Download Differential amygdala activation during emotional decision and

Neuropsychologia 39 (2001) 556– 573
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Differential amygdala activation during emotional decision and
recognition memory tasks using unpleasant words: an fMRI study
Matthias H. Tabert a,b,*, Joan C. Borod a,b, Cheuk Y. Tang c,d,e, Gudrun Lange f,
Tsechung C. Wei c, Ray Johnson b, Annette O. Nusbaum d, Monte S. Buchsbaum c
b
a
Department of Neurology, Mount Sinai Medical Center, New York, NY, USA
Department of Psychology, Queens College and The Graduate Center, City Uni6ersity of New York (CUNY), New York, NY, USA
c
Department of Psychiatry, Mount Sinai Medical Center, New York, NY, USA
d
Department of Radiology, Mount Sinai Medical Center, New York, NY, USA
e
Department of Radiological Sciences, UC Ir6ine, Ir6ine, CA, USA
f
Departments of Psychiatry and Radiology, UMDNJ – New Jersey Medical School, Newark, NJ, USA
Received 14 October 1999; received in revised form 26 October 2000; accepted 17 November 2000
Abstract
This study used fMRI to examine the response of the amygdala in the evaluation and short-term recognition memory of
unpleasant vs. neutral words in nine right-handed healthy adult women. To establish specificity of the amygdala response, we
examined the fMRI BOLD signal in one control region (visual cortex). Alternating blocks of unpleasant and neutral trials were
presented. During the emotional decision task, subjects viewed sets of three unpleasant or three neutral words while selecting the
most unpleasant or neutral word, respectively. During the memory task, subjects identified words that were presented during the
emotional decision task (0.50 probability). Images were detrended, filtered, and coregistered to standard brain coordinates. The
Talairach coordinates for the center of the amygdala were chosen before analysis. The BOLD signal at this location in the right
hemisphere revealed a greater amplitude signal for the unpleasant relative to the neutral words during the emotional decision but
not the memory task, confirmed by Time Course× Word Condition ANOVAs. These results are consistent with the memory
modulatory view of amygdala function, which suggests that the amygdala facilitates long-term, but not short-term, memory
consolidation of emotionally significant material. The control area showed only an effect for Time Course for both the emotional
decision and memory tasks, indicating the specificity of the amygdala response to the evaluation of unpleasant words. Moreover,
the right-sided amygdala activation during the unpleasant word condition was strongly correlated with the BOLD response in the
occipital cortex. These findings corroborate those by other researchers that the amygdala can modulate early processing of visual
information in the occipital cortex. Finally, an increase in subject’s state anxiety (evaluated by questionnaire) while in the scanner
correlated with amygdala activation under some conditions. © 2001 Elsevier Science Ltd. All rights reserved.
Keywords: fMRI; Emotion; State anxiety; Amygdala; Occipital cortex; Unpleasant words; Neutral words; Emotional decision; Emotional memory
1. Introduction
Studies of patients with bilateral amygdala lesions
have provided evidence that the human amygdala plays
a role in the evaluation of emotional facial expressions,
particularly those related to fear and anger [6–
* Corresponding author. Address: New York State Psychiatric
Institute, 722 West 168th Street, Unit 126, Kolb Annex, Rm 417,
New York, NY 10032, USA. Tel.: + 1-212-543-5046; fax: + 1-212369-8764.
E-mail address: [email protected] (M.H. Tabert).
8,27,35,90,91]. Human bilateral lesion studies have also
implicated the amygdala in the recognition of non-verbal threat-related sounds (e.g., screams and growling)
[80] and in the evaluation of words [80] and sentences
denoting negative emotions [4]. These findings are consistent with a large body of animal literature that
implicates the amygdala in the evaluation of cues that
predict danger to the organism [10,60]. These data also
suggest that bilateral amygdala lesions in humans can
result in a modality-independent impairment in the
recognition of threat-related emotional expressions.
Moreover, since the amygdala receives inputs from
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M.H. Tabert et al. / Neuropsychologia 39 (2001) 556–573
multiple sensory modalities [12] and is capable of multimodal processing [11], these data argue that the amygdala is part of an underlying processing mechanism
geared to interpret emotional signals of threat or danger regardless of their source.
It should be noted, however, that not all patients
with bilateral amygdala damage demonstrate selective
emotional processing impairments. A number of studies
have demonstrated that bilateral amygdala damage
does not necessarily impair the ability to evaluate facial
[9,48,49,51] or prosodic [5,13] emotional expressions.
Moreover, amygdala lesions do not appear to block
normal autonomic [19,84] or self-reported reactions
[2,31,49] to salient emotional stimuli. While reasons for
this discrepancy in the bilateral amygdala lesion literature are not fully understood (for possible explanations,
see Refs. [1,5,6,27,48,51]), there is overall convincing
evidence from animal and human studies that the
amygdala does play a role in selectively processing
emotional, particularly threatening, information
[1,9,11,86].
PET and fMRI studies investigating the perception
and evaluation of prototypical emotional facial expressions (e.g., fear, anger, disgust, and happiness) in normal individuals have provided further evidence that the
amygdala plays a role in the evaluation of emotional
information. In a PET-O15 study, Morris and colleagues [68] observed increasing amygdala activation as
a function of the intensity of fearful facial expressions.
Interestingly, in a subsequent analysis of these data,
Morris et al. [67] found that amygdala activation in
response to fearful expressions was strongly correlated
with activity in the occipital cortex, suggesting that the
amygdala can modulate early processing of visual information. Using fMRI, Breiter et al. [26] also observed
amygdala activation to fearful facial expressions. In the
studies of Morris et al. [67] and Breiter et al. [26],
subjects passively viewed facial expressions or made
judgments as to the gender of the posers. Whalen et al.
[88] presented fearful faces to subjects below the
threshold of conscious awareness, using a backward
masking procedure, and found that the amygdala revealed a significant increase in activation to masked
fearful expressions. Phillips and coworkers [73,74] and
Baird et al. [17] have also reported amygdala activation
to facial expressions of fear.
Imaging studies have investigated brain activation in
response to emotionally intoned vocal expressions and
to the emotional content of negatively valenced words.
Phillips et al. [73] reported right amygdala activation in
response to vocal expressions of fear (e.g., screams) in
normal subjects. Kiehl et al. [55] reported right amygdala activation in response to viewing, rehearsing, and
recalling negatively valenced emotional words. These
studies provide further evidence that the amygdala is
involved in processing negatively valenced stimuli, regardless of presentation modality.
557
A large body of behavioral, pharmacological, lesion,
and imaging data also suggests that the amygdala plays
an important role in memory processes related to emotion [1,72]. Normal subjects generally show superior
memory for emotionally arousing stimuli relative to
emotionally neutral stimuli (for review, see Ref. [44]).
Lesion and functional neuroimaging findings have illuminated the importance of the amygdala in facilitating
the acquisition of emotional memories (reviewed by
Phelps and Anderson [72]). Adolphs et al. [2], Babinsky
et al. [16], Cahill et al. [31] and Markowitsch et al. [64]
have all reported selective long-term memory impairment for verbal and non-verbal emotional materials
following bilateral amygdala lesions. Cahill et al.
[32] (using FDG-PET) and Hamann et al. [50] (using
PET-O15) have also found that increases in amygdala
activity in subjects viewing emotional and neutral stimuli are strongly correlated with performance on longterm but not short-term free recall and recognition
memory tasks for emotionally arousing relative to neutral information.
Together, these findings support the memory modulatory theoretical framework of amygdala function, developed by McGaugh and colleagues [30,33,65,66] in
experimental animal research. This view suggests that
when the human amygdala becomes active in the presence of emotionally arousing stimuli (e.g., during encoding), it weighs conscious memory for the triggering
stimuli in proportion to their salience by influencing
long-term memory storage and consolidation via interactions with neurotransmitter systems, particularly the
adrenergic system, and via anatomical connections to
the hippocampus, striatum, and other brain regions
[66]. An important aspect of this view is that the
amygdala’s role in declarative memory is unrelated to
memory for non-emotional material. Moreover, with
respect to emotional material, this view emphasizes that
the amygdala’s involvement is time dependent in that
its memory-enhancing effects only become apparent
after enough time (i.e., several hours to days) has
passed to allow for memory consolidation in remote
brain regions to occur [30,65,66]. The amygdala itself is,
therefore, not thought to be the site where actual
emotional memories are stored and is not thought to
participate directly in the retrieval or recall of emotional information [70]. In this vein, a recent study by
Bianchin et al. [20] demonstrated that the administration of several drugs into the rat amygdala at the time
of training in a one-trial, step-down, inhibitory avoidance paradigm had no effect on either working memory
(tested at 3 s post-training) or short-term memory
(tested at 1.5 h post-training). However, all drugs had
strong modulatory effects on long-term memory (tested
at 24 h post-training), some enhancing (e.g., norepinephrine) and others impairing performance.
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M.H. Tabert et al. / Neuropsychologia 39 (2001) 556–573
In summary, neuroimaging studies corroborate human bilateral amygdala lesion and animal studies, implicating the amygdala in the processing of emotional
stimuli. Further, the amygdala appears to have a special role in the perception of emotional facial expressions. Facial expressions of anger and fear are
especially salient in that they provide potent, possibly
hardwired cues to the presence and source of personal
danger [39,86]. Also, there is evidence from both lesion
and imaging data that vocal expressions of fear [73,80]
and the evaluation of emotionally arousing negative
lexical stimuli (i.e., words and sentences) [4,55,80] involve the amygdala. Finally, there is evidence that
amygdala activity while viewing (encoding) stimuli is
correlated with subsequently enhanced long-term recall
of emotional as compared to neutral information
[32,50].
The purpose of the current study was to further
examine the extent to which the amygdala is recruited
in response to the evaluation, or presumably encoding,
and the immediate recall (via recognition memory) of
highly unpleasant and neutral words. In the current
study, two separate fMRI scans were conducted. During the first scan, subjects were required to explicitly
evaluate the relative emotional significance of highly
unpleasant vs. neutral word sets (i.e., degree to which
the words were perceived as threatening). Subjects were
instructed to base their evaluations of the word sets on
their personal experience with the concepts and connotations conveyed by the words. During the second scan,
which immediately followed the first scan, memory for
the words presented during the first scan was assessed.
Together, these scans were used to examine the differential involvement of the amygdala during the explicit
evaluation vs. the short-term recognition of highly unpleasant as well as neutral words.
We hypothesized that the amygdala would show
greater time-locked activation in response to the evaluation of highly unpleasant than neutral words [55].
Because normal subjects generally show superior immediate and long-term memory for emotional as compared to neutral lexical stimuli (for review, see Ref.
[44]), we hypothesized that subjects would recall more
emotional than neutral words immediately following
the first scan (i.e., evaluation and encoding). However,
on the basis of the memory modulatory view of amygdala function (see above), we predicted that this shortterm memory enhancement would not be related to
amygdala activity.
To establish the specificity of the amygdala response
to unpleasant words, we examined the BOLD signal
waveform in one control region, the occipital cortex
(primary and secondary visual areas). A general response to stimuli (unpleasant and neutral) was expected
in this control region for both tasks (emotional decision
and recognition memory) since the visual cortex re-
sponds selectively to visually-presented stimuli [68].
Moreover, a recent study by Morris et al. [67] found
that while amygdala and occipital activations to fearful
expressions were positively correlated (r= 0.62), amygdala and occipital activations to happy expressions
were inversely correlated (r= − 0.55). These findings
suggest that amygdala activation in response to emotional stimuli modulates the early processing of visually
presented information in the occipital cortex in a category-specific way. Hence, in the current study, we further hypothesized that the response in the occipital
cortex to words in general (i.e., unpleasant and neutral)
would be positively correlated to increases in amygdala
activation during the unpleasant word condition.
A further goal of this study was to investigate the
influence of anxiety created by the scanning procedure
on amygdala activation. Based on our own pilot work
and reports from previous studies [46,47,78], we predicted a significant increase in self-reported state anxiety [81] from subjects’ scores immediately before
entering the scanner to scores reflecting their anxiety
level during the scanning session (measured immediately after the scan). We also conducted exploratory
correlational analyses to assess the relationship between
changes in state anxiety as a result of the scanning
procedure and amygdala activation.
Finally, the a priori focus of this study was on the
amygdala. Hence, only results pertaining to this region
of interest and one control area (occipital cortex) are
discussed at length. To further establish the specificity
of amygdala findings, however, whole brain activation
is presented on an exploratory basis.
2. Methods
2.1. Subjects
Nine women (mean age, 28.2 yr; S.D., 4.7 yr; range,
23–38 yr) participated in this study; all were righthanded and native English-speakers and held a bachelor’s or doctoral degree (Mill Hill vocabulary test [76]:
mean verbal IQ estimate [71], 111; S.D., 7.5). Handedness was determined using the Coren et al. [37] inventory. Subjects had no history of psychiatric,
neurological, or other major medical illness, and had
never been treated with psychotropic medication. Written informed consent was obtained from all subjects,
and each subject was paid for participation. To eliminate sex differences and improve statistical power, only
females were scanned in the current study.
2.2. Procedures
2.2.1. Measure of state anxiety
To assess anxiety related to the scanning procedure,
M.H. Tabert et al. / Neuropsychologia 39 (2001) 556–573
we measured state anxiety with the State Trait Anxiety
Inventory (STAI [81]), both immediately before and
immediately after scanning. During the second administration, subjects were instructed to complete the STAI
in terms of their experience inside the scanner.
2.2.2. Emotional decision scan
The words used in this study came from the database
of Toglia and Battig [83] (Table 1) which includes 2854
words that have been rated on concreteness [from 1
(low concreteness) to 7 (high concreteness)], imagery
[from 1 (low imagery) to 7 (high imagery)], and pleasantness [from 1 (unpleasant) to 7 (pleasant), with 4 as
the neutral midpoint]. For the current study, 30 highly
unpleasant words and 30 neutral words (mean pleasantness ratings= 2.1 vs. 4.0) that did not differ significantly on word length (mean word length= 5.4 vs. 5.7
letters, P=0.509), word frequency [43] (mean frequency of occurrence= 62.1 vs. 61.8 per million, P=
0.989), concreteness (mean concreteness ratings= 4.4
vs. 4.7; P= 0.289), and imagery (mean imagery ratings=5.0 vs. 4.7; P = 0.152) were selected. Although
words were not specifically matched for part of speech,
Table 1
Word stimuli used in the current study, selected from Toglia and
Battig [83]
Neutral
Unpleasant
following
step
referee
rows
academy
cable
size
meant
therefore
loop
chart
pots
glasses
empire
tray
differences
sequel
doorman
suit
age
cents
garment
boot
angle
mile
rapid
wind
tradition
root
chestnut
cancer
murder
slavery
morgue
greedy
kill
gun
polio
measles
misery
war
cruel
hate
crime
poor
failing
pollution
dead
bomb
prejudice
ugly
death
agony
coffin
tragedy
sewer
trouble
hell
rape
vulgar
559
both lists contained nouns, verbs, adjectives, and
adverbs.
The selected words were used to generate unpleasant
and neutral word sets, where each word set comprised
a unique combination of three words. Word sets were
presented in eight alternating unpleasant and neutral
blocks (4 cycles; Fig. 1(a) and (b)). A 2- to 3-min break
occurred halfway through the scan to allow acquired
data to be transferred to a remote computer workstation for storage and analysis. Each block began with a
2-s cue indicating whether the block consisted of unpleasant or neutral trials (Fig. 1b). Five word set trials
were presented during each block, each appearing for 4
s with a 2-s inter-stimulus interval (ISI). Thus, the
BOLD response was recorded to four blocks of unpleasant words and to four blocks of neutral words.
During each ISI, a centrally placed fixation-cross replaced the word set. A 20-s resting baseline preceded
the first block of trials, and a 24-s resting period
separated all subsequent blocks of trials, during which
subjects also viewed a central fixation cross. During
each trial, a word set was projected to the center of the
subject’s field of view via an SVGA computer-controlled projection system that presented stimuli to a
rear-projection screen located at the entrance of the
magnet bore. Subjects viewed stimuli projected to the
screen via a 1.5× 3 in.2 mirror attached to the head coil
and positioned : 6 in. from and directly above the
subject’s eyes. Each word appeared twice over the
course of the scan (i.e., first presentation occurred
during the first two blocks, and the second presentation
during the last two blocks of each stimulus type) within
unique word sets. Word sets were presented in a fixed
pseudo-randomized order across the blocks with the
condition that a word did not reappear until all words
had been presented once. The position of a word within
a word set was counterbalanced across presentations of
that word. The sequence in which blocks of unpleasant
and neutral trials were presented was counterbalanced
across subjects by reversing the trial order for four of
the nine subjects.
Immediately before scanning began, subjects were
given 10 practice trials (5 unpleasant and 5 neutral).
The negative and neutral words presented during practice did not overlap with the experimental words and
were selected from the list of Brown and Ure [28],
which includes 650 words that were also rated for
pleasantness using a 7-point scale.
During unpleasant blocks, subjects were instructed to
select the most unpleasant or most threatening word
from the three negatively valenced words (word set)
presented on each trial. Subjects were instructed to base
their decision on their personal knowledge of and experience with the concepts and connotations conveyed by
the words. Similarly, during neutral blocks, subjects
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M.H. Tabert et al. / Neuropsychologia 39 (2001) 556–573
Fig. 1. (a) Overview of blocked stimulus presentation paradigm for the Emotional Decision Scan. Eight alternating blocks of Neutral (N) and
Unpleasant (U) trials were separated by Rest Periods ( + ). Total scan time was 488 s (8 min and 8 s), yielding 244 images of 14 axial slices (3416
slices). Each slice contains a maximum of 64 × 64 pixels, where each pixel is 3.59 mm2 (FOV= 23 cm2). (b) Summary of the stimulus presentation
parameters within a block of unpleasant and neutral trials for the Emotional Decision Task (one complete cycle of unpleasant and neutral trials).
(i) Block of unpleasant trials and preceding baseline. (ii) Block of neutral trials preceded by a rest period. Each block began with a cue indicating
‘‘unpleasant’’ or ‘‘neutral.’’ Subjects selected a word judged to be the most unpleasant or neutral for each word set by pressing one of the three
buttons.
M.H. Tabert et al. / Neuropsychologia 39 (2001) 556–573
561
Fig. 2. (a) Overview of blocked stimulus presentation paradigm for the Recognition Memory Scan. Twelve alternating blocks of Neutral (N) and
Unpleasant (U) trials were separated by Rest Periods ( +). Total scan time was 520 s (8 min 36 s), yielding 260 images of 14 axial slices (3640
slices). Each slice contains a maximum of 64 × 64 pixels where each pixel is 3.59 mm2 (FOV= 23 cm2). (b) Summary of the stimulus presentation
parameters within a block of unpleasant and neutral trials for the Recognition Memory Task (one complete cycle of unpleasant and neutral trials).
(i) Block of unpleasant trials and preceding baseline. (ii) Block of neutral trials preceded by a rest period. The 30 unpleasant and 30 neutral words
presented during scan 1 (targets) were randomly mixed with 30 foils of each word type (0.5 probability of target appearing). Subjects selected a
word judged to be the most unpleasant or neutral for each word set by pressing one of the three buttons.
selected the word they deemed to be the most neutral
(i.e., non-emotional or non-threatening) from each
word set. Subjects indicated their response by pressing
one of the three buttons on a response pad.
2.2.3. Recognition memory scan
Immediately following the first scan (described
above), a second scan was performed to assess recognition memory for the words presented (targets) during
the emotional decision task. Sixty additional new words
were selected from Toglia and Battig [83] to serve as
foils or distractors in the memory scan (30 highly
unpleasant and 30 neutral). Given the limited number
of words available, particularly for the unpleasant category, the foils were matched to the targets on word
length only. Together, 120 words (60 previously seen
and 60 not previously seen) were presented one at a
time in the center of the subject’s field of view in 12
alternating unpleasant and neutral blocks (6 cycles; Fig.
2(a)). Each block consisted of a fixed random sequence
of 10 words, with a 0.50 probability of being a previously seen word (Fig. 2(b)). Each word was presented
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M.H. Tabert et al. / Neuropsychologia 39 (2001) 556–573
for 2 s and was immediately followed by the next word.
A 20-s resting period preceded the first block of trials
and separated successive blocks, during which time
subjects viewed a central fixation cross. The sequence in
which blocks of unpleasant and neutral trials was presented was counterbalanced across subjects by reversing
the trial order for four of the nine subjects. Subjects
were instructed to press a key with their index finger
whenever they recognized a word from the previous
scan.
This method produces symmetrical brain images
around the midline so that hemispheric contrasts can be
examined. The fMRI data of consecutive images (224
for Scan 1 and 260 for Scan 2) were arranged as a pixel
time-series with each pixel in the image having entries
representing the 2-s time points. The anatomical center
and extent of the amygdala region were obtained a
priori from Talairach and Tournoux [82] atlas coordinates (center: 23, −6, −12; with : 10-mm diameter
corresponding to 3 pixels; 3.6 mm2/pixel).
2.3. Image acquisition and post-processing
2.4. Statistical analyses
An initial T1-weighted sagittal localizer (spoiled gradient recall acquisition in a steady state; SPGR) sequence was acquired using a 1.5 T GE Horizon LX
scanner (General Electric, Milwaukee, WI). Subsequently, 14 axial spin-echo T1-weighted images were
acquired, encompassing the whole brain (TE/TR = 18/
600 ms, FOV =23 mm2, slice thickness= 5 mm, skip =
2.5).
Echoplanar magnetic resonance brain images were
acquired with a multi-slice 2D EPI sequence (64×64
matrix, FOV= 23 cm2, TE =40 ms, TR =2000 ms,
thickness 5-mm, 2.5-mm gap). For the first (emotional
decision) scan, 244 T2*-weighted images depicting
BOLD contrast [69] were acquired over 8 min and 8 s.
For the second (recognition memory) scan, 260 images
were acquired. Each image consisted of 14 near-axial,
non-contiguous slices, providing whole-brain coverage.
Preprocessing of the raw fMRI signal for each scan
involved the removal of the mean, detrending, and
digital filtering to remove low and high frequencies
outside the range of the primary blood flow response.
The mean and linear trends were removed using a least
squares line-fit from each continuous data set. A pixelby-pixel fast Fourier transform (FFT) was then performed, and all frequency components below 0.018 Hz
and above 0.071 Hz were removed. These cut-off frequencies were selected to reduce signal contributions
slower than 1 cycle in 40 s (greater than the block
length) and faster than 1 cycle in 15 s (about 14 of the
block length), based on the on – off cycle period of 56 s.
A new filtered fMRI image dataset was obtained by an
inverse FFT.
The 14 reconstructed anatomical and functional images were visually inspected and matched to standard
axial brain slices from the Talairach and Tournoux [82]
atlas. The edges of the anatomical slices for each subject were traced and midline structures identified and
marked using our own image-processing system program (multi-image processing-system; MIPS). The
traced edges and identified landmarks were used for
coregistration of each subject’s functional and anatomical data and to morph the images into a standardized
stereotactic space derived from 70 normal adults [52].
Each pixel in the images was subjected to a two-way
repeated-measures analysis of variance (ANOVA) involving Word Condition (unpleasant vs. neutral) and
Time Course (28 images for Scan 1 and 20 images for
Scan 2) for a 3-pixel diameter region of interest (ROI)
centered on the left and right amygdala (Talairach
coordinates: 23, − 6, − 12, chosen in advance from the
atlas). A three-way Condition (unpleasant vs. neutral)× Time Course (28 images for Scan 1 and 20
images for Scan 2)× Hemisphere (right vs. left)
ANOVA was conducted to assess hemispheric asymmetries. Habituation of the amygdalar response to the
stimuli across blocks of trials was also examined [threeway Condition (2)× Time Course (28)× blocks (4
blocks of each word type) ANOVA]. It should be noted
that without very high-resolution MRI templates for
each subject, differentiation of the amygdala from the
end of the hippocampus is difficult. However, coordinates from the Talairach atlas were used to identify
activation in this study and thus allow for the replication of our findings by other imaging centers.
To establish the specificity of our results, we also
examined the BOLD response to stimuli in the occipital
cortex. Since the exact location of this control area
(occipital cortex) was not specified a priori, a resampling procedure was used to protect against Type I
error [14,15,53]. A random starting point within the
time-series, subjects, and word type conditions was
selected. From the current sample, each word stimulus
trial was then drawn until the set of two word type
conditions for all nine subjects was completed. Each
cluster containing contiguous pixels with P-values below the 0.05 threshold level was identified: emotional
decision scan, F(27,216)= 1.54; recognition memory
scan, F(19,152)=1.66. Within each cluster so identified, the sum across all pixels of the F-ratio height
above the critical threshold level (1.54 for the emotional
decision scan and 1.66 for the recognition memory
scan) was calculated. For example, the volume for a
cluster with two contiguous pixels with the F-values of
2.54 and 3.54 would be 1+ 2= 3. These pixel cluster
volumes were tabulated across 5000 iterations (from
M.H. Tabert et al. / Neuropsychologia 39 (2001) 556–573
563
Table 2
Whole brain activation sites in Talairach space for the Condition×Time interaction during the emotional decision taska,b
Condition×Time interaction
Location
x
y
z
Volume
F
(a) Unpleasant\neutral
Amygdala
Middle temporal gyrus (BA 21)
Frontal lobe
Parahippocampal gyrus
Temporal lobe
Midbrain
Transverse temporal gyrus (BA 42)
Superior temporal gyrus (BA 39)
Precentral gyrus (BA 6)
Medial frontal gyrus (BA 9)
Superior frontal gyrus (BA 10)
Cuneus (BA 7)
Precentral gyrus (BA 6)
26
63
−7
−24
−44
−4
29
54
58
−2
13
2
−50
−6
−0.5
2
−48
−31
−24
−31
−56
1
47
55
−67
−4
−12
−12
−12
−4
−4
−4
12
20
20
24
24
32
40
8.33
2.74
6.16
3.44
14.14
1.95
2.23
4.43
6.27
7.32
0.73
4.39
1.81
5.81
4.43
6.58
3.90
5.46
3.32
3.76
4.84
4.57
6.54
2.98
4.80
4.57
(b) Neutral\unpleasant
Parahippocampal gyrus (BA 36)
Fusiform gyrus (BA 37)
Superior temporal gyrus (BA 38)
Inferior frontal gyrus (BA 47)**
Parahippocampal gyrus
Internal capsule
Claustrum
Lingual gyrus
Claustrum
Temporal lobe
Inferior frontal gyrus (BA 44)
Inferior frontal gyrus (BA 44)
Frontal lobe
Middle frontal gyrus (BA 46)
Middle frontal gyrus (BA 8)
35
−40
60
−49
21
−24
−33
23
−27
−48
−44
58
−31
−46
35
−33
−56
11
23
−45
−22
0
−79
20
−63
13
12
22
25
38
−12
−12
−12
−12
−4
−4
−4
4
4
12
12
20
24
24
40
4.78
1.93
2.46
3.11
6.12
7.80
4.15
6.47
2.95
6.85
0.25
3.96
4.96
1.54
4.64
5.49
3.02
3.86
4.63
4.29
6.61
3.73
4.47
3.41
4.63
2.55
3.68
3.80
3.56
4.97
a
Sites where the BOLD response during stimulus presentation was greater to the unpleasant than neutral Word Condition.
Sites where the BOLD response during stimulus presentation was greater to the neutral than unpleasant Word Condition. Significance
thresholds were set at PB0.001 for the maximum pixel and a minimum of at least 4 contiguous pixels. The volume index (used to enter the
resampling table for the resampling test) is the number of contiguous pixels in the patch multiplied by the difference between the average F value
across the patch and the PB0.001 F value (see text).
b
nine independent subject and time-interval starting
point samples), and cluster volumes in the fifth percentile or larger anywhere on the brain slice (Talairach
coordinate: z= + 12) were considered statistically significant. Note that this step also adjusts for any inflation of the degrees of freedom in repeated-measures
ANOVA designs because the cluster volume appearing
less than one time in 20 is identified from the empirical
table. The resampling method avoids potentially unwarranted assumptions about image smoothness and
other data features needed to estimate the F-level of
significance with a purely theoretical approach.
Resampling F-tables can be relatively easily calculated via the same computer code used to initially
organize the data and to conduct the pixel-by-pixel
F-tests. The first stage, randomizing the trials and time
starting points, can be conveniently developed from
programs which select the trial data points (in our case,
2-s epochs) from the longer series of blocks with only
minor alterations. The second stage, the ANOVA mapping, supplies the clusters to the third stage (i.e., cluster
identification and volume computation). A fourth sim-
ple operation forms the table of cluster volumes across
the 5000 iterations.
To further establish the specificity of the amygdala
finding, we present in tablular form the whole brain
activation as it relates to the Word Condition by Time
Course interaction (Tables 2 and 3). For these whole
brain exploratory analyses, we set significance
thresholds at P B 0.001 for the maximum pixel within
the cluster and only listed clusters with at least 4
contiguous pixels. Although a significance threshold of
PB 0.001 and the 4-pixel cluster-size constraint are
thought to be adequate corrections for multiple comparisons [42], our resampling criterion was more conservative. None of the activations listed in Tables 2 and
3 met the resampling criterion for statistical significance.
Exploratory analyses examined the correlation between amygdala activation during the emotional decision task and measures of state anxiety. Similarly, the
correlations between performance on the recognition
memory task and amygdala activation during the evaluation (Scan 1) and recall (Scan 2) tasks were assessed.
564
M.H. Tabert et al. / Neuropsychologia 39 (2001) 556–573
Table 3
Whole brain activation sites for the Condition×Time interaction during the recognition memory taska,b
Condition×Time interaction
Location
x
y
z
Volume
F
(a) Unpleasant\neutral
Midbrain
Temporal lobe
Precentral gyrus (BA 6)
Middle frontal gyrus (BA 8)
Superior frontal gyrus
2
48
−53
−24
−10
−29
−40
0
23
16
−4
−4
40
45
55
6.15
2.45
6.73
1.24
3.51
5.52
4.24
5.83
3.57
4.89
(b) Neutral\unpleasant
Superior temporal gyrus (BA 38)
Caudate
Frontal lobe
Precuneus
Medial frontal gyrus (BA 8)
35
13
31
16
3
5
5
36
−60
51
−12
20
24
40
40
3.06
1.40
2.01
5.46
4.08
4.48
2.78
3.91
6.44
5.63
a
Sites where the BOLD response during stimulus presentation was greater to the unpleasant than neutral Word Condition.
Sites where the BOLD response during stimulus presentation was greater to the neutral than unpleasant Word Condition. Significance
thresholds were set at PB0.001 for the maximum pixel and a minimum of at least four contiguous pixels. The volume index (used to enter the
resampling table for the resampling test) is the number of contiguous pixels in the patch multiplied by the difference between the average F value
across the patch and the PB0.001 F value (see text)
b
Finally, in order to replicate findings by Morris et al.
[67] (see above), correlations between amygdala and
occipital (control) activation were computed.
3. Results
3.1. Beha6ioral data
During the emotional decision task scan, all subjects
made an appropriate response (chose one word from
each word set) on 100% of the trials. This demonstrates
that subjects attended to the stimuli and responded as
instructed for the entire duration of the scan.1 During
the recall task scan, subjects recognized more emotionally negative words as compared to neutral words.
Overall, 91% of the unpleasant and 82% of the neutral
targets were correctly identified (paired t(8) = 3.59, P=
0.007), demonstrating a significant memory enhancement for the unpleasant words.
1
Given that the task instructions for the emotional decision task
required subjects to make a subjective choice that was based on their
own personal experiences and knowledge of the words involved in
each word set, we did not include the behavioral data for the first
scan here. As a manipulation check, we questioned subjects immediately following the experiment about their experience in the scanner.
Debriefing revealed that all subjects found the unpleasant word sets
to be highly unpleasant, particularly when compared to the neutral
word sets. This agreed with findings from our pilot work in which a
number of individuals were asked to perform and assess the validity
of the task. In the current study, subjects were not asked to rate each
word separately in terms of emotional valence. Future studies using a
similar lexical paradigm may find such rating data useful as an
additional manipulation check in order to assess the degree to which
subjects agree with the normative data used to select the lexical
stimuli.
3.2. Emotional decision scan
3.2.1. Amygdala Acti6ation
A two-way ANOVA (Word Condition×Time
Course) for the 3-pixel diameter ROI chosen a priori
from the Talairach atlas (ROI: left and right amygdala)
revealed a significant Word Condition× Time Course
interaction (F(27,216)= 5.95, PB0.0001) for the right
amygdala, demonstrating greater time-locked activation
for unpleasant than neutral words. Pixel-by-pixel
ANOVAs surrounding the center of the right amygdala
also revealed a significant Word Condition×Time
Course interaction (F(27,216)=5.81, PB 0.001) for a
total of 9 contiguous pixels (Fig. 3). The pixel with the
maximal response was located approximately at the
center of the amygdala (Talairach coordinates: 26, − 6,
−12) and was highly significant for the Word Condition× Time Course interaction (Fig. 3). A main effect
of Time Course was also observed at this pixel (Fig. 3).
Activation in the left amygdala did not reach significance (F(27,216)= 1.54, P=0.05, for the main effect of
Time Course; F(27,216)=1.40, P=0.10, for the Word
Condition× Time Course interaction).
A three-way ANOVA (Word Condition×Time
Course× Hemisphere) revealed a significant Time
Course× Hemisphere interaction (F(27,216)=2.84,
PB 0.0001) for the ROI analysis. However, the Word
Condition× Time Course ×Hemisphere interaction was
not significant.
To assess habituation effects of the BOLD signal
waveform in the right amygdala across successive
blocks of trials, a two-way ANOVA (Block×Time
Course) was conducted for the emotional condition at
the pixel of maximum activation. No significant effects
were observed with the blocking factor. These data
suggest a sustained amygdala response across the
blocks of trials.
M.H. Tabert et al. / Neuropsychologia 39 (2001) 556–573
3.2.2. Acti6ation in control region
To establish the specificity of the amygdala response
to unpleasant words, we also examined the BOLD
signal waveform in a control region, the bilateral occipital cortex (primary and secondary visual areas). As
predicted, this area showed significant task activation
but no different pattern with neutral and unpleasant
words. Pixel-by-pixel two-way ANOVAs (Word Condition × Time Course) in visual cortex (Brodmann areas
17, 18, and 19; Fig. 4) revealed widespread activation
confirmed for Time Course, but without the Word
Condition ×Time Course interaction observed for the
amygdala. A three-way ANOVA (Word Condition×
Time Course ×Hemisphere) did not reveal any interactions with Hemisphere, suggesting bilateral activation
of visual cortex to both unpleasant and neutral words.
This bilateral time-locked activation in primary and
secondary visual cortices to both unpleasant and neu-
565
tral words is consistent with the well-known role of
these areas in processing visually presented information.
3.2.3. Correlation between amygdala and occipital
acti6ation
The peak BOLD response from the pixel of maximal
activation (Talairach coordinates: 26, − 6, − 12) in the
right amygdala during Scan 1 was correlated with the
peak BOLD response from the pixel of maximal activation (Talairach coordinates: − 21, − 85, 12) in the
occipital cortex. The peak BOLD response for the
neutral and unpleasant blocks was derived by subtracting the maximal pixel intensity value during the stimulus-on period (averaged across the four blocks of each
trial type) from the average value of the baseline preceding the stimulus-on period (Figs. 3 and 4). The
correlation analysis revealed that the peak BOLD re-
Fig. 3. Emotional Decision Task: (Top left) The Condition by Time Course interaction (F(27,216) = 5.25; PB 0.0001) in the pixel with maximum
activation (26, − 6, − 12) within a patch of 9 contiguous pixels surrounding the center of the right amygdala. (Bottom left) The main effect of
Time Course (F(27,216) =2.29, P= 0.0006) for the pixel with the maximal response (26, − 6, − 12) within the same patch of 9 contiguous pixels.
(Right) This 9-pixel patch was the largest area/volume of activation (maximum patch) on this axial slice. Other areas that met the resampling
criteria for significance were omitted for clarity.
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M.H. Tabert et al. / Neuropsychologia 39 (2001) 556–573
Fig. 4. Emotional Decision Task: (Left) The main effect of Time Course (F(27,216) =13.57; P B0.000) for the pixel of maximum activation
(Talairach coordinates: − 21, −85, 12). (Right) The patch of 138 contiguous pixels containing the maximum activation pixel (resampling
volume=342, resampling PB 0.025) was located in visual cortex (Brodmann areas 17, 18, 19). This 138-pixel patch is the largest area/volume of
activation (maximum patch) on this axial slice. Other areas that met the resampling criteria for significance were omitted for clarity.
sponse in the right amygdala to the unpleasant words
was highly correlated with the overall peak BOLD
response (i.e., averaged across Word Condition) in the
occipital cortex (r= 0.87, P =0.003). On the other
hand, the peak BOLD response in the right amygdala
to the neutral words did not correlate with the response
in the occipital cortex (r = −0.04, P = 0.912; Fig. 5).
Correlation analyses between the left amygdala and the
occipital cortex were not performed since significant
amygdala activation was not observed on the left side.
3.2.4. Correlation between measures of anxiety and
amygdala acti6ation
Raw scores for state anxiety [81] were determined. To
assess the effect of anxiety due to the scanning procedure on the statistically significant BOLD response in
the right amygdala, the difference score for the two
time points of the state anxiety measure (during scanning as assessed retrospectively and before scanning)
was correlated with the peak BOLD response from the
pixel of maximal activation (Talairach coordinates: 26,
− 6, −12).
State anxiety ratings went from a mean score of
33.3 99.1 before scanning to 44.29 8.8 after scanning
(paired t(8)= 2.69, P =0.027), demonstrating an overall significant increase in anxiety presumably due to the
scanning procedure. Difference scores for each subject
were also calculated (i.e., score during scan− pre-scan
score). These scores ranged from −8 (relative decrease
in anxiety during scan) to 24 (relative increase in anxiety during scan), with a mean of 8.99 9.9 and a median
of 10.
State anxiety difference scores (scan report−prescan report), reflecting the change in anxiety from the
pre-scan period to the report about the actual scanning
period, were significantly correlated with the peak
BOLD response of the right amygdala to the neutral
(r=0.70, P= 0.035) but not to the unpleasant word
condition (r= 0.33, P= 0.380). Together, these findings
suggest that state anxiety levels do increase as a result
of the scanning procedure. However, while this increase
in state anxiety was related to the amygdala response
during the neutral word condition, it was not related to
the amygdala response during the emotional word
condition.
3.3. Recognition memory scan
3.3.1. Amygdala acti6ation
Analyses similar to those described above for the
emotional decision task were conducted to examine the
amygdala response during the recognition memory test
for words presented during the first scan. Pixel-by-pixel
ANOVAs around the center of the right and left amygdala revealed no significant Word Condition×Time
Course interaction or significant increases to word
recognition in general. These findings suggest that, unlike the emotional decision task scan (see above), amyg-
M.H. Tabert et al. / Neuropsychologia 39 (2001) 556–573
dala activation was not elicited during the recognition
of unpleasant or neutral words that were presented
earlier.
3.3.2. Acti6ation in control region
Activation in the occipital cortex, on the other hand,
demonstrated a somewhat similar activation pattern to
that observed in the emotional decision scan (Fig. 6).
Pixel-by-pixel two-way ANOVAs (Time Course×
Word Condition) in visual cortex (Brodmann areas 17,
18, 19) revealed widespread activation confirmed for
Time Course, but not for the Time Course × Word
Condition interaction. Also, a three-way ANOVA
(Word Condition×Time Course ×Hemisphere) did
567
not reveal higher order interactions with Hemisphere,
again, suggesting bilateral activation of visual cortex to
visually presented information irrespective of
unpleasantness.
3.3.3. Correlation between recognition memory and
amygdala acti6ation
A correlational analysis was conducted to assess the
possibility that the enhanced behavioral performance
on the recognition memory task for the unpleasant
words was related to the amygdala activation observed
during Scan 1. The peak BOLD response of the pixel of
maximal activation (Talairach coordinates: 26, −6,
− 12) in the right amygdala during the presentation of
unpleasant word sets was not significantly correlated
with the number of correct responses (Hits) on the
memory test (unpleasant words: r= − 0.11, P=0.782;
neutral words: r= 0.08, P= 0.840). Similarly, the peak
BOLD response of the pixel of maximal activation
(Talairach coordinates: 26, − 6, − 12) in the right
amygdala during the presentation of neutral word sets
was not significantly correlated with the number of
correct responses (Hits) on the memory test (unpleasant
words: r= −0.05, P= 0.899; neutral words: r=0.48,
P= 0.196). These findings suggest that the differential
enhancement in recognition memory for the unpleasant
words, as described above (Section 3.1), is not related
to the increase in amygdala activation observed during
Scan 1.
4. Discussion
Fig. 5. Scatterplots illustrating the correlation between the peak
BOLD response in the pixel of maximum activation in the right
amygdala (26, − 6, −12) and occipital cortex ( − 21, − 85, 12). (a)
Amygdala response to unpleasant words (Wds) vs. the overall occipital response to words (i.e., unpleasant and neutral). (b) Amygdala
response to neutral words vs. overall occipital response to words.
Regression lines have been fitted to the data (slopes: + 0.989 and
−0.038, respectively; correlation coefficients (r): + 0.866 and −
0.043, respectively).
To date, lesion and imaging studies have demonstrated that the amygdala plays a role in both the
evaluation of emotional information and in the modulation of emotional memories. The amygdala has also
been implicated in the modulation of attentional systems related to the early processing of visually presented emotional information. Evidence for such roles
has come largely from studies using emotional facial
and vocal expressions. The current fMRI activation
paradigm was designed to assess the extent to which the
amygdala is recruited in response to the evaluation and
short-term recognition of highly unpleasant words. A
further goal of this study was to investigate the influence of anxiety created by the scanning procedure on
amygdala activation.
In summary, our results revealed a Time Course×
Word Condition interaction in the right amygdala for
the emotional decision but not the recognition memory
task, demonstrating selective time-locked activation for
the evaluation of unpleasant but not neutral words. In
contrast, a main effect of Time Course was observed in
the occipital cortex for both the emotional decision and
recognition tasks, demonstrating a general time-locked
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M.H. Tabert et al. / Neuropsychologia 39 (2001) 556–573
Fig. 6. Recognition Memory Task: (Left) The main effect of Time Course (F(19,152) =12.88; P B0.0001) for the pixel of maximum activation
(Talairach coordinates: − 29, −81, 12). (Right) The patch of 103 contiguous pixels containing the maximum activation pixel (resampling
volume=197, resampling PB 0.025) was located in visual cortex (Brodmann areas 17, 18, 19). This 103-pixel patch is the largest area/volume of
activation (maximum patch) on this axial slice. Other areas that met the resampling criteria for significance were omitted for clarity.
response to visually presented words irrespective of
valence and task manipulation. Interestingly, the general response observed in the occipital cortex was
strongly correlated with right amygdala activation to
the unpleasant but not neutral words. Although subjects showed significantly enhanced short-term memory
for the emotional as compared to neutral words, this
memory advantage was not correlated with the observed increase in amygdala activation during encoding
(Scan 1). Finally, the increase in state anxiety experienced by subjects while in the scanner was significantly
correlated with amygdala activation during the neutral
but not unpleasant Word Condition.
A number of previous imaging studies presenting
words [18,62,87] have not reported specific amygdala
activation in response to the presentation of unpleasant
words. However, consistent with the findings of Kiehl
et al. [55], the present study found a robust BOLD
signal in the right amygdala that was greater for unpleasant than neutral word sets. The discrepancy between the findings from the current study and those
from previous studies, which did not observe amygdala
activation in response to the presentation of unpleasant
words, may be due to methodological differences.
While previous studies employed more implicit processing tasks, such as passive viewing of emotional words
or counting the number of negative vs. neutral words
on a screen, in the present study, subjects were required
to evaluate a group of highly unpleasant or neutral
words in relation to their own personal experience (i.e.,
the degree to which the words were perceived as unpleasant or threatening).
Careful analysis of the amygdala response in this
study revealed a number of interesting results. First,
consistent with the Kiehl et al. [55] study, amygdala
activation to unpleasant words was statistically confirmed only in the right hemisphere. However, an analysis specifically testing for hemispheric asymmetries
[39,40] (Time Course× Word Condition× Hemisphere
ANOVA) did not reveal significant Word Condition×
Hemisphere or Word Condition× Time Course ×
Hemisphere interactions for the 3-pixel diameter ROI
centered on the amygdala. Asymmetries in the perception, expression, and experience of emotion have been
well-documented in patients with focal unilateral cortical lesions [3,21 –23,45,54,79]. In general, lesion studies
support the notion that the right cerebral hemisphere is
specialized for the processing of emotional information
(i.e., right hemisphere hypothesis) [24]. As the literature
focusing specifically on the amygdala reveals (Section
1), however, selective emotional processing deficits have
primarily been confirmed in patients with bilateral
amygdala damage. Also, no clear consensus about the
laterality of the amygdala response to emotional stimuli
can yet be reached on the basis of imaging studies, as
different imaging studies employing the same experimental conditions have reported left-sided, right-sided,
or bilateral activation. Importantly, Davidson and Ir-
M.H. Tabert et al. / Neuropsychologia 39 (2001) 556–573
win [39,40] have pointed out that although many imaging studies have reported asymmetric changes associated with emotion, the data by-and-large have not been
properly analyzed with specific right – left, laterality-focused contrasts. Although our findings are suggestive of
right greater than left amygdala activation, they underscore the need to perform appropriate laterality tests
before claiming hemispheric asymmetries. Higher resolution BOLD images, larger samples, and anatomical
coregistration may be necessary to confirm lateralization effects. This is particularly true since the right and
left amygdalae may not be centered on the same 5-mm
thick slice.
Second, unlike previous studies [26,29,56,75,88], the
current study did not find habituation of the amygdala
response to emotional stimuli over the course of the
scan. Rather, a sustained amygdala response was observed across the blocks of trials to the unpleasant as
compared with the neutral words. Methodological differences between the current and previous studies may
account for this difference. For example, previous studies that have observed habituation of the amygdala
response presented threat-related facial expressions
[26,75,88] or aversive conditioned stimuli [29,56] for
very brief durations (B 200 ms). In fact, Whalen et al.
[88] presented stimuli below the threshold of conscious
awareness (30 ms) using a backward masking procedure. Further, in these other studies, subjects were kept
naı̈ve as to the emotional manipulations employed in
the experiments (i.e., implicit processing) and were exposed to the same stimuli more than once over the
course of the scan. In contrast, the current study exposed subjects to stimuli for extended periods of time (6
s). Further, subjects were also explicitly made aware of
the word type manipulation used and were instructed to
carefully evaluate the relative emotional significance of
word sets in terms of their own knowledge and experience. Finally, each word set was composed of a unique
combination of words to prevent habituation due to
familiarity with the stimuli.
The selective amygdala response to unpleasant words
observed in the current study is consistent with a large
body of animal and human literature suggesting that
the amygdala plays a role during the evaluation of
emotionally significant and/or biologically relevant
cues, particularly those that predict possible threat to
the organism. However, the exact nature of this role
remains controversial [9]. While a number of studies
have demonstrated selective emotional processing
deficits following bilateral amygdala lesions in humans
[6 – 8,27,36,90,91], others have not [5,9,13,48,59,51].
Moreover, bilateral lesions in humans generally do not
prevent normal autonomic [19,84] and self-reported
emotional reactions [2,31,49] to emotionally significant
stimuli. Similarly, while studies have implicated the
amygdala in the production of conditioned emotional
569
responses and as the location where conditioned memories are indelibly stored [60,61,63], other studies (for
review of this literature, see Ref. [34]) have demonstrated that the amygdala is not necessary for fearbased autonomic responses [84] or for fear-conditioned
learning [85].
The sustained response of the amygdala to the evaluation of unpleasant words in this study may, on the one
hand, reflect retrieval of past emotional experiences for
the purpose of appraising the emotional significance of
current stimuli in the context of the emotional decision
task (i.e., choosing the most unpleasant word from a set
of three highly unpleasant words based on subjective
experience) and guiding related behavioral responses.
Such emotional memories may be stored in the amygdala per se or in widespread associative neural networks of the cortex that are reciprocally connected to
the amygdala through the hippocampal system [38].
This interpretation is consistent with some imaging
studies that have found right amygdala activation during retrieval of highly personal emotional memories [75]
and during the retrieval of affect-laden autobiographical memories with personal emotional significance [41].
On the other hand, a recent PET study by Reiman et
al. [77] found that although viewing emotionally arousing films activated the amydala, recall of previously
experienced emotional events did not. Further, a number of imaging studies [32,50] have reported that amygdala activity while viewing emotional stimuli is strongly
related to long-term memory performance for emotionally significant, as opposed to, neutral material. These
findings are consistent with the memory modulatory
framework [30,33,65] discussed above which suggests
that amygdala activation in response to emotionally
significant stimuli regulates the long-term storage of
this information in other brain areas in a time-dependent manner. Hence, according to this view, the increase in amygdala activity observed here, while
subjects evaluated the unpleasant vs. neutral word sets,
may reflect the encoding and ultimate long-term storage
of the lexical stimuli in general proportion to their
emotional significance [30].
The lack of an amygdala response during the shortterm memory task used in this study (Scan 2) is also
consistent with the memory modulatory view
[20,30,32,50]. During the memory scan, which occurred
immediately after the first (encoding) scan, subjects
were simply instructed to rapidly identify any word that
occurred in the previous scan. Interestingly, although
subjects were able to more accurately recognize the
emotional than non-emotional words, their enhanced
performance on the emotional task was not related to
an increase in amygdala activation. This finding is
consistent with the memory modulatory view, which
posits that the amygdala is not involved in memory
retrieval processes but is involved in memory consolida-
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M.H. Tabert et al. / Neuropsychologia 39 (2001) 556–573
tion. Moreover, similar to the Hamann et al. study [50],
amygdala activation during encoding (Scan 1) was not
correlated with short-term memory performance. This
finding is again consistent with the memory modulatory
view that predicts amygdala activity during encoding to
be correlated with long-term but not short-term memory [20]. In the current study, however, we did not
administer a test of long-term memory for the lexical
stimuli. Of note, both Cahill et al. [32] and Hamann et
al. [50] did find a significant correlation between amygdala activation at encoding and long-term memory
performance (i.e., after 1 month).
To establish the specificity of amygdala activation to
the emotional condition, we also analyzed activation in
a control region – the occipital cortex. For the emotional decision and recognition memory tasks, widespread bilateral activation was observed in the visual
cortex for both unpleasant and neutral words. The
time-locked activation in this region to both unpleasant
and neutral words suggests that visually presented unpleasant and neutral words are processed in primary
and secondary visual cortices independent of the behavioral task used. By contrast, amygdala activation was
specific to the unpleasant word condition and seems to
be more dependent on the behavioral task used, such
that making emotional decisions about highly unpleasant words, and presumably encoding them into longterm memory, activates the right amygdala whereas
identifying unpleasant words stored in short-term memory does not.
In the current study, similar to the findings by Morris
et al. [67], there was a strong correlation between the
overall occipital response to words (i.e., the averaged
response across unpleasant and neutral trials) and the
amygdala response to the unpleasant words (Fig. 5).
This finding is consistent with a number of studies
[26,58,59,67,77,89] that provide support for the notion
that the amygdala modulates early visual processing in
the occipital cortex via reciprocal projections [12]. In
this vein, Whalen [86] has recently proposed that the
amygdala is part of a larger vigilance system that
selectively responds to aversive stimuli that are ambiguous or pose an uncertain threat to the organism. When
activated by the amygdala, this vigilance system potentiates neuronal responsiveness or cortical processing to
gather additional information about the predictive biological significance of the stimulus.
A final goal of the current study was to assess the
effects of anxiety during the scanning procedure on
amygdala activation. Not surprisingly, state anxiety
scores increased significantly due to the scanning procedure. Moreover, this increase in anxiety (i.e., difference
between anxiety level as measured before vs. during the
scan) predicted the response of the right amygdala to
neutral but not unpleasant words. This finding has
several important implications for imaging studies.
First, the fMRI scanning procedure can induce elevated
levels of anxiety in non-claustrophobic, normal adult
subjects [46,47,78]. Similar and possibly more severe
stress reactions can be expected from clinical populations who, by definition, are more sensitive to environmental stressors. Second, it calls into question the
assumption that the anxiety effects of scanning are
similar across the experimental conditions of a particular study. In the present study, the amygdala response
to the neutral words varied as a function of subjects’
anxiety levels, whereas the amygdala response to the
unpleasant words was related to the presentation of
emotional words and not to state-anxiety levels. Direct
comparison of conditions that were differentially affected by extraneous factors, such as anxiety, may
result in confounded results. Hence, it would seem
prudent for imaging studies to pay close attention to
the effect of factors such as anxiety when interpreting
activation patterns in normal and patient populations.
5. Summary and future directions
In summary, the current study has demonstrated that
the amygdala is involved in the explicit evaluation of
unpleasant words. Findings from our study and those
from previous studies support the view that the amygdala is involved in the processing of emotional information independent of the modality of presentation. While
the exact nature of the amygdala’s role in emotional
processing remains controversial, findings from the current study fit best with the memory modulatory view of
amygdala functioning. Although the emotional decision
and short-term recognition memory tasks in this study
elicited the same response from control areas (i.e.,
visual cortex), the latter task did not result in amygdala
activation. Moreover, amygdala activity during encoding was not correlated with short-term memory performance. Together, these findings are consistent with the
notion that the amygdala facilitates the acquisition of
long-term declarative knowledge about emotionally significant material. Given that the current study did not
include a long-term memory condition, we are unable,
however, to directly assess the degree to which amygdala activity during encoding selectively modulates
memory for highly unpleasant words at longer delays.
To more fully assess the memory modulatory view
with respect to lexical stimuli, future studies should
include long-term memory recognition and free recall
tasks. Future studies should also obtain physiological
(e.g., galvanic skin response) and self-report measures
of emotional arousal from subjects while they engage in
similar lexical emotional decision tasks. Such manipulations would make it possible to assess the degree to
which decisions about highly unpleasant words elicit
emotional arousal and, furthermore, the degree to
M.H. Tabert et al. / Neuropsychologia 39 (2001) 556–573
which emotional arousal is related to amygdala activity
during encoding and to the regulation of memory consolidation processes [57]. In addition, including highly
positive words as a third word condition would allow
one to directly assess brain lateralization hypotheses as
a function of emotional valence [25,36,39,40].
Finally, the findings of this study corroborate findings by other research groups that the amygdala’s
response to visually presented emotional information
modulates early processing in the occipital cortex. The
current findings also highlight the importance of evaluating future imaging data in terms of changes in state
anxiety due to the scanning procedure. In the current
study, such changes were shown to have differential
effects in the emotional vs. neutral condition.
Acknowledgements
This study is based on a doctoral thesis conducted by
the first author at Queens College and The Graduate
Center of the City University of New York (CUNY)
and in affiliation with the Departments of Neurology
and Radiology and the Neuroscience Brain Imaging
Laboratory at Mount Sinai Medical Center. This research was supported, in part, by NIMH Grant no.
MH42172 and Professional Staff Congress – CUNY
Research Award no. 69257-0029 to the second author
at Queens College. We are grateful to Drs. Scott W.
Atlas and Ronald Bloom for their useful advice during
the initial stages of this project, to Karen Metroka and
Adam Brickman for their assistance, and to the anonymous reviewers for their helpful suggestions. A portion
of this study was presented at the International Conference on Functional Mapping of the Human Brain in
Düsseldorf, Germany, in June of 1999.
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