Cognitive Neuroscience of Development and Aging (CONDA) Center

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Project Summary Goals of Parent Award (Original Abstract Text) This application for a Center of Biomedical Research Excellence (COBRE) would initiate a formal Center to lead, support, and expand neuroimaging and clinical cognitive neuroscience research in Nebraska, with an emphasis on lifespan development. It is an opportune moment for human neuroscience research in the Omaha community, regionally, and across the world, with many new research tools and government initiatives intended to illuminate the next frontier of biomedicine. The proposed Cognitive Neuroscience of Development and Aging (CONDA) Center will provide critical resources and support to faculty from four institutions: the University of Nebraska Medical Center (UNMC), the Boys Town National Research Hospital, the University of Nebraska – Omaha, and Creighton University. The Administrative Core of the CONDA Center will be housed at UNMC, which is less than two miles from each of the other institutions, and will be comprised of Training, Evaluation, Engagement, Administration, and Mentoring areas (i.e., the TEEAM Core). The new CONDA Center will also include a state- of-the-art Neuroimaging Acquisition and Analysis Core, as well as extensive support for four primary COBRE research projects led by a promising group of NIH-defined early-stage investigators. Upon initiation of the Center, the TEEAM Core would immediately implement a series of new programs that are designed to develop human cognitive neuroscience on the CONDA Campus and across the region. The TEEAM Core would also rapidly implement a comprehensive research support structure that includes the Neuroimaging Core facility, training opportunities, pilot projects and mini-grants programs, a new seminar series, postdoctoral fellowships, intern- ships for growing temporary and long-term laboratory staffing, and a participant registry to enhance recruitment. In parallel, the TEEAM Core would promote the successful launch of the primary COBRE research projects and, through a mentoring network approach, implement a career development and evaluation support system to monitor progress and ensure Junior PIs and their mentoring teams reach critical milestones. As per the new research core, the Neuroimaging Acquisition and Analysis Core facility would be the only core dedicated to human brain research in the state of Nebraska, and would provide regional scientists with state-of-the-art tools for neuroimaging and neuromodulation, including research-dedicated MRI and MEG systems. The new Center would also receive exceptional institutional support, including financial support for CONDA programs, major equipment expenses, and Core staffing. The overall CONDA team includes an established group of PIs in neuro- imaging, brain dynamics, aging, and brain and cognitive development, as well as a strong cohort of emerging junior investigators using innovative cognitive and affective neuroscience methods to address major questions in human neuroscience across the lifespan. Goals of the Team Science Supplement Proposal Our team science supplement proposal responds to NOT-GM-23-034 [Notice of Special Interest (NOSI): Availability of Administrative Supplements to IDeA Awards to Fund Team Science Development Projects], and it proposes research targeting a topic at the core of the CoNDA Center’s mission, studying the cognitive neuroscience of development and aging. Specifically, our proposal is titled “Elucidating the effects of polygenic AD risk on brain, cognitive, socioemotional, and behavioral outcomes in development and aging using a novel multimodal approach and a multigenerational sample”. The central premise of the proposed project is that lifespan development effects of genetic AD risk factors can be assessed with increased speed, rigor, and validity by enriching child samples with a matched, multigenerational sample of familial elders. Building on this premise, we propose to study the effects of Alzheimer’s disease polygenic risk (AD-PRS) on development and aging using an innovative multigenerational approach. Our new study will complement and extend the NIA-funded Polygenic Risk of Alzheimer’s disease in Nebraska Kids study (“PRANK”, R01 AG064247) that has enrolled more than 180 child participants. Here, we will enroll a new sample (N=72) consisting of the familial elders (age 65-85 years) of PRANK enrollees. We will measure brain, cognitive, and neuropsychiatric variables from the older adults along with AD risk factors (genetic) and AD biomarkers (neuropathological). This approach will allow us to pursue our four specific aims: Aim 1) Measure AD-related neuropathology and other brain variables in familial elders of PRANK participants led by Dr. Warren); Aim 2) Evaluate associations between AD-related cognitive/neuropsychiatric status and biological age in familial elders of PRANK participants led by CPL Dr. Beadle; Aim 3) Measure social factors including social network size, relationship quality, and dyadic interactions in familial elders of PRANK participants led by CPL Dr. Chen; and Aim 4) Measure the interactive effect of genetic AD risk factors and family connectedness on multi-modal brain age gaps using machine learning led by CPL Wang. Our innovative approach will provide key findings regarding the effects of AD-PRS in development and aging that would otherwise require decades of longitudinal monitoring of the same participants. Crucially, our team science approach is an essential part of this project. Our team includes diverse expertise in cognitive neuroscience, Alzheimer’s disease, development, aging, multiple neuroimaging methods, genetics, computational neuroscience, neuropathology, biospecimen assays, and more. Only by combining the effort of our outstanding team members could we pursue a project of this scope, and the team we build by completing this project will allow us to pursue additional research funding in the near future.