Dataset Information

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

ABSTRACT:

Background

Alterations in resting-state functional connectivity (rsFC) have been reported in posttraumatic stress disorder (PTSD). Here, we examined pre- and post-treatment 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 pre-treatment amygdala-PCC connectivity; p = .011) and lower pre-treatment global centrality (p = .042).

Conclusions

Our findings suggest neural abnormalities in PTSD and may inform future research examining neural biomarkers of PTSD treatment response.

SUBMITTER: Sheynin J

PROVIDER: S-EPMC7722156 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundPrefrontal subregions, including the ventromedial prefrontal cortex (PFC), dorsomedial PFC, and dorsolateral PFC (DLPFC), are differentially implicated in the pathophysiology of posttraumatic stress disorder (PTSD), though few existing studies have examined subregional differences in resting-state functional connectivity (rsFC). We hypothesized that PTSD would involve weaker positive rsFC between ventromedial PFC, dorsomedial PFC, and other default mode network regions and increased negative rsFC between DLPFC and posterior default mode network regions. Additionally, we hypothesized that prefrontal regions exhibiting group differences in rsFC would be characterized by alterations in cortical thickness.MethodsParticipants included 36 healthy control subjects, 30 trauma-exposed control subjects, and 21 individuals with current DSM-IV PTSD resulting from community-acquired trauma. Participants completed the Clinician Administered PTSD Scale, questionnaires (Childhood Trauma Questionnaire, Adverse Childhood Events, Life Events Checklist, Beck Depression Inventory), structural neuroimaging, and resting-state functional magnetic resonance imaging. rsFC of DLPFC, ventromedial PFC, and dorsomedial PFC seeds was evaluated in SPM12 and CONN. Cortical thickness for regions with significant rsFC findings was assessed using FreeSurfer.ResultsRelative to both healthy control and trauma-exposed control subjects, individuals with PTSD showed increased negative rsFC between the DLPFC and a region of precuneus. This finding was associated with increased overall symptom severity but not with trauma load or childhood trauma exposure. Greater negative DLPFC-precuneus connectivity was associated with greater bilateral precuneus thickness.ConclusionsGiven participation of precuneus subregions in the central executive network, increased anticorrelation between right DLPFC and precuneus in this sample may reflect increased opposition between anterior and posterior central executive network hubs in PTSD.