1. Physiological Basis of fMRI (and Neuroanatomy, in brief)
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2. I.Neurophysiology What brain processes consume energy?
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3. fmri-fig jpg
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4. There are two primary types of information flow in the CNS:
Signaling via action potentials (axonal activity) and
Integration via dendritic activity
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5. Depolarization opens CA2+ channels
Action potential
Depolarization opens CA2+ channels
Vesicles fuse with presynaptic membrane
Neurotransmitter release
Neurotransmitters open ion channels on postsynaptic membrane
fmri-fig jpg
Change in potential
IPSP or EPSP
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6. Energy Demands of Integration/Signaling
Following activity, neurons require energy to restore concentration gradients of key ions.
Sodium-Potassium pump takes sodium out of the cell while bringing potassium into the cell.
Note that for action potentials, the movement of ions is along gradients.
fmri-fig jpg
Key concept: activity of neurons does not itself require energy; restoring membrane potentials afterward does.
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7. What metabolites are the sources of that energy?
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8. Oxygen (via hemoglobin)
Glucose
fmri-fig jpg
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9. Facts about energy supply to brain
30-50 μmol/g/min of ATP for awake brain
10 μmol/g/min of ATP for comatose brain
Information processing accounts for >75% of ATP consumption
54mL/min of blood for each 100 g of brain tissue
Brain is ~3% of body weight, but demands 15-20% of blood flow and ~20% of blood oxygen
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10. Data from rodent models (Attwell & Laughlin, 2001)
Data from rodent models (Attwell & Laughlin, 2001). In humans, integrative activity may be 50% greater.
fmri-fig jpg
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11. Why do neuroenergetics matter?
Information reduction necessitated by energy demands!
How could we increase information transmission?
Decrease membrane resistance  finer-resolution of dendritic activity (~200Hz)
Increase action potential rate (~ Hz)
Decreasing membrane resistance would increase maintenance costs
Increasing action potential rate would rapidly increase signaling costs
The energy available to the brain limits neural information processing
Attwell and Gibb, 2005
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12. How are energy sources (metabolites) delivered?
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13. The brain does not store glucose and oxygen in appreciable quantities.
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14. fmri-fig jpg
Duvernoy, H. M., Delon, S., & Vannson, J. L. (1981). Cortical blood vessels of the human brain. Brain Research Bulletin, 7(5),
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15. Arteries (1-25mm) Arterioles ( microns) precapillary sphincters Capillaries (5-10 microns) Venules (8-50 microns) Veins
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16. Key concepts in vascular system
Vast change in scale from largest arteries to capillaries
Small changes in diameter result in large changes in flow (2x diameter = 16x flow)
Pulsatile flow in arteries smoothed out by resistance vessels (arterioles)
Surface area of capillaries is essential for O2 exchange
Neurons are usually within 20μm from a capillary
Capillaries are not always perfused!
Blood can bypass capillaries
Saves weight, cost (in blood), etc.
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17. fmri-fig jpg
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18. (anastomosis of internal carotids and basilar artery)
fmri-fig jpg
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19. MCA – Anterolateral cortex
ACA – Medial cortex
MCA – Anterolateral cortex
PCA – Posterior temporal and occipital lobes
fmri-fig jpg
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20. Sinus. n. An separation of the dura mater in which blood drains into the venous system.
fmri-fig jpg
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21. FMRI – Week 5 – MR Signal Scott Huettel, Duke University

22. FMRI – Week 5 – MR Signal Scott Huettel, Duke University

23. Distribution of vascularization across cortical layers
fmri-fig jpg
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24. Capillary structure fmri-fig-06-09-0.jpg
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25. How does function map onto blood flow?
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26. Iadecola, Nature Reviews Neuroscience, 2004
“[Mosso] relates of his female subject that one day whilst tracing her brain-pulse he observed a sudden rise with no apparent outer or inner cause. She however confessed to him afterwards that at that moment she had caught sight of a skull on top of a piece of furniture in the room, and that this had given her a slight emotion.”
-James Principles… (1890)
Iadecola, Nature Reviews Neuroscience, 2004
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27. “These facts seem to us to indicate the existence of an automatic mechanism by which the blood supply of any part of the cerebral tissue is varied in accordance with the activity of the chemical changes which underlie the functional action of that part. Bearing in mind that strong evidence exists of localisation of function in the brain, we are of opinion that an automatic mechanism, of the kind just referred to, is well fitted to provide for a local variation of the blood supply in accordance with local variations of the functional activity.” [Roy and Sherrington, 1890, emphasis added]
“Blood very likely may rush to each region of the cortex according as it is most active, but of this we know nothing.” [James, 1890]
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28. Facts about blood flow Aorta peak flow: 90 cm/s
Internal carotid flow: ~ 40 cm/s
Smaller arteries: ~ mm/s
Capillaries: ~ 1 mm/s
Venules and small veins: ~ mm/s
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29. There is a parallel change in blood velocity .
Stimulation of the sciatic nerve (in a rat) results in arteriole dilation in somatosensory cortex.
There is a parallel change in blood velocity .
fmri-fig jpg
But, blood pressure remains relatively constant.
(This is a good thing.)
Adapted from Ngai et al., 1988
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30. Change in diameter of arterioles following sciatic (hindlimb) stimulation
fmri-fig jpg
Adapted from Ngai et al., 1988
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31. Change in arteriole dilation as a function of distance from active neurons
fmri-fig jpg
Iadecola, Nature Reviews Neuroscience, 2004
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32. What triggers changes in blood flow?
K+ : after synaptic activity
Adenosine : follows metabolic activity
Nitric oxide : released by active neurons
Causes smooth muscles surrounding arterioles to relax
NO inhibitors attenuate CBF, BOLD
Neuronal activity ?
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33. Iadecola, Nature Reviews Neuroscience, 2004
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34. How does the vascular system respond to neuronal activity?
Physiological data suggests that blood flow changes may be associated with preponderance of dendritic activity, but disconnections are possible.
Iadecola, Nature Reviews Neuroscience, 2004
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35. Direct neuronal influences?
2 m
400 nm
On small capillaries, there are terminals of dopamine neurons. These appear to have slower influences than necessary for fMRI.
Noradrenergic
Dopamine
Pial Arteries (i.e., larger vessels)
10 m
Krimer, Muly, Williams, Goldman-Rakic, Nature Neuroscience, 1998
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36. Challenges to Neurogenic Control
Slow time scale: DA effects = minutes
DA receptor blockade does not modulate CBF increases w/activation (e.g., Esaki et al., 2002)
Lack of spatial specificity of blood flow responses
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37. Summary of Physiology
Information processing requires (substantial) energy
Energy is needed for restoring membrane potentials
Energy comes from Oxygen and Glucose
Minimal local availability
Metabolites supplied by vascular system
Changes in blood flow with activity
Changes may be disproportionate
Next week: Can we identify some aspect of this process that is measurable using MRI?
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38. II. Neuroanatomy
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39. Terminology: Planes of Section
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40. Terminology: Labels
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41. Brain in skull
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42. Brain covered with dura mater
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43. Gyri (bumps) Sulci (valleys)
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44. corpus callosum falx skull hypothalamus occipital lobe frontal lobe
sinus
thalamus
midbrain
pons
cerebellum
medulla
spinal cord
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45. A midsagittal MRI of the human head
fmri-fig jpg
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46. parietal lobe central sulcus superior parietal lobule precentral gyrus
parieto-occipital
sulcus
occipital lobe
frontal lobe
Sylvian fissure
cerebellum
temporal lobe
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47. Fig 2.15 frontal lobe olfactory nerves Optic chiasma Parahippocampal
gyrus
circle of
Willis
fusiform
gyrus
inferior
temporal
gyrus
basilar
artery
brain stem
substantia nigra
vertebral
arteries
spinal cord
occipital lobe
Fig 2.15
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48. Fig 2.17 frontal lobe anterior corpus callosum caudate ventricle
thalamus
posterior corpus callosum
occipital lobe
Fig 2.17
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49. (Collectively, these are known as the basal ganglia)
Caudate
Corpus Callosum
Putamen
Internal Capsule
Globus Pallidus
Anterior Commissure
(Collectively, these are known as the basal ganglia)
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50. Insula
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51. Corpus Callosum and Indusium Griseum
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52. fmri-fig jpg
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53. fmri-fig jpg
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