Prefrontal Cortical Regulation Of Aggression

The dorsolateral prefrontal cortex receives extensive afferents from multiple posterior neocortical association areas, including dense connections with the inferior parietal lobule, a region responsible for surveying extrapersonal space for relevant stimuli. The orbitofrontal cortex is reciprocally connected to the rest of the neocortex principally via the dorsolat-eral convexity of the frontal lobe. Projections from the hypothalamus through the dorsal medial nucleus of the thalamus and from the rostral temporal lobe through the uncinate fasciculus inform the frontal lobes of both internal (hypothalamus) and external (neocortical association to temporal lobe) stimuli of affective significance.

The prefrontal cortex has direct outputs to the pyramidal motor system, the neostriatum, temporal neocortex, and the hypothalamus. Schematically, prefrontal cortices appear to integrate a current account of the outside world, the state of the internal milieu, and the recognition of drive-relevant objects with knowledge of learned social rules and previous experiences relating to reward and punishment. The prefrontal cortex may play a particularly important role in both working memory and social modeling, maintaining an abstract representation of the world that allows anticipation of the effects of one's actions on other individuals and the likely consequences of such actions. The prefrontal cortices construct a behavioral plan that is consistent with experience and especially the rules of socialization in order to optimize the satisfaction of biological drives.

The simplest summary of these complex functions in humans is judgment, which should not be simply equated with purely rational cost-benefit calculations that may be quite time-consuming and biologically uneconomical. Rather, it has been proposed that, in selecting among alternative response options, prefron-tal cortices are guided by internal, somatic state markers—physiological cues that allow rapid choice of previously rewarded, effective options. Damage to the dorsal convexity in humans results in a diminution of long-term planning and a state of apathy or indifference. On formal neuropsychological testing, shifting of response set and the ability to apply strategy to problem solving are impaired. In contrast, damage to the orbital undersurface of the frontal lobe has classically been described as resulting in superficial, reflexive emotional responses to stimuli in the immediate environment. Patients are impulsive, acting without foresight or consideration of the remote consequences of their actions. Orbital frontal lesions thus lead to episodes of transient irritability. Often, a patient strikes out quickly after a trivial provocation, with little consideration of social prohibitions limiting aggressive behavior or untoward future consequences. The targets of aggression are categorically appropriate, but patients are unable to apply abstract rules that would override the immediate environmental provocation.

Numerous case reports illustrate the tendency of patients with orbitomedial frontal injuries to act impulsively, without regard to long-term consequences or sustained courses of action. Most well-known is the paradigmatic case of Phineas Gage, a railroad worker who suffered an injury primarily to the left orbitomedial frontal lobe when an explosion projected a tamping rod through his skull. Subsequently, in the words of his physician, "he was no longer Gage.'' Previously a temperate, hardworking individual, he became "disrespectful," "irreverent," and "profane." He rejected all attempts to restrain him from satisfying desires of the moment but rapidly abandoned plans he made to achieve these desires.

In addition to detailed single case studies, case series of murderers have demonstrated a high incidence of frontal structural abnormalities on CT and magnetic resonance imaging (MRI), frontal hypofunction on position emission tomography (PET), and abnormal neuropsychologic performance on frontal systems tasks. Frontal ventromedial lesion location independently predicted aggression and violence among 271 America veterans who suffered penetrating head injuries in the Vietnam war.

Convergent evidence for a critical role of the orbitofrontal cortex in evoking internal somatic markers to regulating aggression is supported by studies of neurologically normal individuals with antisocial personality disorder and high psychopathy scale scores, who demonstrate diminished autonomic reactions to negative stimuli, decreased orbitofrontal activity in some functional imaging studies, and reduced prefrontal gray matter volumes on volumetric MRI studies.

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