Dynamic Functional Connectivity of Amygdala and Hippocampus in Posttraumatic Stress Disorder: A Multi-Site Study of the ENIGMA PTSD Consortium

The amygdala and hippocampus are central to neural models of posttraumatic stress disorder (PTSD), yet their dynamic functional interactions with distributed brain networks remain poorly characterized, particularly in large, diverse samples. We analyzed resting-state functional MRI data from the ENIGMA PTSD Working Group, comprising 2,721 participants from 32 international sites: 1,017 individuals with PTSD (38.6±15.2 years; 52.0% female) and 1,704 controls (38.4±17.1 years; 45.8% female; 78.6% trauma-exposed). After standardized preprocessing with HALFpipe, we computed dynamic functional connectivity (DFC) as the standard deviation of functional connectivity across sliding windows (window length = 40 seconds, overlap = 50%) for bilateral amygdala and hippocampal seeds across 1,726 seed-to-parcel connections spanning cortical, subcortical, and cerebellar regions. Linear mixed-effects models through IBMMA tested the effect of PTSD diagnosis across all connections, and within significant connections, secondary analyses examined modulation by sex, age, index trauma, depression severity, and childhood trauma severity, along with associations with overall PTSD symptom severity and symptom clusters (B-E). All findings survived false discovery rate correction (q < .05). Individuals with PTSD compared to controls showed greater DFC between the seeds and 22 regions spanning control, salience/ventral attention, dorsal attention, somatomotor, default mode, and visual networks. Case-control differences were moderated by sex and present in males only. PTSD severity and symptom clusters were positively associated with most of the connections. These findings indicate that PTSD is accompanied by greater temporal variability in connectivity between amygdala and hippocampal seeds and widespread brain networks.