Effects of Exercise on Structural and Functional Brain Patterns in Schizophrenia-Data From a Multicenter Randomized-Controlled Study

Abstract

Background and hypothesis: Aerobic exercise interventions in people with schizophrenia have been demonstrated to improve clinical outcomes, but findings regarding the underlying neural mechanisms are limited and mainly focus on the hippocampal formation. Therefore, we conducted a global exploratory analysis of structural and functional neural adaptations after exercise and explored their clinical implications.

Study design: In this randomized controlled trial, structural and functional MRI data were available for 91 patients with schizophrenia who performed either aerobic exercise on a bicycle ergometer or underwent a flexibility, strengthening, and balance training as control group. We analyzed clinical and neuroimaging data before and after 6 months of regular exercise. Bayesian linear mixed models and Bayesian logistic regressions were calculated to evaluate effects of exercise on multiple neural outcomes and their potential clinical relevance.

Study results: Our results indicated that aerobic exercise in people with schizophrenia led to structural and functional adaptations mainly within the default-mode network, the cortico-striato-pallido-thalamo-cortical loop, and the cerebello-thalamo-cortical pathway. We further observed that volume increases in the right posterior cingulate gyrus as a central node of the default-mode network were linked to improvements in disorder severity.

Conclusions: These exploratory findings suggest a positive impact of aerobic exercise on 3 cerebral networks that are involved in the pathophysiology of schizophrenia.

Clinical trials registration: The underlying study of this manuscript was registered in the International Clinical Trials Database, ClinicalTrials.gov (NCT number: NCT03466112, https://clinicaltrials.gov/ct2/show/NCT03466112?term=NCT03466112&draw=2&rank=1) and in the German Clinical Trials Register (DRKS-ID: DRKS00009804).

Keywords: brain structure; exercise; functional connectivity; randomized-controlled trial; schizophrenia.

Fig. 1.

Analysis approach. The analysis workflows for the structural and functional MRI data are illustrated. MP-Rage, magnetization prepared rapid gradient echo; EPI, echo planar imaging; fMRIPrep, functional magnetic resonance imaging preprocessing pipeline; Nilearn, Python library to process, analyze and visualize multimodal MRI data, AAL, Automated Anatomical Labeling; FC, functional connectivity.

Fig. 2.

Exercise effects on brain structure. The marginal mean difference of (A) brain volumes (corrected by the intracranial volume), (B) cortical thickness, and (C) cortical gyrification between the baseline session (t0) and the session after 6 months of exercise (t6) extracted from the linear mixed model analysis is depicted on the x-axis. The Bayes factor (BF₁₀) of the interaction term in the linear mixed model analysis is displayed on the y-axis. Effects within the aerobic endurance training (AET) group are illustrated on the left, while effects within the flexibility, strengthening, and balance training (FSBT) group are shown on the right. Regions are labeled if BF₁₀ > 2 and if the MCAR assumption is not violated. Full regions' names with their particular abbreviations are provided in Supplementary Table S6.

Fig. 3.

Exercise effects on functional connectivity in schizophrenia-related brain circuits. Boxplots of functional connectivity distributions per session. The regression line illustrates the average change in functional connectivity between the baseline session (t0) and the session after six months of exercise (t6). The aerobic exercise group is illustrated on the left, the control group is displayed on the right. ACC, anterior cingulate cortex; AET, aerobic endurance training; AMY, amygdala; CEREB, cerebellum; DMN, default-mode network; FPN, fronto-parietal network; FSBT, flexibility, strengthening, and balance training; HF, hippocampal formation; MFG, middle frontal gyrus; OCC, occipital lobe; PA, pallidum; SAL, salience network; SENS, sensorimotor cortices; STRIA, striatum; TH, thalamus.