title: Default Mode Hypoconnectivity Underlies a Sex-Related Autism Spectrum.
abstract: BACKGROUND
  Females and males differ significantly in the prevalence and presentation of autism spectrum conditions. One theory of this effect postulates that autistic traits lie on a sex-related continuum in the general population, and autism represents the extreme male end of this spectrum. This theory predicts that any feature of autism in males should 1) be present in autistic females, 2) differentiate between the sexes in the typical population, and 3) correlate with autistic traits. We tested these three predictions for default mode network (DMN) hypoconnectivity during the resting state, one of the most robustly found neurobiological differences in autism.
  
  
  METHODS
  We analyzed a primary dataset of adolescents (N= 121, 12-18 years of age) containing a relatively large number of females and a replication multisite dataset including children, adolescents, and adults (N= 980, 6-58 years of age). We quantified the average connectivity between DMN regions and tested for group differences and correlation with behavioral performance using robust regression.
  
  
  RESULTS
  We found significant differences in DMN intraconnectivity between female controls and females with autism (p =.001 in the primary dataset;p =.009 in the replication dataset), and between female controls and male controls (p =.036 in the primary dataset;p =.002 in the replication dataset). We also found a significant correlation between DMN intraconnectivity and performance on a mentalizing task (p =.001) in the primary dataset.
  
  
  CONCLUSIONS
  Collectively, these findings provide the first evidence for DMN hypoconnectivity as a behaviorally relevant neuroimaging phenotype of the sex-related spectrum of autistic traits, of which autism represents the extreme case.
authors.affiliation: Brain Mapping Unit, Department of Psychiatry; Hughes Hall.
authors.forename: Rolf J F
authors.initials: RJ
authors.lastname: Ypma
authors.affiliation: Brain Mapping Unit, Department of Psychiatry; Bournemouth University, Dorset.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Moseley
authors.affiliation: Autism Research Centre, Department of Psychiatry.
authors.forename: Rosemary J
authors.initials: RJ
authors.lastname: Holt
authors.affiliation: Brain Mapping Unit, Department of Psychiatry.
authors.forename: Naresh
authors.initials: N
authors.lastname: Rughooputh
authors.affiliation: Autism Research Centre, Department of Psychiatry.
authors.forename: Dorothea L
authors.initials: DL
authors.lastname: Floris
authors.affiliation: Autism Research Centre, Department of Psychiatry.
authors.forename: Lindsay R
authors.initials: LR
authors.lastname: Chura
authors.affiliation: Autism Research Centre, Department of Psychiatry.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Spencer
authors.affiliation: Autism Research Centre, Department of Psychiatry; CLASS Clinic, Cambridge.
authors.forename: Simon
authors.initials: S
authors.lastname: Baron-Cohen
authors.affiliation: Behavioural and Clinical Neuroscience Institute, Department of Experimental Psychology; Cambridgeshire and Peterborough Foundation Trust, Cambridge.
authors.forename: John
authors.initials: J
authors.lastname: Suckling
authors.affiliation: Brain Mapping Unit, Department of Psychiatry; Behavioural and Clinical Neuroscience Institute, Department of Experimental Psychology; Cambridgeshire and Peterborough Foundation Trust, Cambridge; ImmunoPsychiatry, Alternative Discovery & Development, GlaxoSmithKline, Stevenage, United Kingdom.
authors.forename: Edward T
authors.initials: ET
authors.lastname: Bullmore
authors.affiliation: Brain Mapping Unit, Department of Psychiatry; ; Churchill College, University of Cambridge, Cambridge; Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia.
authors.forename: Mikail
authors.initials: M
authors.lastname: Rubinov
keywords: Autism; Connectomics; Default mode network; Extreme male brain theory; Functional connectivity; Neuroimaging