fMRI study of cognition, motivation, decision-making, reward, risk, aversion, negative emotion, arousal, craving, impulsivity, and stress in alcohol use disorder

National Institute On Alcohol Abuse And Alcoholism

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Abstract

EMOTIONAL DYSREGULATION - Emotional affect is known to play a critical role in the development and maintenance of alcohol use disorder. Patients with alcohol use disorder might be suffering from extra sensitivity to negative outcomes, and their cognition might be impaired in the presence of alcohol related cues. During this period, we have completed or initiated four studies to further understand neural mechanisms underlying cognitive responses. We had previously reported that data collection for a study of attention bias called the alcohol implicit attention task (AIAT) using functional near infrared spectroscopy (fNIRS) was completed and after some detailed investigation of available tools, we are now beginning to analyze the data. In this study the participants were asked to determine the category of the words or images that are presented to them. The stimuli included neutral and emotionally negative, as well as alcoholic beverage words and images. In a second study we are examining the potential difference in impulsivity of healthy controls and individuals with AUD under duress. Impulsivity, one of the hallmarks of AUD development, is shown to be further exacerbated under negative conditions such as stress, and negative emotionality. We are further studying this phenomenon, known as negative urgency (NU), using a delay discounting task with monetary and alcohol reward. We also are experimenting with another negative emotionality test where the participant becomes aware of the consequence of their choice and its alternate outcome should they have made a different one. In this task the participant is informed of the alternative outcome to their choice. This task which is based on a wheel of fortune paradigm will investigate the neural substrates of a phenomenon known as “regret.” This pilot study would enable us to design future studies investigating neural bases of coping, resilience, or susceptibility mechanisms. REWARD RESPONSE - Alcohol and nicotine interact with the nicotinic acetylcholine receptor (nAChR) system to alter reward-related responses, thereby contributing to the co-use and misuse of these drugs. A missense polymorphism rs16969968 (G>A) in the CHRNA5 gene has shown a strong association with nicotine consumption and dependence, and related smoking phenotypes. In collaborative research with Dr. Ramchandani’s team we are examining the imaging data of this study to determine the effects of this polymorphism on reward neural substrates associated with the interactions between smoking and alcohol use disorder. CUE REACTIVITY - We collaborated with Dr. Leggio’s team that was conducting a phase 2a experimental medicine study in patients with alcohol use disorder (AUD) to investigate the effects of PF-5190457 on alcohol- and food-related outcomes. A sub-set of participants (N=12) performed a CR task during a brain functional magnetic resonance imaging (fMRI) experiment. The study provided evidence of the role of GHSR blockade in behaviors related to food selection. However, we did not see evidence of reduction in alcohol cue-elicited alcohol craving or any influence on neural activation during CR task in the fMRI experiment (Faulkner et al. 2024).