The ability to successfully form memories for arbitrary associations is essential for most acts of daily living. Numerous studies have shown that the hippocampus plays a critical role in associative memory. Recent work indicates that the perirhinal cortex (PRc) is also involved, but its functional role in associative memory is poorly understood. This research program will use functional magnetic resonance imaging (FMRI) and novel behavioral paradigms to test three theories of how the PRc contributes to associative recognition: (1) Unitization theory asserts that the PRc can support familiarity-based recognition of novel associations if the paired items are encoded as a single unit, but that the hippocampus is required for recollection of relations between items that are encoded as separate units. Novel FMRI experiments are proposed to test whether the PRc specifically contributes to recognition of associations between pairs of items that were encoded as a single unit. Parallel behavioral studies will test whether unitization influences indices of familiarity. (2) Domain theory asserts that the PRc supports familiarity- based recognition for associations between items from the same processing domain, but that the hippocampus is required to support recollection for associations between items from different processing domains. Novel FMRI studies are proposed to test whether the PRc supports associations between items from the same processing domains, but not associations between items from different domains. In addition, behavioral studies will test whether within-domain, but not across-domain associations influence the behavioral indices of familiarity. (3) Binding of items and contexts (BIC) theory asserts that the PRc represents item information, the PHc represents context information, and that this information is bound by the hippocampus. FMRI experiments are proposed to test whether recall of item information will be associated with PRc activity, whereas the recall of contextual information will lead to PHc activity. By testing the three theories, this proposal can provide the foundation for the development of a comprehensive theory of MTL function that can incorporate the influences of encoding processing, stimulus domain, and retrieval processing. Several psychiatric (e.g., schizophrenia) and neurological (e.g., Alzheimer's disease and traumatic brain injury) disorders are associated with memory impairments and with medial temporal lobe dysfunction. The proposed research may lead to improved diagnostic and therapeutic approaches to these disorders.

Public Health Relevance

Basic research on the mnemonic functions of the medial temporal lobe region is critically important because several psychiatric (e.g., schizophrenia) and neurological (e.g., Alzheimer's disease and traumatic brain injury) disorders are associated with memory impairments and MTL dysfunction. Such memory disorders can have a devastating effect on patients'quality of life. Research clarifying the basic neural mechanisms of memory can lead to improved diagnosis and treatment of these disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH083734-05
Application #
8403752
Study Section
Neurobiology of Learning and Memory Study Section (LAM)
Program Officer
Osborn, Bettina D
Project Start
2008-12-10
Project End
2014-11-30
Budget Start
2012-12-01
Budget End
2014-11-30
Support Year
5
Fiscal Year
2013
Total Cost
$360,903
Indirect Cost
$123,303
Name
University of California Davis
Department
Neurosciences
Type
Schools of Arts and Sciences
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
Parks, Colleen M; Yonelinas, Andrew P (2015) The importance of unitization for familiarity-based learning. J Exp Psychol Learn Mem Cogn 41:881-903
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Flegal, Kristin E; Marín-Gutiérrez, Alejandro; Ragland, J Daniel et al. (2014) Brain mechanisms of successful recognition through retrieval of semantic context. J Cogn Neurosci 26:1694-704
Koen, Joshua D; Yonelinas, Andrew P (2014) The effects of healthy aging, amnestic mild cognitive impairment, and Alzheimer's disease on recollection and familiarity: a meta-analytic review. Neuropsychol Rev 24:332-54
Gruber, Matthias J; Gelman, Bernard D; Ranganath, Charan (2014) States of curiosity modulate hippocampus-dependent learning via the dopaminergic circuit. Neuron 84:486-96
Bastin, Christine; Bahri, Mohamed Ali; Miévis, Frédéric et al. (2014) Associative memory and its cerebral correlates in Alzheimer?s disease: evidence for distinct deficits of relational and conjunctive memory. Neuropsychologia 63:99-106
Wang, Wei-Chun; Ranganath, Charan; Yonelinas, Andrew P (2014) Activity reductions in perirhinal cortex predict conceptual priming and familiarity-based recognition. Neuropsychologia 52:19-26
Ritchey, Maureen; Yonelinas, Andrew P; Ranganath, Charan (2014) Functional connectivity relationships predict similarities in task activation and pattern information during associative memory encoding. J Cogn Neurosci 26:1085-99
Aly, Mariam; Ranganath, Charan; Yonelinas, Andrew P (2014) Neural correlates of state- and strength-based perception. J Cogn Neurosci 26:792-809
Bastin, Christine; Diana, Rachel A; Simon, Jessica et al. (2013) Associative memory in aging: the effect of unitization on source memory. Psychol Aging 28:275-83

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