FUNCTIONAL AND NEURONAL MECHANISM OF INTERVAL TIMING

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The present proposal is a competing continuation of a project studying the functional and neural mechanisms of temporal processing in patient populations with Parkinson's Disease (PD). The previous work has dissociated storage (encoding) and retrieval (decoding) deficits, and isolated specific neural substrates of temporal processing with distinct cognitive deficits. Parallel effects have been seen with normal aging as well, and are isolated to the time domain. The continuation would follow these results in five different directions: (1) Further work with Parkinson's patients ON/OFF Levodopa medication is designed to clarify the etiology of different dysfunctional components as these develop early (de novo) and later in the disease; (2) chronic deep brain stimulation (DBS) will be used to isolate dysfunctions to particular structures in the basal ganglia, particularly the subthalamic nucleus (STn) and the internal and external portions of the globus pallidus. Stimulation of the pallidus will be contrasted with comparable performance by patients before and after therapeutic pallidotomy; (3) some but not all of the temporal processing dysfunctions observed in PD have been seen in aged populations as well. The role of feedback, shown to be an important factor in temporal learning and memory for the aged is studied with designs which separate memory updating from strategic adjustment; (4) work with rats using comparable procedures to separate storage from retrieval processes under dopamine (DA) antagonists has begun with a single time value. This will be expanded to two time values and DA agonists as well; and finally, (5) theoretical work on the project is ongoing, studying an adaptation of a connectionist pacemaker/accumulator model (Miall, 1992). This modeling permits study of a non-linear stochastic systems, which are forced by retrieval in our DA data.