Dataset Information

Acute Posttrauma Resting-State Functional Connectivity of Periaqueductal Gray Prospectively Predicts Posttraumatic Stress Disorder Symptoms.

ABSTRACT:

Background

Posttraumatic stress disorder (PTSD) is characterized by hyperarousal, avoidance, and intrusive/re-experiencing symptoms. The periaqueductal gray (PAG), which generates behavioral responses to physical and psychological stressors, is also implicated in threat processing. Distinct regions of the PAG elicit opposing responses to threatening or stressful stimuli; the ventrolateral PAG evokes passive coping strategies (e.g., analgesia), whereas the dorsolateral PAG (dlPAG) promotes active responses (e.g., fight or flight). We investigated whether altered PAG resting-state functional connectivity (RSFC) prospectively predicted PTSD symptoms.

Methods

A total of 48 trauma-exposed individuals underwent an RSFC scan 2 weeks posttraumatic injury. Self-report measures, including the visual analog scale for pain and the Impact of Event Scale, were collected at 2 weeks and 6 months posttrauma. We analyzed whether acute bilateral PAG RSFC was a marker of risk for total 6-month symptom severity and specific symptom clusters. In an exploratory analysis, we investigated whether dlPAG RSFC predicted PTSD symptoms.

Results

After adjusting for physical pain ratings, greater acute posttrauma PAG-frontal pole and PAG-posterior cingulate cortex connectivity was positively associated with 6-month total PTSD symptoms. Weaker dlPAG-superior/inferior parietal lobule connectivity predicted both higher hyperarousal and higher intrusive symptoms, while weaker dlPAG-supramarginal gyrus RSFC was associated with only hyperarousal symptoms.

Conclusions

Altered connectivity of the PAG 2 weeks posttrauma prospectively predicted PTSD symptoms. These findings suggest that aberrant PAG function may serve as a marker of risk for chronic PTSD symptoms, possibly by driving specific symptom clusters, and more broadly that connectivity of specific brain regions may underlie specific symptom profiles.

SUBMITTER: Webb EK

PROVIDER: S-EPMC7483700 | 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.