Transcript What are we measuring?

What are we
measuring in fMRI?
Marieke Schölvinck
Overview
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Physics of BOLD signal
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Magnetic fields and pulses
Magnetic properties of oxygen in blood
How we use this to generate a signal
Physiology of BOLD signal
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How neurons cause blood flow increases
Implications for cognitive studies
Correlation with other measures of neural activity
physics
It all starts with hydrogen…
magnetic dipole moment (MDM)
MDMs align with / against uniform
magnetic field Bo
small % more align with Bo  net
magnetization
physics
So what goes on in the scanner?
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Place hydrogen nuclei (brain) in a uniform magnetic field
(scanner)
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Apply radiofrequency (RF) pulse, normally at 90° to magnetic
field. This ‘tips’ MDMs of hydrogen nuclei
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MDMs of hydrogen nuclei are now
at 90° to main field (z), i.e. in x,y plane
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Terminate RF pulse and let nuclei relax: MDMs
return to original (z) orientation; energy released
during relaxation is measured by receiver coil
physics
Phase
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BEFORE the RF pulse:
MDMs are not in phase
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DURING the RF pulse:
MDMs in phase  strong signal in x,y plane
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AFTER the RF pulse:
MDMs begin to dephase  signal decays
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Two reasons for this dephasing:
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inhomogeneities in the magnetic field
‘spin-spin’ interactions between neighbouring nuclei
physics
Time to relax…
T1 relaxation
T2 relaxation
T2* relaxation
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time course for MDMs to return to original (z)
orientation
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time course of breakdown of magnetization
in the x,y plane due to spin-spin interactions
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Different tissues have different T1 and T2
relaxation rates
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time course of breakdown of magnetization
in the x,y plane due to inhomogeneities in the
magnetic field
BOLD…
physics
We measure O2 ratios in blood
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BOLD (Blood Oxygenation Level Dependent) contrast: measures
inhomogeneities in magnetic field due to changes in the level of O2 in
the blood
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deoxyhaemoglobin = magnetic!
oxyhaemoglobin = not magnetic!
So we can use the change in fMRI signal
to infer the relative oxygenation of the blood!
High ratio deoxy:oxygenated blood
 fast decrease in MRI signal
Low ratio deoxy:oxygenated blood
 slow decrease in MRI signal
physics
Summary of the physics
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MDMs of hydrogen nuclei align to magnetic field in scanner
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RF pulse causes them to spin, in phase, in x,y plane
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Once pulse has stopped they fall back to direction of magnetic field,
dephasing as they do so
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Dephasing takes various amount of time, depending in part on
inhomogeneities in magnetic field
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Inhomogeneities are caused by variable ratio of deoxygenated :
oxygenated blood
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Assumption: activity in brain area lowers this ratio and thereby
decreases speed of decay of MRI signal
physiology
What causes BOLD?
The purpose of the increase in blood oxygenation is to
feed neurons…
…so, what makes a neuron hungry?
(neurons can’t store much energy)
…and how does this change the blood flow?
physiology
3Na 2K
Hungry brains
Pre-synaptic neuron
3Na 2K
ATP
ATP
GLN
50-75% of energy
use is action potential
driven; remainder is
spent on housekeeping
ATP
3Na+
GLU
GLUTAMATE
H+
K+
Most energy is spent
on the reuptake of 3Na 2K
glutamate and
reversing ion
movements!
Na +
Na +
Ca 2+
ATP
Glial cell
Post-synaptic neuron
physiology
Vascular density
Vascular density is proportional to synaptic density
physiology
Active control of blood flow
physiology
Neural activity  BOLD: complicated!
No easy relationship
going from neural
activity to BOLD
Relationship cannot
only differ between
brain area and level of
activation, but also
between subjects
physiology
… so what does it imply?
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No summation of BOLD signal!
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No directly comparing different areas…
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Different vasculature
Different neuromodulatory control
Different circuitry
BOLD [X] > BOLD [Y] does NOT mean neural activity [X] > activity [Y]!
physiology
What BOLD does not measure
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Output of an area
Comparisons of activity between areas
Inhibitory synapses (GABA)
What BOLD does (presumably) measure
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Excitatory synaptic activity (input to an area)
Local processing (reuptake of glutamate)
Changes in neuromodulatory substances
physiology
What does a blob in area X mean?
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X has changed its local activity
Change of inputs arriving at X
physiology
Other ways to measure neural activity
Kim et al 2004
physiology
Summary of the physiology
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Most energy is spent locally on synaptic processes
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Blood flow is controlled by monoamines
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BOLD does not measure output of an area, comparisons between
areas, or inhibitory connections
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Instead, BOLD measures changes in local activity and changes in
input to an area
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BOLD signal is most closely correlated with LFP signal
References
Physics:
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Lipton ML (2007) MRI Physics: Understanding the Basics. Springer Verlag
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Weishaupt et al (2003) How Does Mri Work? An Introduction to the Physics And Function of
Magnetic Resonance Imaging. Springer Verlag
Physiology:
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Logothetis NK et al (2001) Neurophysiological investigation of the basis of the fMRI signal. Nature
412:150-157
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Attwell D & Iadecola C (2002) The neural basis of functional brain imaging signals Trends in
Neurosciences 25:621-625
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Kim DS et al (2004) Spatial relationship between neuronal activity and BOLD functional MRI
NeuroImage 21:876-885