title: Altered functional organization within the insular cortex in adult males with high-functioning autism spectrum disorder: evidence from connectivity-based parcellation.
abstract: The insular cortex comprises multiple functionally differentiated sub-regions, each of which has different patterns of connectivity with other brain regions. Such diverse connectivity patterns are thought to underlie a wide range of insular functions, including cognitive, affective, and sensorimotor processing, many of which are abnormal in autism spectrum disorder (ASD). Although past neuroimaging studies of ASD have shown structural and functional abnormalities in the insula, possible alterations in the sub-regional organization of the insula and the functional characteristics of each sub-region have not been examined in the ASD brain.
  
  
  
  Resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from 36 adult males with ASD and 38 matched typically developed (TD) controls. A data-driven clustering analysis was applied to rs-fMRI data of voxels in the left and right insula to automatically group voxels with similar intrinsic connectivity pattern into a cluster. After determining the optimal number of clusters based on information theoretic measures of variation of information and mutual information, functional parcellation patterns in both the left and the right insula were compared between the TD and ASD groups. Furthermore, functional profiles of each sub-region were meta-analytically decoded using Neurosynth and were compared between the groups.
  
  
  
  We observed notable alterations in the anterior sector of the left insula and the middle ventral sub-region of the right insula in the ASD brain. Meta-analytic decoding revealed that whereas the anterior sector of the left insula contained two functionally differentiated sub-regions for cognitive, sensorimotor, and emotional/affective functions in TD brain, only a single functional cluster for cognitive and sensorimotor functions was identified in the anterior sector in the ASD brain. In the right insula, the middle ventral sub-region, which is primarily specialized for sensory- and auditory-related functions, showed a significant volumetric increase in the ASD brain compared with the TD brain.
  
  
  
  The results indicate an altered organization of sub-regions in specific parts of the left and right insula of the ASD brain. The alterations in the left and right insula may constitute neural substrates underlying abnormalities in emotional/affective and sensory functions in ASD.
authors.affiliation: Medical Institute of Developmental Disabilities Research, Showa University, 6-11-11 Kita-karasuyama, Setagaya-ku, Tokyo, Japan.|ATR Brain Information Communication Research Laboratory Group, 2-2-2 Hikaridai, Seika-cho, Sorakugun, Kyoto, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Medical Institute of Developmental Disabilities Research, Showa University, 6-11-11 Kita-karasuyama, Setagaya-ku, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Itahashi
authors.affiliation: Medical Institute of Developmental Disabilities Research, Showa University, 6-11-11 Kita-karasuyama, Setagaya-ku, Tokyo, Japan.|Kinko Hospital, Kanagawa Psychiatric Center, 2-5-1 Serigaya, Yokohama, Kanagawa Japan.
authors.forename: Motoaki
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Medical Institute of Developmental Disabilities Research, Showa University, 6-11-11 Kita-karasuyama, Setagaya-ku, Tokyo, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Medical Institute of Developmental Disabilities Research, Showa University, 6-11-11 Kita-karasuyama, Setagaya-ku, Tokyo, Japan.|Child Mental Health-care Center, Fukushima University, 1 Kanayagawa, Fukusima-shi, Fukushima, Japan.|Department of Child Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongou, Bunkyo-ku, Tokyo, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Kuroda
authors.affiliation: Medical Institute of Developmental Disabilities Research, Showa University, 6-11-11 Kita-karasuyama, Setagaya-ku, Tokyo, Japan.
authors.forename: Haruhisa
authors.initials: H
authors.lastname: Ohta
authors.affiliation: Medical Institute of Developmental Disabilities Research, Showa University, 6-11-11 Kita-karasuyama, Setagaya-ku, Tokyo, Japan.
authors.forename: Chieko
authors.initials: C
authors.lastname: Kanai
authors.affiliation: Medical Institute of Developmental Disabilities Research, Showa University, 6-11-11 Kita-karasuyama, Setagaya-ku, Tokyo, Japan.
authors.forename: Nobumasa
authors.initials: N
authors.lastname: Kato
authors.affiliation: Medical Institute of Developmental Disabilities Research, Showa University, 6-11-11 Kita-karasuyama, Setagaya-ku, Tokyo, Japan.|ATR Brain Information Communication Research Laboratory Group, 2-2-2 Hikaridai, Seika-cho, Sorakugun, Kyoto, Japan.|Department of Language Sciences, Graduate School of Humanities, Tokyo Metropolitan University, 1-1 Minami-Osawa, Hachioji-shi, Tokyo, Japan.|Research Center for Language, Brain and Genetics, Tokyo Metropolitan University, 1-1 Minami-Osawa, Hachioji-shi, Tokyo, Japan.
authors.forename: Ryu-Ichiro
authors.initials: RI
authors.lastname: Hashimoto
mesh_terms: D000328:Adult; D000067877:Autism Spectrum Disorder / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D001931:Brain Mapping / Q000379:methods*; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D016000:Cluster Analysis; D007839:Functional Laterality; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*
keywords: Autism spectrum disorder; Connectivity-based functional parcellation; Insula; Resting-state functional magnetic resonance imaging