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Dimensional Analysis of Executive Dysfunction Comorbidity in ASD and ADHD
Objectives: We first applied a novel data-driven graph theory method, community detection, to identify relevant EF dimensions across ADHD, ASD, and control children, and then examined their neural basis using task-based functional magnetic resonance imaging (fMRI). Our fMRI tasks were designed with the premise that controlling attention in an adaptive and flexible manner subserves EF.
Methods: We included 114 7-14 year-old children matched for age and IQ (35 ASD, 20 ADHD, 59 controls) and collected parent-report of 10 measures, Inattention and Hyperactivity/Impulsivity from ADHD Rating scale and 8 subscales selected from the BRIEF (Inhibit, Shift, Emotion Control, Initiate, Working Memory, Plan/Organize, Organization of materials, Monitor). Community detection was applied using a weight-conserving modularity algorithm not dependent on threshold, yielding 3 communities: #1 defined by worse planning and organizing but relatively better cognitive flexibility and hyperactivity/impulsivity (21 ASD, 6 ADHD, 29 Controls); #2 defined by worse cognitive flexibility but relatively better planning/organizing and hyperactivity/impulsivity (12 ASD, 4 ADHD, 16 controls); and # 3 defined by worse hyperactivity/impulsivity but relatively better planning organizing and cognitive flexibility (2 ASD, 10 ADHD, 14 Controls). Imaging was performed at 3T during 2 runs of a shape-classification task with right-hand response, in which distracters were flashed in the periphery. Runs differed in task-context, the first being stimulus-driven as distractors were irrelevant to the task, and the second requiring top-down control as a distractor was designated as target requiring left-hand response. Activation difference between the first to second run reflected attentional modulation by task-context, termed adaptive flexibility. Images were slice-time and motion-corrected, normalized to EPI template and resliced to 3mm, smoothed with 8mm FWHM and using stringent motion-criteria retained 88 subjects (51 controls, 26 ASD and 16 ADHD). We identified regions reflecting adaptive flexibility by Run x Distractor interaction in whole-brain ANOVA in SPM 8 (p < .05 Monte Carlo corrected; p<.001, k=28 voxels). For each cluster ROI, hierarchical linear regression tested whether clusters accounted for more variance than DSM-based groups.
Results:
Significant Run x Distractor interaction was observed in visual attention regions, bilateral middle frontal gyrus, bilateral insula and putamen, bilateral SPL-TPJ and postcentral gyrus, dorsal ACC, SMA, precuneus, right MTG and left visual cortex and community-based grouping accounted for more variance in right TPJ (p=.04) and right MFG (p=.029) than DSM groups, with greatest flexibility-related activation for community #1, scoring best on measures of attention and flexibility and worse on planning/organizing.
Conclusions:
Our results suggest that executive dysfunction variability across ASD, ADHD and control children is better conceptualized by three distinct functional profiles associated with variability in frontal-parietal cortical engagement during flexible attentional control