Exploring characteristic features of attention-deficit/hyperactivity disorder: findings from multi-modal MRI and candidate genetic data

Abstract

The current study examined whether machine learning features best distinguishing attention-deficit/hyperactivity disorder (ADHD) from typically developing children (TDC) can explain clinical phenotypes using multi-modal neuroimaging and genetic data. Cortical morphology, diffusivity scalars, resting-state functional connectivity and polygenic risk score (PS) from norepinephrine, dopamine and glutamate genes were extracted from 47 ADHD and 47 matched TDC. Using random forests, classification accuracy was measured for each uni- and multi-modal model. The optimal model was used to explain symptom severity or task performance and its robustness was validated in the independent dataset including 18 ADHD and 18 TDC. The model consisting of cortical thickness and volume features achieved the best accuracy of 85.1%. Morphological changes across insula, sensory/motor, and inferior frontal cortex were also found as key predictors. Those explained 18.0% of ADHD rating scale, while dynamic regional homogeneity within default network explained 6.4% of the omission errors in continuous performance test. Ensemble of PS to optimal model showed minor effect on accuracy. Validation analysis achieved accuracy of 69.4%. Current findings suggest that structural deformities relevant to salience detection, sensory processing, and response inhibition may be robust classifiers and symptom predictors of ADHD. Altered local functional connectivity across default network predicted attentional lapse. However, further investigation is needed to clarify roles of genetic predisposition.