Changes in Anterior Cingulate and Amygdala after Cognitive Behavior Therapy of

Posttraumatic Stress Disorder

Author(s): Kim Felmingham, Andrew Kemp, Leanne Williams, Pritha Das, Gerard Hughes,
Anthony Peduto and Richard Bryant
Source: Psychological Science, Vol. 18, No. 2 (Feb., 2007), pp. 127-129
Published by: Sage Publications, Inc. on behalf of the Association for Psychological Science
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Changes
in Anterior
Cingulate
and
Amygdala
After
Cognitive
Behavior
Therapy
of
Posttraumatic Stress Disorder
PSYCHOLOGICAL SCIENCE
Short
Report
Kim
Felmingham,1'2
Andrew
Kemp,1'2
Leanne
Williams,1'2
Pritha
Das,1'3
Gerard
Hughes,1'4
Anthony Peduto,1'4
and Richard
Bryant1'5
1
Brain
Dynamics Centre,
Westmead Millennium
Institute,
Westmead
Hospital, Westmead,
New South
Wales, Australia;
2
Division
of Psychological Medicine,
Western Clinical
School, University of Sydney, Camperdown,
New South
Wales,
Australia;
3Neuroscience Institute
of Schizophrenia
and Allied
Disorders, Darlinghurst,
New South
Wales, Australia;
4MRI
Unit, Department of Radiology,
Westmead
Hospital, Westmead,
New South
Wales, Australia;
and
5
School
of
Psychology, University of
New South
Wales, Kensington,
New South
Wales,
Australia
Posttraumatic stress disorder
(PTSD) may develop
from im-
paired
extinction of conditioned fear
responses. Exposure-based
treatment of PTSD is
thought
to facilitate extinction
learning
(Charney, 2004).
Fear extinction is mediated
by inhibitory
control of the ventromedial
prefrontal
cortex
(vmPFC)
over
amygdala-based
fear
processes (Phelps, Delgado, Nearing,
&
LeDoux, 2004; Quirk, Russo, Barron,
&
LeBron, 2000).
Most
neuroimaging
studies of PTSD reveal reduced vmPFC
activity
(particularly
in rostral anterior
cingulate cortex,
or
rACC;
Lanius et
al., 2001;
Shin et
al., 2005),
and some find increased
amygdala activity during
threat
processing (Shin
et
al., 2005).
In
addition,
increased
amygdala activity during
fear
conditioning
and reduced vmPFC
activity during
extinction have been re-
ported
in PTSD
(Bremner
et
al., 2005).
Although
PTSD
patients
show increased orbitofrontal and
medial
prefrontal activity following
treatment with serotonin
reuptake
inhibitors
(SSRIs;
Fernandez et
al., 2001;
Seedat et
al.,
2004),
no studies have
investigated
neural networks before and
after
exposure-based
treatment of PTSD. We
report
the first such
study.
We
hypothesized
that
symptom
reduction would be as-
sociated with increased rACC
activity
and reduced
amygdala
activity during
fear
processing.
METHOD
Eight
individuals
(5 females)
with PTSD
following
assault
(n
=
4)
or car accidents
(n
=
4)
were recruited from the Westmead
PTSD
Unit,
New South
Wales,
Australia.
Average
time
post
trauma was 65 months
(SD
=
64.0),
and the
subjects'
mean
age
was 36.8
years (SD
=
8.8). Subjects
were assessed
using
the
Clinician- Administered PTSD Scale
(CAPS;
Blake et
al., 1990)
and the Structured Clinical Interview for DSM-IV Axis 1 Dis-
orders
(First, Spitzer, Gibbon,
&
Williams, 1997).
Four
subjects
had comorbid
major depression.
Two
subjects
were medicated
with SSRIs
during
the
period
when the
testing
sessions took
place. Subjects
were excluded if
they
had a
history
of neuro-
logical condition, psychosis,
borderline
personality disorder,
or
substance abuse. After
giving
informed written
consent, par-
ticipants
received
eight once-weekly
sessions of
imaginal
ex-
posure
and
cognitive restructuring (Bryant, Moulds, Guthrie,
Dang,
&
Nixon, 2003).
Patients underwent
scanning prior
to and
6 months
following
treatment.
Magnetic
resonance
imaging (MRI)
scans were
performed
on
a 1.5-T Siemens Vision Plus Scanner
using
an
echoplanar pro-
tocol.
Subjects
viewed 120 fearful and 120 neutral standardized
facial
expressions (Gur
et
al., 2002) presented
in a
pseudo-
random
sequence
of 30 blocks
(8
fearful faces and 8 neutral
faces
per block).
Stimuli were
presented
for 500
ms,
with a
768-ms interstimulus interval.
Ninety
functional T*
2-weighted
volumes were
acquired (6.6
mm
thickness;
time of
repetition,
Address
correspondence
to Kim
Felmingham,
Brain
Dynamics
Cen-
tre,
Westmead
Hospital, Westmead,
NSW
2145, Australia,
e-mail:
kf
elmingham@med
.
usy
d .edu.au.
Volume 18
-
Number 2
Copyright
2007 Association for
Psychological
Science 127
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All use subject to JSTOR Terms and Conditions
Neural
Activity
and Posttraumatic Stress Disorder
TR
=
3.3
s;
echo
time,
TE
=
40
ms; flip angle
=
90;
field of
view,
FOV: 24 x 24
cm2;
matrix size: 128 x
128). Preprocessing
and statistical
analysis
of
blood-oxygenation-level-dependent
(BOLD)
data were conducted
using
SPM2.
BOLD
signal change
was based on the contrast between re-
sponses
to fearful and neutral faces in a
repeated
measures
fixed-effects
analysis
of variance. We used
region-of-interest
(ROI) analyses
for anterior
cingulate
cortex
(ACC)
and
amyg-
dala to test our a
priori hypotheses.
ROIs were defined
by
the
automated anatomical
labeling
masks
(Tzourio-Mazoyer
et
al.,
2002).
The statistical thresholds
employed were/)
< .05
(small-
volume
corrected)
for ROI
analyses and/)
< .001 for whole-brain
analyses.
BOLD
signal change
was correlated with
change
in
total CAPS score from before to after
treatment,
and the statis-
tical threshold for this
analysis wasp
< .01.
RESULTS
Treatment Outcome
The mean CAPS score was 78.1 at
pretest (SD
-
20, range:
55-120)
and was reduced to 28.9 at
posttest (SD
=
20.3, range:
2-52).
All
subjects
revealed at least a 30% reduction in total
CAPS score.
MRI
The ROI
analyses
revealed
significantly greater
activation in
bilateral rACC after treatment than before
treatment,
left
hemisphere: t(l)
=
2.03,/)
=
.021
(Montreal Neurological
In-
stitute, MNI,
coordinates: x
=
-4, y
=
52,
z
=
2;
10
voxels),
right hemisphere: t(l)
=
1.79, p
=
.036
(x
=
4, y
=
44,
z
=
0;
36
voxels).
There were no
significant
activations in
amygdala
be-
fore or after treatment. Whole-brain
analysis
revealed
signifi-
cantly greater
activation before than after treatment in
right
postcentral gyms, t(l)
=
4.18
(x
=
66, y
=
-16,
z
=
32;
172
voxels); right
middle
temporal gyms, t(7)
=
3.59
(x
=
50, y
=
-
62,
z
=
6;
29
voxels),
and left
superior temporal gyms, t(l)
-
3.48
(x
=
-60, y
=
-4,
z
=
4;
41
voxels).
In
contrast,
activation
was
greater
after than before treatment in left middle
temporal
gyms, t(l)
=
3.94
(x
=
-52, y
=
-18,
z
=
-12;
213
voxels);
right
inferior frontal
gyms, t{l)
=
3.75
(x
=
60, y
=
26,
z
=
2;
57
voxels);
left
parietotemporal gyms, t(l)
=
3.74
(x
=
-56, y
=
-62,
z
=
32;
47
voxels);
and
right hippocampus, t(7)
=
3.23,
p
=
.001
(x
=
34, y
=
-24,
z
=
-12;
6
voxels).
A
significant positive
correlation was found between
change
in total CAPS score and
change
in
right
rACC
activity (x
-
8,
y
-
36,
z
-
8)
from before to after treatment
(r
=
.84,/)
<
.01;
see
Fig. 1).
A
negative
correlation was found between activation in
bilateral
amygdala (x
-
18, y
-
4,
z
=
-16)
and
change
in total
CAPS score
(r
=
-.85,/)
<
.01;
see
Fig. 1). Therefore,
as CAPS
scores
improved,
rACC
activity
increased and
amygdala activity
decreased
during
fear
processing.
Fig.
1. Correlation between
changes
in
blood-oxygenation-level-de-
pendent (BOLD) activity
and
changes
in total
severity
of
posttraumatic
stress disorder
(i.e., changes
in total score on the Clinician-Administered
PTSD
Scale,
or
CAPS) following exposure-based
treatment. The func-
tional
maps display
the areas where
changes
in BOLD
activity
in anterior
cingulate
cortex
(ACC)
and
amygdala (AMG)
correlated with
changes
in
total CAPS
score;
the color scale
represents
the
strength
of the correla-
tion. The scatter
plots display
the direction of these correlations
(im-
provement
on total CAPS on the horizontal axis,
extent of BOLD
activity
on the vertical
axis).
DISCUSSION
This
study provides
the first evidence that successful
exposure
therapy
for PTSD is associated with increased rACC and re-
duced
amygdala
activation
during
fear
processing.
This
pattern
is consistent with evidence of vmPFC involvement in fear ex-
tinction
(Quirk
et
al., 2000).
This
study requires replication
in
research
using larger samples, employing
a wait-list control
condition,
and
examining responses
to trauma-related stimuli.
The current data indicate that the neural correlates of fear
processing
after
improvement
in PTSD
symptoms
accord with
evidence that
amygdala
and rACC
activity
underlie the
acqui-
sition and extinction of conditioned fear.
Acknowledgments
-
This research was
supported by
a Na-
tional Health and Medical Research Council
(NHMRC)
Program
Grant
(300304),
an Australian Research Council
Linkage
Grant
(LP0212048),
an NHMRC Peter
Doherty
Fellowship (358770),
and an NHMRC Australian Clinical
Research
Fellowship (358676).
128 Volume 18- Number 2
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All use subject to JSTOR Terms and Conditions
K.
Felmingham
et al.
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