Distinct Frontoparietal Brain Dynamics Underlying the Co-Occurrence of Autism and ADHD

Abstract

Previous diagnostic systems precluded the co-existence of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) in one person; but, after many clinical reports, such diagnostic criteria were updated to allow their co-occurrence. Despite such a clinical change, the neurobiological bases underpinning the comorbidity remain poorly understood, and whether the ASD+ADHD condition is a simple overlap of the two disorders is unknown. Here, to answer this question, we compared the brain dynamics of high-functioning ASD+ADHD children with age-/sex-/IQ-matched pure ASD, pure ADHD, and typically developing children. Regarding autistic traits, the socio-communicational symptom of the ASD+ADHD children was explained by the same over-stable brain dynamics as seen in pure ASD. In contrast, their ADHD-like traits were grounded on a unique neural mechanism that was unseen in pure ADHD: the core symptoms of pure ADHD were associated with the overly flexible whole-brain dynamics that were triggered by the unstable activity of the dorsal-attention network and the left parietal cortex; by contrast, the ADHD-like cognitive instability of the ASD+ADHD condition was correlated with the atypically frequent neural transition along a specific brain state pathway, which was induced by the atypically unstable activity of the frontoparietal control network and the left prefrontal cortex. These observations need to be validated in future studies using more direct and comprehensive behavioural indices, but the current findings suggest that the ASD+ADHD comorbidity is not a mere overlap of the two disorders. Particularly, its ADHD-like traits could represent a unique condition that would need a specific diagnosis and bespoke treatments.Significance statementChildren with autism spectrum disorder (ASD) have cognitive rigidity and tend to persist in specific thoughts, whereas those with ADHD exhibit overly flexible cognition and have trouble with concentration. Despite such contrast, clinically, the two neurodevelopmental disorders are often reported to co-exist in one person. How can such a co-occurrence happen? By investigating the global and local brain dynamics, this study found that the comorbidity of ASD and ADHD is not a simple overlap of the two conditions. Instead, the cognitive instability seen in ASD+ADHD children was underpinned by unique brain dynamics that were not observed in pure ADHD. These findings indicate that the comorbid condition would need a bespoke diagnosis and treatment.

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“…Recent neuroimaging studies have suggested differences between pure ADHD and comorbid ADHD and ASD [65] and these two groups may need distinct treatment [66]. Future studies investigating the behavioral phenotypes of PNE humans and animals will help us to establish a more efficient treatment for comorbid ADHD and ASD in PNE children.…”