The overall goal of this project is to use evoked potentials (EPs) to track the sequential activation of different brain systems during human cognition. Depth recordings supported by this grant have established that the Medial Temporal Lobe (MTL) generates large EPs with similar latency ranges and task correlates as the scalp EP components N2, N4 and P3. Scalp recordings after left or right Anterior Temporal Lobectomy (ATL) have established that the major generating sites for these scalp EP components are outside the MTL. However, left ATL abolished the influence of repetition on the N4/P3 to words. MTL units fired to particular words or faces during the N4. These and other data suggest that the N4/P3 are generated by neural activity that divergently/convergently associates a particular stimulus with its context. In the next 5 years, we propose to expand these studies in 3 respects. First, by virtue of our collaboration with a different neurosurgical group, we will be able to map the N2/N4/P3 in almost every neocortical and limbic area using direct intracranial recordings. We also will be able to test the effects on scalp EPs of selective removals outside the temporal lobe, including the temporo-parieto- occipital junction and the frontal lobe. For example, our preliminary observations suggest a modality-specific N2 generator in the planum temporale and/or Heschl's g. Second, we propose to use laminar and unit recordings in the hippocampus' planum temporale/Heschl's g., and other structures to suggest the generating synaptic pathways and functional significance of the N2/N4/P3. Finally, we propose to study additional EP components using the above methods. We especially seek to distinguish and localize various negativities evoked in the 150-310 msec latency range in sensory association areas. These negativities appear to be generated by specific neural encoding of the stimuli per se, more localized anatomically and antecedant to the widespread contextual association reflected by the N4/P3. Overall, the proposed studies will deepen and broader our knowledge of cognitive EP in humans. This will permit: integrated neurocognitive models testable using scalp recordings in normal subjects; precise validation criteria for animal models of cognitive EPs, leading to basic neurophysiological studies; and direct functional tests for specific synaptic systems using scalp EPs in patients with neurological or psychiatric disease.
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