This is a study of human memory at the neuronal level in the hippocampus and neighboring regions in conscious awake human subjects. At the center of this proposal is the unique role of medial temporal lobe structures in conscious retrieval. The neuronal basis for this role is unknown and is virtually impossible to study in animals, since humans are the only species that can """"""""declare"""""""" their memory. The study is based on unique opportunity to record single unit activity outside the operating theater in awake patients with intractable seizures who are implanted with depth electrodes for more precise localization of the epileptogenic focus. Using recent advances in stereotaxis guided by magnetic resonance imaging, electrodes carrying bundles of microelectrodes are implanted in five medial temporal lobe sites including amygdala, anterior hippocampus, middle hippocampus, entorhinal cortex and posterior parahippocampal gyrus. thus, single unit activity can be recorded simultaneously at precisely defined sites during presentation of memory tasks. The central hypothesis of the study pertains to the role of hippocampus in both encoding and retrieval of information. It states that: 1) The hippocampal formation, together with entorhinal and parahippocampal cortices, constitutes a neuronal matrix that, in a context- and time-dependent fashion, binds complex attributes of stimuli into a memory trace. 2) This memory trace then affects hippocampal neuronal activity when the stimulus is explicitly, but not implicitly, retrieved later. 3) Neuronal activity during explicit retrieval depends on the similarity of the original stimulus to the retrieval cue. The focus of the experimental design is upon direct comparison of neuronal activity in the hippocampus and associated structures during implicit and explicit retrieval of verbal and nonverbal information. This is accomplished through two paradigms, one using word-stem cures and the other using structurally possible and impossible figures. Two other tasks will be used as well: one is the delayed non-match to sample task using face, object and work stimuli; the other is an episodic recognition task designed to examine the persistence of long-term traces in the hippocampus and its neighboring regions.
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