Stroke, Chronic, Aging, Cognitive Decline, Motor Dysfunction, Neuroplasticity
Conditions
Keywords
Transcranial Magnetic Stimulation (TMS), Cortical Inhibition, Neuroplasticity, Aerobic Exercise, Motor Learning, Aging, Stroke Rehabilitation, Cortical Excitability, GABAergic Inhibition
Brief summary
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 at an intensity that elevates lactate levels, one performing 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 (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.
Detailed description
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) moderate intensity aerobic exercise, (3) low-intensity aerobic exercise, or (4) education-only control. 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 three 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.
Interventions
BEHAVIORALHigh intensity cycling
Participants cycle on a stationary ergometer at an intensity prescribed to reach their lactate threshold, guided by VO2 max results and lactate sampling. The session lasts approximately 20 minutes and is preceded and followed by TMS assessments and a structured motor learning task. This condition is designed to evaluate the effect of exercise-induced metabolic stress on cortical inhibition and motor learning.
BEHAVIORALLow-intensity cycling
Participants perform 20 minutes of cycling at a light workload below their lactate threshold. Exercise intensity is individualized using heart rate and perceived exertion (Borg RPE scale), avoiding significant metabolic activation. TMS and motor learning are assessed pre- and post-exercise. This condition serves as an active comparator to assess the impact of exercise intensity.
BEHAVIORALHealth education session
Participants receive a 20-minute session of health education content (e.g., wellness, healthy aging). No exercise is performed. Participants undergo TMS and motor learning testing before and after the session. This condition is used to control for attention and cognitive engagement without physical activity.
BEHAVIORALModerate Intensity Aerobic Exercise
Participants cycle on a stationary ergometer at an intensity prescribed to surround, but not exceed their lactate threshold, guided by VO2 max results and lactate sampling. The session lasts approximately 20 minutes and is preceded and followed by TMS assessments and a structured motor learning task. This condition is designed to evaluate the effect of moderate exercise-induced metabolic stress on cortical inhibition and motor learning.
Sponsors
University of Alabama at Birmingham
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
Participants are randomized into one of four parallel groups: (1) aerobic exercise at lactate threshold, (2) moderate intensity exercise, (3) low-intensity aerobic exercise, or (4) education-only control. Outcomes are assessed at multiple time points to examine changes in cortical inhibition, motor performance, and cognitive function.
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
Yes
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 (40-85): * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Motor Learning Performance (12-Digit Serial Reaction Time Task) | Baseline, Day 2, Day 3, Day 4, and Day 5 | Motor learning is assessed using the 12-digit Serial Reaction Time Task (SRTT), a computer-based measure of implicit motor sequence learning. Participants respond to visual cues by pressing buttons in a fixed or random sequence. Learning is quantified by changes in reaction time and accuracy across structured and unstructured trials. A learning index is derived by comparing performance between patterned (learning) and random sequences. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Long-Interval Intracortical Inhibition (LICI) | Baseline, Day 5 | LICI is measured using a 100 ms interstimulus interval to assess GABA\<sub\>B\</sub\>-mediated inhibition. Recorded before and after each intervention session. |
| Change in Intracortical Facilitation (ICF) | Baseline, Day 5 | ICF is assessed using paired-pulse TMS with a 10-15 ms interstimulus interval to evaluate cortical excitability. |
| Change in Blood Lactate Concentration | Day 2, Day 3, Day 4 | Measured via fingerstick blood samples pre-, mid-, and post-exercise. |
| Change in Executive Function (D-KEFS Verbal Fluency and Stroop Tests) | Day 1 and Day 5 | Executive function neuropsychological tests. |
Countries
United States
Contacts
CONTACTKeith M McGregor, PhD
CONTACTAyat Najmi, BS
PRINCIPAL_INVESTIGATORKeith McGregor, PhD
Keith McGregor
Outcome results
None listed