Treating Depression and Enhancing Locomotor Recovery Post-stroke

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Depression is the most common neuropsychiatric manifestation following stroke and current treatments are largely ineffective. Depression has both direct and indirect effects on response to rehabilitation treatment; thus subjects with post-stroke depression (PSD) are routinely excluded from rehabilitation trials and treatment options for these individuals are extremely limited. We propose to determine the impact of two known anti-depressive treatments shown to be effective in non-stroke related depression - aerobic exercise training (AET) and repetitive transcranial magnetic stimulation (rTMS) - on post-stroke depressive symptoms. Further, we will determine if depression limits gains in walking function in response to treatment and if successful reduction in depressive symptoms facilitates improved walking. This project is based on the premise that depression negatively affects the potential for the brain to adapt in response to treatment such that rehabilitation may not produce the same brain changes that it does in non-depressed individuals. We propose that effective treatment for PSD would result in a virtuous cycle where reducing depression enhances brain changes, thereby facilitating functional gains. That is, effectively treating depression will make the brain better able to recover from stroke. Furthermore, in addition to its beneficial effects on depression, AET is known to improve post-stroke walking, thus providing an attractive option for treating depression as well as an established vehicle to study the effects of PSD on response to locomotor rehabilitation. The experiments proposed as part of this project are designed to address critical questions related to the: 1) effects of AET and/or rTMS on depressive symptoms; 2) potential for PSD to limit improvements in locomotor function; 3) impact of combining AET and rTMS treatments; and 4) relationship between baseline subject attributes and response to treatment(s). Successful completion of this project will provide a foundation for larger scale therapeutic trials to establish the effectiveness of AET and/or rTMS on post-stroke depression and walking as well as identify the mechanisms that may be responsible for the changes that occur in response to treatment.