Exercise and Brain Stimulation for Post-stroke Depression

This project will assess the effects of aerobic exercise training (AET), repetitive transcranial magnetic stimulation (rTMS) or their combination on depressive severity as well as locomotor function in persons with post-stroke depression (PSD). Both AET and rTMS are established stand-alone treatments for non-stroke related depression, though neither has been adequately studied post-stroke. Furthermore, substantive research indicates that AET improves post-stroke locomotor function, thus offering a novel approach for treating PSD as well as an established vehicle to study the effects of PSD on response to rehabilitation.

The purpose of this project is to determine the impact of AET, rTMS and their combination (AET+rTMS) treatments on post-stroke depressive symptoms and locomotor function so as to guide the development of a future clinical trial. A total of 40 depressed post-stroke subjects will be randomly assigned to one of four groups 1) AET; 2) rTMS; 3) combined AET and rTMS (AET+rTMS) or 4) control (sham rTMS) group (n=10 per condition; equally distributed with mild and moderate MDD). Further, an additional 10 non-depressed post-stroke subjects will complete 8 weeks of AET so as to allow us to determine the effects of PSD on response to training (Aim 2). Training (AET, rTMS and AET+rTMS) will take place over an 8-week period, three times per week on non-consecutive days. Measures of depression (HRSD17) as well as self-selected walking speed (SSWS) will be performed prior to the initial treatment session of each week as well as 8 weeks following cessation of treatment. Additional measures of locomotor function (walking endurance and amount of daily community stepping) will be assessed prior to training (pre), following 4 weeks of training (mid), upon completion of 8 weeks of training (post) as well as 8 weeks following cessation of training (follow-up), allowing determination of the efficacy (and persistence) of training on these outcomes.


Eligibility Criteria:
Inclusion Criteria:

* 1) age 50-70
* 2) stroke within the past 6 to 60 months,
* 3) major depressive disorder (PHQ-9 \> 10) and diagnosed using the Structured Clinical Interview for Depression (SCID) according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV),
* 4) residual paresis in the lower extremity (Fugl-Meyer LE motor score \<34),
* 5) ability to walk without assistance and without an AFO on the treadmill ≥ 30 seconds at speeds ranging from 0.2-0.8 m/s,
* 6) no antidepressant medications or clinically able to discontinue medications,
* 7) HRSD question #9 regarding suicide \<2,
* 8) provision of informed consent. In addition, all subjects who meet criteria for the training portion must complete an exercise tolerance test and be cleared for participation by the study cardiologist.

Exclusion Criteria:

1. Unable to ambulate at least 150 feet prior to stroke, or experienced intermittent claudication while walking;
2. history of congestive heart failure, unstable cardiac arrhythmias, hypertrophic cardiomyopathy, severe aortic stenosis, angina or dyspnea at rest or during ADL's;
3. History of oxygen dependence;
4. Preexisting neurological disorders, dementia or previous stroke;
5. History of major head trauma;
6. Legal blindness or severe visual impairment;
7. history of psychosis or other Axis I disorder that is primary;
8. Life expectancy \<1 yr.;
9. Severe arthritis or other problems that limit passive range of motion;
10. History of DVT or pulmonary embolism within 6 months;
11. Uncontrolled diabetes with recent weight loss, diabetic coma, or frequent insulin reactions;
12. Severe hypertension with systolic \>200 mmHg and diastolic \>110 mmHg at rest;
13. attempt of suicide in the last 2 years or at suicidal risk assessed by SCID interview;
14. Previous or current enrollment in a clinical trial to enhance motor recovery; 15) currently exercising ≥ 2 times per week (≥20 minutes);

16) Presence of non-MR compatible implants, pregnancy or severe claustrophobia.