ONLINE FIRST ORIGINAL ARTICLE Neural Correlates of Affect Processing and Aggression in Methamphetamine Dependence

Context:Methamphetamine abuse is associatedwith high rates of aggression but few studies have addressed the con-tributing neurobiological factors. Objective: To quantify aggression, investigate func-tion in the amygdala and prefrontal cortex, and assess relationships between brain function and behavior in methamphetamine-dependent individuals. Design: In a case-control study, aggression and brain activation were compared between methamphetamine-dependent and control participants. Setting: Participants were recruited from the general community to an academic research center. Participants: Thirty-nine methamphetamine-depen-dent volunteers (16 women) who were abstinent for 7 to 10 days and 37 drug-free control volunteers (18 women) participated in the study; subsets completed self-report and behavioral measures. Functional magnetic resonance imaging (fMRI)was performed on 25methamphetamine-dependent and 23 control participants. Main Outcome Measures: We measured self-reported andperpetrated aggression and self-reported alexi-thymia. Brain activation was assessed using fMRI during visual processing of facial affect (affectmatching) and sym-bolic processing (affect labeling), the latter representing an incidental form of emotion regulation. Results:Methamphetamine-dependent participants self-reportedmore aggression andalexithymia than control par-ticipants and escalated perpetrated aggression more fol-lowing provocation. Alexithymia scores correlated with measures of aggression. During affect matching, fMRI showed no differences between groups in amygdala acti-vation but found lower activation in methamphetamine-dependent than control participants in the bilateral ven-tral inferior frontal gyrus.Duringaffect labeling,participants recruited the dorsal inferior frontal gyrus and exhibited de-creased amygdala activity, consistentwith successful emo-tion regulation; therewas no groupdifference in this effect. Themagnitudeofdecrease inamygdala activityduringaffect labeling correlated inverselywith self-reported aggression in control participants andperpetrated aggression in all par-ticipants. Ventral inferior frontal gyrus activation corre-lated inversely with alexithymia in control participants