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Attention-deficit/hyperactivity disorder (ADHD) is a developmental condition that often persists into adulthood with extensive negative consequences on quality of life. Despite emerging evidence indicating the genetic basis of ADHD, investigations into the familial expression of latent neurocognitive traits remain limited.
In a group of adult ADHD probands (n = 20), their unaffected first-degree relatives (n = 20) and typically developing control participants (n = 20), we assessed endophenotypic alterations in the default mode network (DMN) connectivity during resting-state functional magnetic resonance imaging in relation to cognitive performance and clinical symptoms. In an external validation step, we also examined the dimensional nature of this neurocognitive trait in a sample of unrelated healthy young adults (n = 100) from the Human Connectome Project (HCP).
The results illustrated reduced anti-correlations between the posterior cingulate cortex/precuneus and right middle frontal gyrus that was shared between adult ADHD probands and their first-degree relatives, but not with healthy controls. The observed connectivity alterations were linked to higher ADHD symptoms that was mediated by performance in a sustained attention task. Moreover, this brain-based neurocognitive trait dimensionally explained ADHD symptom variability in the HCP sample.
Alterations in the default mode connectivity may represent a dimensional endophenotype of ADHD, hence a significant aspect of the neuropathophysiology of this disorder. As such, brain network organisation can potentially be employed as an important neurocognitive trait to enhance statistical power of genetic studies in ADHD and as a surrogate efficacy endpoint in the development of novel pharmaceuticals.
Attention-deficit/hyperactivity disorder (ADHD) is a developmental condition that profoundly affects quality of life. Although mounting evidence now suggests uncontrolled mind-wandering as a core aspect of the attentional problems associated with ADHD, the neural mechanisms underpinning this deficit remains unclear. To that extent, competing views argue for (i) excessive generation of task-unrelated mental content, or (ii) deficiency in the control of task-relevant cognition.
In a cross-sectional investigation of a large neurotypical cohort (n = 184), we examined alterations in the intrinsic brain functional connectivity architecture of the default mode (DMN) and frontoparietal (FPN) networks during resting state functional magnetic resonance imaging in relation to ADHD symptomatology, which could potentially underlie changes in ongoing thought within variable environmental contexts.
The results illustrated that ADHD symptoms were linked to lower levels of detail in ongoing thought while the participants made more difficult, memory based decisions. Moreover, greater ADHD scores were associated with lower levels of connectivity between the DMN and right sensorimotor cortex, and between the FPN and right ventral visual cortex. Finally, a combination of high levels of ADHD symptomology with reduced FPN connectivity to the visual cortex was associated with reduced levels of detail in thought.
The results of our study suggest that the frequent mind-wandering observed in ADHD may be an indirect consequence of the deficient control of ongoing cognition in response to increasing environmental demands, and that this may partly arise from dysfunctions in the intrinsic organisation of the FPN at rest.
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