A multicenter cross-sectional study to elucidate altered resting-state functional connectivity of the insular cortex in anorexia nervosa, segmented by functional localization

Abstract Although changes in insular function have been thought to play a central role in the pathophysiology of anorexia nervosa (AN), due to factors such as insufficient sample size, there have been no studies examining changes in resting-state functional connectivity (rsFC) between insula and who...

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Main Authors: Yusuke Sudo, Rio Kamashita, Tsunehiko Takamura, Sayo Hamatani, Noriko Numata, Koji Matsumoto, Yasuhiro Sato, Yumi Hamamoto, Tomotaka Shoji, Tomohiko Muratsubaki, Motoaki Sugiura, Shin Fukudo, Michiko Kawabata, Momo Sunada, Tomomi Noda, Keima Tose, Masanori Isobe, Naoki Kodama, Shingo Kakeda, Masatoshi Takahashi, Hiroaki Adachi, Shu Takakura, Motoharu Gondo, Kazufumi Yoshihara, Yoshiya Moriguchi, Eiji Shimizu, Atsushi Sekiguchi, Yoshiyuki Hirano
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Language:English
Published: Nature Portfolio 2025-05-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-03641-0
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author Yusuke Sudo
Rio Kamashita
Tsunehiko Takamura
Sayo Hamatani
Noriko Numata
Koji Matsumoto
Yasuhiro Sato
Yumi Hamamoto
Tomotaka Shoji
Tomohiko Muratsubaki
Motoaki Sugiura
Shin Fukudo
Michiko Kawabata
Momo Sunada
Tomomi Noda
Keima Tose
Masanori Isobe
Naoki Kodama
Shingo Kakeda
Masatoshi Takahashi
Hiroaki Adachi
Shu Takakura
Motoharu Gondo
Kazufumi Yoshihara
Yoshiya Moriguchi
Eiji Shimizu
Atsushi Sekiguchi
Yoshiyuki Hirano
author_facet Yusuke Sudo
Rio Kamashita
Tsunehiko Takamura
Sayo Hamatani
Noriko Numata
Koji Matsumoto
Yasuhiro Sato
Yumi Hamamoto
Tomotaka Shoji
Tomohiko Muratsubaki
Motoaki Sugiura
Shin Fukudo
Michiko Kawabata
Momo Sunada
Tomomi Noda
Keima Tose
Masanori Isobe
Naoki Kodama
Shingo Kakeda
Masatoshi Takahashi
Hiroaki Adachi
Shu Takakura
Motoharu Gondo
Kazufumi Yoshihara
Yoshiya Moriguchi
Eiji Shimizu
Atsushi Sekiguchi
Yoshiyuki Hirano
author_sort Yusuke Sudo
collection DOAJ
description Abstract Although changes in insular function have been thought to play a central role in the pathophysiology of anorexia nervosa (AN), due to factors such as insufficient sample size, there have been no studies examining changes in resting-state functional connectivity (rsFC) between insula and whole brain in AN, based on functional localization of insula. Here, we subdivided insula into 6 regions per side based on functional localization and reanalyzed previously published functional magnetic resonance imaging data from 114 female patients with AN and 135 female healthy controls (HC). We calculated the rsFCs between ROIs and compared the results between groups, with the 12 insular regions serving as seed ROIs and 142 regions of the whole brain as target ROIs. Compared to HC, AN patients had a increased rsFC between dorsal anterior insula (daIC) and amygdala, and a decreased rsFC between posterior division of dorsal middle insula (pdmIC) and opercular cortex (false discovery rate [FDR] corrected p-value < 0.05 with analysis-level correction, which means that FDR correction was applied to all seed ROIs and all target ROI combinations). These rsFC changes may be the neurological basis for AN symptoms, such as hypersensitivity to negative stimuli, taste disorder, and enhanced taste aversion learning.
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spelling doaj-art-c9ce85d0480f4c6ab38d29ef71a4f5942025-08-20T03:16:52ZengNature PortfolioScientific Reports2045-23222025-05-0115111410.1038/s41598-025-03641-0A multicenter cross-sectional study to elucidate altered resting-state functional connectivity of the insular cortex in anorexia nervosa, segmented by functional localizationYusuke Sudo0Rio Kamashita1Tsunehiko Takamura2Sayo Hamatani3Noriko Numata4Koji Matsumoto5Yasuhiro Sato6Yumi Hamamoto7Tomotaka Shoji8Tomohiko Muratsubaki9Motoaki Sugiura10Shin Fukudo11Michiko Kawabata12Momo Sunada13Tomomi Noda14Keima Tose15Masanori Isobe16Naoki Kodama17Shingo Kakeda18Masatoshi Takahashi19Hiroaki Adachi20Shu Takakura21Motoharu Gondo22Kazufumi Yoshihara23Yoshiya Moriguchi24Eiji Shimizu25Atsushi Sekiguchi26Yoshiyuki Hirano27Research Center for Child Mental Development Chiba UniversityResearch Center for Child Mental Development Chiba UniversityDepartment of Behavioral Medicine, National Institute of Mental Health, National Center of Neurology and PsychiatryResearch Center for Child Mental Development Chiba UniversityResearch Center for Child Mental Development Chiba UniversityDepartment of Radiology, Chiba University HospitalDepartment of Psychosomatic Medicine, Tohoku University HospitalResearch Institute of Electrical Communication, Tohoku UniversityDepartment of Psychosomatic Medicine, Tohoku University HospitalDepartment of Psychosomatic Medicine, Tohoku University HospitalDepartment of Human Brain Science, Institute of Development, Aging and Cancer, Tohoku UniversityDepartment of Psychosomatic Medicine, Tohoku University HospitalDepartment of Psychiatry, Kyoto University Graduate School of MedicineDepartment of Psychiatry, Kyoto University Graduate School of MedicineDepartment of Psychiatry, Kyoto University Graduate School of MedicineDepartment of Psychiatry, Kyoto University Graduate School of MedicineDepartment of Psychiatry, Kyoto University Graduate School of MedicineDivision of Psychosomatic Medicine, Department of Neurology, University of Occupational and Environmental HealthDepartment of Radiology, Hirosaki University Graduate School of MedicineDivision of Psychosomatic Medicine, Department of Neurology, University of Occupational and Environmental HealthDepartment of Neurology, University of Occupational and Environmental Health School of MedicineDepartment of Psychosomatic Medicine, Kyushu University HospitalDepartment of Psychosomatic Medicine, Kyushu University HospitalDepartment of Psychosomatic Medicine, Kyushu University HospitalDepartment of Behavioral Medicine, National Institute of Mental Health, National Center of Neurology and PsychiatryResearch Center for Child Mental Development Chiba UniversityDepartment of Behavioral Medicine, National Institute of Mental Health, National Center of Neurology and PsychiatryResearch Center for Child Mental Development Chiba UniversityAbstract Although changes in insular function have been thought to play a central role in the pathophysiology of anorexia nervosa (AN), due to factors such as insufficient sample size, there have been no studies examining changes in resting-state functional connectivity (rsFC) between insula and whole brain in AN, based on functional localization of insula. Here, we subdivided insula into 6 regions per side based on functional localization and reanalyzed previously published functional magnetic resonance imaging data from 114 female patients with AN and 135 female healthy controls (HC). We calculated the rsFCs between ROIs and compared the results between groups, with the 12 insular regions serving as seed ROIs and 142 regions of the whole brain as target ROIs. Compared to HC, AN patients had a increased rsFC between dorsal anterior insula (daIC) and amygdala, and a decreased rsFC between posterior division of dorsal middle insula (pdmIC) and opercular cortex (false discovery rate [FDR] corrected p-value < 0.05 with analysis-level correction, which means that FDR correction was applied to all seed ROIs and all target ROI combinations). These rsFC changes may be the neurological basis for AN symptoms, such as hypersensitivity to negative stimuli, taste disorder, and enhanced taste aversion learning.https://doi.org/10.1038/s41598-025-03641-0Eating disorderAnorexia nervosaResting-state functional connectivityInsulaTaste
spellingShingle Yusuke Sudo
Rio Kamashita
Tsunehiko Takamura
Sayo Hamatani
Noriko Numata
Koji Matsumoto
Yasuhiro Sato
Yumi Hamamoto
Tomotaka Shoji
Tomohiko Muratsubaki
Motoaki Sugiura
Shin Fukudo
Michiko Kawabata
Momo Sunada
Tomomi Noda
Keima Tose
Masanori Isobe
Naoki Kodama
Shingo Kakeda
Masatoshi Takahashi
Hiroaki Adachi
Shu Takakura
Motoharu Gondo
Kazufumi Yoshihara
Yoshiya Moriguchi
Eiji Shimizu
Atsushi Sekiguchi
Yoshiyuki Hirano
A multicenter cross-sectional study to elucidate altered resting-state functional connectivity of the insular cortex in anorexia nervosa, segmented by functional localization
Scientific Reports
Eating disorder
Anorexia nervosa
Resting-state functional connectivity
Insula
Taste
title A multicenter cross-sectional study to elucidate altered resting-state functional connectivity of the insular cortex in anorexia nervosa, segmented by functional localization
title_full A multicenter cross-sectional study to elucidate altered resting-state functional connectivity of the insular cortex in anorexia nervosa, segmented by functional localization
title_fullStr A multicenter cross-sectional study to elucidate altered resting-state functional connectivity of the insular cortex in anorexia nervosa, segmented by functional localization
title_full_unstemmed A multicenter cross-sectional study to elucidate altered resting-state functional connectivity of the insular cortex in anorexia nervosa, segmented by functional localization
title_short A multicenter cross-sectional study to elucidate altered resting-state functional connectivity of the insular cortex in anorexia nervosa, segmented by functional localization
title_sort multicenter cross sectional study to elucidate altered resting state functional connectivity of the insular cortex in anorexia nervosa segmented by functional localization
topic Eating disorder
Anorexia nervosa
Resting-state functional connectivity
Insula
Taste
url https://doi.org/10.1038/s41598-025-03641-0
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