Abstract
Stroke is a global cause of death and neurological disability. Survivors of stroke experience impaired quality of life because of post-stroke motor disorders, which are the primary driver of stroke-associated healthcare expenditures. Neuromodulatory techniques offer a promising avenue for addressing these post-stroke motor disorders. Post-stroke motor disorders are thought to be related to ongoing maladaptive responses and abnormal brain network reorganization; this offers insights into the inadequacy of most current treatments. In the present review, we summarize the following models involved in post-stroke motor disorders: the dual-pathway model of the basal ganglia, the cerebrocerebellar model, and the interhemispheric inhibition model. By identifying these critical elements, it will be clinically possible to explore mechanism-based therapeutics. On the basis of this physiological understanding, we review progress in the clinical application of the main therapeutic modalities; namely, invasive deep brain stimulation (DBS) and noninvasive transcranial magnetic stimulation (TMS), both of which are currently under investigation for neuromodulation in stroke. Both DBS and TMS are approved by the Food and Drug Administration because of their safety and efficacy. Although little is known about their underlying molecular mechanisms, recent studies have indicated that DBS and TMS promote post-stroke neurogenesis and neuroplasticity, suggesting potential pathways for restoring post-stroke motor disorders. Moreover, we focus specifically on the interactions between TMS and DBS, and discuss the ways in which combined DBS and TMS—for the future personalization of treatment strategies—will further ameliorate post-stroke motor disorders. For example, TMS can be used safely in movement disorder patients with DBS, and pairing DBS with TMS at specific intervals and patterns produces long-term potentiation-like effects related to cortical plasticity. A further characterization of the precise repair mechanisms, together with technological innovations, is likely to substantially improve the efficacy of treatments for post-stroke motor disorders.