Abstract

Background: Drug-related cue-reactivity, dysfunctional negative emotion processing, and response-disinhibition constitute three core aspects of methamphetamine use disorder (MUD). These phenomena have been studied independently, but the neuroscientific literature on their interaction in addictive disorders remains scant.Methods: 62 individuals with MUD were scanned when responding to the geometric Go or No-Go cues superimposed over blank, neutral, negative-emotional and drug-related background images. Neural correlates of drug and negative-emotional cue-reactivity, response-inhibition and their interactions were estimated, and methamphetamine cue-reactivity was compared between individuals with MUD and 23 healthy controls. Relationships between behavioral characteristics and observed activations were investigated.Results: Individuals with MUD had longer reaction times and more errors in drug and negative-emotional compared to blank blocks, and more omission errors in drug compared to neutral blocks. They showed higher drug cue-reactivity than controls across prefrontal, fusiform, and visual regions (Z > 3.1, p-corrected<0.05). Response-inhibition was associated with precuneal, inferior parietal, anterior cingulate, temporal, and inferior frontal activations (Z > 3.1, p-corrected<0.05). Response-inhibition in drug cue blocks coincided with higher activations in the visual cortex and lower activations in the paracentral lobule and superior and inferior frontal gyri, while inhibition during negative-emotional blocks led to higher superior parietal, fusiform, and lateral occipital activations (Z > 3.1, p-corrected<0.05).Conclusion: Drug cue-reactivity may impair response inhibition partly through activating dis-inhibitory regions, while temporal and parietal activations associated with response-inhibition in negative blocks suggest compensatory activity. Results suggest that drug and negative-emotional cue-reactivity influence responseinhibition, and the study of these interactions may aid mechanistic understanding of methamphetamine use disorder.