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Proc Natl Acad Sci U S A. 2001 September 25; 98(20): 11818–11823. doi: 10.1073/pnas.191355898. | PMCID: PMC58814 |
Copyright © 2001, The National Academy of Sciences Psychology Intensely pleasurable responses to music correlate with activity
in brain regions implicated in reward and emotion Anne J. Blood* and Robert J. Zatorre Montreal Neurological Institute, McGill University, Montreal, QC, Canada H3A 2B4 Received July 11, 2001. We used positron emission tomography to study neural mechanisms
underlying intensely pleasant emotional responses to music.
Cerebral blood flow changes were measured in response to
subject-selected music that elicited the highly pleasurable
experience of “shivers-down-the-spine” or “chills.”
Subjective reports of chills were accompanied by changes in heart rate,
electromyogram, and respiration. As intensity of these chills
increased, cerebral blood flow increases and decreases were observed in
brain regions thought to be involved in reward/motivation, emotion,
and arousal, including ventral striatum, midbrain, amygdala,
orbitofrontal cortex, and ventral medial prefrontal cortex. These brain
structures are known to be active in response to other
euphoria-inducing stimuli, such as food, sex, and drugs of abuse. This
finding links music with biologically relevant, survival-related
stimuli via their common recruitment of brain circuitry involved in
pleasure and reward. The ubiquity of music in
human culture is indicative of its ability to produce pleasure and
reward value. Many people experience a particularly intense, euphoric
response to music which, because of its frequent accompaniment by an
autonomic or psychophysiological component, is sometimes described as
“shivers-down-the-spine” or “chills” ( 1– 3). Because such
chills are a clear, discrete event and are often highly reproducible
for a specific piece of music in a given individual ( 2), they provide a
good model for objective study of emotional responses to music. In a prior positron emission tomography (PET) study, we observed that
activity in paralimbic brain regions correlated with unpleasant or
mildly pleasant emotions elicited by varying amounts of musical
dissonance ( 4). These regions, including parahippocampal gyrus,
orbitofrontal, subcallosal, and frontal polar cortex, have been
previously implicated in emotional responses more generally ( 5– 10).
For example, regional cerebral blood flow (rCBF) increases in
parahippocampal gyrus have been observed during unpleasant emotional
states evoked by pictures with negative emotional valence ( 8), and
patients with lesions in subcallosal and other ventral medial
prefrontal cortex (VMPF) regions are impaired in identification of
emotional expression ( 7). In contrast, the paralimbic regions
associated with musical dissonance differed from neocortical regions
known to be involved in music perception and cognition, such as right
superior temporal and right prefrontal cortices ( 11– 14). While the previous PET study focused primarily on unpleasant responses
to music, the present study was designed to investigate neural
correlates of intensely pleasurable responses to music. Animal studies
have shown that reinforcement and motivation in relation to
administration of a variety of drugs of abuse involve recruitment of
brain regions such as the ventral striatum [particularly the nucleus
accumbens (NAc) and ventral pallidum], ventral tegmental area (VTA),
amygdala, hippocampus, VMPF, hypothalamus, and dorsal midbrain areas,
such as periaqueductal gray (PAG) and pedunculopontine tegmental
nucleus (PPT) ( 15). Animal studies of endogenous reward in
response to natural stimuli, such as food and sex, show involvement of
brain activity in similar regions. For example, both food and sexual
activity have been shown to increase dopamine activity in NAc ( 16, 17),
although the exact site of activity in NAc may differ between drug and
natural reward ( 18). Human studies of rewarding stimuli, such as drugs of abuse and food,
have also suggested that intensely pleasurable emotions are accompanied
by activity in neural systems underlying reward/motivation, emotional
(limbic), and arousal processes. For example, fMRI activity changes in
NAc, VTA, basal forebrain, thalamus, insula, cingulate, hippocampus,
and amygdala have been observed during cocaine craving or cocaine rush
in cocaine-dependent humans ( 19). The pleasant experience of chocolate
consumption in humans has been found to be correlated with activity in
midbrain, insula, the subcallosal region, and orbitofrontal cortex
(OfC) ( 20). In the present study, PET was used to measure rCBF changes while
subjects listened to music that they selected to predictably elicit the
euphoric experience of chills. We hypothesized that activity changes in
reward/motivation, limbic, paralimbic, and arousal brain regions
would correlate with the intensity of these chills. We also wished to
determine whether any of these regions were similar to those recruited
by mildly pleasant emotion in the dissonance PET study ( 4). Subjects. Subjects were McGill University students (age range: 20–30), five
female and five male, with at least 8 years of music training.
Musicians were used in this experiment based on the premise that this
population is more likely to experience strong emotional responses to
music; however, music training is not necessary to experience these
responses. Individual subjects were selected on the basis of their
reports of frequent, reproducible experiences of chills in response to
certain pieces of music. All subjects gave informed consent to
participate after the procedures and possible consequences of the
study were explained. Stimuli. Each subject selected one piece of music that consistently elicited
intensely pleasant emotional responses, including chills. Because music
preference is highly individual, subject-selected music was the most
reliable way to produce intense emotional responses ( 21). All music
selections were of the classical genre, and included pieces such as
Rachmaninoff's Piano Concerto No. 3 in D Minor, Opus
30, Intermezzo Adagio [Fig.
, subject 1 (Chills)], and Barber's
Adagio for Strings [Fig. , subject 2 (Chills) and subject
1 (Ctrl)]. No words were associated with the selected or any other
version of the pieces. Subjects reported that their emotional responses
were intrinsic to the music itself, producing minimal personal
associations and/or memories. Because chills are known to occur
consistently in the same part of a music selection for a given subject,
we determined these times before scanning. One 90-sec excerpt,
including the section that elicited chills, was taken from each
subject's music selection and used as “subject-selected music”
for that subject.
Each subject's selected music was used as another subject's
emotionally “neutral” control, such that group-averaged data
analysis involved comparison of identical sets of stimuli. For example,
if stimulus A evoked chills in subject 1, and stimulus B evoked chills
in subject 2, then stimulus B might serve as control music for subject
2, and stimulus A might serve as control music for subject 2. Each
music stimulus was used only once as a control. Subjects were asked to
rate the emotional intensity of their responses to each of the other
nine music selections; to qualify as a neutral control, emotional
intensity ratings were required to be ≤3 on a scale of 0 to 10
(10 = most intense). Subjects were familiarized with their control
music before scanning to minimize responses attributable to effects of
novelty. Scanning Procedures. PET scans were performed and registered with MRI scans as described in
our previous PET study ( 4). During each 60-sec PET scan, subjects
listened passively to one of four stimuli [selected music, control
music, and two baseline conditions: amplitude-matched noise ( 4, 14) and
silence]. Stimulus onset occurred ≈15 sec before scan onset to
establish and stabilize subjects' responses to the stimulus.
Each condition was repeated three times; stimulus presentation order
was pseudorandomized. Measurements of heart rate (HR), electromyogram (EMG), respiration
depth (RESP), electrodermal response, and skin temperature were made
during PET scans by using an F1000 polygraph instrumentation System
[Biofeedback Instrument Corp. (New York); manufactured by Focused
Technology (Ridgecrest, CA)]. After each PET scan, subjects rated
their emotional reactions to each stimulus by using analog rating
scales. Ratings were acquired for “chills intensity” (0 to 10),
“emotional intensity” (0 to 10), and “unpleasant versus
pleasant” (−5 to +5). Data Analysis. Regression maps ( 22) were calculated to assess the significance of the
relationship between chills intensity rating and CBF (i.e., their
linear regression). The dataset for this analysis consisted of
normalized CBF values obtained in each subject during each of the
subject-selected and control music scans, yielding a total of 60 image
volumes. Because subjects did not experience chills during the control
music condition (see Results), chills intensity ratings were
set to zero for all control scans. The effect of the variation in
chills response was assessed by means of analysis of covariance ( 23),
with subjects as a main effect and the chills intensity rating as a
covariate. The following model was fitted:
E( yij) =
ai +
β Prij, were
yij is the normalized CBF of subject
i on scan j, and rij is
the rating for subject i at scan j. The subject
effect ( ai) is removed and the parameter of
interest is the slope β P of the effect of the
chills rating on CBF. The subject effect regressor was subtracted from
the analysis to remove the influence of individual differences in
response that would have been implicitly removed in a comparison of
means model (task-baseline) ( 24). Removal of this effect allowed
grouping of within and between subject data in the regression analysis.
Values equal to or exceeding a criterion of t = 3.53
were considered significant ( P < 0.01, two-tailed),
yielding a false-positive rate of 0.58 in 182 resolution elements (each
of which has dimensions 14 × 14 × 14 mm), if the volume of
brain gray matter is 500 cm 3 ( 24). To control for within-subject differences in familiarity that may have
existed between the subject-selected and control music conditions, the
regression with chills intensity was recalculated to include scans from
only the subject-selected music condition. Because specific regions
were hypothesized to be active in this analysis, significance
(P < 0.05) was determined by using a standard
one-tailed t test analysis. In addition, rCBF values from left ventral striatum, left dorsal
midbrain, left hippocampus/amygdala, right amygdala, and VMPF were
extracted from individual scans (subject-selected music condition only)
and plotted against subject ratings of chills intensity. A Pearson
correlation was used to determine the correlation coefficient for each
of these regions. For these regional plots and correlations only, rCBF
values were extracted before normalization; to correct for this, both
rCBF values and chills intensity ratings were normalized to the lowest
value for each subject, such that lowest values were set to zero. As a complementary analysis, we performed a subtraction of the control
music condition from the subject-selected music condition. Because each
stimulus was used twice across subjects (once in the subject-selected
music condition and once in the control music condition), across the
entire group, the stimuli used in these two conditions differed in
emotional valence but not in physical features such as musical style or
tempo. Therefore, when these two conditions were averaged separately
and subtracted from each other, these potential confounding factors
were eliminated. Subtraction of baseline conditions (noise, silence)
from music conditions was also used to confirm that rCBF decreases were
actually decreases from baseline and not merely differences between
subject-selected and control music conditions. Two further regression analyses were used to investigate the
relationship between psychophysiological activity and rCBF. In the
first, rCBF was covaried with HR, EMG, and RESP measurements. In the
second, the regression with chills intensity was recalculated to remove
effects of all individual psychophysiological measurements ( 22),
including HR, EMG, RESP, electrodermal response, and skin temperature. Subjects reported experiencing chills during 77% of scans when
their own selected music was played. HR ( t = 3.02,
P < 0.01), EMG ( t = 2.41,
P < 0.05), and RESP ( t = 3.82,
P < 0.001) increased significantly during the highest
rated chills music condition relative to the control music condition
(Fig. ), while electrodermal and skin temperature measurements did not
differ significantly between these conditions. Chills intensity ratings
ranged from 1 to 9 (see Fig. 4, which is published as supporting
information on the PNAS web site, www.pnas.org), varying both within
and between subjects. Within subjects, ratings did not vary
systematically over time (see Fig. 4); there was no significant effect
of stimulus repetition number on chills intensity ratings (repeated
measures ANOVA; F = 0.57, P = 0.57).
Chills were never reported for control music, noise, or silence
conditions. Ratings of pleasantness and emotional intensity tended to
be higher than chills intensity, suggesting that pleasantness and
emotional intensity must reach a certain level before chills are
experienced. The average rating of chills intensity for
subject-selected music was 4.5 out of 10, whereas the average ratings
for emotional intensity and pleasantness were, respectively, 7.4 out of
10 and 4.4 out of 5.0 (see Tables 3 and 4, which are published as
supporting information on the PNAS web site, for correlations of these
ratings with CBF and see supporting Results, which are
published on the PNAS web site, for further information). Regression analysis correlating rCBF with increasing chills intensity
ratings in the subject-selected and control music conditions identified
rCBF increases in left ventral striatum, dorsomedial midbrain,
bilateral insula, right OfC, thalamus, anterior cingulate cortex
(AC), supplementary motor area (SMA), and
bilateral cerebellum (Table 1, all music, and Fig.
). rCBF decreases with increasing chills
intensity were observed in right amygdala, left hippocampus/amygdala,
VMPF, and in widespread, bilateral posterior neocortical regions,
particularly in cuneus/precuneus regions (Table 1, all music, and
Fig. ). Subtraction of noise and silent baseline conditions from
subject-selected and control music conditions verified that right
amygdala, left hippocampus/amygdala, and VMPF activity decreased from
baseline during subject-selected music, whereas no rCBF changes were
observed in these structures during control music as compared with the
noise and silent baselines.
| Table 1Regressions correlating rCBF with ratings of
chills intensity |
When the regression with chills intensity was recalculated to include
scans from only the subject-selected music condition, increases in left
ventral striatum, left dorsomedial midbrain, right thalamus, AC, SMA,
and left cerebellum, and decreases in right amygdala, left
hippocampus/amygdala, and VMPF remained significant (Table 1, s-s
music; see also Fig. 5, which is published as supporting information on
the PNAS web site). The locations of peak values for this regression
were within 9 mm of the locations identified in the all-music
regression, except for AC and SMA. When rCBF was measured in left
ventral striatum, left dorsal midbrain, left hippocampus/amygdala,
right amygdala, and VMPF, correlation coefficients were similar for
left ventral striatum (0.49) and dorsomedial midbrain (0.40), as well
as for left hippocampus/amygdala (−0.40) and right amygdala (−0.30)
(Fig. ).
A complementary subtraction analysis comparing the subject-selected and
control music conditions (subject-selected minus control music)
revealed CBF increases in regions similar to those observed in the
regressions: left ventral striatum, dorsomedial midbrain, bilateral
insula, right OfC, thalamus, AC, SMA, and bilateral cerebellum (Table
2; see also Fig. 6, which is published as
supporting information on the PNAS web site). rCBF decreases were
observed in right amygdala, left hippocampus/amygdala, VMPF, and in
widespread, bilateral neocortical regions, including occipital,
parietal, and temporal cortices (Table 2 and Fig. 6). Because certain
regions were already hypothesized to be active, some t
values below 3.53 are included here.
| Table 2Subtraction analysis: subject-selected music minus
controlmusic |
To determine whether rCBF activity in certain regions correlated with
changes in psychophysiological activity, regression analyses were used
to correlate rCBF with individual measurements of HR, EMG, and RESP.
Increases in psychophysiological activity correlated with rCBF
increases in several structures, including thalamus, AC, OfC, insula,
cerebellum, and SMA. None of these psychophysiological measurements
correlated significantly with rCBF changes in ventral striatum,
dorsomedial midbrain, amygdala, hippocampus/amygdala, or VMPF. When
effects of all psychophysiological activity were removed from the
chills intensity regression, significant rCBF changes remained, not
only in ventral striatum, dorsomedial midbrain, amygdala, and
hippocampus/amygdala, but also in thalamus and AC. Subjects experienced chills of varying intensity while listening
to their selected music. These chills were associated with increases in
HR, EMG, and RESP relative to the control music condition, indicating
changes in autonomic and other psychophysiological activity. Regression
analysis assessing the relationship between increasing chills intensity
ratings and PET measurements of rCBF identified changes in brain
structures that have been associated with brain reward circuitry (refs.
15, 26, 27; Table 1 and Fig. ). These included rCBF increases in left
ventral striatum and dorsomedial midbrain, and rCBF decreases in right
amygdala, left hippocampus/amygdala, and VMPF. These structures
remained active when control music was removed from the regression
analysis, and in the subtraction analysis, verifying that these
structures were active specifically in correlation with chills, and not
simply due to differences in attention, familiarity, or acoustic
features between subject-selected and control music. rCBF increases
with chills intensity were also observed in paralimbic regions
(bilateral insula, right OfC) and in regions associated with arousal
(thalamus and AC) and motor (SMA and cerebellum) processes. The pattern of activity observed here in correlation with music-induced
chills is similar to that observed in other brain imaging studies of
euphoria and/or pleasant emotion ( 19, 20, 28). For example, activity
in NAc, VTA, thalamus, insula, and AC has been reported to increase,
and in left amygdala and VMPF to decrease, in response to cocaine
administration in cocaine-dependent subjects ( 19). In addition, animal
studies support a critical role for ventral striatum (NAc, in
particular), several midbrain areas (e.g., VTA, PAG, and PPT),
amygdala, hippocampus, and medial prefrontal cortex in circuitry
underlying reward processes, including hedonic impact, reward learning,
and motivation ( 15, 26, 27). Activity in these regions in relation to
reward processes is known to involve dopamine and opioid systems, as
well as other neurotransmitters. Dopaminergic activity in either NAc and/or VTA appears to be the
common mechanism underlying reward response to all naturally rewarding
stimuli (e.g., food and sex) ( 16, 27, 29), and to drugs with
euphorogenic properties and/or abuse potential ( 27). For example,
self-administration of i.v. drugs, such as cocaine or heroin, in rats
correlates strongly with activity increases in NAc as measured by
microdialysis ( 30, 31), as well as behavioral indices of satiety, while
consequent declines in NAc dopamine levels were highly correlated with
onset of further self-stimulation. NAc is also rich in opiate receptors
and is modulated by enkephalins ( 15). Efferent projections from NAc
also are largely opioid, and are thought to be specifically responsible
for reward-related behavior ( 27). Although the resolution and
registration methods of PET do not allow us to conclude specifically
that the ventral striatum activity observed in the present study is in
the NAc, the coordinates of this activity peak do, indeed, overlie the
NAc coordinates in the Talairach atlas. Similarly, although PET methods do not allow us to determine
definitively which specific midbrain nuclei were active in the present
study, the dorsomedial location of the response suggests that this
activity may be either in PAG or in PPT. Because activity in this
region did not covary with psychophysiological activity, it is unlikely
that the midbrain response was in the reticular formation, part of the
arousal system. Both PAG and PPT play an integral role in reward
responses. PAG is rich in opioid receptors and endogenous
opioids such as endorphin and enkephalin, and is involved in
opioid-mediated reward ( 32) as well as analgesia ( 33). Support for
involvement of opioid systems specifically in response to music comes
from a preliminary study that demonstrated that blocking opioid
receptors with naloxone decreased or inhibited the chills response in
some subjects ( 1). The PPT is thought to be involved specifically in
the acquisition of drug-rewarded behavior ( 15), receiving descending
NAc projections via the ventral pallidum, and sending projections to
structures such as substantia nigra, VTA, thalamus, amygdala, and
cerebellum. The observation of rCBF decreases in the amygdala and hippocampus
during music-induced chills is compatible with the key role played by
these structures in both reward and emotion ( 10, 15, 26, 34– 36). The
amygdala sends glutamatergic afferents to both NAc and VTA ( 27) and,
along with hippocampus, PAG, and NAc, is a key structure in
opioid-mediated responses ( 33, 37, 38). The possibility of a direct
functional interaction between hippocampus/amygdala and midbrain in
the present study is supported by the exactly opposite correlation of
dorsomedial midbrain and left hippocampus/amygdala rCBF with chills
intensity (Fig. ). Decreases in the left amygdala have been previously
observed in fMRI studies of cocaine and procaine administration ( 19,
28). In the cocaine study, amygdala decreases correlated with ratings
of “craving” rather than “rush,” suggesting that the
amygdala decreases observed in the present study may have occurred more
in relation to anticipation of the chills response than to the chills
response itself. In other studies, however, amygdala activity has been
shown to increase during states of euphoria ( 17, 39), indicating that
modulation of amygdala may be complex. Amygdala decreases accompanied by ventral striatum increases may also
indicate gating between behaviorally antagonistic “approach” and
“withdrawal” systems. The amygdala is known to be involved in
fear and other aversive emotions, as well as evaluative processes
associated with socially and biologically relevant emotions ( 10,
34– 36), whereas ventral striatum mediates evaluative processes
associated with reward and motivation/approach behavior. Thus,
activation of the reward system by music may maximize pleasure, not
only by activating the reward system but also by simultaneously
decreasing activity in brain structures associated with negative
emotions. The amygdala and hippocampus both receive inhibitory
presynaptic input from cholinergic neurons intrinsic to NAc ( 15),
suggesting a possible mechanism for decreased activity in these regions
as a consequence of activity increases in ventral striatum. Significant increases in psychophysiological activity were observed
during the chills, relative to the control music condition, consistent
with previous reports of psychophysiological activity changes during
emotional responses to music ( 40). Although activity changes in ventral
striatum, dorsomedial midbrain, amygdala, and hippocampus may be
involved in producing states of reward and motivation associated with
music-induced chills, other structures may have been active more in
relation to the autonomic/psychophysiological component of the chills
response. Specifically, thalamus and AC are thought to be centrally
involved in mechanisms of general arousal and attentional processes
( 41). rCBF increases in both thalamus and AC were found to correlate
positively with increasing psychophysiological activity, indicating a
possible role for these regions in psychophysiological processes.
However, because rCBF increases in thalamus and AC were not eliminated
when effects of psychophysiological activity were removed from the
chills intensity regression analysis, it appears that these structures
may have mediated other arousal and/or reward processes as well. Brain structures correlating with intensely pleasant emotion in the
present study differed considerably from those observed during
unpleasant or pleasant responses to musical dissonance or consonance in
our previous study ( 4). In particular, right parahippocampal activity
previously observed to correlate with unpleasant responses to
dissonance did not correlate with chills intensity here, supporting the
notion that parahippocampal activity may be specifically related to
negative emotion. In addition, regions associated with
reward/motivation circuitry, such as ventral striatum, dorsomedial
midbrain, amygdala, and hippocampus, were found to correlate with
chills intensity but not with the more mildly pleasant emotion
associated with consonance. These discrepancies provide further
evidence that different emotions are associated with activity in
different groups of brain structures. In contrast, VMPF and OfC
activity changes were seen in correlation with pleasant emotion in both
this and the previous music study, although VMPF subregions differed
between studies. Lesion and imaging studies have implicated medial
prefrontal and OfC regions in integration of reward and/or punishment
information to make behavioral judgments about stimuli ( 6, 9). This
integrative capacity suggests that these regions may subserve multiple
emotional functions and therefore may respond to more than one type of
emotion. We have shown here that music recruits neural systems of reward and
emotion similar to those known to respond specifically to biologically
relevant stimuli, such as food and sex, and those that are artificially
activated by drugs of abuse. This is quite remarkable, because music is
neither strictly necessary for biological survival or reproduction, nor
is it a pharmacological substance. Activation of these brain systems in
response to a stimulus as abstract as music may represent an emergent
property of the complexity of human cognition. Perhaps as formation of
anatomical and functional links between phylogenically older,
survival-related brain systems and newer, more cognitive systems
increased our general capacity to assign meaning to abstract stimuli,
our capacity to derive pleasure from these stimuli also increased. The
ability of music to induce such intense pleasure and its putative
stimulation of endogenous reward systems suggest that,
although music may not be imperative for survival of the human species,
it may indeed be of significant benefit to our mental and physical
well-being. We are grateful to Dr. Alan C. Evans for making available the
facilities of the McConnell Brain Imaging Centre. We thank Drs. Pascal
Belin and Alain Dagher for editorial comments, and Marc Bouffard,
Pierre Ahad, and Sylvain Milot for their technical expertise. We also
thank the technical staff of the McConnell Brain Imaging Unit and of
the Medical Cyclotron Unit for their assistance. This work was
supported by a National Institute of Mental Health postdoctoral
(National Research Service Award) fellowship and the Jeanne Timmins
Costello fellowship in Neuroscience to A.J.B. and by grants from the
Canadian Institutes of Health Research and the McDonnell-Pew Cognitive
Neuroscience Program to R.J.Z. | | PET | positron emission tomography | | | rCBF | regional
cerebral blood flow | | | VMPF | ventral medial prefrontal cortex | | | NAc | nucleus accumbens | | | VTA | ventral tegmental area | | | OfC | orbitofrontal
cortex | | | HR | heart rate | | | EMG | electromyogram | | | RESP | respiration depth | | | AC | anterior cingulate | | | SMA | supplementary motor area | | | PAG | periaqueductal gray | | | PPT | pedunculopontine nucleus |
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