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 pre-treatment 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.
Highlights
Trauma-focused cognitive behavior therapy (TF-CBT)is the preferred treatment for post-traumatic stress disorder (PTSD), yet at least half of patients do not respond to this approach[1,2]
The network-based statistic (NBS) analysis identified a connectomic signature comprising 122 interregional connections between 88 brain nodes, which was significantly associated with treatment response
We found an overall lower-than-normal pre-treatment connectivity to be associated with better treatment response, whereas greater-than-normal connectivity was associated with nonresponse to TF-CBT
Summary
Trauma-focused cognitive behavior therapy (TF-CBT)is the preferred treatment for post-traumatic stress disorder (PTSD), yet at least half of patients do not respond to this approach[1,2]. Korgaonkar et al Translational Psychiatry (2020)10:270 associated with some of these brain regions correlates with treatment, with greater suppression of amygdala–insula connectivity during cognitive reappraisal of negative-valence images[7], and that of insula–pregenual anterior cingulate connectivity during processing of sad facial expressions associated with symptom improvement[8] While such a focused approach has been useful to identify neural regions underlying TF-CBT response, it is limited because it does not address how treatment response may be predicted by task-independent coreintrinsic connectivity within and between brain networks. The second study identified that pre-treatment superior frontal and presupplementary motor-resting connectivity could distinguish veterans with PTSD who respond to TF-CBT from nonresponders[12] These studies are limited in that they focus either on specific regions or networks, and lack detailed examination of all connections in the brain
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