Insula-Retrosplenial Cortex Overconnectivity Increases Internalizing via Reduced Insight in Autism

Jeremy Hogeveen, Marie K. Krug, Matthew V. Elliott, Marjorie Solomon Friedman

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Background: Internalizing symptoms like anxiety and depression are common and impairing in autism spectrum disorder (ASD). Here, we test the hypothesis that aberrant functional connectivity among three brain networks (salience network [SN], default mode network [DMN], and frontoparietal network [FPN]) plays a role in the pathophysiology of internalizing in ASD. Methods: We examined the association between resting-state functional connectivity and internalizing in 102 adolescents and young adults with ASD (n = 49) or typical development (n = 53). Seed-to-target functional connectivity was contrasted between adolescents and young adults with ASD and typically developing subjects using a recent parcellation of the human cerebral cortex, and connections that were aberrant in ASD were analyzed dimensionally as a function of parent-reported internalizing symptoms. Results: Three connections demonstrated robust overconnectivity in ASD: 1) the anterior insula to the retrosplenial cortex (i.e., SN-DMN), 2) the anterior insula to the frontal pole (i.e., SN-FPN), and 3) the dorsolateral prefrontal cortex to the retrosplenial cortex (i.e., FPN-DMN). These differences remained significant after controlling for age, and no age-related effects survived correction. The SN-DMN connection was associated with greater internalizing in ASD, mediated by a bigger difference between self- and parent-reported internalizing. Control analyses found that the other two connections were not associated with internalizing, and SN-DMN connectivity was not associated with a well-matched control measure (externalizing symptoms). Conclusions: The present findings provide novel evidence for a specific link between SN-DMN overconnectivity and internalizing in ASD. Further, the mediation results suggest that intact anterior insula-retrosplenial connectivity may play a role in an individual's generating insight into his or her own psychopathology.

Original languageEnglish (US)
JournalBiological Psychiatry
StateAccepted/In press - Jan 1 2018


  • Anterior insula
  • Anxiety
  • Autism spectrum disorder
  • Internalizing
  • Retrosplenial cortex
  • Salience network

ASJC Scopus subject areas

  • Biological Psychiatry


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