title: Altered resting state connectivity of the insular cortex in individuals with fibromyalgia.
abstract: The insular cortex (IC) and cingulate cortex (CC) are critically involved in pain perception. Previously we demonstrated that fibromyalgia (FM) patients have greater connectivity between the insula and default mode network at rest, and that changes in the degree of this connectivity were associated with changes in the intensity of ongoing clinical pain. In this study we more thoroughly evaluated the degree of resting-state connectivity to multiple regions of the IC in individuals with FM and healthy controls. We also investigated the relationship between connectivity, experimental pain, and current clinical chronic pain. Functional connectivity was assessed using resting-state functional magnetic resonance imaging in 18 FM patients and 18 age- and sex-matched healthy controls using predefined seed regions in the anterior, middle, and posterior IC. FM patients exhibited greater connectivity between 1) right mid IC and right mid/posterior CC and right mid IC, 2) right posterior IC and left CC, and 3) right anterior IC and left superior temporal gyrus. Healthy controls displayed greater connectivity between left anterior IC and bilateral medial frontal gyrus/anterior cingulate cortex; and left posterior IC and right superior frontal gyrus. Within the FM group, greater connectivity between the IC and CC was associated with decreased pressure-pain thresholds.
  
  
  CONCLUSIONS
  These data provide further support for altered resting-state connectivity between the IC and other brain regions known to participate in pain perception/modulation, which may play a pathogenic role in conditions such as FM. We speculate that altered IC connectivity is associated with the experience of chronic pain in individuals with FM.
authors.affiliation: Department of Anesthesiology, Chronic Pain and Fatigue Research Center, University of Michigan, Ann Arbor, Michigan. Electronic address: eichesco@med.umich.edu.
authors.forename: Eric
authors.initials: E
authors.lastname: Ichesco
authors.affiliation: Department of Anesthesiology, Chronic Pain and Fatigue Research Center, University of Michigan, Ann Arbor, Michigan; Department of Neurology, Bergmannsheil, Ruhr University Bochum, Bochum, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Schmidt-Wilcke
authors.affiliation: Department of Anesthesiology, Chronic Pain and Fatigue Research Center, University of Michigan, Ann Arbor, Michigan; Neurology Department, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Rupal
authors.initials: R
authors.lastname: Bhavsar
authors.affiliation: Department of Anesthesiology, Chronic Pain and Fatigue Research Center, University of Michigan, Ann Arbor, Michigan.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Clauw
authors.affiliation: Functional MRI Laboratory, University of Michigan, Ann Arbor, Michigan.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Peltier
authors.affiliation: MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, Massachusetts.
authors.forename: Jieun
authors.initials: J
authors.lastname: Kim
authors.affiliation: MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, Massachusetts; Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Department of Radiology, Logan College of Chiropractic, Chesterfield, Missouri.
authors.forename: Vitaly
authors.initials: V
authors.lastname: Napadow
authors.affiliation: Department of Anesthesiology, Chronic Pain and Fatigue Research Center, University of Michigan, Ann Arbor, Michigan.
authors.forename: Johnson P
authors.initials: JP
authors.lastname: Hampson
authors.affiliation: Department of Anesthesiology, Chronic Pain and Fatigue Research Center, University of Michigan, Ann Arbor, Michigan; Department of Psychology, University of Colorado Denver, Denver, Colorado.
authors.forename: Anson E
authors.initials: AE
authors.lastname: Kairys
authors.affiliation: Department of Anesthesiology, Chronic Pain and Fatigue Research Center, University of Michigan, Ann Arbor, Michigan.
authors.forename: David A
authors.initials: DA
authors.lastname: Williams
authors.affiliation: Department of Anesthesiology, Chronic Pain and Fatigue Research Center, University of Michigan, Ann Arbor, Michigan.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Harris
mesh_terms: D000328:Adult; D000342:Affective Symptoms / Q000209:etiology; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000098:blood supply / Q000503:physiopathology*; D005260:Female; D005356:Fibromyalgia / Q000150:complications / Q000473:pathology*; D007839:Functional Laterality; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000098:blood supply / Q000503:physiopathology*; D010100:Oxygen / Q000097:blood; D010147:Pain Measurement; D058748:Pain Perception / Q000502:physiology*; D011569:Psychiatric Status Rating Scales; D012146:Rest; D055815:Young Adult
chemical_list: D010100:Oxygen
keywords: Fibromyalgia; chronic pain; cingulate cortex; insular cortex; resting-state connectivity