Reward circuit connectivity relates to delay discounting in children with attention-deficit/hyperactivity disorder

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent psychiatric disorder that has poor long-term outcomes and remains a major public health concern. Recent theories have proposed that ADHD arises from alterations in multiple neural pathways. Alterations in reward circuits are hypothesized as one core dysfunction, leading to altered processing of anticipated rewards. The nucleus accumbens (NAcc) is particularly important for reward processes; task-based fMRI studies have found atypical activation of this region while the participants performed a reward task. Understanding how reward circuits are involved with ADHD may be further enhanced by considering how the NAcc interacts with other brain regions. Here we used the technique of resting-state functional connectivity MRI (rs-fcMRI) to examine the alterations in the NAcc interactions and how they relate to impulsive decision making in ADHD. Using rs-fcMRI, this study: examined differences in functional connectivity of the NAcc between children with ADHD and control children; correlated the functional connectivity of NAcc with impulsivity, as measured by a delay discounting task; and combined these two initial segments to identify the atypical NAcc connections that were associated with impulsive decision making in ADHD. We found that functional connectivity of NAcc was atypical in children with ADHD and the ADHD-related increased connectivity between NAcc and the prefrontal cortex was associated with greater impulsivity (steeper delayed-reward discounting). These findings are consistent with the hypothesis that atypical signaling of the NAcc to the prefrontal cortex in ADHD may lead to excessive approach and failure in estimating future consequences; thus, leading to impulsive behavior.

Figure 1. Voxelwise resting state functional connectivity maps for the nucleus accumbens (NAcc)

Results for control children and children with combined type ADHD (ADHD-C) (A); and direct comparison between groups (B). Results show atypical functional connectivity of the NAcc in children with ADHD-C. For all analyses Monte Carlo simulation was applied to correct for multiple comparisons (minimum Z>2.25, p<0.05, corrected).

Figure 2. Correlation between functional connectivity of NAcc and delayed-reward discounting gradient

The map displays the correlation between NAcc connectivity and ln(k) – natural log of the discounting gradient (k). Warm colors represent NAcc connections that were positively correlated with ln(k). There were no connections negatively correlated with ln(k). Results show strong correlation between delay discounting gradient and connectivity from the NAcc to the prefrontal cortex (PFC; indicated by the arrows), including the ventromedial PFC and the left anterior PFC. For all analyses Monte Carlo simulation was applied to correct for multiple comparisons (minimum Z>2.25, p<0.05, corrected).

Figure 3. Identification of regions associated with ADHD and related to impulsive decision making (as measured by the delay discounting task)

Volume maps show connections with NAcc that were both, associated with ADHD (from the comparison map – section 1), and correlated with delay discounting gradient (section 2). Results are adjusted for the effects of age and gender. Scatter plots display the correlation. Lines represent the best fitted lines for: all children (black), control children (blue), children with ADHD (red). Dots represent: control subjects (blue), children with ADHD combined type (red), inattentive type (green) and hyperactive/impulsive type (dark red). Results suggest that atypical connection between NAcc and anterior PFC is associated with impulsive decision making in children with ADHD.