AMPLIFI: Adaptive Modulation of Plasticity Through Lactate and Fitness Interventions

The AMPLIFI study (Adaptive Modulation of Plasticity through Lactate and Fitness Interventions) investigates how short-term aerobic exercise influences brain plasticity and learning in older adults and stroke survivors. The study compares three groups: one performing aerobic cycling exercise at an intensity that increases lactate levels, one doing low-intensity exercise, and one receiving health education without exercise.

All participants will complete motor learning tasks and undergo brain stimulation testing (using transcranial magnetic stimulation, or TMS) to assess how well the brain responds to training. The goal is to understand whether different types of exercise can improve brain function, movement, and memory, and how the body's response to exercise (like lactate levels) might support brain health.

This research may help identify low-cost, non-invasive interventions-such as targeted exercise-that improve motor and cognitive outcomes in aging and stroke recovery.

The AMPLIFI study is a mechanistic clinical trial designed to investigate the neurophysiological effects of acute aerobic exercise on cortical plasticity and motor learning in older adults and individuals with chronic stroke. Participants are randomized into one of three groups: (1) moderate-to-high intensity aerobic exercise at lactate threshold, (2) low-intensity aerobic exercise, or (3) education-only control. A crossover component allows each participant to undergo both exercise and motor learning-only conditions on separate days, with condition order randomized.

The primary outcome measure is cortical inhibition, assessed using transcranial magnetic stimulation (TMS) measures including short-interval intracortical inhibition (SICI), long-interval intracortical inhibition (LICI), and intracortical facilitation (ICF). Secondary outcomes include performance on upper extremity motor tasks, measures of verbal and executive function, and blood lactate levels.

Participants complete five sessions over 2-3 weeks, including baseline assessments, VO2 max testing, multiple blood draws, and cognitive and motor testing. The exercise intervention is delivered via stationary cycling at intensities tailored using individual VO2 max data and lactate monitoring. Genetic and biochemical assays will be performed on blood samples to explore associations between metabolic and neural response.

This study will clarify how lactate-related exercise intensity impacts cortical inhibition and whether those effects support improvements in motor learning. Findings may help define the mechanisms by which exercise promotes neuroplasticity and support individualized rehabilitation strategies for aging and post-stroke populations.

Eligibility Criteria:
Inclusion Criteria:

For All Participants:

* Able to provide informed consent
* Right-handed (for TMS consistency)
* English-speaking
* Clearance for moderate-intensity aerobic exercise
* Able to safely sit and pedal a stationary cycle ergometer
* No contraindications to TMS (e.g., no metal in skull, pacemakers, or seizure history)

Younger Adults (18-35):

* No history of neurological or psychiatric conditions
* Not currently on medications that affect the central nervous system

Older Adults (60-85):

* No diagnosis of dementia
* Independent in activities of daily living
* No stroke history

Stroke Survivors (18-85):

* At least 6 months post-stroke (chronic phase)
* Medically stable and cleared for aerobic exercise
* Able to engage in motor learning task (with or without hemiparetic adaptations)

Exclusion Criteria:

* History of epilepsy or seizures
* Current substance abuse or uncontrolled psychiatric disorder
* Severe cardiovascular disease or unstable medical condition
* Pregnancy
* Contraindications to TMS or exercise testing (e.g., implanted neurostimulators, severe hypertension)
* Participation in another interventional trial within the past 30 days