title: Sex and disease-related alterations of anterior insula functional connectivity in chronic abdominal pain.
abstract: Resting-state functional magnetic resonance imaging has been used to investigate intrinsic brain connectivity in healthy subjects and patients with chronic pain. Sex-related differences in the frequency power distribution within the human insula (INS), a brain region involved in the integration of interoceptive, affective, and cognitive influences, have been reported. Here we aimed to test sex and disease-related alterations in the intrinsic functional connectivity of the dorsal anterior INS. The anterior INS is engaged during goal-directed tasks and modulates the default mode and executive control networks. By comparing functional connectivity of the dorsal anterior INS in age-matched female and male healthy subjects and patients with irritable bowel syndrome (IBS), a common chronic abdominal pain condition, we show evidence for sex and disease-related alterations in the functional connectivity of this region: (1) male patients compared with female patients had increased positive connectivity of the dorsal anterior INS bilaterally with the medial prefrontal cortex (PFC) and dorsal posterior INS; (2) female patients compared with male patients had greater negative connectivity of the left dorsal anterior INS with the left precuneus; (3) disease-related differences in the connectivity between the bilateral dorsal anterior INS and the dorsal medial PFC were observed in female subjects; and (4) clinical characteristics were significantly correlated to the insular connectivity with the dorsal medial PFC in male IBS subjects and with the precuneus in female IBS subjects. These findings are consistent with the INS playing an important role in modulating the intrinsic functional connectivity of major networks in the resting brain and show that this role is influenced by sex and diagnosis.
authors.affiliation: Gail and Gerald Oppenheimer Family Center for Neurobiology of Stress, Division of Digestive Diseases, Department of Bioengineering, University of California, Los Angeles, Los Angeles, California 90095.
authors.forename: Jui-Yang
authors.initials: JY
authors.lastname: Hong
authors.affiliation: Gail and Gerald Oppenheimer Family Center for Neurobiology of Stress, Pain and Interoception Imaging Network, Department of Medicine, Division of Digestive Diseases.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Kilpatrick
authors.affiliation: Gail and Gerald Oppenheimer Family Center for Neurobiology of Stress, Pain and Interoception Imaging Network, Department of Medicine, Brain Research Institute, Division of Digestive Diseases.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Labus
authors.affiliation: Gail and Gerald Oppenheimer Family Center for Neurobiology of Stress, Department of Medicine, Division of Digestive Diseases.
authors.forename: Arpana
authors.initials: A
authors.lastname: Gupta
authors.affiliation: Gail and Gerald Oppenheimer Family Center for Neurobiology of Stress.
authors.forename: David
authors.identifier: http://orcid.org/0000-0003-4027-093X
authors.initials: D
authors.lastname: Katibian
authors.affiliation: Gail and Gerald Oppenheimer Family Center for Neurobiology of Stress, Pain and Interoception Imaging Network, Department of Medicine, Division of Digestive Diseases.
authors.forename: Cody
authors.identifier: http://orcid.org/0000-0002-8021-7212
authors.initials: C
authors.lastname: Ashe-McNalley
authors.affiliation: Gail and Gerald Oppenheimer Family Center for Neurobiology of Stress, Department of Medicine, Division of Digestive Diseases.
authors.forename: Jean
authors.initials: J
authors.lastname: Stains
authors.affiliation: Gail and Gerald Oppenheimer Family Center for Neurobiology of Stress, Department of Medicine, Division of Digestive Diseases.
authors.forename: Nuwanthi
authors.initials: N
authors.lastname: Heendeniya
authors.affiliation: Gail and Gerald Oppenheimer Family Center for Neurobiology of Stress, Department of Medicine, Division of Digestive Diseases.
authors.forename: Suzanne R
authors.initials: SR
authors.lastname: Smith
authors.affiliation: Gail and Gerald Oppenheimer Family Center for Neurobiology of Stress, Pain and Interoception Imaging Network, Department of Medicine, Division of Digestive Diseases.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Tillisch
authors.affiliation: Gail and Gerald Oppenheimer Family Center for Neurobiology of Stress, Pain and Interoception Imaging Network, Department of Medicine, Brain Research Institute, Division of Digestive Diseases.
authors.forename: Bruce
authors.initials: B
authors.lastname: Naliboff
authors.affiliation: Gail and Gerald Oppenheimer Family Center for Neurobiology of Stress, Pain and Interoception Imaging Network, Department of Medicine, Brain Research Institute, Division of Digestive Diseases, Department of Psychiatry, Ahmanson Lovelace Brain Mapping Center, David Geffen School of Medicine, and emayer@ucla.edu.
authors.forename: Emeran A
authors.identifier: http://orcid.org/0000-0003-3923-3349
authors.initials: EA
authors.lastname: Mayer
mesh_terms: D015746:Abdominal Pain / Q000175:diagnosis / Q000503:physiopathology*; D000328:Adult; D002540:Cerebral Cortex / Q000503:physiopathology*; D059350:Chronic Pain / Q000175:diagnosis / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000503:physiopathology*; D012727:Sex Characteristics; D011795:Surveys and Questionnaires; D055815:Young Adult
keywords: IBS; fMRI; insula; pain; sex difference