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

Abstract

BackgroundPosttraumatic 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. MethodsA 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. ResultsAfter 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. ConclusionsAltered 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.