Cue-Induced Craving and Negative Emotion Disrupt Response Inhibition in Methamphetamine Use Disorder: Behavioral and fMRI Results from a Mixed Go/No-Go Task

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 fMRI data were collected from 62 individuals with MUD 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 response-inhibition during drug and negative-emotional blocks were estimated, and methamphetamine cue-reactivity was compared between MUDs and 23 healthy controls (HCs). Relationships between clinical and behavioral characteristics and observed activations were subsequently investigated. Results MUDs had longer reaction times and more errors in drug and negative-emotional blocks compared to neutral and blank ones. MUDs showed higher drug cue-reactivity than HCs across prefrontal regions, fusiform gyrus, and visual cortices (Z>3.1, p-corrected<0.05). Response-inhibition was associated with activations in the precuneus, inferior parietal lobule, and anterior cingulate, temporal and inferior frontal gyri (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 Higher visual cortical activations and lower parietal and prefrontal activations during drug-related response-inhibition suggest the down-regulation of inhibitory regions and up-regulation of bottom-up drug cue-reactivity. Our results suggest that drug and negative-emotional cue-reactivity influence response-inhibition, and the study of these interactions may aid mechanistic understandings of addiction and biomarker discovery.