Characterising resting-state functional connectivity in a large sample of adults with ADHD

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is a common childhood psychiatric disorder that often persists into adulthood. While several studies have identified altered functional connectivity in brain networks during rest in children with ADHD, few studies have been performed on adults with ADHD. Existing studies have generally investigated small samples. We therefore investigated aberrant functional connectivity in a large sample of adult patients with childhood-onset ADHD, using a data-driven, whole-brain approach. Adults with a clinical ADHD diagnosis (N=99) and healthy, adult comparison subjects (N=113) underwent a 9-minute resting-state fMRI session in a 1.5T MRI scanner. After elaborate preprocessing including a thorough head-motion correction procedure, group independent component analysis (ICA) was applied from which we identified six networks of interest: cerebellum, executive control, left and right frontoparietal and two default-mode networks. Participant-level network maps were obtained using dual-regression and tested for differences between patients with ADHD and controls using permutation testing. Patients showed significantly stronger connectivity in the anterior cingulate gyrus of the executive control network. Trends were also observed for stronger connectivity in the cerebellum network in ADHD patients compared to controls. However, there was considerable overlap in connectivity values between patients and controls, leading to relatively low effect sizes despite the large sample size. These effect sizes were slightly larger when testing for correlations between hyperactivity/impulsivity symptoms and connectivity strength in the executive control and cerebellum networks. This study provides important insights for studies on the neurobiology of adult ADHD; it shows that resting-state functional connectivity differences between adult patients and controls exist, but have smaller effect sizes than existing literature suggested.

Keywords: Adult ADHD; Cerebellum; Executive control network; Independent component analysis; Resting-state functional connectivity.

Figure 1

Six components of interest from group ICA representing networks of interest (green), overlayed on a MNI-template brain (grey). Networks were thresholded at Z > 5.

Figure 2

Stronger connectivity in ADHD patients compared to controls in A) the executive control network and B) the cerebellum network. On the left, significant clusters are depicted in red-yellow at a threshold of p < 0.05 (FWE-corrected). On the right, histograms of connectivity strength of the peak voxel from the clusters on the left are shown for control participants (blue) and ADHD patients (orange). Purple-shaded areas reflect overlap between the two groups.

Figure 3

Significant correlations between hyperactivity/impulsivity symptoms and functional connectivity strength in the executive control network (A) and the cerebellum network (B). Hot colours represent significant regions, thresholded at p < 0.05. Scatterplots represent the correlation between connectivity strength (y-axis; parameter estimates from dual regression, corrected for age and gender) and hyperactivity / impulsivity symptoms (x-axis). In A, the peak voxel is located in the right superior frontal gyrus (MNI 10; 50; 24). In B, the peak voxel is located in the left cerebellum vermis VI (MNI −6; −58; −28). See Table 3 for details.