Transcript An Introduction to Functional MRI

Physiological Basis of fMRI
(and Neuroanatomy, in brief)
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I.Neurophysiology
What brain processes consume energy?
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There are two primary
types of information
flow in the CNS:
1) Signaling via action
potentials (axonal
activity) and
2) Integration via
dendritic activity
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Action potential
Depolarization opens CA2+
channels
Vesicles fuse with
presynaptic membrane
Neurotransmitter release
Neurotransmitters open ion
channels on postsynaptic
membrane
Change in potential
IPSP or EPSP
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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.
Key concept: activity of neurons does not itself require energy;
restoring membrane potentials afterward does.
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What metabolites are the
sources of that energy?
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Oxygen (via
hemoglobin)
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Glucose
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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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Data from rodent models (Attwell &
Laughlin, 2001). In humans,
integrative activity may be 50%
greater.
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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
(~100-300Hz)
• 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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How are energy sources
(metabolites) delivered?
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The brain does not store glucose and
oxygen in appreciable quantities.
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Duvernoy, H. M., Delon, S., &
Vannson, J. L. (1981).
Cortical blood vessels of the
human brain. Brain Research
Bulletin, 7(5), 519-579.
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Arteries (1-25mm)
Arterioles (10 - 300 microns)
precapillary sphincters
Capillaries (5-10 microns)
Venules (8-50 microns)
Veins
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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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(anastomosis of internal
carotids and basilar artery)
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ACA – Medial cortex
MCA – Anterolateral cortex
PCA – Posterior temporal and
occipital lobes
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Sinus. n. An separation of the
dura mater in which blood
drains into the venous system.
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Distribution of vascularization across
cortical layers
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Capillary structure
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How does function map onto blood
flow?
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“[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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“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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Facts about blood flow
•
•
•
•
•
Aorta peak flow: 90 cm/s
Internal carotid flow: ~ 40 cm/s
Smaller arteries: ~10-250 mm/s
Capillaries: ~ 1 mm/s
Venules and small veins: ~10-250 mm/s
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Stimulation of the sciatic nerve
(in a rat) results in arteriole
dilation in somatosensory cortex.
There is a parallel change in
blood velocity .
But, blood pressure remains
relatively constant.
(This is a good thing.)
Adapted from Ngai et al., 1988
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Change in diameter of arterioles following
sciatic (hindlimb) stimulation
Adapted from Ngai et al., 1988
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Change in arteriole dilation as a function of
distance from active neurons
Iadecola, Nature Reviews Neuroscience, 2004
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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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Iadecola, Nature Reviews Neuroscience, 2004
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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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Direct neuronal influences?
On small capillaries, there are
terminals of dopamine neurons.
These appear to have slower
influences than necessary for fMRI.
2 m
400 nm
2 m
400 nm
Noradrenergic
Pial Arteries
(i.e., larger
vessels)
Dopamine
10 m
Krimer, Muly, Williams, Goldman-Rakic, Nature Neuroscience, 1998
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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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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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II. Neuroanatomy
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Terminology: Planes of Section
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Terminology: Labels
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Brain in skull
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Brain covered with dura mater
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Gyri (bumps)
Sulci (valleys)
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corpus callosum
falx
skull
hypothalamus
frontal lobe
occipital lobe
sinus
thalamus
midbrain
pons
cerebellum
medulla
spinal cord
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A midsagittal MRI of the human head
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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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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
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Fig 2.15
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frontal lobe
anterior corpus callosum
caudate
ventricle
thalamus
posterior corpus callosum
occipital lobe
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Fig 2.17
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Caudate
Corpus
Callosum
Putamen
Internal
Capsule
Anterior
Commissure
Globus
Pallidus
(Collectively, these
are known as the
basal ganglia)
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Insula
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Corpus Callosum and Indusium Griseum
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