close

Enter

Log in using OpenID

09_MEEG_DCM_for_stead

embedDownload
Dynamic Causal Modelling
For Cross-Spectral Densities
Rosalyn Moran
Virginia Tech Carilion Research Institute
Bradley Department of Electrical & Computer Engineering
Department of Psychiatry and Behavioral Medicine, VTC School of Medicine
Outline
Data Features in DCM for CSD
Generative Models in the time domain
Generative Models in the frequency domain
DCM Inversion procedure
Example 1: L-Dopa Modulations of theta spectra using DCM for CSD
Example 2: Propofol Modulations of Delta and Gamma spectra using DCM for CSD
Outline
Data Features in DCM for CSD
Generative Models in the time domain
Generative Models in the frequency domain
DCM Inversion procedure
Example 1: L-Dopa Modulations of theta spectra using DCM for CSD
Example 2: Propofol Modulations of Delta and Gamma spectra using DCM for CSD
Dynamic Causal Modelling: Generic Framework
Electromagnetic
forward model:
neural activity EEG
MEG
LFP
Hemodynamic
forward model:
neural activity BOLD
Time Domain Data
Time Domain ERP Data
Phase Domain Data
Time Frequency Data
Spectral Data
Resting State Data
dx
 F ( x , u,  )
dt
Neural state equation:
fMRI
simple neuronal model
(slow time scale)
EEG/MEG
detailed neuronal model
(synaptic time scales)
Hemodynamic
forward model:
neural activity BOLD
Time Domain Data
Resting State Data
Electromagnetic
forward model:
neural activity EEG
MEG
LFP
Time Domain ERP Data
Phase Domain Data
Time Frequency Data
Spectral Data
“theta”
Power (mV2)
Dynamic Causal Modelling: Generic Framework
Frequency (Hz)
dx
 F ( x , u,  )
dt
Neural state equation:
fMRI
simple neuronal model
(slow time scale)
EEG/MEG
detailed neuronal model
(synaptic time scales)
DCM for Steady State Responses
Under linearity and stationarity assumptions, the model’s
biophysical parameters (e.g. post-synaptic receptor density and
time constants) prescribe the cross-spectral density of responses
measured directly (e.g. local field potentials) or indirectly through
some lead-field (e.g. electroencephalographic and
magnetoencephalographic data).
Steady State
Statistically:
A “Wide Sense Stationary” signal has 1st and 2nd moments that do
not vary with respect to time
Dynamically:
A system in steady state has settled to some equilibrium after a
transient
Data Feature:
Quasi-stationary signals that underlie Spectral Densities in the
Frequency Domain
Dynamic Causal Modelling: Framework
Competing Hypotheses (Models)
Generative Model
Bayesian Inversion
Empirical Data
Optimization
under model constraints
Model Structure/ Model
Parameters
Explanandum
Spectral Densities
Spectral Density in Source 1
30
20
15
10
5
0
0
5
10
15
20
25
30
Frequency (Hz)
Power (uV2)
Power (uV2)
25
30
Spectral Density in Source 2
25
20
15
10
5
0
0
5
10
15
20
25
30
Frequency (Hz)
Power (uV2)
Spectral Densities
25
Cross-Spectral Density between Sources 1 & 2
20
15
10
Spectral Density in Source 1
30
5
25
0
0
5
10
15
20
20
25
30
Frequency (Hz)
15
10
5
0
0
5
10
15
20
25
30
Frequency (Hz)
Power (uV2)
Power (uV2)
30
30
Spectral Density in Source 2
25
20
15
10
5
0
0
5
10
15
20
25
30
Frequency (Hz)
EEG - MEG – LFP Time Series
Cross Spectral Density: The Data
1
3
1
2
3
4
1
2
3
4
A few LFP channels or EEG/MEG spatial modes
4
Cross Spectral Density
2
Cross Spectral Density: The Data
Autoregressive Model used to extract spectral representations from data
Imaginary Numbers Retained
Averaged over trial types
y n   1 y n 1   2 y n  2 ....   p y n  p  e n
H ij ( ) 
Default order 8
1
1 e
ij
iw
2e
ij
iw 2
 ......   p e
ij
iwp
g ( ) ij  H ij ( )  ij H ( ) ij

AR coefficients prescribe the spectral densities
Real and
Imaginary
Data features
Outline
Data Features in DCM for CSD
Generative Models in the time domain
Generative Models in the frequency domain
DCM Inversion procedure
Example 1: L-Dopa Modulations of theta spectra using DCM for CSD
Example 2: Propofol Modulations of Delta and Gamma spectra using DCM for CSD
A selection of intrinsic architectures in SPM
A suite of neuronal population models
including neural masses, fields and
conductance-based models…expressed in
terms of sets of differential equations
Neural Mass Models in DCM
EEG/MEG/LFP
signal
Properties of tens of thousands of
neurons approximated by their average
response
Intrinsic
Connections
Supragranular
Layer
neuronal (source) model
Granular
Layer
Internal
Parameters
x  F  x , u ,  
Infragranular
Layer
Extrinsic
Connections
State equations
Conductance-Based
Neural Mass Models in DCM
Two governing equations: V = IR ……….. Ohms Law
I = C dV/dt ……. for a capacitor
Conductance
Current in
Potential Difference
C V  g (V rev  V )  
Noise Term: Since properties of tens of
thousands of neurons approximated by
their average response
g   (  aff  (  aff  V threshold ,  aff )  g )  
Conductance-Based
Neural Mass Models in DCM
Two governing equations: V = IR ……….. Ohms Law
I = C dV/dt ……. for a capacitor
Conductance
Current in
Potential Difference
C V  g (V rev  V )  
Noise Term: Since properties of tens of
thousands of neurons approximated by
their average response
g   (  aff  (  aff  V threshold ,  aff )  g )  
Time constant: κ
Afferent Spikes :
Strength of connection x σ
Channels already
open: g
Conductance-Based
Neural Mass Models in DCM
Two governing equations: V = IR ……….. Ohms Law
I = C dV/dt ……. for a capacitor
Conductance
Current in
Noise Term: Since properties of tens of
thousands of neurons approximated by
their average response
Potential Difference
C V  g (V rev  V )  
g   (  aff  (  aff  V threshold ,  aff )  g )  
Time constant: κ
Afferent Spikes :
Strength of connection x σ
σ
μ-V
Channels already
open: g
Conductance-Based
Neural Mass Models in DCM
Intrinsic Afferents
C V  g (V rev  V )  
Extrinsic Afferents
g   (  aff  (  aff  V threshold ,  aff )  g )  
Conductance-Based
Neural Mass Models in DCM
CV = gE (VE -V ) + gNMDA fMG (VNMDA -V ) + gI (VI -V ) + G
gE = k E (g s (mV -VT , S ) - gE ) + G
gI = k I (gs (mV() -VT , S ) - gI) ) + G
gNMDA = k NMDA (gs (mV -VT , S ) - gNMDA )+ G
Different Neurotransmitters and Receptors?
Different Cell Types in 3/6 Layers?
Conductance-Based Neural
Mass Models in DCM

Inhibitory cells in extragranular layers
(2)
C V
 g L (V L  V
I
22
(2)
)  g E (V E  V
(2)
(2)
)  g I (V I  V
(2)
(2)
)  V
(2)
E
(3)
(3)
(2)
g E   E (  23  (  V  V R ,  )  g E )   E
(2)
I
(2)
(2)
(2)
g I   I (  22  (  V  V R ,  )  g I )   I

I
 32
Inhibitory
interneuron
Exogenous
input
Spiny stellate
cells
Excitatory spiny cells in granular layers
C V
 g L (V L  V
(1 )
(1 )
)  g E (V E  V
(1 )
(1 )
E
 31
 13E
Pyramidal
cells
Measured
response
Excitatory pyramidal cells in extragranular layers
(3)
C V  g L (V L  V
g
g (V
Current
Conductance
)
(3)
E
(3)
  E (  ( 
E
31
)  g E (V E  V
(1 )
V
(3)
 VR , 
(1 )
Reversal Pot – Potential Diff
Firing Variance
g   (  aff  (  aff  V threshold ,  aff )  g )  
Time Constant
) g
(3)
)  g I (V I  V
(3)
E
)  E
(3)
(3)
I
(2)
(2)
(3)
g I   I (  32  (  V  V R ,  )  g I )   I
C V  g (V rev  V )  
Conductance
)  I  V
(1 )
E
(3)
(3)
(1 )
g E   E (  13  (  V  V R ,  )  g E )   E
I (t )
(3)
E
23
Afferent Firing
Unit noise
No. open channels
(3)
)  V
Convolution-Based Neural Mass
Models in DCM
Extrinsic Backward Input
Extrinsic Forward Input
Inhibitory
interneuron
Spiny stellate
cells
Pyramidal
cells
Extrinsic Backward Input
Synaptic Kernel
Parameterised Sigmoid
g
H

k
Intrinsic
connectivity
v  h;
 H  t .e   t ; t  0 
h (t )  

;t  0 
 0
v  i
2
i   e / i H e / i   ( v aff )  2  e / i i   e / i v
Maximum
Post
Synaptic
Potential
Inverse
Time
Constant
t
v
 h ( t   ) d 

Convolution-Based Neural Mass
Models in DCM
Extrinsic Backward Input
Extrinsic Forward Input
Inhibitory cells in extragranular layers
v 4  i 4
Inhibitory
interneuron
2
i4   e H e  3 ( v 6 )  2  e i 4   e v 4
5
v 5  i5
2
i5   i H i  5 ( v 7 )  2  i i5   i v 5
v 7  i 4  i5
Spiny stellate
cells

Exogenous
input
Pyramidal
cells
I (t )
4
Excitatory spiny cells being granular layers
v1  i1
2
i1   e H e  1 ( ( v 6 )  I )  2 e i1   e v1
1
Extrinsic Backward Input

2
v 2  i 2
Synaptic Kernel
Parameterised Sigmoid
g
H

k
Intrinsic
connectivity
v  h;
 H  t .e   t ; t  0 
h (t )  

;t  0 
 0
v  i
2
i   e / i H e / i   ( v aff )  2  e / i i   e / i v
Maximum
Post
Synaptic
Potential
Inverse
Time
Constant
 h ( t   ) d 

v 3  i 3
2
i3   i H i  4  ( v 7 )  2  i i 3   i v 3
v 6  i 2  i 3
Excitatory pyramidal
cells in extragranular layers
t
v
2
i2   e H e  2  ( v1 )  2  e i 2   e v 2
Measured
response
g (v6 )

3
4 population Canonical
Micro-Circuit (CMC)
Inhibitory
interneuron
Superficial
pyramidal
Extrinsic Backward Input
Forward
Extrinsic Output
Extrinsic Backward Input
Spiny stellate
Extrinsic Forward Input
Extrinsic Forward Input
Spiny stellate
Inhibitory
interneuron
Extrinsic Backward Input
Extrinsic Backward Input
Extrinsic Output
Pyramidal
cells
GABA Receptors
AMPA Receptors
NMDA Receptors
Deep
pyramidal
C V  g (V rev  V )  
g   (  aff  (  aff  V threshold ,  aff )  g )  
Temporal Derivatives
Backward
Extrinsic Output
4-subpopulation
Canonical Microcircuit
Outline
Data Features in DCM for CSD
Generative Models in the time domain
Generative Models in the frequency domain
DCM Inversion procedure
Example 1: L-Dopa Modulations of theta spectra using DCM for CSD
Example 2: Propofol Modulations of Delta and Gamma spectra using DCM for CSD
State equations to Spectra
Time Differential
Equations
State Space
Characterisation
x  f ( x )  Bu
x  Ax  Bu
y  l( x)
y  Cx
Transfer Function
Frequency Domain
H ( s )  C ( sI  A ) B
Linearise
mV
u: spectral innovations
White and colored noise
Moran, Kiebel, Stephan, Reilly, Daunizeau, Friston (2007) A neural mass model of spectral responses in electrophysiology. NeuroImage
Generative Model of Spectra
Populated According to the neural mass model equations
0


0


0

2
  e

 e H e 2 g


0
A 
0

State Space
Characterisation








x  Ax  Bu
y  Cx
C
T
0
 
0
0
 
0
 
0
 
0
  
0
0
 
1
0
 
0
 
0
0
0
1
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
 2 e
0
0
0
0
 e H e 1 g
0
0
 e
0
0
 2 e
0
0
0
0
0
0
0
 i
0
0
 2 i
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
 e
 2 e
 e H e 3 g
0
0
0
0
0
0
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
 i
 2 i
0
0
0
0
0
0
0
1
0
0
1
 0 


 0 
 0 


 eH e 


0


 0 
B 

 0 
 0 


 0 
 0 


 0 


 0 
2
2
2
2




0

0


0

 i H i  4. g 

0


0

0


0

 i H i 5 g 

0

0
0
The Input State
(Stellate Cells)
The Output State
(Pyramidal Cells)
Moran, Kiebel, Stephan, Reilly, Daunizeau, Friston (2007) A neural mass model of spectral responses in electrophysiology. NeuroImage
Generative Model of Spectra
State Space
Characterisation
x  Ax  Bu
y  Cx
0


0


0

2
  e

 e H e 2 g


0
A 
0









0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
 2 e
0
0
0
0
 e H e 1 g
0
 e
0
0
0
 2 e
0
0
0
0
0
0
0
 i
0
0
 2 i
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
 e
 2 e
 e H e 3 g
0
0
0
0
0
0
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
 i
 2 i
0
0
0
0
0
0
0
1
0
0
1
2
2
2
2


0


0

0


0

 i H i  4. g 

0


0

0


0

 i H i 5 g 

0

0
C
T
0
 
0
0
 
0
 
0
 
0
  
0
0
 
1
0
 
0
 
0
 0 


 0 
 0 


 eH e 


0


 0 
B 

 0 
 0 


 0 
 0 


 0 


 0 
Output Spectrum (Y) = Modulation Transfer Function x Spectrum of Innovations
Y (s) = H (s)U(s)
H (s) = C(sI - A)-1 B
Modulation Transfer Function
An analytic mixture of state
space parameters
Generative Model of Spectra
Posterior Cingulate Cortex
3.5
6
Log Power
Frequency
4
8
10
12
3
2.5
2
1.5
1
14
16
Posterior Cingulate Cortex
4
0.5
4
5
6
7
NMDA connectivty
0
2
8
4
6
Anterior Cingulate Cortex
 VR ,  )  g
(2)
NMDA
)
6
8
10
12
14
16
10
8
6
4
14
16
12
Anterior Cingulate Cortex
Log Power
  I (  NMDA  ( 
(2)
Frequency
g
(2)
V
10
12
4
(2)
NMDA
8
Frequency
2
4
5
6
7
NMDA connectivty
8
0
2
4
6
8
10
Frequency
12
14
16
Observer Model in the Frequency Domain
H 1( )  f ( : H e / i ,  e , i ..)
H 12 ( )  f ( : H e / i ,  e , i ..)
Power (mV2)
Spectrum channel/mode 1 Cross-spectrum modes 1& 2
Power (mV2)
Frequency (Hz)
Frequency (Hz)
Power (mV2)
H 2 ( )  f ( : H e / i ,  e , i ..)
+ White Noise in Electrodes
Frequency (Hz)
Spectrum mode 2
Summary: Neural Mass Models in DCM
Sensor Level
Spectral Responses
Lead
Field
Interconnected
Neural mass
models
Outline
Data Features in DCM for CSD
Generative Models in the time domain
Generative Models in the frequency domain
DCM Inversion procedure
Example 1: L-Dopa Modulations of theta spectra using DCM for CSD
Example 2: Propofol Modulations of Delta and Gamma spectra using DCM for CSD
Dynamic Causal Modelling: Inversion & Inference
Empirical Data
Electromagnetic
forward model:
Neural
Generative Model
Bayesian Inversion
Hemodynamic
forward model:
Model Structure/ Model
Parameters
fMRI
state equation:
EEG/MEG
Dynamic Causal Modelling: Inversion & Inference
Bayes’ rules:
p ( | y , m ) 
p ( y |  , m ) p ( | m )
p( y | m)
Bayesian Inversion
Free Energy:
F  ln p ( y m )  D ( q ( ) p ( y , m ) )
max
Inference on models
Inference on parameters
Model 1
Model 2
Model 1
0.8
Model comparison via Bayes factor:
p ( y | m1 )
BF 
p( y | m2 )
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
-2
accounts for both accuracy and complexity of the model
allows for inference about structure (generalisability) of the model
-1
0
1
2
3
4
5
p ( conn  0 | y )  99 . 1 %
Dynamic Causal Modelling: Inversion & Inference
Bayes’ rules:
p ( | y , m ) 
p ( y |  , m ) p ( | m )
p( y | m)
Free Energy:
F  ln p ( y m )  D ( q ( ) p ( y , m ) )
max
Bayesian Inversion
Inference on parameters
Inference on models
A Neural Mass Model
Model 1
Model 2
Model 1
0.8
Model comparison via Bayes factor:
p ( y | m1 )
BF 
p( y | m2 )
0.7
q ( )  p ( y , m )
0.6
0.5
0.4
0.3
0.2
0.1
0
-2
accounts for both accuracy and complexity of the model
allows for inference about structure (generalisability) of the model
-1
0
1
2
3
4
5
p ( conn  0 | y )  99 . 1 %
Inversion in the real & complex domain
prediction and response: E-Step: 32
prediction and response: E-Step: 32
3.5
1
0.8
3
0.6
0.4
imaginary
real
2.5
2
1.5
1
0.2
0
-0.2
-0.4
-0.6
0.5
-0.8
0
0
10
20
30
40
-1
50
0
10
Frequency (Hz)
20
30
40
50
Frequency (Hz)
conditional [minus prior] expectation
1.5
1
0.5
0
-0.5
-1
-1.5
-2
0
10
20
30
40
parameter
50
60
70
80
Outline
Data Features in DCM for CSD
Generative Models in the time domain
Generative Models in the frequency domain
DCM Inversion procedure
Example 1: L-Dopa Modulations of theta spectra using DCM for CSD
Example 2: Propofol Modulations of Delta and Gamma spectra using DCM for CSD
Dopaminergic modulation in Humans
Aim: Infer plausible synaptic effects of dopamine in humans via non-invasive
imaging
Approach:
Double blind cross-over (within subject) design, with participants on placebo
or levodopa
Use MEG to measure effects of increased dopaminergic transmission
Study a simple paradigm with “known” dopaminergic effects (from the animal
literature): working memory maintenance
Apply DCM to one region (a region with sustained activity throughout
maintenance prefrontal)
Moran, Symmonds, Stephan, Friston, Dolan (2011) An In Vivo Assay of Synaptic Function Mediating Human Cognition, Current Biology
Working Memory
•
Animal unit recordings have shown
selective persistent activity of
dorsolateral prefrontal neurons
during the delay period of a delayedresponse visuospatial WM task
(Goldman-Rakic et al, 1996)
•
The neuronal basis for sustained
activity in prefrontal neurons involves
recurrent excitation among pyramidal
neurons and is modulated by
dopamine (Gao, Krimer, GoldmanRakic, 2001)
•
Dose dependant inverted U
Dopamine in Working Memory
Wang et al, 1999
•
DA terminals converge on pyramidal cells
and inhibitory interneurons in PFC (Sesack
et al, 1998)
•
Gao et al, 2001
DA modulation occurs through several pre
and post synaptic mechanisms (Seamans
& Yang, 2004)
Seamans et al, 2001
- Increase in NMDA mediated responses in pyramidal cells – postsynaptic D1 mechanism
- Decrease in AMPA EPSPs in pyramidal cells – presynaptic D1 mechanism
- Increase in spontaneous IPSP Amplitude and Frequency in GABAergic interneurons
- Decrease in extrinsic input current
WM Paradigm in MEG on and off levodopa
Memory
Memory
Target Image
300 ms
Load titrated to 70% accuracy
(predrug)
300 ms
Probe Image
4 sec
2 sec
e.g. match
e.g. no match
Behavioural Results
77
*
76
Memory
Target Image
75
Probe Image
% Accuracy
match
74
73
72
71
Titration
70
69
68
Placebo
L-Dopa
SustainedActivity
Activity during
maintenance:
at memory
sensors
during
Sensor Space
maintenance
• Significant effects of memory in different frequency bands
(channels over time)
• Sustained effect throughout maintenance in delta - theta - alpha bands
• Localised main effect and interaction in right prefrontal cortex
c
P
A
P
A
P
A
Frequency (Hz)
Time (s)
sensors
Normalised Power (a.u.)
Interaction: Memory and Dopamine
Broad Band Low Frequency Activity
1.4
1.3
1.2
1.1
L-Dopa
Placebo
1
0.9
0.8
0.7
0
2
4
6
8
10
12
Frequency (Hz)
Time
(msec)
14 16
18
DCM Architecture
 3,2
 3,3
Cell Populations
 3 ,1
 2 ,3
Spiny Stellates (Population 1)
Inhibitory Interneurons (Population 2)
 1, 2
Pyramidal Cell (Population 3)
Receptor Types
 1,3
AMPA receptors
NMDA receptors
GABAa receptors
γ : The strengths of presynaptic inputs to and postsynaptic conductances of transmitter-receptor pairs
i.e. a coupling measure that absorbs a number of biophysical processes, e.g.:
Receptor Density
Transmitter Reuptake
Synaptic Hypotheses
(2)
C V
 g L (V L  V
Extrinsic Cortical Input (u)
g
(2)
AMPA
(2)
)  g AMPA (V E  V
(2)
  AMPA (  2 , 3 ( 
(3)
V
 VR , 
(3)
(2)
) g
)  g NMDA f Mg (V
(2)
(2)
AMPA
)( V E  V
(2)
)  V
inhibitory
interneurons
)   AMPA
(2)
(3)
(3)
(2)
g NMDA   NMDA (  2 , 3 (  V  V R ,  )  g NMDA )   NMDA
(1 )
C V  g L (V L  V
pyrami
dal spiny
stellate
cells
cells
pyrami
dal
pyramidal
cells
cells
 2 ,3
 1, 2
 3,2
(1 )
)  g AMPA (V E  V
(1 )
(1 )
)  g GABAa (V I  V
(1 )
(1 )
)  V
(1 )
(3)
(3)
(1 )
g AMPA   AMPA (  1, 3 (  V  V R ,  )  g AMPA )   AMPA
(1 )
(2)
(2)
(1 )
g GABAa   GABAa (  1, 2 (  V  V R ,  )  g GABAa )  GABAa
(3)
C V  g L (V L  V
(3)
1
 3 ,1
 1,3
 3,3
(2)
)  g AMPA (V E  V
(3)
(3)
)  g NMDA f Mg (V
(3)
(3)
)( V E  V
0.8
(3)
)  g GABAa (V I  V
(3)
(3)
(1 )
(1 )
(3)
(3)
(3)
g AMPA   AMPA ([  3 ,1 (  V  V R ,  )   3 , 3 (  V  V R ,  )]  g AMPA )   AMPA
g
(3)
NMDA
g
(3)
GABAa
  NMDA ([  3 ,1 ( 
(1 )
V
 VR , 
(1 )
)   3 , 3 ( 
  GABAa (  3 , 2 ( 
(2)
V
 VR , 
(2)
) g
(3)
GABAa
(3)
V
 VR , 
(3)
)]  g
(3)
NMDA
)   NMDA
(3)
)  V
0.6

0.4
0.2
0
-100
)  GABAa
-50
Membrane Potential (mV)
L-Dopa relative to Placebo, Memory – No Memory Trials
1.
2.
3.
4.
0
Decrease in AMPA coupling (decreased γ1,3)
Increased sensitivity by NMDA receptors (increased α)
Increase in GABA coupling (increased γ3,2)
Decreased exogenous input (decreased u)
50
Parameter Estimates
L-Dopa : Memory – No Memory:
Interaction of Parameter and Task on L-Dopa ( p = 0.009)
MAP Parameter estimates
L-Dopa : Memory – No Memory
0
0.16
-0.01
-0.02
*
x 10-4
0.08
0
0.14
0.07
-1
0.12
0.06
-2
0.1
0.05
-3
0.08
0.04
-4
0.06
0.03
-5
0.04
0.02
-6
0.02
0.01
-7
0
γ 3,2
-0.03
-0.04
-0.05
-0.06
-0.07
-0.08
-0.09
γ1,3
u
0
α
-8
*
u
L-Dopa relative to Placebo, Memory – No Memory Trials
1.
2.
3.
4.
Decrease in AMPA coupling (decreased γ1,3)
Increased sensitivity by NMDA receptors (increased α)
Increase in GABA coupling (increased γ3,2)
Decreased exogenous input (decreased u)
Moran, Symmonds, Stephan, Friston, Dolan (2011) An In Vivo Assay of Synaptic Function Mediating Human Cognition, Current Biology
Individual Behaviour
L-Dopa : Memory – No Memory
MAP Parameter estimates
*
x 10-4
0
0.16
0.08
0
-0.01
0.14
0.07
-1
0.12
0.06
-2
0.1
0.05
-3
0.08
0.04
-4
0.06
0.03
-5
0.04
0.02
-6
0.02
0.01
-7
-0.02
-0.03
-0.04
-0.05
• Decrease in AMPA coupling (decreased γ1,3)
• Increased sensitivity by NMDA receptors
(increased α)
-0.06
-0.07
-0.08
*
γ1,3
-0.09
0
α
γ 3,2
0
-8
u
0.12
R = -0.51
p < 0.05
0.2
NMDA Nonlinearity α
AMPA connectivity γ1,3
0.3
0.1
0
-0.1
-0.2
0.1
0.08
0.06
0.04
0.02
0
-0.02
-0.04
-0.3
-0.4
-10
R = 0.59
p < 0.05
-0.06
-5
0
5
10
Performance Increase
15
20
-0.08
-10
-5
0
5
10
15
Performance Increase
Moran, Symmonds, Stephan, Friston, Dolan (2011) An In Vivo Assay of Synaptic Function Mediating Human Cognition, Current Biology
20
Outline
Data Features in DCM for CSD
Generative Models in the time domain
Generative Models in the frequency domain
DCM Inversion procedure
Example 1: L-Dopa Modulations of theta spectra using DCM for CSD
Example 2: Propofol Modulations of Delta and Gamma spectra using DCM for CSD
Connectivity changes underlying
spectral EEG changes during
propofol-induced loss of
consciousness.
Wake
Mild Sedation: Responsive to command
Deep Sedation: Loss of Consciousness
Boly, Moran, Murphy, Boveroux, Bruno, Noirhomme, Ledoux, Bonhomme, Brichant, Tononi, Laureys, Friston, J Neuroscience, 2012
Propofol-induced loss of consciousness
Wake
Mild Sedation: Responsive to command
Deep Sedation: Loss of Consciousness
Anterior
Cingulate
/mPFC
Precuneus
/Posterior Cingulate
Propofol-induced loss of consciousness
Wake
Mild Sedation: Responsive to command
Deep Sedation: Loss of Consciousness
Anterior
Cingulate
/mPFC
Precuneus
/Posterior Cingulate
Murphy et al. 2011
Increased gamma power in Propofol vs Wake
Increased low frequency power when consiousness is lost
Propofol-induced loss of consciousness
Wake
Mild Sedation
Deep Sedation
Bayesian Model Selection
ACC
ACC
PCC
PCC
ACC
PCC
Thalamus
Thalami
Propofol-induced loss of consciousness
Wake
Mild Sedation
Deep Sedation
ACC
ACC
PCC
PCC
ACC
PCC
Thalamus
Thalami
Propofol-induced loss of consciousness
ACC
PCC
Parameters of Winning Model
Wake
Thalamus
Propofol-induced loss of consciousness
ACC
PCC
Wake
Thalamus
ACC
PCC
Thalamus
Mild Sedation
:Increase in thalamic excitability
Propofol-induced loss of consciousness
ACC
PCC
Wake
Thalamus
ACC
PCC
ACC
PCC
Thalamus
Mild Sedation
:Increase in thalamic excitability
Thalamus
Loss of Consciousness
:Breakdown in Cortical Backward Connections
Propofol-induced loss of consciousness
ACC
PCC
Thalamus
Loss of Consciousness
:Breakdown in Cortical
Backward Connections
Boly, Moran, Murphy,
Boveroux, Bruno, Noirhomme,
Ledoux, Bonhomme, Brichant,
Tononi, Laureys, Friston, J Neuroscience, 2012
Summary
•
DCM is a generic framework for asking mechanistic questions of neuroimaging data
•
Neural mass models parameterise intrinsic and extrinsic ensemble connections and
synaptic measures
•
DCM for SSR is a compact characterisation of multi- channel LFP or EEG data in the
Frequency Domain
•
Bayesian inversion provides parameter estimates and allows model comparison for
competing hypothesised architectures
•
Empirical results suggest valid physiological predictions
Thank You
•
FIL Methods Group
Author
52   documents Email
Document
Category
Uncategorized
Views
1
File Size
5 114 KB
Tags
1/--pages
Report inappropriate content