BOLD and its discontents: age-differences in the neurophysiology of fMRI signal

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 DESCRIPTION (provided by applicant): 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.