limbic response to music

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

Cerebral Cortex December 2007;17:2828--2840

doi:10.1093/cercor/bhm011

Advance Access publication March 29, 2007

� The Author 2007. Published by Oxford University Press. All rights reserved.

For Permissions, please email: [email protected]

by guest on February 27, 2014http://cercor.oxfordjournals.org/

Dow

nloaded from

http://cercor.oxfordjournals.org/


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).

Cerebral Cortex December 2007, V 17 N 12 2829


Dow

nloaded from



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

2830 Feeling the Real World d Eldar et al.


Dow

nloaded from



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.



Dow

nloaded from



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).



Dow

nloaded from



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.



Dow

nloaded from



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).



Dow

nloaded from



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.



Dow

nloaded from



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.



Dow

nloaded from



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



Dow

nloaded from



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



Dow

nloaded from



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.

References

Adolphs R, Gosselin F, Buchanan TW, Tranel D, Schyns P, Damasio AR.

2005. A mechanism for impaired fear recognition after amygdala

damage. Nature. 433:68--72.

Amaral DG, Price JL, Pitkanen A, Carmichael ST. 1992. Anatomical

organization of the primate amygdaloid complex. In: Aggleton W,

editor. The amygdala: neurobiological aspects of emotion, memory

and mental dysfunction memory and mental dysfunction. New York:

Wiley-Liss. p. 1--66.

Armony JL, Dolan RJ. 2000. Modulation of auditory neural responses

by a visual context in human fear conditioning. Neuroreport.

12:3407--3411.

Bachevalier J, Malkova L. 2006. The amygdala and development of social

cognition: theoretical comment on Bauman, Toscano, Mason,

Lavenex, and Amaral. Behav Neurosci. 120(4):989--991.

Barbas H. 2000. Connections underlying the synthesis of cognition,

memory, and emotion in primate prefrontal cortices. Brain Res Bull.

52:319--330.

Beauregard M, Levesque J, Bourgouin PJ. 2001. Neural correlates of

conscious self-regulation of emotion. J Neurosci. 21:1--6.

Bechara A, Damasio H, Damasio AR, Lee GP. 1999. Different contribu-

tions of the human amygdala and ventromedial prefrontal cortex to

decision-making. J Neurosci. 19:5473--5481.

Bleich-Cohen M, Mintz M, Pianka P, Andelman F, Rotshtein P, Hendler T.

2006. Differential stimuli and task effects in the amygdala and

sensory areas. Neuroreport. 17(13):1391--1395.

Blood AJ, Zatorre RJ. 2001. Intensely pleasurable responses to music

correlate with activity in brain regions implicated in reward and

emotion. Proc Natl Acad Sci USA. 98:11818--11823.

Blood AJ, Zatorre RJ, Bermudez P, Evans AC. 1999. Emotional responses

to pleasant and unpleasant music correlate with activity in para-

limbic brain regions. Nat Neurosci. 2:382--387.

Boltz MG. 2001. Musical soundtracks as a schematic influence on the

cognitive processing of filmed events. Music Perception.

18:427--454.

Booth JR, Burman DD, Meyer JR, Gitelman DR, Parrish TB, Mesulam MM.

2002. Modality independence of word comprehension. Hum Brain

Mapp. 16:251--261.

Burgess N, Maguire EA, O’Keefe J. 2002. The human hippocampus and

spatial and episodic memory. Neuron. 35:625--641.

Bushara KO, Hanakawa T, Immisch I, Toma K, Kansaku K, Hallett M.

2002. Neural correlates of cross-modal binding. Nat Neurosci.

6:190--195.

Calvert GA, Hansen PC, Iversen SD, Brammer MJ. 2001. Detection of

audio-visual integration sites in humans by application of electro-

physiological criteria to the BOLD effect. Neuroimage. 14:427--438.

Clore GJ, Ortony A. 2000. Cognition in emotion: always, sometimes, or

never? In: Lane RD, Nadel L, Ahern GL, Allen JJB, Kaszniak AW,

Rapcsak SZ, Schwartz GE, editors. Cognitive neuroscience of

emotion. New York: Oxford University Press. p. 24--61.

Cohen AJ. 2001. Music as a source of emotion in film. In: Juslin PN,

Sloboda JA, editors. Music and emotion. New York: Oxford Univer-

sity Press. p. 249--272.

Darwin C. 1998. The expression of the emotions in man and animals. 3rd

ed. New York: Oxford University Press.

Dolan RJ, Morris JS, de Gelder B. 2001. Crossmodal binding of fear in

voice and face. Proc Natl Acad Sci USA. 98:10006--10010.

Epstein R, GrahamKS, Downing PE. 2003. Viewpoint-specific scene repre-

sentations in human parahippocampal cortex. Neuron. 37:865--876.

Faw B. 2003. Pre-frontal executive committee for perception, working

memory, attention, long-term memory, motor control, and thinking:

a tutorial review. Conscious Cogn. 12:83--139.

Freud S. 1957. Mourning and melancholia. In: Strachey J, editor and

translator. The standard edition of the complete psychological works

of Sigmund Freud, Vol. 14. London: Hogarth Press. p. 152--170

[Original work published in 1917].

Fuster JM. 2001. The prefrontal cortex—an update: time is of the

essence. Neuron. 30:319--333.

Gosselin N, Peretz I, Noulhiane M, Hasboun D, Beckett C, Baulac M,

Samson S. 2005. Impaired recognition of scary music following

unilateral temporal lobe excision. Brain. 128:628--640.

Grill-Spector K, Kushnir T, Edelman S, Avidan G, Itzchak Y, Malach R.

1999. Differential processing of objects under various viewing condi-

tions in the human lateral occipital complex. Neuron. 24:187--203.

Hamann S, Herman RA, Nolan CL, Wallen K. 2004. Men and women differ

in amygdala response to visual sexual stimuli. Nat Neurosci.

7:411--416.

Jarrell TW, Gentile CG, Romanski LM, McCabe PM, Schneiderman N.

1987. Involvement of cortical and thalamic auditory regions in

retention of differential bradycardiac conditioning to acoustic

conditioned stimuli in rabbits. Brain Res. 412:285--294.

Kahn I, Yeshurun Y, Rotshtein P, Fried I, Ben-Bashat D, Hendler T. 2002.

The role of the amygdala in signaling prospective outcome of choice.

Neuron. 33:983--994.

Kanwisher N, McDermott J, Chun MM. 1997. The fusiform face area:

a module in human extrastriate cortex specialized for face percep-

tion. J Neurosci. 17:4302--4311.

Kaplan HI, Sadock BJ. 1998. Synopsis of psychiatry. 8th ed. Baltimore

(MA): Lippincott. p. 581--628.

Koelsch S, Fritz T, v.Cramon DY, Muller K, Friederici AD. 2006.

Investigating emotion with music: an fMRI study. Hum Brain Mapp.

27(3):239--250.

Kreiman G, Koch C, Fried I. 2000. Category-specific visual responses of

single neurons in the human medial temporal lobe. Nat Neurosci.

3:946--953.

Lang PJ, Greenwald MK, Bradley MM, Hamm AO. 1993. Looking at

pictures: affective, facial, visceral and behavioral reactions. Psycho-

physiology. 30:261--273.

Lazarus RS. 1991. Cognition and motivation in emotion. Am Psychol.

46:352--367.

LeDoux JE. 2000. Emotion circuits in the brain. Annu Rev Neurosci.

23:155--184.

Lerner Y, Ganor O, Eldar E, Hendler T. 2005. Emotion in the dark:

auditory-related valence processing in the human brain depends on

visual input. Soc Neurosci. Program No. 935.5.

Levitin DJ, Menon V. 2003. Musical structure is processed in ‘‘language’’

areas of the brain: a possible role for Brodmann area 47 in temporal

coherence. Neuroimage. 20:2142--2152.

Lipscomb SD, Kendall RA. 1994. Perceptual judgment of the relationship

between musical and visual components in film. Psychomusicology.

13:60--98.

Maddock RJ, Garrett AS, Buonocore MH. 2003. Posterior cingulate

cortex activation by emotional words: fMRI evidence from a valence

decision task. Hum Brain Mapp. 18:30--41.



Dow

nloaded from

http://www.cercor.oxfordjournals.org/

http://www.cercor.oxfordjournals.org/



Martin A, Chao LL. 2001. Semantic memory and the brain: structure and

process. Curr Opin Neurobiol. 11:194--201.

Mesulam MM. 1998. From sensation to cognition. Brain. 121:1013--1052.

Miller EK, Cohen JD. 2001. An integrative theory of prefrontal cortex

function. Annu Rev Neurosci. 24:167--202.

Morgan MA, Romanski LM, LeDoux JE. 1993. Extinction of emotional

learning: contribution of medial prefrontal cortex. Neurosci Lett.

163(1):109--113.

Nobre AC, Sebestyen GN, Gitelman DR, Mesulam MM, Frackowiak RS,

Frith CD. 1997. Functional localization of the system for visuo-

spatial attention using positron emission tomography. Brain. 120:

515--533.

Perlstein WM, Elbert T, Stenger VA. 2002. Dissociation in human

prefrontal cortex of affective influences on working memory-related

activity. Proc Natl Acad Sci USA. 99:1736--1741.

Pessoa L, Padmala S, Morland T. 2005. Fate of unattended fearful faces in

the amygdala is determined by both attentional resources and

cognitive modulation. Neuroimage. 28:249--255.

Phan KL, Wager TD, Taylor SF, Liberzon I. 2002. Functional neuroanat-

omy of emotion: a meta-analysis of emotion activation studies in PET

and fMRI. Neuroimage. 16:331--348.

Phelps EA. 2004. Human emotion and memory: interactions of

the amygdala and hippocampal complex. Curr Opin Neurobiol.

14:198--202.

Rotshtein P, Malach R, Hadar U, Graif M, Hendler T. 2001. Feeling or

features: different sensitivity to emotion in high-order visual cortex

and amygdala. Neuron. 32:747--757.

Sander K, Brechmann A, Scheich H. 2003. Audition of laughing and

crying leads to right amygdala activation in a low-noise fMRI setting.

Brain Res Brain Res Protoc. 11:81--91.

Sander K, Scheich H. 2001. Auditory perception of laughing and crying

activates human amygdala regardless of attentional state. Brain Res

Cogn Brain Res. 12:181--198.

Schmithorst VJ, Holland SK. 2003. The effect of musical training on

music processing: a functional magnetic resonance imaging study in

humans. Neurosci Lett. 348:65--68.

Seifritz E, Esposito F, Neuhoff JG, Luthi A, Mustovic H, Dammann G,

von Bardeleben U, Radue EW, Cirillo S, Tedeschi G, et al. 2003.

Differential sex-independent amygdala response to infant crying and

laughing in parents versus non-parents. Biol Psychiatry. 54:

1367--1375.

Shapleske J, Rossell SL, Woodruff PW, David AS. 1999. The planum

temporale: a systematic, quantitative review of its structural, func-

tional and clinical significance. Brain Res Brain Res Rev. 29:26--49.

Talairach J, Tournoux P. 1988. Co-planar stereotaxic atlas of the human

brain. New York: Thieme.

Vuilleumier P, Richardson MP, Armony JL, Driver J, Dolan RJ. 2004.

Distant influences of amygdala lesion on visual cortical activation

during emotional face processing. Nat Neurosci. 7:1271--1278.

Westbury CF, Zatorre RJ, Evans AC. 1999. Quantifying variability in the

planum temporale: a probability map. Cereb Cortex. 9:392--405.

Wright TM, Pelphrey KA, Allison T, McKeown MJ, McCarthy G. 2003.

Polysensory interactions along lateral temporal regions evoked by

audiovisual speech. Cereb Cortex. 13:1034--1043.



Dow

nloaded from



limbic response to music

Documents