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Aerobic exercise improves executive function after traumatic brain injury via changes to the functional connectivity of the anterior cingulate cortex

Tinney, E. M.; Nwakamma, M. C.; Perko, M. L.; Espanya-Irla, G.; Kong, L.; Chen, C.; Hwang, J.; O'Brien, A.; Sodemann, R. L.; Caefer, J.; Manczurowsky, J.; Hillman, C. H.; Stillman, A. M.; Morris, T. P.

2026-03-02 rehabilitation medicine and physical therapy
10.64898/2026.02.27.26347275 medRxiv
Show abstract

Executive dysfunction affects nearly 50% of individuals with traumatic brain injuries (TBI), yet interventions targeting the underlying neural mechanisms remain limited. This study examined whether aerobic exercise modulates functional connectivity to improve executive function in individuals with mild TBI and identified the neural pathways mediating these improvements. In this secondary analysis of a 12-week pilot randomized controlled trial, participants with mild TBI (n=24) were randomized to aerobic exercise (n=12) or active balance control (n=12). Resting-state fMRI with multivariate pattern analysis revealed that aerobic exercise selectively altered functional connectivity patterns of the anterior cingulate cortex (ACC) compared to balance control. Post-hoc seed-to-voxel analyses identified widespread ACC connectivity differences between groups post-intervention while controlling for baseline, across 19 cortical regions spanning default mode, frontoparietal control, and salience networks. Critically, greater anticorrelation between the ACC and insula following aerobic exercise was associated with improved Trail Making Test B-A performance in the aerobic group ({beta}=46.92, p=0.04) but not the balance group, indicating that participants who developed stronger ACC-insula functional segregation showed greater reductions in executive function completion times. These findings establish the ACC-insula circuit as a critical neural substrate mediating exercise-induced executive function recovery after TBI and identify this pathway as a promising therapeutic target for exercise-based rehabilitation interventions.

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