The Episodic Memory System: Neurocircuitry and Disorders

The ability to encode and retrieve our daily personal experiences, called episodic memory, is supported by the circuitry of the medial temporal lobe (MTL), including the hippocampus, which interacts extensively with a number of specific distributed cortical and subcortical structures. In both animals and humans, evidence from anatomical, neuropsychological, and physiological studies indicates that cortical components of this system have key functions in several aspects of perception and cognition, whereas the MTL structures mediate the organization and persistence of the network of memories whose details are stored in those cortical areas. Structures within the MTL, and particularly the hippocampus, have distinct functions in combining information from multiple cortical streams, supporting our ability to encode and retrieve details of events that compose episodic memories. Conversely, selective damage in the hippocampus, MTL, and other structures of the large-scale memory system, or deterioration of these areas in several diseases and disorders, compromises episodic memory. A growing body of evidence is converging on a functional organization of the cortical, subcortical, and MTL structures that support the fundamental features of episodic memory in humans and animals

A pathophysiological framework of hippocampal dysfunction in ageing and disease

The hippocampal formation has been implicated in a growing number of disorders, from Alzheimer's disease and cognitive ageing to schizophrenia and depression. How can the hippocampal formation, a complex circuit that spans the temporal lobes, be involved in a range of such phenotypically diverse and mechanistically distinct disorders? Recent neuroimaging findings indicate that these disorders differentially target distinct subregions of the hippocampal circuit. In addition, some disorders are associated with hippocampal hypometabolism, whereas others show evidence of hypermetabolism. Interpreted in the context of the functional and molecular organization of the hippocampal circuit, these observations give rise to a unified pathophysiological framework of hippocampal dysfunction