An independent components and functional connectivity analysis of resting state fMRI data points to neural network dysregulation in adult ADHD

Abstract

Spontaneous fluctuations can be measured in the brain that reflect dissociable functional networks oscillating at synchronized frequencies, such as the default mode network (DMN). In contrast to its diametrically opposed task-positive counterpart, the DMN predominantly signals during a state of rest, and inappropriate regulation of this network has been associated with inattention, a core characteristic of attention-deficit/hyperactivity disorder (ADHD). To examine whether abnormalities can be identified in the DMN component of patients with ADHD, we applied an independent components analysis to resting state functional magnetic resonance imaging data acquired from 22 male medication-naïve adults with ADHD and 23 neurotypical individuals. We observed a stronger coherence of the left dorsolateral prefrontal cortex (dlPFC) with the DMN component in patients with ADHD which correlated with measures of selective attention. The increased left dlPFC-DMN coherence also surfaced in a whole-brain replication analysis involving an independent sample of 9 medication-naïve adult patients and 9 controls. In addition, a post hoc seed-to-voxel functional connectivity analysis using the dlPFC as a seed region to further examine this region's suggested connectivity differences uncovered a higher temporal coherence with various other neural networks and confirmed a reduced anticorrelation with the DMN. These results point to a more diffuse connectivity between functional networks in patients with ADHD. Moreover, our findings suggest that state-inappropriate neural activity in ADHD is not confined to DMN intrusion during attention-demanding contexts, but also surfaces as an insufficient suppression of dlPFC signaling in relation to DMN activity during rest. Together with previous findings, these results point to a general dysfunction in the orthogonality of functional networks.

Altered temporal features of intrinsic connectivity networks in boys with combined type of attention deficit hyperactivity disorder

“…Specially, the significant correlations between fDMN and performance IQ might reflect the dysfunction of facial and emotional recognition in ADHD [30]. The significantly altered correlations between WMN and performance IQ might reflect the dysfunction of left dorsolateral prefrontal cortex in ADHD [4,15].…”

Microstructural abnormalities of the brain white matter in attention-deficit/hyperactivity disorder

“…It is active in a state of rest and deactivated during tasks that make cognitive demands, with stronger deactivation corresponding to increasing attentional demands. 48,49 Increasingly, ADHD is considered as a DMN disorder 50 in which attentional lapses derive from an inappropriate persistence of DMN activation 49 ; for example, a study using a stop signal task found that failure to suppress the DMN was associated with greater errors. 51 Recent pathophysiological models of ADHD recognize it as a disorder encompassing large-scale neural networks, such as the cognitive control network and limbic networks, not only abnormal connectivity within the DMN itself.…”

Neurobiology of Adult ADHD: Emerging Evidence for Network Dysfunctions

“…6 Another study that included two groups of medication naïve adults with ADHD reported increased connectivity between the DMN and a small region within left lateral PFC based on independent component analysis ( Figure 3). 7 In addition, higher levels of resting state activity within that area of PFC were associated with lower levels of performance on an attentional tasks. Increased connectivity between some DMN areas in ADHD relative to controls has also been reported.…”

“…A resting state fMRI study in medication naive adults with ADHD reported positive connectivity between an area in lateral prefrontal cortex and default mode network areas identified by independent component analysis. 7 The location and extent are approximated on a lateral view of the cortical surface (violet). Higher resting state activity in this region was inversely correlated with attentional performance (higher activity, lower performance).…”