Altered cortico-striatal-thalamic connectivity in relation to spatial working memory capacity in children with ADHD

Abstract

Introduction: Attention deficit hyperactivity disorder (ADHD) captures a heterogeneou group of children, who are characterized by a range of cognitive and behavioral symp toms. Previous resting-state functional connectivity MRI (rs-fcMRI) studies have sough to understand the neural correlates of ADHD by comparing connectivity measurement 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 cor-related 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 develop ing 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 uti lize known thalamo-cortical loops and rs-fcMRI to identify functional boundaries in the thalamus. Results/Conclusion: Using these thalamic regions, we found atypical rs-fcMR between specific thalamic groupings with the basal ganglia. To identify the thalamic con nections 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 dor-sal 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. © 2012 Mills, Bathula, Dias, Iyer, Fenesy, Musser, Stevens, Thurlow, Carpenter, Nagel, Nigg and Fair.