The Neural Correlates of Emotional Memory in

Posttraumatic Stress Disorder

Kathryn Handwerger Brohawn, Reid Offringa, Danielle L. Pfaff, Katherine C. Hughes, and Lisa M. Shin
Background: Posttraumatic stress disorder (PTSD) is marked by intrusive, chronic, and distressing memories of highly emotional events.
Previous research has highlighted the role of the amygdala and its interactions with the hippocampus in mediating the effect of enhanced
memory for emotional information in healthy individuals. As the functional integrity of these regions may be compromised in PTSD, the
current study examined the neural correlates of emotional memory in PTSD.

Methods: We used functional magnetic resonance imaging and an event-related subsequent memory recognition paradigm to study
amygdala and hippocampus activation in 18 individuals with PTSD and 18 trauma-exposed non-PTSD control participants.

Results: Memory enhancement for negative, relative to neutral, pictures was found across all subjects, without significant differences
between groups. Relative to the trauma-exposed non-PTSD group, the PTSD group showed exaggerated amygdala activation during the
encoding of negative versus neutral pictures. This effect was even more pronounced when the analysis included data from only pictures that
were subsequently remembered 1 week later. In the PTSD group, degree of amygdala activation during the encoding of negative versus
neutral pictures was positively correlated with hippocampal activation and current PTSD symptom severity. The PTSD group also showed
exaggerated hippocampal activation in response to negative pictures that were remembered versus forgotten. Finally, hippocampal
activation associated with the successful encoding of negative relative to neutral pictures was significantly greater in the PTSD group.

Conclusions: Exaggerated amygdala activation during the encoding of emotionally negative stimuli in PTSD is related to symptom severity
and to hippocampal activation.

Key Words: Amygdala, emotion, hippocampus, magnetic reso-
nance imaging, memory, neuroimaging, posttraumatic, stress
disorders
motionally arousing stimuli or events are typically remem-
Importantly, amygdala activation has been shown to be in-
creased in PTSD during the recollection of traumatic events and the
viewing of trauma-unrelated emotionally negative stimuli (14 –19).
Furthermore, degree of amygdala activation is positively correlated
with PTSD symptom severity (e.g., 17,18,20,21). Given this exagger-

E bered better than neutral ones (1). This phenomenon can be

beneficial, as it helps us to remember sources of potential
danger and avoid them in the future. However, memories of highly
emotional events can become intrusive, chronic, and extremely
distressing, as in the case of individuals with posttraumatic stress
disorder (PTSD). The mediating neuroanatomy of enhanced mem-
ory for emotional information has been studied extensively in ro-
dents and healthy humans, but little is known about the neural
correlates of this phenomenon in individuals with PTSD.
Neuroscience research has revealed that the effect of emotion
on memory is mediated, at least in part, by activation in the amyg-
dala and by interactions between the amygdala and hippocampus
(2–9). These two structures are anatomically connected, and effer-
ent projections from the amygdala to the hippocampus are
thought to play a role in the emotional modulation of memory
(3,10). While the amygdala appears to be responsible for assigning
emotional significance to stimuli, the hippocampus assigns contex-
tual meaning to them (11). Basic research has highlighted the role
of norepinephrine and glucocorticoids in mediating the effects of
emotion on memory via their actions on these two structures
(2,12,13).
From the Department of Psychology (KHB, RO, DLP, KCH, LMS), Tufts Univer-
sity, Medford; Department of Psychiatry (KHB, KCH, LMS), Massachusetts
General Hospital and Harvard Medical School, Boston; and Schizophre-
nia and Bipolar Disorders Program (DLP), McLean Hospital, Belmont,
Massachusetts.
Address correspondence to Kathryn Handwerger Brohawn, Ph.D., Tufts Uni-
versity, Department of Psychology, 490 Boston Avenue, Medford, MA
02155; E-mail: katiebrohawn@gmail.com.
Received Dec 8, 2009; revised Jul 14, 2010; accepted Jul 16, 2010.
ated amygdala activation, individuals with PTSD may show en-
hanced memory for novel emotional stimuli. Indeed, this behav-
ioral finding has been documented in PTSD ([11,22–24]; but see
[25,26]).
The effect of emotional arousal on memory may also depend on
amygdala-hippocampal interactions (5,27). Although some studies
have reported diminished hippocampal activation in PTSD (26,28 –
32), others have reported exaggerated hippocampal activation
(31,33–38). The direction of hippocampal abnormalities in PTSD
may depend on the type of task and/or analysis performed (39).
Admon et al. (40) recently reported a delicate interplay between the
amygdala and hippocampus in response to stressful life events.
While prestress amygdala activation was associated with greater
symptoms after stress, such symptoms also depended on the de-
gree of hippocampal plasticity following stress, highlighting the
need to study both structures in trauma-exposed individuals.
Recently, subsequent memory paradigms have highlighted the
role of the amygdala and hippocampus in the emotional modula-
tion of memory in healthy humans (6,41). In these paradigms, brain
activation during encoding is analyzed based on whether items are
later remembered or forgotten (42,43). The term difference due to
memory (Dm) refers to greater brain activation for remembered
than forgotten items and is thought to reflect successful encoding
processes (44,45). In healthy individuals, amygdala and hippocam-
pal/parahippocampal activation are associated with successful
subsequent memory of emotional relative to neutral stimuli (41,43).
Whether the neural correlates of the successful subsequent mem-
ory of emotional stimuli differ in individuals with PTSD is unclear.
To date, only two studies have used subsequent emotional
memory paradigms to examine amygdala and hippocampal activa-
tion in PTSD. Neither study explored a direct functional relationship

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doi:10.1016/j.biopsych.2010.07.018 © 2010 Society of Biological Psychiatry
1024 BIOL PSYCHIATRY 2010;68:1023–1030
Table 1. Demographic and Psychometric Data
PTSD
Mean SD Range
Age 28.2 7.8 19–46
Education 15.0 2.3 10–18
CAPS Current 57.7 15.8 34–85
CAPS Lifetime 86.1 12.0 66–105
BDI 15.3 12.0 0–41
BDI, Beck Depression Inventory; CAPS, Clinician Administered PTSD Scale; PTSD, posttraumatic stress disorder;
TENP, trauma-exposed non-PTSD.
between these structures. Dickie et al. (46) examined subsequent
memory for fearful and neutral faces in PTSD. They reported a
significant positive correlation between PTSD symptom severity
and amygdala activation in response to successfully remembered
fearful versus neutral faces. However, because all subjects had
PTSD, whether those with PTSD differ from trauma-exposed indi-
viduals without the disorder is unknown. More recently, Thomaes et
al. (37) used a subsequent memory paradigm to study nine individ-
uals with PTSD associated with childhood abuse and multiple co-
morbid psychiatric disorders. Relative to the control group, the
PTSD group showed significantly greater hippocampal activation in
response to subsequently remembered deeply encoded negative
words compared with a low-level baseline (but not when compared
with neutral words). However, this study had a small sample size,
used a trauma-unexposed control group, and reported no group
differences in the amygdala.
In the current study, we examined the neural correlates of the
emotional modulation of memory in PTSD. Specifically, we used
functional magnetic resonance imaging (fMRI) to study amygdala
and hippocampal function during the encoding of negative, com-
pared with neutral, pictures in trauma-exposed individuals with
and without PTSD. A recognition memory test was administered
outside of the scanner 1 week later. We predicted that both groups
would remember more negative pictures than neutral pictures, but
given that PTSD is primarily a disorder of intrusive emotional mem-
ories, we predicted that the PTSD group would remember more
negative versus neutral pictures than the trauma-exposed non-
PTSD (TENP) group. Additionally, we predicted that the PTSD group
would show exaggerated amygdala and hippocampal activation
during the encoding of negative versus neutral pictures, especially
those that were subsequently remembered. Our prediction of ex-
aggerated amygdala activation in PTSD was based on similar previ-
ous findings in the literature (e.g., 21,47,48). Our prediction of
greater hippocampal activation in PTSD was based on a previous
finding (37) and on our reasoning that enhanced memory for neg-
ative versus neutral pictures in PTSD should be accompanied by
greater hippocampal activation. Furthermore, based on the find-
ings of subsequent memory studies (6,41), we predicted that fMRI
signal changes in the amygdala and hippocampus would be posi-
tively correlated, especially in the PTSD group. Finally, based on
previous findings (17,18,20,21,46), we predicted that fMRI signal
changes in the amygdala would be positively correlated with symp-
tom severity in the PTSD group. Due to limited prior evidence, we
had no predictions regarding a correlation between hippocampal
activation and symptom severity.
Methods and Materials
Participants
Participants were 42 individuals who reported experiencing cri-
terion A traumatic events, including motor vehicle accidents, sexual
www.sobp.org/journal
K. Handwerger Brohawn et al.
TENP Stats
Mean SD Range t(34) p
26.2 4.5 20–36 .914 .369
16.8 1.6 14–20 2.765 .009
3.6 5.9 0–24 13.620 ⬍.001
11.3 8.8 0–33 21.254 ⬍.001
1.6 1.7 0–5 4.810 ⬍.001
or physical abuse, assault, and witnessing serious injury/death. Ac-
cording to the Clinician-Administered PTSD Scale for DSM-IV (CAPS)
(49), 21 had current PTSD and 21 never had PTSD (TENP group).
Participants were right-handed (50) with no history of head injury,
neurological disorders, or other major medical conditions. No par-
ticipants were pregnant or using psychotropic or cardiovascular
medication at the time of study. Two PTSD participants were ex-
cluded from analyses due to excessive head movement during
scanning. Three TENP participants were excluded due to below-
chance memory performance. One PTSD participant failed to return
for the memory test. The final sample consisted of 18 (3 male) in the
PTSD group and 18 (6 male) in the TENP group (Table 1).
The Structured Clinical Interview for DSM-IV (51) was used to
assess other Axis I disorders. Current comorbidity included major
depression (n ⫽ 4 PTSD, n ⫽ 1 TENP), panic disorder (n ⫽ 2 PTSD),
and specific phobia (n ⫽ 1 PTSD). The Partners Healthcare System
(Boston, Massachusetts) Institutional Review Board approved this
study. Written informed consent was obtained from each partici-
pant.
Materials
Stimuli consisted of 80 negative, 80 neutral, and 80 positive
pictures selected from the International Affective Picture System
(IAPS) (52). The negative and positive pictures did not differ on
normative arousal ratings. Pictures within each type were divided
into two separate sets (A and B); one set was used for encoding and
the other as foils in the subsequent recognition test. Sets were
counterbalanced across subjects in each group and were matched
for valence and arousal ratings within each picture type (negative,
neutral, positive).
Experimental Design
Functional magnetic resonance imaging data were gathered
while participants viewed the stimuli, which were presented in an
event-related paradigm via the stimulus-presentation program
MacStim (MacStim 3.2.1; Darby, White Ant Occasional Publishing;
West Melbourne, Australia) using a Sharp Notevision6 (XG-NV6XU)
LCD projector (Osaka, Japan). Each full-color PICT file was presented
for 5 seconds followed by a fixation cross ranging in duration from 1
to 11 seconds. The duration of each of the two functional scans was
8 minutes, 8 seconds. Immediately following the scan, participants
completed the Beck Depression Inventory (BDI) to quantify de-
pressed mood (53).
One week later, participants returned to the laboratory. At this
visit, they completed a surprise recognition memory test outside of
the scanner. Participants viewed all 240 pictures (sets A and B), only
half of which they saw during fMRI scanning. Participants indicated
whether they had seen the picture during scanning (old) or
whether it was a novel picture that they had not previously seen
(new). They also reported their confidence in each selection on a
three-point scale. After completing the memory test, participants
K. Handwerger Brohawn et al.
again viewed the 120 pictures they originally saw during scanning
and rated each picture on 9-point Likert scales of arousal (1 ⫽ calm,
9 ⫽ excited) and valence (1 ⫽ negative, 5 ⫽ neutral, 9 ⫽ positive).
fMRI Procedures
Scans were obtained from a Symphony/Sonata 1.5 Tesla whole
body scanner (Siemens Medical Systems, Iselin, New Jersey) with a
three-axis gradient head coil. After shimming procedures were per-
formed (54), high-resolution, three-dimensional, magnetization-
prepared rapid acquisition gradient-echo scans (repetition time/
echo time/flip angle ⫽ 2730 msec/3.39 msec/7°; slice thickness ⫽
1.33 mm) were collected. Functional magnetic resonance imaging
(blood oxygen-level dependent [BOLD]) (55) images were acquired
using a gradient echo T2*-weighted sequence (repetition time/
echo time/flip angle ⫽ 2000 msec/40 msec/90°). Functional images
were collected in 26 coronal slices angled perpendicular to the
anterior commissure-posterior commissure line (slice thickness ⫽ 4
mm, skip ⫽ 1 mm; voxel size ⫽ 3.1 ⫻ 3.1 ⫻ 4 mm).
Behavioral Analysis
Hits (number of pictures correctly remembered 1 week later),
misses, false alarms, correct rejections, and the sensitivity index (d’)
for each picture type (negative, neutral, positive) were calculated
for each participant. The d’, a signal detection statistic, was included
because it takes into account both hits and false alarms (d’ ⫽ Z[hit]
– Z[false alarm]). Hit rate and d’ data were analyzed using two
separate 2(group: PTSD, TENP) ⫻ 3(picture-type: negative, neutral,
positive) analyses of variance (ANOVAs). However, preliminary anal-
ysis of behavioral data revealed no significant differences on any of
the memory measures between positive and neutral pictures either
between or within diagnostic groups. Additionally, positive pic-
tures were reported as significantly less arousing than negative
pictures, despite initial matching of pictures based on IAPS nor-
mative ratings. Given this, we limit our reported fMRI analyses to
comparisons between negative and neutral pictures only. Hit
rate and d’ data were then analyzed using two separate 2(group:
PTSD, TENP) ⫻ 2(picture-type: negative, neutral) ANOVAs.
fMRI Data Analysis
Image preprocessing and statistical analyses were performed
using SPM2 (http://www.fil.ion.ucl.ac.uk/spm/;Wellcome Depart-
ment of Imaging Neuroscience, London, United Kingdom). Func-
tional data were motion-corrected, coregistered to subjects’ ana-
tomical images, spatially normalized into a standard stereotaxic
space (Montreal Neurological Institute [MNI]), and spatially
smoothed using a 4-mm Gaussian kernel. The BOLD responses were
modeled as events convolved with the canonical hemodynamic
response function in SPM2. For each condition (negative, neutral,
and fixation), all trials were averaged to estimate BOLD responses.
Five main contrasts of interest were examined. In the negative
versus neutral contrast, BOLD signal in response to all negative
pictures was compared with that of all neutral pictures. In the neg-
ative remembered (NegR) versus neutral remembered (NeutR)
comparison, BOLD signal in response to negative pictures that were
subsequently remembered was compared with that of neutral pic-
tures that were subsequently remembered. The NegR versus nega-
tive forgotten (NegF) contrast (i.e., negative Dm) examined BOLD
signal in response to negative pictures that were subsequently
remembered relative to those that were forgotten. The NeutR ver-
sus neutral forgotten (NeutF) contrast (i.e., neutral Dm) examined
BOLD signal in response to neutral pictures that were subsequently
remembered relative to those that were forgotten. Lastly, the neg-
BIOL PSYCHIATRY 2010;68:1023–1030 1025
ative Dm versus neutral Dm comparison showed the difference in
BOLD signal between NegR ⫺ NegF and NeutR ⫺ NeutF.
The negative versus neutral contrast ought to best probe the
role of the amygdala, as it compares different emotion conditions
and does not take subsequent memory into consideration. In the
NegR versus NegF contrast (i.e., negative Dm), one would expect
primary involvement of the hippocampus, as the emotional va-
lence is held steady on both sides of the contrast, and the subse-
quent memory of stimuli is of key interest. The negative Dm versus
neutral Dm contrast assesses the role of emotion in the successful
subsequent memory of stimuli and should reveal activation in both
the amygdala and hippocampus.
For each of these contrasts, our general approach was the same.
First, we created a voxelwise contrast image for each subject. Next,
we submitted the contrast images for all subjects to a voxelwise,
one-sample t test to assess the main effect of condition (collapsing
across groups). If significant activations were found in our a priori
regions of interest (amygdala and hippocampus), we used the
MarsBaR program (MRC Cognition and Brain Sciences Unit, Cam-
bridge, United Kingdom) to extract fMRI data from all voxels within
the clusters of significantly activated voxels. Extracted data were
then submitted to independent sample t tests (in SPSS; SPSS Inc,
Chicago, Illinois) to determine whether fMRI signal changes differed
between PTSD and TENP groups. This method of analysis (21) cre-
ates an unbiased functional region of interest (ROI) and thus per-
mits the use of a .05 significance threshold for the subsequent
(two-tailed) between-group comparisons on extracted data. This
method also benefits from the ability to use a larger sample size
when creating the functional ROI. Whole-brain voxelwise between-
group analyses were also conducted, and those results were nearly
identical to those reported herein. Additionally, whole-brain voxel-
wise analyses confirmed that BOLD signal changes in our a priori
regions of interest were indeed in the same direction in both
groups, thus further supporting the use of this method of analysis.
For all contrasts in which activation was found in both amygdala
and hippocampus, bivariate correlations were run between the
extracted values from these regions within groups to test our hy-
potheses concerning the relationship between activation of these
two structures. Extracted values from the amygdala and hippocam-
pus were also tested for correlations with CAPS and BDI scores
within groups.
Statistics
The voxelwise statistical parametric maps resulting from the
one-sample t tests (main effect of condition) were inspected for
activations in a priori regions of interest. Given our strong, direc-
tional a priori hypotheses, we used a significance threshold of
p ⬍ .001, uncorrected (z score ⱖ 3.09) for activations in these
regions. Because the procedure of correcting p values based on
the region size is biased toward finding significance in relatively
small structures, we chose to employ the above-stated constant
significance threshold (17,48). For regions about which we had
no a priori prediction, we used a more conservative constant
significance threshold of p ⬍ .00001, uncorrected (z score ⱖ
4.27) (31,48).
Results
Valence/Arousal Ratings
Two separate 2(group: PTSD, TENP) ⫻ 2(picture type: negative,
neutral) ANOVAs were used to analyze valence and arousal ratings.
Valence. The main effect of picture type was significant
[F (1,34) ⫽ 89.77, p ⬍ .001]. Negative pictures were rated signifi-
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1026 BIOL PSYCHIATRY 2010;68:1023–1030 K. Handwerger Brohawn et al.

Figure 1. The functional image on the left displays activation in the right amygdala (Montreal Neurological Institute ⫽ 26, ⫺2, ⫺18; z ⫽ 4.52) in the negative ⬎ neutral
condition collapsing across groups. The bar graph on the right shows magnetic resonance signal change in this region relative to fixation baseline by diagnostic
status. Fix, fixation baseline; Neg, negative; Neut, neutral; PTSD, posttraumatic stress disorder; TENP, trauma-exposed non-PTSD.

cantly lower in valence than neutral pictures. The main effect of
group and the picture type by group interaction were not signifi-
cant (p’s ⬎ .33).
Arousal. The main effect of picture type was significant
[F (1,34) ⫽ 109.45, p ⬍ .001]. Negative pictures were rated signifi-
cantly more arousing than neutral pictures. The main effect of
group and the picture type by group interaction were not signifi-
cant (p’s ⬎ .15).
Memory Performance
Two separate 2(group: PTSD, TENP) ⫻ 2(picture type: negative,
neutral) ANOVAs were used to analyze hits and d’. With regard to
hits, the main effect of picture type was significant [F (1,34) ⫽ 71.85,
p ⬍ .001]. Negative pictures were remembered significantly better
than neutral pictures (Figure S1 in Supplement 1). The main effect
of group and the picture type by group interaction were not signif-
icant (p’s ⬎ .25). The same pattern of results was found when
assessing d’: only the main effect of picture type was significant
[F (1,34) ⫽ 9.299, p ⫽ .004] (all other p’s ⬎ .80).
There were no significant correlations between memory mea-
sures (hits or d’ for either valence category) and CAPS or BDI scores.
fMRI Results
Negative Versus Neutral. Collapsing across groups, the neg-
ative versus neutral comparison revealed significant activation in
both the amygdala and hippocampus bilaterally and in other un-
predicted regions (Table S1 in Supplement 1). Functional magnetic
resonance imaging data were extracted from significant functional
activations (ROIs) in the amygdala and hippocampus. Independent
sample t tests on the differences scores of the extracted data re-
vealed significantly greater right amygdala activation in the PTSD
compared with the TENP group (Figure 1).
In the PTSD group, significant positive correlations were found
between BOLD signal increases in the right hippocampus (MNI ⫽
22, ⫺28, ⫺6) and in both the left [r(16) ⫽ .564, p ⫽ .015: MNI ⫽ ⫺18,
⫺4, ⫺14] and right [r(16) ⫽ .513, p ⫽ .029: MNI ⫽ 18, ⫺4, ⫺12;
Figure 2A] amygdala. In the TENP group, no such correlations were
found between BOLD signal in the right hippocampus and either
the left [r(16) ⫽ .037, p ⫽ .883] or right [r(16) ⫽ ⫺.005, p ⫽ .983]
amygdala. Additionally, PTSD subjects’ current CAPS scores were
positively correlated with activation in the left [r(16) ⫽ .563, p ⫽
.015; Figure 2B] but not right [r(16) ⫽ .339, p ⫽ .169] amygdala.
Analogous correlations were not found in the TENP group [left:

Figure 2. (A) Correlation between blood oxygen-level dependent activation in the right hippocampus (Montreal Neurological Institute [MNI] ⫽ 22, ⫺28, ⫺6)
and right amygdala (MNI ⫽ 18, ⫺4, ⫺12) in the negative ⬎ neutral contrast in the posttraumatic stress disorder group only (r ⫽ .513, p ⫽ .029). (B) Correlation
between blood oxygen-level dependent activation in the left amygdala (MNI ⫽ ⫺26, ⫺4, ⫺22) and current Clinician-Administered PTSD Scale for DSM-IV
scores in the negative ⬎ neutral contrast in the posttraumatic stress disorder group only (r ⫽ .563, p ⫽ .015). CAPS, Clinician-Administered PTSD Scale for
DSM-IV; PTSD, posttraumatic stress disorder.

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K. Handwerger Brohawn et al. BIOL PSYCHIATRY 2010;68:1023–1030 1027

Figure 3. (A) The functional image on the left displays activation in the right amygdala (Montreal Neurological Institute ⫽ 26, ⫺2, ⫺20; z ⫽ 4.31) in the
negative remembered ⬎ neutral remembered condition collapsing across groups. The bar graph on the right shows magnetic resonance signal change in this
region relative to fixation baseline by diagnostic status. (B) The functional image on the left displays activation in the left amygdala (Montreal Neurological
Institute ⫽ ⫺20, ⫺8, ⫺12; z ⫽ 4.46) in the negative remembered ⬎ neutral remembered condition collapsing across groups. The bar graph on the right shows
magnetic resonance signal change in this region relative to fixation baseline by diagnostic status. NegRvFix, negative remembered relative to fixation
baseline; NeutRvFix, neutral remembered relative to fixation baseline; PTSD, posttraumatic stress disorder; TENP, trauma-exposed non-PTSD.

r(16) ⫽ ⫺.340, p ⫽ .168; right: r(16) ⫽ ⫺.143, p ⫽ .573]. No
significant correlations were found between BDI scores and
amygdala or hippocampal activation in either group.
Negative Remembered Versus Neutral Remembered. Col-
lapsing across groups, we found significantly greater activation in
response to subsequently remembered negative pictures than to
subsequently remembered neutral pictures in the left hippocam-
pus and bilateral amygdala. Extracted values in these functionally
defined ROIs were submitted to two separate independent sam-
ple t tests. Activation in the right [t (34) ⫽ 2.122, p ⫽ .041] and left
[t (34) ⫽ 2.053, p ⫽ .048] amygdala was significantly greater in the
PTSD group than the TENP group (Figure 3). In the PTSD group only,
a significant positive correlation was found between activation in
the left hippocampus and the left amygdala [r(16) ⫽ .614, p ⫽ .007;
Figure 4A]. The analogous correlation was not found in the TENP
group [r (16) ⫽ .082, p ⫽ .746]. No significant correlations were
found between activation in these NegR versus NeutR ROIs and
CAPS or BDI scores in the PTSD group.
Negative Remembered Versus Negative Forgotten. Col-
lapsing across groups, we found significantly greater activation in
response to negative pictures that were subsequently remembered
than to those that were forgotten in the right amygdala and hip-
pocampus bilaterally. No between-group differences in amygdala
activation were found. Right hippocampal activation was greater in
the PTSD group than in the TENP group [t (34) ⫽ 1.919, p ⫽ .064].
Activation in the right amygdala was positively correlated with
current CAPS scores in the PTSD group [r(16) ⫽ .451, p ⫽ .030;
Figure 4B] but not in the TENP group [r(14) ⫽ .062, p ⫽ .410].
Activation in the right hippocampus was positively correlated with
BDI scores in the PTSD group [r(16) ⫽ .512, p ⫽ .030].
Negative Dm Versus Neutral Dm. Collapsing across groups,
this analysis revealed significantly greater activation in the negative
Dm versus the neutral Dm in the amygdala bilaterally and the right
hippocampus. Amygdala activation did not significantly differ be-
tween groups. The PTSD group had significantly greater hippocam-
pal activation than the TENP group [t (32) ⫽ 2.211, p ⫽ .034; Figure
5]. No significant correlations were found between activation in
either the amygdala or hippocampus and CAPS or BDI in either
group.
All analyses that yielded significant findings were repeated after
temporarily removing the data of participants with current comor-
bid major depression. All findings remained significant, with one
exception: the p value for the between-group difference in the right
amygdala in the NegR versus NeutR contrast changed from .041 to
.075. Additionally, despite group differences in years of education,
there were no significant correlations between years of education
and amygdala or hippocampal activation in any of the ROIs defined
in the aforementioned contrasts in either group.
Discussion
Our subsequent recognition memory paradigm revealed the
expected memory enhancement for negative versus neutral pic-
tures after a 1-week retention interval. Contrary to our hypotheses,

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1028 BIOL PSYCHIATRY 2010;68:1023–1030 K. Handwerger Brohawn et al.

Figure 4. (A) Correlation between blood oxygen-level dependent activation in the left hippocampus (Montreal Neurological Institute [MNI] ⫽ ⫺18, ⫺28, ⫺6)
and left amygdala (MNI ⫽ ⫺20, ⫺8, ⫺12) in the negative remembered ⬎ neutral remembered condition in the posttraumatic stress disorder group only (r ⫽
.614, p ⫽ .007). (B) Correlation between blood oxygen-level dependent activation in the right amygdala (MNI ⫽ 22, 4, ⫺16) and current Clinician-Administered
PTSD Scale for DSM-IV score in the negative remembered ⬎ negative forgotten condition in the posttraumatic stress disorder group only (r ⫽ .451, p ⫽ .030).
CAPS, Clinician-Administered PTSD Scale for DSM-IV; PTSD, posttraumatic stress disorder.

this effect was not significantly greater in the PTSD group than the
TENP group. This finding is contrary to previous reports of better
memory for emotional versus neutral material in PTSD (11,22–24)
but is consistent with the findings of Bremner et al. (26), who found
no evidence for enhanced memory for emotional versus neutral
word pairs in PTSD. Our 1-week retention interval may not have
been long enough to reveal behavioral between-group differences
(both groups remembered over 80% of the negative stimuli after 1
week). Additionally, group differences in memory may be more
likely to emerge when the stimuli are more directly related to par-
ticipants’ traumatic events. However, a lack of behavioral differ-
ences between groups may actually make the between-group dif-
ferences in brain activation more interpretable.
Our findings of exaggerated amygdala activation in the PTSD
group relative to the TENP group during the encoding of negative
versus neutral pictures (especially those that were subsequently
remembered) add to the existing literature documenting exag-
gerated amygdala responses in PTSD (e.g., [14,15,17]; for a re-
view see [56]). Additionally, our correlation between amygdala
activation during the encoding of negative stimuli and symptom
severity in the PTSD group parallels that of Dickie et al. (46). Positive
correlations between symptom severity and amygdala activation
have also been reported in previous studies (17,18,20,21).
The degree of hippocampal activation in both the negative ver-
sus neutral and negative remembered versus neutral remembered
contrasts did not differ between groups. Similarly, Thomaes et al.
(37) did not find enhanced hippocampal activation in response to
negative words in PTSD when using neutral pictures as a compari-
son condition. However, our finding of a significant positive corre-
lation between amygdala and hippocampal activation in these con-
trasts only in the PTSD group supports the idea of exaggerated
functional connectivity between these two structures in PTSD. Ad-
ditionally, hippocampal activation was greater in the PTSD group
than the TENP group when directly assessing remembered (vs.
forgotten) negative pictures.
Consistent with previous research (41), greater bilateral amyg-
dala activation was found in response to the negative Dm than to
the neutral Dm in both groups pooled together. However, this
amygdala activation did not differ between diagnostic groups. This
lack of a between-group difference may help account for the lack of
a behavioral difference between groups. However, we did find
greater hippocampal activation in PTSD subjects than in TENP sub-
jects in response to the negative Dm versus neutral Dm contrast.
Splitting subjects by diagnosis revealed that only the PTSD group
displayed significant hippocampal activation in response to this
contrast. This finding lies in contrast to that of Dolcos et al. (41), who

Figure 5. The functional image on the left displays activation in the right hippocampus (Montreal Neurological Institute ⫽ 28, ⫺30, ⫺22; z ⫽ 3.46) in the
negative difference due to memory ⬎ neutral difference due to memory condition collapsing across groups. The bar graph on the right shows magnetic
resonance signal change in this region relative to fixation baseline by diagnostic status. NegRvFix, negative remembered relative to fixation baseline;
NeutRvFix, neutral remembered relative to fixation baseline; PTSD, posttraumatic stress disorder; TENP, trauma-exposed non-PTSD.

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K. Handwerger Brohawn et al.
reported enhanced hippocampal activation in response to the
emotional Dm versus neutral Dm in a sample of healthy individuals.
We were not able to replicate the Dm effect in our control group.
However, Dolcos et al. (41) used both positive and negative pictures
and a cued-recall task and a 45-minute retention interval, whereas the
current study used a recognition test and a 1-week retention interval.
These paradigm differences may have accounted for differences in
results, as these two types of memory are believed to be mediated by
different regions within the medial temporal lobe, with recall requiring
more hippocampal involvement than recognition (57).
Limitations and Conclusions
In the current study, we excluded individuals who were taking
psychiatric medications and who had current comorbid disorders
other than depression and anxiety disorders. While comorbid de-
pression in the PTSD group may be viewed as a limitation, given the
high comorbidity rates between PTSD and depression (58), exclud-
ing PTSD patients with depression would have severely compro-
mised external validity. Nearly all analyses remained significant
when data from participants with comorbid depression were tem-
porarily removed. In addition, in the PTSD group, amygdala activa-
tion was correlated with CAPS scores but not BDI scores. Neverthe-
less, future studies of emotional memory in PTSD should employ
psychiatric control groups. It is also important to note that the
restricted range of CAPS scores in the TENP group could explain the
lack of significant correlations with BOLD signal changes in this
group. Finally, using the main effect of condition maps to define
functional ROIs cannot reveal areas of functional activation in which
the direction of effects differ between the PTSD and TENP groups.
However, whole-brain voxelwise analyses confirmed that BOLD sig-
nal changes in our a priori regions of interest were indeed in the
same direction in both groups, thus supporting use of this method.
In conclusion, we document for the first time that amygdala
activation related to the subsequent memory of negative, trauma-
unrelated versus neutral pictures is exaggerated in PTSD. Addition-
ally, enhanced hippocampal activation in PTSD is related to the
successful encoding of negative pictures, and functional coupling
between the amygdala and hippocampus during the encoding of
negative pictures also appears exaggerated. Together, these find-
ings point toward an interaction between these two structures in
the pathophysiology of this disorder.
That these functional abnormalities were not accompanied by
relatively enhanced memory for negative versus neutral stimuli
suggests that fMRI measures may be more sensitive to group differ-
ences than behavioral measures in this paradigm. Because our
comparison group was exposed to criterion A trauma but did not
have PTSD, trauma exposure cannot account for the group differ-
ences reported herein. Future studies using longitudinal or twin
designs should attempt to determine whether these functional
abnormalities are acquired characteristics of PTSD or rather repre-
sent risk factors for the development of PTSD after psychological
trauma.
KHB was supported by a National Science Foundation graduate
student fellowship. LMS received support from Tufts University and a
National Alliance for Research on Schizophrenia and Depression
Young Investigator Award.
We thank the individuals who served as research participants;
Doug Greve, Mary Foley, Clas Linnman, and Lawrence White for their
technical assistance; Caroline Davit for assistance with scanning and
participant recruitment; and Matt Nathanson, Lisanne Petracca, and
Elizabeth Hammond for pilot testing the paradigm.
BIOL PSYCHIATRY 2010;68:1023–1030 1029
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