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

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Presentation on theme: "Neuronal Activity & Hemodynamics John VanMeter, Ph.D. Center for Functional and Molecular Imaging Georgetown University Medical Center."— Presentation transcript:

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 History of BOLD contrast Relationship between neuronal glucose metabolism and blood flow Theories about properties of BOLD contrast mechanisms

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 Ca 2+ –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 Glucose Aerobic 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!

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14 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

15 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

16 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

17 Arteries & Veins of the Brain

18 Major Arteries & Veins

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22 Blood Flow Increase in neuronal activity supported by increase in blood flow Rate varies due to vessel diameter, blood pressure, density of red blood cells, amount of O 2 and CO 2 –40 cm/s in internal carotid –10-250 mm/s in smaller arteries –1 mm/s in capillaries

23 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

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

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

26 Spatial Extent of Vasodilation

27 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 spatial resolution

28 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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