fMRI Investigation of Sequence Learning in Humans
Project 1 will use functional magnetic resonance imaging (fMRI) to investigate the role of the hippocampus and related medial temporal lobe (MTL) structures in sequence memory. These studies are guided by our recent findings with fMRI indicating that the human hippocampus is activated in early stages of sequence learning (Schendan et al., Neuron, 2003), and also our recent animal and modeling studies that suggest the hippocampus is critical in memory for temporal order (Fortin et al., 2002), and for the disambiguation of overlapping sequences of events in memory (Sohal and Hasselmo, 1998; Agster et al., 2002). The proposed project has three specific aims. The first aim is to use fMRI to explore the scope of hippocampal involvement in sequence learning in humans. We will examine hippocampal, parahippocampal, prefrontal, and striatal activity during the encoding, delay, and retrieval components of encoding tasks that will contrast learning and memory performance for items, sequences of items, and spatial context information. These event-related fMRI studies directly parallel studies that have been and will be carried out in animal models. The second aim is to use fMRI to explore the role of the hippocampus in sequence disambiguation. Experiments directly parallel studies in animal models (Agster et al., 2002; Wood, et al , 2000). The third aim is to use fMRI to contrast the medial temporal lobe, prefrontal, and striatal systems in sequence learning. The combined studies will provide a hypothesis-driven examination of episodic sequence learning that closely parallels the animal studies and models proposed in Projects 2-4.