Evidence for a dysfunctional prefrontal circuit in patients with an impulsive aggressive disorder

Abstract

Humans with lesions to the orbital/medial prefrontal cortex and interconnected areas display impulsive aggressive behavior. To examine further the relationship between impulsive aggression and orbital/medial prefrontal dysfunction, we measured the behavioral performance of psychiatric patients with a disorder characterized by impulsive aggression, Intermittent Explosive Disorder (IED). Presently, no evidence exists for a localized brain lesion in IED subjects. However, on the basis of the location of brain lesions that produce acquired impulsive aggression, we hypothesized that IED subjects would exhibit test performance similar to patients with lesions to the orbital/medial prefrontal cortex. Subjects with IED and controls were administered three tests sensitive to lesions of the orbital/medial prefrontal circuit: the Iowa Gambling Task, facial emotion recognition, and odor identification, and two control tests of working memory. On the gambling task, IED subjects continued to make disadvantageous decisions throughout the 100 trials, whereas controls learned to avoid disadvantageous decisions. On the facial recognition test, IED subjects were impaired at recognizing "anger," "disgust," and "surprise," and they were biased to label neutral faces with "disgust" and "fear." On odor identification, IED subjects were mildly anosmic and were impaired relative to controls. However, on the working memory control tests, both groups performed similarly. Across tests, the performance of IED subjects resembles the performance of patients with orbital/medial prefrontal lesions in previous studies. These results extend the link between dysfunction of the orbital/medial prefrontal circuit and impulsive aggressive behavior.

Figure 1

Subjects with IED did not learn to avoid disadvantageous decks on the Iowa Gambling Task. (A) Percentage of cards selected from disadvantageous decks across time. IED subjects and controls (Con) showed a different pattern of responding across the four blocks of trials. (In this and all subsequent figures, error bars indicate ± 1 SEM.) (B) Ratio of disadvantageous picks from last 25 trials (quadrant 4) to first 25 trials (quadrant 1). IED subject ratio was significantly greater, which indicates that they were impaired at learning to avoid the disadvantageous decks over time. *, P < 0.015.

Figure 2

Subjects with IED made more errors and were biased to perceive negative facial expressions. (A) Number of errors made by each group for four facial expressions. Subjects with IED made significantly more errors for anger, disgust, and surprise. (B) Number of times subjects labeled neutral faces with each of the five expressions. Subjects with IED were more likely than controls (Con) to label neutral faces with disgust and fear. **, P < 0.025; *, P < 0 05.

Figure 3

Subjects with IED were impaired at olfactory identification. Bars indicate percentile scores on the UPSIT for all subjects or the subset of subjects who were nonsmokers for 10 years [control (Con), n = 17; IED, n = 16]. IED group scores were significantly lower. **, P < 0.002; *, P < 0.01.

Figure 4

Subjects with IED showed normal performance on working-memory tests. (A) Performance on the self-ordered pointing test was not significantly different between groups. (B) Performance on the Two-back test and the Two-back control test was not significantly different between groups. Con, controls.