Brain function distinguishes female carriers and non-carriers of familial risk for autism
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RESEARCH
Brain function distinguishes female carriers and non‑carriers of familial risk for autism Adam T. Eggebrecht1,5* , Ally Dworetsky2, Zoë Hawks3, Rebecca Coalson2, Babatunde Adeyemo2, Savannah Davis4, Daniel Gray4, Alana McMichael2, Steven E. Petersen2, John N. Constantino4† and John R. Pruett Jr4†
Abstract Background: Autism spectrum disorder (ASD) is characterized by high population-level heritability and a threeto-one male-to-female ratio that occurs independent of sex linkage. Prior research in a mixed-sex pediatric sample identified neural signatures of familial risk elicited by passive viewing of point light motion displays, suggesting the possibility that both resilience and risk of autism might be associated with brain responses to biological motion. To confirm a relationship between these signatures and inherited risk of autism, we tested them in families enriched for genetic loading through undiagnosed (“carrier”) females. Methods: Using functional magnetic resonance imaging, we examined brain responses to passive viewing of point light displays—depicting biological versus non-biological motion—in a sample of undiagnosed adult females enriched for inherited susceptibility to ASD on the basis of affectation in their respective family pedigrees. Brain responses in carrier females were compared to responses in age-, SRS-, and IQ-matched non-carrier-females—i.e., females unrelated to individuals with ASD. We conducted a hypothesis-driven analysis focused on previously published regions of interest as well as exploratory, brain-wide analyses designed to characterize more fully the rich responses to this paradigm. Results: We observed robust responses to biological motion. Notwithstanding, the 12 regions implicated by prior research did not exhibit the hypothesized interaction between group (carriers vs. controls) and point light displays (biological vs. non-biological motion). Exploratory, brain-wide analyses identified this interaction in three novel regions. Post hoc analyses additionally revealed significant variations in the time course of brain activation in 20 regions spanning occipital and temporal cortex, indicating group differences in response to point light displays (irrespective of the nature of motion) for exploration in future studies. Limitations: We were unable to successfully eye-track all participants, which prevented us from being able to control for potential differences in eye gaze position. Conclusions: These methods confirmed pronounced neural signatures that differentiate brain responses to biological and scrambled motion. Our sample of undiagnosed females enriched for family genetic loading enabled discovery of numerous contrasts between carriers and non-carriers of risk of ASD that may index variations in visual attention
*Correspondence: [email protected] † John N. Constantino and John R. Pruett, Jr contributed equally as senior authors 1 Mallinckrodt Institute of Radiology, Washington University School of Medicine, 660 S. Euclid Ave, St Louis, MO 63110,
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