Studies are proposed to improve understanding of the structure and organization of declarative memory and the function of the hippocampus and related medial temporal lobe structures. In particular, the studies will test two contrasting views of hippocampal function, one that emphasizes memory and one that emphasizes spatial cognition. The work involves 8 separate studies, organized as two related topics: A. Memory and spatial cognition; B. Autobiographical memory and construction of episodes. A salient aspect of the proposed work is the continuing opportunity to study memory-impaired patients with bilateral hippocampal lesions or larger medial temporal lobe lesions that are well characterized in terms of quantitative neuroanatomy. Topic A attempts to reconcile two traditions of work on the hippocampus, one emphasizing memory and memory impairment and the other focusing on spatial navigation and spatial cognition. Topic B grows out of the recent explosion of interest in autobiographical memory, future imagining, scene construction, and the broad topic of mental time travel. A1 and A2 will study navigation and map reading ability in hippocampal patients and healthy volunteers in conditions where the burden on memory is minimal. A3 will test the ability of hippocampal patients to make horizontal shifts in perspective in extra-personal space. A4 will test the ability of hippocampal patients to accomplish shifts in perspective from overhead views to ground-level views of an environment. B1 will examine autobiographical memory and future imagining in hippocampal patients in conditions when minimal prompts are provided, following one of the protocols that have been used in this kind of work. B2 will explore these same abilities in hippocampal patients using extensive probing, following the main alternative protocol that has been used. A number of novel methods will be brought to the analysis of narrative constructions, including the unique opportunity to exchange data with another laboratory (full transcripts) in order to explore why laboratories have obtained different results when analyzing autobiographical narratives. B3 will use fMRI to ask whether hippocampal activity during the recollection of episodes correlates with particular aspects of narrative content, including the amount of spatial detail in the narratives. A second study asks in individuals with hippocampal lesions what other structures support recollection of episodic detail and whether activity in these structures correlates with aspects of narrative content. B4 involves a prospective, naturalistic, study of the capacity of hippocampal patients to construct episodic recollections about a structured event in which they participate. The proposed studies involve brain structures known to be important for declarative memory and for understanding memory impairment as it occurs in a number of psychiatric conditions. The work should provide new tests, improved understanding of the conditions that affect memory, and better insights about the ways that declarative memory is affected in mental disorders.
Impairments of conscious, declarative memory are a common feature of many kinds of mental illness. Through study of memory-impaired patients with hippocampal damage and fMRI the proposed work will illuminate the structure and organization of declarative memory, its relation to spatial cognition, and the organization of narratives. The introduction of novel analytic methods and the availability of a rich data base (e.g., narratives rather than test items) promise to improve understanding of remembering and imagining, which are important products of declarative memory.
| Urgolites, Zhisen J; Hopkins, Ramona O; Squire, Larry R (2017) Medial temporal lobe and topographical memory. Proc Natl Acad Sci U S A 114:8626-8630 |
| Squire, Larry R (2017) Memory for relations in the short term and the long term after medial temporal lobe damage. Hippocampus 27:608-612 |
| Ocampo, Amber C; Squire, Larry R; Clark, Robert E (2017) Hippocampal area CA1 and remote memory in rats. Learn Mem 24:563-568 |
| Smith, Christine N; Squire, Larry R (2017) When eye movements express memory for old and new scenes in the absence of awareness and independent of hippocampus. Learn Mem 24:95-103 |
| Urgolites, Zhisen J; Kim, Soyun; Hopkins, Ramona O et al. (2016) Map reading, navigating from maps, and the medial temporal lobe. Proc Natl Acad Sci U S A 113:14289-14293 |
| Sapiurka, Maya; Squire, Larry R; Clark, Robert E (2016) Distinct roles of hippocampus and medial prefrontal cortex in spatial and nonspatial memory. Hippocampus 26:1515-1524 |
| Dede, Adam J O; Wixted, John T; Hopkins, Ramona O et al. (2016) Autobiographical memory, future imagining, and the medial temporal lobe. Proc Natl Acad Sci U S A 113:13474-13479 |
| Dede, Adam J O; Frascino, Jennifer C; Wixted, John T et al. (2016) Learning and remembering real-world events after medial temporal lobe damage. Proc Natl Acad Sci U S A 113:13480-13485 |
| Smith, Christine N; Jeneson, Annette; Frascino, Jennifer C et al. (2014) When recognition memory is independent of hippocampal function. Proc Natl Acad Sci U S A 111:9935-40 |
| Smith, Christine N (2014) Retrograde memory for public events in mild cognitive impairment and its relationship to anterograde memory and neuroanatomy. Neuropsychology 28:959-72 |
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