Introduction: One of the core features of posttraumatic stress disorder (PTSD) is reexperiencing the trauma. Th anterior insula (AI) was proposed to play a crucial role in these intrusive experiences. However, the dynamic function of the AI in reexperiencing trauma, as well as its putative modulation by effective therapy, still need to be specified. Methods: Thirty PTSD patients were enrolled and exposed to chemo-facilitated traumatic memory reactivation therapy. Resting-state fMRI scans were acquired before and after treatment. To explore AI directed influences over the rest of the brain, we referred to a mixed-model using pre/post Granger causality analysis seeded on the AI as a within-subject factor and treatment response as a between-subject factor. To further identify correlates of reexperiencing trauma, we investigated how intrusive severity affected : (i) causality maps and (ii) the spatial stability of other intrinsic brain networks. Results: We observed dynamic changes in AI effective connectivity in PTSD patients. Many within- and between-network causal paths were found to be less influenced by the AI after effective therapy. Insular influences were found positively correlated with flashback severity, while reexperiencing was linked with a stronger default mode network (DMN) and more unstable central executive network (CEN) connectivity. Discussion: We showed that directed changes in AI signalling to the DMN and CEN at rest may underlie the degree of intrusive symptoms in PTSD. A positive response to treatment further induced changes in network-to-network anticorrelated patterns. Such findings may guide targeted neuromodulation strategies in PTSD patients not suitably improved by conventional treatment.
bioRxiv Subject Collection: Neuroscience