booklet). Outcome assessment at baseline, 6 and 9?months include Rivermead Mobility Index; Timed Up and Go Test; modified Patient-Specific Functional Scale; 7-day accelerometry; Stroke Self-efficacy Questionnaire, exercise diary, Fatigue Assessment Scale, exercise beliefs and self-efficacy questionnaires, SF-12, EQ-5D-5L, Stroke Quality of Life, Carer Burden Index and Service Receipt Inventory. Feasibility, acceptability and process outcomes include recruitment and retention rates; with measurement burden and trial experiences being explored in qualitative interviews (20 participants, 3 intervention providers). Analyses include descriptive statistics, with 95% CI where appropriate; qualitative themes; intervention fidelity from videos and session checklists; rehearsal of health economic analysis. ETHICS AND DISSEMINATION:National Health Service (NHS) National Research Ethics Service approval granted in April 2015; recruitment started in June. Preliminary studies suggested low risk of serious adverse events; however (minor) falls, transitory muscle soreness and high levels of postexercise fatigue are expected. Outputs include pilot data to inform whether to proceed to a definitive RCT and support a funding application; finalised Trainer and Intervention Delivery manuals for multicentre replication of ReTrain; presentations at conferences, public involvement events; internationally recognised peer-reviewed journal publications, open access sources and media releases. TRIAL REGISTRATION NUMBER:NCT02429180; Pre-results.

Dataset Information

Finding an optimal rehabilitation paradigm after stroke: enhancing fiber growth and training of the brain at the right moment.

Publications

Finding an optimal rehabilitation paradigm after stroke: enhancing fiber growth and training of the brain at the right moment.

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