Stroke is one of the top three causes of human disability. In middle- and high-income countries around the world, stroke is the leading neurological cause of lost disability-adjusted life years. Motor deficits are among the most common results of stroke and contribute substantially to post-stroke disability. An estimated 6,600,000 American adults have had a symptomatic stroke, with a prevalence that increases with age. Each year, 795,000 people experience a stroke, of which 610,000 are first-ever symptomatic strokes. The mean survival after stroke is 6-7 years, with approximately 85% of patients living past the first year of stroke. With the decline in stroke mortality accompanying advances in acute stroke care and aging of the population, the disease burden is projected to increase. Thus, most patients survive their stroke and live with enduring disability for years to come.

Between 55% and 75% of patients have enduring motor deficits after stroke, which are associated with reduced quality of life, and 65% of patients at 6 months are unable to incorporate the affected hand effectively into daily activities. Subjective well-being is decreased one year after stroke, and some research attributes this decrease directly to arm motor impairments. In the long term after a stroke, at least half of patients have to rely on human assistance for basic activities of daily living (ADLs) such as feeding, self-care, and mobility. Upper extremity function is a key part of this disability after stroke. Needs assessments from patients include expectations of recovery, occupation-specific needs that may require strength vs fine motor skills, and activities of daily living, all of which will reduce overall disability measures. Upper extremity function (as measured by the Wolf Motor Function Test \[WMFT\]) has been shown as a predictor of quality-of-life scores.

Current therapies for a new stroke reduce disability in only a subset of patients. The only drug approved to treat acute ischemic stroke remains tissue plasminogen activator (tPA). Only a minor fraction of patients receive this medicine in large part due to the narrow time window for safe drug administration. The fraction of patients who receive endovascular therapy is even smaller. Moreover, of those so treated, half or more have significant long-term disability.

Physical therapy remains the mainstay of treatment, and advances in remote teletherapy and other home or gaming options may further increase its utilization. Non-invasive exoskeleton use has also been approved for upper extremity therapy. These existing approaches to rehabilitation have been used for decades and are widely recognized to provide important benefits. Nevertheless, the efficacy of these rehabilitation approaches is equally widely recognized to be limited such that some patients do not respond to rehabilitation, and some only show partial recovery. These important limitations in the efficacy of existing rehabilitation approaches are likely due to the very nature of physical rehabilitation: they engage peripheral nerves and muscles and likely only have indirect effects on damaged physiology in the brain. It is equally expected that direct and targeted manipulation of brain physiology has the potential to rehabilitate people with chronic stroke more effectively. Thus, there has been a growing interest in using electric or magnetic stimulation of the cortex or cortical pathways to promote brain recovery and to enhance structural and functional brain plasticity.

The study proposes to investigate the effectiveness of promoting interactions between affected and intact cortical regions by inducing neural plasticity through specific protocols. By inducing plasticity through the use of closed-loop stimulation delivered simultaneously with conventional activity-based therapy, the study results are expected to enhance recovery beyond what is achievable with therapy alone.