Paired associative stimulation (PAS) combining repeated pairing of electrical stimulation of a peripheral nerve with transcranial magnetic stimulation (TMS) over the primary motor cortex (M1) can induce neuroplastic adaptations in the human brain and enhance motor learning in neurologically-intact individuals. However, the extent to which PAS is an effective technique for inducing associative plasticity and improving motor function in individuals post-stroke is unclear. Objective: The objective of this pilot study was to investigate the effects of a single session of PAS to modulate corticomotor excitability and motor skill performance in individuals post-stroke. Methods: Seven individuals with chronic stroke completed two separate visits separated by at least one week. We assessed general corticomotor excitability, intracortical network activity and behavioral outcomes prior to and at three time points following PAS and compared these outcomes to those following a sham PAS condition (PAS SHAM). Results: Following PAS, we found increased general corticomotor excitability but no significant difference in behavioral measures between PAS conditions. There was a relationship between PAS-induced corticomotor excitability increase and enhanced motor skill performance across post-PAS testing time points. Conclusion: These results provide preliminary evidence for the potential of PAS to increase corticomotor excitability that could favorably impact motor skill performance in chronic individuals post-stroke and are an important first step for future studies investigating the clinical application and behavioral relevance of PAS interventions in post stroke patient populations.

OBJECTIVE: Constraint-induced movement therapy (CIMT) has been shown to improve upper extremity voluntary movement and change cortical movement representation after stroke. Direct comparison of the differential degree of cortical reorganization according to chronicity in stroke subjects receiving CIMT has not been performed and was the purpose of this study. We hypothesized that a higher degree of cortical reorganization would occur in the early (less than 9 months post-stroke) compared to the late group (more than 12 months post-stroke).METHODS: 17 early and 9 late subjects were enrolled. Each subject was evaluated using transcranial magnetic stimulation (TMS) and the Wolf Motor Function Test (WMFT) and received CIMT for 2 weeks. RESULTS: The early group showed greater improvement in WMFT compared with the late group. TMS motor maps showed persistent enlargement in both groups but the late group trended toward more enlargement. The map shifted posteriorly in the late stroke group. The main limitation was the small number of TMS measures that could be acquired due to high motor thresholds, particularly in the late group. CONCLUSION: CIMT appears to lead to greater improvement in motor function in the early phase after stroke. Greater cortical reorganization in map size and position occurred in the late group in comparison. SIGNIFICANCE: The contrast between larger functional gains in the early group vs larger map changes in the late group may indicate that mechanisms of recovery change over the several months following stroke or that map changes are a time-dependent epiphenomenon.

Background. Tools chosen to measure poststroke upper-extremity rehabilitation outcomes must match contemporary theoretical expectations of motor deficit and recovery because an assessmentg's theoretical underpinning forms the conceptual basis for interpreting its score. Objective. The purpose of this study was to investigate the theoretical framework of the Wolf Motor Function Test (WMFT) by (1) determining whether all items measured a single underlying trait and (2) examining the congruency between the hypothesized and the empirically determined item difficulty orders. Methods. Confirmatory factor analysis (CFA) and Rasch analysis were applied to existing WMFT Functional Ability Rating Scale data from 189 participants in the EXCITE (Extremity Constraint-Induced Therapy Evaluation) trial. Fit of a 1-factor CFA model (all items) was compared with the fit of a 2-factor CFA model (factors defined according to item object-grasp requirements) with fit indices, model comparison test, and interfactor correlations. Results. One item was missing sufficient data and therefore removed from analysis. CFA fit indices and the model-comparison test suggested that both models fit equally well. The 2-factor model yielded a strong interfactor correlation, and 13 of 14 items fit the Rasch model. The Rasch item difficulty order was consistent with the hypothesized item difficulty order. Conclusion. The results suggest that WMFT items measure a single construct. Furthermore, the results depict an item difficulty hierarchy that may advance the theoretical discussion of the person ability versus task difficulty interaction during stroke recovery.

Human brains are highly plastic throughout the life­span, even after brain injuries. The possible modulation of functions due to neural plasticity in various brain regions contributes to the learning and adaptation of unlearnt as well as new behaviors. Over the past decade, research on brain-behavior relationships has grown exponentially. In addition to behavioral assessments, electrophysiology and neuroimaging methods have been widely used to examine the neural networks, structural and functional abnormalities, and the effects of the therapeutic training in aged adults or individuals with neurological disorders. The five contributions to this special issue address the relationships between brain and behavior and have implications for present and future research and practice in neurorehabilitation.

Background Residual disability after stroke is substantial; 65% of patients at 6 months are unable to incorporate the impaired upper extremity into daily activities. Task-oriented training programs are rapidly being adopted into clinical practice. In the absence of any consensus on the essential elements or dose of task-specific training, an urgent need exists for a well-designed trial to determine the effectiveness of a specific multidimensional task-based program governed by a comprehensive set of evidence-based principles. The Interdisciplinary Comprehensive Arm Rehabilitation Evaluation (ICARE) Stroke Initiative is a parallel group, three-arm, single blind, superiority randomized controlled trial of a theoretically-defensible, upper extremity rehabilitation program provided in the outpatient setting. The primary objective of ICARE is to determine if there is a greater improvement in arm and hand recovery one year after randomization in participants receiving a structured training program termed Accelerated Skill Acquisition Program (ASAP), compared to participants receiving usual and customary therapy of an equivalent dose (DEUCC). Two secondary objectives are to compare ASAP to a true (active monitoring only) usual and customary (UCC) therapy group and to compare DEUCC and UCC. Methods/design Following baseline assessment, participants are randomized by site, stratified for stroke duration and motor severity. 360 adults will be randomized, 14 to 106 days following ischemic or hemorrhagic stroke onset, with mild to moderate upper extremity impairment, recruited at sites in Atlanta, Los Angeles and Washington, D.C. The Wolf Motor Function Test (WMFT) time score is the primary outcome at 1 year post-randomization. The Stroke Impact Scale (SIS) hand domain is a secondary outcome measure. The design includes concealed allocation during recruitment, screening and baseline, blinded outcome assessment and intention to treat analyses. Our primary hypothesis is that the improvement in log-transformed WMFT time will be greater for the ASAP than the DEUCC group. This pre-planned hypothesis will be tested at a significance level of 0.05. Discussion ICARE will test whether ASAP is superior to the same number of hours of usual therapy. Pre-specified secondary analyses will test whether 30 hours of usual therapy is superior to current usual and customary therapy not controlled for dose. Trial registration http://www.ClinicalTrials.gov webcite Identifier: NCT00871715

Background At 6 months poststroke, most patients cannot incorporate their affected hand into daily activities, which in turn is likely to reduce their perceived quality of life. Objective This preliminary study explored change in patient-reported, health-related quality of life associated with robotic-assisted therapy combined with reduced therapist-supervised training. Design and Setting A single-blind, multi-site, randomized clinical trial was conducted. Participants Seventeen individuals who were 3 to 9 months poststroke participated. Intervention Sixty hours of therapist-supervised repetitive task practice (RTP) was compared with 30 hours of RTP combined with 30 hours of robotic-assisted therapy. Measurements Participants completed the Stroke Impact Scale (SIS) at baseline, immediately postintervention, and 2 months postintervention. Change in SIS score domains was assessed in a mixed model analysis. Results The combined therapy group had a greater increase in rating of mood from preintervention to postintervention, and the RTP-only group had a greater increase in rating of social participation from preintervention to follow-up. Both groups had statistically significant improvement in activities of daily living and instrumental activities of daily living scores from preintervention to postintervention. Both groups reported significant improvement in hand function postintervention and at follow-up, and the magnitude of these changes suggested clinical significance. The combined therapy group had significant improvements in stroke recovery rating postintervention and at follow-up, which appeared clinically significant; this also was true for stroke recovery rating from preintervention to follow-up in the RTP-only group. Limitations Outcomes of 30 hours of RTP in the absence of robotic-assisted therapy remain unknown. Conclusion Robotic-assisted therapy may be an effective alternative or adjunct to the delivery of intensive task practice interventions to enhance hand function recovery in patients with stroke.

Background This study determined the reliability of topographic motor cortical maps and MEP characteristics in the extensor digitorum communis (EDC) evoked by single-pulse TMS among patients with chronic stroke. Methods Each of ten patients was studied on three occasions. Measures included location of the EDC hotspot and center of gravity (COG), threshold of activation and average amplitude of the hotspot, number of active sites, map volume, and recruitment curve (RC) slope. Results Consistent intrahemispheric measurements were obtained for the three TMS mapping sessions for all measured variables. No statistically significant difference was observed between hemispheres for the number of active sites, COG distance or the RC slope. The magnitude and range of COG movement between sessions were similar to those reported previously with this muscle in able-bodied individuals. The average COG movement over three sessions in both hemispheres was 0.90 cm. The average COG movement in the affected hemisphere was 1.13 (± 0.08) cm, and 0.68 (± 0.04) cm) for the less affected hemisphere. However, significant interhemispheric variability was seen for the average MEP amplitude, normalized map volume, and resting motor threshold. Conclusion The physiologic variability in some TMS measurements of EDC suggest that interpretation of TMS mapping data derived from hemiparetic patients in the chronic stage following stroke should be undertaken cautiously. Irrespective of the muscle, potential causes of variability should be resolved to accurately assess the impact of pharmacological or physical interventions on cortical organization as measured by TMS among patients with stroke.

This third chapter discusses the evidence for the rehabilitation of the most common movement disorders of the upper extremity. The authors also present a framework, building on the computation, anatomy, and physiology (CAP) model, for incorporating some of the principles discussed in the 2 previous chapters by Frey et al and Sathian et al in the practice of rehabilitation and for discussing potentially helpful interventions based on emergent neuroscience principles.

Background: Externally guided (EG) and internally guided (IG) movements are postulated to recruit two parallel neural circuits, in which motor cortical neurons interact with either the cerebellum or striatum via distinct thalamic nuclei. Research suggests EG movements rely more heavily on the cerebello-thalamo-cortical circuit, whereas IG movements rely more on the striato-pallido-thalamo-cortical circuit (1). Because Parkinson's (PD) involves striatal dysfunction, individuals with PD have difficulty generating IG movements (2). Objectives: Determine whether individuals with PD would employ a compensatory mechanism favoring the cerebellum over the striatum during IG lower limb movements. Methods: 22 older adults with mild-moderate PD, who had abstained at least 12 h from anti-PD medications, and 19 age-matched controls performed EG and IG rhythmic foot-tapping during functional magnetic resonance imaging. Participants with PD tapped with their right (more affected) foot. External guidance was paced by a researcher tapping participants' ipsilateral 3rd metacarpal in a pattern with 0.5 to 1 s intervals, while internal guidance was based on pre-scan training in the same pattern. BOLD activation was compared between tasks (EG vs. IG) and groups (PD vs. control). Results: Both groups recruited the putamen and cerebellar regions. The PD group demonstrated less activation in the striatum and motor cortex than controls. A task (EG vs. IG) by group (PD vs. control) interaction was observed in the cerebellum with increased activation for the IG condition in the PD group. Conclusions: These findings support the hypothesized compensatory shift in which the dysfunctional striatum is assisted by the less affected cerebellum to accomplish IG lower limb movement in individuals with mild-moderate PD. These findings are of relevance for temporal gait dysfunction and freezing of gait problems frequently noted in many people with PD and may have implications for future therapeutic application.