EEG and unit activity during cognitive tasks will be recorded from the human Medial Temporal Lobe (MTL: hippocampus, parahippocampal gyrus, and amygdala). Electrodes are implanted for 2 to 5 weeks in order to localize a seizure focus. Large Event-related Potentials (ERPs) with similar task correlates and latency ranges as the scalp-N2, P3 and N4 have been identified in the MTL where they have distinct voltage topographies. MTL-N2 and P3 are larger to infrequent attended events. The MTL-N4 is recorded during verbal processing, and declines in amplitude to words as they are repeated after a delay. These and other MTL-ERP components will be further distinguished on the basis of their depth topography, supplemented by simultaneous unit recordings. Auditory discrimination, word recognition, and related tasks that differentially affect the latency and/or amplitude of MTL-ERP components, will be used to help distinguish and then characterize these components. The MTL-P3 and -N4 are probably generated within the MTL. Their relationship to scalp-ERPs will be evaluated across tasks, patients, and single trials. Possible volume-conduction of MTL-ERPs to the scalp will be evaluated by: scalp-ERP recordings before and after unilateral ATL removal for seizure relief and in amnesics with probable MTL damage; ERP recordings from neocortical and fronto-limbic sites; and comparison of the relative scalp attenuation for MTL-ERP components versus MTL epileptiform spike-wave complexes. Detailed ERP distribution across hippocampal laminae, unit recordings from single physiologically identified hippocampal neurons, and changes in scalp-ERPs under scopolamine or naloxone will be combined to help define possible synaptic generators of MTL-ERP components. Unit recordings will be further examined for evidence of specificity in synaptic activation. These studies will be useful for defining the neural basis of cognitive activity, especially in recent memory, and for evaluating the validity of proposed animal models of ERP components. Studies of scalp/depth ERP correlations may lead to noninvasive monitoring of MTL synapses, a potentially powerful tool for understanding the neural basis of normal aging and of neurological disease.
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