Exposure-based therapy changes amygdala and hippocampus resting-state functional connectivity in patients with posttraumatic stress disorder

Lee, Seonjoo; Suarez‐Jimenez, Benjamin; Lazarov, Amit; Helpman, Liat; Papini, Santiago; Lowell, Ari; Durosky, Ariel; Lindquist, Martin A.; Markowitz, John C.; Schneier, Franklin R.; Wager, Tor D.; Neria, Yuval

doi:10.1002/da.22816

Cited by 74 publications

(70 citation statements)

References 56 publications

(86 reference statements)

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“…Our study also provides insight into how TF-CBT impacts neural connectivity based on heterogeneity of treatment response. TF-CBT has shown to increase amygdala and hippocampal connectivity to the orbitofrontal and medial prefrontal brain cortices 9 . This increase has been associated with improved capacity for inhibition and re-evaluation of threat and heightened memory ability 9 .…”

Section: Discussionmentioning

confidence: 99%

“…TF-CBT has shown to increase amygdala and hippocampal connectivity to the orbitofrontal and medial prefrontal brain cortices 9 . This increase has been associated with improved capacity for inhibition and re-evaluation of threat and heightened memory ability 9 . Importantly, this increase in connectivity was to normal levels at the end of treatment.…”

Section: Discussionmentioning

confidence: 99%

“…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 core-intrinsic connectivity within and between brain networks. The few studies investigating changes in resting-state connectivity following TF-CBT have reported increases between the amygdala and hippocampal limbic network structures with the executive top-down control prefrontal brain regions 9 , and a reduction in salience network connectivity 10 . Two recent studies have also evaluated the extent to which pre-treatment resting connectivity is associated with TF-CBT response.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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“…Interestingly, Abdallah, Averill, Ramage, Averill, Alkin, et al (2019) found that in combat PTSD patients, PCT decreased connectivity within SN, whereas cognitive processing therapy increased connectivity within the Central Executive Network. In another study, X. Zhu et al (2018) reported increased rsFC in patients with PTSD between amygdala, hippocampus, and prefrontal regions following exposure therapy—a possible reflection of fear inhibition/extinction and memory processing.…”

Section: Introductionmentioning

confidence: 99%

Associations between resting‐state functional connectivity and treatment response in a randomized clinical trial for posttraumatic stress disorder

Sheynin

Duval

King

et al. 2020

Depression and Anxiety

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Background: Alterations in resting-state functional connectivity (rsFC) have been reported in posttraumatic stress disorder (PTSD). Here, we examined pre-and posttreatment rsFC during a randomized clinical trial to characterize alterations and examine predictors of treatment response. Methods: Sixty-four combat veterans with PTSD were randomly assigned to prolonged exposure (PE) plus placebo, sertraline plus enhanced medication management, or PE plus sertraline. Symptom assessment and resting-state functional magnetic resonance imaging (fMRI) scans occurred before and after treatment. Twenty-nine trauma-exposed combat veterans without PTSD served as a control group at intake. Seed-based and region of interest (ROI)-to-ROI connectivities, as well as an exploratory connectome-based approach were used to analyze rsFC patterns. Based on previously reported findings, analyses focused on Salience Network (SN) and Default-Mode Network (DMN). Results: At intake, patients with PTSD showed greater DMN-dorsal attention network (DAN) connectivity (between ventromedial prefrontal cortex and superior parietal lobule; family-wise error corrected p = .011), greater SN-DAN connectivity (between insula and middle frontal gyrus; corrected p = .003), and a negative correlation between re-experiencing symptoms and within-DMN connectivity (between posterior cingulate cortex (PCC) and middle temporal gyrus; corrected p < .001). We also found preliminary evidence for associations between rsFC and treatment response. Specifically, high responders (≥50% PTSD symptom improvement), compared with low responders, had greater SN-DMN segregation (i.e., less pretreatment amygdala-PCC connectivity; p = .011) and lower pre-treatment global centrality (p = .042).

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“…The majority of treatment studies focused on intrinsic brain activity, i.e., in rest and without a specific task (Napadow et al, 2012; Harris et al, 2013; Bosma et al, 2018). The effects of EXP specifically have also only been investigated using resting-state fMRI (Zhu et al, 2018), showing that patients with post-traumatic stress disorder showed enhanced post-treatment resting-state functional connectivity between the amygdala, orbitofrontal cortex, hippocampus and the medial PFC. To date, there have been no studies investigating how (EXP) treatment modulates the circuitry underlying pain-related fear in chronic pain.…”

Section: Introductionmentioning

confidence: 99%

Exposure in vivo Induced Changes in Neural Circuitry for Pain-Related Fear: A Longitudinal fMRI Study in Chronic Low Back Pain

et al. 2019

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Exposure in vivo (EXP) is a cognitive-behavioral treatment aimed at reducing pain-related fear in chronic pain, and has proven successful in reducing pain-related disability in patients with chronic low back pain (cLBP). The current longitudinal study aimed to reveal the neural correlates of changes in pain-related fear as a result of EXP. Twenty-three patients with cLBP were included in this study. Patients with cLBP underwent MRI scanning pre-treatment (pre-EXP), post-treatment (post-EXP), and 6 months after end of treatment (FU-EXP). Pain-free controls were scanned at two time points. In the scanner, participants were presented with pictures involving back-related movements, evoking pain-related fear in patients. Pre-treatment, functional MRI revealed increased activation in right posterior insula and increased deactivation in medial prefrontal cortex (mPFC) in patients compared to controls. Post-treatment, patients reported reduced fear and pre-EXP group differences were no longer present. Contrasting pre- to post- and FU-EXP in patients revealed that stimulus-evoked neural responses changed in sensorimotor as well as cognitive/affective brain regions. Lastly, exploratory analyses revealed a tendency toward an association between changes in neural activation and changes in fear ratings, including the hippocampus and temporal lobe (pre- to post-EXP changes), and mPFC and posterior cingulate cortex (pre- to FU-EXP changes). Taken together, we show evidence that neural circuitry for pain-related fear is modulated by EXP, and that changes are associated with self-reported decreases in pain-related fear.

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Exposure-based therapy changes amygdala and hippocampus resting-state functional connectivity in patients with posttraumatic stress disorder

Cited by 74 publications

References 56 publications

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

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

Associations between resting‐state functional connectivity and treatment response in a randomized clinical trial for posttraumatic stress disorder

Exposure in vivo Induced Changes in Neural Circuitry for Pain-Related Fear: A Longitudinal fMRI Study in Chronic Low Back Pain

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