In a variety of neurological and psychiatric diseases, impairments in social judgement are one of the most disabling, yet poorly studied aspects. The difficulty in understanding this problem arises partly from the possibility that poor judgement can be thought of as a consequence of other difficulties, such as memory loss in Alzheimer's disease, elevated mood in mania, and delusional thinking in schizophrenia. However, isolated poor social judgement with preservation of cognitive function has been described in a relatively small group of patients with lesions in ventromedial and orbital prefrontal cortex, which raises the possibility that there are distinct neurobiological mechanisms underlying this phenomenon. These patients also fail to demonstrate the usual autonomic responses to important social stimuli, such as mutilation, while being able to describe these verbally without difficulty. The goal of this project is to create a model of this phenomenon in non-human primates and to analyze it from a behavioral and anatomical standpoint. The effects of these lesions on social behavior in controlled settings will be examined. The effects of reversible lesions of ventromedial and orbitofrontal cortex on recognition of socially relevant stimuli and the associated autonomic responses will also be assessed. In addition, the projections of the ventromedial and orbitofrontal cortex to autonomically related structures will be mapped using anterograde tracers. In addition to these research activities, this proposal is submitted as part of an overall plan of training and career development. Activities are outlined over a five-year period that will provide the Principal Investigator a unique opportunity to develop as a research scientist and help to insure his success in academic neurology.
