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Exploring cortical activation and connectivity in infants with and without familial risk for autism during naturalistic social interactions: A preliminary study.

ABSTRACT: Behavioral signs of Autism Spectrum Disorder (ASD) are typically observable by the second year of life and a reliable diagnosis of ASD is possible by 2 to 3 years of age. Studying infants with familial risk for ASD allows for the investigation of early signs of ASD risk within the first year. Brain abnormalities such as hyper-connectivity within the first year may precede the overt signs of ASD that emerge later in life. In this preliminary study, we use functional near-infrared spectroscopy (fNIRS), an infant-friendly neuroimaging tool that is relatively robust against motion artifacts, to examine functional activation and connectivity during naturalistic social interactions in 9 high-risk (HR; older sibling with ASD) and 6 low-risk (LR; no family history of ASD) infants from 6 to 9 months of age. We obtained two 30-second baseline periods and a 5-minute social interaction period. HR infants showed reduced right and left-hemispheric activation compared to LR infants based on oxy (HbO2) and deoxy (HHb) signal trends. HR infants also had greater functional connectivity than LR infants during the pre- and post-social periods and showed a drop in connectivity during the social period. Our findings are consistent with previous work suggesting early differences in cortical activation associated with familial risk for ASD, and highlight the promise of fNIRS in evaluating potential markers of ASD risk during naturalistic social contexts.

SUBMITTER: Bhat AN

PROVIDER: S-EPMC6875633 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Exploring cortical activation and connectivity in infants with and without familial risk for autism during naturalistic social interactions: A preliminary study.

Bhat A N AN McDonald N M NM Eilbott J E JE Pelphrey K A KA

Infant behavior & development 20190823

Behavioral signs of Autism Spectrum Disorder (ASD) are typically observable by the second year of life and a reliable diagnosis of ASD is possible by 2 to 3 years of age. Studying infants with familial risk for ASD allows for the investigation of early signs of ASD risk within the first year. Brain abnormalities such as hyper-connectivity within the first year may precede the overt signs of ASD that emerge later in life. In this preliminary study, we use functional near-infrared spectroscopy (fN ...[more]

PMID: 31450025

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Project description:ImportanceWhat 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.ObjectiveTo assess whether alternation of functional maturation of social brain circuits is associated with a family history of ASD in newborns.Design, setting, and participantsIn 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 measuresRegions 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.ResultsThe 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 relevanceSynchronous 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.

Project description:BackgroundDifferences in face processing in individuals with ASD is hypothesized to impact the development of social communication skills. This study aimed to characterize the neural correlates of face processing in 12-month-old infants at familial risk of developing ASD by (1) comparing face-sensitive event-related potentials (ERP) (Nc, N290, P400) between high-familial-risk infants who develop ASD (HR-ASD), high-familial-risk infants without ASD (HR-NoASD), and low-familial-risk infants (LR), and (2) evaluating how face-sensitive ERP components are associated with development of social communication skills.Methods12-month-old infants participated in a study in which they were presented with alternating images of their mother's face and the face of a stranger (LR = 45, HR-NoASD = 41, HR-ASD = 24) as EEG data were collected. Parent-reported and laboratory-observed social communication measures were obtained at 12 and 18 months. Group differences in ERP responses were evaluated using ANOVA, and multiple linear regressions were conducted with maternal education and outcome groups as covariates to assess relationships between ERP and behavioral measures.ResultsFor each of the ERP components (Nc [negative-central], N290, and P400), the amplitude difference between mother and stranger (Mother-Stranger) trials was not statistically different between the three outcome groups (Nc p = 0.72, N290 p = 0.88, P400 p = 0.91). Marginal effects analyses found that within the LR group, a greater Nc Mother-Stranger response was associated with better expressive language skills on the Mullen Scales of Early Learning, controlling for maternal education and outcome group effects (marginal effects dy/dx = 1.15; p < 0.01). No significant associations were observed between the Nc and language or social measures in HR-NoASD or HR-ASD groups. In contrast, specific to the HR-ASD group, amplitude difference between the Mother versus Stranger P400 response was positively associated with expressive (dy/dx = 2.1, p < 0.001) and receptive language skills at 12 months (dy/dx = 1.68, p < 0.005), and negatively associated with social affect scores on the Autism Diagnostic Observation Schedule (dy/dx = - 1.22, p < 0.001) at 18 months.ConclusionsIn 12-month-old infant siblings with subsequent ASD, increased P400 response to Mother over Stranger faces is positively associated with concurrent language and future social skills.

Dataset Information

Exploring cortical activation and connectivity in infants with and without familial risk for autism during naturalistic social interactions: A preliminary study.

Publications

Exploring cortical activation and connectivity in infants with and without familial risk for autism during naturalistic social interactions: A preliminary study.

Similar Datasets

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