Neurocognitive aging theories are based on age differences in blood-oxygen-level-dependent signal (BOLD) as measured with functional magnetic resonance imaging (fMRI). However, there is a growing recognition that BOLD age-changes result from many physiologic, neural, and cognitive factors that remain poorly understood and complicate interpretation of BOLD as a straightforward index of age-related neural change. More precise neurocognitive aging hypotheses can be formulated once the physiologic factors underlying age-related BOLD change are disentangled and measured separately. Three such factors are changes in cerebral blood flow (CBF), that deliver O2 to active neurons, change of the cerebral oxygen metabolism rate (CMRO2), an estimate of metabolic neural activity, and event-related potential (ERP), an estimate of post-synaptic neural activity. These factors have not been studied as extensively in aging as we propose to here. Using a dual-echo BOLD/ASL MRI pulse sequence, we have recently demonstrated that these important physiologic factors can be measured in brain aging studies, simultaneously with conventional BOLD signal. In this proposal, we plan to conduct a more systematic study to assess the relationship between age and task-evoked physiologic responses in blood flow, blood oxygenation, brain metabolism, as well as the influence of task-demand on these factors. We propose a general model on age-related changes in brain physiology that can reconcile diverse results in neurocognitive aging literature. We test the model in three Aims.
Aims 1 and 2 are to measure age differences in visual and motor cortex BOLD, ERP, CMRO2, and CBF response to sensory and motor task-demands of varying strength.
In Aim 3 we will assess the role of CBF-CMRO2 uncoupling in age- related working memory and processing speed changes. Achieving our grant aims will yield new knowledge about (1) basic mechanisms of age-changes in neural function, (2) age-related neural-vascular changes that give rise to BOLD changes, and (3) how these basic mechanisms are tied to performance.

Public Health Relevance

Current brain aging theories are based on functional magnetic resonance imaging (fMRI) signal. However, there is a growing recognition that this signal does not accurately reflect age differences in brain activity. We propose new fMRI techniques to measure diverse brain-activity indices, permitting a greater understanding of how brain aging leads to the mental slowing and memory changes that characterize the adult human life-span.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG047972-02
Application #
9134043
Study Section
Neuroscience and Ophthalmic Imaging Technologies Study Section (NOIT)
Program Officer
Wagster, Molly V
Project Start
2015-09-01
Project End
2020-04-30
Budget Start
2016-05-01
Budget End
2017-04-30
Support Year
2
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Psychiatry
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
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Li, Yang; Mao, Deng; Li, Zhiqiang et al. (2018) Cardiac-triggered pseudo-continuous arterial-spin-labeling: A cost-effective scheme to further enhance the reliability of arterial-spin-labeling MRI. Magn Reson Med 80:969-975
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Wei, Zhiliang; Chen, Lin; Lin, Zixuan et al. (2018) Optimization of phase-contrast MRI for the estimation of global cerebral blood flow of mice at 11.7T. Magn Reson Med :
Jiang, Dengrong; Liu, Peiying; Li, Yang et al. (2018) Cross-vendor harmonization of T2 -relaxation-under-spin-tagging (TRUST) MRI for the assessment of cerebral venous oxygenation. Magn Reson Med 80:1125-1131
Lin, Zixuan; Li, Yang; Su, Pan et al. (2018) Non-contrast MR imaging of blood-brain barrier permeability to water. Magn Reson Med 80:1507-1520
Hubbard, Nicholas A; Sanchez Araujo, Yoel; Caballero, Camila et al. (2017) Evaluation of Visual-Evoked Cerebral Metabolic Rate of Oxygen as a Diagnostic Marker in Multiple Sclerosis. Brain Sci 7:

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