Connectivity Changes Following Episodic Future Thinking in Alcohol Use Disorder.

[Please note that in order to respond to reviewers request we had exceed the 300 word limit. The following is NOT revised from the first submission, please see the actual revised manuscript file for the reviewer-driven changes].

Introduction: Recent addiction and obesity-related research suggest that episodic future thinking (EFT) can serve as a promising intervention to promote healthy decision making. This study investigated the neural effects of EFT in alcohol use disorder (AUD).

Methods: Participants received either a brief EFT or control intervention to examine differences in resting-state connectivity. We then used these findings to characterize psychophysiological interaction (PPI) differences during a delay discounting (DD) fMRI task. In addition, we used a second control group of AUD participants without any intervention to reproduce and aid in interpreting our key findings.

Results: EFT participants, but not controls, showed statistically improved discounting rates - a behavioral marker for addiction. Resting state analyses of the left hippocampus revealed connectivity differences in the frontal poles. The directionality of this difference suggested that EFT reduced a hypoconnectivity relationship between these regions in AUD. We also found resting state connectivity differences between the salience network and the right dorsolateral prefrontal cortex (R DLPFC), which then led us to discover R-to-L DLPFC PPI differences during DD. Moreover, the resting state salience-to-DLPFC functional connectivity showed an inverse relationship to discounting rate while hyperconnectivity between left and right DLPFC reflected slower reaction times during difficult DD trials.

Discussion: These findings suggest that EFT produces beneficial changes in neural connectivity patterns in AUD. The alterations in connectivity highlight potential mechanisms underlying the effectiveness of EFT in improving decision-making in AUD. Understanding these neural effects may contribute to the further development of targeted interventions for AUD and related disorders.