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

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

doi:10.1038/s41598-025-03641-0

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

Sci Rep. 2025 May 31;15(1):19118. doi: 10.1038/s41598-025-03641-0.

Authors

Yusuke Sudo^{1

2

3}, Rio Kamashita^{1

4}, Tsunehiko Takamura⁵, Sayo Hamatani^{1

6

7}, Noriko Numata^{1

2

6}, Koji Matsumoto⁸, Yasuhiro Sato⁹, Yumi Hamamoto^{10

11}, Tomotaka Shoji^{9

12

13}, Tomohiko Muratsubaki^{9

14}, Motoaki Sugiura^{15

16}, Shin Fukudo^{9

14

17

18}, Michiko Kawabata¹⁹, Momo Sunada¹⁹, Tomomi Noda¹⁹, Keima Tose¹⁹, Masanori Isobe¹⁹, Naoki Kodama²⁰, Shingo Kakeda²¹, Masatoshi Takahashi²⁰, Hiroaki Adachi²², Shu Takakura²³, Motoharu Gondo²³, Kazufumi Yoshihara²³, Yoshiya Moriguchi⁵, Eiji Shimizu^{1

2

6}, Atsushi Sekiguchi⁵, Yoshiyuki Hirano^{24

25

26}

Affiliations

¹ Research Center for Child Mental Development Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba, 260-8670, Japan.
² Department of Cognitive Behavioral Physiology, Chiba University, Chiba, Japan.
³ Division of Medical Treatment and Rehabilitation, Center for Forensic Mental Health, Chiba University, Chiba, Japan.
⁴ Department of Rehabilitation, Faculty of Health Sciences, Hiroshima Cosmopolitan University, Hiroshima, Japan.
⁵ Department of Behavioral Medicine, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Japan.
⁶ United Graduate School of Child Development, The University of Osaka, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Suita, Japan.
⁷ Research Center for Child Mental Development University of Fukui, Eiheizi, Japan.
⁸ Department of Radiology, Chiba University Hospital, Chiba, Japan.
⁹ Department of Psychosomatic Medicine, Tohoku University Hospital, Sendai, Japan.
¹⁰ Research Institute of Electrical Communication, Tohoku University, Sendai, Japan.
¹¹ Frontier Research Institute for Interdisciplinary Science, Tohoku University, Sendai, Japan.
¹² Department of Internal Medicine, Nagamachi Hospital, Sendai, Japan.
¹³ Department of Psychosomatic Medicine, Tohoku University School of Medicine, Sendai, Japan.
¹⁴ Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
¹⁵ Department of Human Brain Science, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
¹⁶ Cognitive Sciences Lab, International Research Institute of Disaster Science, Tohoku University, Sendai, Japan.
¹⁷ Research Center for Accelerator and Radioisotope Science, Tohoku University, Sendai, Japan.
¹⁸ Department of Psychosomatic Medicine, Japanese Red Cross Ishinomaki Hospital, Ishinomaki, Japan.
¹⁹ Department of Psychiatry, Kyoto University Graduate School of Medicine, Kyoto, Japan.
²⁰ Division of Psychosomatic Medicine, Department of Neurology, University of Occupational and Environmental Health, Kitakyushu, Japan.
²¹ Department of Radiology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
²² Department of Neurology, University of Occupational and Environmental Health School of Medicine, Kitakyushu, Japan.
²³ Department of Psychosomatic Medicine, Kyushu University Hospital, Fukuoka, Japan.
²⁴ Research Center for Child Mental Development Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba, 260-8670, Japan. hirano@chiba-u.jp.
²⁵ United Graduate School of Child Development, The University of Osaka, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Suita, Japan. hirano@chiba-u.jp.
²⁶ Applied MRI Research, Department of Molecular Imaging and Theranostics, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba, Japan. hirano@chiba-u.jp.

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.

Keywords: Anorexia nervosa; Eating disorder; Insula; Resting-state functional connectivity; Taste.

Publication types

Multicenter Study

MeSH terms

Adolescent
Adult
Anorexia Nervosa* / diagnostic imaging
Anorexia Nervosa* / physiopathology
Brain Mapping
Case-Control Studies
Cerebral Cortex* / physiopathology
Connectome
Cross-Sectional Studies
Female
Humans
Insular Cortex* / diagnostic imaging
Insular Cortex* / physiopathology
Magnetic Resonance Imaging
Rest
Young Adult

Abstract

Publication types

MeSH terms

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