Two brain regions--the Medial temporal cortex and prefrontal cortex--contribute prominently to aspects of human learning, storage, and retrieval. It is generally viewed that the medial temporal cortex is critical for the establishment and storage of new memories. The prefrontal cortex is involved in controlling and monitoring information that is to be stored or retrieved from memory. The specific aim of this project is to define and characterize more succinctly the functional contributions of these two brain regions and determine how they interact with each other and with memory representations stored in posterior cortical (associational) areas. Specifically, the proposal will focus n the analysis of medial temporal and prefrontal function in terms of the storage and binding of novel representations, proactive interference, and novelty encoding. One unique aspect of human memory is the establishment of complex representations--such as memory for episodic events or for newly learned semantic knowledge. Such representations can be formed, stored and often retrieved in a facile manner. The binding of such representations is proposed to be a key role of the medial temporal cortex. With respect to learning and remembering, prefrontal function serves to make this binding mechanism more efficient by selecting and maintaining appropriate encoding and retrieval strategies. For example, successful learning and retrieval depends of the ability to select relevant information and filter irrelevant information (e.g., reducing proactive interference). In addition, memory processes and be made more efficient by marking distinctive or novel events and disregarding familiar or usual ones. It is proposed that executive control processes associated with prefrontal cortex facilitate efficient memory processes by filtering irrelevant neural activity and selecting relevant (i.e., distinctive or novel) activity. In the proposed research, patients with medial temporal lesions and patients with frontal lobe lesions will be assessed on a variety of memory paradigms. Related studies using functional neuroimaging methods (fMRI, ERP) are proposed to define the dynamic relation between medial temporal and prefrontal activity.