New Scholar Award in Aging
Anthony D. Wagner, Ph. D.
Stanford University

Age-related Changes in the Functional Neurobiology of Memory

Memory is crucial for many aspects of human behavior, from day-to-day behaviors, such as remembering to take medications, to more fundamental cognitive abilities, such as reasoning and problem solving. The centrality of memory for these and other cognitive behaviors is too often painfully evident when memory fails due to neurodegenerative disease, such as Alzheimer's (AD). Unfortunately, the frustrations and costs of memory failure in the elderly are not restricted to those suffering from AD. Anecdotal accounts and extensive behavioral research indicate that human memory declines during healthy cognitive aging. For example, relative to younger adults, older adults demonstrate impairments in item memory, which refers to the ability to later remember specific items or events that have occurred, such as recognizing a person that you previously met. In addition, healthy aging is associated with declines in relational memory, which refers to the ability to later remember that two items previously co-occurred, such as remembering the name associated with the face of a new acquaintance. Changes in both item and relational memory pose daily challenges for the elderly.

Memory is a by-product of the computations performed by large-scale neural circuits of the human brain. As a foundation for investigating the functional neurobiology of memory in the elderly, our laboratory has focused on characterizing how neural structures in the frontal lobes and the medial temporal lobes support memory formation in healthy younger adults. In this research, we use recently developed brain imaging methods - functional magnetic resonance imaging (fMRI) - to measure neural activity in the healthy human brain while the brain is in the throes of building new memories. Initial results indicate that distinct neural circuits contribute to item memory and relational memory in younger adults, including an inferior frontal-parahippocampal circuit implicated in item memory and a middle frontal-hippocampal circuit implicated in relational memory. Moreover, recent findings indicate that memory for linguistic items (such as words and names) and memory for visual items (such as faces, objects, and scenes) depend on distinct frontal lobe regions, respectively, revealing that the frontal lobes perform multiple distinct computations in support of memory.

The objective of the proposed research is to explore how the memory deficits that accompany healthy aging relate to changes in the neurobiological systems supporting item and relational memory. In the proposed research, we will use fMRI to scan the brains of healthy younger and healthy older adults with the aim of determining whether and how changes to the inferior frontal-parahippocampal and the middle frontal-hippocampal circuits relate to age-related declines in item and relational memory, respectively. Aim 1 is to test the hypothesis that the elderly are less likely to engage the circuits underlying item memory, but that when they are engaged these circuits are capable of supporting normal item learning. Aim 2 is to test the hypothesis that while distinct circuits in the left and right hemispheres of the inferior frontal lobes support linguistic and visual item memory in the young, the recruitment of these neurobiological systems is less sharply tuned in the elderly contributing to their memory difficulties. Aim 3 is to test the hypothesis that the middle frontal-hippocampal circuit associated with relational memory formation is more susceptible to age-related impairments relative to the item memory circuit, suggesting that changes in this circuit may be particularly relevant for understanding the memory deficits accompanying healthy aging. This endeavor holds the promise of providing important new insights into how the functional neurobiology of memory changes with age.

Contact Dr. Wagner.