The Influence of Exercise on Neuroplasticity and Motor Learning After Stroke (EX-ML3)

Participants will complete 11 sessions. These include screening, 5 sessions where exercise or rest (according to group assignment) are paired with practice of a motor task, MRI and Transcranial Magnetic Stimulation (TMS) before and after the intervention will be used to assess neuroplasticity (ability for the brain to reorganize and create new connections).

All participants will complete baseline sessions: 1) sub-maximal exercise test to ensure safe participation in aerobic exercise (testing session [s] 1); and 2) magnetic resonance imaging (MRI) to assess brain structure and function, and 3) clinical assessments of motor function and activity. The MRI and clinical tests will be completed on s2. Between the exercise test and MRI sessions individuals will wear accelerometers for 3 days to index usual activity levels. A custom computer program will then assign participants quasi-randomly to either the rest or exercise groups stratified on age, sex, and baseline motor function. Cortical excitability will be assessed before and after either a single session of priming aerobic exercise, or rest, by group (s3). Next, priming exercise will be paired with skilled motor practice for 5 sessions (s4-8). Practice sessions will be separated by 48 hours. Importantly motor learning will be assessed via delayed, no-exercise retention tests 24-hours (s9) and 30-days (s11) after the last practice session. Activity levels (3 day accelerometry), TMS and MRI measures will be re-assessed after the second retention test (s10).

Individuals will complete 20 minutes of exercise on a recumbent bicycle before practicing a novel motor task.

Individuals will rest for 20 minutes before practicing a novel motor task. Attention will be controlled during this time.

Inclusion Criteria: Between the ages of 40 - 85 Had a stroke at least 12 months ago OR are a healthy adult who does not have a history of neurodegenerative disorders Have the ability to understand English Exclusion Criteria: Contraindication to brain stimulation (such as a history of seizure or epilepsy) Contraindication to MRI (such as a pacemaker, metal in the eyes / brain or fear of enclosed spaces) Neurodegenerative disorder ( such as Parkinson disease, Alzheimers disease or Multiple Sclerosis) Contraindications to exercise

Clark B, Whitall J, Kwakkel G, Mehrholz J, Ewings S, Burridge J. The effect of time spent in rehabilitation on activity limitation and impairment after stroke. Cochrane Database Syst Rev. 2021 Oct 25;10(10):CD012612. doi: 10.1002/14651858.CD012612.pub2.