Importance: What is inherited or acquired in neurodevelopmental conditions such as autism spectrum disorder (ASD) is not a fixed outcome, but instead is a vulnerability to a spectrum of traits, especially social difficulties. Identifying the biological mechanisms associated with vulnerability requires looking as early in life as possible, before the brain is shaped by postnatal mechanisms and/or the experiences of living with these traits. Animal studies suggest that susceptibility to neurodevelopmental disorders arises when genetic and/or environmental risks for these conditions alter patterns of synchronous brain activity in the perinatal period, but this has never been examined in human neonates.

Objective: To assess whether alternation of functional maturation of social brain circuits is associated with a family history of ASD in newborns.

Design, Setting, and Participants: In this cohort study of 36 neonates with and without a family history of ASD, neonates underwent magnetic resonance imaging at St Thomas Hospital in London, England, using a dedicated neonatal brain imaging system between June 23, 2015, and August 1, 2018. Neonates with a first-degree relative with ASD (R+) and therefore vulnerable to autistic traits and neonates without a family history (R-) were recruited for the study. Synchronous neural activity in brain regions linked to social function was compared.

Main Outcomes and Measures: Regions responsible for social function were selected with reference to a published meta-analysis and the level of synchronous activity within each region was used as a measure of local functional connectivity in a regional homogeneity analysis. Group differences, controlling for sex, age at birth, age at scan, and group × age interactions, were examined.

Results: The final data set consisted of 18 R+ infants (13 male; median [range] postmenstrual age at scan, 42.93 [40.00-44.86] weeks) and 18 R- infants (13 male; median [range] postmenstrual age at scan, 42.50 [39.29-44.58] weeks). Neonates who were R+ had significantly higher levels of synchronous activity in the right posterior fusiform (t = 2.48; P = .04) and left parietal cortices (t = 3.96; P = .04). In addition, there was a significant group × age interaction within the anterior segment of the left insula (t = 3.03; P = .04) and cingulate cortices (right anterior: t = 3.00; P = .03; left anterior: t = 2.81; P = .03; right posterior: t = 2.77; P = .03; left posterior: t = 2.55; P = .03). In R+ infants, levels of synchronous activity decreased over 39 to 45 weeks' postmenstrual age, whereas synchronous activity levels increased in R- infants over the same period.

Conclusions and Relevance: Synchronous activity is required during maturation of functionally connected networks. This study found that in newborn humans, having a first-degree relative with ASD was associated with higher levels of local functional connectivity and dysmaturation of interconnected regions responsible for processing higher-order social information.

Original languageEnglish
Article numbere191868
JournalJAMA Network open
Issue number4
Early online date5 Apr 2019
Publication statusPublished - Apr 2019


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