Abstract
<h3>ABSTRACT</h3> <h3>Introduction</h3> 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. <h3>Methods</h3> Thirty PTSD patients were enrolled and exposed to traumatic memory reactivation therapy (chemofacilitated or not). 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. <h3>Results</h3> 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 <i>default mode network</i> (DMN) and more unstable <i>central executive network</i> (CEN) connectivity. <h3>Discussion</h3> 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.
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