Decomposing risky decision-making in methamphetamine use disorder: Behavioral updating and D2 dopamine receptors.

Abstract

Escalating misuse of amphetamine-type stimulants, mainly methamphetamine, has led to a staggering rise in associated overdose deaths and a pressing need to understand the basis of methamphetamine use disorder (MUD). MUD is characterized by disadvantageous decision-making, and people with MUD perform below controls on the Balloon Analogue Risk Task (BART), a laboratory test of decision-making under uncertainty. The BART presents a series of choices with progressively higher stakes-greater risk of loss and greater potential monetary reward. This research aimed to clarify whether impaired behavioral updating contributes to maladaptive performance on the BART. Two groups (28 drug-abstinent participants with MUD and 16 healthy control participants) were compared on BART performance. Using a computational model, we deconstructed behavior into risk-taking and behavioral updating. A subset of participants (22 MUD, 15 healthy control) underwent [¹⁸F]fallypride positron emission tomography scans to measure dopamine D2-type receptor availability (BPND) in the striatum (caudate and accumbens nuclei and putamen) and the globus pallidus. Participants with MUD exhibited slower behavioral updating than the healthy controls (p = 0.0004, d=1.77). BPND in all four bilateral volumes of interest were higher in the healthy control group (ps < 0.005, ds < 2.16), and updating rate correlated positively with BPND in the caudate nucleus (p = 0.002), putamen (p = 0.002), and globus pallidus (p = 0.03). The findings indicate that behavioral updating contributes to maladaptive decision-making in MUD and suggest that dysregulation of D2-type receptor signaling in the striatum and globus pallidus contributes to this behavioral deficit.