Running Therapy Reorganizes Dynamic Brain Networks Linked to Symptom Improvement in Affective Disorders

ABSTRACTs Background Exercise therapy reduces depressive and anxiety symptoms, but its neural mechanisms remain unclear. We examined whether running therapy reorganizes dynamic brain functional connectivity in affective disorders. Methods Resting-state fMRI was analyzed at baseline in 66 healthy controls and 50 individuals with affective disorders. Co-activation pattern (CAP) analysis identified recurring whole-brain states and their temporal dynamics. After baseline comparisons, patients received 16 weeks of running therapy or antidepressant treatment. We then examined treatment-related CAP changes and their associations with symptom improvement. Results At baseline, individuals with affective disorders showed fewer occurrences and shorter dwell time of the visual-somatosensory-subcortical CAP (VS-SC CAP ) than controls (both p ≤ 0.04, η 2 p ≈ 0.04 to 0.05). Running therapy induced a treatment-specific reorganization of brain dynamics, with decreased default mode CAP (DM CAP ) occurrences (F = 8.18, p = 0.01, η 2 p = 0.13) and dwell time (F = 11.51, p < 0.001, η 2 p= 0.19), and increased VS-SC CAP occurrences (F = 8.10, p = 0.01, η 2 p = 0.13) and entries (F = 5.39, p = 0.03, η 2 p = 0.08). Greater reductions in DM CAP entries and transitions from DM CAP to VS-SC CAP were associated with greater improvement in anxiety- and fear-related symptoms (rho = -0.54 to -0.45, all p FDR ≤ 0.03). Conclusions Running therapy was associated with treatment-specific reorganization of large-scale brain dynamics in affective disorders. Symptom improvement was linked to changes in default mode CAP dynamics and transitions between default mode and visual-somatosensory states .