Protocol for the development of joint attention-based subclassification of autism spectrum disorder and validation using multi-modal data.

Background: Heterogeneity in clinical manifestation and underlying neuro-biological mechanisms are major obstacles to providing personalized interventions for individuals with autism spectrum disorder (ASD). Despite various efforts to unify disparate data modalities and machine learning techniques for subclassification, replicable ASD clusters remain elusive. Our study aims to introduce a novel method, utilizing the objective behavioral biomarker of gaze patterns during joint attention, to subclassify ASD. We will assess whether behavior-based subgrouping yields clinically, genetically, and neurologically distinct ASD groups.

Methods: We propose a study involving 60 individuals with ASD recruited from a specialized psychiatric clinic to perform joint attention tasks. Through the examination of gaze patterns in social contexts, we will conduct a semi-supervised clustering analysis, yielding two primary clusters: good gaze response group and poor gaze response group. Subsequent comparison will occur across these clusters, scrutinizing neuroanatomical structure and connectivity using structural as well as functional brain imaging studies, genetic predisposition through single nucleotide polymorphism data, and assorted socio-demographic and clinical information.

Conclusions: The aim of the study is to investigate the discriminative properties and the validity of the joint attention-based subclassification of ASD using multi-modality data.

Trial Registration: Clinical trial, KCT0008530, Registered 16 June 2023, https://cris.nih.go.kr/cris/index/index.do .