Adapted physical activity enhances cortical surface area and modulates functional connectivity of default-mode and frontoparietal networks in schizophrenia

Adapted physical activity (APA) may benefit patients with schizophrenia (SZPs), but neurobiological effects remain underexplored. We investigated whether a 16-week web-based APA program (e-APA) induces brain plasticity in SZPs and whether brain changes relate to cardiorespiratory fitness and clinical symptoms.

In secondary analyses of a randomized controlled trial, 31 SZPs were assigned to e-APA (n = 16) or e-health education (e-HE, n = 15), matched to 23 healthy controls (HCs). Structural and resting-state functional MRI were acquired pre- and post-intervention to assess cortical surface area, thickness, and functional connectivity (FC). Relationships with VO₂max and symptom changes were examined.

Compared to SZPs-HE, SZPs-APA showed greater surface area changes in the left superior frontal, right precentral and right cuneus cortices. Separately, within SZPs-APA, VO₂max improvement was associated with changes in the left precentral and inferior temporal cortices and right insula, while reductions in apathy and positive symptoms were associated with changes in the right fusiform, rostral middle frontal, inferior temporal cortices and left supramarginal cortex. Greater FC changes within the frontoparietal network (FPN) were observed in e-APA versus e-HE, and within the default-mode network in SZPs-APA versus SZPs-HE, at the uncorrected level (neither survived multiple-comparison correction). FPN changes were associated with VO₂max gains. No significant structural and functional differences occurred between SZPs-APA and HCs-APA.

e-APA induced cortical plasticity in motor, visual, and associative regions in SZPs. Brain changes were associated with improvements in cardiorespiratory fitness and clinical symptoms, while uncorrected FC findings require cautious interpretation. e-APA may represent a promising adjunct to the treatment of schizophrenia.