limbic response to music
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Feeling the Real World: Limbic Responseto Music Depends on Related Content
Eran Eldar1,2, Ori Ganor1,2, Roee Admon1,2, Avraham Bleich2,4
and Talma Hendler1,2,3
1Wohl Institute for Advanced Imaging, Tel-Aviv Sourasky
Medical Center, Israel, 2Sackler Faculty of Medicine, Tel-Aviv
University, Israel, 3Psychology Department, Tel-Aviv
University, Israel and 4Lev-Hasharon Mental Health Center,
Israel
Eran Eldar and Ori Ganor contributed equally to this work.
Emotions are often object related—they are about someone orsomething in the world. It is yet an open question whether emotionsand the associated perceptual contents that they refer to areprocessed by different parts of the brain or whether the brainregions that mediate emotions are also involved in the processingof the associated content they refer to. Using functional magneticresonance imaging, we showed that simply combining music (richin emotion but poor in information about the concrete world) withneutral films (poor in emotionality but rich in real-world details)yields increased activity in the amygdala, hippocampus, and lateralprefrontal regions. In contrast, emotional music on its own did notelicit a differential response in these regions. The finding that theamygdala, the heart of the emotional brain, responds increasingly toan emotional stimulus when it is associated with realistic scenessupports a fundamental role for concrete real-world content inemotional processing.
Keywords: amygdala, emotion, fMRI, hippocampus, prefrontal cortex
Introduction
Emotions have evolved as evaluations of events in the world that
guide adaptive behavior (Lazarus 1991; Clore and Ortony 2000).
In order to serve this function, they must be closely linked to
information about the concrete real world (i.e., be grounded).
For example, when being attacked by a bear, for an appropriate
emotion (i.e., fear of the bear) and response (i.e., running away)
to emerge, the evoked emotion must refer to the perceived
representation of the bear and the danger it presents. When
looking into the brain from this perspective, it is reasonable to
expect that a neural mechanism that mediates an emotional
state will also be involved in processing aspects of its associated
content. It has been demonstrated that areas traditionally
thought to be involved solely in cognitive processes, such as
working memory and perception, can be modulated by emotion
(Rotshtein et al. 2001; Perlstein et al. 2002). However, the
sensitivity of emotion-related brain regions to associated
perceptual content has not been sufficiently considered.
In order to study the relative involvement of a given brain
region in processing emotions and associated content, one
needs to manipulate them independently. To achieve that, in
the present study, 12 healthy subjects passively watched short
film clips and listened to short music clips in a cross-modal
design while their brain activity was measured by functional
magnetic resonance imaging (fMRI). Subjects were presented
with music clips—rich in emotion but poor in concrete
content; film clips—poor in emotion but rich in concrete real-
world details; and music and film clips in combination. Music
clips were of negative, positive, or neutral emotional character,
whereas film clips were all emotionally neutral. Thus, when
neutral film and music clips appeared together, the neutral film
acquired the emotional valence provided by the music (Fig. 1).
Emotions elicited by music are relatively abstract, as music
provides no representation of the immediate real world. On the
other hand, when music is embedded in a film, the cinematic
scene, rich in details and objects, grounds the abstract musical
emotion in the real world and gives it a concrete meaning
(Cohen 2001). As was shown before, music cannot only set the
emotional tone of a film but also radically affect the way in
which the film is interpreted and remembered (Lipscomb and
Kendall 1994; Boltz 2001). Thus, in our paradigm, the emotion
elicited by the combination of film and music differed from the
film alone in its emotionality and from the music alone in its
added concrete content. Accordingly, we assumed that brain
regions that process an emotion together with the concrete
content it refers to would be preferentially activated by the
emotional combination compared with the separate film and
music.
It is an open question whether such an integrated process
recruits a unique neural mechanism or involves dedicated
neural systems that handle each process alone, such as amygdala
for emotion and prefrontal cortex (PFC) and visual cortex for
associated perceptual content.
The amygdala comprises the heart of the brain’s emotional
system. It might be specifically relevant to our question because
in a rodent model of fear conditioning, it was shown to
be critical for tying emotional responses to external stimuli
(LeDoux 2000). Based on primate studies, it was proposed that
the amygdala is acting as a modulator to ensure that emotional
responses are appropriate to the external stimuli and to the
social context (Bachevalier and Malkova 2006). Moreover,
together with the hippocampus, the amygdala is thought to
facilitate the association of emotions to spatial and episodic
information about the world (Phelps 2004). Altogether, it seems
that the amygdala serves a comparable role in various emotional
tasks differing greatly in complexity and explicit cognitive load,
such as simple fear conditioning, contextual conditioning,
recognition of fearful facial expressions, and emotion-guided
decision making (Bechara et al. 1999; Adolphs et al. 2005).
However, because the activity in the amygdala was not directly
compared between these different tasks, it left open the
possibility that the associated content by itself modulates its
function. It has been shown that an attention-based task
decreases amygdalar response to unrelated emotional stimuli
(Phan et al. 2002; Pessoa et al. 2005). However, in these studies,
the perceptual tasks were deliberately unrelated to the emo-
tional processing and were therefore in competition with it for
neural resources. To the best of our knowledge, the significance
of perceptual content that constitutes a part of an emotional
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doi:10.1093/cercor/bhm011
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processing, rather than interferes with it, has not yet been
assessed. The question remains whether the amygdala mediates
not only the affective aspect of emotional processing but also its
associated content. In our study, differential amygdala response
to music alone and to its combination with movies would
support the latter.
The PFC is thought to play an important role in behavioral
control, mediating perception and action (Fuster 2001), partic-
ularly when guided by internal states, such as affect and
motivation (Miller and Cohen 2001). Miller and Cohen also
suggested that the PFC achieves this function by maintaining
patterns of activity relating to both visual perception and
emotional evaluations among other processes. Specifically, the
medial PFC has been implicated in emotion-guided decisions
and conflict processing, whereas the lateral PFC has been
implicated in guiding and shaping perceptual decisions
(Bechara et al. 1999; Miller and Cohen 2001). Interestingly, a
functional connection between the emotionally associated me-
dial PFC and the cognition-associated lateral PFC has been
suggested before, based on their widespread anatomical con-
nections in primates (Barbas 2000).
Consistent with such an integrative role, the PFC has
widespread connections to other brain regions, including the
amygdala, the hippocampus, high-order visual and auditory
cortices, and the lateral temporal cortex (Fuster 2001). It was
therefore reasonable to expect prefrontal regions to also be
involved in binding abstract emotional states (as evoked by the
music clips) with perceived representations of the world (as
presented in the movie clips).
Materials and Methods
SubjectsFourteen healthy, right-handed volunteers (aged 23--30 years, 6 females)
participated in the imaging experiment. All signed an informed consent
form that was approved by the Tel Aviv Sourasky Medical Center and Tel
Aviv University ethical committees. Subjects with previous knowledge
about the experiment were not recruited. Two subjects (1 female) were
excluded from the final analysis due to excessive head movements
during the scan. Fifteen subjects (aged 20--29 years, 6 females)
participated in the behavioral emotional judgments of the stimuli.
Nine female subjects (aged 25--38 years) participated in the behavioral
concrete content judgments of the stimuli. No subjects participated in
both the behavioral and the imaging studies.
Visual and Auditory StimuliThe visual stimuli consisted of 12 film clips of 12 s each. The film clips
were selected from commercial films according to the following
requirements: 1) film clips were of emotionally neutral character;
2) coupled with emotional music, film clips could be interpreted as
both negative and positive; 3) film clips contained no dialogue; and
4) film clips portrayed no widely familiar actors or scenes.
The auditory stimuli consisted of 12 music clips, 12 s each. The music
clips contained no human voices or sounds related to specific objects
(e.g., a clock ticking, footsteps, etc.). The music clips were of positive
(joyful), negative (scary), or neutral (simple and monotonic) emotional
tones (4 clips of each type). The neutral music was used to control for
the effect of nonemotional auditory stimuli. Positive music clips were
selected from commercial popular music. Two negative clips were
composed (cut and edited) from a horror film sound track and from
a classical music piece (using Wavelab 4.0 from Steinberg, Steinberg
Media Technologies, GmbH, Hamburg, Germany). Two negative clips and
all the neutral clips were created in-house usingmusic software (Cubase
Figure 1. The experimental paradigm. All subjects were shown negative, positive, and neutral stimuli (shown here and through the text as black, dark gray, and light gray,respectively). Each subject was presented with 12 neutral video clips and 12 emotional music clips (4 negative, 4 positive, 4 neutral) both separately and in combination. Specificfilms were not associated with a specific type of music: a film clip that was combined with positive music in one third of the subjects was combined with negative music in anotherthird and with neutral music in the remaining third. All conditions were order-balanced and pseudorandomly distributed. The clips were 12 s long and separated by 9-s blank epochs.Readers are encouraged to view and listen to examples of the stimuli provided in the online supplementary material (Supplemental Video 1--8, Supplemental Audio 1--6).
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VST 5 from Steinberg, Reaktor 3.0 and Kontakt 1.0 from Native Instru-
ments Software Synthesis, GmbH, Berlin, German). The average decibel
level of all music clips was made equal using Wavelab 4.0 from Steinberg.
Experimental ParadigmEach subject was presented with 12 emotionally neutral film clips and
12 music clips of negative, positive, or neutral valence. The stimuli were
presented as 12-s epochs separated by 9-s blank epochs (gray screen).
Arrangement of the stimuli was done with film-editing software (Adobe
Premiere 5) and then burned on a DVD disc, which was used for both
the behavioral and imaging experiments.
Within-subject arrangement: film clips (F), music clips (M), and their
combination (FM) were order balanced in the 6 combinatorial possibil-
ities of presentation (F FMM; FM FM; M F FM etc.). The clips of a specific
‘‘trio’’ (F1 FM1 M1) were distanced from each other as far as possible
(average distance = 11.875 epochs per 3.94 min, standard deviation 1.32
epochs per 0.462 min). To avoid priming effects, all emotionally neutral
conditions (silent film, neutral music, and neutral combination) were
equally positioned after negative and positive conditions. An additional
film clip combined with calm music was positioned as the first epoch,
which was ignored in the data analysis.
Across-subject arrangement: three versions of the paradigm were
created, each presented to a third of the subjects (see Supplementary
Table 1). Please note that although all versions consisted of the exact
same set of stimuli, the specific film--music coupling is different per each
group of subjects. This way, a specific film was not associated with
a specific valence type of music across subjects. For example, a film clip
that was combined with positive music in one version was combined
with negative music in the second and with neutral music in the third.
This design was used in order to avoid any bias due to specific film
features.
Stimulus Judgment ExperimentA preceding behavioral study was performed in a quiet room using the
same experimental paradigm as in the imaging experiment. Subjects
viewed the experimental paradigm on a TV screen using a DVD player.
As customary in studies of emotion, subjects were requested to rate
each stimulus on 2 scales (Lang et al. 1993). One was a ‘‘valence’’ scale, in
which the valence of the emotion elicited by each clip was rated on
a 10-level bipolar scale (–5, ‘‘very negative’’ to +5, ‘‘very positive’’).
Subjects were instructed using these examples: ‘‘an example of negative
emotion is fear and an example of positive emotion is joy.’’ The other
scale was an ‘‘arousal’’ scale, in which the arousal of the emotion elicited
by each clip was rated on a unipolar scale of 10 points (0, ‘‘not arousing’’
to 10, ‘‘very arousing’’). Film and music clips that were not rated as
expected separately or in combination were discarded, and alternative
clips were used instead. All clips included in the experiment were rated
by 15 subjects. A different group of 9 subjects rated to what extent the
various clips contained concrete content (0, ‘‘not concrete’’ to 10, ‘‘very
concrete’’). In accordance with Oxford Dictionary’s definition, ‘‘con-
crete’’ was defined as ‘‘something you can touch, the opposite of
abstract.’’ To allow enough time for rating, the presentation was paused
during the blank epochs when needed. Statistical analyses were
performed with Student’s t-tests using Microsoft Excel software.
fMRI Experimental ProcedureThe experimental paradigm was played on a DVD player and projected
via an LCD projector (Epson MP 7200) onto a translucent tangent
screen located on the head coil in front of the subject’s forehead.
Subjects viewed the screen through a tilted mirror fixed to the head coil.
Subjects were 1) instructed to avoid head movements throughout the
scan and 2) focus on the presented visual and auditory stimuli and keep
their eyes on the screen throughout the functional scan and 3)
encouraged to naturally experience the stimuli. As both explicit and
implicit experimental tasks have been shown to alter limbic activity,
neither was used (Phan et al. 2002).
MRI SetupImaging was performed on GE 3-T echo planar imaging system. All
images were acquired using a standard quadrature head coil. The
scanning session included anatomical and functional imaging. Three-
dimensional (3D) sequence spoiled gradient echo sequence, with high-
resolution and 2 mm slice thickness (field of view [FOV] = 24 3 24,
matrix: 256 3 256, time repetition/time echo [TR/TE] = 20/3 ms), was
acquired for each subject. This anatomical study allowed for volume
statistical analyses of signal changes during the experiment. Functional
T2*-weighted (TR/TE/flip angle = 3000/50/90; with FOV 24 3 24 cm2,
matrix size 128 3 128) images were acquired (24 oblique slices,
thickness: 4 mm, gap: 1 mm, covering the whole cerebrum) in runs of
6288 images (262 images per slice). An oblique angle, individually
determined based on the occipital end and orbitofrontal surface of each
brain, was used in order to maximize the signal from limbic structures.
Functional Imaging Data AnalysisImaging data were analyzed using BrainVoyager 2000 software package
(Brain Innovation, Maastricht, The Netherlands). Raw functional images
were superimposed and incorporated into the 3D data sets through
trilinear interpolation. The complete data set was transformed into
Talairach space (Talairach and Tournoux 1988). Preprocessing of
functional scans included head movement assessment (scans with
head movement >1.5 mm were rejected) and correction of high-
frequency temporal filtering by the removal of linear trends. To allow for
T2*-equilibration effects, the first 6 images of each functional scan were
rejected. The 3D group statistical parametric maps were calculated
using a general linear model (GLM), in which all stimuli conditions were
defined as positive predictors. The GLM consisted of 9 conditions: 3
modality types (film, music, and combination) 3 3 musical valence types
(negative, positive, and neutral). A uniform lag of 1 repetition was used
to account for the hemodynamic response shift.
Region of Interest AnalysisRegion of interest (ROI) analysis was applied to the PFC, the amygdala,
and the hippocampus. In addition, visual and auditory regions were also
examined, including the lateral occipital complex (LOC), the para-
hippocampal place area (PPA), the fusiform face area (FFA), and the
planum temporale (PT) (the rationale for choosing these specific
regions is elaborated in Results). The ROIs were defined based on
a conjunction of functional and anatomical criteria: 1) Only voxels
activated by a contrast of all ‘‘combination’’ conditions versus baseline in
a multisubject GLM (n = 12, P < 0.005, fixed effects model, uncorrected)
were included. This contrast marks the network of regions generally
involved in processing visual and/or auditory stimuli. As negative,
positive, and neutral conditions are all included in this contrast, it holds
no bias in terms of emotion. 2) Anatomical boundaries were defined in
Talairach space for each ROI. The PFC, the amygdala, and the
hippocampus were marked using the Talairach atlas (Talairach and
Tournoux 1988). The PFC was defined as Brodmann areas 9, 10, 11, 12,
25, 32, 45, 46, and 47. Special care was taken to avoid regions that are
known to be involved in premotor or visuomotor functions (Brodmann
areas 6, 8, and 44) (Faw 2003). The LOC was marked as a box-shaped
region encompassing Talairach coordinates reported by Grill-Spector
et al. (1999). The PPA and FFA were marked as 10 3 10 3 10 voxels box-
shaped regions centered around Talairach coordinates reported by
Epstein et al. (2003) and Kanwisher et al. (1997), respectively. The PT
was marked according to Talairach coordinates reported by Westbury
et al. (1999). The central Talairach coordinates and the number of
voxels of each ROI are reported in Supplementary Table 2 online. ROIs
that were combined together were averaged according to their relative
number of voxels.
For each ROI, time courses were collected from all subjects. In each
time course, average percent signal change was calculated for each
epoch relative to implicit baseline (the average signal during all blank
epochs) using Microsoft Excel. Two-way analysis of variance, with
modality (combination, film, and music) and specific film--combination--
music triplets (triplet 1, triplet 2, triplet 3, and triplet 4) as factors, was
separately applied to each type of emotion using STATISTICA software.
Thus, within each subject, the exact same stimuli were compared
between the combined and each of the separate conditions. A second
comparison was attempted between the combination and the summa-
tion of the separate condition.
Correlation AnalysisCorrelation of ROI time courses was examined between the amygdala
and anterior hippocampus during the separate and combined film and
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music conditions. For each subject, all readings of the blood oxygena-
tion level--dependent (BOLD) signal were collected for each condition
in each of the ROIs, and then the data sets from the amygdala and
anterior hippocampus ROIs were correlated with linear regression
analysis using Microsoft Excel for each condition separately. The degree
of correlation was then compared between the different conditions on
the group level using a paired t-test (n = 12).
Isolation of a Combination-Specific NetworkFirst, a conjunction analysis of [combination > film] and [combination >
music] was performed (n = 12, random effects analysis, P < 0.002
uncorrected, extent threshold = 2 voxels per 1.65 mm3). Then, the
resulting gray matter clusters were masked by an inclusive mask
obtained by the contrast [combination > baseline] and by exclusive
masks obtained separately by the contrasts [music > baseline] and [film> baseline] (n = 12, random effects analysis, P < 0.05 uncorrected,
extent threshold = 2 voxels per 1.65 mm3). This 2-step analysis
identified clusters of activation that were active exclusively in response
to the combination (and not to the separate conditions) and whose
activity was significantly higher in response to the combination
compared with the separate conditions. This same procedure was
performed for the negative, positive, and neutral conditions separately.
Results
Behavioral Experiment
In a preceding study, 15 subjects (different from the fMRI
subjects) rated the emotion elicited by the various clips in terms
of valence and arousal. Figure 2A--F shows that all film clips and
neutral music clips were rated as relatively nonemotional
(nonarousing and neutral), whereas the negative and positive
music clips were rated as highly arousing and clearly negative or
positive. Most importantly, the combinations of music and film
were rated similarly to the same music clips on their own.
The various clips were also rated in terms of their concrete
content in an additional behavioral study. The film clips and the
combinations were similarly rated as very concrete, whereas the
music was rated as significantly less concrete (Fig. 2G--I). Thus,
as was the case in Boltz’s study (Boltz 2001), it was the music
that determined the emotional tone of the combination,
whereas the films provided the music with concrete content.
fMRI Experiment
Emotion and Content at the Limbic Level
The amygdala and anterior hippocampus were examined with
a ROI approach (see Materials and Methods). The ROIs were
anatomically marked out of a general functional cluster that was
obtained by the contrast of all the combination conditions
versus baseline (Fig. 3C). This contrast marks the network of
regions generally involved in processing visual and/or auditory
stimuli and holds no bias in terms of emotion. As discussed
above, the amygdala and anterior hippocampus are known to
closely cooperate on various aspects of emotional processing
(LeDoux 2000; Phelps 2004) and when collected separately
indeed showed a similar pattern of results. The results of the
amygdala and anterior hippocampus ROIs are therefore de-
scribed side by side.
The averaged percent signal change was obtained for each
region and analyzed within each valence type. The rationale
behind this approach is to compare ‘‘physically identical’’ stimuli
Figure 2. Behavioral study. The emotional properties of the various clips were rated in terms of valence (A--C) and arousal (D--F), n 5 15. Valence was rated on a scale of þ5(positive) to�5 (negative). Arousal was rated on a scale of 0 (nonarousing) to 10 (highly arousing). The clips were also rated in terms of their concrete content (E--G) on a scale of0 (not concrete) to 10 (very concrete), n5 9. Note that the combinations and the music clips on their own were rated similarly in their emotional properties but differently in theirconcrete content. Error bars represent standard error of mean. *P\ 0.05, **P\ 0.00001, and ns, nonsignificant.
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within each subject (see Materials and Methods for more details
and Supplemental note 1 for further discussion). In both the
amygdala and anterior hippocampus, response was greater
during the negative combinations than during both films and
negative music clips separately (Fig. 3A,B). This effect is also
evident in statistical parametric maps obtained for the separate
and combined film and negative music (Fig. 4). The positive
conditions elicited a similar effect only in the amygdala ROI
(Fig. 3A). In contrast, for the neutral control condition, both the
amygdala and hippocampus did not show additional activity in
response to the combination compared with the film clips
alone. Thus, additional activation was obtained only when the
music provided an emotional theme to the film and not simply
because of salient simultaneous processing of music and film.
Moreover, this occurs despite the fact that neither the amygdala
nor the anterior hippocampus was differentially responsive to
emotional music by itself (see Fig. 3). As verified in the
preceding behavioral study (Fig. 2), the combination of film
and emotional music did not differ from the samemusic alone in
the emotional properties of valence and arousal, assuring that
the addition of film did not affect ‘‘emotionality’’; rather, it added
‘‘concrete content.’’ Hence, it is demonstrated that manipulating
associated content and emotions can modulate both amygdalar
and hippocampal activities. For an additional analysis confirming
that the selective response to the combined film and music
conditions does not stem from a different response to the film-
alone condition, see Supplemental note 2. A further comparison
between the combination and the summation of the separate
conditions was attempted and yielded no statistically significant
results. It is presumed that the lack of significance is due to
Figure 3. Limbic ROIs. Averaged activations during the combined and separate music and film in the amygdala (A) and anterior hippocampus (B). The ROIs in the right and lefthemispheres did not significantly differ in the contrast of interest and are presented together. Error bars represent standard error of mean. *P\0.05 and ns, nonsignificant; n5 12.The amygdala and the anterior hippocampus ROIs are delineated on an axial section (C). The ROIs were anatomically marked out of a general functional cluster that was obtained bythe contrast of all the combination conditions versus baseline (P\ 0.005, uncorrected, fixed effect) (see Materials and Methods).
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great signal variance in the indicated ROIs, but it may also reflect
the neural mechanism of integration, which is not necessarily
a linear summation of the separate conditions.
We then asked whether the mere combination of film and
music affects not only the level of activity in the amygdala and
hippocampus but also the synchronization between them. The
time courses of activation of the amygdala and anterior
hippocampus ROIs (Fig. 3C) showed a statistically significant
correlation during all conditions. However, a borderline signif-
icant increase in correlation (P < 0.055) was found between the
right amygdala and hippocampus when the film and negative
music were combined compared with the correlation during
the separate film and music (Fig. 5). In contrast, no increase in
correlation was found during the neutral and positive combi-
nations compared with the separate film and music. These
results suggest that the functional association of the amygdala
and the hippocampus was selectively strengthened when
a negative emotion was integrated with concrete content.
Emotion and Content at the Prefrontal Level
The PFC ROI was defined as all voxels within the PFC that were
activated by all the conditions of combined films and music (see
Materials and Methods). The PFC ROI encompassed some
heterogeneous areas in the lateral aspect of the PFC, including
Brodmann areas 9, 45, 46, and 47 (Fig. 6B). Despite its
recognized role in emotional processing, no significant activa-
tions were obtained in the medial PFC (Brodmann areas 10, 11,
12, 25, and 32). However, this negative finding should be
interpreted with caution because relatively low BOLD signals
were obtained in most subjects from medial prefrontal areas
that may indicate on susceptibility artifacts. The fact that the
tasks in our paradigm were all implicit may also contribute to
Figure 4. Activity in response to the combined and separate conditions. Activations obtained for the film condition (A), negative combination condition (B), and negative musiccondition (C) compared with baseline (P\ 0.002, uncorrected, random effects analysis, n 5 12). Talairach coordinates x 5 43, y 5 �13, z 5 �17.
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the diminished activation of the medial PFC, a region known for
its part in explicit tasks such as appraisal (Bechara et al. 1999).
Averaged activation in the lateral PFC ROI demonstrated
enhanced activity in response to the negative and positive
combination conditions in comparison with the film and music
alone (Fig. 6A). This effect is also evident in statistical para-
metric maps obtained for the separate and combined film and
negative music (Fig. 4). In contrast, no additional activity was
found in response to the neutral combination in comparison
with the film or music on their own. Hence, it was the
combination of a concrete visual scene with ‘‘emotional’’ music
that preferentially activated the lateral PFC. These results
suggest that the lateral PFC is involved in associating concrete
content about the world with abstract emotions.
A Neural Network that Integrates Emotions and
Concrete Content
We next set out to isolate, with no a priori hypothesis, a network
of regions that selectively mediate emotions with concrete
content (elicited by the combination of music and films) but are
not involved in processing abstract emotions or concrete
content by themselves (elicited by the separate music and
films, respectively). A 2-step whole-brain analysis first identified
clusters of activation whose activity was significantly higher in
response to the combination than in response to the separate
conditions. Then, using a masking procedure, only those
clusters that responded exclusively to the combination (and
not to the separate conditions) were isolated (see Materials and
Methods).
For the negative conditions, such combination-specific clus-
ters were obtained in a number of regions including the right
amygdala, right hippocampus, middle and inferior frontal gyri,
and lateral temporal regions (Table 1, negative combination
effect). For the positive conditions, combination-specific clus-
ters were seen in similar frontal and lateral temporal areas
(Table 1, positive combination effect). Combination-specific
clusters were much fewer for the neutral conditions and in
areas distinct from those found for the negative and positive
conditions (Table 1, neutral combination effect). Thus, it seems
that this distinct network of regions, which includes our a priori
hypothesized ROIs, participates in processing a property that is
unique to the combined emotional music and film and not
present in each alone, namely, an emotion with a concrete real
world--based content.
Figure 5. Time course correlation between the right amygdala and hippocampusROIs. Linear correlation between the BOLD signal of the right amygdala and anteriorhippocampus during the separate and combined conditions. Averaged correlationcoefficients were compared between the separate and combined conditions, witha paired t-test. Resulting with a t value of 1.73 between film and combo coefficientsand a t value of 2.0 between music and combo coefficients. Error bars representstandard error of mean. *P\ 0.055, n 5 12.
Figure 6. Prefrontal ROI. Averaged activations during the combined and separatemusic and films (A). The ROIs in the right and left hemispheres did not differ in thecontrast of interest and are presented together. Error bars represent standard error ofmean. *P\ 0.05, **P\ 0.001, ns, nonsignificant; n 5 12. The prefrontal ROI isdelineated on sagittal and axial sections. (B) The ROIs were anatomically marked out ofa general functional cluster that was obtained by the contrast of all combinationconditions versus baseline (P\ 0.005, uncorrected, fixed effect).
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Emotion and Content at the Sensory Level
A linkage between emotions and representations of the external
world may begin already at the sensory level of processing.
Indeed, previous imaging studies have shown modulation of
activity in visual regions by the emotional valence of visual
stimuli, and such modulation was shown to be mediated by the
amygdala (Rotshtein et al. 2001; Phan et al. 2002; Vuilleumier
et al. 2004). However, most of these studies have not manipu-
lated emotions independently of their visual content.
We examined whether high-order sensory areas are also
involved in the association of abstract emotions with concrete
scenes by ROI analysis that was applied to high-order visual
areas. Areas that were previously shown to be modulated by
emotion include the LOC, the FFA, and the PPA. The PT, which
is thought to constitute the secondary auditory cortex
(Shapleske et al. 1999), was analyzed as the auditory ROI. As
expected, the high-order visual areas showed a preference for
visual stimuli but no additional activation when music was
added to the film. No significant difference was found between
the different visual ROIs, and so only results from the LOC ROI
are presented (Fig. 7A). As a mirror image, the PT showed
a preference for auditory stimuli, with equal or even diminished
activation when film was added (Fig. 7B). Thus, no additional
activity was found in response to the combination of music and
film in the sensory ROIs.
To examine whether this result was produced due to our
specific choice of sensory regions, we performed a whole-brain
analysis using the contrast of [positive combination + negative
combination > same films without music] in all the regions that
were activated by films on their own (P < 0.05, uncorrected,
random effects analysis). This contrast isolates all visually
responsive clusters that demonstrated increased activity in
response to the addition of emotional music. No significant
activations were found at a threshold of P < 0.002 (uncorrected,
random effects analysis). Thus, our data do not demonstrate
emotional modulation of high-order visual areas. This is not
surprising because we did not manipulate the emotional
content of the visual stimuli; we manipulated emotions in-
dependently of their visual content.
Discussion
Using a novel cross-modal approach with emotional music and
neutral film clips, we were able to demonstrate selective brain
responses to musical emotions depending on the presence of
concrete contents conveyed by films. In both ROI and whole-
brain analyses, the amygdala, the anterior hippocampus, and the
lateral PFC exhibited additional activity in response to the
combination of negative music and neutral film clips compared
with the same clips presented separately. Interestingly, these
regions, including the amygdala, were not activated selectively
by emotionality in music when presented without a film. These
findings strongly suggest that the brain exerts a preferential
response to emotional stimuli when these are associated with
concrete content. The cognitive approach in affective science
defines emotions as evaluations of events in the world that guide
adaptive behavior. It thus predicts that emotions are processed
together with the contextual representations they refer to
(Lazarus 1991). The present findings demonstrate that even in
the amygdala, a core region of the limbic system, emotional
processing is closely linked to its associated content.
Integrative Emotional Processing in Limbic Areas:Associated Content and Valence
In line with numerous neuroimaging studies (Blood et al. 1999;
Levitin and Menon 2003; Schmithorst and Holland 2003), music
in the present study elicited no activity above baseline in the
amygdala when presented on its own. A few studies have shown
increased or decreased amygdalar response to emotional music
(Koelsch et al. 2006; Blood and Zatorre 2001, respectively).
However, in these studies, the selective responses were elicited
by comparing types of music and not by contrasting the
unpleasant condition to baseline and may therefore reflect
a differential amygdalar response to the music itself rather than
sensitivity to emotionality in music. Our results may also appear
to conflict with a study by Gosselin et al. (2005), in which
patients with medial temporal lesions were impaired in emo-
tional recognition of fear elicited by music presented alone,
leading to the conclusion that the amygdala plays a role in the
recognition of danger in a musical context. However, although
the impairment was attributed to a damaged amygdala, the
lesions that were studied consistently encompassed extensive
temporal and paralimbic regions, including the parahippocam-
pal gyrus, an area previously implicated in emotional processing
of music (Blood et al. 1999).
Strikingly, in our study, the same emotional music clips that
did not elicit an amygdalar response when presented on their
own did evoke a significant additional effect in the amygdala
when combined with neutral film clips. To explain this finding,
one might suggest that the amygdala is more sensitive to
emotional stimuli associated with visual input (Phan et al.
2002). This claim corresponds with evidence in primates of
widespread anatomical projections from the amygdala to
virtually all levels of the visual cortex (Amaral et al. 1992) as
Table 1Combination-specific clusters
Region x y z Clustersize
Averaget value
Negative combination effectRight amygdala (anterolateral portion) 26 �2 �17 6 4.81Right hippocampus (anterior portion) 23 �11 �18 7 4.28Right middle frontal gyrus (BA 9) 47 16 34 2 4.10Right inferior frontal gyrus (BA 47) 32 38 �9 3 4.08Left anterior superior temporal gyrus (BA 38) �49 8 �9 11 4.53Left middle temporal gyrus (BA 37) �37 �57 3 12 5.20Right inferior temporal gyrus (BA 37) 51 �56 �15 14 4.29Left fusiform gyrus (BA 37) �46 �44 �20 7 4.29Left posterior cerebellar lobe �1 �67 �18 4 4.57Right posterior cerebellar lobe 26 �61 �21 10 4.64
Positive combination effectRight inferior frontal gyrus (BA 47) 41 22 �8 8 4.40Right middle frontal gyrus (BA 11) 29 34 �6 8 4.67Left middle cingulate gyrus (BA 31) �10 �13 36 14 4.49Right temporal pole (BA 38) 47 20 �15 5 5.16Right superior temporal gyrus (BA 22) 50 14 �3 9 4.68Right posterior superior temporal sulcus (BA 22) 62 �20 0 2 4.60Right middle temporal gyrus (BA 21) 62 �38 �6 8 4.26Right inferior temporal gyrus (BA 21) 59 �29 �9 5 4.37Left cerebellum/inferior temporal gyrus (BA 37) �49 �62 �18 4 4.16Left superior colliculi �7 �32 �4 34 4.81Midbrain �3 �26 �3 2 4.46
Neutral combination effectRight Inferior frontal gyrus (BA 45) 45 25 18 2 4.43Left lingual gyrus (BA 19) �13 �59 0 2 4.54Left posterior cerebellar lobe �7 �68 �15 3 4.46
Note: Clusters activated in a conjunction analysis of [combination[ film] and [combination[music] within an inclusive masking map obtained by [combination[ baseline] and not within
exclusive masking maps obtained by [film[ baseline] and [music[ baseline]. P\ 0.002,
random effects analysis, without correction for multiple comparisons. x, y, z 5 Talairach
coordinates of cluster center. BA, Brodmann area.
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well as with numerous neuroimaging studies in humans
showing close relations between activation in the amygdala
and high-order visual areas (e.g., Rotshtein et al. 2001; Bleich-
Cohen et al. 2006). On the other hand, imaging studies showed
that the human amygdala was activated during anticipation of
outcome following risky choices in a computerized game,
regardless of the external stimuli (Kahn et al. 2002). Moreover,
extensive evidence from animal lesion studies supports the role
of the amygdala in processing affective auditory information in
a conditioning context (LeDoux 2000). Similarly, several human
imaging studies have shown amygdalar activations in response
to affective auditory stimuli such as unpleasant words, laughter,
and crying (Sander and Scheich 2001; Maddock et al. 2003;
Sander et al. 2003). Altogether, these various data make the
possibility that the amygdala only processes information con-
veyed by external visual modality very unlikely.
In light of these previous studies, our results point to another
possibility whereby amygdala’s activation may be driven by the
emotion-related perceptual content of a stimulus that deter-
mines the goal of action in the world. In all the aforementioned
studies that report amygdalar activation, the emotion studied by
various modalities had a ‘‘concrete and immediate meaning,’’
related to approach or withdrawal behavior. A fearful face,
a fearful voice, a conditioned stimulus, and a risky choice: these
can all signal concrete and immediate danger; a recalled
emotion or unfamiliar music alone cannot. The amygdala is
a relatively primitive neural structure that has undergone little
change throughout mammalian evolution (LeDoux 2000). It
thus makes sense that its role may be specific for processing
emotions that have a clear adaptive survival value. Accordingly,
in the present experiment, an emotion that refers to real-world
content (elicited by the combination of music and film) yielded
Figure 7. Sensory ROIs. Averaged activation during the combined and separate music and films in the LOC (A) and PT (C) ROIs. The right and left ROIs did not significantly differ inthe contrast of interest and are presented together. Error bars represent standard error of mean. *P\0.05, **P\0.001, ns, nonsignificant; n5 12. The LOC (B) and PT (D) ROIsare delineated on sagittal and axial sections (see Materials and Methods). The ROIs were all anatomically marked based on its own reported Talairach coordinates.
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amygdalar response, even though emotionality was conveyed
through an abstract music. Finally, Seifritz et al. (2003) showed
that the sound of infants crying does not elicit amygdalar
activation in nonparents, but does so in parents, and so the
authors claimed that parenthood causes neuroplastic changes
in the brain. We suggest that parenthood alters the interpreta-
tion of the sound of infants crying and gives it concrete and
immediate subjective emotional meaning. Similarly, in a recent
neuroimaging study, it was shown that the amygdala was more
active with closed than open eyes in the dark while subjects
were listening to the same emotional music (Lerner et al. 2005).
This finding suggests that concrete and immediate emotional
meaning is not necessarily dependent on external cues but
rather can be elicited by focusing on the self-oriented world.
That said, it has to be mentioned that our ROI analysis was
limited to those regions of the amygdala that reacted to the
combination of music and film. It is quite possible that these
regions primarily carry out an integrative processing role,
whereas other regions in the amygdala have a more confined,
abstract emotional processing role.
Like the amygdala, the anterior hippocampus also demon-
strated increased activations to negative emotional music when
combined with neutral films in comparison with emotional
music alone. Whereas the amygdala has been implicated in
emotional processing (LeDoux 2000), the hippocampus has
been implicated in processing spatial representations and
episodic memories (Burgess et al. 2002). Also, it seems that
both the amygdala and hippocampus have access to conceptual
information about the world, as a large proportion of their
neurons selectively responds to category-specific stimuli as
shown by single-cell recordings in humans (Kreiman et al.
2000). Moreover, the amygdala and the hippocampus were
suggested to play complementary roles in binding emotional
memories to contextual cues in fear conditioning (Phelps
2004). Our results extend previous findings in showing that
even when emotionality remains unchanged, emotion-related
episodic information by itself (provided by the film) modulates
amygdalar activity. Furthermore, without a concrete visual
scene, an abstract musical emotion elicited no amygdalar
response, suggesting that reference to concrete meaning may
be necessary for amygdalar emotional processing. Finally,
correlation of right amygdalar and hippocampal activities was
significantly increased when film and negative music were
combined. We thus propose that grounding of an abstract
emotion in the concrete world primarily involves the amygdala,
the hippocampus, and the interaction between them. We
cannot ignore a possible ROI overlap between those 2 anatom-
ically neighboring regions. That said, it has to be remembered
that the increase in correlation was found only for the
combined condition of the negative emotional valence. If the
correlation was a result of overlaps, we would not have seen
such valence-dependent differences in correlation levels.
The results of the present study regarding the amygdala and
the hippocampus proved to be more consistent for negative
emotions than for positive ones. No increase in response to the
positive combination was found in the hippocampus. Also, the
correlation of activity between the amygdala and the hippo-
campus was not significantly increased during the positive
combination compared with the neutral one. Finally, no clusters
of activation were found in limbic regions for the positive
conditions in the whole-brain analysis. These results are
consistent with previous literature that mainly links the
amygdala to negative emotions such as fear (Phan et al. 2002).
However, various studies also link the amygdala to appetitive
emotions such as sexual arousal, which are usually considered
positive (Beauregard et al. 2001; Hamann et al. 2004). It thus
seems that the amygdala does not specifically process negative
or positive emotions, but rather, as suggested above, emotions
related to an immediate behavioral response, such as approach
or withdrawal. In the present experiment, scary and joyful
music clips were used to induce negative and positive emotions,
respectively. Clearly, fear is more directly related to an
immediate behavioral response than joy, which may account
for the more consistent response that the limbic system shows
to films coupled with emotionally negative music in our study.
Several caveats to the finding in the amygdala should be
noted. First, it cannot be excluded that the subjects in the fMRI
study did experience stronger emotions while viewing the
music and film together in comparison with the separate
conditions. However, given that in the stimulus judgment
experiment subjects reacted similarly, in terms of both valence
and arousal, to the combined and separate conditions, we
believe this to be unlikely (see Fig. 1). Second, it can also be
claimed that the increased amygdalar response to the combi-
nation is an effect of salience. The combination of music and
film might be more salient than each on its own and thus evoke
a greater brain response. What stands against this interpretation
is the fact that the combination of film and neutral music did not
produce an increased response; rather, an increased response
was obtained only when the film was combined with music that
attributed an emotional tone to it. Third, it can be noted that the
lack of increased amygdalar response to the neutral combina-
tion is at least partially a result of an increased response to the
neutral film on its own when compared with the films that were
combined with negative or positive music. As the different film
conditions consist of different films shown to different subjects,
the differential response most probably represents individual
variability. In fact, all between-valence comparisons in the
present study suffer from the same variability, and none of
them show statistically significant effects. Therefore, the most
reliable way of analyzing the data is by comparing the different
conditions only within valence. Using this method, a significant
effect was obtained in the amygdala only for the negative and
positive combinations and not for the neutral combination.
Fourth, although the music clips were generally not familiar to
the subjects (as most of them were composed in-house), we
must consider that familiarity could have made the combination
appear less novel and novelty could have affected the amygdalar
response.
Integrative Emotional Processing in the outside limbicregions: Flexibility and Specificity
Similar to the amygdala and hippocampus, lateral prefrontal and
lateral temporal regions were implicated in the integration of
emotions and concrete content (see Table 1). What, then, is
their additional contribution? The present study cannot distin-
guish between the different possible roles that these regions
may have in emotional processing. Nevertheless, based on these
results and previous research, a sensible model can be pro-
posed. One property that the amygdala by itself seems to lack is
flexibility in stimulus--response associations. This was first
proposed by Morgan et al. (1993) who showed that extinction
of fear-conditioned stimulus--response associations, whose
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formation depends on the amygdala, became difficult after
medial PFC damage. Unlike the amygdala, routine or automatic
responses do not usually engage the lateral PFC, and its primary
role is thought to be in enabling flexibility of stimulus-response
associations (Fuster 2001; Miller and Cohen 2001). It is
therefore reasonable that PFC’s role in emotional processing is
enabling flexible associations or responses between content
and emotional tone.
Another property that the amygdala lacks is specificity to
a particular stimulus type. As suggested by Ledoux, it seems that
processing in the amygdala level is done in a relatively crude
manner. For example, whereas fear conditioning of an auditory
stimulus depends on an intact amygdala, the specificity of the
fear response to a distinct tone (and not to other similar sounds)
might depend on intact auditory cortex (Jarrell et al. 1987;
LeDoux 2000). Also, human amygdalar and hippocampal neu-
rons do not discriminate between particular cases of a general
category, such as different houses or different faces (Kreiman
et al. 2000). In contrast, lateral temporal regions have been
suggested to facilitate processing of particular object concepts,
following a posterior--anterior axis of increasingly specific
representations, from the broader category level (i.e., faces in
general) to the particular object (i.e., Michael Jordan’s face)
(Martin and Chao 2001). Thus, it is possible that lateral temporal
regions, such as the superior temporal sulcus and the temporal
pole, mediate the tying of emotion to representations of
particular objects, people, or situations.
Modality Selectivity in Integrative Emotional Processing
Our cross-modal approach provided a unique platform for
studying modality selectivity in emotional processing. The visual
cortex did not show increased activation in response to the
combination of auditory emotional stimuli and visual scenes.
Furthermore, statistical parametric maps contrasting the emo-
tional combinations with films alone revealed no emotional
modulation effect in visual regions. This is in contrast to
previous studies that have shown modulation of high-order
visual regions by emotion (Rotshtein et al. 2001; Phan et al.
2002; Vuilleumier et al. 2004). However, the present study
differs from these previous studies in that the emotional
character of the visual stimuli in the combination was conveyed
through a different modality, suggesting that emotion modu-
lates sensory processing only within the same modality through
which it is conveyed. Still, this finding seems to conflict with
those of Dolan et al. (2001), which show that emotionally
congruent compared with emotionally incongruent visual and
auditory stimuli yield enhanced fusiform response. However,
this enhanced response may reflect an inhibition that results
from incongruence and not enhancement due to congruency,
similar to the inhibitory effect that asynchronous audiovisual
speech has in visual areas (Calvert et al. 2001). A trend toward
decreased activation of sensory regions during multimodal
conditions can also be observed in our data (Fig. 7). It is also
possible that emotional modulation occurs only in category-
specific visual regions during processing of stimuli from that
category (e.g., faces in the FFA); as our visual stimuli were not
specific to one category, an emotional modulation effect could
have been diluted.
Interestingly, the auditory cortex showed a significantly de-
creased response to the negative and neutral music when they
were combined with film clips. This is in line with the findings
of Bushara et al. (2002) which showed that cross-modal binding
of sound and sight involves decreased activation of unimodal
auditory and visual areas coupled with increased activation of
multimodal areas. On the other hand, Armony and Dolan (2000)
showed that emotional visual context can increase auditory
cortex response. However, in their study, context was not
manipulated independently of emotion but rather used to elicit
it. Therefore, it is possible that it was the resulting emotionality,
and not visual context per se, that modulated auditory cortex
activity. Further research is needed to clarify the ways through
which integration of multimodal information conveying emo-
tionality and context involves unimodal sensory areas.
Cross-Modal Approach in Affective Neuroscience
So far, cross-modal methodology has proven successful mostly
in locating sites of integration of perceptual information, such as
the anterior superior temporal sulcus for audiovisual speech
perception (Wright et al. 2003) and the intraparietal sulcus for
spatial location (Nobre et al. 1997). We believe that the
potential of cross-modal methodology is far greater, in that it
offers an effective way for studying conceptual functions.
Mesulam (1998) proposed that high cognitive functions in-
variably involve sites of multimodal convergence. Accordingly,
Booth et al. (2002) used a conjunction of visual and auditory
stimuli to isolate multimodal regions that are involved in
semantic decoding. Following this line of thought, we took
the basic, commonly used, cross-modal paradigm and extended
it. As done before, stimuli in 2 modalities were presented
separately and combined, but instead of having the 2 modalities
convey the same conceptual information, here the whole
concept emerges only in the combination. An emotion with
concrete meaningful content is only evoked when the film and
music are combined. The benefits of such a design are sub-
stantial. First, a specific conceptual function is isolated from
underlying processes as it is only elicited when the 2 modalities
are combined. Second, the perceptual features of the stimuli are
afforded the ultimate control—identical film and music clips
were contrasted in the separate and the combined conditions.
Finally, stimuli that are lively, animated, dynamic, and complex
like music and films can be used in a strictly controlled
experiment addressing a specific hypothesis.
In conclusion, the current study exhibits a possible neural
basis for the known contingency between emotion and cogni-
tion in humans, keeping in mind that in this study, cognition was
confined to perceptual-associated content. Animals and humans
share the same basic set of emotions, including emotions such
as fear, joy, or sadness (Darwin 1998). However, human
cognitive abilities have become extremely sophisticated and
involved in all aspects of behaviors including emotions. With
such developed cognition, emotions no longer seem like
meaningless forces that overrule all other aspects of behavior.
For instance, the human phenomenon of anxiety is not merely
an emotional expression of fear but rather the maladaptive
interpretation associated with the fear in regard to occurrences
in the world (Kaplan and Sadock 1998). Freud has proposed that
in order to overcome melancholy, one needs to understand its
real-world context so that mourning and resolution can take
place (Freud 1957). Indeed, in the process of treating emotional
problems, psychotherapy often focuses on grounding emotions
in the real world of interpersonal relations. The current finding
that associated content modulates neural activity even at the
2838 Feeling the Real World d Eldar et al.
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heart of the emotional brain adds support to the fundamental
role of real-world content in processing emotions.
Supplementary Material
Supplementary materials can be found at: http://www.cercor.
oxfordjournals.org/.
Notes
This study was funded by the Israeli Science Foundation (Bikura
Program 1440/04, TH), the Israeli Ministry of Science and Sport. We
thank Dr. Pazit Pianka for assistance during data acquisition, Dr. Arnon
Neufeld and Mr. Oren Levin for technical assistance with data
acquisition, Dr. Itamar Kahn for most insightful discussions over the
data, Dr. Ricardo Tarrasch for statistical assistance, Dr. David Papo for
comments on the manuscript, and Ms. Nirit Binyamini for assistance
with the graphics.
This work was done in cooperation with the Levi Edersheim Gitter
Institute for Functional Brain Imaging, Tel Aviv University.
This work was performed in partial fulfillment of the MD thesis
requirements of the Sackler Faculty of Medicine, Tel Aviv University.
Conflict of Interest: None declared.
Address correspondence to Talma Hendler, Tel Aviv Sourasky Medical
Center, 6 Weizmann Street, Tel Aviv 64239, Israel. Email: talma@
tasmc.health.gov.il.
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