Inter-individual heterogeneity of functional brain networks in children with autism spectrum disorder

Abstract

Background Autism spectrum disorder (ASD) is a neurodevelopmental disorder with considerable clinical heterogeneity. This study aimed to explore the heterogeneity of ASD based on inter-individual heterogeneity of functional brain networks. Methods Resting-state functional magnetic resonance imaging data from the Autism Brain Imaging Data Exchange database were used in this study for 105 children with ASD and 102 demographically matched typical controls (TC) children. Functional connectivity (FC) networks were first obtained for ASD and TC groups, and inter-individual deviation of functional connectivity (IDFC) from the TC group was then calculated for each individual with ASD. A k-means clustering algorithm was used to obtain ASD subtypes based on IDFC patterns. The FC patterns were further compared between ASD subtypes and the TC group from the brain region, network, and whole-brain levels. The relationship between IDFC and the severity of clinical symptoms of ASD for ASD subtypes was also analyzed using a support vector regression model. Results Two ASD subtypes were identified based on the IDFC patterns. Compared with the TC group, the ASD subtype 1 group exhibited a hypoconnectivity pattern and the ASD subtype 2 group exhibited a hyperconnectivity pattern. IDFC for ASD subtype 1 and subtype 2 was found to predict the severity of social communication impairments and the severity of restricted and repetitive behaviors in ASD, respectively. Limitations Only male children were selected for this study, which limits the ability to study the effects of gender and development on ASD heterogeneity. Conclusions These results suggest the existence of subtypes with different FC patterns in ASD and provide insight into the complex pathophysiological mechanism of clinical manifestations of ASD.

Heterogeneity of dynamic synergetic configurations of salience network in children with autism spectrum disorder

“…The joint recurrence quantification technique was used to quantify the synergy of brain configuration dynamics in ASD, and then clustered for subtyping based on the quantization results. ASD subtypes with altered and heterogeneous FC patterns were reported in previous studies (Chen et al, 2019; Guo, Zhai, et al, 2022; Reardon et al, 2022). And previous studies have found that there are 2–4 subtypes of ASD, therefore we predict that ASD can be divided into 2–4 subtypes with heterogeneous and atypical synergy of SN, that is, ASD can be divided into subtypes with different patterns of functional interaction of SN (Guo, Zhai, et al, 2022; Hong et al, 2018; Hrdlicka et al, 2005).…”

“…In DSM V, the diagnostic criteria for ASD, Autistic Disorder, Asperger's Disorder, and Pervasive Developmental Disorder are unified as ASD, which shows that ASD cannot be simply divided into Autistic Disorder, Asperger's Disorder, or Pervasive Developmental Disorder (American Psychiatric Association, 2013). ASD has complex neural mechanisms, and the complex neural mechanisms are associated with heterogeneous symptoms so that the neurological subtypes of ASD need to be investigated from more perspectives (Guo, Zhai, et al, 2022; van Rentergem et al, 2021). The present study is consistent with the results of previous ASD subtype studies, where ASD could be classified into 2–4 subtypes (Guo, Zhai, et al, 2022; Hong et al, 2018; Hrdlicka et al, 2005).…”

“…ASD has complex neural mechanisms, and the complex neural mechanisms are associated with heterogeneous symptoms so that the neurological subtypes of ASD need to be investigated from more perspectives (Guo, Zhai, et al, 2022; van Rentergem et al, 2021). The present study is consistent with the results of previous ASD subtype studies, where ASD could be classified into 2–4 subtypes (Guo, Zhai, et al, 2022; Hong et al, 2018; Hrdlicka et al, 2005). For example, an individual neuroanatomy‐based ASD subtype study revealed three ASD subtypes with different patterns of neuroanatomical variability (Chen et al, 2019).…”

“…The high heterogeneity of ASD has hindered biomarker research, clinical diagnosis, and treatment. Previous neuroanatomical studies revealed that there are 2–4 ASD subtypes in ASD (Guo, Zhai, et al, 2022; Hong et al, 2018; Hrdlicka et al, 2005). Although future studies are required to replicate these identified subtypes, subtyping ASD studies remains to be an effective way to reveal the high heterogeneity that ASD exhibits at multiple levels (Guo, Zhai, et al, 2022; Hong et al, 2018; Hrdlicka et al, 2005).…”

Integrated analysis of endoplasmic reticulum stress regulators’ expression identifies distinct subtypes of autism spectrum disorder

“…Recently, based on the inter-individual deviation of functional connectivity (IDFC), Xiaonan Guo and colleagues found two ASD subtypes, each with a different level of social communication deficits and confined and repetitive behaviors ( 64 ). Ada J S Chan and his colleagues discovered that distinct genetic subtypes of ASD can enable the prediction of developmental outcomes ( 65 ).…”