In the present grant proposal the major purpose will be to test first whether there is a correspondence between animals and humans in terms of prefrontal cortex mediation of memory function and second to determine whether specific subregions of the prefrontal cortex differentially mediate specific memory functions. It has been proposed that the basic deficits in humans with prefrontal cortex damage are a) the inability to chronologically order sequential information on a short-term basis, b) a difficulty in coding egocentric spatial information, i,e,, they are not able to remember responses which depend upon accurate assessment of one's body orientation in space, and c) an impairment in appropriate processing of affect information as indicated by marked changes in emotional responsiveness and expression. Previous research has suggested that the prefrontal cortex in rats also mediates temporal structuring of information as well as egocentric localization and affect, suggesting a correspondence between animals and humans. In order to elaborate further on the role of the various subregions of the prefrontal cortex in processing temporal information, a behavioral model has been developed in rats in which one can measure a) a temporal memory LaA function for a list of spatial locations, b) memory for temporal configurations, c) memory for duration of a single stimulus or duration of time between the occurrence of specific stimuli, d) memory for egocentric localization using a memory for a response task and e) memory for affect using a memory for magnitude of reinforcement task. I propose to use this animal model as a means of continuing the investigation of the role of the prefrontal cortex in mediating temporal ordering, egocentric localization and affect information. It is hoped that the information gleaned from these studies will provide an understanding of the frontal lobe syndrome such that a rational therapeutic intervention can be developed.
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