Muscle and mind: rewiring cognitive-motor recovery through exercise-responsive neurophysiology in neurological populations.

Research overview

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Exercise in neurological rehabilitation is often prescribed to improve mobility, yet its influence extends to cognition through interacting peripheral, central, and behavioral pathways. This narrative review synthesizes evidence on how skeletal muscle activity can engage peripheral biomarkers and system-level interactions that become clinically meaningful only when translated into behaviorally relevant cognitive-motor integration (CMI). We examine neurotrophic, metabolic, immune, vascular, and endocrine relays, then consider central translation through synaptic plasticity, metabolic adaptation, neurovascular coupling, white matter integrity, and functional network reorganization. The central argument is that cognitive benefit cannot be inferred from biomarker change alone. Exercise is most likely to support recovery when biological pathway engagement is paired with attentionally demanding movement, dual-task control, gait automaticity, error-based adaptation, and context-sensitive learning. Research in stroke, Parkinson's disease, multiple sclerosis, and traumatic brain injury illustrates the heterogeneous benefits of exercise. This heterogeneity may be shaped by lesion topology, inflammatory activity, fatigue, autonomic stability, medication state, baseline fitness, and exercise tolerance, all of which alter the internal biological dose generated by a given external training prescription. Virtual reality, robotics, wearable sensing, and non-invasive brain stimulation may strengthen this framework when they manipulate task complexity, salience, repetition, feedback, and ecological monitoring for a defined mechanistic purpose. Current evidence supports exercise as a biologically and behaviorally meaningful adjunct in neurorehabilitation, but it cautions against uniform prescriptions and overly direct biomarker interpretations. A more precise next generation of trials should integrate exercise prescription, mechanistic readouts, technology-enabled assessment, and ecologically valid cognitive-motor outcomes within the same translational logic. Across the review, CMI is treated as the behavioral test of whether exercise-responsive biology has been recruited into adaptive function, rather than as a separate concept appended after conditioning.

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