Frontal theta as a mechanism of aging-related differences in cognitive control

Project Summary/Abstract Aging is associated with declines in cognitive control, the mental process that facilitates goal- oriented behaviors. Declining cognitive control affects older adults' ability to have healthy and productive personal and professional interactions, which decreases quality of life and increases hospitalization and mortality rates. There are currently few effective therapies to treat age-related declines in cognitive control. Thus, there is an unmet need to develop new treatments for aging-related cognitive decline. However, there is a gap in our understanding of the underlying mechanisms of aging-related cognitive decline. Cognitive control is associated with coordinated patterns of brain activity across a network of brain regions that includes the frontal cortex. In particular, low-frequency oscillations in the theta frequency band (4-7 hz) in the frontal cortex have been shown to be important for cognitive control. The overall goal of the proposed research is to identify how aging affects these circuit mechanisms. My overall hypothesis is that the medial region of the frontal cortex oscillates at theta-band frequency to support cognitive control, and attenuated midfrontal cortex theta oscillations in older adults accounts for aging-related differences in cognitive control. I will employ two distinct experimental designs to test this overall hypothesis. First, I will test the hypothesis that theta oscillations in the medial regions of the frontal cortex demonstrate task-relevant theta power to a great extent than lateral regions in the frontal cortex. I will test this hypothesis using human intraoperative recordings during intracranial surgeries in cognitively-intact Parkinson's disease and essential tremor patients. Second, I will examine brain activity of both young and older adults as they complete two tasks designed to engage cognitive control. Here I will test the hypothesis that aging- related differences in cognitive control correspond to reduced theta oscillations in the frontal cortex. This hypothesis predicts that theta-band oscillations will be lower in older adults compared to young adults, and reduced theta oscillations will be associated with worse cognitive control. Together, the proposed experiments will contribute to a model establishing how changes in large- scale oscillatory dynamics in precise regions of the frontal cortex correspond to aging-related declines in cognitive control. An outcome of the data from this proposal is expected to be knowledge of candidate targets for therapies for cognitive impairment. This is highly relevant for aging and for aging-related disorders such as Alzheimer's Disease and other Alzheimer's disease-related dementias and Parkinson's disease.