Over the last century, we have witnessed an astonishing rise in the prevalence of cognitive decline and dementia in older adults 1-3, which is expected to grow even faster in coming years as the global population rapidly ages 3-5. For decades, deficits in working memory - the ability to hold behaviorally useful information ?in mind? over a period of seconds - have characterized a central feature of the normal cognitive decline observed across the adult lifespan and the abnormal rapid cognitive deterioration associated with dementias, such as Alzheimer's disease 6-10. These facts motivate the need to advance greater understanding of the brain mechanisms underlying age-related working memory deficits, and develop effective methods to maintain or even improve cognitive performance in older adults 11-13. Here, we propose to examine the mechanisms of age-related working memory impairment in healthy humans from a physiologically inspired perspective centered on large-scale brain networks and how they interact through synchronized electrophysiological rhythms 14-18. We focus on neural coding schemes (i.e., cross-frequency coupling and phase synchronization) hypothesized to index flexible large-scale circuits that integrate information across multiple temporal and spatial scales during cognition. We combine high-density electroencephalographic (EEG) measurements of synchronized rhythms with individually customized high-definition transcranial alternating-current stimulation (HD-tACS) 19-21 to determine whether it is possible to modify components of frontotemporal networks and cause improvements in working memory performance for older adults. Our preliminary data are highly encouraging and indicate that we can causally manipulate the synchronization of long-range low-frequency rhythms, increase local phase-amplitude coupling, and rapidly improve working memory behavior in older adults aged 60-76 years to accuracy levels equivalent to those of 20-year-olds. The goals of the research program are to use novel neuroscience tools and analysis procedures to gain a deeper understanding of the brain mechanisms underlying age-related working memory impairment, and contribute new knowledge to the development of effective, non-pharmacological interventions for improving cognition in healthy aging and clinical populations.
Working memory is a fundamental building block of human cognitive information processing architecture, and impairments in working memory are a central feature of the normal cognitive decline in healthy aging as well as the rapid cognitive deterioration associated with dementias, such as Alzheimer's disease. This project combines the measurement of synchronized electrophysiological rhythms with improved neuromodulation technology to provide original and otherwise unapproachable causal insights into the neural architecture of top- down control and working memory in aging humans. This project also aims to lay the basic science groundwork for developing the next generation of drug-free strategies for improving cognition in age-related neurodegenerative disorders.
