Intrinsic connectomes underlying response to trauma-focused psychotherapy in post-traumatic stress disorder

Abstract

Although trauma-focused cognitive behavior therapy (TF-CBT) is the frontline treatment for post-traumatic stress disorder (PTSD), up to one-half of patients are treatment nonresponders. To understand treatment nonresponse, it is important to understand the neural mechanisms of TF-CBT. Here, we used whole-brain intrinsic functional connectivity analysis to identify neural connectomic signatures of treatment outcome. In total, 36 PTSD patients and 36 healthy individuals underwent functional MRI at pre-treatment baseline. Patients then underwent nine sessions of TF-CBT and completed clinical and follow-up MRIs. We used an established large-scale brain network atlas to parcellate the brain into 343 brain regions. Pairwise intrinsic task-free functional connectivity was calculated and used to identify pretreatment connectomic features that were correlated with reduction of PTSD severity from pretreatment to post treatment. We formed a composite metric of intrinsic connections associated with therapeutic outcome, and then interrogated this composite metric to determine if it distinguished PTSD treatment responders and nonresponders from healthy control status and changed post treatment. Lower pre-treatment connectivity for the cingulo-opercular, salience, default mode, dorsal attention, and frontoparietal executive control brain networks was associated with treatment improvement. Treatment responders had lower while nonresponders had significantly greater connectivity than controls at pretreatment. With therapy, connectivity significantly increased for responders and decreased for nonresponders, while controls remain unchanged over this time period. We provide evidence that the intrinsic functional architecture of the brain, specifically connectivity within and between brain networks associated with external vigilance, self-awareness, and cognitive control, may characterize a positive response to TF-CBT for PTSD.

Individual prediction of trauma-focused psychotherapy response in youth with posttraumatic stress disorder using resting-state functional connectivity

“…In adults treated with prolonged exposure, Etkin, et al [23] found a classification accuracy of >85%, using a combination of pre-treatment rs-fMRI connectivity within the ventral attention network and delayed recall performance in a verbal memory task. In another study, pre-treatment functional connectivity within- and between-the default mode, dorsal attention, cingulo-opercular, salience, and central executive network during task-free fMRI predicted response to TF-CBT with an accuracy of 71.4% [20]. Finally, we have previously shown the feasibility of the same approach as outlined here to predict response to trauma-focused therapy in veterans with PTSD with 81.4% accuracy [17], with an ICN centered on the pre-supplementary motor area providing the best predictive accuracy.…”

“…Interestingly, relatively few studies have investigated the relationship between treatment-response and large-scale brain network connectivity. In adults with PTSD pre-treatment difference between trauma-focused psychotherapy responder and non-responder groups have been observed in activity and functional connectivity both during resting-state and task-based fMRI [16-20]. Findings from these studies suggest that activity and connectivity within regions and networks involved in working memory as well as emotional processing and modulation differed between responders and non-responders [16,17].…”

“…Multivariate supervised machine learning analysis can be used to make predictions for individual patients instead. Several studies have utilized machine learning methods and rs-fMRI to predict treatment-response in adults with PTSD, with accuracies ranging between 71-90% [17,20,23]. However, to the best of our knowledge, there are no studies available that have investigated the utility of rs-fMRI to predict treatment-response for individual patients in youth with PTSD.…”

Intrusive Experiences In Post-Traumatic Stress Disorder: Treatment Response Induces Changes In The Effective Connectivity of The Anterior Insula

“…The present fMRI study was designed to explore how an effective response to traumatic memory reactivation therapy (with or without propranolol) for intrusive symptoms in PTSD could modulate AI causal influences over the brain. Many fMRI studies measured pre/post functional connectivity using correlations (Etkin et al, 2019; Korgaonkar et al, 2020; Santarnecchi et al, 2019; Zhu et al, 2018), but only a limited number of studies reported effective connectivity changes in PTSD (Fonzo et al, 2021; Rangaprakash et al, 2018b), with no particular focus on intrusive symptoms in a whole brain approach. We focused on the AI since this region is known to be: (i) a central integration hub serving sensory, emotional, motivational and cognitive functions, (ii) potentially involved in re-experiencing trauma.…”

Post-trauma behavioral phenotype predicts vulnerability to fear relapse after extinction

“…However, in many patients, even successful EBT in the clinic is followed by a relapse of symptoms in the course of the patients' daily lives. The pathophysiological mechanisms underlying such interindividual variations in vulnerability to relapse remain unknown (Etkin et al 2019;Zhutovsky et al 2019;Korgaonkar et al 2020), and a crucial endeavor in fear extinction research is to identify clear biomarkers of such differences.…”