Functional connectivity alterations in post-traumatic stress disorder: A resting-state fMRI study of brain network...

Emerging evidence positions post-traumatic stress disorder (PTSD) as a disease fundamentally involving disturbances in whole-brain network coordination. Nonetheless, comprehensive studies systematically integrating time-invariant connectivity metrics with time-resolved dynamic assessments remain limited.

This case-control investigation enrolled 33 PTSD patients and 33 healthy controls who completed resting-state functional magnetic resonance imaging and cognitive assessment using the Addenbrooke's Cognitive Examination-III. We evaluated static connectivity via functional connectivity density mapping and assessed dynamic connectivity using sliding-window analysis to identify recurrent brain states and quantify temporal properties including state transitions and connection-level variability, while controlling for age, sex, education, and comorbidity.

Patients with PTSD demonstrated increased global connectivity density in the left insula, indicating aberrant salience processing and impaired global network reconfiguration flexibility. Connection-level analysis revealed 25 significantly altered connections with elevated temporal variability in PTSD across sensorimotor, limbic, paralimbic, striatal, and thalamocortical circuits. Notably, after adjusting for comorbidity, no group differences were found in dynamic state transitions. In healthy controls, lower orbitofrontal and medial prefrontal connectivity variability correlated positively with cognitive performance, whereas in PTSD patients, elevated variability in sensorimotor, paralimbic, striatal and cingulate-temporal connections was negatively associated with attention and memory function.

Our findings identify a profile of PTSD pathophysiology defined by left insular hyperconnectivity and circuit-specific temporal instability. These results reinforce the model of PTSD as a disorder of whole-network dysregulation and provide a foundation for developing biomarkers targeting its distinct spatiotemporal connectivity signatures.