Using lifelike narratives to probe age-related differences in cortico-hippocampal functionality and episodic memory

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PROJECT SUMMARY Real-life events have a complex structure, yet we do not understand how the human brain supports structured representations of real-life events. Furthermore, we do not know how aging impacts the neural representation of realistic events, or recall of structured events from memory. This gap in our knowledge of human memory and cognitive aging is likely due to the fact that most investigations have employed stimuli (e.g. lists of words) that do not simulate the complexity of real-life events. Recently, lifelike stimuli (e.g. stories) have offered a new way to probe memory for real-life events, as well as the neural substrates which underlie the representation of real-life events. Studies which present lifelike stimuli during functional magnetic resonance imaging (fMRI) have found that activity in a posterior medial cortical network (PM network) may represent the structure of events in human memory. Coincidentally, the PM network is particularly vulnerable to Alzheimer’s pathology, at a “preclinical” stage when current neuropsychological tests, which do not simulate lifelike events, do not detect impairment. In order to set the stage for new, more sensitive cognitive tests that can detect early cognitive impairment, there is a need to study the functional relevance of the PM network to real-life memory in the absence of dementia. This proposal will use fMRI and state-of-the-art Representational Similarity Analysis techniques (RSA) to study how the PM network contributes to the representation of structured events in lifelike narratives, as well as the impact of aging on this representation (Aim 1). This proposal will then study the impact of aging on recall of events that comprise a structured narrative (Aim 2). Experiments will be conducted in older and younger adults via a two-day protocol with fMRI (Aim 1) and tests of recall (Aim 2). Aims will utilize an innovative, lifelike narrative paradigm which has already yielded a promising behavioral study in younger adults, and which, when paired with fMRI, will enable testing specific hypotheses about the neural representation of structured events. These Aims test hypotheses derived from a general theory: that the PM network is a substrate for prior knowledge about event classes (“event schemas”) that is used to parse our everyday experiences, and that this knowledge is reflected in the manner in which humans recall events at a later time. Moreover, it has been theorized that older adults develop these event schemas over the course of a lifetime. Aim 1 will test whether aging enhances the neural representation of structured events (in the PM network), and Aim 2 will test whether structured events exhibit preserved recall among older adults. Following pursuit of these Aims, exploratory translational studies will be pursued which correlate neural or behavioral measures of lifelike memories with available biomarkers of neurodegeneration. Any findings from proposed experiments will advance our understanding of human memory and cognitive aging, and set the stage for the development of more sensitive cognitive tests that detect cognitive impairment preceding overt dementia.