Multi-Site Classification of Autism Spectrum Disorder Using Spatially Constrained ICA on Resting-State fMRI Networks

Background/Objectives: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by differences in social communications and restricted, repetitive patterns of behaviors and interests, affecting approximately 1% of children globally. While functional magnetic resonance imaging (fMRI) has provided insights into altered brain connectivity patterns in ASD, classification based on neuroimaging remains a challenging due to the heterogeneity of the disorder and variability in imaging data across sites. This study employs a network-based approach using large-scale, multi-site rs-fMRI dataset from the Autism Brain Imaging Data Exchange (ABIDE I and II) to classify ASD and healthy controls using machine learning. Methods: A semi-blind Independent Component Analysis method, specifically the spatial constraint reference ICA, is applied to identify functional brain networks, and the ComBat harmonization technique is used to address site-specific variability across 11 independent datasets, ensuring consistency in feature representation. Support Vector Machines (SVMs) are employed for classification, focusing on three key networks: the Default Mode Network (DMN), Sensorimotor Network (SMN), and Visual Sensory Network (VSN). Results: The results demonstrate high classification accuracy, with the VSN achieving the highest performance (83.23% accuracy, 87.90% AUC), followed by the DMN (81.43% accuracy, 84.53% AUC) and the SMN (80.52% accuracy, 84.96% AUC), positioned with their recognized roles in social cognition and sensory–motor processing, respectively. Conclusions: The integration of ICA-based feature extraction with ComBat harmonization significantly improved classification accuracy compared to previous studies. These findings point out the potential of network-based approaches in ASD classification and point out the importance of integrating multi-site neuroimaging data for identifying reproduceable network-level features.