emotional memory: separating content and context

www.elsevier.com/locate/psychresns

Psychiatry Research: Neuroim

Emotional memory: Separating content and context

Nicholas Medforda,T, Mary L. Phillipsa, Barbara Brierleya, Michael Brammerb,

Edward T. Bullmorec, Anthony S. Davida

aSection of Cognitive Neuropsychiatry, PO Box 68, Department of Psychological Medicine, Institute of Psychiatry and GKT School of Medicine,

King’s College, London SE5 8AF, UKbDepartment of Biostatics and Computing, Institute of Psychiatry, London, UK

cDepartment of Psychiatry, University of Cambridge, Cambridge, UK

Received 3 February 2004; received in revised form 23 September 2004; accepted 26 October 2004

Abstract

It is now well established that emotion enhances episodic memory. However, it remains unclear whether the same neural

processes underlie enhancement of memory for both emotional stimuli and neutral stimuli encoded in an emotive context. We

designed an experiment that specifically attempted to separate these effects and that was validated on 30 participants. We then

used functional magnetic resonance imaging (fMRI) to examine the neural correlates of encoding and retrieval of the two classes

of stimuli in 12 healthy male volunteers. We predicted that aversive emotional context would enhance memory regardless of

content and that activation of anterior cingulate would be inversely related to retrieval of aversive items. Both predictions were

supported. Furthermore we demonstrated apparent asymmetrical lateralisation of activation in the hippocampal/parahippocampal

complex during recognition of words from aversive sentences: more left-sided activation for neutral words from aversive

contexts, and more right-sided activation for aversive content words. These findings, if applicable to the wider population, may

have application in a range of psychiatric disorders where interactions between emotion and cognition are relevant.

D 2005 Elsevier Ireland Ltd. All rights reserved.

Keywords: Emotion; Memory; Amygdala; Hippocampus; Anterior cingulate cortex; Functional MRI

1. Introduction tively valenced assessments of the past, while post-

Interactions between emotion and memory play an

important role in psychiatry. For example, cognitive

theories of depression emphasize the role of nega-

0925-4927/$ - see front matter D 2005 Elsevier Ireland Ltd. All rights re

doi:10.1016/j.pscychresns.2004.10.004

T Corresponding author. Tel.: +44 20 7 848 0138; fax: +44 20 7

848 0572.

E-mail address: [email protected] (N. Medford).

traumatic stress disorder (PTSD) arises as a conse-

quence of an aversive event and the handling of that

event by memory and other cognitive systems. While

there is strong evidence that memory is enhanced by

emotional arousal at the time of encoding (Burke et

al., 1992; Sierra and Berrios, 1999), the specific

neural and cognitive mechanisms remain elusive.

Animal research (Gallagher and Chiba, 1996;

LeDoux, 1998) has implicated the amygdaloid com-

aging 138 (2005) 247–258

served.

N. Medford et al. / Psychiatry Research: Neuroimaging 138 (2005) 247–258248

plex (AC) in the formation of conditioned fear

responses, leading to the idea that this structure may

be involved in the formation of emotional memories

in man.

There is now good evidence for amygdala involve-

ment in human emotional memory. Patients with

amygdala lesions have deficits in recognizing the

emotions of others (Adolphs et al., 1994; Broks et al.,

1998), and may also lose the enhancement of memory

normally conferred by emotion (Phelps and Anderson,

1997). A study examining the memory of people with

Alzheimer’s disease for an emotional event (a

devastating earthquake in Kobe, Japan) found that

impairment of memory for this event was correlated

with the density of amygdala damage (Mori et al.,

1999). A landmark PET study (Cahill et al., 1996) in

which subjects viewed emotionally arousing video

clips found that amygdala activation at encoding was

correlated with subsequent recall of the emotional

material, suggesting that amygdala arousal may

modulate the formation of memories for emotional

material. This idea is supported by studies using

pharmacological manipulation to influence arousal

(McGaugh et al., 1996; O’Carroll et al., 1999), and by

an event-related fMRI study (Canli et al., 2000) in

which, within individual subjects, amygdala activa-

tion at encoding was found to correlate with intensity

of emotional response to stimuli. With regard to a

possible role for the amygdala in retrieval, animal

studies suggest that an intact amygdala is required for

encoding (McGaugh et al., 1996), but not recall, of

emotional material, although elsewhere (Dolan et al.,

2000) it has been suggested that the left amygdala

may have a specific role in retrieval of emotional

memories. A more recent study (Dolcos et al., 2004)

supports the idea that interactions between the

amygdala and the medial temporal lobe (MTL)

memory system underlie the emotional enhancement

of memory, and suggests that more anterior parts of

the MTL have a specific role in encoding emotional

information.

In considering emotional memory, relative contri-

butions of, firstly, emotional material (content) and,

secondly, the context in which this material occurs are

of particular relevance in understanding the role of

emotional memory in psychopathology. Studies of

these effects have yielded conflicting results (Burke et

al., 1992). After an emotional event, while recall of

the event itself is enhanced, memory for surrounding

contextual information is variously found to be either

enhanced or diminished, raising the possibility that

memory for content and context are subserved by

different neural networks. Indeed, work by Kensinger

et al. (2002) showed that the direct enhancement

effect on memory of emotional content is preserved in

normal ageing while that of context is diminished.

Patients with Alzheimer’s disease, presumed to have

diffuse brain disease, showed loss of emotional

enhancement from both content and context.

A small number of functional imaging studies

have attempted to address these issues. Maratos et al.

(2001) examined memory for emotional context by

testing recognition memory for neutral words pre-

sented in emotional sentences. However, there was

no test of recall for words whose content was

intrinsically emotive, and thus no comparison of

the neural correlates of emotional content and

context recognition memory. Erk et al. (2003)

examined the effect of emotional context at encoding

on subsequent memory performance, but scanning

data were only obtained during encoding. One recent

study (Smith et al., 2004) examined contextual

influences on both encoding and recognition memory

by the use of pictorial stimuli presented on either

emotional or neutral backgrounds. However, this

method of associating stimulus with context may not

be analogous to real-life situations, where contextual

information is likely to have more semantic rele-

vance than an arbitrary association. In this study, we

aimed to examine the neural correlates of memory

for both content and context, encoded in such a way

that they were semantically linked.

In addition to studying temporal lobe structures

involved in emotion and memory, we wished to

examine the role of anterior cingulate cortex (ACC) in

encoding and subsequent recognition of emotional

material. It has been suggested (Hamner et al., 1999)

that the ACC interprets and contextualises emotional

information, thus brationalisingQ and dampening the

emotional response, this being consistent with a study

(Bremner et al., 1999) in which war veterans with

post-traumatic stress disorder (PTSD) showed less

ACC activation in response to combat-related stimuli

than veterans without PTSD. Thus this area has

particular significance for understanding the role of

context in emotional memory.

Table 2

Examples of emotional and neutral sentence pairs

Emotional sentence Neutral sentence

He stood on the balcony

and watched the riot.

He stood on the balcony

and watched the tide.

He would abuse the

children at every party.

He would amuse the children

at every party.

There was a scream in the hall. There was a carpet in the hall.

The parcel contained a bomb. The parcel contained a bowl.

Each pair differs by one word. In the above examples, briotQ andbtideQ are matched to within one standard deviation on measures of

written frequency, imageability, concreteness and familiarity.

Similarly, babuseQ and bamuseQ, bscreamQ and bcarpetQ, bbombQand bbowlQ are all matched pairs. For clarity of explanation,

embedded words are shown underlined, but were not underlined

when presented to subjects.

N. Medford et al. / Psychiatry Research: Neuroimaging 138 (2005) 247–258 249

2. Methods

This study employed a modified version of a test of

verbal emotional memory designed by the authors

(NM and BB) and utilized in previous studies of

emotional memory following temporal lobectomy

(Brierley et al., 2004) and Alzheimer’s disease (Ken-

singer et al., 2002). Forty-two emotionally aversive

btargetQ words were selected from a list rated on

measures of arousal and valence (Bradley and Lang,

1999). Each word was used to create a sentence. A

psycholinguistic database (Coltheart, 1981) was then

used to generate a further set of btargetQ words that

were matched to the emotional words for length, and

for frequency, imageability, concreteness and familiar-

ity (Table 1), but that were affectively neutral. From

this, a second, neutral set of 42 sentences was created,

identical to the emotional sentences except for the

neutral–emotional word swap (see Table 2 for

examples). These were arranged into two sets,

designated bXQ and bYQ sets, each containing 21

emotional and 21 neutral sentences.

Sentences were printed on cards in plain text, and

in an initial experiment conducted outside the scanner,

30 normal volunteers (17 male, 13 female, age 17–43,

mean age 27.8) performed three tasks. Firstly, encod-

ing, in which subjects were asked to silently read each

sentence. Half of the subjects were shown the bXQ setand the other half viewed the bYQ. A three-alternative

forced-choice recognition test followed after a 5-min

delay. For each item, three words were presented, of

Table 1

Psycholinguistic variables: comparisons between emotional and

neutral target words on measures of frequency (FREQ), concrete-

ness (CONC), imageability (IMAG), and familiarity (FAM)

Word type N Mean SD df t Sig

(2-tailed)

FREQ Emotional 42 31.12 38.73 81.7 �0.85 0.933

Neutral 42 31.86 40.98

CONC Emotional 40 456.55 109.11 79.9 �1.52 0.133

Neutral 42 493.31 110.10

IMAG Emotional 41 524.24 62.18 75.7 0.68 0.502

Neutral 42 513.33 83.73

FAM Emotional 42 505.79 49.58 81.0 �1.24 0.219

Neutral 42 520.00 55.34

There are no significant differences between the groups (SD=stan-

dard deviation, df=degrees of freedom).

which one had been seen before in the sentences at

encoding, the other two being distracters. Subjects

were asked to indicate which word had been seen

previously. Half of the correct responses were btargetQwords, and half were neutral bembeddedQ words. Theincorrect distracters were words matched to the

correct responses for emotional valence, word length

and to within one standard deviation for frequency

and familiarity.

Twenty volunteers independently rated all target

and embedded words used in the study for emotional

valence and arousal. This confirmed that words

designated as being emotive were indeed signifi-

cantly different from neutral words on these measures

(data available on request). In addition to these

ratings of individual words, 10 different volunteers

rated each set of sentences for arousal and valence.

Arousal was rated from 1 to 7 where 1=dno reactionTand 7=dstrongest reaction imaginableT, while valence

was rated from 1 to 7 on a scale where 1=dveryunpleasantT, 4=dneutralT, and 7=dvery pleasantT. Forthe dXT set, aversive sentences were significantly

different from neutral sentences on both measures:

For arousal, the mean score for the 21 aversive

sentences was 3.3, SD 0.84, while for the 21 neutral

sentences, the mean arousal score was 2.1, SD 0.4

(t=�5.94, Pb0.001, two-tailed test of significance).

For valence, the mean for aversive sentences was 2.7,

SD 0.56, and for neutral sentences 4.3, SD 0.4

(t=10.81, Pb0.001). For the dYT set, the mean arousal

score for aversive sentences was 3.1, SD 0.69, and

for neutral 2.0, SD 0.28 (t=�6.94, Pb0.001), while


mean valence for aversive sentences was 2.95, SD

0.35, and for neutral sentences 4.1, SD 0.31 (t=11.81,

Pb0.001). It is of note that for each set, the mean

valence for neutral sentences was approximately 4,

the neutral point on our valence scale, confirming

that these sentences did not have any significant

emotional valence, either positive or negative. (Rat-

ings from individual volunteers, and for individual

sentences, are available on request.)

2.1. Functional MRI experiments

Twelve different volunteers (right-handed males,

age range 22–34 years, mean 27.8) then underwent

three 5-min functional imaging data acquisitions

while performing equivalent tasks in the scanner. In

the encoding task, subjects silently read a set of 42

sentences plus eight bfillersQ, a total of 50 sentences,

each sentence being projected onto a screen for 6 s.

No sentence was repeated. After reading each

sentence, subjects pressed a button (this was simply

to confirm they had read it). bFillersQ–extra sentences

(rated as affectively neutral by the same individuals

who rated the test sentences) that were projected but

not included in the scoring–were used to simplify the

timing of sentence projection and to ensure that each

sentence was onscreen for the same length of time.

bFillersQ were equally distributed across aversive and

neutral blocks (see below). Two forced-choice recog-

nition tasks followed. For ease of presentation, two-

choice, rather than three-choice, recognition memory

tests were used. Pairs of words (targets plus matched

distracters) were projected onto the screen and

subjects pressed a button to indicate which word

had been in the sentences at encoding. In one task, the

correct responses were btargetQ words, and in the

other, the correct responses were neutral bembeddedQwords. In total, therefore, there were three (one

encoding and two recognition) 5-min tasks. Within

each task, 50 items were presented according to

block-design methodology. This involves presenting

alternating blocks of different classes of stimuli

(aversive and neutral, in this case). Thus, brain

activation in response to each class of stimuli can be

measured separately, allowing emotional vs. neutral

comparisons within each task. This enabled identi-

fication of brain areas selectively activated by the

aversive items in each task.

For the encoding task, the block design depended

on the fact that both bXQ and bYQ sentence sets

contained equal numbers of emotional and neutral

sentences. To control for possible order effects, each

set was arranged into groups (blocks) of emotional

and neutral, prior to onscreen projection. Subjects

viewed alternating blocks of aversive and neutral

sentences (five sentences per block, each block

lasting 30 s). The within-task order of these blocks

was randomized across subjects, although they were

always presented such that emotional blocks alter-

nated with neutral blocks. The eight bfillerQ stimuli

were equally distributed across emotional and neutral

blocks to give a total of 50 sentences for each

subject. For the target and embedded word recog-

nition tasks, 50 word pairs per task were presented in

alternating blocks so that in one block the correct

responses were words from emotional sentences, and

in the next, correct responses were from neutral

sentences. In the embedded word task, one subject’s

data were excluded due to technical failure. Thus

n=12 for target word recognition testing, n=11 for

embedded word recognition. In all three tasks,

stimuli (sentences or word pairs) were presented

every 6 s. To control for different reading speeds

between subjects, stimuli disappeared from the

screen once the subject pressed a response button.

For example, in the encoding task, if a subject

pressed the button after 3 s, the sentence would then

disappear and the screen would be blank for 3 s

before the next sentence appeared.

2.2. Image acquisition

Gradient echo echoplanar images were acquired

on a GE Signa 1.5 T Neurovascular system (General

Electric, Milwaukee, WI, USA) at the Maudsley

Hospital, London. One hundred T2*-weighted

images depicting BOLD (blood oxygenation level

dependent) contrast (Ogawa et al., 1990) were

acquired over 5 min (for each task) at each of 14

near-axial non-contiguous 5-mm thick planes parallel

to the intercommissural (AC-PC) line: TE 40 ms, TR

3 s, in-plane resolution 5 mm, and interslice gap 0.5

mm. This EPI dataset provided complete coverage of

the temporal lobes and almost complete coverage of

the frontal, occipital and parietal lobes (Simmons et

al., 1999).

Table 3

Recognition memory scores for the initial experiment with 30

subjects outside the scanner

Recognition memory comparison MeanFSD t P

Emotional target words 16.63F2.20 5.13 b0.001

Neutral target words 13.10F3.17

Embedded words (E) 13.63F2.61 3.60 0.001

Embedded words (N) 11.67F2.50

E=embedded words from emotional sentences, N=embedded words

from neutral sentences. Maximum possible score on each recog

nition memory subtest is 21. All significance tests two-tailed

Degrees of freedom=29.


2.3. Statistical analysis

Following motion correction (Bullmore et al.,

1999), periodic change in T2*-weighted signal

intensity at the (fundamental) experimentally deter-

mined frequency of alternation between A and B

conditions (=1/60 Hz in all experimental conditions)

was estimated by an iterated least squares fit of a

sinusoidal regression model to the fMRI time series

observed at each voxel. A standardized test statistic,

the standardized power (SP), was obtained for each

voxel (Bullmore et al., 1996). Parametric maps

representing SP observed at each intracerebral voxel

were constructed. To sample the distribution of SP

under the null hypothesis that observed values of SP

were not determined by experimental design (with

few assumptions), the 99 images observed in each

anatomical plane were randomly permuted and SP

was estimated exactly as above in each permuted

time series. This process was repeated 10 times at

each voxel, resulting in 10 permuted parametric maps

of SP at each plane for each subject. Thus, this

analysis is based on a random effects model, fully

described elsewhere (Brammer et al., 1997). The

observed and randomized SP maps were transformed

into standard space (Talairach and Tournoux, 1988)

and smoothed by a 2D Gaussian filter with full width

at half maximum=11 mm. This procedure is

described in detail elsewhere (Brammer et al., 1997;

Bullmore et al., 1996) but essentially involves

normalization onto a standard template (an average

of 10 IR images already transformed into standard

Talairach space). The median observed SP at each

intracerebral voxel in standard space was tested

against a critical value of the null distribution of

median SPs constructed from the permuted SP maps

(Brammer et al., 1997). For a test at any desired P-

value, the critical value is extracted from the random-

ization distribution such that 1/P of the random-

izations exceed that value. In the observed data,

voxels with SPs exceeding this critical value had a

probability under the null hypothesis less than or

equal to the chosen P-value. The particular P-value

was determined by setting the expected number of

false-positive voxels (EPI), so that P=EPI/total search

volume. For this study the EPI was set at 50 voxels

so that the threshold P-value was 50/20,000 (approx-

imate search volume) or 0.0025.

To estimate the differences in mean SP between the

two recognition memory experimental conditions

(target and embedded), we fitted repeated measures

analysis of variance (ANOVA) models at each voxel

of the observed SP maps in standard space. Differ-

ences in mean SP between the two conditions were

tested for significance only at voxels generically

activated by one or both of the conditions considered

independently, thereby substantially reducing the

search volume or number of tests conducted.

Other methodological considerations: Each subject

completed the National Adult Reading Test (NART),

the Beck Depression Inventory (BDI), and the Beck

Anxiety Inventory (BAI). Subjects’ verbal IQ, as

predicted by the NART, ranged from 105 to 126

(mean 114.3). Subjects had no history of neurological

or psychiatric illness, were on no medications, and all

scored below clinical cut-offs on the BDI and BAI.

Subjects were paid o20 for their participation.

3. Results

3.1. Behavioural data

The initial experiment conducted outside the

scanner (results summarised in Table 3) showed that

memory for emotional target words was significantly

superior to matched neutral words (Pb0.001), evi-

dence of emotional memory enhancement. In addition,

memory for neutral words that were bembeddedQin emotional sentences–either before or after the

aversive word–was also enhanced to a significant

albeit lesser extent (P=0.001). These significant

findings were essentially unchanged in further experi-

ments in which the interval between encoding and

-

.


recognition testing (here 5 min) was varied from 30

min to 24 h (data available on request).

In the subsequent fMRI study, recognition memory

for words from emotional sentences was significantly

greater than that from neutral sentences [33.6 (SD 4.2)

vs. 31.0 (SD 4.3); t=2.58, P=0.027]. There were

trends for emotional target vs. neutral words [17.8

(SD 2.59) vs. 16.5 (SD 2.28), P=0.1], and neutral

words embedded in aversive sentences vs. neutral

words in neutral sentences to be better remembered

[15.8 (2.4) vs. 14.4 (2.5), P=0.08], but the contrasts

failed to reach statistical significance.

Neuroimaging findings are summarised in Table 4.

Encoding of aversive sentences caused significant

additional activation over matched neutral sentences

in the left anterior cingulate gyrus and left precuneus.

Table 4

Number

of voxels

Talairach

co-ordinates

Side Brain area

(approx. BA)

P

Areas activated by encoding of emotional sentences

17 �11 33 31 L Anterior cingulate

gyrus (32)ER, Content0.000009

6 �7 �52 31 L Precuneus (7) 0.00004

Areas activated by recall of target emotional words

84 15 �52 �13 R Cerebellum 0.000009

53 �4 39 �13 L Medial prefrontal

cortex (11)ER, Content0.000007

42 15 46 �2 R Anterior cingulate

gyrus (32)

0.000028

18 �47 17 4 L Inferior frontal

gyrus (47)Content0.00017

73 �7 �43 37 L Posterior cingulate

gyrus (31)Content0.000007

50 �4 �46 31 L Precuneus (7) 0.000007

78 �40 �60 26 L Middle temporal

gyrus (39/21)Content0.000007

23 �40 13 �2 L Anterior insula

(47)ER, Content0.00002

28 �40 13 �13 L Superior temporal

gyrus (38)

0.000007

18 25 �43 �2 R Parahippocampal

gyrus (30)

0.00002

12 36 �10 �7 R Amygdaloid complex 0.00002

8 40 �10 �13 R HippocampusER, Content 0.0002

Areas activated by recall of embedded words from emotional

sentences

5 �26 �33 �13 L Parahippocampal

gyrus (36)

0.0007

5 �26 �36 42 L Inferior

parietal lobule (40)

0.0012

Recognition of aversive target words—compared with

neutral target words—activated anterior and posterior

cingulate gyrus, inferior frontal and areas of medial

prefrontal cortex, precuneus, anterior insula, right

amygdaloid complex, right hippocampus, right para-

hippocampal gyrus, and right cerebellum.

Embedded word recognition: Recognition of

embedded words from emotional sentences—com-

pared with those from neutral sentences—activated

areas of left parahippocampal and inferior parietal

lobule. Specific P-values for individual activations

are shown in Table 4.

Since automatic encoding of new distracter words

occurs during recognition testing, it is necessary to

carry out further contrasts to refine the activation

maps corresponding to retrieval alone. Comparing

retrieval of emotional targets with encoding of emo-

tional sentences showed significantly greater activa-

tion in left medial frontal lobe, left insula, right

hippocampus, and right anterior cingulate cortex

during retrieval. Retrieval of emotional target words

confounds emotional content (the word itself) and

context (the meaning of the sentence in which the

word was encoded). Hence, we contrasted target

recognition (content plus context) with embedded

word recognition (context only) to refine the activa-

tion corresponding to emotional retrieval. This

showed significantly greater activation for target

emotional word recognition in left anterior and

posterior cingulate cortex, left middle temporal gyrus,

left medial frontal cortex, left anterior insula and right

hippocampus (Fig. 1). To explore further the robust-

ness of the medial temporal lobe laterality effects

observed for the two recognition memory tasks, we

also looked specifically at the area of the left

parahippocampal gyrus activated during the embed-

ded word recognition task, extracting the mean SP for

this area from each subject’s data and comparing it

with the mean SP from the same area during the target

recognition task (see Fig. 2). When a single outlying

value was excluded, a paired t-test showed signifi-

cantly greater SP in the embedded word condition for

this left parahippocampal region (t=2.06, df=10,

P=0.034, one-tailed test).

The anterior cingulate cortex, which has reciprocal

connections with the amygdala and the hippocampus,

emerged as crucial in the encoding of emotional

content. Previous neuroimaging research (Bremner et

Fig. 1. Regional brain activation during recognition of aversive target words. Key areas of activation are labeled (amyg=amygdala,

hippo=hippocampus, ACC=anterior cingulate cortex, ant ins=anterior insula, cx=cortex). (a) Shows an axial slice at the Talairach level z=�13,

(b) is a slice at level z=�2.


al., 1999; Hamner et al., 1999) has suggested that this

region modulates or inhibits activation in limbic

structures. To test for this inverse relationship in our

subjects, the mean SP scores (see above) for each

subject were extracted from the area of this region

activated in the encoding condition. These scores

were significantly negatively correlated with perform-

ance on the emotional target word recognition task—

the greater the degree of anterior cingulate activation,

the fewer emotional target words correctly recognized

(Fig. 3). When all 12 subjects were considered

together, Kendall’s tau=�0.46, P=0.044. When one

outlying subject (see Fig. 2) was excluded, tau=�0.53,

P=0.027. There was also a weak, non-significant

negative correlation between the same SP scores and

the number of neutral target words correctly recog-

nized (tau=�0.39, P=0.083, all 12 subjects included

in analysis).

4. Discussion

The behavioural data support the idea that

emotionally salient verbal material is better remem-

bered than affectively neutral, but otherwise similar,

material. This effect extends to context words as

well as words that are emotionally salient. This

does not necessarily imply, however, that this

contextual bemotional memory effectQ would extend

to other contextual information in different settings

(e.g. incidental visuospatial material in emotional

scenes).

The neuroimaging data suggest that mechanisms

for emotional retrieval differ according to the type

of information to be recalled. The right amygdala

complex and right hippocampus were activated by

the recognition of target emotional words, but not

by the encoding or embedded recognition condi-

tions. In the embedded word recognition condition,

activation was present in the left parahippocampal

gyrus when the words to be retrieved came from

emotional contexts. Thus areas involved in retrieval

are activated more by emotional than neutral

content. Of particular interest is the finding that

hippocampal/parahippocampal activations were on

the right in the target word recognition task and on

the left for the embedded recognition task. Directly

comparing the target and embedded word tasks

showed that the right hippocampus was one of the

areas significantly more activated during the former

condition, while comparing each subject’s SP for

the left parahippocampal gyrus across the two

conditions showed a significant difference (with

more activation in the embedded word condition)

when a single outlying value was excluded from the

analysis. Thus, these laterality differences appear

highly robust when subjected to further levels of

analysis. This implies a laterality difference in the

recall of material that is emotive in and of itself, as

compared with material that is emotive only by

Fig. 3. Scatterplot showing inverse relationship between ACC

activation at time of encoding and subsequent score for recognition

of target emotional words. Outlying value in brackets.

Fig. 2. Scatterplot showing mean standardized power (SP) in left

parahippocampal cortex for each subject during target (TARG) and

embedded (EMB) word recognition tasks. Outlying value in

brackets.


association (in other words, content as compared

with context).

There are two possible ways of interpreting the

activation of the right amygdala seen in the target

recognition condition. One interpretation is that the

amygdala is involved in recall of emotional material.

This runs counter to the view (discussed in Section 1)

that the amygdala acts at the time of encoding to

modulate memory storage, but is not involved in the

subsequent process of recall. The second interpreta-

tion is that the amygdala activation is due to the

viewing of pairs of emotional words, from which

subjects had to choose their responses. In other words,

it reflects the response to emotional material rather

than the process of recognition per se. This latter

interpretation sits more comfortably with other work

in this field, and at the time of writing it is the one we

favour.

A study of recognition memory of words from

emotive contexts (Maratos et al., 2001) found left

amygdala and hippocampus were selectively activated

by recognition of neutral words from aversive emo-

tional sentences, broadly in line with our findings,

although the methodology did not involve content vs.

context, or encoding vs. recognition comparisons. Erk

et al. (2003) examined the effect of context on

subsequent memory performance by presenting neu-

tral words paired with unrelated images, which could

be affectively positive, negative, or neutral, and then

assessing free recall of the presented words. The recall

phase was performed outside the scanner, so that the

neuroimaging findings relate only to the encoding

phase, but the authors were able to identify a network

of right-sided MTL structures in which the degree of

activation was apparently predictive of subsequent

memory performance for words presented in pos-

itively valenced contexts. Interestingly, they found an

emotional enhancement of memory for words pre-

sented in positive, but not negative, contexts, and

suggest that this may be because the impact of the

negatively valenced pictures is such that encoding of


associated, but semantically unrelated, stimuli is

adversely affected. This is likely to be the case, and

such a phenomenon is probably in part responsible for

the conflicting results found in previous studies of

emotional memory effects (Burke et al., 1992). A

striking, if extreme, example of this is the bweaponfocusQ effect described in victims or witnesses of

violent crime (Loftus and Burns, 1982), where

attention is narrowed to the weapon, and memory

for peripheral but crucial information (e.g. the dress

and appearance of the person holding the weapon)

may thus be unreliable. It is likely that negative

words, as used in our study, have less impact in this

sense than the intensely aversive images used by Erk

et al. (and employed in many other studies of

emotional processing), and this may also explain

why, in contrast to other studies using emotional

images, we did not find any amygdala activation

during the encoding phase. Another difference

between our study and that of Erk et al. that is

relevant here is that our study uses semantically

related stimuli—in a sentence where a single word is

aversive, the context depends on understanding the

meaning of the whole sentence. A recent commentary

(Lewis and Critchley, 2003) outlines a bsemantic-

network approachQ to the study of emotion–memory

interactions, and it is likely that stimuli which are

indeed semantically related are better suited to study-

ing such networks. This is not to dismiss the

usefulness of other means of establishing context, as

in real life contextual information may be highly

variable in terms of its relevance to an emotional

event—it may be directly relevant, entirely coinci-

dental, or anywhere between these poles. These

considerations are also relevant to a more recent

study (Smith et al., 2004), where contextual memory

effects were probed using pictures of objects paired

with neutral or emotional picture backgrounds. As in

our study, both encoding and recognition were studied

in the scanner, and the authors identified left para-

hippocampal gyrus as having a specific role in

contextual recall. Our data support this finding,

although the foregoing caveats about the possible

significance of different methods of establishing

context must also be borne in mind.

The possibility of laterality effects in emotional

function has been extensively explored in both

animals and humans (Heilman, 2000), and a range

of experimental and empirical findings support a

model based on two basic circuits: approach and

withdrawal (see Davidson, 2000, for a review). Our

findings support the idea that aversive material (the

emotional target, or content, words) selectively

activates the right amygdala, while the finding of a

left hemisphere bias for recognition memory of

neutral words from aversive contexts underlines the

idea that contextual processing may be served by

different circuitry from that used for content. All the

emotional stimuli in our study were negatively

valenced, which is more relevant to psychopathology,

so while our findings may have relevance to prior

work on the withdrawal circuit, we cannot comment

here on the approach circuit. The use of positively

valenced content/context stimuli may be a fruitful

avenue for future work.

Despite the tightly controlled parameters in our

experiment, retrieval of emotional words produced

widespread activation. This could reflect the tendency

for emotive stimuli to trigger many associations.

Posterior cingulate gyrus was activated by the emo-

tional component of the target retrieval task, lending

weight to the suggestion (Maddock, 1999) that it has a

key role in the integration of emotion and episodic

memory processes. The anterior insula is known to be

involved in processing emotionally aversive stimuli

(Phillips et al., 1997), and its activation during

emotional target recognition is consistent with this,

although this activation may be due to viewing

emotional word pairs rather than recognition memory.

The anterior cingulate cortex (ACC) was strongly

activated by reading emotional sentences, and by the

recognition of target emotional words. The finding

that ACC activation was negatively correlated with

emotional target recognition provides direct evidence

that this region modulates the impact of emotionally

salient material, thus influencing how it is encoded

and retrieved. Data from neuroimaging studies and

animal work suggest that the ACC can be considered

as having cognitive and affective subdivisions (Bush

et al., 2000). The activation observed in the encoding

phase lies in the cognitive subdivision, while that seen

in the target recognition phase falls within the

affective division, but it is the former that appears to

have a crucial effect on the subsequent recognition of

aversive target words. This area is known to be

activated by tasks that involve competing categories


of information (Bush et al., 2000). In the encoding

phase, subjects were merely asked to read each

sentence, not to provide any ratings of bemotionalityQ.It may be that in these circumstances, the affective

content of the aversive sentences is treated as a con-

flicting information stream by the ACC. This would

account for the inverse correlation seen between

activation of this area of the ACC at encoding and

the subsequent recognition memory score for target

emotional words—the greater the ACC activation, the

more the response to affective content is inhibited, and

thus the emotional memory effect is diminished.

However, this interpretation needs to be approached

with some caution, as there is also a weak non-

significant negative correlation between the same

ACC SP values during encoding and the subsequent

recognition scores for neutral emotional words. This

suggests that activity of this area during encoding may

have a more general limiting effect on subsequent

recognition memory, besides any specific modulation

of the bemotional memory effectQ. It may be that a

particular attentional style, associated with activity in

this region of the ACC, affects the encoding and

subsequent memory trace for verbal material. Other

attentional processes may potentiate the emotional

memory effect: while most accounts of emotional

memory emphasize the role of arousal (see Section 1),

it is at least possible that improved recognition

memory for aversive target words need not rely

entirely on arousal-mediated mechanisms. Differences

in valence between matched targets could account for

the observed pattern of recognition memory due to a

bpop-outQ effect (Nakayama and Joseph, 1998): the

aversive targets could be more perceptually salient,

and therefore memorable without invoking a separate

mechanism based on arousal (see also Worthen et al.,

2000). The matching of aversive and neutral words for

psycholinguistic variables provides some safeguard

against such effects. However, even after matching of

individual words, there may still be sentence-level

effects.

In contrast to the activation of the cognitive

division of the ACC seen in encoding, during target

word recognition, the affective division was activated

by the aversive phase. This may reflect the viewing of

aversive word pairs rather than any specific retrieval

process (cf. amygdala activation during this phase, see

above). It is likely that reading individual words

produces a more affectively driven response than does

reading entire sentences, where the emphasis is on the

meaning of the sentence construct, the latter task thus

engaging more cognitive areas. Activations in middle

temporal gyrus probably reflect the use of verbal

stimuli, but they are nonetheless confined to the

emotional phase. Thus, it appears that emotionally

salient material exerts a modulatory effect on areas

involved with higher cognitive functions such as

language and memory, perhaps analogous to the

modulatory effect previously described in sensory

cortex (Morris et al., 1998).

The present study has a number of limitations.

The use of a block-design paradigm does not permit

analysis of specific memory effects for individual

items (see, for example, Dolcos et al., 2004), and

does carry the risk that the data can be contaminated

by bfalse alarmsQ. The technique of alternating task

blocks does not allow computing deactivation asso-

ciated with the task condition, so that areas which

show significantly different activation when neutral

conditions are subtracted from emotional conditions

may include deactivations under the neutral con-

dition, although this need not necessarily imply a

different interpretation. Furthermore, it is possible

that the encoding task was easier than the recog-

nition memory tasks, so that differences in activation

patterns between conditions may in part reflect

differences in task difficulty or differences in

stimulus complexity. In addition, our design did

not permit any separation of the effects of stimulus

valence and arousal, but other work has suggested

that these variables may have dissociable effects

(including effects relating to laterality) on emotional

responses (Canli et al., 1998) and emotional memory

(Canli et al., 2002; Libkuman et al., 2004), while a

study specifically examining memory for emotional

words concluded that both valence and arousal

contribute to emotional enhancement of verbal

memory (Kensinger and Corkin, 2003). Future work,

involving the concurrent acquisition of fMRI and

galvanic skin response data, may be able to address

the relative contributions of arousal and valence to

content–context interactions. The study by Canli et

al. (2002) explored gender differences using fMRI,

and enlarges on earlier work (Cahill et al., 2001) in

suggesting a gender difference in lateralisation of

amygdala function, but our data do not allow us to


comment on gender differences as there were no

female subjects in our fMRI experiment. However, if

our interpretation of the right amygdala activation

seen in our target recognition condition is correct,

this is in line with the finding (Cahill et al., 2001)

that emotional material selectively activates the right

amygdala in males. However, the applicability of the

initial behavioural study, which was conducted with

both male and female participants, to the subsequent

fMRI study (male participants only), may be

compromised by the fact that other studies have

shown that female subjects tend to describe more

intense responses to emotional stimuli (e.g. Canli et

al., 2002).

Interactions between emotion and high-level cog-

nitive processes remain relatively unexplored in

neuroimaging, in which simpler stimuli such as

emotional faces and sounds are frequently used, and

further work is required in this regard. We have shown

the ACC to be critical in emotional memory enhance-

ment of verbal material. In addition our data suggest

that emotional content enhances memory through

increased activation of the hippocampus, and that

right and left medial temporal lobe structures play

different roles with regard to content and context in

the formation of emotional memories. These findings

enlarge on previous work on the neural basis of

emotional memory and its role in both normal and

pathological affect.

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