Evaluating the Neural Underpinnings of Motivation for Walking Exercise.

OBJECTIVE: Motivation is critically important for rehabilitation, exercise, and motor performance, but its neural basis is poorly understood. Recent correlational research suggests that the dorsomedial prefrontal cortex (dmPFC) may be involved in motivation for walking activity and/or descending motor output. This study experimentally evaluated brain activity changes in periods of additional motivation during walking exercise and tested how these brain activity changes relate to self-reported exercise motivation and walking speed. METHODS: Adults without disability (N = 26; 65% women; 25 [standard deviation = 5] years old) performed a vigorous exercise experiment involving 20 trials of maximal speed overground walking. Half of the trials were randomized to include "extra-motivation" stimuli (lap timer, tracked best lap time, and verbal encouragement). Wearable near-infrared spectroscopy measured oxygenated hemoglobin responses from frontal lobe regions, including the dmPFC, primary sensorimotor, dorsolateral prefrontal, anterior prefrontal, supplementary motor, and dorsal premotor cortices. RESULTS: Compared with standard trials, participants walked faster during extra-motivation trials (2.43 vs 2.67 m/s; P < .0001) and had higher oxygenated hemoglobin responses in all tested brain regions, including dmPFC (+842 vs +1694 µM; P < .0001). Greater dmPFC activity was correlated with more self-determined motivation for exercise between individuals (r = 0.55; P = .004) and faster walking speed between trials (r = 0.18; P = .0002). dmPFC was the only tested brain region that showed both of these associations. CONCLUSION: Simple motivational stimuli during walking exercise seem to upregulate widespread brain regions. Results suggest that dmPFC may be a key brain region linking affective signaling to motor output. IMPACT: These findings provide a potential biologic basis for the benefits of motivational stimuli, elicited with clinically feasible methods during walking exercise. Future clinical studies could build on this information to develop prognostic biomarkers and test novel brain stimulation targets for enhancing exercise motivation (eg, dmPFC).

Optimal Intensity and Duration of Walking Rehabilitation in Patients With Chronic Stroke: A Randomized Clinical Trial.

Importance: For walking rehabilitation after stroke, training intensity and duration are critical dosing parameters that lack optimization. Objective: To assess the optimal training intensity (vigorous vs moderate) and minimum training duration (4, 8, or 12 weeks) needed to maximize immediate improvement in walking capacity in patients with chronic stroke. Design, Setting, and Participants: This multicenter randomized clinical trial using an intent-to-treat analysis was conducted from January 2019 to April 2022 at rehabilitation and exercise research laboratories. Survivors of a single stroke who were aged 40 to 80 years and had persistent walking limitations 6 months or more after the stroke were enrolled. Interventions: Participants were randomized 1:1 to high-intensity interval training (HIIT) or moderate-intensity aerobic training (MAT), each involving 45 minutes of walking practice 3 times per week for 12 weeks. The HIIT protocol used repeated 30-second bursts of walking at maximum safe speed, alternated with 30- to 60-second rest periods, targeting a mean aerobic intensity above 60% of the heart rate reserve (HRR). The MAT protocol used continuous walking with speed adjusted to maintain an initial target of 40% of the HRR, progressing up to 60% of the HRR as tolerated. Main Outcomes and Measures: The main outcome was 6-minute walk test distance. Outcomes were assessed by blinded raters after 4, 8, and 12 weeks of training. Results: Of 55 participants (mean [SD] age, 63 [10] years; 36 male [65.5%]), 27 were randomized to HIIT and 28 to MAT. The mean (SD) time since stroke was 2.5 (1.3) years, and mean (SD) 6-minute walk test distance at baseline was 239 (132) m. Participants attended 1675 of 1980 planned treatment visits (84.6%) and 197 of 220 planned testing visits (89.5%). No serious adverse events related to study procedures occurred. Groups had similar 6-minute walk test distance changes after 4 weeks (HIIT, 27 m [95% CI, 6-48 m]; MAT, 12 m [95% CI, -9 to 33 m]; mean difference, 15 m [95% CI, -13 to 42 m]; P = .28), but HIIT elicited greater gains after 8 weeks (58 m [95% CI, 39-76 m] vs 29 m [95% CI, 9-48 m]; mean difference, 29 m [95% CI, 5-54 m]; P = .02) and 12 weeks (71 m [95% CI, 49-94 m] vs 27 m [95% CI, 3-50 m]; mean difference, 44 m [95% CI, 14-74 m]; P = .005) of training; HIIT also showed greater improvements than MAT on some secondary measures of gait speed and fatigue. Conclusions and Relevance: These findings show proof of concept that vigorous training intensity is a critical dosing parameter for walking rehabilitation. In patients with chronic stroke, vigorous walking exercise produced significant and meaningful gains in walking capacity with only 4 weeks of training, but at least 12 weeks were needed to maximize immediate gains. Trial Registration: ClinicalTrials.gov Identifier: NCT03760016.