title: A small number of abnormal brain connections predicts adult autism spectrum disorder.
abstract: Although autism spectrum disorder (ASD) is a serious lifelong condition, its underlying neural mechanism remains unclear. Recently, neuroimaging-based classifiers for ASD and typically developed (TD) individuals were developed to identify the abnormality of functional connections (FCs). Due to over-fitting and interferential effects of varying measurement conditions and demographic distributions, no classifiers have been strictly validated for independent cohorts. Here we overcome these difficulties by developing a novel machine-learning algorithm that identifies a small number of FCs that separates ASD versus TD. The classifier achieves high accuracy for a Japanese discovery cohort and demonstrates a remarkable degree of generalization for two independent validation cohorts in the USA and Japan. The developed ASD classifier does not distinguish individuals with major depressive disorder and attention-deficit hyperactivity disorder from their controls but moderately distinguishes patients with schizophrenia from their controls. The results leave open the viable possibility of exploring neuroimaging-based dimensions quantifying the multiple-disorder spectrum.
authors.affiliation: Department of Youth Mental Health, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.|Diagnostic Imaging Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555, Japan.|Department of Decoded Neurofeedback, ATR Brain Information Communication Research Laboratory Group, Kyoto 619-0288, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Yahata
authors.affiliation: Department of Brain Robot Interface, ATR Brain Information Communication Research Laboratory Group, Kyoto 619-0288, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Morimoto
authors.affiliation: Department of Decoded Neurofeedback, ATR Brain Information Communication Research Laboratory Group, Kyoto 619-0288, Japan.|Medical Institute of Developmental Disabilities Research, Showa University Karasuyama Hospital, Tokyo 157-8577, Japan.|Department of Language Sciences, Tokyo Metropolitan University, Tokyo 192-0397, Japan.
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Hashimoto
authors.affiliation: Department of Brain Robot Interface, ATR Brain Information Communication Research Laboratory Group, Kyoto 619-0288, Japan.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lisi
authors.affiliation: Department of Decoded Neurofeedback, ATR Brain Information Communication Research Laboratory Group, Kyoto 619-0288, Japan.|Department of Cognitive, Linguistic and Psychological Sciences, Brown University, Rhode Island 02912, USA.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Shibata
authors.affiliation: Department of Child Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kawakubo
authors.affiliation: Disability Services Office, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kuwabara
authors.affiliation: Department of Child Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.|Child Mental Health-Care Center, Fukushima University, Fukushima 960-1296, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Kuroda
authors.affiliation: Department of Decoded Neurofeedback, ATR Brain Information Communication Research Laboratory Group, Kyoto 619-0288, Japan.|Medical Institute of Developmental Disabilities Research, Showa University Karasuyama Hospital, Tokyo 157-8577, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Department of Decoded Neurofeedback, ATR Brain Information Communication Research Laboratory Group, Kyoto 619-0288, Japan.|Institute of Cognitive Neuroscience, University College London, London WC1N 3AZ, UK.
authors.forename: Fukuda
authors.identifier: http://orcid.org/0000-0002-8608-4756
authors.initials: F
authors.lastname: Megumi
authors.affiliation: Department of Decoded Neurofeedback, ATR Brain Information Communication Research Laboratory Group, Kyoto 619-0288, Japan.|Department of Psychology, Graduate School of Humanities and Sociology, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Imamizu
authors.affiliation: School of Social and Behavioral Sciences, Arizona State University, Phoenix, Arizona 85306, USA.
authors.forename: José E
authors.initials: JE
authors.lastname: Náñez
authors.affiliation: Department of Psychiatry, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Psychiatry and Neurosciences, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Okamoto
authors.affiliation: Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Kiyoto
authors.initials: K
authors.lastname: Kasai
authors.affiliation: Medical Institute of Developmental Disabilities Research, Showa University Karasuyama Hospital, Tokyo 157-8577, Japan.
authors.forename: Nobumasa
authors.initials: N
authors.lastname: Kato
authors.affiliation: Department of Decoded Neurofeedback, ATR Brain Information Communication Research Laboratory Group, Kyoto 619-0288, Japan.|Department of Cognitive, Linguistic and Psychological Sciences, Brown University, Rhode Island 02912, USA.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Sasaki
authors.affiliation: Department of Decoded Neurofeedback, ATR Brain Information Communication Research Laboratory Group, Kyoto 619-0288, Japan.|Department of Cognitive, Linguistic and Psychological Sciences, Brown University, Rhode Island 02912, USA.
authors.forename: Takeo
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Department of Decoded Neurofeedback, ATR Brain Information Communication Research Laboratory Group, Kyoto 619-0288, Japan.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Kawato
mesh_terms: D000293:Adolescent; D000328:Adult; D000465:Algorithms; D000067877:Autism Spectrum Disorder / Q000175:diagnosis / Q000503:physiopathology*; D001921:Brain / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008959:Models, Neurological; D009415:Nerve Net / Q000503:physiopathology*; D009434:Neural Pathways / Q000503:physiopathology*; D011379:Prognosis; D055815:Young Adult