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

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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 .

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