Blunted Frontostriatal Blood Oxygen Level-Dependent Signals Predict Stimulant and Marijuana Use

Abstract

Background: Occasional recreational stimulant (amphetamine and cocaine) use is an important public health problem among young adults because 16% of those who experiment develop stimulant use disorder. This study aimed to determine whether behavioral and/or neural processing measures can forecast the transition from occasional to problematic stimulant use.

Methods: Occasional stimulant users completed a Risky Gains Task during functional magnetic resonance imaging and were followed up 3 years later. Categorical analyses tested whether blood oxygen level-dependent (BOLD) responses differentiated occasional stimulant users who became problem stimulant users (n = 35) from those who desisted from stimulant use (n = 75) at follow-up. Dimensional analyses (regardless of problem stimulant user or desisted stimulant use status; n = 144) tested whether BOLD responses predicted baseline and follow-up stimulant and marijuana use.

Results: Categorical results indicated that relative to those who desisted from stimulant use, problem stimulant users 1) made riskier decisions after winning feedback; 2) exhibited lower frontal, insular, and striatal BOLD responses to win/loss feedback after making risky decisions; and 3) displayed lower thalamic but greater temporo-occipital BOLD responses to risky losses than to risky wins. In comparison, dimensional results indicated that lower BOLD signals to risky choices than to safe choices in frontal, striatal, and additional regions predicted greater marijuana use at follow-up.

Conclusions: Taken together, blunted frontostriatal signals during risky choices may quantify vulnerability to future marijuana consumption, whereas blunted frontostriatal signals to risky outcomes mark risk for future stimulant use disorder. These behavioral and neural processing measures may prove to be useful for identifying ultra-high risk individuals prior to onset of problem drug use.

Keywords: Amphetamine; Cocaine; Decision making; Reward; Stimulant; fMRI.

Figure 1

Overview of study design and data analyses. At baseline, occasional stimulant users (OSU) completed questionnaires, a clinical interview, and a functional magnetic resonance imaging (fMRI) scan recorded during the Risky Gains Task (RGT). OSU then completed a follow-up clinical interview three years later that included assessment of interim drug use. Only OSU with both usable fMRI data at baseline and complete follow-up drug use data were included in longitudinal analyses. Categorical analysis of baseline self-report and fMRI data included a subset of OSU who either met criteria for problem stimulant user (PSU) or desisted stimulant user (DSU) groups on the basis of interim drug use patterns and follow-up interview diagnostic criteria. Dimensional analysis included all OSU and compared relationships between interim stimulant and marijuana use to baseline self-report and fMRI data, controlling for baseline stimulant and marijuana use.

Figure 2

Depiction of trial types presented during the Risky Gains Task (RGT): (A) lose 80; (B) win 20; (C) win 40; and (D) lose 40. The blue arrow indicates which value the participant chose (Connolly et al., 2014).

Figure 3

Group x Decision Interaction: Problem stimulant users (PSU) displayed greater BOLD signal in precuneus and cingulate regions for risky than safe decisions when compared to desisted stimulant users (DSU).

Figure 4

Outcome Group Main Effect: Across risky wins and losses, problem stimulant users (PSU) exhibited lower BOLD signal than desisted stimulant users (DSU) in left frontal, central, parietal and limbic regions as well as right posterior cingulate and precuneus.

Figure 5

Group x Outcome Interaction: Problem stimulant users exhibited greater BOLD signal to risky wins than risky losses when compared to desisted stimulant users (DSU) in right thalamus and left middle/inferior temporal and occipital gyri.

Figure 6

Interim marijuana use predicting BOLD Signal for Risky minus Safe Decisions: Higher interim marijuana use was linked to lower superior/middle/inferior frontal gyri, inferior parietal lobule, superior/middle temporal gyri, thalamus, and precuneus activation for risky compared to safe decisions at baseline.