title: Alterations of local spontaneous brain activity and connectivity in adults with high-functioning autism spectrum disorder.
abstract: BACKGROUND
  Previous autism research has hypothesized that abnormalities of functional connectivity in autism spectrum disorder (ASD) may vary with the spatial distance between two brain regions. Although several resting-state functional magnetic resonance imaging (rsfMRI) studies have extensively examined long-range (or distant) connectivity in the adult ASD brain, short-range (or local) connectivity has been investigated in less depth. Furthermore, the possible relationship between functional connectivity and brain activity level during the resting state remains unclear.
  
  
  METHODS
  We acquired rsfMRI data from 50 adults with high-functioning ASD and 50 matched controls to examine the properties of spontaneous brain activity using measures of local and distant connectivity together with a measure of the amplitude of brain activity, known as fractional amplitude of low-frequency fluctuation (fALFF). The two connectivity measures were calculated using a common graph-theoretic framework. We also examined the spatial overlaps between these measures and possible relationships of these disrupted functional measures with autistic traits assessed by the Autism-Spectrum Quotient (AQ).
  
  
  RESULTS
  Compared to the controls, participants with ASD exhibited local over-connectivity in the right superior frontal gyrus and middle frontal gyrus, accompanied by local under-connectivity in the bilateral fusiform gyri (FG) and right middle temporal gyrus (MTG). On the other hand, we did not find any significant alterations in distant connectivity. Participants with ASD also exhibited reduced fALFF in the right middle occipital gyrus, lingual gyrus, and FG. Further conjunction and spatial overlap analyses confirmed that the spatial pattern of reduced fALFF substantially overlapped with that of local under-connectivity, demonstrating the co-occurrence of disrupted connectivity and spontaneous activity level in the right inferior occipital gyrus, posterior MTG (pMTG), and FG. Finally, within the ASD group, disrupted local connectivity in the right pMTG significantly correlated with the "social interaction" subscale score of the AQ.
  
  
  CONCLUSIONS
  These findings revealed local functional disruptions in the occipital and temporal regions, especially the right FG and pMTG, in the form of co-occurrence of spontaneous brain activity level and local connectivity, which may underline social and communicative dysfunctions in adult ASD.
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 ; Department of Psychiatry, School of Medicine, Showa University, 6-11-11 Kita-karasuyama, Setagaya-ku, Tokyo Japan ; ATR Brain Information Communication Research Laboratory Group, 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 ; Department of Psychiatry, School of Medicine, Showa University, 6-11-11 Kita-karasuyama, Setagaya-ku, Tokyo Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Department of Psychiatry, School of Medicine, Showa University, 6-11-11 Kita-karasuyama, Setagaya-ku, Tokyo Japan ; Kanagawa Psychiatric Center, Kinko Hospital, 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 ; Department of Psychiatry, School of Medicine, 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: Department of Psychiatry, School of Medicine, Showa University, 6-11-11 Kita-karasuyama, Setagaya-ku, Tokyo Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Iwanami
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 ; Department of Language Sciences, Graduate School of Humanities, Tokyo Metropolitan University, 1-1 Minami-Osawa, Hachioji-shi, Tokyo Japan.
authors.forename: Ryu-Ichiro
authors.initials: R
authors.lastname: Hashimoto
keywords: Amplitude of low-frequency fluctuation; Autism spectrum disorder; Local connectivity; Resting-state functional magnetic resonance imaging; Spontaneous activity