Incentive-elicited mesolimbic activation and externalizing symptomatology in adolescents

Abstract

Background: Opponent-process theories of externalizing disorders (ExD) attribute them to some combination of overactive reward processing systems and/or underactive behavior inhibition systems. Reward processing has been indexed by recruitment of incentive-motivational neurocircuitry of the ventral striatum (VS), including nucleus accumbens (NAcc).

Methods: We used functional magnetic resonance imaging (fMRI) with an incentive task to determine whether externalizing symptomatology in adolescence is correlated with an enhanced VS recruitment by cues for rewards, or by deliveries of rewards. Twelve community-recruited adolescents with externalizing disorders (AED) and 12 age/gender-matched controls responded to targets to win or avoid losing $0, $0.20, $1, $5, or an unknown amount (ranging from $0.20 to $5).

Results: Cues to respond for rewards activated the NAcc (relative to cues for no incentive), in both subject groups similarly, with greatest NAcc recruitment by cues for the largest reward. Loss-anticipatory NAcc signal increase was detected in a volume-of-interest analysis - but this increase occurred only in trials when subjects hit the target. Relative to controls, AED showed significantly elevated NAcc activation by a linear contrast between reward notification versus notification of failure to win reward. In a post hoc reanalysis, VS and pregenual anterior cingulate activation by the reward versus non-reward outcome contrast also directly correlated with Child Behavior Checklist (CBCL) Externalizing total scores (across all subjects) in lieu of a binary diagnosis. Finally, both groups showed right insula activation by loss notifications (contrasted with avoided losses).

Conclusions: Externalizing behavior, whether assessed dimensionally with a questionnaire, or in the form of a diagnostic categorization, is associated with an exaggerated limbic response to outcomes of reward-directed behavior. This could be a neurobiological signature of the behavioral sensitivity to laboratory reward delivery that is characteristic of children with externalizing symptomatology. Of interest is future research on incentive-motivational processing in more severe, clinically referred AED.

Figure 1. Monetary incentive delay (MID) task

Six-second trials were contiguously presented in two, 9.5-minute runs. In each trial, the subject saw one of nine cues indicating the opportunity to either win money (circle series), avoid losing money (square series), or win/lose no money (triangle) by pressing a button while a white square target was presented on the screen a moment later. The subject then saw feedback of whether he or she hit the target, as well as cumulative earnings for that run.

Figure 2. Activation by anticipation of responding for rewards or to avoid losses

Coronal and axial images are right-left reversed per radiological convention, with the Talairach coordinate of the image plane indicated. Group-wise activations survive False Discovery Rate correction to q < .05. Anticipation of responding for rewards contrasted with anticipation of non-reward activated the ventral striatum in both controls (A) and in adolescents with externalizing disorders (AED) (B). Anticipation of responding to avoid losses, however, did not activate any brain regions above threshold in either AED or controls.

Figure 3. Activation by notification of rewards and losses

Coronal and axial images are right-left reversed per radiological convention, with the Talairach coordinate of the image plane indicated. Group-wise activations survive False Discovery Rate correction to q < .05. Notification of rewards (contrasted with notification of failure to win reward) activated the ventral striatum (VS) in both controls (A) and in adolescents with externalizing disorders (AED) (B), with a significant voxelwise group difference in activation by this contrast depicted in (D). Reward notification also activated mesial frontal cortex in both in controls (D) and in AED (E), with significant voxel-wise group differences depicted in (F). Notification of all losses (versus notification of successful loss avoidance) activated right anterior insula in both controls (G) and in AED (H).

Figure 4. Reward cue-elicited peak signal change in nucleus accumbens VOI

Trial-type-averaged time series data were extracted from a mask custom-drawn for each subject in the nucleus accumbens (NAcc; center). Peak anticipatory signal occurred 6 s after cue presentation. NAcc recruitment increased with incentive magnitude in both controls (upper-most graphs), and in adolescents with externalizing disorders (AED; lower graphs). Analysis of variance across all trial magnitudes indicated that signal change did not significantly differ between trials when the subject did (solid bars) or did not (empty bars) hit the target (ANOVA p = .97). There were no main or interactive effects of subject group on reward-anticipatory NAcc signal change. ** denotes p <.05 per simple-effect two-tailed paired t-test.

Figure 5. Loss-avoidance cue-elicited peak signal change in nucleus accumbens VOI

Trial-type-averaged time series data were extracted from a mask custom-drawn for each subject in the nucleus accumbens (NAcc; center). Peak anticipatory signal occurred 6 s after cue presentation. NAcc recruitment did not increase with incentive magnitude in either controls (upper-most graphs) or in adolescents with an externalizing disorder (AED; lower graphs). Analysis of variance across all trial magnitudes indicated that signal change was significantly blunted in trials when the subject did not hit the target (empty bars) relative to successful trials (solid bars)(ANOVA p < .01). There were no main or interactive effects of subject group on loss-anticipatory peak NAcc signal change. * denotes p <.10 and ** denotes p < .05 per simple-effect two-tailed paired t-test.

Figure 6. Relationship between NAcc signal change and psychometric measures

After controlling for Child Behavior Checklist (CBCL) externalizing total scores, individual differences in net reward-related signal change partially correlated with subjects’ self-report ratings of net “excitement” at seeing the cue for maximum reward in the left nucleus accumbens (NAcc) (A), with a trend in the right NAcc (B). Solid circles denote adolescents with externalizing disorders (AED). Hollow squares denote controls.