INVITED COMMENTARY Hippocampal Function, Declarative Memory, and Schizophrenia: Anatomic and Functional Neuroimaging Considerations

Introduction Memory permits an organism to bridge the past with the present, providing information about prior encounters with a stimulus or context that can serve to build predictive models for the present. At the neurobiologic level, it is well established that the hippocampus and surrounding medial temporal lobe (MTL) cortices play an essential role in declarative memory (ie, long-term memory for general facts and specific events) [1–5]. The MTL memory circuit is composed of multiple structures, including the hippocampal formation and the surrounding entorhinal, perirhinal, and parahippocampal cortices. The hippocampal formation is further composed of the dentate gyrus, the fields of the cornu Ammonis (CA), and subiculum. Recent investigations of MTL processing have sought to characterize the mnemonic function of specific MTL substructures. Hypotheses regarding functional segregation within the MTL have largely focused on the hierarchical connectivity of the region, emphasizing potential functional differences between the hippocampus and surrounding cortices [6–8]. Recent studies have also explored potential functional distinctions between substructures within the hippocampus, such as CA3 and subiculum [7–10]. Hypotheses regarding the functions of MTL substructures draw heavily on knowledge of the anatomic connectivity of the region with structures in neocortex, as well as information about the intrinsic connectivity within MTL. Such anatomically guided hypotheses may prove particularly insightful when investigating disease processes that affect MTL. Schizophrenia is associated with memory impairments together with abnormalities in specific hippocampal substructures [11–14]. In particular, schizophrenic patients are impaired on declarative memory tasks [13,15], and functional neuroimaging studies have begun to reveal correlated hippocampal abnormalities. The present commentary reviews recent functional neuroimaging data regarding MTL function in the healthy brain and in schizophrenia. These initial observations are placed within the context of knowledge about projections to and within the MTL circuit, as anatomically informed models are likely to facilitate understanding of diseaserelated MTL dysfunction, potentially pointing to new avenues for intervention.