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Frontal lobe activation mediates the
activation of the amygdala during
cognitive
-
emotional learning : an
effective connectivity study
Branislava Ćurčić
-
Blake,
Marte Swart
and André Aleman
Cognitive Neuropsychiatry group,
Neuroimaging center (NIC), University
medical center Groningen (UMCG), The
Netherlands
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Overview
•
Quick introduction and key points regarding DCM
•
Our emotional learning study
•
Questions and suggestions welcome at any point
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Phenomenon of brain connectivity?
•
Anatomical : The connections between brain areas by means
of white matter tracts (groups of axons)
•
Functional :
Analyses of inter
-
regional effects: what are the interactions between
the elements of a given neuronal system? How functionally
specialised regions interact with each other
•
a) Functional connectivity:
the temporal correlation between
spatially remote
neurophysiological events
•
b) Effective connectivity
the influence that the
elements of a neuronal
system exert on each other
A
B
A
B
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DCM
•
Neat method to establish effective connectivity
(as defined by Friston!)
•
A well
-
defined model or set of models is required
•
The fMRI data dynamics are modeled
•
Make inferences about processes that underlie
measured time series
•
Idea is to estimate parameters of a reasonably
realistic neuronal system model
such that
predicted BOLD corresponds as close as
possible to measured BOLD
From Burkhard Pleger, Functional Imaging Lab, University College London
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What DCM can do and what
cannot
•
DCM can make inferences about how
much the activity in area A can induce
change of activation in area B!
•
DCM cannot make inferences about
speed of the processes, nor timing.
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hemodynamic
model
effective connectivity
modulation of
connectivity
The bilinear model
Cu
z
B
u
A
z
j
j
)
(
λ
z
y
integration
Neural state equation
)
,
,
(
n
u
z
F
z
DCM
Conceptual
overview
Friston et al. 2003,
NeuroImage
u
z
u
F
C
z
z
u
u
z
F
B
z
z
z
F
A
j
j
j
2
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Important coefficients
•
A
–
Effective
connectivity
•
B
–
modulatory
effects
•
C
-
Inputs
BOLD
y
y
y
Input
u(t)
activity
z
2
(t)
activity
z
1
(t)
activity
z
3
(t)
direct inputs
c
1
b
23
a
12
neuronal
states
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•
Combining the neural and
h
e
modynamic states gives the
complete
forward model
.
•
An
observation model
includes
measurement
error
e
and confounds
X
(e.g.
drift).
•
Bayesian parameter estimation
•
Result:
Gaussian a posteriori parameter
distributions
, characterised by
mean
η
θ
|y
and
covariance
C
θ
|y
and posterior covariance of
noise
C
e
.
How it works in practice:
parameter estimation
η
θ
|y
)
(
x
y
e
X
u
h
y
)
,
(
observation model
)
(
)
|
(
)
|
(
p
y
p
y
p
posterior
likelihood ∙ prior
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Choosing the model
Bayes Theorem
Bayes factor
Akaike information
criterion (AIC):
Bayesian
information
criterion (BIC):
p
m
accuracy
m
y
AIC
)
(
)
|
(
Penny et al. 2004,
NeuroImage
S
N
p
m
accuracy
m
y
BIC
log
2
)
(
)
|
(
)
|
(
)
|
(
)
,
|
(
)
,
|
(
m
y
p
m
p
m
y
p
m
y
p
)
|
(
)
|
(
j
m
y
p
i
m
y
p
B
ij
Here
p
is the number of parameters and
N
s
is the number of data points
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The DCM cycle
Design a study that
allows to investigate
that system
Extraction of
time series
from
SPMs
Parameter estimation
for all
DCMs
considered
Bayesian model
selection of
optimal DCM
Statistical test
on parameters
of optimal model
Hypothesis about
a neural system
Definition of
DCMs
as system
models
Data acquisition
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Cognitive
-
Emotional learning study
•
What is known about emotional learning
•
Our idea
•
Our experiments
•
Results and Conclusions
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Emotional learning
•
“Emotional memories constitute the core of our
personal history” (La Bar 2006)
•
Learning is enhanced or inhibited by emotions
(Phelps 2004, Richter
-
Levin 2004)
•
Emotions can
•
Enhance memory (Learning emotional words or faces;
Kensinger 2004)
•
Modulate memory (LeDeux)
•
Inhibit memory (spatial learning followed by stress
–
rats in
water maze: reviewed in Richter
-
Levin 2004)
1.
LaBar,K.S. & Cabeza,R. Cognitive neuroscience of emotional memory. Nat Rev Neurosci 7, 54
-
64 (2006).
2.
Phelps,E.A. Human emotion and memory: interactions of the amygdala and hippocampal complex. Curr. Opin. Neurobiol. 14, 198
-
202 (2004).
3.
Richter
-
Levin,G. The amygdala, the hippocampus, and emotional modulation of memory. Neuroscientist. 10, 31
-
39 (2004).
4.
Kensinger,E.A. & Corkin,S. Two routes to emotional memory: distinct neural processes for valence and arousal. Proc. Natl. Aca
d.
Sci. U. S. A 101, 3310
-
3315 (2004).
5.
LeDoux,J. The emotional brain: misterious underpinnings of emotional life. Simon & Schuster, New York (1996).
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Emotional learning
•
Amygdala and Hippocampus complex are anatomically
connected (Ameral 1992; Stefanacci 1996);
•
Emotional enhancement of learning:
–
Amygdala modulates encoding and storage of Hippocampal
memories.
–
Hippocampal complex (episodic representations,
interpretations of events) can influence the amygdala response
to emotional stimuli.
•
Hippocampus
–
Amygdala effective connectivity is
modulated by positive and negative emotions during
emotional retrieval (Smith et al. 2006).
•
Amygdala modulates parahippocampal and frontal regions
during emotional memory storage (Kilpatric 2003) and
encoding item for + and
–
stimuli (Kensinger 2006) etc.
1. D. G. Amaral, J. L. Price, A. Pitkänen, S. T. Carmichael, in The Amygdala: Neurobiological aspects of emotion, memory and
mental dysfunction, J. P. Aggleton, Ed. (Wiley Liss, New York, 1992).
2. L. Stefanacci, W. A. Suzuki, D. G. Amaral, J.Comp Neurol. 375, 552
-
582 (1996).
3. E. A. Phelps, Curr.Opin.Neurobiol. 14, 198
-
202 (2004).
4. E. A. Kensinger and D. L. Schacter, J.Neurosci. 26, 2564
-
2570 (2006).
5. L. Kilpatrick and L. Cahill, Neuroimage. 20, 2091
-
2099 (2003).
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•
The emotional situations influence memory on its
every stage:
–
Encoding (LeDeux 1996; Kensinger 2006)
–
Consolidation (Richter
-
Levin 2004)
–
Storage (Kilpatric 2003; Phelps 2004)
–
Retrieval (Smith 2006)
1.
LeDoux,J. The emotional brain: misterious underpinnings of emotional life. Simon & Schuster, New York (1996).
2.
E. A. Kensinger and D. L. Schacter, J.Neurosci. 26, 2564
-
2570 (2006).
3.
Richter
-
Levin,G. The amygdala, the hippocampus, and emotional modulation of memory. Neuroscientist. 10, 31
-
39 (2004).
4.
E. A. Phelps, Curr.Opin.Neurobiol. 14, 198
-
202 (2004).
5.
L. Kilpatrick and L. Cahill, Neuroimage. 20, 2091
-
2099 (2003).
6.
Smith,A.P., Stephan,K.E., Rugg,M.D. & Dolan,R.J. Task and content modulate amygdala
-
hippocampal connectivity in emotional
retrieval. Neuron 49, 631
-
638 (2006).
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Brain areas involved
Functional MRI (fMRI) activation is monitored
while healthy adults encode high
-
arousing
negative words, low
-
arousing negative words
(valence only) and neutral words.
Data pooled across nine experiments
consistently show haemodynamic
changes evoked by conditioned fear
stimuli in the amygdala and subjacent
periamygdaloid cortex (coronal
sections, left), and the thalamus and
anterior cingulate/dorsomedial
prefrontal cortex (ACC/DMPFC, mid
-
sagittal section, right).
LaBar,K.S. & Cabeza,R. Cognitive neuroscience of emotional memory. Nat Rev Neurosci 7, 54
-
64 (2006).
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MFcortex and IFcortex
•
Emotional memory studies show also involvement
of MFC and IFC
•
MFC is sensitive to tasks involving emotions,
mental state attribution (1), monitoring for and
detecting errors (2), and mentalizing (3).
•
IFC is engaged in emotion regulation, processing
semantic aspects of face recognition, and
language tasks. The left IFG selects the task
-
relevant information (emotional connotation as
target information from specific competing
semantic alternatives; 4).
1.
Olsson,A. & Ochsner,K.N. The role of social cognition in emotion. Trends Cogn Sci. 12, 65
-
71 (2008).
2.
Summerfield,C. et al. Predictive Codes for Forthcoming Perception in the Frontal Cortex. Science 314, 1311
-
1314 (2006).
3.
Amodio,D.M. & Frith,C.D. Meeting of minds: the medial frontal cortex and social cognition. Nat Rev Neurosci 7, 268
-
277 (2006).
4.
Ethofer,T. et al. Cerebral pathways in processing of affective prosody: A dynamic causal modeling study. NeuroImage 30, 580
-
587
(2006)
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Model of Amygdala involvement in
Emotional Learning
•
Potential mechanisms by which the amygdala mediates the
influence of emotional arousal on memory
.
LaBar,K.S. & Cabeza,R. Cognitive neuroscience of emotional memory. Nat Rev Neurosci 7, 54
-
64 (2006).
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Our aim
•
how the emotions and cognition interact during
cognitive emotional learning ?
•
whether the emotions revealed by activation of
the amygdala modulate the way in which the
cognition works during an associative emotional
learning task that engages
HIGHER COGNITIVE
PROCESSES
during the learning of emotional
stimuli.
•
We incorporate both positive and negative
emotional stimuli in order to see whether these
circles differ and if so, how.
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Starting point
•
Data obtained from experiments by Marte Swart
•
Students: 20 LOW score on BVAQ (Bermond
-
Vorst Alexithymia Questionnaire).
•
An emotional picture
-
word associate learning task
(ALT)
•
Thus cognitive emotional processing
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The task
Roomijs
(= ice
-
cream in English)
)
Do
picture and word fit?
Memorize
2
-
8sec
3sec
Task ALT
•
An emotional picture (International Affective
Picture System) and a word were displayed for 3
seconds.
•
2
-
8 seconds to
decide
if the word and picture
fitted together AND to
remember
them
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Results
•
bilateral amygdala (AMY),
•
inferior frontal gyrus (IFG),
•
medial frontal gyrus (MFG), and
•
fusiform gyrus (FG) during the ALT.
RFX analysis
ALT emotional > neutral
for low
-
alexithymia subjects
(p<0.005, T>2.92, unc.).
Crosshair
[12,
-
16,
-
14], MNA.
FGR
AmyR
AmyR
IFGR
MFGR
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The DCM ROI selection
Fig. 3 Contrast as it is
used to define VOI’s: ALT
emotional >fixation point
(random effects t
-
test) for
20 subjects. The IFG,
MFG and Amy are circled
for illustration (p<0.001,
T>3.3, unc.).
Crosshair [
-
22,
-
4,
-
16],
MNI.
AmyL
AmyL
AmyL
IFGL
IFGL
MFGL
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The maximum activation per ROI
BA
x
y
z
Z
AMY L
-
22
-
4
-
16
4.45
AMY R
22
-
4
-
18
4.8
IFG L
45
-
56
22
14
7.01
IFG R
45
56
28
18
4.63
MFG L
10
-
6
8
50
7.28
MFG R
10
6
8
50
6.2
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The creation of VOI’s
•
The VOI’s for each subject !
•
created by choosing the closest supra
-
threshold
(
p
< 0.05
) voxel
•
within the Maximum Probability Maps (of the
Anatomical Toolbox in SPM5)
•
Belongs to the region (visual inspection)
•
Sphere of 4 mm drawn around
•
10
-
33 voxels
•
Time series extracted
•
1
st
Principal Component (PA)
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Checking for input
Fig 4. Full DCM models with different areas of input for the selection of input area(s).
Input is illustrated by black arrows, and effective connectivity by grey arrows.
Model M
MF
IF
AMY
Model I
MF
IF
AMY
Model A
MF
IF
AMY
Model MI
MF
IF
AMY
Model AI
MF
IF
AMY
Model MA
MF
IF
AMY
Model
ABf
PER
MI/M L
4.6*10
11
8/4
MI/M R
26.8
6/2
MI/I L
2.6*10
12
7/6
MI/M R
3.06
7/5
MI/A L
3.8*10
11
8/4
MI/A R
14.4
8/2
MI/MA L
20.4
10/7
MI/MA R
74
13/3
MI/AI L
16.2
11/4
MI/AI R
135
14/2
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Choosing the best connectivity mod
Fig 5.Illustration of models of effective connectivity during an ALT. Input consisting of
positive, negative and neutral conditions goes parallel to the IFG and MFG. In Model #1
the IF and MF communicate directly and with the Amy as opposed to #2 and #3 where
the IF and MF communicate through the Amy. Models #4,5 and 6 are variations of model
#1. The winning model #1 was also compared to the full MI model. The results are
presented in Table 3.
Model #1
IF
MF
AMY
Model #2
IF
MF
AMY
Model #3
IF
MF
AMY
Model #4
IF
MF
AMY
Model #6
IF
MF
AMY
Model #5
IF
MF
AMY
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The resulting connectivities and
modulatory effects
Mean
SD
t
Sig.
MFG to Amy
.16
.12
5.9
<.00
MFG to IFG
.27
.33
3.4
.003
IFG to MFG
.21
.35
2.6
.02
IFG to Amy
.16
,15
4.6
<.00
Pos MFG to Amy
-
.01
.08
-
.7
.5
Pos MFG to IFG
.01
.08
0.4
.6
Pos IFG to MFG
.01
.06
1
.3
Pos IFG to Amy
-
.015
.07
-
0.9
0.4
Neg MFG to Amy
-
.03
.08
-
1.6
.1
Neg MFG to IFG
.04
.07
2.52
.02
Neg IFG to MFG
.04
.08
2.45
.03
Neg IFG to Amy
-
.03
.08
-
1.5
.2
neu MFG to Amy
-
.02
.097
-
.9
.35
neu MFG to IFG
.04
.07
.5
.6
neu IFG to MFG
.03
.09
1.4
.2
neu IFG to Amy
-
.003
.1
-
.1
.9
Table 4
b. Right
Mean
SD
t
Sig.
MFG to Amy
.12
.14
3.8
.001
MFG to IFG
.2
.3
3.0
.008
IFG to MFG
.2
.3
2.5
.02
IFG to Amy
.14
,15
4.5
<.00
Pos MFG to Amy
.01
.05
-
.8
.4
Pos MFG to IFG
.02
.06
1.6
.1
Pos IFG to MFG
.03
.07
2.2
.04
Pos IFG to Amy
-
.03
.05
-
2.2
0.04
Neg MFG to Amy
-
.01
.07
-
.5
.6
Neg MFG to IFG
.05
.08
2.97
.008
Neg IFG to MFG
.02
.03
2.99
.008
Neg IFG to Amy
.01
.09
-
0.7
.5
neu MFG to Amy
-
.03
.07
-
1.9
.07
neu MFG to IFG
.01
.07
.8
.4
neu IFG to MFG
.04
.08
2.3
.03
neu IFG to Amy
-
0.04
.07
-
.45
.02
Table 4 a. Left
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The resulting connectivities and
modulatory effects
Fig 6. Modulatory effects of the best DCM model. Increasing effect (red bold arrows) and
decreasing effect (blue dashed arrow) are presented with the % of influence on the effective
connectivity and the significance level (in brackets).
Amy
N(15%;0.02)
N(20%;0.03)
IF
MF
N(27%;0.008)
P(18%;0.05),
N(13%;0.008),
n(22;0.03)
P(-17%,0.05),
n(-26%;0.02)
Amy
IF
MF
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Lateralization yes or no?
•
t
–
test between modulatory effects for left and
right hemisphere showed NO significant
difference between mean values of modulatory
effects for each pair.
•
Thus, we can not claim that there is lateralization.
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Conclusions
•
The area involved in basic emotional learning (the
amygdala) does not affect the change in activity
of the cognitive areas (the IFG and MFG).
•
The subjects appear to pay more attention to the
context and evaluation of the given stimuli, and
these processes were not affected by emotions.
•
In our case it seems that the subjects
concentrated on the task and suppressed their
emotions to some extent
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Main conclusion
•
In conclusion, it is evident that complex emotional
learning is led by a “top
-
down” process from the
frontal areas
-
the MFG and IFG
-
to the amygdala.
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Pitfall
•
There are gender differences (Cahil et al
2001;2002):
–
Correlations between Left Amygdala
–
emotional
memory enhancements for Females
–
Correlations between Right Amygdala
–
emotional
memory enhancements for Males
•
We found no significant gender differences due to
low statistical power for such a comparison
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Still
•
We have demonstrated that complex emotional
learning is led by top
-
down processes from the
frontal lobe toward the amygdala.
•
This type of learning is more complicated than
conditioned fear therefore the learning circuit is
more complex.
•
The top
-
down processes demonstrate that the
cognition here is “emotion free”.
•
The amygdala might still play a role in the
modulation of learning material delivered to the
memory areas. (it does! data not shown here ;
-
D)
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