This study aims to develop imaging-based biomarkers to assess which chronic stroke participant with lower extremity disability may respond or resist high intensity interval training (HIIT).

Previous research suggests that physical exercise training is safe and could help improve the walking speed of non-ambulatory stroke survivors. However, inter-individual variability in response to exercise is extraordinarily high regardless of adherence, and predictors of response remain elusive.

Chronic stroke survivors with lower limb disability resulting in slow walking speeds will participate in 12 weeks of cycling exercise at Emory University under the guidance of a physical exercise instructor, 3 days a week, for 25-60 minutes. During some of the exercise sessions, the investigators will collect blood lactate with a finger prick. Brain scans with an MRI before and after the 12 weeks of exercise will be done; motor function tests that include walking, sitting down, standing up, and turning around will be collected. Participants' memory and thinking will be assessed, and participants will fill out questionnaires about their health before and after their stroke, and well as questions about their diet.

The participation will last between 14-16 weeks (up to 42 study visits).

This study will enroll 55 participants with chronic subcortical stroke in the 12-week HIIT intervention. Each chronic subcortical stroke participant will be asked to participate in the overall study protocol with pre-, during-, and post-intervention measurements. The HIIT consists of three weekly 25-60 minute cycling sessions for 12 weeks at Emory University, administered by a trained exercise physiologist, for a total of 36 HIIT sessions. To accommodate stroke participants with lower limb disability, the study team will use a wheelchair accessible whole body trainer that uses a cycling motion. Each exercise session will start with a 5 minute warm up, followed by 20 minutes or more of moderate to intense cycling. Each session, the time will increase by one minute. The trained exercise physiologist may ask the participant to cruise (cycle at a comfortable pace), sprint (cycle faster), or climb (increase gear) in order to generate intervals of moderate and high intensity exercise during the session. The goal is to work the participant in a heart rate reserve (HRR) of 60-90%. The heart rate will constantly be monitored during the session. During HIIT sessions 1, 4, 7, 10, and 28 the participant's blood lactate will be measured via finger prick 7 times each session (for a total of 35 finger pricks) to assess if their lactate threshold is surpassed during HIIT. One week before the intervention and one week after, the participant will be asked to take part in an assessment of lower extremity motor function including walking speed, and a 90-minute MRI session for a brain scan. The overall goal of this study is to determine if the investigators can identify neurophysiological and imaging-derived biomarkers to predict whether a chronic subcortical stroke patient with lower extremity disability will respond to a 12-week HIIT intervention. Supported by preliminary data, the study team will build a model to consider the combined effects of blood lactate, baseline GABA, baseline CBF, baseline leg weakness, pre-stroke fitness, baseline VO2-max, age, sex, and comorbidities to predict improvements in walking speed after 12 weeks of HIIT.

Inclusion Criteria:

• chronic left or right subcortical stroke as defined by 6 months or more after a cardiovascular accident
• lower extremity motor impairment due to stroke that causes a walking speed of less than 0.6 m/s during a 10m walk,
• age 18-80 years old, and
• Screen pass of the Stress test or Physician sign-off from the participant's health care team that they are cleared for a 12 week exercise intervention

Exclusion Criteria:

• MRI contraindications, including implanted cardiac pacemakers and severe claustrophobia
• any neurodegenerative condition other than stroke that may lead to lower extremity impairment
• visual or auditory impairment that may hinder study procedures, and
• any medical condition that would preclude from participation in a physical exercise intervention program.

Raw images and interstitial processed images (including lesion masks), as well as demographic and motor testing data.

The data will become available 6 months after the last participant's data is collected

Data will be made available to investigators at research institutions, for secondary analyses, upon written request.