Explosive outbursts tied to prefrontal cortex dysfunction

People prone to episodes of impulsive, explosive aggression show deficits on cognitive tests that resemble those seen in people with lesions of a specific region of the frontal cortex, according to a new study.

Mary Best and colleagues studied 24 individuals (20 male and 4 female) diagnosed with intermittent explosive disorder (IED), a psychiatric disorder characterized by multiple serious acts of impulsive violence or property destruction that are grossly disproportional to a situation. The researchers administered neuropsychological tests to the subjects, comparing them to 22 control subjects.

Each group participated in three tests sensitive to lesions of the orbital/medial prefrontal cortex: a facial emotion recognition task, an odor identification test, and the Iowa Gambling Task, in which participants draw cards from four different card decks (two high- reward/high-risk decks that lead to an overall loss of money, and two lower-reward/lower-risk decks leading over the long term to an overall gain).

As a control, the researchers also administered two tests of working memory that measure the function of a different area of the prefrontal cortex.

The researchers report that IED subjects' performance on these control tests resembled the performance of the other subjects, while IED subjects were significantly impaired on all three tests of orbital/medial prefrontal function:

• On the Iowa Gambling Task, subjects with IED continued to pick cards from the disadvantageous decks at high rates, while controls shifted steadily to the more advantageous decks. This indicates, the researchers say, that the IED subjects "had difficulty learning to consistently avoid making choices that were associated with high levels of punishment." This is consistent with IED, they say, as "in everyday life, these patients continually use problem-solving strategies that involve aggression, even though it is socially inappropriate and frequently leads to injury or incarceration."
• On the facial recognition test, subjects with IED were impaired in identifying expressions of surprise, anger, and disgust, and frequently labeled neutral expressions as negative (while controls tended to label neutral expressions as positive). "Expressions such as anger or disgust can be warning signals of impending physical or psychological danger," the researchers say, "but subjects with IED may miss these signals until a dangerous situation has escalated. In addition, subjects with IED are primed to perceive negative emotion in neutral situations, which might explain why [they] seem to be easily provoked into negative interactions and conflicts with others."
• On the olfactory test, the average performance of subjects with IED was approximately two standard deviations below the population mean. Best and colleagues note that this finding is a particularly powerful piece of evidence linking IED to orbital/medial prefrontal cortical dysfunction, because it is well established that the neural pathways involved in odor detection and recognition include this brain region.

Symptoms of prefrontal dysfunction appear to be less severe in IED than in brain-injured patients, the researchers say, indicating that "subjects with IED simply have a milder form of brain insult because of a genetic and/or developmental abnormality." They suggest that IED may involve a disturbance in the prefrontal cortex's inhibitory effects on the amygdala, a brain area activated in response to emotional or fear- provoking situations. The brain dysfunction underlying IED, they say, is likely to involve the neurotransmitter serotonin, as impulsive aggressive individuals show evidence of reduced serotonergic activity and some cases of IED can be successfully managed with serotonin reuptake inhibitors such as Prozac and Paxil.

"Evidence for a dysfunctional prefrontal circuit in patients with an impulsive aggressive disorder," Mary Best, J. Michael Williams, and Emil F. Coccaro, Proceedings of the National Academy of Sciences, Vol. 99, No. 12, June 11, 2002, 8448-8453. Address: Mary Best, Department of Psychology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, bestm@emailchop.edu.