Network Changes Predict Transdiagnostic Depressive Symptom Improvement Following Cognitive Behavioral Therapy in MDD and PTSD

Abstract Despite widespread use of cognitive behavioral therapy (CBT) in clinical practice, its mechanisms with respect to brain networks remain sparsely described. In this study, we applied tools from graph theory and network science to better understand the transdiagnostic neural mechanisms of this treatment for depression. A sample of 64 subjects was included in a study of network dynamics: 33 patients (15 MDD, 18 PTSD) received longitudinal fMRI resting state scans before and after 12 weeks of CBT. Depression severity was rated on the Montgomery-Asberg Depression Rating Scale (MADRS). Thirtyone healthy controls were included to determine baseline network roles. Univariate and multivariate regression analyses were conducted on the normalized change scores of within- and between-system connectivity and normalized change score of the MADRS. Penalized regression was used to select a sparse set of predictors in a data-driven manner. Univariate analyses showed greater symptom reduction was associated with an increased functional role of the Ventral Attention (VA) system as an incohesive provincial system (decreased between- and decreased within-system connectivity). Multivariate analyses selected between-system connectivity of the VA system as the most prominent feature associated with depression improvement. Observed VA system changes are interesting in light of brain controllability descriptions: attentional control systems, including the VA system, fall on the boundary between-network communities, and facilitate integration or segregation of diverse cognitive systems. Thus, increasing segregation of the VA system following CBT (decreased between-network connectivity) may result in less contribution of emotional attention to cognitive processes, thereby potentially improving cognitive control.