Blunted ventral striatal responses to anticipated rewards foreshadow problematic drug use in novelty-seeking adolescents

Abstract

Novelty-seeking tendencies in adolescents may promote innovation as well as problematic impulsive behaviour, including drug abuse. Previous research has not clarified whether neural hyper- or hypo-responsiveness to anticipated rewards promotes vulnerability in these individuals. Here we use a longitudinal design to track 144 novelty-seeking adolescents at age 14 and 16 to determine whether neural activity in response to anticipated rewards predicts problematic drug use. We find that diminished BOLD activity in mesolimbic (ventral striatal and midbrain) and prefrontal cortical (dorsolateral prefrontal cortex) regions during reward anticipation at age 14 predicts problematic drug use at age 16. Lower psychometric conscientiousness and steeper discounting of future rewards at age 14 also predicts problematic drug use at age 16, but the neural responses independently predict more variance than psychometric measures. Together, these findings suggest that diminished neural responses to anticipated rewards in novelty-seeking adolescents may increase vulnerability to future problematic drug use.

Figure 1. fMRI activity during anticipation of large versus small gains for control and PDU subjects combined (n=144).

Overlaid on a mean structural magnetic resonance scan showing a coronal (left) and an axial (right) section, activation display threshold is P<0.05 (whole brain corrected, t-test).

Figure 2. Subcortical brain activity in anticipation of large versus small gains for control subjects (n=72) versus problematic drug users (n=72).

The PDU group showed decreased activation in bilateral ventral striatum (left, right) and midbrain (bottom). Overlaid on a mean structural magnetic resonance scan, activation display threshold is P<0.005 (uncorrected, t-test). Highlighted areas indicate volumes of interest in the ventral striatum (VS foci: ±14, 8, –8) and midbrain (VTA foci: ±9, –15, –15). Error bars=±s.e.m. *Significant at threshold of P<0.0083 uncorrected or P<0.05 corrected (n=144, t-test).

Figure 3. Cortical brain activity in anticipation of large versus small gains for control subjects (n=72) versus problematic drug users (n=72).

The PDU group showed decreased activation in the right dorsolateral prefrontal cortex (for VOI-based statistics, see Table 2). Overlaid on a mean structural magnetic resonance scan, activation display threshold is P<0.005 (uncorrected, t-test). Highlighted areas indicate volumes of interest in the dorsolateral prefrontal cortex (PFC foci: ±35, 36, 32). Error bars=±s.e.m. *Significant at threshold of P<0.0083 uncorrected or P<0.05 corrected (n=144, t-test).

Figure 4. Cortical differences in grey matter volume for control subjects (n=72) versus prospective problematic drug users (PDU) (n=72).

(a) Increased grey matter density was observed for the PDU group in the right dorsolateral prefrontal cortex. (b) The location of increased grey matter density (green) lies adjacent to reduced activation in the Monetary Incentive Delay (MID) task for the prospective problematic drug users (red). Overlaid on a mean structural magnetic resonance scale, volumetric display threshold is P<0.005 (uncorrected, t-test). Highlighted areas indicate volumes of interest in the prefrontal cortex. Error bars=±s.e.m. *Significant at threshold of P<0.0083 uncorrected or P<0.05 corrected (n=144, t-test).

Figure 5. Experimental design diagram depicting subject selection procedure.

Out of 1090 subjects with full datasets, the top quarter of novelty seekers who had not already met criteria for problematic drug use at age 14 were selected. Those who showed problematic drug use at age 16 were matched with those who did not with respect to drug use at age 14 (n=72 per group, 144 total).

Figure 6. Adapted Monetary Incentive Delay (MID) task trial structure.

An initial cue signalled potential gain for each trial (no gain: 0 points; small gain: 2 points; or large gain: 10 points). After a variable delay, a target briefly appeared. Responding during target display yielded the indicated gain, whereas late or early responses yielded no gain. Target durations adapted to approximate a 66% hit rate for each subject.