Regional brain network organization distinguishes the combined and inattentive subtypes of Attention Deficit Hyperactivity Disorder

Abstract

Attention Deficit Hyperactivity Disorder (ADHD) is characterized clinically by hyperactive/impulsive and/or inattentive symptoms which determine diagnostic subtypes as Predominantly Hyperactive-Impulsive (ADHD-HI), Predominantly Inattentive (ADHD-I), and Combined (ADHD-C). Neuroanatomically though we do not yet know if these clinical subtypes reflect distinct aberrations in underlying brain organization. We imaged 34 ADHD participants defined using DSM-IV criteria as ADHD-I (n = 16) or as ADHD-C (n = 18) and 28 matched typically developing controls, aged 8-17 years, using high-resolution T1 MRI. To quantify neuroanatomical organization we used graph theoretical analysis to assess properties of structural covariance between ADHD subtypes and controls (global network measures: path length, clustering coefficient, and regional network measures: nodal degree). As a context for interpreting network organization differences, we also quantified gray matter volume using voxel-based morphometry. Each ADHD subtype was distinguished by a different organizational profile of the degree to which specific regions were anatomically connected with other regions (i.e., in "nodal degree"). For ADHD-I (compared to both ADHD-C and controls) the nodal degree was higher in the hippocampus. ADHD-I also had a higher nodal degree in the supramarginal gyrus, calcarine sulcus, and superior occipital cortex compared to ADHD-C and in the amygdala compared to controls. By contrast, the nodal degree was higher in the cerebellum for ADHD-C compared to ADHD-I and in the anterior cingulate, middle frontal gyrus and putamen compared to controls. ADHD-C also had reduced nodal degree in the rolandic operculum and middle temporal pole compared to controls. These regional profiles were observed in the context of no differences in gray matter volume or global network organization. Our results suggest that the clinical distinction between the Inattentive and Combined subtypes of ADHD may also be reflected in distinct aberrations in underlying brain organization.

Keywords: ACC, anterior cingulate cortex; ADHD; ADHD, Attention Deficit Hyperactivity Disorder; ADHD-C, combined presentation; ADHD-HI, predominantly hyperactive-impulsive; ADHD-I, predominantly inattentive presentation; ADHD-RS-IV, Attention Deficit/Hyperactivity Disorder Rating Scale; CPRS-LV, Conners' Parent Rating Scale–Revised: Long Version; Combined type; DICA, Diagnostic Interview for Children and Adolescents; DMN, default mode network; DSM-V, Diagnostic Manual of Statistical Disorders fifth edition; GM, gray matter; Graph theory; MINI Kid, Mini International Neuropsychiatric Interview; MPH, methylphenidate; Predominantly inattentive type; Structural connectome; Volume; iSPOT-A, international study to predict optimized treatment in ADHD.

Fig. 1

T1 images were parcellated into 92 cortical and subcortical gray matter regions defined using the AAL atlas to create structural covariance networks in each group.

Fig. 2

Group Comparison of regional nodal degree between the Combined (ADHD-C) and Inattentive (ADHD-I) subtypes. Regions with significant group differences in regional degree for networks thresholded at a minimum density of full connectivity overlaid on the ICBM152 surface template. The ADHD-I type exhibited greater nodal degree in the Calcarine (left), Hippocampus (left), the Superior occipital (right), and the Supramarginal gyrus (right). The ADHD-C type exhibited greater nodal degree in the Cerebellum (left). The color bar represents log (1/P-value). Hot colors indicate regions with higher degree in ADHD-I compared with ADHD-C, while cold colors indicate regions with higher degree in ADHD-C compared with ADHD-I.