The effects of nalmefene on the impulsive and reflective system in alcohol use disorder: A resting-state fMRI study

Abstract

Rationale: Central aspects of alcohol use disorder (AUD) are the irresistible desire for alcohol and impaired control over its intake. According to the triadic neurocognitive model of addiction, this arises from aberrant functioning of different neural and cognitive systems: an impulsive system, a reflective system, and the abnormal dynamics between both systems based on an insular-dependent system.

Objectives: In this study, we examined the effects of a single dose of nalmefene on resting-state functional connectivity (rsFC) patterns within and between these addiction-related neural systems in AUD.

Methods: Non-treatment seeking participants with AUD (N = 17; 19-66 years, 6 female) took part in a randomized, placebo-controlled, double-blind, crossover study and received either a single dose of 18 mg nalmefene or a placebo. Using seed-based correlation analyses on resting-state functional magnetic resonance imaging data, we examined the effects of nalmefene on key nodes related to the (1) impulsive system; (2) reflective system; (3) salience network; and (4) default mode network.

Results: Under nalmefene, participants showed reduced rsFC between components of the impulsive system (Nucleus accumbens-putamen/pallidum/insula). Reduced rsFC was found between elements of the reflective system and impulsive system (orbitofrontal cortex-insula/putamen/pallidum), salience network (orbitofrontal cortex-insula/inferior frontal gyrus), and default mode network (lateral prefrontal cortex-precuneus/cuneus). Components of the salience network showed both increased (anterior cingulate cortex) and decreased (insular cortex) rsFC to elements of the reflective system.

Conclusion: A single dose of nalmefene impacts rsFC and alters the interaction between key nodes of addiction-related neural systems in non-treatment seeking participants with AUD. Nalmefene may normalize rsFC patterns by weakening the impulsive system while strengthening the reflective system.

Trial registration: clinicaltrials.gov: NCT02372318.

Keywords: Alcohol use disorder; Impulsive system; Nalmefene; Pharmacotherapy; Reduced drinking; Reflective system; Resting-state functional connectivity; Salience network.