Social Brain Functional Maturation in Newborn Infants With and Without a Family History of Autism Spectrum Disorder
Authors: Judit Ciarrusta, Jonathan O'Muircheartaigh, Ralica Dimitrova, Dafnis Batalle, Lucilio Cordero-Grande, Anthony Price, Emer Hughes, Johannes Klaus Steinweg, Johanna Kangas, Emily Perry, Ayesha Javed, Vladimira Stoencheva, Ranjit Akolekar, Suresh Victor, Joseph Hajnal, Declan Murphy, David Edwards, Tomoki Arichi, Grainne McAlonan
Journal: JAMA Network Open (2019)

<h3>Importance</h3> 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. <h3>Objective</h3> To assess whether alternation of functional maturation of social brain circuits is associated with a family history of ASD in newborns. <h3>Design, Setting, and Participants</h3> 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. <h3>Main Outcomes and Measures</h3> 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. <h3>Results</h3> 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 (<i>t</i> = 2.48;<i>P</i> = .04) and left parietal cortices (<i>t</i> = 3.96;<i>P</i> = .04). In addition, there was a significant group × age interaction within the anterior segment of the left insula (<i>t</i> = 3.03;<i>P</i> = .04) and cingulate cortices (right anterior:<i>t</i> = 3.00;<i>P</i> = .03; left anterior:<i>t</i> = 2.81;<i>P</i> = .03; right posterior:<i>t</i> = 2.77;<i>P</i> = .03; left posterior:<i>t</i> = 2.55;<i>P</i> = .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. <h3>Conclusions and Relevance</h3> 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.