Alterations in Neural Networks Underlying Cognitive Aging

2006 new Scholar Award in aging

Cognitive aging in humans is characterized by performance deficits in older adults that cross multiple domains, including attention, short-term memory and long-term memory. These deficits impact the ability of older individuals to lead productive, high-quality lives. The goal of my research is to identify alterations in common neural mechanisms that underlie a wide range of cognitive deficits, so that we may generate a unified principle of cognitive aging. Understanding alterations in mechanisms associated with cognitive deficits is an essential step towards developing interventions to alleviate this burden.

To accomplish this goal, we study brain region interactions, or neural networks, that subserve top-down modulation and evaluate how these networks change with age. Top-down modulation is the process by which we enhance neural activity associated with relevant information and suppress activity for irrelevant information; it establishes a foundation for both memory and attention and is thus an ideal system to search for a unifying principle. We have recently discovered an age-related deficit in top-down modulation. Specifically, healthy older adults exhibit an inability to effectively suppress neural activity associated with distracting information, which is correlated with their short-term memory impairment.

This project will expand on this finding by utilizing a novel approach coupling multivariate analyses and an integration of three converging methodologies of human neurophysiology: transcranial magnetic stimulation (TMS), functional MRI (fMRI), and electroencephalography (EEG). Top-down modulation is driven by cortico-cortical projections from prefrontal cortices to sensory cortices. I hypothesize that prefrontal projections underlying top-down suppression are compromised in normal aging, resulting in the suppression deficit we recently reported. We will adopt a two-tiered approach to address this hypothesis: 1) Apply multivariate analyses, newly developed in our laboratory, to study alterations in top-down modulation networks in aging, 2) Use TMS to transiently disrupt prefrontal regions identified with fMRI in young adults and assess the consequences on cognitive performance and top-down modulation in sensory regions using EEG. Thus, we will determine if by selectively inhibiting prefrontal pathways in young adults, both neural measures of top-down modulation and cognitive performance can be made to mimic the pattern seen in older adults. These experiments will allow us to explore alterations in neural networks that underlie a wide-range of age-related cognitive deficits.