Atypical brain network development of infants at elevated likelihood for autism spectrum disorder during the first year of life

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by behavioral features that appear early in life. Although studies have shown that atypical brain functional and structural connectivity are associated with these behavioral traits, the occurrence and initial alterations of brain networks have not been fully investigated. The current study aimed to map early brain network efficiency and information transferring in infants at elevated likelihood (EL) compared to infants at typical likelihood (TL) for ASD in the first year of life. This study used a resting-state functional near-infrared spectroscopy (fNIRS) approach to obtain the length and strength of functional connections in the frontal and temporal areas in 45 5-month-old and 38 10-month-old infants. Modular organization and smallworld properties were detected in both EL and TL infants at 5 and 10 months. In 5-month-old EL infants, local and nodal efficiency were significantly greater than age-matched TL infants, indicating overgrown local connections. Furthermore, we used a support vector machine (SVM) model to classify infants with or without EL based on the obtained global properties of the network, achieving an accuracy of 77.6%. These results suggest that infants with EL for ASD exhibit inefficiencies in the organization of brain networks during the first year of life. Lay SummaryThe brain networks of 5-and 10-month-old infants are able to support efficient communication of information in the brain. Neural networks of 5-month-old with an elevated likelihood (EL) for autism spectrum disorder (ASD) show an overgrowth in local functional connection, which may not support efficient communication between distant brain regions, while we found no such differences in 10-month-old infants with or without EL for ASD.

The use of functional near-infrared spectroscopy in tracking neurodevelopmental trajectories in infants and children with or without developmental disorders: a systematic review

“…Most studies only included Typically Developing (TD) infants/children/adults (n = 71), 6 studies included preterm infants, 4 studies included infants at risk for (n = 2) or children with ASD (n = 2), 2 studies included children with ADHD, and 1 study included children with Dyslexia ( Figure 2C ). Specifically, infants were classified as high-risk ASD if they had siblings with ASD diagnoses ( 19 , 20 ). Among the 2 studies that centered on children with ASD, diagnostic confirmation involved medical records and assessment tools such as Autism Diagnostic Observation Schedule (ADOS) and Childhood Autism Rating Scale (CARS), without specific reference to comorbidities ( 21 , 22 ).…”

“…For example, Watanabe et al found similar developmental changes in hPod (in-phase to anti-phase) in preterm and full-term infants during the first 2 months of age, but the development in early preterm infants preceded that of late preterm and full-term infants and progressed at a slower pace ( 39 ). In infants with an elevated risk for developing ASD (e.g., those with a family history of ASD), there tended to be an initial outgrowth followed by a later decrease in functional connectivity compared to their neurotypical peers ( 19 , 20 ). Specifically, Keehn et al found greater intrinsic (i.e., cortical connectivity when task-related signal fluctuations were removed) and co-activation connectivity (i.e., cortical connectivity when task-related activation was not removed) at 3 months but decreased connectivity at 12 months in high-risk compared to low-risk infants ( 19 ), while Zhang et al found greater frontal and temporal connectivity in high-risk than low-risk infants at 5 months but not at 10 months ( 20 ).…”

“…In infants with an elevated risk for developing ASD (e.g., those with a family history of ASD), there tended to be an initial outgrowth followed by a later decrease in functional connectivity compared to their neurotypical peers ( 19 , 20 ). Specifically, Keehn et al found greater intrinsic (i.e., cortical connectivity when task-related signal fluctuations were removed) and co-activation connectivity (i.e., cortical connectivity when task-related activation was not removed) at 3 months but decreased connectivity at 12 months in high-risk compared to low-risk infants ( 19 ), while Zhang et al found greater frontal and temporal connectivity in high-risk than low-risk infants at 5 months but not at 10 months ( 20 ). During childhood, children with ASD showed a U-shaped developmental trajectory of connectivity over the left middle frontal gyrus and age-related decreases in nodal metrics over the right temporoparietal junction, which is opposed to their TD peers ( 21 ).…”

“…Compared to typically developing children, children with developmental disorders, such as ASD ( 19–22 ), ADHD ( 23 , 24 ), and Dyslexia ( 25 ), demonstrate atypical neurodevelopmental trajectories during resting-state and when performing executive functioning tasks. Studies using fNIRS indicate that children with ASD show an initial outgrowth followed by a later decrease in resting-state functional connectivity ( 19 , 20 ). For example, infants who had an elevated risk for developing ASD demonstrated greater functional connectivity at 3 months but lower connectivity at 12 months compared to their typically developing peers ( 19 ).…”

Annual Research Review: Early intervention viewed through the lens of developmental neuroscience

“…A growing body of research is investigating functional connectivity patterns in children at early intervention age. Three themes emerge from this work: (a) in both infants at elevated and low likelihood for autism, functional connectivity patterns change over the first years of life (Ciarrusta et al., 2019; Gabard‐Durnam, Tierney, Vogel‐Farley, Tager‐Flusberg, & Nelson, 2015; Keehn, Müller, & Townsend, 2013; Liu, Xu, Li, Yu, & Yu, 2020; Rolison, Lacadie, Chawarska, Spann, & Scheinost, 2022; Zhang, Moerman, Niu, Warreyn, & Roeyers, 2022), (b) early patterns of functional connectivity, including those observed between 3 and 6 months of age, can predict autism symptomology in toddlerhood (Bhat et al., 2019; Dickinson et al., 2021; Emerson et al., 2017; Lewis et al., 2017; Tran et al., 2021), (c) experience influences connectivity such that, by 24 months, connections underlying gross motor and social communication behaviors increase and become more widely distributed than 1 year prior (Eggebrecht et al., 2017; Marrus et al., 2018). These often replicated findings point to early differences in connectivity between regions studied in attention, particularly shifting or re‐focusing attention, for example, left insula (Varjačić et al., 2018), cingulate cortices (Ng, Noblejas, Rodefer, Smith, & Poremba, 2007), right temporo‐parietal (Krall et al., 2015), facial and emotional processing, for example, posterior fusiform (Weiner & Zilles, 2016), left insula (Quarto et al., 2016), cingulate cortices (Hornak et al., 2003), and motor preparation or visually guided movements, for example, left parietal cortices (Rushworth, Walton, Kennerley, & Bannerman, 2004) and extrastriate cortices.…”