Abstract
Introduction: Attention deficit hyperactivity disorder (ADHD) captures a heterogeneous group of children, who are characterized by a range of cognitive and behavioral symptoms. Previous resting-state functional connectivity MRI (rs-fcMRI) studies have sought to understand the neural correlates of ADHD by comparing connectivity measurements between those with and without the disorder, focusing primarily on cortical–striatal circuits mediated by the thalamus. To integrate the multiple phenotypic features associated with ADHD and help resolve its heterogeneity, it is helpful to determine how specific circuits relate to unique cognitive domains of the ADHD syndrome. Spatial working memory has been proposed as a key mechanism in the pathophysiology of ADHD. Methods: We correlated the rs-fcMRI of five thalamic regions of interest (ROIs) with spatial span working memory scores in a sample of 67 children aged 7–11 years [ADHD and typically developing children (TDC)]. In an independent dataset, we then examined group differences in thalamo-striatal functional connectivity between 70 ADHD and 89 TDC (7–11 years) from the ADHD-200 dataset. Thalamic ROIs were created based on previous methods that utilize known thalamo-cortical loops and rs-fcMRI to identify functional boundaries in the thalamus. Results/Conclusion: Using these thalamic regions, we found atypical rs-fcMRI between specific thalamic groupings with the basal ganglia. To identify the thalamic connections that relate to spatial working memory in ADHD, only connections identified in both the correlational and comparative analyses were considered. Multiple connections between the thalamus and basal ganglia, particularly between medial and anterior dorsal thalamus and the putamen, were related to spatial working memory and also altered in ADHD. These thalamo-striatal disruptions may be one of multiple atypical neural and cognitive mechanisms that relate to the ADHD clinical phenotype.
Highlights
Attention deficit hyperactivity disorder (ADHD) captures a heterogeneous group of children, who are characterized by a range of cognitive and behavioral symptoms
Drawing on subcortical–cortical models of attention deficit hyperactivity disorder (ADHD) (Nigg and Casey, 2005), we examined the functional connectivity between five thalamic regions of interest (ROI) and the basal ganglia
In a separate comparative analysis, we found that these same connections between the prefrontal thalamic ROI and putamen were atypical in children with ADHD-C
Summary
Attention deficit hyperactivity disorder (ADHD) captures a heterogeneous group of children, who are characterized by a range of cognitive and behavioral symptoms. Multiple connections between the thalamus and basal ganglia, between medial and anterior dorsal thalamus and the putamen, were related to spatial working memory and altered in ADHD These thalamo-striatal disruptions may be one of multiple atypical neural and cognitive mechanisms that relate to the ADHD clinical phenotype. One would apply a dimensional method in the same or, preferably, an independent sample to identify how atypical circuits relate to cognitive domains, even if they are not atypical in all participants with the disorder (Insel et al, 2010) This approach would extend our understanding of how differences in brain connectivity observed in children with ADHD relate to specific observed deficits in cognition and behavior, and potentially set the stage for refined diagnostics or refined phenotyping/subtyping based on brain physiology (Insel et al, 2010)
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