BOLD physiology

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BOLD physiology

• What do we (not) measure with fMRI?

Meike J. Grol Leiden Institute for Brain and
Cognition (LIBC), Leiden, The Netherlands Leiden
University - Institute for Psychological Research
(LU-IPR), Leiden, The Netherlands Department of
Radiology, Leiden University Medical Center F.
C. Donders Centre for Cognitive NeuroImaging,
Nijmegen, The Netherlands
Zürich SPM CourseFebruary 27, 2008
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Ultrashort MR physics overview
4T magnet
RF Coil
Magnet
RF Coil
source fmri4newbies.com
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Step 1 Put Subject in Big Magnet
Protons (hydrogen atoms) have spins (like
tops). They have an orientation and a frequency.
When you put a material (like your subject) in an
MRI scanner, some of the protons become oriented
with the magnetic field.
source fmri4newbies.com
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Step 2 Apply Radio Waves
After you turn off the radio waves, as the
protons return to their original orientations,
they emit energy in the form of radio waves.
When you apply radio waves (RF pulse) at the
appropriate frequency, you can change the
orientation of the spins as the protons absorb
energy.
source fmri4newbies.com
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Step 3 Measure Radio Waves
source fmri4newbies.com
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We also have T2 weighted images these are
sensitive to local magnetic field
inhomogeneities. These T2 weighted images have
artifacts near junctions between air and tissue
sinuses, ear canals
This is usually not so nice, but...
Based on Robert Coxs web slides
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The BOLD Contrast
BOLD (Blood Oxygenation Level Dependent) contrast
measures inhomogeneities in the magnetic field
due to changes in the level of O2 in the blood
Oxygenated blood? Non-magnetic No signal loss
B0
Deoxygenated blood? Magnetic! Signal loss!!!
Images from Huettel, Song McCarthy, 2004,
Functional Magnetic Resonance Imaging
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BOLD signal
REST

• neural activity ? ? blood flow ? ? oxyhemoglobin
  ? ? T2 ? ? MR signal

ACTIVITY
Source fMRIB Brief Introduction to fMRI
Source Jorge Jovicich
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The Haemodynamic Response Function (HRF)
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Physiology of the BOLD signal
Source Arthurs Boniface, 2002, Trends in
Neurosciences
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Three open questions

1. Is BOLD more informative about spiking/action
   potentials or local field potentials (LFP)?
2. How does the BOLD reflect the energy demands of
   the brain?
3. What does a negative BOLD signal mean?

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Electrophysiological BOLD-correlates
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Action potentials vs. synaptic activity I

• Local Field Potentials (LFP)
• reflect post-synaptic potentials
• similar to what EEG (ERPs) and MEG measure
• Multi-Unit Activity (MUA)
• reflects action potentials/spiking
• similar to what most electrophysiology measures
• Logothetis et al. (2001)
• combined BOLD fMRI and electrophysiological
  recordings
• found that BOLD activity is more closely related
  to LFPs than MUA

Source Logothetis et al., 2001, Nature
Courtesy Jody Culham
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Action potentials vs. synaptic activity II
(Mukamel et al., 2005)
(Heeger et al., 2000)

• BOLD-Signal strongly correlated with both action
  potentials and synaptic activity

Courtesy Tobias Sommer
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Dissociation between action potentials and CBF

• bicuculline increased spiking activity without
  increase CBF and vice versa
• normal neurovascular coupling

? local CBF-increase can be independent from
spiking activity, but is always correlated to LFPs
(Thomsen et al. 2004)
(Lauritzen et al. 2003)
Courtesy Tobias Sommer
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BOLD seems to be correlated to postsynaptic
activity
BOLD seems to reflect the input of a cortical
area as well as its intracortical processing
(Lauritzen et al. 2005)
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Localisation of energy metabolism

• Energy metabolism takes place at the synapses,
  not at the cell body.

Schwartz et al. 1979
Courtesy Tobias Sommer
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• How does the BOLD reflect the energy demands of
  the brain?

• Uncoupling of CBF and CMRO2 functional
  hyperaemia
• Does the need for oxygen drive the blood flow?

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Lack of energy?

• the initial dip shows that it is possible to get
  more
• O2 from the blood without increasing the blood
  flow,
• which happens later in time.
• Although oxygen usage associated with neuronal
  activity must colocalize with the activity, the
  subsequent increase of blood flow occurs in a
  larger area.
• When subjects breath air with reduced oxygen
  content the oxygen availability in circulating
  blood is decreased. Surprisingly, the expected
  compensatory blood flow response was not observed
  (Mintun et al, 2000).

Blood flow seems to be controlled by factors
other than a lack of energy.
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Lack of energy? II
4. Sustained visual stimulation is associated
with an increase in blood flow far in excess of
oxygen consumption. But over time, oxygen
consumption begins to increase as blood flow
falls (Mintun, 2002).
Blood flow seems to be controlled by factors
other than a lack of energy.
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Blood flow might be directly driven by excitatory
postsynaptic processes
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Feedforward system
Glutamate
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Active control of blood flow
Courtesy Marieke Scholvinck
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Hungry brains
50-75 of energy use is action potential driven
remainder is spent on housekeeping
Most energy is spent on the reuptake of glutamate
and reversing ion movements (Atwell and Laughlin,
2001)
3Na
Courtesy Marieke Scholvinck
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Glutamate transport in astrocytes triggers
glucose metabolism
Courtesy Tobias Sommer
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Synaptic inhibition can modulate blood flow
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Leading to negative BOLD signals?
-gt Synaptic inhibition could result in a
negative BOLD signal
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Summary

• BOLD seems to be more informative about local
  field potentials (LFP) than spiking activity.
  BOLD seems to reflect the input of a cortical
  area as well as its intracortical processing, not
  the output level of firing of the neuron.
• Blood flow seems to be actively controlled by
  neurotransmitters leading to vasodilation.
• Glutamate transport in astrocytes triggers
  glucose metabolism
• Synaptic inhibition might result in a negative
  BOLD signal.

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Fortunately, BOLD is tightly coupled to synaptic
activity

• But we have to be alert

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Potential Physiological Influences on BOLD
cerebrovascular disease
structural lesions (compression)
blood flow
medications
autoregulation (vasodilation)
blood volume
hypoxia
volume status
BOLD contrast
hypercarbia
biophysical effects
anesthesia/sleep
anemia
smoking
oxygen utilization
degenerative disease
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Medication effects
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