Methamphetamine (MA) abuse is associated with a propensity for irritability, hostility, and aggression, resulting in high rates of interpersonal violence, emergency room/trauma center visits, assault and weapons charges1-9
, and ultimately public health and safety burdens10, 11
. Despite the frequent co-occurrence of aggression with MA abuse12-14
, however, the nature of their relationship remains under debate15-17
. Few laboratory studies have evaluated socio-emotional function in MA-abusing individuals18, 19
, and only one has directly assessed aggression20
. The aim of the present study, therefore, was to delineate possible relationships between brain function, emotion processing, and aggression in individuals who abuse MA.
Aggression (particularly impulsive aggression) is defined as any action toward another person that is elicited by provocation, driven by anger, and intended to cause harm. Its generation is conceptualized by the General Aggression Model21
, in which internal states are translated into either impulsive aggression or thoughtful action, depending on the success of appraisal and decision processes. These processes require introspection (i.e., appraisal and evaluation of one’s internal state) but they are only deployed if sufficient cognitive resources are available. As such, both cognitive capacity and emotional insight are necessary to produce a thoughtful outcome, while failure of either faculty can result in aggression.
Both faculties have been investigated in MA-abusing individuals. Studies of cognitive capacity22, 23
have suggested deficits in attentional control24
, response inhibition25, 26
, cognitive flexibility27
, and decision-making28-30
. Similarly, studies of emotional insight31, 32
have described poor self-awareness33
and difficulty with facial affect recognition and theory of mind19
. Disturbances in either capacity described by the General Aggression Model could therefore contribute to MA-related aggression, but these links have not been tested directly.
Neurobiologically, aggression is associated with emotion processing circuitry, particularly the amygdala and prefrontal cortex (PFC)34
. Whereas the amygdala mediates rapid, automatic responses to social stimuli35, 36
, especially emotional facial expressions37, 38
, PFC mediates the more deliberative aspects of emotion processing39
, with its ventral sectors implicated in semantic processing and integration of emotional information40-42
, as well as response selection and behavior control43
. The PFC can modulate amygdala activity through direct and indirect connections44-46
, and aggressive behavior relies on the integrity of this connectivity. Low PFC activity, high amygdala activity, and disruption of their connections have been linked to aggressive behavior in violent and psychiatric populations47-53
, and healthy individuals performing emotion regulation tasks, including restraint from aggression54
, exhibit PFC activation, reduced amygdala activity55-61
, and lowered markers of physiological arousal and subjective distress62-64
. These studies have consistently demonstrated involvement of the inferior frontal gyrus (IFG), often on the right side,55, 65, 66
which contributes to inhibitory control67
Individuals who abuse methamphetamine show abnormalities in this circuitry, suggesting a link between neurobiological deficits and their propensity for aggression. In PFC (particularly IFG68
), numerous structural, neurochemical, and metabolic differences have been identified69, 70
, and functional magmetic resonance imaging (fMRI) has uncovered deficits in PFC activation during cognitive27, 29, 71, 72
and socio-emotional tasks18, 73
. Examination of subcortical regions has also uncovered MA-related neurochemical and metabolic abnormalities in the amygdala20, 74, 75
. These neurobiological differences have been linked to moods, psychiatric states, and personality traits that can influence aggression70, 74-78
, and in one study, related to psychiatric states, and personality traits that can influence aggression70, 74-78
, and in one case related to aggression itself20
. However, no study has directly linked functional differences to emotion processing and aggression.
To address this issue, we previously conducted a fMRI study investigating neural responses to emotional facial expressions in MA-dependent individuals18
. Surprisingly, the study found no difference between MA dependent and Control participants in amygdala response but revealed activation differences in the right IFG. Because one of the roles ascribed to the right IFG is inhibitory control79
, including control over emotional responses80
, we reasoned that the IFG finding may relate to emotion dysregulation in the MA group. However, because the task did not assess emotion regulation directly, it was not possible to test this hypothesis. The study presented here therefore extended the task to include such a condition.
The added task condition (affect labeling) involves verbal labeling of emotional facial expressions, which, unlike the previously used visual matching condition (affect matching), requires symbolic representation of affect. In healthy individuals, affect labeling produces neural activation patterns that are consistent with emotion regulation (i.e., increased right IFG and lowered amygdala activity55-57
), and is accompanied by decreased markers of negative emotion57, 81
. Putting feelings into words, therefore incidentally recruits PFC resources whose activity can influence the amygdala, thereby regulating those feelings82
This study used fMRI to investigate the integrity of the PFC-amygdala circuit in MA dependent and Control participants and used self-report and behavioral measures to relate brain function to aggression and associated traits. Specific objectives of the study were 1) to quantify and compare aggression in MA and Control participants, (2) determine whether the previously observed difference in right IFG activation18
reflects a deficit in emotion regulation, and (3) investigate how these activation patterns relate to aggression.