Simon Zhornitsky1, Sheng Zhang1, Jaime S Ide1, Herta H Chao2, Wuyi Wang1, Thang M Le1, Robert F Leeman3, Jinbo Bi4, John H Krystal5, Chiang-Shan R Li6. 1. Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut. 2. Department of Medicine, Yale University School of Medicine, New Haven, Connecticut; VA Connecticut Healthcare System, West Haven, Connecticut. 3. Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; Department of Health Education & Behavior, University of Florida, Gainesville, Florida. 4. Department of Computer Science & Engineering, School of Engineering, University of Connecticut, Storrs, Connecticut; Department of Community Medicine and Health Care, School of Medicine, University of Connecticut Health Center, Farmington, Connecticut. 5. Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; Department of Neuroscience, Yale University School of Medicine, New Haven, Connecticut; Interdepartmental Neuroscience Program, Yale University, New Haven, Connecticut. 6. Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; Department of Neuroscience, Yale University School of Medicine, New Haven, Connecticut; Interdepartmental Neuroscience Program, Yale University, New Haven, Connecticut. Electronic address: chiang-shan.li@yale.edu.
Abstract
BACKGROUND: Positive alcohol expectancy (AE) contributes to excessive drinking. Many imaging studies have examined cerebral responses to alcohol cues and how these regional processes related to problem drinking. However, it remains unclear how AE relates to cue response and whether AE mediates the relationship between cue response and problem drinking. METHODS: A total of 61 nondependent drinkers were assessed with the Alcohol Expectancy Questionnaire and Alcohol Use Disorder Identification Test and underwent functional magnetic resonance imaging while exposed to alcohol and neutral cues. Imaging data were processed and analyzed with published routines, and mediation analyses were conducted to examine the interrelationships among global positive score of the Alcohol Expectancy Questionnaire, Alcohol Use Disorder Identification Test score, and regional responses to alcohol versus neutral cues. RESULTS: Alcohol as compared with neutral cues engaged the occipital, retrosplenial, and medial orbitofrontal cortex as well as the left caudate head and red nucleus. The bilateral thalamus showed a significant correlation in cue response and in left superior frontal cortical connectivity with global positive score in a linear regression. Mediation analyses showed that global positive score completely mediated the relationship between thalamic cue activity as well as superior frontal cortical connectivity and Alcohol Use Disorder Identification Test score. The alternative models that AE contributed to problem drinking and, in turn, thalamic cue activity and connectivity were not supported. CONCLUSIONS: The findings suggest an important role of the thalamic responses to alcohol cues in contributing to AE and at-risk drinking in nondependent drinkers. AEs may reflect a top-down modulation of the thalamic processing of alcohol cues, influencing the pattern of alcohol use.
BACKGROUND: Positive alcohol expectancy (AE) contributes to excessive drinking. Many imaging studies have examined cerebral responses to alcohol cues and how these regional processes related to problem drinking. However, it remains unclear how AE relates to cue response and whether AE mediates the relationship between cue response and problem drinking. METHODS: A total of 61 nondependent drinkers were assessed with the Alcohol Expectancy Questionnaire and Alcohol Use Disorder Identification Test and underwent functional magnetic resonance imaging while exposed to alcohol and neutral cues. Imaging data were processed and analyzed with published routines, and mediation analyses were conducted to examine the interrelationships among global positive score of the Alcohol Expectancy Questionnaire, Alcohol Use Disorder Identification Test score, and regional responses to alcohol versus neutral cues. RESULTS:Alcohol as compared with neutral cues engaged the occipital, retrosplenial, and medial orbitofrontal cortex as well as the left caudate head and red nucleus. The bilateral thalamus showed a significant correlation in cue response and in left superior frontal cortical connectivity with global positive score in a linear regression. Mediation analyses showed that global positive score completely mediated the relationship between thalamic cue activity as well as superior frontal cortical connectivity and Alcohol Use Disorder Identification Test score. The alternative models that AE contributed to problem drinking and, in turn, thalamic cue activity and connectivity were not supported. CONCLUSIONS: The findings suggest an important role of the thalamic responses to alcohol cues in contributing to AE and at-risk drinking in nondependent drinkers. AEs may reflect a top-down modulation of the thalamic processing of alcohol cues, influencing the pattern of alcohol use.
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