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The ipsilesional arm of stroke patients often has functionally limiting deficits in motor control and dexterity that depend on the side of the brain that is lesioned and that increase with the severity of paretic arm impairment. However, remediation of the ipsilesional arm has yet to be integrated into the usual standard of care for upper limb rehabilitation in stroke, largely due to a lack of translational research examining the effects of ipsilesional-arm intervention. We now ask whether ipsilesional-arm training, tailored to the hemisphere-specific nature of ipsilesional-arm motor deficits in participants with moderate to severe contralesional paresis, improves ipsilesional arm performance and generalizes to improve functional independence. We assessed the effects of this intervention on ipsilesional arm unilateral performance [Jebsen–Taylor Hand Function Test (JHFT)], ipsilesional grip strength, contralesional arm impairment level [Fugl–Meyer Assessment (FM)], and functional independence [Functional independence measure (FIM)] ( N = 13). Intervention occurred over a 3 week period for 1.5 h/session, three times each week. All sessions included virtual reality tasks that targeted the specific motor control deficits associated with either left or right hemisphere damage, followed by graded dexterity training in real-world tasks. We also exposed participants to 3 weeks of sham training to control for the non-specific effects of therapy visits and interactions. We conducted five test-sessions: two pre-tests and three post-tests. Our results indicate substantial improvements in the less-impaired arm performance, without detriment to the paretic arm that transferred to improved functional independence in all three posttests, indicating durability of training effects for at least 3 weeks. We provide evidence for establishing the basis of a rehabilitation approach that includes evaluation and remediation of the ipsilesional arm in moderately to severely impaired stroke survivors. This study was originally a crossover design; however, we were unable to complete the second arm of the study due to the COVID-19 pandemic. We report the results from the first arm of the planned design as a longitudinal study.

Background We previously characterized hemisphere-specific motor control deficits in the ipsilesional, less-impaired arm of unilaterally lesioned stroke survivors. Our preliminary data indicate these deficits are substantial and functionally limiting in patients with severe paresis. Methods We have designed an intervention (“IPSI”) to remediate the hemisphere-specific deficits in the ipsilesional arm, using a virtual-reality platform, followed by manipulation training with a variety of real objects, designed to facilitate generalization and transfer to functional behaviors encountered in the natural environment. This is a 2-site (primary site – Penn State College of Medicine, secondary site – University of Southern California), two-group randomized intervention with an experimental group, which receives unilateral training of the ipsilesional arm throughout 3 one-hour sessions per week for 5 weeks, through our Virtual Reality and Manipulation Training (VRMT) protocol. Our control group receives a conventional intervention on the contralesional arm, 3 one-hour sessions per week for 5 weeks, guided by recently released practice guidelines for upper limb rehabilitation in adult stroke. The study aims to include a total of 120 stroke survivors (60 per group) whose stroke was in the territory of the middle cerebral artery (MCA) resulting in severe upper-extremity motor impairments. Outcome measures (Primary: Jebsen-Taylor Hand Function Test, Fugl-Meyer Assessment, Abilhand, Barthel Index) are assessed at five evaluation points: Baseline 1, Baseline 2, immediate post-intervention (primary endpoint), and 3-weeks (short-term retention) and 6-months post-intervention (long-term retention). We hypothesize that both groups will improve performance of the targeted arm, but that the ipsilesional arm remediation group will show greater improvements in functional independence. Discussion The results of this study are expected to inform upper limb evaluation and treatment to consider ipsilesional arm function, as part of a comprehensive physical rehabilitation strategy that includes evaluation and remediation of both arms. Trial Registration This study is registered with ClinicalTrials.gov (Registration ID: NCT03634397 ; date of registration: 08/16/2018).

Background Stroke often results in motor impairments, with recovery involving complex interactions between the lesioned (ipsilesional) and non-lesioned (contralesional) hemispheres. This scoping review investigates the role of the contralesional primary motor cortex (M1) in motor recovery of the paretic upper limb following stroke, examining its structural and functional changes and compensatory roles. Methods A systematic search for scoping review was conducted in PubMed, Embase, Web of Science, and Google Scholar following PRISMA-ScR guidelines. Studies examining contralesional M1 contributions to upper limb recovery in humans and animal models were included. Data were extracted, synthesized qualitatively, and assessed for risk of bias using SYRCLE and Cochrane tools. Results A total of 38 studies were included in the analysis, consisting of 34 focused on stroke patients and 4 utilizing animal models. The findings revealed the dual and task-specific role of the contralesional primary motor cortex (M1) in upper limb recovery after stroke. In patients with severe motor impairments, contralesional M1 supported recovery through compensatory mechanisms, such as increased neuronal recruitment and functional reorganization. However, in cases with mild impairments, its activation was associated with inhibitory effects on ipsilesional reorganization, potentially delaying optimal recovery. Animal studies provided evidence of structural and functional plasticity, including dendritic remodeling and enhanced neuronal connectivity, which paralleled improvements in motor function. In human studies, contralesional M1 activation was task-dependent, with pronounced engagement during demanding tasks and unimanual movements. Ipsilateral motor deficits, including reduced dexterity, strength, and coordination, were commonly reported and underscored the disrupted interhemispheric dynamics influencing recovery. Neuromodulation techniques showed promise in modulating interhemispheric interactions and enhancing motor outcomes. These results emphasize the complex interplay between compensatory and inhibitory processes mediated by contralesional M1 in stroke recovery. Conclusion The contralesional M1 plays a complex, task-specific role in upper limb recovery after stroke, acting as both a compensatory resource and a potential inhibitory factor. Future research should stratify patients by impairment severity to refine therapeutic approaches. Clinical trial number Not applicable.