Striatal sensitivity during reward processing in attention-deficit/hyperactivity disorder

Abstract

Objective: Attention-deficit/hyperactivity disorder (ADHD) has been linked to deficits in the dopaminergic reward-processing circuitry; yet, existing evidence is limited, and the influence of genetic variation affecting dopamine signaling remains unknown. We investigated striatal responsivity to rewards in ADHD combined type (ADHD-CT) using functional magnetic resonance imaging (fMRI), and whether it is modulated by variation in the dopamine transporter gene (DAT1).

Method: We tested 29 male adolescents with ADHD-CT and 30 age-, handedness-, and gender-matched healthy controls who were selected for DAT1(10/6) haplotype dosage. Based on previous research, we focused our analysis on the ventral striatum and the caudate nucleus.

Results: Three main findings emerged. First, male adolescents with ADHD-CT did not differ from controls in terms of blood oxygen-level dependent (BOLD) fMRI response to reward-predicting cues (gain or loss-avoidance) in the ventral striatum. Second, male adolescents with ADHD-CT showed a relative increase, compared with controls, in the striatal BOLD response to successful outcomes. Third, DAT1(10/6) dosage differentially modulated neural activation to reward-predicting cues in the caudate nucleus in the ADHD-CT and control groups.

Conclusions: The findings challenge the idea of a deficit in anticipation-related activation in the ventral striatum in male adolescents with ADHD-CT, while suggesting that the processing of reward outcomes is dysfunctional, consistent with a recent neurobiological model of the disorder. Preliminary evidence suggests that polymorphic variations in genes affecting dopamine signaling need to be taken into consideration when investigating reward-related deficits in ADHD-CT.

Figure 1

Motivated incidental learning task (MILT). Note: ITI = inter-trial interval.

Figure 2

Ventral striatum (VS): response to incentive-predicting cues. Note: Cue-induced activation in the VS increased with incentive magnitude in gain (p < .001) and loss-avoidance (p = .006) trials. Main effects for diagnosis, dopamine transporter gene (DAT1_10/6) dosage or their interaction were not significant. ADHD-CT = attention deficit hyperactivity disorder combined type; DAT1 = dopamine transporter gene; SE = standard error.

Figure 3

Caudate nucleus body: Blood oxygen level dependent (BOLD) response to incentive-predicting cues. Note: BOLD response to incentive-predicting cues in the caudate nucleus body, averaged over task valence (gain or loss-avoidance), incentive magnitude (£1 or £5) and brain hemisphere. ADHD-CT = attention deficit hyperactivity disorder combined type; DAT1 = dopamine transporter gene; SE = standard error.