An fMRI-Based Neural Signature of Decisions to Smoke Cannabis

Abstract

Drug dependence may be at its core a pathology of choice, defined by continued decisions to use drugs irrespective of negative consequences. Despite evidence of dysregulated decision making in addiction, little is known about the neural processes underlying the most clinically relevant decisions drug users make: decisions to use drugs. Here, we combined functional magnetic resonance imaging (fMRI), machine learning, and human laboratory drug administration to investigate neural activation underlying decisions to smoke cannabis. Nontreatment-seeking daily cannabis smokers completed an fMRI choice task, making repeated decisions to purchase or decline 1-12 placebo or active cannabis 'puffs' ($0.25-$5/puff). One randomly selected decision was implemented. If the selected choice had been bought, the cost was deducted from study earnings and the purchased cannabis smoked in the laboratory; alternatively, the participant remained in the laboratory without cannabis. Machine learning with leave-one-subject-out cross-validation identified distributed neural activation patterns discriminating decisions to buy cannabis from declined offers. A total of 21 participants were included in behavioral analyses; 17 purchased cannabis and were thus included in fMRI analyses. Purchasing varied lawfully with dose and cost. The classifier discriminated with 100% accuracy between fMRI activation patterns for purchased vs declined cannabis at the level of the individual. Dorsal striatum, insula, posterior parietal regions, anterior and posterior cingulate, and dorsolateral prefrontal cortex all contributed reliably to this neural signature of decisions to smoke cannabis. These findings provide the basis for a brain-based characterization of drug-related decision making in drug abuse, including effects of psychological and pharmacological interventions on these processes.

Figure 1

(a) Percentage of choices bought for self-administration as a function of cannabis dose (placebo 0.0% THC vs active 5.5–5.6% THC) and cost per puff (in USD). Data are mean percentages (±SEM). Significant differences between doses, *p<0.01. (b) Effects of dose (placebo 0.0% THC vs active 5.5–5.6% THC) on ratings of desire to smoke the cannabis in each offer, as rated before presentation of item cost. Data are mean ratings (±SEM) on a scale from 1 to 4. Significant difference between doses, *p<0.05. CN, cannabis.

Figure 2

The signature map consisting of voxels that reliably contributed to prediction of decisions to smoke or to decline cannabis. The signature was subject to FDR correction at q<0.1 for display purposes only; all voxels contributed to prediction. Areas that predicted decisions to buy cannabis are weighted positively, whereas negatively weighted regions predicted decisions to decline cannabis.

Figure 3

Signature response in brain maps from bought cannabis offers, declined offers, active cannabis offers, and placebo cannabis offers, calculated by computation of the cross-product of the out-of-training-sample individual's activation maps and the signature pattern derived from the other 16 participants to estimate the signature response in each individual's activity maps (averaged across all voxels). Data are means (±SEM). a.u.=arbitrary units.