Physiological Basis of the BOLD Signal...Images: Step 2: Apply radio waves When you apply radio...
Transcript of Physiological Basis of the BOLD Signal...Images: Step 2: Apply radio waves When you apply radio...
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Physiological Basis of the BOLD Signal
Kerstin PreuschoffSocial and Neural systems Lab
University of Zurich
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From Stimulus to Bold
Source: Arthurs & Boniface, 2002
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Overview
• Physics of BOLD signal
- Magnetic fields and pulses
- Magnetic properties of oxygen in blood
• Physiology of BOLD signal
- Correlations with other measures or neural activity
- How neurons cause blood flow increases
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MRI Physics
• Step 1: Place an object/subject in a big magnet
• Step 2: Apply radio waves• Step 3: Measure emitted radio waves
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Step 1: Place subject in a big magnet
Protons have “spins” (like gyroscopes). They have an
orientation and a frequency.
When you put any material in an MRI scanner, the protons
align with the direction of the magnetic field.
Images: www.fmri4newbies.com
B
M
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Images: www.fmri4newbies.com
Step 2: Apply radio waves
When you apply radio waves (RF pulse) at the appropriate frequency (Larmor frequency),
you can change the orientation of the spins as the protons absorb energy.
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Step 3a: Turn off radio waves
After you turn off the RF pulse, as the protons return to their original orientations, they emit energy in the form of radio waves.
T2
T1
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Step 3b: Measure emitted radio waves (T1)
T1 = time constant of how quickly the protons realign with the magnetic field
fat has high signal bright
CSF has low signal dark
T1-WEIGHTED ANATOMICAL IMAGE
Images: fmri4newbies.com
T2
T1
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Step 3b: Measure emitted radio waves (T2 or T2*)
T2 = time constant of how quickly the protons emit energy when recovering to equilibrium
T2-WEIGHTED ANATOMICAL IMAGE
fat has low signal -> dark
CSF has high signal -> bright
Images: fmri4newbies.com
T2
T1
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T2* weighted images
• Two factors contribute to the decay of transverse magnetization:
1. molecular interactions
2. local inhomogeneities of the magnetic field (dephasing of spins)
• The combined time constant is called T2* (<T2).
• fMRI uses acquisition techniques (e.g. EPI) that are sensitive to changes in T2*.
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The general principle of MRI
• excite spins in static field by RF pulses & detect the emitted RF
• use an acquisition technique that is sensitive to local differences in T1, T2 or T2*
• construct a spatial image
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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 is diamagnetic -> no signal loss
Deoxygenated blood is paramagnetic -> signal loss
High ratio deoxy/oxygenated blood -> fast decrease in MRI signal
Low ratio deoxy/oxygenated blood -> slow decrease in MRI signal
Huettel, Song, McCarthy, 2004
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The BOLD contrast
Source: Jorge Jovicich, fMRIB Brief Introduction to fMRI
↑ neural activity ↑ blood flow ↑ oxyhemoglobin ↑ T2* ↑ MR signal
REST
ACTIVITY
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Summary MRI Physics
• Magnetic dipole moments of hydrogen nuclei align to magnetic field in scanner
• RF pulse causes them to spin, in phase
• Once pulse has stopped dipole moments realign to the magnetic field, dephasing as they do so
• Dephasing takes various amounts of time, depending in part on inhomogeneities in magnetic field
• Inhomogeneities are caused by variable ratio of deoxygenated : oxygenated blood
• Assumption: activity in brain area lowers this ratio and thereby decreases speed of decay of MRI signal
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Overview
• Physics of BOLD signal
- Magnetic fields and pulses
- Magnetic properties of oxygen in blood
• Physiology of BOLD signal
- Correlations with other measures or neural activity
- How neurons cause blood flow increases
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Three important questions
• Is the BOLD signal more strongly related to neuronal action potentials or to local field potentials (LFP)?
• How does the BOLD signal reflect the energy demands of the brain?
• What does a negative BOLD signal mean?
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Neurophysiological basis of the BOLD signal: soma or synapse?
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In early experiments comparing human BOLD signals and monkey electrophysiological data, BOLD signals were found to be correlated with action potentials.
BOLD & action potentials
Heeger et al 2000, Nat. Neurosci.Rees et al. 2000, Nat. Neurosci.
Red curve: “average firing rate in monkey V1, as a function of contrast,estimated from microelectroderecordings (333 neurons).”
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Logothetis et al., 2001, Nature
Action potentials vs. postsynaptic activity
Local Field Potentials (LFP)• reflect summation of post-synaptic
potentials
Multi-Unit Activity (MUA)• reflects action potentials/spiking
Logothetis et al. (2001)• combined BOLD fMRI and
electrophysiological recordings • found that BOLD activity is more
closely related to LFPs than MUA
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BOLD & LFPs
Logothetis & Wandell 2004, Ann. Rev. Physiol.
blue: LFPred: BOLDgrey: predicted BOLD
BriefStimulus
Undershoot
InitialUndershoot
Peak
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Thomsen et al. 2004, J. Physiol.
⇒ rCBF-increase can be independent from spiking activity, but seems to be always correlated to LFPs
• GABAA antagonist picrotoxine increased spiking activity without increase in rCBF...
• ... and without disturbing neurovascular coupling per se
Lauritzen et al. 2003
Dissociation between action potentials and rCBF
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Current conclusion: BOLD signal seems to be more strongly correlated
to postsynaptic activity
Lauritzen 2005, Nat. Neurosci. Rev.
BOLD seems to reflect the input to a neuronal population as well as its intrinsic processing.
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Three important questions
• Is the BOLD signal more strongly related to neuronal action potentials or to local field potentials (LFP)?
• How does the BOLD signal reflect the energy demands of the brain?
• What does a negative BOLD signal mean?
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Is the BOLD signal driven by energy demands or synaptic processes?
synaptic activity neuronal metabolism
neurovascularcoupling
D’Esposito et al. 2003
rCBF
deoxy-Hb/oxy-Hb
? ?
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Estimated Energy Consumption
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Energetic consequences of postsynaptic activity
Attwell & Iadecola 2002, TINS.
• action potentials at pre-synaptic cell
• release glutamate• open ion-channels on
post-synaptic cell• re-uptake of glutamate by
astrocytes triggers glucose metabolism• pump ions out of cell again to restore ionic gradients• uses energy (50-75% for glu re-uptake) and oxygen➡ How does the energy and oxygen need affect the regional
cerebral blood flow?
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Blood flow might be directly driven by excitatory postsynaptic
processes
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Glutamatergic synapses: A feedforward system for eliciting
the BOLD signal?
Lauritzen 2005, Nat. Neurosci. Rev.
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Forward control of blood flow
Peppiatt & Attwell, Nature 2004; Zonta et al Nature Neurosci 2003;
Mulligan & MacVicar Nature 2004Gordon et al Nature 2008
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Three important questions
• Is the BOLD signal more strongly related to neuronal action potentials or to local field potentials (LFP)?
• How does the BOLD signal reflect the energy demands of the brain?
• What does a negative BOLD signal mean?
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Shmuel et al. 2006, Nat. Neurosci.
Negative BOLD is correlated with decreases in LFPs
positive BOLD negative BOLD
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Impact of inhibitory postsynaptic potentials (IPSPs) on blood flow
Lauritzen 2005, Nat. Neurosci. Rev.
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Negative BOLD signals due to IPSPs?
Lauritzen 2005, Nat. Neurosci. Rev.
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From Stimulus to Bold
action potentials at pre-synaptic cell -> release glutamate -> open ion-channels on post-synaptic cell -> re-uptake of glutamate & pump ions out of cell again -> uses energy and oxygen
-> triggers blood vessel dilation -> decrease ratio of deoxygenated/oxygenated blood -> decrease in paramagnetism -> increase in T2* -> increase in signal strength -> more power to the SPM Is this statistically significant?
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The BOLD signal
• seems to be more strongly related to LFPs than to spiking activity.
• seems to reflect a neuronal population’s input as well as its intrinsic processing, and not its output.
BriefStimulus
Undershoot
InitialUndershoot
Peak
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Blood flow seems to be controlled in a forward fashion by postsynaptic processes leading to the release of vasodilators.
Negative BOLD signals may result from IPSPs.
Various drugs can interfere with the BOLD response.
BriefStimulus
Undershoot
InitialUndershoot
Peak
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BOLDcontrast
bloodflow
bloodvolume
oxygenutilization
structural lesions(compression)
autoregulation(vasodilation)
cerebrovasculardisease
medications
hypoxia
anemiasmoking
hypercapnia
degenerative disease
volume status
anesthesia/sleep biophysical effects
Potential physiological influences on BOLD
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Thank you for your attention.