title: Insistence on sameness relates to increased covariance of gray matter structure in autism spectrum disorder.
abstract: BACKGROUND
  Autism spectrum disorder (ASD) is characterized by atypical development of cortical and subcortical gray matter volume. Subcortical structural changes have been associated with restricted and repetitive behavior (RRB), a core component of ASD. Behavioral studies have identified insistence on sameness (IS) as a separable RRB dimension prominent in high-functioning ASD, though no simple brain-behavior relationship has emerged. Structural covariance, a measure of morphological coupling among brain regions using magnetic resonance imaging (MRI), has proven an informative measure of anatomical relationships in typical development and neurodevelopmental disorders. In this study, we use this measure to characterize the relationship between brain structure and IS.
  
  
  METHODS
  We quantified the structural covariance of cortical and subcortical gray matter volume in 55 individuals with high-functioning ASD using 3T MRI. We then related these structural metrics to individual IS scores, as assessed by the Repetitive Behavior Scale-Revised (RBS-R).
  
  
  RESULTS
  We found that increased coupling among subcortical regions and between subcortical and cortical regions related to greater IS symptom severity. Most pronounced, the striatum and amygdala participated in a plurality of identified relationships, indicating a central role for these structures in IS symptomatology. These structural associations were specific to IS and did not relate to any of the other RRB subcomponents measured by the RBS-R.
  
  
  CONCLUSIONS
  This study indicates that behavioral dimensions in ASD can relate to the coordination of development across multiple brain regions, which might be otherwise obscured using typical brain-behavior correlations. It also expands the structures traditionally related to RRB in ASD and provides neuroanatomical evidence supportive of IS as a separate RRB dimension.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01031407.
authors.affiliation: Laboratory of Brain and Cognition, National Institute of Mental Health, Bethesda, MD USA.
authors.forename: Ian W
authors.initials: IW
authors.lastname: Eisenberg
authors.affiliation: Laboratory of Brain and Cognition, National Institute of Mental Health, Bethesda, MD USA ; Department of Speech and Hearing Sciences, The George Washington University, Washington, DC USA.
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Wallace
authors.affiliation: Center for Autism Spectrum Disorders, Children's National Medical Center, Rockville, MD USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Kenworthy
authors.affiliation: Laboratory of Brain and Cognition, National Institute of Mental Health, Bethesda, MD USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Gotts
authors.affiliation: Laboratory of Brain and Cognition, National Institute of Mental Health, Bethesda, MD USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Martin
keywords: Autism; Insistence on sameness; MRI; Repetitive behavior; Structural covariance; Subcortex