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. 2016 Oct 8;12:796-805.
doi: 10.1016/j.nicl.2016.10.006. eCollection 2016.

Functional Connectivity in Cortico-Subcortical Brain Networks Underlying Reward Processing in Attention-Deficit/Hyperactivity Disorder

Free PMC article

Functional Connectivity in Cortico-Subcortical Brain Networks Underlying Reward Processing in Attention-Deficit/Hyperactivity Disorder

Marianne Oldehinkel et al. Neuroimage Clin. .
Free PMC article


Background: Many patients with attention-deficit/hyperactivity disorder (ADHD) display aberrant reward-related behavior. Task-based fMRI studies have related atypical reward processing in ADHD to altered BOLD activity in regions underlying reward processing such as ventral striatum and orbitofrontal cortex. However, it remains unclear whether the observed effects are region-specific or related to changes in functional connectivity of networks supporting reward processing. Here we use resting-state fMRI to comprehensively delineate the functional connectivity architecture underlying aberrant reward processing in ADHD.

Methods: We assessed resting-state functional connectivity of four networks that support reward processing. These networks showed high spatial overlap with the default mode, fronto-parietal, lateral visual, and salience networks, yet only activity within the salience network was effectively sensitive to reward value. We parcelled these networks into their functional cortical and subcortical subregions and obtained functional connectivity matrices by computing Pearson correlations between the regional time series. We compared functional connectivity within each of the four networks between participants with ADHD and controls, and related functional connectivity to dimensional ADHD symptom scores across all participants (N = 444; age range: 8.5-30.5; mean age: 17.7).

Results: We did not observe significant ADHD-related alterations in functional connectivity of the salience network, which included key reward regions. Instead, levels of inattention symptoms modulated functional connectivity of the default-mode and fronto-parietal networks, which supported general task processing.

Conclusions: The present study does not corroborate previous childhood evidence for functional connectivity alterations between key reward processing regions in adolescents and young adults with ADHD. Our findings could point to developmental normalization or indicate that reward-processing deficits result from functional connectivity alterations in general task-related networks.

Keywords: ADHD; Default mode network; Fronto-parietal network; Functional connectivity; Functional parcellation; Resting-state fMRI; Reward.


Fig. 1
Fig. 1
K-means clustered profiles and spatial maps of non-noise components. These components were obtained by applying a meta-ICA analysis to fMRI data of 60 control participants performing the monetary incentive delay task (MID). Black lines in the task condition profiles indicate mean for each cluster. Spatial maps of independent components are averaged across cluster and thresholded (Z > 2.3). Major networks that correspond with the different clusters are: 1) default mode network, 2) fronto-parietal network, 3) lateral visual network, and 4) salience network. Abbreviations: RwdCue = reward cue, NrwCue = no-reward cue, RwdHit = reward hit, RwdMiss = reward miss, NrwHit = no-reward hit, NrwMiss = no-reward miss, RwdCue-NrwCue = reward cue versus no-reward cue (reward anticipation), RwdHMvsNrwHM = reward hit and miss versus no-reward hit and miss (reward outcome). For details see von Rhein et al. in revision and our Supplementary material.
Fig. 2
Fig. 2
The obtained cortical and subcortical subregions for each of the four networks. The four cortical subregions resulting from the ICP parcellation of each network are shown on the left side of the figure. The delineated network-specific subcortical subregions are shown on the right side of the figure in matching colors (i.e., the subcortical regions are displayed in the same color as the cortical region with which they exhibited the strongest functional connectivity).
Fig. 3
Fig. 3
Group-average connectivity matrices showing z-transformed Pearson and partial correlations between timeseries of the different subcortical and cortical subregions in the four networks. No significant differences in correlations were present between the ADHD and control group in any of the four networks. Connectivity matrices for the unaffected siblings and subthreshold ADHD participants can be found in Supplementary Fig. S8.
Fig. 4
Fig. 4
Matrices indicating the correlation of inattention and hyperactivity/impulsivity (hyp/imp) symptom scores with connectivity (i.e., Pearson correlations) between the timeseries of the different subcortical and cortical subregions in the four networks across all participants (N = 444). Inattention and hyperactivity/impulsivity scores were based on the Conners parent rating scale (CPRS; Conners et al. 1998a). Asterisks (*) indicate significant correlations in network 1 after correction for covariates (age, sex, scan location, and comorbid ODD/CD) and multiple comparisons (FDR; p < 0.05). Similarly diamonds (◇) indicate significant connections of the brown subnetwork within network 2. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

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