Imaging the Connectome in Autism and ADHD: What' s Distinct and What's Shared?

Background:  Although Autism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD) were conceptualized as distinct disorders, their symptoms co-occur more often than expected by the prevalence of each alone. On one hand, this is consistent with recent models highlighting the dimensional nature of psychopathological domains across diagnostic categories. On the other hand, whether these co- occurring conditions stem from similar underlying biological mechanisms remains unknown. Recent advances suggest pediatric imaging is well positioned to address this question. In particular, several lines of evidence support the notion that both ASD and ADHD are neurodevelopmental connectopathies, i.e., disorders that stem from anomalies in the connections between brain regions, rather than from localized anomalies. Unfortunately, however, with a few exceptions, most brain imaging studies have examined individuals with ADHD and ASD separately.

Objectives:   To present our empirical work examining the extent to which abnormalities in the functional architecture of the connectome is shared between ASD and ADHD.

Methods:   Findings from resting-state fMRI studies of over 150 children with ASD, ADHD and typically developing controls (aged 7-13 years) stratified by symptom domains will be presented and integrated with the current literature.

Results:   Results from a full-brain exploration of the functional connectome using network centrality identified several loci of dysconnections; some appeared specific to ADHD or ASD, others were shared between these conditions. When we accounted for ADHD comorbidity in children with ASD, we identified ADHD-related network abnormalities beyond categorical diagnoses. Specifically, children with ADHD and those with ASD and comorbid ADHD showed increased degree centrality in cognitive and motor striatal regions relative to either ASD without ADHD comorbidity or TDC. Notably, the degree of abnormal connectivity was significantly related to dimensional measures of ADHD symptom severity. This initial study was not designed to also assess autistic traits in both children with ASD and ADHD. Accordingly, we examined functional connectivity between two ‘social brain’ nodes in an extended sample of children with ADHD and ASD. We found that reduced connectivity between the right fusiform face area and rostral anterior cingulate was reduced in children with ADHD presenting autistic traits similarly to those with ASD, regardless of ADHD comorbidity. 

Conclusions: This initial work illustrates the utility of eschewing extreme comparisons (i.e., only focusing on ASD vs. TDC) as it allows identifying potential biomarkers specific to and shared across psychiatric conditions. When this is combined with stratifying participants as a function of the degree of psychopathology, additional shared dysfunctions are identified. This suggests that hybrid models of psychopathology (categorical AND dimensional) should be considered for brain imaging analyses as well as for identification and treatment.