title: Distinct neural bases of disruptive behavior and autism symptom severity in boys with autism spectrum disorder.
abstract: BACKGROUND
  Disruptive behavior in autism spectrum disorder (ASD) is an important clinical problem, but its neural basis remains poorly understood. The current research aims to better understand the neural underpinnings of disruptive behavior in ASD, while addressing whether the neural basis is shared with or separable from that of core ASD symptoms.
  
  
  METHODS
  Participants consisted of 48 male children and adolescents: 31 ASD (7 had high disruptive behavior) and 17 typically developing (TD) controls, well-matched on sex, age, and IQ. For ASD participants, autism symptom severity, disruptive behavior, anxiety symptoms, and ADHD symptoms were measured. All participants were scanned while viewing biological motion (BIO) and scrambled motion (SCR). Two fMRI contrasts were analyzed: social perception (BIO > SCR) and Default Mode Network (DMN) deactivation (fixation > BIO). Age and IQ were included as covariates of no interest in all analyses.
  
  
  RESULTS
  First, the between-group analyses on BIO > SCR showed that ASD is characterized by hypoactivation in the social perception circuitry, and ASD with high or low disruptive behavior exhibited similar patterns of hypoactivation. Second, the between-group analyses on fixation > BIO showed that ASD with high disruptive behavior exhibited more restricted and less DMN deactivation, when compared to ASD with low disruptive behavior or TD. Third, the within-ASD analyses showed that (a) autism symptom severity (but not disruptive behavior) was uniquely associated with less activation in the social perception regions including the posterior superior temporal sulcus and inferior frontal gyrus; (b) disruptive behavior (but not autism symptom severity) was uniquely associated with less DMN deactivation in the medial prefrontal cortex (MPFC) and lateral parietal cortex; and (c) anxiety symptoms mediated the link between disruptive behavior and less DMN deactivation in both anterior cingulate cortex (ACC) and MPFC, while ADHD symptoms mediated the link primarily in ACC.
  
  
  CONCLUSIONS
  In boys with ASD, disruptive behavior has a neural basis in reduced DMN deactivation, which is distinct and separable from that of core ASD symptoms, with the latter characterized by hypoactivation in the social perception circuitry. These differential neurobiological markers may potentially serve as neural targets or predictors for interventions when treating disruptive behavior vs. core symptoms in ASD.
authors.affiliation: Autism and Neurodevelopmental Disorders Institute, The George Washington University and Children's National Health System, 2300 I St NW, Washington, DC 20052 USA ; Child Study Center, Yale University School of Medicine, New Haven, CT 06519 USA.
authors.forename: Y J Daniel
authors.initials: YJ
authors.lastname: Yang
authors.affiliation: Child Study Center, Yale University School of Medicine, New Haven, CT 06519 USA.
authors.forename: Denis G
authors.initials: DG
authors.lastname: Sukhodolsky
authors.affiliation: Child Study Center, Yale University School of Medicine, New Haven, CT 06519 USA ; Division of Psychology and Language Sciences, University College London, London, WC1H 0AP UK.
authors.forename: Jiedi
authors.initials: J
authors.lastname: Lei
authors.affiliation: Department of Radiology and Biomedical Research Imaging Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 USA.
authors.forename: Eran
authors.initials: E
authors.lastname: Dayan
authors.affiliation: Autism and Neurodevelopmental Disorders Institute, The George Washington University and Children's National Health System, 2300 I St NW, Washington, DC 20052 USA.
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Pelphrey
authors.affiliation: Child Study Center, Yale University School of Medicine, New Haven, CT 06519 USA.
authors.forename: Pamela
authors.initials: P
authors.lastname: Ventola
keywords: ADHD; Anxiety disorders; Autism spectrum disorder; Comorbidity; Default mode network; Disruptive behavior; Neuroimaging; Oppositional defiant disorder; Social perception