Project Summary
Traditional rehabilitation approaches following stroke involve 1:1 motor learning-based training to facilitate
recovery of upper extremity (UE) and lower extremity (LE) function. These time- and personnel-intensive
approaches are costly, yet leave ~75% of stroke survivors with residual disability. More effective alternative
approaches to facilitate motor recovery following stroke have not been adopted clinically due to excessive time
and cost. To advance clinical care, both effectiveness and cost of a candidate intervention must be considered
simultaneously. Aerobic exercise (AE) is known to improve cardiovascular function following stroke and central
nervous system (CNS) function in older adults and neurological populations. Strong theoretical arguments
suggest that AE may facilitate motor recovery following stroke. A protocol that rigorously tests this theory in the
subacute stroke population is warranted. Animal studies, coupled with our preliminary data, indicate a specific
type of exercise – forced aerobic exercise (FE), where volitional movements are mechanically supplemented –
improves motor recovery following stroke. The mechanical assistance provided by FE enables patients to
achieve a more rapid and consistent exercise pattern beyond their volitional capabilities while maintaining their
aerobic effort within a beneficial range. In our initial studies, persons completing FE cycling followed by a
reduced dose of UE motor task practice exhibited greater recovery of UE motor function compared to those
completing unassisted AE and motor task practice or extended sessions of motor task practice alone. Animal
studies have shown that FE triggers the release of brain-derived neurotrophic factor (BDNF) and insulin-like
growth factor-1 (IGF-1), thought to be critical building blocks for neuroplasticity. Project Hypothesis: FE
facilitates high-intensity AE, which triggers growth factors essential for neuroplasticity, thereby `priming' the
CNS to facilitate motor recovery associated with motor retraining therapies. We propose a prospective,
pragmatic clinical trial to determine effects of FE in facilitating UE and LE motor recovery post-stroke in an
outpatient rehabilitation setting, to elucidate neural and biochemical substrates of FE-induced motor recovery,
and to evaluate cost effectiveness of a FE-centered intervention compared to traditional stroke rehabilitation.
Aim 1: Determine effects of FE+rehab vs. time-matched rehab on the recovery of UE motor function.
Aim 2: Determine effects of FE+rehab vs. time-matched rehab on recovery of lower extremity motor function.
Aim 3: Determine effects of FE+rehab vs. rehab on electrophysiological and biochemical markers of
neuroplasticity.
Aim 4: Evaluate cost-effectiveness of FE+rehab vs. rehab. The global effect of FE has the potential to enhance
recovery in a growing population of stroke survivors in a cost-effective manner, thus accelerating its clinical
acceptance. Our mechanistic aim will elucidate the effects of each approach on substrates underlying
neuroplasticity.