Schulte T2,3, Sullivan EV1, Pfefferbaum A1,2, Müller-Oehring EM1,2
1Dept. of Psychiatry and Beh. Sciences, Stanford University School of Medicine, Stanford, CA, USA
2Neuroscience Program, SRI International, Menlo Park, CA, USA
3 Pacific Graduate School of Psychology, Palo Alto University, Palo Alto, CA, USA
Emotion regulation skills are key to relapse prevention in alcohol use disorder (AUD). Emotional dysregulation may result from disturbed inhibitory mechanisms. We therefore tested emotion cue reactivity and inhibitory mechanisms using negative priming (NP). NP describes the phenomenon that when an object is ignored, subsequent responses to an object of the same semantic category are slower through spreading of the inhibition to related objects. To test the neural correlates of cue reactivity and NP, 26 AUD and 26 age-matched control subjects underwent functional MRI and performed a color match-to-sample NP task. Subjects matched the ink color of a word (e.g., the word RED printed in red ink) to the color of a prior sample by pressing a yes-key for color matches (e.g. red sample) and a no-key for non-matches (e.g., blue sample). Task-irrelevant emotion and alcohol-related information was presented as a picture or word with emotion/alcohol content. In trials containing both, alcohol/emotion pictures and words, the picture always primed the semantic content of the word, i.e., a happy face picture preceded the word HAPPY, a wine glass picture preceded the word WINE. Behaviorally, both groups showed response facilitation to picture cue trials and response inhibition to NP trials. For cue reactivity to emotion and alcohol pictures, AUD showed midbrain-limbic activation, confirming previous findings of a prepotent midbrain-limbic response to emotion and alcohol-related content. By contrast, controls activated frontoparietal executive control regions. Greater midbrain and hippocampal activation in AUD correlated with higher amounts of lifetime alcohol consumption, higher anxiety and impulsivity scores, which is frequently associated with relapse risk. With NP, AUD exhibited frontal cortical but not midbrain-hippocampal activation, similar to the pattern observed in controls. Higher frontal and less hippocampal activation with alcohol and emotion NP in AUD was associated with less alcohol craving. A diagnosis-by-content interaction revealed more extrastriate activation to positive emotion NP and less extrastriate activation to alcohol-related NP in AUD that was related to better mood. The findings suggest that neurofunctional systems in abstinent alcoholics can be primed to deal with upcoming emotion- and alcohol-related conflict and can overcome the prepotent midbrain-limbic cue reactivity response.