Simon W. Davis - US grants

[unreadable] DESCRIPTION (provided by applicant): A number of functional magnetic resonance imaging (fMRI) studies have show that older individuals often show increased activation outside of the cortical networks typically associated with successful task performance in young adults. Many of these studies have shown that high-performing older adults show both a bilateral pattern of brain activity not observed in young adults or in their low-performing counterparts, as well as a general trend to shift processing from posterior sensory regions to anterior association regions. The models of these patterns, the Hemispheric Asymmetry Reduction in Older adults (HAROLD), and the Posterior to Anterior Shift in Aging (PASA) posit that increases in contralateral and anterior recruitment (CR and AR, respectively) act as compensatory mechanisms for the increase in resource demands brought about by the biological degradation associated with normal aging. To further the understanding of changes in the reorganization of brain networks in aging we seek to identify the neural correlates of CR and AR. We will first seek to show that older adults benefit from bilateral more than unilateral processing (bilateral field advantage: BFA) in a split-visual field paradigm (Specific Aim 1). We will use diffusion tensor imaging (DTI) to evaluate both the structural morphology of the connection that mediate BFA (Specific Aim 2), as well as the influence of white matter integrity on functional networks of activation supporting BFA (Specific Aim 3). We therefore propose a series of multimodal experiments that rely on lateralized matching tasks designed to manipulate intra- and intrahemispheric communication demands between contralateral and ipsilateral brain regions. We expect activations associated with successful performance in older adults to observe a more frontal and bilateral pattern relative to young adult subjects, and that greater fiber integrity will mediate increases in cognitive performance, supporting compensatory accounts of aging. The proposed research program offers several novel approaches to the study of age-related reorganization of effective brain networks, and will clarify the role of white-matter connectivity in supporting healthy aging. Furthermore, this project seeks to characterize mechanisms that help to offset the detrimental effects of aging, and suggests cognitive therapies in both healthy and pathological aging populations. [unreadable] [unreadable] [unreadable]

Project Summary This is an application for an Funded Extension (Administrative Supplement award) to an existing project, Using fMRI-guided TMS to increase central executive function in older adults. This award will provide our team with the support necessary to extend our existing EEG-TMS paradigm to patients with a prodromal form of Alzheimer?s Disease (AD) known as amnestic Mild Cognitive Impairment (MCI), and investigate the role of brain health factors in mediating the TMS-related memory performance benefits associated with communication between a network of frontoparietal brain regions in these populations. The main goal of the project is to address develop a novel approach to memory-based neurostimulation therapies. Neurostimulation affects multiple sites within a cortical network, but these global effects have not been used as targets for stimulation because of limited knowledge about what influence these localized sites have on global changes in brain state. To address this problem, we will use multimodal neuroimaging tools and network modeling approaches developed though the parent U01 project, to demonstrate how focal neurostimulation improves the efficacy of TMS for enhancing memory function. These goals will be addressed in the Administrative Supplement under our three specific aims. In Aim 1, Dr. Davis will establish the spatial specificity of bilateral brain mechanisms with combination of behavior and high-resolution structural neuroimaging in cortical sites known to be active during memory encoding. In Aim 2, Dr. Davis will establish the underlying dynamics of interhemispheric frontal communication using a novel combination of single-sided TMS, rTMS entraining conditions, and electroencephalography (EEG) to establish the coordinated activity between the hemispheres; Lastly, in Aim 3, Dr. Davis will use the rTMS entraining parameters delineated in Aim 2 to promote specific cross- hemispheric communication, applied to participants performing a Word Encoding task, a general task of memory performance. The ongoing work will provide an important tool for studying the dynamics of network connectivity of memory states in the aging brain, as well as new information on the effectiveness of brain stimulation technologies as a therapeutic approach for cognitive decline. The parent K01 project has made foundational advances towards these goals, as we have demonstrated the ability of to selectively modulate memory-related neural functions in healthy older adults and MCI. The project has proceeded successfully through Years 1-3, with multiple conference publications and prepared manuscripts, and the achievement of developmental goals in Clinical and Electrophysiology didactics. However, as outlined in the Budget Justification, the project has incurred a significant delay due to the COVID- 19 global pandemic, and in order to complete the project we request additional funds through this Supplement. The scientific goals and approach remain unchanged from the original proposal.