Neural basis of fMRI signals - McGill University basis … · Neural basis of fMRI signals Amir...
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Neural basis of fMRI signals
Amir ShmuelMNI, McConnel Brain Imaging Centre
McGill University, Montreal, QC, Canada
MontrealNeurological Institute
McGillUniversity
BIC seminar / NEUR 570November 18th, 2013
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From sensory stimuli to fMRI maps
T2* / T2 / CBFStimulus
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From sensory stimuli to fMRI maps
T2* / T2 / CBFChange in CBFNeuronal activityStimulus
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MRI / PET / OImeasurement
Neurovascularcoupling
From sensory stimuli to fMRI maps
T2* / T2 / CBFChange in CBFNeuronal activityStimulus
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MRI / PET / OImeasurement
T2* / T2 / CBFChange in CBFStimulus
From sensory stimuli to fMRI maps
Neurovascularcoupling
Neuronal activity
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MRI / PET / OImeasurement
T2* / T2 / CBFChange in CBFStimulus
From sensory stimuli to fMRI maps
Neuronal activity
Neurovascularcoupling
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Overview: Thursday’s lecture- Neuronal mechanisms underlying less conventional fMRI responses
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Thursday’s lecture: Neuronal activity underlying resting state BOLD
Shmuel and Leopold (2008)
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1cm1cmAnterior
Right
P < 3.010-9
0.38-0.38 0.8-0.8
P < 5.010-2
0.17-0.17 0.8-0.8
Shmuel et al., Neuron (2002)
Thursday’s lecture: Negative BOLD Responses
BOLD (GE-EPI) Cerebral blood flow (FAIR)
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Overview- Basics of intra-cranial neurophysiology
- Vascular mechanisms of BOLD response
Quantitative relationship and neuronal mechanisms:
- Metabolic response and Spiking activity
- Positive BOLD response and spiking activity
- Positive BOLD response and synaptic activity
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MRI / PET / OImeasurement
T2* / T2 / CBFChange in CBFStimulus Neuronal activity
From sensory stimuli to fMRI maps
Neurovascularcoupling
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Locally measured neuronal activity: extracellular recordings (majority of studies)
A neuron is considered to be embedded in an extracellular medium that acts as a volume conductor (Lorente de No´1947; Freeman 1975).
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Locally measured neuronal activity: extracellular recordings
When the membrane potential between two separate regions of such a neuron is different, there is a flow of current in the neuron matched by a return current through the extra-cellular path.
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Local Field Potentials and Multi-Unit Activity
• The potential measured by an electrode with respect to a distant site reflects action potentials, superimposed on other waves of lower frequency.
• A filter cut-off is used in most recordings to obtain MUA (above 400 Hz) and LFPs (below 150 Hz).
• LFPs can be further classified to frequency bands used in EEG - delta, theta, alpha, beta, and gamma. Logothetis, 2002
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Freq < 150Hz
Freq > 400Hz
The Mean Extracellular Potential & its Components
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Components of the Mean Extracellular Potential
Single event duration: Approx 1 msec, Spatial summation: Radius of 100-200microns
Represents: Mainly activity of the projection neurons that form the output of a cortical area
Single event duration: 10 - 100 msec, Spatial summation: Radius of 1-2mm
Represent: Population Synaptic Potentials (PSPs) Voltage-gated membrane oscillations Represent the input of a given cortical area as well as its
local intra-cortical processing (including the activity of excitatory and inhibitory neurons) Logothetis, 2002
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Density of neurons in cerebral cortex12 × 104 / mm3
1 × 106 / 2 × 2 × 2 mm3
Density of synapses in cerebral cortex9 × 108 / mm3
7.2 × 109 / 2 ×2×2 mm3
Shuez A and Briatenberg V, 1998
fMRI signal is an indicator of overall activity of very many neurons and processes
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Overview- Basics of intra-cranial neurophysiology
- Vascular mechanisms of BOLD response
Quantitative relationship and neuronal mechanisms:
- Metabolic response and Spiking activity
- Positive BOLD response and spiking activity
- Positive BOLD response and synaptic activity
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MRImeasurement
Stimulus
From sensory stimuli to fMRI maps
Neuronal activity
Neurovascularcoupling
T2* / T2 / CBFChange in CBF
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Blood Oxygenation Level Dependent:BOLD functional MRI signal
• indirect detection of neuronal activity
– magnetic properties of hemoglobin• deoxyhemoglobin acts as a contrast agent
Seiji Ogawa
From B. Pike, MNI
Linus Pauling(1901-1994)Nobel laureate
Oxyhemoglobin ~ -0.3
B0
longer T2, T2*
BOLD upon activation
Deoxyhemoglobin ~ 1.6
shorter T2,T2*
BOLD at rest
oxyRBCdeoxyRBC
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Cortical blood vessels
• Duvernoi et al., 1981
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Cortical blood vessels: control of blood flow
Peppiatt, Attwell et al., 2006. Harrison et al., 2002.
Potential control sites of cerebral hemodynamic response: arteriolar smooth muscle, and pericytes on capillaries.
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- BOLD is inversely proportional to deoxyHb in capillaries and veinsPhysiological parameters influencing BOLD signal:
CMRO2CBFCBV
DeoxyHB BOLD
CMRO2CBFCBV
DeoxyHB BOLD
CMRO2CBFCBV
BOLDDeoxyHB
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Mechanisms of the positive BOLD response
neural activity oxygen consumption blood flow
oxy-Hb deoxy-Hb T2* MR signal
• normal flow• basal level [deoxy-Hb]• basal CBV• normal MR signal
• increased flow• decreased [deoxy-Hb]• increased CBV• increased MR signal
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Time course of BOLD signal
Yacoub E, Le TH, Ugurbil K, Hu X (1999) Magn Res Med 41(3):436-41
Deoxy-Hb
CMRO2 CBV
Vel
+ +
--
Deoxy-Hb
CMRO2 CBV
Vel
+ +
--
Deoxy-Hb
CMRO2 CBV
Vel
+ +
--
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Question on BOLD Signal:
What is the origin the signal: arteries,
arterioles, capillaries, venules or veins?
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Question on BOLD Signal:
What is the origin the signal: arteries,
arterioles, capillaries, venules or veins?
Answer: mainly capillaries, venules, and
veins, because in arteries and arterioles
there is almost no deoxy-hemoglobin.
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BOLD and neurophysiology:
1. Time lag2. Which blood vessels do we get our BOLD signals from?
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- Optical imaging of Intrinsic Signals
Bonhoeffer andGrinvald (1996)
605 nm
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- Optical imaging of Intrinsic Signals
Bonhoeffer andGrinvald (1996)
605 nm
Absorption spectra
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- Time-course of Intrinsic Signals
605 nm
0 2 4 6 8Time (s)
Bonhoeffer andGrinvald (1996)
Shtoyerman et al. (2000)
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- Optical imaging of Voltage Sensitive Dyes
630 nm
Shoham et al. (1999)
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Intracellular recording vs.Voltage Sensitive Dyes Imaging
Modified from Cohen L et al., 1972
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Overview- Basics of intra-cranial neurophysiology
- Vascular mechanisms of BOLD response
Quantitative relationship and neuronal mechanisms:
- Metabolic response and Spiking activity
- Positive BOLD response and spiking activity
- Positive BOLD response and synaptic activity
![Page 36: Neural basis of fMRI signals - McGill University basis … · Neural basis of fMRI signals Amir Shmuel MNI, McConnel Brain Imaging Centre McGill University, Montreal, QC, Canada Montreal](https://reader033.fdocuments.in/reader033/viewer/2022052519/5f0f1bad7e708231d44287ea/html5/thumbnails/36.jpg)
MRI / PET / OImeasurement
T2* / T2 / CBFChange in CBFStimulus
From sensory stimuli to fMRI maps
Neuronal activity
Neurovascularcoupling
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Estimating neuronal activity based on hemodynamic & metabolic signals
- Quatitative relationship
- Which type of neuronal activity is reflected in thesesignals: spikes or synaptic activity?
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Time course of BOLD signal
Yacoub E, Le TH, Ugurbil K, Hu X (1999) Magn Res Med 41(3):436-41
Deoxy-Hb
CMRO2 CBV
Vel
+ +
--
Deoxy-Hb
CMRO2 CBV
Vel
+ +
--
Deoxy-Hb
CMRO2 CBV
Vel
+ +
--
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Overview- Basics of intra-cranial neurophysiology
- Vascular mechanisms of BOLD response
Quantitative relationship and neuronal mechanisms:
- Metabolic response and Spiking activity
- Positive BOLD response and spiking activity
- Positive BOLD response and synaptic activity
![Page 40: Neural basis of fMRI signals - McGill University basis … · Neural basis of fMRI signals Amir Shmuel MNI, McConnel Brain Imaging Centre McGill University, Montreal, QC, Canada Montreal](https://reader033.fdocuments.in/reader033/viewer/2022052519/5f0f1bad7e708231d44287ea/html5/thumbnails/40.jpg)
Quantitative relationship of BOLD and neurophysiology:Are metabolic responses proportional to changes in neurophysiological activity?
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Optical imaging of intrinsic signals
Image Display
Visual Stimulator
CCD Camera
Computer
Light Guide Illuminator
Digital Camera Controller
Video-projector
Projection-screen
605nm
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Optical imaging of intrinsic signals
Image Display
Visual Stimulator
CCD Camera
Computer
Light Guide Illuminator
Digital Camera Controller
Video-projector
Projection-screen
605nm
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Optical imaging (deoxyHB – oxyHb)& targeted electrical recording: the ‘dip’
++
+ ++ + +
++
++
++++
+
+
1mmShmuel and Grinvald, 1996
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Metabolic response vs. multi-unit spikes
1.0
-0.6
-0.2
0.2
0.6
-1.00 5 10 15 20 25 30
Frac
tiona
l cha
nge
Spikes per seconds
X10-3 Var(intrinsic) = 0.46X10-7
r = 0.79
Shmuel and Grinvald, 1996
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Metabolic response vs. multi-unit spikes
-0.6
-0.4
-0.2
0
0.2
0.4
0.6
0 0.2 0.4 0.6 0.8 1.0
Frac
tiona
l cha
nge
Normalized multi-unit response
X10-3 Var(intrinsic) = 0.77X10-8
r = 0.76
Shmuel and Grinvald, 1996
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Quantitative relationship of BOLD and neurophysiology:Are positive BOLD responses proportional to changes in neurophysiological activity?
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Time course of BOLD signal
Yacoub E, Le TH, Ugurbil K, Hu X (1999) Magn Res Med 41(3):436-41
Deoxy-Hb
CMRO2 CBV
Vel
+ +
--
Deoxy-Hb
CMRO2 CBV
Vel
+ +
--
Deoxy-Hb
CMRO2 CBV
Vel
+ +
--
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Positive BOLD responses in human V1 are proportional to average firing rates in monkey V1
Heeger et al. (2000) Nat Neurosci 3:631-633
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- The initial oxygen consumption deoxyHb –OxyHb response in the visual cortex is ~proportional to the local spiking activity
- Positive BOLD responses in human V1 are proportional to average firing rates in the corresponding areas of the monkey cortex
Conclusions
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- The initial deoxyHb – OxyHb response in thevisual cortex is ~ to the local spiking activity
- Postive BOLD responses in human V1 are proportional to average firing rates in the corresponding areas of the monkey cortex
- So – does BOLD reflect spiking activity?
Conclusions
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- The initial deoxyHb – OxyHb response in thevisual cortex is ~ to the local spiking activity
- Postive BOLD responses in human V1 are proportional to average firing rates in the corresponding areas of the monkey cortex
- So – does BOLD reflect spiking activity?The detected linearity does not imply on the origin of the hemodynamic response (spikes vs. synaptic activity: correlation = causation).
Conclusions
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Quantitative relationship of BOLD and neurophysiology:Are hemodynamic responses proportional to changes in Local Field Potentials?
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Cereberral Blood Flow versus LFPs
Mathiesen, Caesar, Akgören, Lauritzen (1998), J Physiol 512.2:555-566
CBF versus ∑LFP duringclimbing fibre stimulation
CBF versus ∑LFP duringparallel fibre stimulation
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Cereberral Blood Flow versus LFPs:
Increasing, linear and non-linear responses
Mathiesen, Caesar, Akgören, Lauritzen (1998), J Physiol 512.2:555-566
∑LFP ∑LFP
% C
BF
CBF versus ∑LFP duringclimbing fibre stimulation
CBF versus ∑LFP duringparallel fibre stimulation
2
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- Which type of neuronal activity is reflected by BOLD: spikes or synaptic activity ?
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Mathiesen, Caesar, Akgören, Lauritzen (1998), J Physiol 512.2:555-566
Time / s0 50 100 150
Time / s
Numberof spikes
CBF
Divergence of spike rate and blood flow during parallel fibre stimulation
Activity-dependent CBF increases evoked by stimulation of cerebellar parallel fibres are dependent on synaptic excitation, including excitation of inhibitory interneurons, whereas the net activity of Purkinje cells, the principal neurons of the cerebellar cortex, is unimportant for the vascular response.
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Conclusions
The hemodynamic response is in many instances ~ linear with the underlying neuronal spike activity.
Non-linearities between the hemodynamic response and LFP / spiking activity have been observed.
Cereberral Blood Flow does not depend on spiking activity.
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fMRI & Recordings: Cerebral Cortex, V1
Logothetis et al.
Nature (2001)
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BOLD ~ neuronal activity
Logothetis et al.
Nature (2001)
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SNR for Neural & Hemodynamic Signals
0
10
20
30
40
50
60
70
NEU
RA
L SD
Uni
ts
0
0.4
0.8
1.2
1.6
2
2.4
2.8
BO
LD S
D U
nits
7 8 9 10 11 12 13 14 1615
Time in Seconds
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Dissociation of MUA and BOLD-Signal
0 5 10 15 20 25 30 35 40-3.00
0.00
3.00
6.00
9.00BOLDLFP MUA SDF
0 5 10 15 20 25 30 35 40-3.00
0.00
3.00
6.00
9.00BOLD Signal: ePts
0 5 10 15 20 25 30 35 40-3.00
0.00
3.00
6.00
9.00
Time in SecondsBO
LD S
igna
l Cha
nge
(SD
Uni
ts)
0 5 10 15 20 25 30 35 40-2.00
0.00
2.00
4.00
6.00
NEU
RA
L Si
gnal
Cha
nge
(SD
Uni
ts)
0 5 10 15 20 25 30 35 40-2.00
0.00
2.00
4.00
6.00
0 5 10 15 20 25 30 35 40-3.00
0.00
3.00
6.00
9.00
Logothetis NK, Pauls J, Augath M, Trinath T, Oeltermann A (2001) Nature 412: 150-157.
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Conclusions• The BOLD response directly reflects a local increase
in neural activity assessed by the mean Extra-cellular Field Potential signal
• The Signal to Noise Ratio (SNR) of the neural signals is much higher than that of the fMRI signals. Thresholding methods are likely to underestimate a great deal of actual neural activity related to the stimulus or task
• The BOLD response reflects changes in LFP / synaptic activity / input to- and local processing in a region, more than MUA / output of a region