Intrinsic Functional Connectivity in the Default Mode Network Differentiates the Combined and Inattentive Attention Deficit Hyperactivity Disorder Types

Abstract

Neuroimaging studies have revealed neurobiological differences in ADHD, particularly studies examining connectivity disruption and anatomical network organization. However, the underlying pathophysiology of ADHD types remains elusive as it is unclear whether dysfunctional network connections characterize the underlying clinical symptoms distinguishing ADHD types. Here, we investigated intrinsic functional network connectivity to identify neural signatures that differentiate the combined (ADHD-C) and inattentive (ADHD-I) presentation types. Applying network-based statistical (NBS) and graph theoretical analysis to task-derived intrinsic connectivity data from completed fMRI scans, we evaluated default mode network (DMN) and whole-brain functional network topology in a cohort of 34 ADHD participants (aged 8–17 years) defined using DSM-IV criteria as predominantly inattentive (ADHD-I) type (n = 15) or combined (ADHD-C) type (n = 19), and 39 age and gender-matched typically developing controls. ADHD-C were characterized from ADHD-I by reduced network connectivity differences within the DMN. Additionally, reduced connectivity within the DMN was negatively associated with ADHD-RS hyperactivity-impulsivity subscale score. Compared with controls, ADHD-C but not ADHD-I differed by reduced connectivity within the DMN; inter-network connectivity between the DMN and somatomotor networks; the DMN and limbic networks; and between the somatomotor and cingulo-frontoparietal, with ventral attention and dorsal attention networks. However, graph-theoretical measures did not significantly differ between groups. These findings provide insight into the intrinsic networks underlying phenotypic differences between ADHD types. Furthermore, these intrinsic functional connectomic signatures support neurobiological differences underlying clinical variations in ADHD presentations, specifically reduced within and between functional connectivity of the DMN in the ADHD-C type.

Cortical structural and functional coupling during development and implications for attention deficit hyperactivity disorder

“…Children with ADHD have been reported to have aberrant structural connectivity predominantly in fronto-striatal connections and other tracts connecting parietal, temporal, and left occipital regions [ 87 , 88 ]. Moreover, disruptions in functional connections have been demonstrated in the FPN, DMN, DAN, and visual network, and prior cross-sectional studies [ 76 , 80 , 89 – 91 ], and our recent longitudinal study has reported age-related differences in functional connections between various higher-order cognitive networks [ 35 ]. Previous studies demonstrating aberrant functional and structural connections in DMN, SAL, DAN, and visual network have suggested that this could be the reason for deficits in attention, impulsivity, and executive functions in children with ADHD [ 79 , 92 – 94 ].…”