title: Abnormal cross-network functional connectivity in chronic pain and its association with clinical symptoms.
abstract: 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.
authors.affiliation: Krembil Research Institute, Toronto Western Hospital, University Health Network, Toronto, ON, Canada.|Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
authors.forename: Kasey S
authors.initials: KS
authors.lastname: Hemington
authors.affiliation: Krembil Research Institute, Toronto Western Hospital, University Health Network, Toronto, ON, Canada.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Psychiatry, Harvard Medical School, Boston, MA, USA.|Department of Psychiatry, Massachusetts General Hospital, Charlestown, MA, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Kucyi
authors.affiliation: Krembil Research Institute, Toronto Western Hospital, University Health Network, Toronto, ON, Canada.|Department of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Inman
authors.affiliation: Krembil Research Institute, Toronto Western Hospital, University Health Network, Toronto, ON, Canada. kdavis@uhnres.utoronto.ca.|Institute of Medical Science, University of Toronto, Toronto, ON, Canada. kdavis@uhnres.utoronto.ca.|Department of Surgery, University of Toronto, Toronto, ON, Canada. kdavis@uhnres.utoronto.ca.|Toronto Western Hospital, 399 Bathurst Street, Room MP14-306, Toronto, ON, M5T 2S8, Canada. kdavis@uhnres.utoronto.ca.
authors.forename: Karen D
authors.initials: KD
authors.lastname: Davis
mesh_terms: D000328:Adult; D001288:Attention / Q000502:physiology; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D059350:Chronic Pain / Q000209:etiology / Q000503:physiopathology*; D005260:Female; D006179:Gyrus Cinguli / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000503:physiopathology; D009434:Neural Pathways / Q000503:physiopathology; D013167:Spondylitis, Ankylosing / Q000150:complications; D055815:Young Adult
keywords: Chronic pain; Default mode network; Functional connectivity; Salience network; resting state fMRI