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. 2015 Sep;36(9):3373-86.
doi: 10.1002/hbm.22850. Epub 2015 Jun 24.

Disrupted Functional Connectivity of Cerebellar Default Network Areas in Attention-Deficit/Hyperactivity Disorder

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Free PMC article

Disrupted Functional Connectivity of Cerebellar Default Network Areas in Attention-Deficit/Hyperactivity Disorder

Aaron Kucyi et al. Hum Brain Mapp. .
Free PMC article

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is increasingly understood as a disorder of spontaneous brain-network interactions. The default mode network (DMN), implicated in ADHD-linked behaviors including mind-wandering and attentional fluctuations, has been shown to exhibit abnormal spontaneous functional connectivity (FC) within-network and with other networks (salience, dorsal attention and frontoparietal) in ADHD. Although the cerebellum has been implicated in the pathophysiology of ADHD, it remains unknown whether cerebellar areas of the DMN (CerDMN) exhibit altered FC with cortical networks in ADHD. Here, 23 adults with ADHD and 23 age-, IQ-, and sex-matched controls underwent resting state fMRI. The mean time series of CerDMN areas was extracted, and FC with the whole brain was calculated. Whole-brain between-group differences in FC were assessed. Additionally, relationships between inattention and individual differences in FC were assessed for between-group interactions. In ADHD, CerDMN areas showed positive FC (in contrast to average FC in the negative direction in controls) with widespread regions of salience, dorsal attention and sensorimotor networks. ADHD individuals also exhibited higher FC (more positive correlation) of CerDMN areas with frontoparietal and visual network regions. Within the control group, but not in ADHD, participants with higher inattention had higher FC between CerDMN and regions in the visual and dorsal attention networks. This work provides novel evidence of impaired CerDMN coupling with cortical networks in ADHD and highlights a role of cerebro-cerebellar interactions in cognitive function. These data provide support for the potential targeting of CerDMN areas for therapeutic interventions in ADHD.

Keywords: attention-deficit/hyperactivity disorder; cerebellum; default mode network; functional connectivity; inattention; resting state.

Figures

Figure 1
Figure 1
Cerebellar default mode network (CerDMN) seed and its functional connectivity (FC) in the healthy control (HC) and attention-deficit/hyperactivity disorder (ADHD) groups. A) The CerDMN seed (based on (Buckner et al., 2011)) from which the resting state fMRI time series were extracted. B) Voxels showing significant positive FC with the CerDMN in the HC and ADHD groups [FWE-corrected Z > 2.3 (threshold increased to 3.5 for display purposes); cluster-based p < 0.05]. HF, hippocampal formation; LPC, lateral parietal cortex; mPFC, medial prefrontal cortex; PCC, posterior cingulate cortex; PCu, precuneus; Thal, thalamus.
Figure 2
Figure 2
Regions showing higher CerDMN resting FC in ADHD patients and their classification by network. A) Voxels showing significantly greater FC in ADHD compared to HC (FWE-corrected Z > 2.3; cluster-based p < 0.05). B) Polar plot (left) shows voxels from A) quantified in terms of volume (mm3) that overlaps with each of seven networks defined by Yeo et al. (Yeo et al., 2011). Brain images (right, top) show networks in blue and their overlap with ADHD > HC CerDMN FC maps (transparent red/yellow). Bar plots (right, bottom) show mean FC within each group across voxels in each network that overlapped with ADHD > HC CerDMN FC maps (ADHD, red; HC, black). Error bars depict standard error of the mean. COPE, contrast of parameter estimate; Cun, cuneus; DAN, dorsal attention network; DMN, default mode network; Ins, insula; FEF, frontal eye fields; FPN, frontoparietal network; Ling, lingual gyrus; MCC, mid-cingulate cortex; Rsp, retrosplenial cortex; SMN, sensorimotor network; SPL, superior parietal lobule.
Figure 3
Figure 3
Differences between ADHD and HC groups in the relationship between ASRS inattention and resting CerDMN FC. A) Voxels showing a stronger inattention-CerDMN FC association in HC compared to ADHD (FWE-corrected Z > 2.3; cluster-based p < 0.05). B) Polar plot (left) shows voxels from A) quantified in terms of volume (mm3) that overlaps with each of seven networks defined by Yeo et al. (Yeo et al., 2011). Scatter plots (right) show, in each group, individual inattention scores versus mean CerDMN FC across voxels from A) that overlap with the labeled networks (HC, black; ADHD, red). ASRS, Adult ADHD Self-Report Scale; COPE, Contrast Of Parameter Estimate; DAN, dorsal attention network; DMN, default mode network; FPN, frontoparietal network; Fus, fusiform gyrus; LOC, lateral occipital complex; SMN, sensorimotor network; SPL, superior parietal lobule.
Figure 4
Figure 4
Overlap of voxels showing increased CerDMN FC in ADHD compared to HC (red) and a weaker association of inattention with CerDMN FC in ADHD compared to HC (green).
Figure 5
Figure 5
Regions showing higher resting FC with right and left CerDMN subregions in ADHD patients compared to healthy controls. A) Right CerDMN Crus I seed region (left) and voxels showing significantly greater FC in ADHD compared to HC (right; FWE-corrected Z > 2.3; cluster-based p < 0.05). B) Left CerDMN Crus I seed region (left) and voxels showing significantly greater FC in ADHD compared to HC (right; FWE-corrected Z > 2.3; cluster-based p < 0.05).

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