During the current funding period, we have formulated a theory to account for the defects in decision-making, planning and social conduct which are so salient in patients with frontal lobe lesions. It suggests that those defects result from defective activation of somatic markers that normally function as signposts for making decisions advantageous for the organism. The theory, based on previous data and on principles outlined in the SMR framework discussed in Project #1, will form the basis for testing a series of specific hypotheses regarding the composition of the neural network presumed to underlie the process of somatic marker activation. Psychophysiological measures (skin conductance, heart rate, facial EMG) will be used as indexes of somatic state activation, and we will study patients with focal lesions in the regions hypothesized to comprise the somatic state neural network. Among them are the ventromedial frontal, dorsolateral prefrontal, and somatosensory cortices. We will also investigate the judgment and decision-making capacities of target patients in a set of field experiments, and we will study the psychopathological manifestations of such patients using a comprehensive set of standard inventories and rating scales. Elucidation of the neural substrates of "executive functions" will advance neuroscience by contributing fundamental knowledge regarding decision- making and planning in social and other realms, and by promoting better diagnosis of the numerous patients who suffer from disturbances of executive function caused by neurological diseases such as head injury, stroke, and surgical ablation of tumors. Knowledge gained from this project will also permit the design of rehabilitation techniques which may allow patients to compensate for their defects and obtain gainful employment and more rewarding interpersonal relationships. Other applications include the extension of the theoretical constructs of this project to conditions such as psychopathy, obsessive-compulsive disorder, and the psychosocial consequences of chronic alcoholism and other forms of addiction. We anticipate that the results will have an impact on the field of education, and on the management of individuals with developmental forms of social conduct defect.