Abnormal cross-network functional connectivity in chronic pain and its association with clinical symptoms

Cortical functioning within the default mode network (DMN) and salience network (SN) is altered in chronic pain patients. The mechanisms underlying these alterations are unknown, but a novel unexamined source is cross-network communication. Aberrant functional connectivity (FC) between the DMN and SN, whose activity is normally anticorrelated, reflects disease severity in many brain disorders. Further, stronger FC between the posterior cingulate cortex (PCC) and anterior insula has been reported in chronic pain, pointing to abnormal DMN-SN interactions. Here, we tested the hypothesis that cross-network FC between the DMN and SN is abnormal in chronic pain, and is related to pain and associated symptoms. We used resting state fMRI to examine FC within and between the DMN and SN in 20 patients with chronic pain due to ankylosing spondylitis and 20 healthy controls. A whole-network analysis revealed that compared to healthy controls, patients exhibited less anticorrelated FC between the SN and DMN, and the degree of cross-network abnormality tracked pain and disease-related symptoms. This suggests that cross-network FC is a metric of functional brain abnormality in chronic pain. In a complementary seed-based analysis, the PCC was strongly connected with the SN and weakly connected with the DMN in chronic pain compared to healthy controls, suggesting that the PCC acts as a hub for altered network interaction. Sensorimotor cortex cross-network FC correlated with measures of physical function, suggesting that physical functioning also impacts brain network interaction in chronic pain. Our study implicates altered communication between brain networks as a key factor underlying chronic pain.