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Neuronal Activity & Hemodynamics John VanMeter, Ph.D. Center for Functional and Molecular Imaging

Neuronal Activity & Hemodynamics John VanMeter, Ph.D. Center for Functional and Molecular Imaging Georgetown University Medical Center. Outline. BOLD contrast fMRI conceptually Relationship between BOLD contrast and hemodynamics Cellular energy processes

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Neuronal Activity & Hemodynamics John VanMeter, Ph.D. Center for Functional and Molecular Imaging

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  1. Neuronal Activity & Hemodynamics • John VanMeter, Ph.D. • Center for Functional and Molecular Imaging • Georgetown University Medical Center

  2. Outline • BOLD contrast fMRI conceptually • Relationship between BOLD contrast and hemodynamics • Cellular energy processes • Properties of the vasculature and blood flow • Relationship between neuronal glucose metabolism and blood flow

  3. BOLD Contrast fMRI • BOLD = Blood Oxygen Level Dependent contrast method • Fundamentally BOLD contrast is an indirect measure of blood flow • BOLD contrast as a measure of neuronal activity relies on: • Properties of the blood (deoxygenated hemoglobin concentration) • Relationship between blood flow and neuronal activity

  4. Basic Model of Relationship Between BOLD fMRI & Neuronal Activity

  5. Neuron

  6. Neuronal Activity • Integrative Activity • “Sum” of inputs at dendrites and/or soma (cell body) • Signaling Activity • Output from integrative activity resulting in signal transmission • Action Potential generates wave of depolarization down axon resulting in influx of Ca2+ • Subsequent release of neurotransmitter into synaptic cleft

  7. Neurotransmitter Release

  8. Brain Energy Budget(Rat Gray Matter) • Majority of energy used by brain related to integrative and signaling done in neurons • Thus, measures of energy consumption indicative of neuronal activity

  9. Cerebral Metabolism • fMRI cannot measure changes at the level of individual neurons • Functional imaging techniques fundamentally rely on measures of neuronal energy components • Glucose • Oxygen

  10. Nitty Gritty Details of Cellular Energy • ATP - adenosine triphosphate basic unit of cellular energy • Contains 3 phosphate groups • Hydrolysis • Energy is released when a phosphate group is removed by insertion of a water molecule • ATP produced from glucose (and pyruvate)

  11. ATP from GlucoseAerobic Metabolism • Three step process • Glycolysis • Glucose molecule is broken down in the cell resulting in pyruvate • 2 ATP consumed, 4 ATP produced = net increase +2 ATP • TCA cycle (aka Krebs cycle) • Oxygen (2 molecules) extracted from hemoglobin to oxidize pryuvate • Electron transport chain • Ultimate output of +34 ATP molecules

  12. ATP from Glucose Anaerobic Metabolism • Glycolysis still occurs • Pyruvate is reduced to lactate • Fast source of ATP but inefficient • 100 times faster than aerobic glycolysis • Only get 2 ATP molecules!

  13. Oxygen-to-Glucose Index (OGI) • Aerobic processing uses 6 molecules of oxygen for every 1 molecule of glucose • Empirical measurements at rest have shown OGI to be 5.5:1 • Implies most metabolism in neurons is aerobic but a small portion is anaerobic

  14. Delivery of Glucose & Oxygen • Vascular system (blood supply) is used to delivery basic components of cellular energy • fMRI measures changes in the oxygenated state of hemoglobin • fMRI intimately linked to vascular system

  15. Components of Vasculature • Arteries, arterioles, capillaries delivery oxygenated (oxy) blood and glucose to cells • Veins carry waste and deoxygenated (de-oxy) blood back to the heart • Oxygen & glucose extraction occurs at surface of capillaries

  16. Arteries & Veins of the Brain

  17. Major Arteries & Veins

  18. Blood Flow • Increase in neuronal activity supported by increase in blood flow • Rate varies as a function of vessel diameter, blood pressure, density of red blood cells, amount of O2 and CO2 • 40 cm/s in internal carotid • 10-250 mm/s in smaller arteries • 1 mm/s in capillaries

  19. Blood Flow • Blood flow is volume of blood delivered per unit of time • Proportional to blood pressure difference at either end of the blood vessel divided by resistance • Resistance determined by vessel radius • Small changes in vessel diameter results in major changes in flow • Flow controlled in part by resistance in vessels

  20. Stimulation, Arteriole Dilation, Blood Velocity, Blood Pressure • Stimulation results in dilation • Increasing velocity of blood • But blood pressure remains constant

  21. Vasodilation Spatial Extent • Winn, et al. localized neurons activated by stimulation by measuring changes in field potentials • Changes in vasodilation are localized

  22. Spatial Extent of Vasodilation

  23. Why is Spatial Extent of Vasodilation Important? • Ultimately the area over which the vasculature changes in response to neuronal activity determines spatial specificity of blood flow changes and thus a lower bound on spatial resolution for fMRI • BOLD fMRI is limited to ~1-2mm of effective spatial resolution

  24. Summary • fMRI BOLD signal arises from increase in blood flow • Blood flow is primary means for delivering oxygen and glucose to neurons for production of energy • Aerobic and anaerobic glycolysis implies different amounts of ATP (energy) production and oxygen requirements

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