Post-traumatic stress symptoms are associated with altered cognitive circuits and threat pathways in chronic pain

Chronic pain and post-traumatic stress symptoms (PTSS) frequently co-occur. However, how they interact in the brain to influence cognition and emotion is not well understood. Here, we examined how PTSS affects working memory-related networks during an N-back task. In addition, we examined how these networks interact with subcortical threat regions and influence working memory and pain symptoms. Fifty-three chronic low back pain participants completed the N-back task during fMRI. Brain activation was analyzed in relation to PTSS as both a continuous measure and as high-versus-low groups, using whole-brain parcellation across task loads (FDR corrected). We also examined whether abnormally activated regions were functionally connected to periaqueductal gray subregions, the amygdala, or hippocampus, and how these connections related to PTSS. Although higher PTSS did not affect task performance, it was associated with reduced activation in dorsal and inferior lateral frontal regions during the 3-back condition. PTSS was also associated with increased functional connectivity between the dorsolateral prefrontal cortex and periaqueductal gray, but not with the amygdala or hippocampus. Reduced prefrontal activations and high connectivity with periaqueductal gray predicted higher depression and catastrophizing symptoms. Thus, in chronic pain, PTSS selectively disrupts prefrontal circuits, suggesting that greater trauma symptoms interact with prefrontal circuits when cognitive demand is high. PTSS strengthens coupling between prefrontal regions and brainstem threat/pain circuits, suggesting cognitive-affective coupling. These neural alterations occur even when working memory performance is intact and are linked to higher depression and pain catastrophizing. Larger studies are needed to confirm and clarify these mechanisms.