Objective: To demonstrate the feasibility of algorithmic prediction using a model of baseline arm movement, genetic factors, demographic characteristics, and multimodal assessment of the structure and function of motor pathways. To identify prognostic factors and the biological substrate for reductions in arm impairment in response to repetitive task practice. Design: This prospective single-group interventional study seeks to predict response to a repetitive task practice program using an intent-to-treat paradigm. Response is measured as a change of ≥5 points on the Upper Extremity Fugl-Meyer from baseline to final evaluation (at the end of training). Setting: General community. Participants: Anticipated enrollment of community-dwelling adults with chronic stroke (N=96; onset≥6mo) and moderate to severe residual hemiparesis of the upper limb as defined by a score of 10-45 points on the Upper Extremity Fugl-Meyer. Intervention: The intervention is a form of repetitive task practice using a combination of robot-assisted therapy coupled with functional arm use in real-world tasks administered over 12 weeks. Main Outcome Measures: Upper Extremity Fugl-Meyer Assessment (primary outcome), Wolf Motor Function Test, Action Research Arm Test, Stroke Impact Scale, questionnaires on pain and expectancy, magnetic resonance imaging, transcranial magnetic stimulation, arm kinematics, accelerometry, and a saliva sample for genetic testing. Results: Methods for this trial are outlined, and an illustration of interindividual variability is provided by example of 2 participants who present similarly at baseline but achieve markedly different outcomes. Conclusion: This article presents the design, methodology, and rationale of an ongoing study to develop a predictive model of response to a standardized therapy for stroke survivors with chronic hemiparesis. Applying concepts from precision medicine to neurorehabilitation is practicable and needed to establish realistic rehabilitation goals and to effectively allocate resources. Keywords: Magnetic resonance imaging, Prognosis, Rehabilitation, Stroke, Transcranial magnetic stimulation
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