Amanda Elton1, Adriana Di Martino2, Heather Cody Hazlett3, Wei Gao4. 1. Biomedical Research Imaging Center (AE), University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. 2. Phyllis Green and Randolph Cowen Institute for Pediatric Neuroscience at the Child Study Center (ADM), New York University Langone Medical Center, New York, New York. 3. Department of Psychiatry and Carolina Institute for Developmental Disabilities (HCH), University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. 4. Department of Radiology and Biomedical Research Imaging Center (WG), University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Biomedical Imaging Research Institute (WG), Department of Biomedical Sciences and Imaging, Cedars-Sinai Medical Center, Los Angeles, California. Electronic address: Wei.Gao@csmc.edu.
Abstract
BACKGROUND: Autism spectrum disorder (ASD) encompasses a complex manifestation of symptoms that include deficits in social interaction and repetitive or stereotyped interests and behaviors. In keeping with the increasing recognition of the dimensional characteristics of ASD symptoms and the categorical nature of a diagnosis, we sought to delineate the neural mechanisms of ASD symptoms based on the functional connectivity of four known neural networks (i.e., default mode network, dorsal attention network, salience network, and executive control network). METHODS: We leveraged an open data resource (Autism Brain Imaging Data Exchange) providing resting-state functional magnetic resonance imaging data sets from 90 boys with ASD and 95 typically developing boys. This data set also included the Social Responsiveness Scale as a dimensional measure of ASD traits. Seed-based functional connectivity was paired with linear regression to identify functional connectivity abnormalities associated with categorical effects of ASD diagnosis, dimensional effects of ASD-like behaviors, and their interaction. RESULTS: Our results revealed the existence of dimensional mechanisms of ASD uniquely affecting each network based on the presence of connectivity-behavioral relationships; these were independent of diagnostic category. However, we also found evidence of categorical differences (i.e., diagnostic group differences) in connectivity strength for each network as well as categorical differences in connectivity-behavioral relationships (i.e., diagnosis-by-behavior interactions), supporting the coexistence of categorical mechanisms of ASD. CONCLUSIONS: Our findings support a hybrid model for ASD characterization that includes a combination of categorical and dimensional brain mechanisms and provide a novel understanding of the neural underpinnings of ASD.
BACKGROUND:Autism spectrum disorder (ASD) encompasses a complex manifestation of symptoms that include deficits in social interaction and repetitive or stereotyped interests and behaviors. In keeping with the increasing recognition of the dimensional characteristics of ASD symptoms and the categorical nature of a diagnosis, we sought to delineate the neural mechanisms of ASD symptoms based on the functional connectivity of four known neural networks (i.e., default mode network, dorsal attention network, salience network, and executive control network). METHODS: We leveraged an open data resource (Autism Brain Imaging Data Exchange) providing resting-state functional magnetic resonance imaging data sets from 90 boys with ASD and 95 typically developing boys. This data set also included the Social Responsiveness Scale as a dimensional measure of ASD traits. Seed-based functional connectivity was paired with linear regression to identify functional connectivity abnormalities associated with categorical effects of ASD diagnosis, dimensional effects of ASD-like behaviors, and their interaction. RESULTS: Our results revealed the existence of dimensional mechanisms of ASD uniquely affecting each network based on the presence of connectivity-behavioral relationships; these were independent of diagnostic category. However, we also found evidence of categorical differences (i.e., diagnostic group differences) in connectivity strength for each network as well as categorical differences in connectivity-behavioral relationships (i.e., diagnosis-by-behavior interactions), supporting the coexistence of categorical mechanisms of ASD. CONCLUSIONS: Our findings support a hybrid model for ASD characterization that includes a combination of categorical and dimensional brain mechanisms and provide a novel understanding of the neural underpinnings of ASD.
Authors: Marcel Adam Just; Vladimir L Cherkassky; Timothy A Keller; Rajesh K Kana; Nancy J Minshew Journal: Cereb Cortex Date: 2006-06-13 Impact factor: 5.357
Authors: Adriana Di Martino; Zarrar Shehzad; Clare Kelly; Amy Krain Roy; Dylan G Gee; Lucina Q Uddin; Kristin Gotimer; Donald F Klein; F Xavier Castellanos; Michael P Milham Journal: Am J Psychiatry Date: 2009-07-15 Impact factor: 18.112
Authors: John N Constantino; Christian P Gruber; Sandra Davis; Stephanie Hayes; Natalie Passanante; Thomas Przybeck Journal: J Child Psychol Psychiatry Date: 2004-05 Impact factor: 8.982
Authors: Mark Jenkinson; Christian F Beckmann; Timothy E J Behrens; Mark W Woolrich; Stephen M Smith Journal: Neuroimage Date: 2011-09-16 Impact factor: 6.556
Authors: Rogier B Mars; Franz-Xaver Neubert; Maryann P Noonan; Jerome Sallet; Ivan Toni; Matthew F S Rushworth Journal: Front Hum Neurosci Date: 2012-06-21 Impact factor: 3.169
Authors: A Di Martino; C-G Yan; Q Li; E Denio; F X Castellanos; K Alaerts; J S Anderson; M Assaf; S Y Bookheimer; M Dapretto; B Deen; S Delmonte; I Dinstein; B Ertl-Wagner; D A Fair; L Gallagher; D P Kennedy; C L Keown; C Keysers; J E Lainhart; C Lord; B Luna; V Menon; N J Minshew; C S Monk; S Mueller; R-A Müller; M B Nebel; J T Nigg; K O'Hearn; K A Pelphrey; S J Peltier; J D Rudie; S Sunaert; M Thioux; J M Tyszka; L Q Uddin; J S Verhoeven; N Wenderoth; J L Wiggins; S H Mostofsky; M P Milham Journal: Mol Psychiatry Date: 2013-06-18 Impact factor: 15.992
Authors: Benjamin E Yerys; Birkan Tunç; Theodore D Satterthwaite; Ligia Antezana; Maya G Mosner; Jennifer R Bertollo; Lisa Guy; Robert T Schultz; John D Herrington Journal: Biol Psychiatry Cogn Neurosci Neuroimaging Date: 2019-01-09
Authors: Dina R Dajani; Catherine A Burrows; Mary Beth Nebel; Stewart H Mostofsky; Kathleen M Gates; Lucina Q Uddin Journal: Brain Connect Date: 2019-11
Authors: Yuta Aoki; Yuliya N Yoncheva; Bosi Chen; Tanmay Nath; Dillon Sharp; Mariana Lazar; Pablo Velasco; Michael P Milham; Adriana Di Martino Journal: JAMA Psychiatry Date: 2017-11-01 Impact factor: 21.596
Authors: Sanam J Lalani; Tyler C Duffield; Haley G Trontel; Erin D Bigler; Tracy J Abildskov; Alyson Froehlich; Molly B D Prigge; Brittany G Travers; Jeffrey S Anderson; Brandon A Zielinski; Andrew Alexander; Nicholas Lange; Janet E Lainhart Journal: J Clin Exp Neuropsychol Date: 2017-10-26 Impact factor: 2.475