This project will investigate the role of the hippocampus and related medial temporal lobe (MTL) structures insequence memory. These studies are guided by our recent findings with functional magetic resonanceimaging (fMRI) indicating that the human hippocampus is activated in early stages of sequence learning(Schendan et a)., 2003), and also our recent animal and modeling studies that suggest the hippocampus iscritical in memory for temporal order (Fortin et al., 2002), and for the disambiguation of overlappingsequences of events in memory (Sohal and Hasselmo, 1998; Agster et al., 2002). The proposed project hasthree specific aims.
The first aim i s to use fMRI to explore the scope of hippocampal involvement insequence learning in humans. Experiments 1 and 2 will examine hippocampal, parahippocampal, prefrontal,and striatal activity during the encoding, delay, and retrieval components of encoding tasks that will contrastlearning and memory performance for items, sequences of items, and spatial context information. Theseevent-related fMRI studies directly parallel studies that have been and will be carried out in animal models.Our hypothesis is that the hippocampus is critical not only for associative and contextual learning, but alsofor remembering the order of events in unique experiences. We further predict that perirhinal activity willrelate to item learning, but not contextual or sequence learning.
The second aim i s to use fMRI to explore therole of the hippocampus in sequence disambiguation. Experiments directly parallel studies in animal models(Agster et al., 2002; Wood, et al, 2000). Exp. 3 will examine hippocampal activation in encoding overlappingversus non-overlapping non-spatial sequences. Exp. 4 is the spatial analog of Exp. 3, and will examinenavigation through virtual reality mazes using overlapping and non-overlapping paths.
The third aim i s touse fMRI to contrast the medial temporal lobe, prefrontal, and striatal systems in sequence learning. Exp. 5examines implicit sequence learning in a sequence embedded in a 'prefrontal' N-back task. Exp. 6examines learning of first order (FOG) or second order conditional (SOC) sequences in an incidental pictureencoding task. The prediction is that FOG sequences will activate the striatum but not the MTL, whereasSOC sequences will activate the MTL. The combined studies will provide a hypothesis-driven examination ofepisodic sequence learning that closely parallels the studies and models proposed.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Specialized Center (P50)
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Special Emphasis Panel (ZMH1-ERB-A (03))
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Boston University
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Brown, Thackery I; Hasselmo, Michael E; Stern, Chantal E (2014) A high-resolution study of hippocampal and medial temporal lobe correlates of spatial context and prospective overlapping route memory. Hippocampus 24:819-39
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