Aerobic Exercise Alters Brain Function and Structure in Parkinson's Disease: A Randomized Controlled Trial

Abstract

Objective: Randomized clinical trials have shown that aerobic exercise attenuates motor symptom progression in Parkinson's disease, but the underlying neural mechanisms are unclear. Here, we investigated how aerobic exercise influences disease-related functional and structural changes in the corticostriatal sensorimotor network, which is involved in the emergence of motor deficits in Parkinson's disease. Additionally, we explored effects of aerobic exercise on tissue integrity of the substantia nigra, and on behavioral and cerebral indices of cognitive control.

Methods: The Park-in-Shape trial is a single-center, double-blind randomized controlled trial in 130 Parkinson's disease patients who were randomly assigned (1:1 ratio) to aerobic exercise (stationary home trainer) or stretching (active control) interventions (duration = 6 months). An unselected subset from this trial (exercise, n = 25; stretching, n = 31) underwent resting-state functional and structural magnetic resonance imaging (MRI), and an oculomotor cognitive control task (pro- and antisaccades), at baseline and at 6-month follow-up.

Results: Aerobic exercise, but not stretching, led to increased functional connectivity of the anterior putamen with the sensorimotor cortex relative to the posterior putamen. Behaviorally, aerobic exercise also improved cognitive control. Furthermore, aerobic exercise increased functional connectivity in the right frontoparietal network, proportionally to fitness improvements, and it reduced global brain atrophy.

Interpretation: MRI, clinical, and behavioral results converge toward the conclusion that aerobic exercise stabilizes disease progression in the corticostriatal sensorimotor network and enhances cognitive performance. ANN NEUROL 2022;91:203-216.

FIGURE 1

Trial profile flowchart diagram. DWI = diffusion‐weighted imaging; fMRI = functional MRI; MRI = magnetic resonance imaging.

FIGURE 2

Methods. (A) Bilateral seed regions in posterior (yellow) and anterior (cyan) putamen and the sensorimotor network (red). (B) Average b0 image (right) and heat map (left) showing overlap between masks in posterior substantia nigra. (C) Conditions of the oculomotor cognitive control task. (D) Cognitive control networks (blue; left and right frontoparietal and executive control networks). (E) Longitudinal design.

FIGURE 3

Motor‐related effects of aerobic exercise. (A) Group differences in the balance of corticostriatal sensorimotor connectivity. (B) Group differences in connectivity between posterior putamen and sensorimotor cortex. (C) Change in connectivity between subregions of the putamen and Brodmann area (BA) 3b. Lower and upper whiskers of bar graphs correspond to the first and third quantiles, and extend from the hinge to the largest or smallest value no further than 1.5 × interquartile range (outlying data points beyond this range are plotted individually). Imaging results are displayed at p < 0.05, familywise error (fwe)‐corrected, overlaid on a study‐specific anatomical Montreal Neurological Institute template. *p < 0.05. AP = anterior putamen; PP = posterior putamen; T1 = baseline; T2 = follow‐up; Δ = follow‐up – baseline.

FIGURE 4

Effect of aerobic exercise on global brain atrophy and substantia nigra free water. (A) Group difference in percentage‐based global brain volume. (B) Group difference in posterior substantia nigra free water. (C) Heat map (upper) of substantia nigra masks overlaid on an average b0 image. Yellow indicates high overlap between masks, red indicates partial overlap. Average free water image (lower) shows hyperintense values in the posterior substantia nigra. Lower and upper whiskers of bar graphs correspond to the first and third quantiles and extend from the hinge to the largest or smallest value no further than 1.5 × interquartile range (outlying data points beyond this range are plotted individually). *p < 0.05, ***p < 0.001. fv = fractional volume; Δ = follow‐up – baseline.

FIGURE 5

Cognitive control‐related effects of aerobic exercise. (A) Group difference in antisaccade error rate and prosaccade amplitude. (B) Group differences in right frontoparietal network connectivity. (C) Correlation between change in fitness and right frontoparietal network connectivity. Lower and upper whiskers of bar graphs correspond to the first and third quantiles and extend from the hinge to the largest or smallest value no further than 1.5 × interquartile range (outlying data points beyond this range are plotted individually). Imaging results are displayed at p < 0.05, familywise error (fwe)‐corrected, overlaid on a study‐specific anatomical Montreal Neurological Institute template. +p = 0.055, *p < 0.05. BA = Brodmann area; DLPFC = dorsolateral prefrontal cortex; RFPN = right frontoparietal network; rho = Spearman correlation coefficient; T1 = baseline; T2 = follow‐up; VO2max = maximal oxygen consumption.