fMRI of the Medial Temporal Lobe Memory System

Johns Hopkins University, Baltimore MD

Investigators

Abstract

FMRI of Medial Temporal Lobe Memory System Abstract With National Science Foundation support, Dr. Stark will conduct a three-year study using eight functional magnetic resonance imaging (fMRI) experiments are proposed to explore the contributions to declarative memory that are made by the hippocampal region (the hippocampus proper, dentate gyrus, and subiculum) and the entorhinal, perirhinal, and parahippocampal cortices. The project is divided into three sub-projects, with each aimed at addressing a specific set of questions. In the first subproject, the relationship between the neural substrates for encoding and retrieval is investigated. The experiments here attempt to determine whether incidental, automatic encoding can be observed during a recognition memory task. These experiments make use of the finding that the level of activity during an intentional encoding task can predict participants' subsequent memory (Brewer et al., 1998; Wagner et al., 1998). Experiments 1 and 2 assess whether activity associated with the novel foil items during a recognition memory task can predict whether participants will be able to remember those items when a second recognition memory task is administered outside the scanner. The observation of encoding-related activity during memory retrieval would help explain several null results in the literature, including several recent studies that demonstrated activity in the hippocampal region under some conditions, but not others. The second sub-project (Experiments 3-5) asks whether the hippocampus is particularly involved in declarative memory tasks that require the formation and use of associations. Several variations of this hypothesis are represented strongly in the literature, but the current data are inconclusive as to whether an associative / non-associative distinction adequately captures the division between the role of the hippocampal region and the role of the adjacent cortical structures. Experiment 3 uses the Remember / Know procedure to explore this hypothesis. Experiment 4 is an fMRI version of a continuous recognition memory task that has been previously used to explore single-item and associative memory in amnesic patients. Finally, Experiment 5 seeks to determine whether medial temporal lobe activity during retrieval is affected by the number of associations that constitute a memory. In the third sub-project, the neural substrates of false memories are explored, with the hypothesis that understanding how memories fail, and understanding how true and false memories might differ, will further our understanding of how the declarative memory system operates. Experiment 6 is an fMRI extension of a recent ERP study of reality monitoring errors (misattributing a memory as originating from a real rather than an imagined event). Experiments 7a and 7b use a "misinformation" paradigm also to study distortions of memory source. Here, we propose to trace the activity associated with a memory from its original encoding, through the encoding of subsequent contradictory misinformation, and to relate activity at both stages to the likelihood of retrieval of either the original or the subsequent misinformation. These studies will help address a central issue in the field: whether misinformation impairs or interferes with the actual memory of the original event, or whether it has no effect on the memory for the original event. Using fMRI to address questions about the medial temporal lobe poses an array of significant challenges. Signals are noisy and weak, there is significant distortion due to magnetic field inhomogeneity, simple techniques to anatomically normalize participants often perform poorly, and the medial temporal lobe often appears to be active, despite our best attempts to make it otherwise. However, the techniques in the proposed projects are specifically designed to alleviate these concerns and to make fMRI of declarative memory in the medial temporal lobes more viable. By focusing on the medial temporal lobes, scanning parameters, alignment techniques, baseline tasks, and other aspects of experimental design can be tuned to optimize the quality of the data, and therefore the impact of the results.