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

Investigators

Linked publications & trials

Abstract

1. Study of cognitive functions a. Inhibitory response - We have assessed the potential interaction of cognitive and motor processes in alcohol use disorder is currently using the inhibitory interference of response task (IIRT) developed in CNIRC. The analysis of this data will be conducted as planned. b. Altruistic decision making - We have completed and published the results of a study of the neural correlates of decision making when making choices about whether to give money to charitable causes. Previous studies find that charitable decision making is associated with integration of value computing (from the ventral striatum) with social cognitive processing (such as in the insula and temporoparietal junction) through the ventromedial prefrontal cortex The above mentioned regions have also been implicated in AUD and our goal was whether such an fMRI task would provide further granularity in the decision making process of AUD patients as a biomarker. Twenty-nine participants subjectively rated ten charities on their value, effectiveness, and the subjects personal chance of donating. Participants then completed an fMRI task requiring them to decide to donate to certain charities given the probability of the donation helping, their personal preference for the charity, and whether the donation came at cost to themselves. Probability of a donation being helpful and how much the subject favored a charity moderated PCC and left IFG engagement. Interestingly, reward neurocircuitry did not demonstrate similar sensitivity to these variations. Our secondary interest in utilizing this task as an AUD biomarker, there were no significant differences compared to healthy controls when controlled for multiple comparisons at the whole brain level (Fede et al., 2021). 2. fMRI Studies of Stress Epigenomic study - We also collaborated with Dr. Lohoff's Lab in their DNA methylation epigenome-wide association study (EWAS). This study identified novel epigenetic probes relevant to AUD such as Growth Arrest Specific 5 gene (GAS5). Endophenotypic analyses using peripheral cortisol levels and neuroimaging paradigms showed that methylomic variation in GAS5 network related probes were associated with stress phenotypes. During a fear acquisition functional MRI significant associations were observed in the left amygdala, and both left and right insula with DNA methylation variation potentially associated with AUD. The results in this study suggested that DNA methylation changes in response to alcohol exposure may mediate altered brain activity patterns through alteration of HPA axis activity and stress sensitivity. There was also an association of hippocampal volume with this AUD related epigenetic variation (Lohoff, et al., 2020).