Transcript BOLD physiology What do we (not) measure with fMRI? Meike J. Grol Leiden Institute for Brain and Cognition (LIBC), Leiden, The Netherlands Leiden University -

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 Course
February 27, 2008
Ultrashort MR physics overview
4T magnet
RF Coil
Magnet
source: fmri4newbies.com
RF Coil
Step 1: Put Subject in Big
Magnet
Protons (hydrogen atoms) have
“spins” (like tops). They have
an orientation and a frequency.
source: fmri4newbies.com
When you put a material (like
your subject) in an MRI
scanner, some of the protons
become oriented with the
magnetic field.
Step 2: Apply 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
After you turn off the radio waves, as the
protons return to their original
orientations, they emit energy in the
form of radio waves.
Step 3: Measure Radio Waves
T2 measures how quickly the protons give
off energy as they recover to equilibrium
T1 measures how quickly the protons
realign with the main magnetic field
fat has high
signal  bright
CSF has low
signal  dark
source:
fmri4newbies.com
T1-WEIGHTED ANATOMICAL IMAGE
fat has low
signal  dark
CSF has high
signal  bright
T2-WEIGHTED ANATOMICAL IMAGE
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
sinuses
ear
canals
This is usually not so nice, but...
Based on Robert Cox’s web slides
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
B0
Oxygenated blood?
Non-magnetic
No signal loss…
Deoxygenated blood?
Magnetic!
Signal loss!!!
Images from Huettel, Song & McCarthy, 2004, Functional Magnetic Resonance Imaging
BOLD signal
REST
neural activity   blood flow   oxyhemoglobin   T2*   MR signal
ACTIVITY
Source: fMRIB Brief Introduction to fMRI
Source: Jorge Jovicich
The Haemodynamic Response
Function (HRF)
Physiology of the BOLD signal
Source: Arthurs & Boniface, 2002, Trends in Neurosciences
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?
Electrophysiological BOLD-correlates
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
Source: Logothetis et al., 2001, Nature
Courtesy: Jody Culham
Logothetis et al. (2001)
• combined BOLD fMRI and
electrophysiological recordings
• found that BOLD activity is more closely
related to LFPs than MUA
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
Dissociation between action potentials
and CBF
• bicuculline increased spiking
activity without increase CBF
and vice versa
• normal neurovascular coupling
Courtesy: Tobias Sommer
(Thomsen et al. 2004)
 local CBF-increase can be
independent from spiking activity,
but is always correlated to LFPs
(Lauritzen et al. 2003)
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)
Localisation of energy metabolism
 Energy metabolism
takes place at the
synapses,
not at the cell body.
Schwartz et al. 1979
Courtesy: Tobias Sommer
• Does the need for oxygen
drive the blood flow?
PET
fMRI
Neuronal Activity →
O2-consumption (CMRO2)
• Uncoupling of CBF and
CMRO2 “functional
hyperaemia“
CBF & Glucose consumption
How does the BOLD reflect the
energy demands of the brain?
Lack of energy?
1. 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.
2. Although oxygen usage associated with neuronal
activity must colocalize with the activity, the subsequent
increase of blood flow occurs in a larger area.
3. 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.
Blood flow might be directly driven by
excitatory postsynaptic processes
Feedforward system
Glutamate
Active control of blood flow
Courtesy: Marieke
Scholvinck
Hungry brains
3Na 2K
Pre-synaptic neuron
3Na 2K
ATP
ATP
50-75% of energy
use is action potential
driven; remainder is
spent on housekeeping
GLN
ATP
3Na+
GLU
GLUTAMATE
H+
K+
Most energy is spent
2K
Na +
on the reuptake of
3Na
glutamate and
ATP
reversing ion
movements
(Atwell and Laughlin,
2001)
Na +
Ca 2+
Glial cell
Post-synaptic neuron
Courtesy: Marieke
Scholvinck
Glutamate transport in astrocytes
triggers glucose metabolism
Courtesy: Tobias Sommer
Synaptic inhibition can
modulate blood flow
Leading to negative BOLD signals?
Lauritzen,
2005
Raichle et al, 1998
-> Synaptic inhibition could result in a negative
BOLD signal
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.
Fortunately, BOLD is tightly
coupled to synaptic activity
But we have to be alert…
Potential Physiological Influences on BOLD
cerebrovascular
disease
medications
structural lesions
(compression)
blood
flow
blood
volume
hypoxia
hypercarbia
anesthesia/sleep
autoregulation
(vasodilation)
volume status
BOLD
contrast
biophysical
effects
anemia
smoking
oxygen
utilization
degenerative
disease
Medication effects
Coronary heart disease
Painkillers