Neural correlates of impulsive aggressive behavior in subjects with a history of alcohol dependence

Alcohol-related aggression is a complex and problematic phenomenon with profound public health consequences. We examined neural correlates potentially moderating the relationship between human aggressive behavior and chronic alcohol use. Thirteen subjects meeting DSM-IV criteria for past alcohol-dependence in remission (AD) and 13 matched healthy controls (CONT) participated in an fMRI study adapted from a laboratory model of human aggressive behavior (Point Subtraction Aggression Paradigm, or PSAP). Blood oxygen level dependent (BOLD) activation was measured during bouts of operationally defined aggressive behavior, during postprovocation periods, and during monetary-reinforced behavior. Whole brain voxelwise random-effects analyses found group differences in brain regions relevant to chronic alcohol use and aggressive behavior (e.g., emotional and behavioral control). Behaviorally, AD subjects responded on both the aggressive response and monetary response options at significantly higher rates than CONT. Whole brain voxelwise random-effects analyses revealed significant group differences in response to provocation (monetary subtractions), with CONT subjects showing greater activation in frontal and prefrontal cortex, thalamus, and hippocampus. Collapsing data across all subjects, regression analyses of postprovocation brain activation on aggressive response rate revealed significant positive regression slopes in precentral gyrus and parietal cortex; and significant negative regression slopes in orbitofrontal cortex, prefrontal cortex, caudate, thalamus, and middle temporal gyrus. In these collapsed analyses, response to provocation and aggressive behavior were associated with activation in brain regions subserving inhibitory and emotional control, sensorimotor integration, and goal directed motor activity.