Nonparametric Motion Control in Functional Connectivity Studies in Children with Autism Spectrum Disorder

TL;DR

This paper introduces MoCo, a nonparametric estimator that improves the analysis of functional connectivity in children with ASD by effectively controlling for motion artifacts without excluding participants.

Contribution

The study presents a novel nonparametric motion control method, MoCo, that leverages machine learning to reduce bias and improve data utilization in ASD neuroimaging studies.

Findings

MoCo reduces motion artifacts more effectively than standard participant removal.

MoCo utilizes all participants, increasing data efficiency.

The estimator is shown to be large-sample efficient and robust.

Abstract

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition associated with difficulties with social interactions, communication, and restricted or repetitive behaviors. To characterize ASD, investigators often use functional connectivity derived from resting-state functional magnetic resonance imaging of the brain. However, participants' head motion during the scanning session can induce motion artifacts. Many studies remove participants with excessive motion, and then estimate the effect of diagnosis on functional connectivity using linear regression. However, participant exclusions and linearity assumptions can cause biases. We propose an estimand that quantifies the difference in average functional connectivity in autistic and non-ASD children while standardizing motion relative to the low motion distribution in scans that pass motion quality control. We introduce a nonparametric estimator for motion control, called MoCo, that uses all participants and flexibly models the impacts of motion and other relevant features using an ensemble of machine learning methods. We establish large-sample efficiency and multiple robustness of our proposed estimator. The framework is applied to estimate the difference in functional connectivity between 132 autistic and 245 non-ASD children, of which 34 and 126 pass motion quality control, respectively. MoCo appears to dramatically reduce motion artifacts compared to a standard approach with no participant removal, while more efficiently utilizing participant data and accounting for possible selection biases compared to participant removal.