The specific aim of this project is to experimentally examine the effect of alcohol on aggressive and impulsive responding, and on social-emotional information processing (SEIP) responses to threat, in individuals as a function of Alcohol Use Disorder (AUD) and prominent history of recurrent, problematic, impulsive aggressive behavior (AGG). While alcohol use is associated with impulsive aggression, little is known about the system neuroscience nature of this association except that the link between alcohol and aggression is most clear, and strongest, in individuals who are already high in trait aggression. Recent reports suggest that history of high lifetime alcohol use, in addition to acute alcohol dosing, dampens both cortical and subcortical responses to threat. In addition, acute alcohol administration appears to reduce cortical-subcortical connectivity, which some suggest is the primary correlate of alcohol-related aggressive behavior. However, this cannot explain all cases of alcohol-related aggression because neuronal correlates of aggression in non-alcoholics include an over, rather than under-activation of subcortical structures (i.e., amygdala) in the alcohol-free state. To advance our understanding of these complex relationships, we propose to study neuronal responses to socio-emotional threat in four groups of subjects: a) AUD and AGG (AUD+AGG); b) AUD without AGG (AUD); c) IED without AUD (AGG); and d) Healthy Controls (AUD-/AGG-), to uncover behavioral and neuro-circuitry differences in impulsive aggression and in the neuronal response to threat as a function of a history of AUD. Specifically, this study proposes to test the hypothesis that alcohol intoxication (0.08 mg%) is associated with increases in aggressive responding, and impairment in measures of SEIP, and to test the hypothesis that alcohol intoxication further affects cortico-limbic function in ways to increase the risk of impulsive aggression, though, perhaps, by different neuronal mechanisms as a function of AUD. Subjects will complete two (2) study sessions, in randomized order, in which each will receive intravenous alcohol (using alcohol clamp methodology), with alcohol doses clamped to achieve steady state alcohol breath levels of 0.08 mg%. Subjects will then complete a human laboratory aggression task and then an fMRI scanning session including two social-emotional information processing tasks: a) one that taps into the processing of explicit emotional cues of threat and, b) one that taps into the processing of ambiguous social cues of threat.
If successful, this would be the first study to experimentally demonstrate that: 1) aggression is increased, and social-emotional information processing is impaired, during controlled alcohol infusion and, 2) neuronal responses to explicit, and ambiguous, threat will be differentially influenced as a function of baseline aggression and of life history of AUD. Currently, little is known about the nature of social-emotional information processing to threat (processes that increase the risk of impulsive aggression in social contexts) and alcohol and little is known about system neuroscience processes that underlie alcohol intoxication. We expect that the data collected in this project will lead to insights into how to better treat impulsive aggression in the context of the of alcohol misuse.
