Exercise-primed Upper Extremity Motor Practice in Chronic Stroke

With a surviving cohort of nearly 7 million individuals, stroke is the leading cause of long-term disability in the United States. Of the ~795,000 new strokes occurring annually, approximately 2/3rds of survivors will have some degree of long term disability. The prevalence of post-stroke disability coupled with the fact that more people are surviving stroke reflects an increasing need to develop effective rehabilitation strategies aimed at reducing disability and improving quality of life for the millions of stroke survivors, their families and caregivers.

The overwhelming majority of stroke survivors, >75%, exhibit upper extremity (UE) hemiparesis, and only 15% will recover fully. Furthermore, residual UE impairment is closely linked to long-term disability and reduced quality of life. Current meta-analytic evidence supports virtual reality stroke rehabilitation interventions for improving UE function suggesting that this is a promising area for further therapeutic development.

Duck Duck Punch (DDP) is an interactive computer game deliberately designed to enhance UE movement quality via individualized progressive movement practice along with an array of performance metrics allowing for within-session feedback on movement performance. Although response to UE virtual reality rehabilitation interventions, such as DDP, involves a multitude of factors, neuroplastic changes are a primary mechanism underlying functional recovery. Thus, pairing DDP with a priming intervention to facilitate a 'neuroplastic-friendly' environment may make the CNS more amenable, and enhance response to DDP rehabilitation and ultimately improve outcomes.

Aerobic exercise (AEx) training has positive benefits on overall brain function including enhanced global cognition, executive function, and processing speed and attention in healthy, older adults. Additionally, a single session of AEx acutely improves motor memory and learning in younger, healthy adults. Although AEx has been used to improve cardiovascular function following stroke, its neurofacilitatory effects in stroke have yet to be tested empirically. Candidate mechanisms through which AEx enhances brain function and motor learning include changes in circulating brain-derived neurotrophic factor (BDNF) and corticomotor excitability. BDNF is believed to play an integral role in several neuroplastic processes and promotes the strengthening of synaptic connections, i.e. long-term potentiation (LTP) and current research indicates that AEx can acutely and chronically increase circulating BDNF. Corticomotor excitability (CME) is often used as an indicator of LTP-like neuroplasticity and may underlie improvements in motor memory and learning. Similarly to BDNF, AEx can acutely enhance corticomotor excitability in control and chronic stroke subjects. Facilitating central nervous system function provides rationale to determine the role of AEx in 'prime' the brain for a subsequent intervention to maximize neuroplastic potential.

Movement-based priming for neurorehabilitation involves performing movement or exercise before, or concurrent to, a therapeutic intervention with the goal of improving the efficacy of the therapeutic intervention. Emerging evidence supports AEx as a potential priming tool for UE stroke rehabilitation. AEx combined with UE task training can improve UE function and self-reported health status in chronic stroke survivors. Despite the promising results, there are gaps in the literature involving: 1) the clinical applicability of an AEx priming session; and 2) mechanisms contributing to changes in UE functions in response to AEx-primed UE rehabilitation. Addressing these gaps will be necessary to develop an AEx primer that is potent and time efficient, with respect to current clinical models. Therefore, the purpose of this pilot proposal will be to establish initial feasibility and tolerability benchmarks via the following aims:

1. Demonstrate the feasibility of pairing AEx + DDP in stroke survivors with UE hemiparesis
2. Quantify the magnitude of the effect of the AEx + DDP intervention on UE impairment and function
3. Examine the relationship of biomarkers of neuroplasticity (BDNF and corticomotor excitability) and response to AEx + DDP

To accomplish these aims, chronic stroke survivors with moderate UE hemiparesis will undergo 18 sessions of AEx + DDP training. Each week, for six weeks, subjects will undergo three sessions of AEx + DDP. During each session subjects will complete 15 minutes of aerobic exercise followed by 200 repetitions of DDP. Assessment of UE function and biomarkers of neuroplasticity will be assessed before and after the AEx + DDP intervention.