Default Mode and Striatal Connectivity in Youth with Co-Occurring Autism Spectrum Disorder and ADHD

Background: It is currently estimated that ~70% of youth with autism spectrum disorders (ASD) have at least one co-occurring psychiatric condition, with Attention Deficit Hyperactivity Disorder (ADHD) being one of the most common (Leyfer et al., 2006; Simonoff et al., 2008). These two conditions share various behavioral symptoms including deficits in executive function and social communication, and atypical neural phenotypes have been observed in both ADHD and ASD within default mode network (DMN; Assaf et al., 2010; Lynch, 2013; Uddin, 2008) and corticostriatal networks (Bush et al., 2005; Cao et al., 2009; DiMartino et al., 2011); however, little is known about the shared and distinct neural connectivity patterns of individuals with ASD with co-occurring ADHD.

Objectives: This study aims to parse apart the neural heterogeneity within the DMN and striatal regions of individuals with ASD and co-occurring ADHD (ASD+ADHD) as compared to age-, IQ-, and gender-matched individuals with ASD without ADHD (ASD-), ADHD without ASD (ADHD-), and typically developing controls (TDC). Understanding the common and unique neural signatures across co-occurring psychiatric conditions in ASD may serve to inform diagnosis, as well as guide research by addressing heterogeneity within ASD samples.

Methods: Resting state functional magnetic resonance imaging (rs-fMRI) data from the ABIDE and ADHD-200 initiatives included 33 ASD-, 46 ADHD-, 29 ASD+ADHD and 51 TDC youths (ages 5-14; see Table 1). The present study used Group Iterative Multiple Model Estimation (GIMME), a causal search algorithm that can identify patterns in neural connectivity across individuals and groups. Specifically, the GIMME confirmatory subgrouping algorithm was employed using diagnostic subgroups (group cutoff: 0.65, subgroup cutoff: 0.5) to examine resting state connectivity patterns within the DMN and striatal regions (see Table 2). Participants with maximum head motion >2mm in any direction were excluded, and all volumes with framewise displacement >.3mm were removed.

Results: At the group level (i.e., significant for participants across all groups), there were several significant bilateral connections and connections between anatomically close regions; however, there were few group-level, long-range pathways linking anterior and posterior regions (see Figure 1). Indeed, subgroup-level analyses revealed differences between diagnostic subgroups in connections from parietal to frontal regions (see Figure 1). In addition, both ASD groups showed attenuated striatal connectivity compared to the TDC and ADHD- groups. Neither of the ADHD groups recruited the anterior medial prefrontal cortex. Furthermore, the ASD+ADHD group showed anterior to posterior connections most similar to the ASD- group, and both ASD groups omitted connections between the posterior cingulate cortex and restrosplenial cortex.

Conclusions: The psychiatric subgroups, primarily the ASD subgroups, showed relatively reduced between network (i.e., DMN, striatal) interaction compared to the TDC subgroup. These findings also provide evidence of both distinct and shared neural connectivity patterns across individuals with ASD, ADHD, and ASD+ADHD that may have implications for core symptoms of each disorder.

Table 1. Participant Demographics.

	ASD- (n=33)	ADHD- (n=46)	ASD+ADHD (n=29)	TDC (n=51)
FSIQ	105.48 (15.55)	109.85 (15.51)	110.00 (20.23)	105.48 (15.55)
Age	10.01 (2.78)	10.23 (1.89)	9.57 (2.10)	10.27 (2.60)
% Female	9.09%	21.74%	10.34%	17.65%