Project 2 is a direct extension of Project 1 utilizing the same controlled manipulations of glucose and insulin in the same normal young and older adults and patients with T2DM. The proposed experiments in Project 2 will employ fMRI BOLD imaging in the resting state (quiet wakefulness) to probe the effect of changes in glucose and insulin availability on the ongoing functional organization within and among brain systems and during the performance of a task designed to explore the acute mnemonic effects of hyperinsulinemia. To accomplish these aims we utilize fMRI BOLD imaging in two ways. First, we will evaluate the patterns of spatial coherence in the resting-state (quiet wakefulness) fMRI BOLD signal which have been shown to delineate relationships both within and among the major brain systems and their subcortical connections and to exhibit changes in patients with Alzheimer's disease particularly in relation to the brain's DMN. Second, we will evaluate regional, task-induced changes in the fMRI BOLD signal based on the observation that increasing insulin levels can improve cognitive performance, particularly in the memory domain. We propose to use a task, face-name recall, which can be implemented in the scanner, is commonly used in AD researchand exhibits stable test-retest reliability in older adults. Experiments in Project 2 also dovetail with and are greatly enriched by the studies in Project 3 which uses optical intrinsic signal (OIS) imaging a technique based on the same underlying physiology. fMRI and OIS are posited to depend on changes in glycolysis linked to blood flow and largely independent of oxygen consumption. We consider the changes they detect to be largely a glycolytically-driven, synaptic signal resulting in changes in hemoglobin oxygenation detectable by MRI and OIS imaging.
Project 2 will provide fMRI measures of the brain's functional status, both during task performance and in the resting state, to be correlated with PET metabolic measures in humans and corresponding functional measures (lactate and fcOIS) in mice.
|Kraft, Andrew W; Mitra, Anish; Bauer, Adam Q et al. (2017) Visual experience sculpts whole-cortex spontaneous infraslow activity patterns through an Arc-dependent mechanism. Proc Natl Acad Sci U S A 114:E9952-E9961|
|Su, Yi; Vlassenko, Andrei G; Couture, Lars E et al. (2017) Quantitative hemodynamic PET imaging using image-derived arterial input function and a PET/MR hybrid scanner. J Cereb Blood Flow Metab 37:1435-1446|
|Andrew, Robert J; Fernandez, Celia G; Stanley, Molly et al. (2017) Lack of BACE1 S-palmitoylation reduces amyloid burden and mitigates memory deficits in transgenic mouse models of Alzheimer's disease. Proc Natl Acad Sci U S A 114:E9665-E9674|
|Mitra, Anish; Snyder, Abraham Z; Hacker, Carl D et al. (2016) Human cortical-hippocampal dialogue in wake and slow-wave sleep. Proc Natl Acad Sci U S A 113:E6868-E6876|
|Harris, Richard A; Tindale, Lauren; Lone, Asad et al. (2016) Aerobic Glycolysis in the Frontal Cortex Correlates with Memory Performance in Wild-Type Mice But Not the APP/PS1 Mouse Model of Cerebral Amyloidosis. J Neurosci 36:1871-8|
|Stanley, Molly; Macauley, Shannon L; Caesar, Emily E et al. (2016) The Effects of Peripheral and Central High Insulin on Brain Insulin Signaling and Amyloid-? in Young and Old APP/PS1 Mice. J Neurosci 36:11704-11715|
|Su, Yi; Rubin, Brian B; McConathy, Jonathan et al. (2016) Impact of MR-Based Attenuation Correction on Neurologic PET Studies. J Nucl Med 57:913-7|
|Su, Yi; Blazey, Tyler M; Owen, Christopher J et al. (2016) Quantitative Amyloid Imaging in Autosomal Dominant Alzheimer's Disease: Results from the DIAN Study Group. PLoS One 11:e0152082|
|McAvoy, Mark; Mitra, Anish; Coalson, Rebecca S et al. (2016) Unmasking Language Lateralization in Human Brain Intrinsic Activity. Cereb Cortex 26:1733-46|
|Jin, Yan; Su, Yi; Zhou, Xiao-Hua et al. (2016) Heterogeneous multimodal biomarkers analysis for Alzheimer's disease via Bayesian network. EURASIP J Bioinform Syst Biol 2016:12|
Showing the most recent 10 out of 28 publications