Symposium 12: Behavioural Disinhibition and its Relation to Affective Disorders

underlying the generation of brain pathology, we have studied the possible involvement of these molecules in the cognitive effects induced by glucocorticoids. Our results have highlighted CAMs regulation at the level of the hippocampus and the frontal cortex, as a correlate of time-dependent effects of stress and glucocorticoids on learning and memory processes. WITH Patients with bilateral damage to the ventromedial prefrontal cortex (VMF) develop severe impairments in personal and social decision-making, in spite of otherwise largely preserved intellectual abilities. This class of patients can be described as intelligent and creative before their brain damage. After the damage, they begin to pursue actions that often lead to losses of diverse orders, e.g., financial losses, losses in social standing, losses of family and friends. The choices these patients make are no longer advantageous, and are remarkably different from the kinds of choices they were known to make in the pre-morbid period. These patients often decide against their best interests. They are unable to learn from previous mistakes as reflected by repeated engagement in decisions that lead to negative consequences. Hence, we ascribed to them the term "acquired sociopaths". For many years, the condition of these patients has posed a double challenge. The first, although the decision-making impairment is obvious in the real life of these patients, there had been no laboratory probe to detect and measure this impairment. The second, there had been no satisfactory account of the neural and cognitive mechanisms underlying the impairment. Over the past few years, we succeeded in overcoming these challenges by, first, the development of the "gambling task" which enabled us to detect these patients' elusive impairment in the laboratory, measure it, and investigate its possible causes. Second, by making progress in understanding the nature of this impairment at the behavioral, physiological, and cognitive levels. In this paper, we review evidence suggesting that decision-making is a process guided by emotional signals (somatic states), which we define as the bio-regulatory responses that are aimed at maintaining homeostasis and ensuring survival. Damage to the VMF precludes the enactment of emotional (somatic) states in anticipation of future consequences, and consequently lead to disadvantageous decisions. The nature of this defect is discussed in relation to other mechanisms of the frontal lobe, including working memory, impulsiveness and response inhibition.