Default Mode Network Hypoalignment of Function to Structure Correlates With Depression and Rumination

Recent studies have begun to examine how signals in the brain correspond to the underlying white matter structure using tools from the field of graph signal processing to quantify brain function alignment to brain network topology. Here, we applied this framework for the first time toward a transdiagnostic cohort of individuals with internalizing psychopathologies, including mood and anxiety disorders, to uncover how such alignment within the default mode network (DMN) is related to depression and rumination symptoms. Both diffusion-weighted and resting-state functional magnetic resonance imaging were obtained from participants at baseline (n = 60 patients, n = 19 healthy control participants). Patients were randomized to 12 weeks of treatment with either a selective serotonin reuptake inhibitor or cognitive behavioral therapy, and symptom scales were readministered posttreatment (n = 46 patients at follow-up). Using graph signal processing methodology, we quantified the alignment of functional signals to their underlying white matter structural networks. We found that signal alignment within the posterior DMN was decreased in patients with internalizing psychopathologies compared with healthy control participants and was inversely (negatively) correlated with baseline depression and rumination scales. Signal alignment within the posterior DMN was also correlated with the ratio of total within-DMN to extra-DMN functional connectivity for these regions. These findings are consistent with previous literature regarding pathological promiscuity of posterior DMN connectivity and provide the first graph signal processing–based analyses in a transdiagnostic cohort of patients with internalizing psychopathologies.