Abstract

Abstract Background: There is a critical need to understand neurotheraputic mechanisms in the brain to develop more effective interventions to improve cognitive abilities in schizophrenia. Both aerobic exercise and cognitive training separately have been found to improve brain plasticity and improve cognitive functioning in schizophrenia to a moderate degree. However, animal models have shown that the addition of cognitive training to an exercise program can augment the neuromodulatory effects of exercise. This study is the first to report on the effects of a combined exercise and cognitive training intervention on brain plasticity measures in first-episode schizophrenia patients. Methods: Whole-brain structural MRI scans (MPRAGE) were collected on a 3T MRI scanner at UCLA to extrapolate cortical thickness measures at baseline and at 6-month follow-up in 37 first-episode schizophrenia patients undergoing a pilot RCT of cognitive training and exercise. Patients were randomly assigned to either a combined cognitive training and exercise (CT&E, N = 20) or cognitive training without exercise (CT, N = 17) program for 6 months. We used brain plasticity-based computer programs from Posit Science (BrainHQ and SocialVille) for cognitive training. To examine the hypothesized role of neuroplasticity-inducing physical exercise the CT&E group also participated in an aerobic conditioning exercises for 150 minutes per week, including 45 minutes at UCLA 2 days a week and 30 minutes at home 2 days a week. Both treatment groups participated in these cognitive training sessions at UCLA 2 days a week, 2 hours a day. The MCCB cognitive battery was also administered at baseline and 6 month follow-up. Results: Significant Group Ă— Time interactions for cortical thickness were found only in prefrontal regions and only as increases in the C&TE but not in the CT group. Focal increases were found in the left rostral middle frontal (DLPFC) (F = 5.71, P = .02), right superior frontal (F = 6.35, P = .02) and right medial orbitofrontal (OFC) (F = 4.01, P = .05) cortices. Conclusion: These structural brain findings highlight the role of exercise to bolster increases in volume which can lead to more efficient functional organization in the prefrontal cortex and drive improvements in executive functioning. This research has the potential to elucidate the neurobiological mechanisms driving cognitive improvement in this combined intervention and help to guide treatment development in the early phase of schizophrenia.

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