Social Brain Functional Maturation in Newborn Infants With and Without a Family History of Autism Spectrum Disorder

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

doi:10.1001/jamanetworkopen.2019.1868

Social Brain Functional Maturation in Newborn Infants With and Without a Family History of Autism Spectrum Disorder

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

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Abstract

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 language	English
Article number	e191868
Journal	JAMA Network open
Volume	2
Issue number	4
Early online date	5 Apr 2019
DOIs	https://doi.org/10.1001/jamanetworkopen.2019.1868
Publication status	Published - Apr 2019

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Social Brain Functional Maturation_CIARRUSTA_Accepted10February2019_GOLD VoRFinal published version, 1.74 MBLicence: CC BY

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Ciarrusta, J., O'Muircheartaigh, J., Dimitrova, R., Batalle, D., Cordero-Grande, L., Price, A., Hughes, E., Steinweg, J. K., Kangas, J., Perry, E., Javed, A., Stoencheva, V., Akolekar, R., Victor, S., Hajnal, J., Murphy, D., Edwards, D., Arichi, T., & McAlonan, G. (2019). Social Brain Functional Maturation in Newborn Infants With and Without a Family History of Autism Spectrum Disorder. JAMA Network open, 2(4), Article e191868. https://doi.org/10.1001/jamanetworkopen.2019.1868

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title = "Social Brain Functional Maturation in Newborn Infants With and Without a Family History of Autism Spectrum Disorder",

abstract = "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.",

author = "Judit Ciarrusta and Jonathan O'Muircheartaigh and Ralica Dimitrova and Dafnis Batalle and Lucilio Cordero-Grande and Anthony Price and Emer Hughes and Steinweg, {Johannes Klaus} and Johanna Kangas and Emily Perry and Ayesha Javed and Vladimira Stoencheva and Ranjit Akolekar and Suresh Victor and Joseph Hajnal and Declan Murphy and David Edwards and Tomoki Arichi and Grainne McAlonan",

year = "2019",

month = apr,

doi = "10.1001/jamanetworkopen.2019.1868",

language = "English",

volume = "2",

journal = "JAMA Network open",

issn = "2574-3805",

publisher = "American Medical Association",

number = "4",

}

Ciarrusta, J , O'Muircheartaigh, J , Dimitrova, R , Batalle, D , Cordero-Grande, L , Price, A, Hughes, E, Steinweg, JK, Kangas, J, Perry, E , Javed, A , Stoencheva, V, Akolekar, R, Victor, S , Hajnal, J , Murphy, D , Edwards, D , Arichi, T & McAlonan, G 2019, 'Social Brain Functional Maturation in Newborn Infants With and Without a Family History of Autism Spectrum Disorder', JAMA Network open, vol. 2, no. 4, e191868. https://doi.org/10.1001/jamanetworkopen.2019.1868

TY - JOUR

T1 - Social Brain Functional Maturation in Newborn Infants With and Without a Family History of Autism Spectrum Disorder

AU - Ciarrusta, Judit

AU - O'Muircheartaigh, Jonathan

AU - Dimitrova, Ralica

AU - Batalle, Dafnis

AU - Cordero-Grande, Lucilio

AU - Price, Anthony

AU - Hughes, Emer

AU - Steinweg, Johannes Klaus

AU - Kangas, Johanna

AU - Perry, Emily

AU - Javed, Ayesha

AU - Stoencheva, Vladimira

AU - Akolekar, Ranjit

AU - Victor, Suresh

AU - Hajnal, Joseph

AU - Murphy, Declan

AU - Edwards, David

AU - Arichi, Tomoki

AU - McAlonan, Grainne

PY - 2019/4

Y1 - 2019/4

N2 - 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.

AB - 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.

U2 - 10.1001/jamanetworkopen.2019.1868

DO - 10.1001/jamanetworkopen.2019.1868

M3 - Article

C2 - 30951164

SN - 2574-3805

VL - 2

JO - JAMA Network open

JF - JAMA Network open

IS - 4

M1 - e191868

ER -

Social Brain Functional Maturation in Newborn Infants With and Without a Family History of Autism Spectrum Disorder

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