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Anatomically distinct dopamine release during anticipation and experience of peak emotion to music

February 2011
Nature Neuroscience 14(2):257-62

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Music, an abstract stimulus, can arouse feelings of euphoria and craving, similar to tangible rewards that involve the striatal dopaminergic system. Using the neurochemical specificity of [(11)C]raclopride positron emission tomography scanning, combined with psychophysiological measures of autonomic nervous system activity, we found endogenous dopamine release in the striatum at peak emotional arousal during music listening. To examine the time course of dopamine release, we used functional magnetic resonance imaging with the same stimuli and listeners, and found a functional dissociation: the caudate was more involved during the anticipation and the nucleus accumbens was more involved during the experience of peak emotional responses to music. These results indicate that intense pleasure in response to music can lead to dopamine release in the striatal system. Notably, the anticipation of an abstract reward can result in dopamine release in an anatomical pathway distinct from that associated with the peak pleasure itself. Our results help to explain why music is of such high value across all human societies.

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nature neurOSCIenCe VOLUME 14 | NUMBER 2 | FEBRUARY 2011 257

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Humans experience intense pleasure to certain stimuli, such as food,

psychoactive drugs and money; these rewards are largely mediated

by dopaminergic activity in the mesolimbic system, which has been

implicated in reinforcement and motivation (see ref. 1 for a review).

These rewarding stimuli are either biological reinforcers that are

necessary for survival, synthetic chemicals that directly promote

dopaminergic neurotransmission, or tangible items that are secondary

rewards. However, humans have the ability to obtain pleasure from

more abstract stimuli, such as music and art, which are not directly

essential for survival and cannot be considered to be secondary

or conditioned reinforcers. These stimuli have persisted through

cultures and generations and are pre-eminent in most people’s lives.

Notably, the experience of pleasure to these abstract stimuli is highly

specific to cultural and personal preferences, which can vary tremen-

dously across individuals.

Most people agree that music is an especially potent pleasurable

stimulus2 that is frequently used to affect emotional states. It has

been empirically demonstrated that music can effectively elicit highly

pleasurable emotional responses3,4 and previous neuroimaging stud-

ies have implicated emotion and reward circuits of the brain during

pleasurable music listening5–8, particularly the ventral striatum5–7,

suggesting the possible involvement of dopaminergic mechanisms9.

However, the role of dopamine has never been directly tested. We

used ligand-based positron emission tomography (PET) scanning to

estimate dopamine release specifically in the striatum on the basis of

the competition between endogenous dopamine and [11C]raclopride

for binding to dopamine D2 receptors10. Pleasure is a subjective pheno-

menon that is difficult to assess objectively. However, physiological

changes occur during moments of extreme pleasure, which can be

used to index pleasurable states in response to music. We used the

‘chills’ or ‘musical frisson’11 response, a well-established marker of

peak emotional responses to music5,12–14. Chills involve a clear and

discrete pattern of autonomic nervous system (ANS) arousal15, which

allows for objective verification through psychophysiological meas-

urements. Thus, the chills response can be used to objectively index

pleasure, a subjective phenomenon that would otherwise be difficult

to operationalize, and allows us to pinpoint the precise time of maxi-

mal pleasure.

Previous studies have typically used experimenter-selected musi-

cal stimuli6–8. However, musical preferences are highly individual-

ized; thus, to ensure maximal emotional responses, participants were

asked to select their own highly pleasurable music. After extensive

screening (Online Methods), we recruited a group of people who

consistently experienced objectively verifiable chills during their peak

emotional responses so that we could quantify both the occurrence

and the timing of the most intense pleasurable responses. We also

collected psychophysiological measurements (heart rate, respiration

rate, electrodermal skin conductance, blood volume pulse amplitude

and peripheral temperature) during the PET scans to verify ANS dif-

ferences between conditions. To account for psychoacoustical differ-

ences across self-selected stimuli, we matched musical excerpts using

a previously established procedure5, such that participants listened to

one another’s choices, which served as either pleasurable or neutral

stimuli. We predicted that if the rewarding aspects of music listen-

ing are mediated by dopamine, substantial [11C]raclopride binding

potential differences would be found between neutral and pleasurable

conditions in mesolimbic regions.

The second aim of our study was to explore the temporal dynamics

of any dopaminergic activity, as distinct anatomical circuits are thought

to underlie specific phases of reward responses16,17. That is, if there is

dopamine release, we wanted to examine whether it is associated with

the experience of the reward or with its anticipation18. Music provides

1Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada. 2International Laboratory for Brain, Music and Sound Research, Montreal, Quebec,

Canada. 3Centre for Interdisciplinary Research in Music Media and Technology, Montreal, Quebec, Canada. 4Centre for Intelligent Machines, McGill University,

Montreal, Quebec, Canada. Correspondence should be addressed to V.N.S. (valorie.salimpoor@mail.mcgill.ca) or R.J.Z. (robert.zatorre@mcgill.ca).

Received 7 October 2010; accepted 25 November 2010; published online 9 January 2011; doi:10.1038/nn.2726

Anatomically distinct dopamine release during

anticipation and experience of peak emotion to music

Valorie N Salimpoor1–3, Mitchel Benovoy3,4, Kevin Larcher1, Alain Dagher1 & Robert J Zatorre1–3

Music, an abstract stimulus, can arouse feelings of euphoria and craving, similar to tangible rewards that involve the striatal

dopaminergic system. Using the neurochemical specificity of [11C]raclopride positron emission tomography scanning, combined

with psychophysiological measures of autonomic nervous system activity, we found endogenous dopamine release in the striatum

at peak emotional arousal during music listening. To examine the time course of dopamine release, we used functional magnetic

resonance imaging with the same stimuli and listeners, and found a functional dissociation: the caudate was more involved

during the anticipation and the nucleus accumbens was more involved during the experience of peak emotional responses to

music. These results indicate that intense pleasure in response to music can lead to dopamine release in the striatal system.

Notably, the anticipation of an abstract reward can result in dopamine release in an anatomical pathway distinct from that

associated with the peak pleasure itself. Our results help to explain why music is of such high value across all human societies.

25 8 VOLUME 14 | NUMBER 2 | FEBRUARY 2011 nature neurOSCIenCe

a r t I C l e S

an innovative means of assessing this distinction because the temporal

unveiling of tonal arrangements elicits anticipatory responses that are

based on cognitive expectations and prediction cues11,19,20. These can

be examined to isolate the functional components that precede peak

pleasurable responses. As PET does not afford the temporal resolu-

tion required to examine this distinction, we combined the temporal

specificity of functional magnetic resonance imaging (fMRI) with the

neurochemical specificity of PET. We acquired fMRI scans with the

same participants and stimuli to examine the temporal profile of blood

oxygenation level–(BOLD) response specifically in those regions that

also showed dopamine release with PET. Striatal dopamine release and

BOLD responses are known to be correlated, although the relationship

is complex9,21. We predicted that regions revealing dopamine activity

in the PET data would show the largest increases in hemodynamic

response during peak emotional experiences. We separately analyzed

the BOLD data from epochs of peak pleasure and the time immediately

preceding these responses (that is, anticipation), based on participants’

real-time behavioral responses of when chills were experienced. Spatial

conjunction analyses were used to confine the analysis to those striatal

voxels showing both dopamine release from PET and increased BOLD

during fMRI, which ensured that we were measuring the hemodynamic

signal only from regions known to release dopamine in response to

the same stimuli. This multimodal procedure revealed a temporally

mediated distinction in dopamine release to anticipatory and consum-

matory responses in the dorsal and ventral striatum, respectively.

RESULTS

PET data: dopamine release and emotional arousal

PET scanning took place over two sessions. Participants listened to

either pleasurable music or neutral music during the entire session

while both subjective and objective indicators of emotional arousal

were collected. Subjective responses from rating scales included self-

reports of number of chills, intensity of chills and degree of pleasure

experienced from each excerpt. The mean number of chills for each

pleasurable music excerpt was 3.7 (s.d. = 2.8). A paired-samples t test

confirmed that greater pleasure was experienced during the pleasur-

able music condition over the neutral music condition (t(49) = 25.0,

P < 0.001). Notably, there was a significant positive correlation

between the reported intensity of chills and the reported degree of

pleasure (r = 0.71, P < 0.001), suggesting that the chills response is a

good representation of pleasure experienced amongst this group.

Objective measures of psychophysiological signals indicative of emo-

tional arousal collected during the two PET scanning sessions showed

significantly higher ANS activity during the pleasurable music condition

in all of the variables that we measured: namely, increases in heart rate

(P < 0.05), respiration (P < 0.001) and electrodermal response (P < 0.05),

and decreases in temperature (P < 0.01) and blood volume pulse ampli-

tude (P < 0.001; for values, see (Supplementary Table 1). Subjective

reports of the intensity of the chills response

collected via rating scales during PET scanning

were significantly correlated with the degree of

ANS arousal on all measures: increases in heart

rate (P < 0.05), respiration (P < 0.05) and elec-

trodermal response (P < 0.01), and decreases

Skin

conductance

Temperature

Blood volume pulse

amplitude

Heart rate

Respiration

Intensity of chills

∆ µS∆ °C∆

reflectance

∆ beats

per min

4 6 8 10

–1

–2

4 6 8 10

–1

–2

4 6 8 10

–1

–2

4 6 8 10

–1

–2

4 6 8 10

∆ breaths

per min

–1

–2

Figure 1 Positive correlation between emotional arousal and intensity

of chills during PET scanning. The mean intensity of chills reported

by each participant during the PET scanning session was significantly

correlated with psychophysiological measurements that were also acquired

during the scan. These are indicative of increased sympathetic nervous

system activity, suggesting that the intensity of chills is a good marker of

peak emotional arousal (Supplementary Table 1). The y axis represents

standardized z scores for each biosignal. See main text for P-values.

Left caudate

Neutral

Left putamen

Left NAcc/ventral

putamen

Right NAcc

Right putamen

Chills Neutral Chills

3.6 ∆6.4%

∆6.6% ∆7.4%

∆6.5% ∆9.2%

∆7.9%

∆BP

3.0

2.4

1.8

Neutral Chills Neutral Chills

3.6

∆BP

3.0

2.4

1.8

Neutral Chills

3.6

∆BP

3.0

2.4

1.8

Neutral Chills

3.6

∆BP

3.0

2.4

1.8

3.6

∆BP

3.0

2.4

1.8

3.6

3.0

2.4

1.8

Right caudate

Caudate

x = 10 y = 19 z = 7

x = 23 y = 1 z = 1

x = 10 y = 12 z = –10

Putamen

NAcc

Figure 2 Evidence for dopamine release during

pleasurable music listening. (a) Statistical

parametric maps (t statistic on sagittal,

coronal and axial slices) reveal significant

(P < 0.001) [11C]raclopride binding potential (BP)

decreases bilaterally in the caudate, putamen

and NAcc (white arrows) during pleasurable

compared with neutral music listening

(Supplementary Table 2), indicating increased

dopamine release during pleasurable music.

(b) Changes in binding potential (BP) values

plotted separately for each individual; note that

the change was consistent for the majority of

people at each site.

nature neurOSCIenCe VOLUME 14 | NUMBER 2 | FEBRUARY 2011 259

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in temperature (P < 0.05) and blood volume pulse amplitude (P < 0.05;

(Fig. 1 and Supplementary Table 1). This finding further verified that

the chills response is a good objective representation of peak emotional

arousal in this group.

Analysis of PET data (Supplementary Methods) revealed increased

endogenous dopamine transmission, as indexed by decreases in

[11C]raclopride binding potential, bilaterally in both the dorsal and

ventral striatum (P < 0.001; Fig. 2a) when contrasting the pleasurable

music with the neutral music condition. The percentage of dopamine

binding potential change was highest in the right caudate and the right

nucleus accumbens (NAcc; Fig. 2b and Supplementary Table 2). These

results indicate that the experience of pleasure while listening to music

is associated with dopamine release in striatal reward systems.

fMRI data: temporal specificity of reward responses

To gain information about the dynamics of dopamine release over time,

we acquired fMRI scans during presentation of pleasurable and neutral

music excerpts. Listeners indicated by button press when they experi-

enced chills (mean = 3.1 chills per excerpt, s.d. = 0.9); these responses

were then used post hoc to identify anticipation and peak experience

time periods (Fig. 3a). Anticipation epochs were defined as 15 s before

the peak experiences. BOLD responses for each of these epochs were

compared with periods in which participants reported feeling neutral

during the same musical excerpts. The result of this contrast for each

of the events was then spatially conjoined with a mask of regions that

had released dopamine according to the [11C]raclopride PET scan. We

found that hemodynamic activity in the regions showing dopamine

release was not constant throughout the excerpt, but was restricted

to moments before and during chills and, critically, was anatomically

distinct. During peak pleasure experience epochs, as compared with

neutral epochs, there was increased BOLD response in the right NAcc

(x, y, z = 8, 10, −8; t = 2.8; Fig. 3b). In contrast, increased BOLD

response was also found during the anticipation epochs, but was largely

confined to the right caudate (x, y, z = 14, −6, 20; t = 3.2; Fig. 3b).

The temporal dynamics of the reward response and its relationship

to the caudate and NAcc clusters can be more specifically analyzed

by examining the percent BOLD signal change occurring over time

in relation to peak pleasure. To avoid the ‘circularity’ problem22 , we

Figure 3 Combined fMRI and PET results

reveal temporal distinctions in regions showing

dopamine release. (a) [11C]raclopride PET

scan results were spatially conjoined with the

fMRI results by creating a mask of significant

dopamine release overlayed on BOLD response

t maps during each condition. (b) Hemodynamic

responses and dopamine activity were maximal

in the caudate during anticipatory phases,

but shifted more ventrally to NAcc during

peak emotional responses. (c) Percent signal

change in BOLD response relative to the

mean was calculated from the peak voxel of

the caudate and NAcc clusters based on the

[11C]raclopride PET data. Voxels showing

maximum dopamine release in the caudate and

NAcc (Supplementary Table 2) were identified

and percent BOLD signal change was calculated

during the fMRI epochs associated with peak

emotional responses; values were interpolated

for each second preceding this response for

each individual, up to 15 s, which was defined as the anticipatory period based on previous findings15 (see Online Methods for additional details). We

found increased activity during anticipation (A1-A15) and decreased activity during peak emotional response (C1-C4) for the caudate, but a continuous

increase in activity in NAcc with a maximum during peak emotional responses. The mean signal for neutral epochs for the NAcc and caudate clusters

are also plotted for reference, as are the 5 s preceding the anticipation epochs.

fMRI

Hemodynamic

(BOLD)

Neurochemical

(dopamine

binding)

VOI

Mean neutral

Time series of peak dopaminergic voxels

–5

–4

–3

–2

–1

A10

A11

A12

A13

A14

A15

–1

Percent signal

change

PET

Temporally mediated BOLD response

in dorsal and ventral striatum

fMRI

PET

Anticipation Experience 0

y = 4 y = 11

Anticipation Experience

Right caudate

Right NAcc

Figure 4 Brain and behavior relationships

involving temporal components of pleasure

during music listening. Left, coronal slices

showing binding potential differences in dorsal

(top) and ventral (bottom) striatum that also

show hemodynamic activity during anticipation

versus experience of chills, respectively. Right,

behavioral ratings of the number and intensity

of chills and pleasure reported during the

PET scans plotted against [11C]raclopride

binding potential changes in the two clusters.

The number of chills reported was positively

correlated with percent binding potential

change in the caudate (*P < 0.05), which was

linked to BOLD response immediately preceding

chills (that is, anticipatory periods), consistent

with the idea that a greater number of chills

would result in greater anticipation and result in more activity in the areas associated with anticipation. The mean intensity of chills and reported

pleasure were positively correlated with the NAcc (**P < 0.01), which was linked to BOLD response during chills, confirming that this region is involved

in the experience of the highly pleasurable component of music listening.

Percentage change

in BP

Combined hemodynamic and

neurochemical activity

Immediately preceding chills

Number

of chills

10 20 30 40 1086 1086

r = 0.71*

r = 0.80*

r = 0.84**

Intensity

of chills

[11C]raclopride PET

Reported

pleasure

During experience of chills

Percentage change

in BP

Caudate

y = 4

NAcc

y = 11

26 0 VOLUME 14 | NUMBER 2 | FEBRUARY 2011 nature neurOSCIenCe

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derived our voxels of interest (VOIs) from the PET data, which are

independent of the fMRI data. This procedure also allowed us to

better integrate the hemodynamic and neurochemical results. We

found that activity in both the caudate and NAcc was increased during

anticipation as compared with the mean signal during the neutral

epochs for the same pieces of music, with larger increases occurring in

the caudate (Fig. 3c). During the peak emotional response, however,

activity in the caudate decreased, whereas activity in the NAcc con-

tinued to increase. These findings support our fMRI contrast results

and provide temporal information as to how hemodynamic activity

in the regions showing dopamine release may contribute to reward

processing in real time.

Brain-behavior relationships

Once we had identified, via fMRI, the caudate and NAcc as contrib-

uting to the anticipation and experience, respectively, of peak plea-

sure moments during music listening, we used our PET scan data to

further explore the brain and behavior relationships in these clus-

ters. Mean [11C]raclopride binding potential values from the NAcc

and caudate clusters was plotted against behavioral data obtained

during PET scanning, which required participants to indicate the

total number of chills, mean intensity of chills and mean subjective

pleasure experienced during each piece of music. We found that the

number of chills was significantly correlated (P < 0.05) with binding

potential differences in the right caudate, but not the NAcc, whereas

the intensity of chills and overall degree of pleasure experienced were

most significantly correlated (P < 0.01) with binding potential change

in the right NAcc, but not the caudate (Fig. 4 and Supplementary

Table 3). This finding further supports a functional dissociation in

the contribution of these anatomical regions to pleasure associated

with music listening.

An additional question is whether increases in pleasure alone, in

the absence of chills, result in increased hemodynamic responses in

the same areas as during the experience of chills, although perhaps

not to the same extent. We examined this question by determining

whether there was a linear relationship between increases in plea-

sure and hemodynamic activity in the right NAcc, irrespective of

chills, and how this compared with other striatal regions showing

dopamine release. This analysis was done by excluding all of the

epochs during which individuals experienced chills and examining

BOLD signal changes that related to increasing pleasure in the right

NAcc. Using the voxel that showed the maximum dopamine release

in the NAcc during the [11C]raclopride scan, we calculated the per-

cent BOLD signal change as subjective pleasure ratings increased

from neutral to low pleasure to high pleasure (excluding chills) for

each individual. Note that this analysis, unlike the one presented

above, does not take into account the temporal component, as all

epochs rated as having the same pleasure were averaged, regardless

of when they occurred with respect to chills. A regression analysis

revealed a significant linear trend in which the percent signal change

in the right NAcc accounted for 67% of the variability in subjective

pleasure ratings (t(19) = 6.18, P < 0.001). This finding suggests that

increases in subjective pleasure correspond to increases in neural

activity in the NAcc, in the same regions as those involved in the

chills responses and those that showed dopamine release in the PET

study, even though this analysis excluded all chills epochs.

Next, to ensure that increases in pleasure, irrespective of chills, are

not better predicted by activity in regions of the striatum other than

the right NAcc, we performed a similar analysis in all anatomical

clusters that had shown dopamine release in the PET study. We first

selected peak voxels from each cluster showing dopamine release from

the PET data and then extracted the percent BOLD signal change as

listeners reported increases in pleasure from the fMRI data; as before,

all chills epochs were excluded. A stepwise multiple regression analy-

sis was performed to examine which cluster’s hemodynamic responses

were best able to predict pleasure states. We found that hemodynamic

increase in the NAcc cluster was the most significant predictor

(P < 0.01) of increasing subjective pleasure (Supplementary Table 4).

However, at a lower statistical threshold of P < 0.05, bilateral caudate

clusters and the left NAcc/ventral putamen cluster could also pre-

dict pleasure states, but to a lower degree (31% and 43% for left and

right caudate, respectively, and 37% for the NAcc/ventral putamen).

Recruitment of the caudate is not surprising considering that anticipa-

tory periods result in a culmination of pleasurable emotional experi-

ences and the caudate was recruited during these pleasant anticipatory

moments. Indeed, the mean subjective pleasure rating provided by

listeners during the anticipatory epochs was 2.51 (s.d. = 0.55), which

was significantly higher than that of the entire excerpt (mean = 2.11,

s.d. = 0.019; t(246) = 8.5, P < 0.001).

Finally, when the percent BOLD signal change during the chills

epochs was included in the multiple regression analysis (Fig. 5), it was

apparent that the experience of chills represents the highest point of

hemodynamic activity in the NAcc. These findings converge to sug-

gest that the dorsal and ventral subdivisions of the striatum are most

involved during anticipation and experience of the peak emotional

responses during music listening, respectively.

DISCUSSION

Our results provide, to the best of our knowledge, the first direct evi-

dence that the intense pleasure experienced when listening to music

is associated with dopamine activity in the mesolimbic reward system,

including both dorsal and ventral striatum. This phylogenetically

ancient circuitry has evolved to reinforce basic biological behaviors

with high adaptive value. However, the rewarding qualities of music

listening are not obviously directly adaptive. That is, musical stimuli,

1.1

0.5

–0.5

1.1

0.5

–0.5

L caudate

(–13, 11, 7)

L putamen

(–29, –12, –8)

L Nacc/ventral

putamen (–21, 9, –10)

R caudate

(12, 6, 15)

R putamen

(26, –2, 0)

R NAcc

(14, 10, –10)

Percent signal change

Neut LP HP Chills Neut LP HP Chills Neut LP HP Chills

Real-time subjective pleasure rating

Figure 5 Brain and behavior relationships involving parametric increases

in pleasure during music listening. Relationship between real-time ratings

of pleasure during music listening and percent BOLD signal change

relative to the mean in regions showing dopamine release as identified via

PET. The chills epochs (shaded) were excluded from the analysis (values

shown here only for reference) to examine activity related to increases in

pleasure irrespective of chills. A regression analysis revealed that the NAcc,

and to a lesser extent the left and right caudate, significantly predicted

increases in pleasure ratings during each of the conditions (P < 0.05 and

P < 0.001, respectively; Supplementary Table 4). This analysis indicates

that activity in these regions increased with pleasure even when no chills

were experienced.LP, low pleasure; HP, high pleasure.

nature neurOSCIenCe VOLUME 14 | NUMBER 2 | FEBRUARY 2011 261

a r t I C l e S

similar to other aesthetic stimuli, are perceived as being rewarding

by the listener, rather than exerting a direct biological or chemical

influence. Furthermore, the perception that results in a rewarding

response is relatively specific to the listener, as there is large vari-

ability in musical preferences amongst individuals. Thus, through

complex cognitive mechanisms, humans are able to obtain pleasure

from music2, a highly abstract reward consisting of just a sequence

of tones unfolding over time, which is comparable to the pleasure

experienced from more basic biological stimuli.

One explanation for this phenomenon is that it is related to enhance-

ment of emotions3,15,20. The emotions induced by music are evoked,

among other things, by temporal phenomena, such as expectations,

delay, tension, resolution, prediction, surprise and anticipation11,19.

Indeed, we found a temporal dissociation between distinct regions

of the striatum while listening to pleasurable music. The combined

psychophysiological, neurochemical and hemodynamic procedure

that we used revealed that peaks of ANS activity that reflect the expe-

rience of the most intense emotional moments are associated with

dopamine release in the NAcc. This region has been implicated in

the euphoric component of psychostimulants such as cocaine23 and

is highly interconnected with limbic regions that mediate emotional

responses, such as the amygdala, hippocampus, cingulate and ven-

tromedial prefrontal cortex24. In contrast, immediately before the

climax of emotional responses there was evidence for relatively greater

dopamine activity in the caudate. This subregion of the striatum is

interconnected with sensor y, motor and associative regions of the

brain24,25 and has been typically implicated in learning of stimulus-

response associations24,26 and in mediating the reinforcing qualities

of rewarding stimuli such as food27. Our findings indicate that a sense

of emotional expectation, prediction and anticipation in response to

abstract pleasure can also result in dopamine release, but primarily in

the dorsal striatum. Previous studies have found that amphetamine-

induced dopamine release in the NAcc spreads to more dorsal regions

after repeated exposure to the drug28, which suggests that this area

may be involved in improved predictability and anticipation of a

reward. Similarly, previous studies involving rewards such as food

and smoking that contain a number of contextual predicting cues

(for example, odor and taste) also found dorsal striatum dopamine

release27,29. Conversely, in studies in which there were no contextual

cues or experience with the drugs involved, dopamine release was

largely observed in the ventral striatum30,31. Finally, evidence from

animal research also suggests that, as rewards become better pre-

dicted, the responses that initiated in the ventral regions move more

dorsally in the striatum32. These results are consistent with a model in

which repeated exposure to rewards associated with a specific context

gradually shift the response from ventral to dorsal and further suggest

that contextual cues that allow prediction of a reward, in our case the

sequences of tones leading up to the peak pleasure moments, may also

act as reward predictors mediated via the dorsal striatum.

Another noteworthy finding is the correspondence between behavio-

ral and imaging results, which strengthens the evidence for the distinct

roles of dorsal and ventral striatum. We found a positive correlation

between subject-reported intensity of chills and dopamine release in the

NAcc during [11C]raclopride PET scanning (Fig. 4), which confirms the

fMRI results that peak pleasure responses are associated with this region.

Furthermore, the number of chills reported by listeners during the PET

scan was correlated with dopamine release in the caudate (Fig. 4),

which is consistent with the fMRI results showing increased activity in

this region during anticipation of peak emotional responses; as greater

number of chills suggests increased incidence of anticipation, greater

dopamine release would be expected in this area.

It is important to note that chills are not necessarily pleasurable

per se, as they can be unpleasant in other contexts (for example, as

a result of intense fear). Instead, chills are physiological markers of

intense ANS arousal5,15,33,34, which in turn is believed to underlie

peak pleasure during music listening5,15; we used chills here only to

allow objective quantification of a highly subjective response that

would be otherwise difficult to measure and because they afford preci-

sion as to the time at which the peak pleasure occurred. As such, chills

are byproducts, and not a cause of the emotional responses. Thus,

it is important to clarify that, although chills index peak emotional

responses in this group of people, the specific experience of chills is

not necessary to result in neural activity in the striatum, a finding

that is consistent with less-specific analyses performed in previous

studies6–8. This conclusion is confirmed by our findings that, even

when the chills epochs were excluded from the analysis, there was still

a significant linear relationship between increases in self-reported

pleasure and increases in hemodynamic activity in the regions that

showed dopamine release (Fig. 5). Furthermore, when chills were

reported, maximal signal was seen in the NAcc voxels that showed

a linear increase as participants progressed from neutral to low plea-

sure to high pleasure, further confirming that chills represented the

peak of pleasure in this group. This finding is also consistent with the

finding that the degree of binding potential decrease in the NAcc for

each participant was positively correlated with the degree of pleasure

reported from listening to the musical excerpts, irrespective of the

number of chills that were experienced (Fig. 4).

It should be noted that there was some activity in the ventral stria-

tum during the anticipation phase at lower statistical thresholds,

consistent with other studies using different stimuli24. However, we

found that, during the anticipatory phase, there was also increased

BOLD response in the caudate (more so than the NAcc), which then

shifted more ventromedially as participants reported experiencing

peak reward (Fig. 3). This is an important finding because the stimu-

lus that we are using is a dynamic reward with a temporal component,

allowing examination of the reward in real time as it progresses from

anticipation to peak pleasure states, which is generally not possible

because of limitations with movement inside the PET scanner. Some

studies administered the pleasurable stimulus (for example, food)

immediately before the scan and measured subsequent dopamine

release27, in which case anticipation and consumption cannot be dis-

tinguished. Other studies measured the anticipation phase online,

with the promise of the delivery of the tangible reward after the scan,

in which case the consumption phase is missed35,36. Music is a unique

reward that allows assessment of all reward phases online, from the

point that a single note is heard to the point at which maximum plea-

sure is reached.

The anatomical dissociation between the anticipatory and consum-

matory phases during intensely pleasurable music listening suggests

that distinct mechanisms are involved. This distinction may map onto

the ‘wanting’ and ‘liking’ phases of a reward in an error prediction

model37. The anticipatory phase, set off by temporal cues signaling

that a potentially pleasurable auditory sequence is coming, can trigger

expectations of euphoric emotional states and create a sense of want-

ing and reward prediction. This reward is entirely abstract and may

involve such factors as suspended expectations and a sense of resolu-

tion. Indeed, composers and performers frequently take advantage

of such phenomena, and manipulate emotional arousal by violating

expectations in certain ways or by delaying the predicted outcome

(for example, by inserting unexpected notes or slowing tempo) before

the resolution to heighten the motivation for completion. The peak

emotional response evoked by hearing the desired sequence would

26 2 VOLUME 14 | NUMBER 2 | FEBRUARY 2011 nature neurOSCIenCe

a r t I C l e S

represent the consummatory or liking phase, representing fulfilled

expectations and accurate reward prediction. We propose that each

of these phases may involve dopamine release, but in different sub-

circuits of the striatum, which have different connectivity and func-

tional roles.

The notion that dopamine can be released in anticipation of an

abstract reward (a series of tones) has important implications for

understanding how music has become pleasurable. However, the pre-

cise source of the anticipation requires further investigation. A sense

of anticipation may arise through one’s familiarity with the rules that

underlie musical structure, such that listeners are anticipating the next

note that may violate or confirm their expectations, in turn leading

to emotional arousal, or alternatively it may arise through familiarity

with a specific piece and knowing that a particularly pleasant section

is coming up11. These components are not mutually exclusive, as the

second likely evolves from the first, and the overall anticipation is

likely to be a combination of both. Nonetheless, the subtle differences

that exist between them will need to be disentangled through future

experiments that are specifically designed to parse out this distinc-

tion. Abstract rewards are largely cognitive in nature and our results

pave the way for future work to examine nontangible rewards that

humans consider rewarding for complex reasons.

Dopamine is pivotal for establishing and maintaining behavior. If

music-induced emotional states can lead to dopamine release, as our

findings indicate, it may begin to explain why musical experiences

are so valued. These results further speak to why music can be effec-

tively used in rituals, marketing or film to manipulate hedonic states.

Our findings provide neurochemical evidence that intense emotional

responses to music involve ancient reward circuitry and serve as a

starting point for more detailed investigations of the biological sub-

strates that underlie abstract forms of pleasure.

METHODS

Methods and any associated references are available in the online

version of the paper at http://www.nature.com/natureneuroscience/.

Note: Supplementary information is available on the Nature Neuroscience website.

ACKNOWLEDGMENTS

We thank the staff of the Montreal Neurological Institute PET and MR Units

and the staff of the Centre for Interdisciplinary Research in Music Media and

Technology for help with data acquisition, M. Ferreira and M. Bouffard for their

assistance with data analysis, and G. Longo for assistance with stimulus preparation.

This research was supported by funding from the Canadian Institutes of Health

Research to R.J.Z., a Natural Science and Engineering Research Council stipend to

V.N.S., a Jeanne Timmins Costello award to V.N.S. and Centre for Interdisciplinary

Research in Music Media and Technology awards to V.N.S. and M.B.

AUTHOR CONTRIBUTIONS

V.N.S., R.J.Z. and A.D. designed the study. V.N.S. and M.B. performed all experiments.

V.N.S., M.B. and K.L. analyzed the data. V.N.S. and R.J.Z. wrote the manuscript.

COMPETING FINANCIAL INTERESTS

The authors declare no competing financial interests.

Published online at http://www.nature.com/natureneuroscience/.

Reprints and permissions information is available online at http://www.nature.com/

reprintsandpermissions/.

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doi:10.1038/nn.2726

ONLINE METHODS

Participant screening and stimulus selection. 217 individuals responded to

advertisements requesting people who experience chills to music; after five rounds

of screening, the final group included eight participants. First, individuals pro-

vided ten pieces of instrumental music to which they experience intense pleasure

and “chills” without restrictions to the genre of music, which included classical,

folk, jazz, electronica, rock, punk, techno and tango (see http://www.zlab.mcgill.

ca/supplements/supplements_intro.html for samples). Next, an email question-

naire was completed to determine whether their chills were experienced at times

of extreme pleasure, consistently at the same point in the music without diminish-

ing on multiple listening, in different environments, and the selected music was

not specifically or generally associated with an episodic memory. 45 individuals

continued to the third screening session, where a history of medical, psychiatric

illness, or substance abuse was ruled out. 40 participants continued to the fourth

screening session, where control stimuli were selected for each individual using

a paradigm where one individual’s pleasurable music is used as another person’s

neutral music5,15. This way, group-averaged data analysis involves comparison

of similar sets of stimuli. Although we were not able to match perfectly between

the control and pleasurable pieces used for all participants, efforts were made to

ensure that pieces were as evenly distributed as possible. Each individual rated

other participants’ music on a scale of 1–10 (neutral to extremely pleasurable).

From the pieces rated neutral, the ones that were most familiar to that subject

were selected to minimize differences in familiarity between pleasurable music

and neutral music conditions. Individuals whose music was found to be “neutral”

by at least one other participant were asked to continue. Participants were asked

not to listen to those pieces anymore during the course of the study to ensure

maximal responses during testing. 28 individuals participated in the final screen-

ing session to verify the chills response at prespecified times through subjective

and physiological responses. Participants listened to their chills-inducing music

while providing subjective ratings of pleasure through button presses and indi-

cating when they experienced a chill (see ref. 15 for additional details). The ten

participants (five female, five male) who most reliably experienced chills during

their peak pleasure responses to music accompanied by clear increases in ANS

activity were selected for the study. The final group of participants was between

the ages of 19 and 24 (M = 20.8, ± 1.9 years) and had a wide range of musical

experiences from no training to 15 years of experience.

Procedures. Ethical approval for the study was granted by the Montreal

Neurological Institute (MNI) Research Ethics Board. All individuals gave writ-

ten informed consent before participating in the study. Testing took place over

three sessions. The first two sessions involved PET scanning (Supplementary

Fig. 1) and psychophysiological recording (Supplementary Fig. 2) and the third

session involved fMRI scanning (Supplementary Fig. 3).

Statistical analysis. Signal filtering was performed to remove noise and artifacts

(see ref. 15 for additional details). Data were downsampled to 1-s epochs and

compared across neutral music and pleasurable music conditions. To account

for unequal variances across conditions, we used Welch’s t test. A second analysis

was performed to examine the relationship between the intensity of chills expe-

rienced and psychophysiological responses. Outliers beyond four s.d. from the

mean were removed for each excerpt and for each participant individually (2–5%

of the data points). Subjective ratings for one individual were not recorded and

BVP amplitude data for one participant demonstrated excessive artifacts, thus

these data were not included in the analysis. Z score values of each biosignal

were calculated for each excerpt and plotted against subjective ratings of chills

intensity that subjects reported after hearing each excerpt (Fig. 1). Correlation

coefficients were calculated for the intensity of chills and changes in each of the

psychophysiological measures (Supplementary Table 1).

For [11C]raclopride PET, we discarded two datasets because of participant

discomfort during the first session. Data from the remaining eight participants

were analyzed. PET emission frames were reconstructed and corrected for

gamma ray attenuation and scatter. All PET images were corrected for head

motion using a co-registration–based method, which performs interframe

realignment and compensates for emission-transmission mismatches38. The

motion-corrected PET data were summed over the time dimension and aligned

to the subject’s anatomical magnetic resonance image. Anatomical MRI were

transformed into standardized stereotaxic space by means of automated feature

matching algorithm to the MNI template39. All transformed images were visually

inspected to ensure that there were no alignment errors.

Parametric images were generated in the native PET space by computing

[11C]raclopride binding potential (binding potential = BAvail / KD, where BAvail

is the density of available receptors and KD is the dissociation constant) at each

voxel of interest40,41. Voxelwise [11C]raclopride binding potential was calculated

using a simplified reference region method40,41, with the cerebellum chosen as

reference region because it does not contain specific D2 receptor–like binding

sites and can be used for the determination of nonspecific binding and free radio-

ligand in the brain42. The gray matter of the cerebellum assigned as reference

region was initially segmented in Talairach space from a probabilistic atlas43

and a neural net classifier44. The [11C]raclopride binding potential maps were

then transformed into MNI space39 using the previously determined transforma-

tion parameters. Statistical parametric t maps of binding potential change were

produced by comparing the parametric binding potential maps of the two scan

sessions (pleasurable music and neutral music), using a previously described

method45. This calculation uses the residuals of the least-squares fit of the com-

partmental model, which improves the sensitivity to small changes by providing

better estimates of the s.d. at the voxel and by increasing the degrees of freedom.

It is assumed that a reduction in [11C]raclopride binding potential is indicative

of an increase in extracellular dopamine concentration46. Clusters of significant

change were defined as all contiguous striatal voxels on the t map exceeding a

magnitude threshold of 3.11. This threshold was considered to be significant

(P < 0.05, corrected for multiple comparisons) for a search volume equal to the

striatum and an effective spatial resolution of 8-mm full-width at half maximum

(FWHM)47. Mean binding potential values were extracted from each significant

cluster for each individual and percent change in binding potential was calculated

as [(BPneutral − BPpleasurable) × 100 / BPneutral], and compared with subjectively

reported post-listening ratings of the number of chills, intensity of chills and

degree of pleasure experienced.

fMRI. One scan was terminated because of claustrophobia. fMRI data were cor-

rected for motion using in-house software. To increase the signal-to-noise ratio,

we spatially smoothed the images (or low-pass filtered) with an 8-mm FWHM

isotropic Gaussian kernel. Image analyses were performed with fMRISTAT, which

consists of a series of MATLAB scripts that utilize the general linear model for

analyses48. The general linear model (Y = Xβ + ε) expresses the response vari-

able (BOLD signal) Y in terms of a linear combination of explanatory variables

(events) X, the parameter estimates (effects of interest) β and the error term ε.

Temporal drift was modeled as cubic splines and removed by inclusion into the

general linear model as a variable of non-interest. The linear model was solved

for the parameter estimates β with least squares, yielding estimates of effects,

standard errors and t statistics for each contrast and for each run.

Before group statistical maps for each contrast of interest were generated, in-

house software was used to linearly transform anatomical and functional images

from each subject into standard MNI stereotaxic coordinate space using the MNI

305 template39. A mixed-effects linear model was subsequently used to combine

data across subjects; the s.d. images were smoothed with a Gaussian filter so that

the ratio of the random-effects variance divided by the fixed-effects variance

results in approximately 100 degrees of freedom. Because the main purpose of

the fMRI analyses was to measure BOLD activity in predefined striatal regions,

we adopted an uncorrected statistical threshold of P < 0.01.

For the main analysis, three events were defined: the peak emotional response

(PER) condition represented all epochs during which the participant was pressing

the chills, the anticipation condition represented 15-s epochs immediately pre-

ceding the onset of the PER condition defined post hoc, and the neutral condition

represented all epochs during which participants were pressing down the neutral

button. Note that these neutral epochs are different from the neutral music condi-

tion, which were not used in this case, as the neutral music condition contrasted

with the pleasurable music condition shows less activity in the striatum. As such,

any epoch selected from the pleasurable music condition, even those not related

to peak pleasure, could have shown increased striatal activity and overestimated

the results of the study. The anticipation period was defined as the 15 s before

the PER based on previous findings that this is the time frame during which

psychophysiological responses begin to increase significantly relative to mean

responses throughout the excerpt15. The times at which participants pressed the

low pleasure and high pleasure buttons were also included in the model to ensure

nature neurOSCIenCe doi:10.1038/nn.2726

that they did not contribute to baseline. A 0.1-s epoch was incorporated into the

model each time a button was pressed to account for neural activity involved in

button pressing. The BOLD data from times when participants were responding

to questions were excluded from the analysis. The planned comparisons for the

main analysis were then entered into the analysis: anticipation of PER = anticipa-

tion condition minus neutral condition and experience of PER = PER condition

minus neutral condition.

Time series analysis. To further investigate the temporal dynamics of the reward

response, we calculated the time series of hemodynamic activity in the caudate and

NAcc clusters. To avoid the circularity problem22, we derived our VOIs from the

PET data, which are independent of the fMRI data. We first identified the voxel

showing the maximum dopamine release during the [11C]raclopride PET scan,

in the caudate and NAcc clusters. We then extracted the mean signal for each

VOI during the entire fMRI run obtained from each volume and calculated the

percent BOLD signal change relative to the mean of the run during the epochs in

which PERs were reported. Participants often experienced multiple chills one after

another. For the purposes of this analysis, the percent signal change during the

first chill of the series was used, which ranged in duration from 1–4 s. The BOLD

response for each of those seconds is plotted in Figure 3c. Mean signal change

for each second preceding this response for each individual, up to 15 s, was also

plotted to demonstrate hemodynamic time series during the anticipation period.

As a result of cardiac gating, a different number of frames were acquired for each

person during this 15-s period and acquisition time varied from 2.1 to 3 s depend-

ing on the individual’s heart rate. As such, the VOI values obtained at each frame

were interpolated to provide an estimate of signal during each second preceding

the peak response. The mean number of frames sampled for calculating time

series was 5.3 (s.d. = 1.3) during anticipation and 1.6 (s.d. = 1.2) during chills. The

mean signal change during neutral button presses was also calculated for each VOI

separately and plotted in Figure 3d for reference. Finally, the percent signal change

for 5 s preceding the anticipatory response were also plotted for reference.

Conjunction analysis. Because [11C]raclopride binds with D2 receptors mainly

in the striatum49, our fMRI data analysis was also limited to this region, masked

by areas that showed dopamine release. A spatial conjunction analysis was

performed to examine the temporal aspects of hemodynamic activity in areas

that had shown changes in [11C]raclopride binding potential on PET. A mask of

striatal areas that had revealed substantial changes in binding potential using the

stated threshold (t ≥ 3.11) was created to spatially mask both contrasts (outlined

in the fMRI data analysis section): anticipation of PER and experience of PER.

This procedure allowed us to measure BOLD changes only in voxels that had

shown binding potential differences in the PET study.

38. Costes, N. et al. Motion correction of multi-frame PET data in neuroreceptor

mapping: simulation based validation. Neuroimage 47, 1496–1505 (2009).

39. Collins, D.L., Peters, T.M. & Evans, A.C. Automatic 3D intersubject registration of

MR volumetric data in standardized Talirach space. J. Comput. Assist. Tomogr. 18,

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tomography neuroreceptor ligand data. Neuroimage 12, 245–256 (2000).

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PSYCHO-ONCOLOGIE

Background and object: The research on the impact of music therapy in alleviating psychological distress and improving the quality of life in perioperative cancer patients remains inconclusive. The primary objective of this study is to analyze the effects of music therapy on psychological distress and quality of life in patients undergoing cancer surgery. Method: A search strategy was used with PubMed, Embase, Cochrane Library, and Web of Science. The search period covered all records from database inception to November 2024. This systematic review and meta-analysis followed the publishing guidelines as set forth by PRISMA and was registered with PROSPERO (registration number CRD 42024587929). The selection criteria were based on randomized clinical trials evaluating pain, anxiety, quality of life, and sleep in patients undergoing perioperative surgery for cancer. This study used the Cochrane Risk of Bias Assessment Tool to determine. Meta-analysis was performed using Stata 18.0 software and Revman 5.4. Results: patients’ pain, the pain relief in the intervention group was significantly better than that in the control group at 4 h after extubation [SMD = −2.95 (95% CI: −3.58, −2.31)], and during longer follow-up, it was found that the patients’ pain relief was significantly better as the duration of the intervention increased, with 1–2 weeks being [SMD = −0.70 (95% CI: −1.58, 0.18)], 4–6 weeks [SMD = −1.01 (95% CI: −1.83, −0.19)], > 6 weeks [SMD = −1.51 (95% CI: −2.17, −0.85)]. The study of patient anxiety found that pre-surgical music therapy did not significantly alleviate anxiety [SMD = −0.37 (95% CI: −0.81, 0.08)], and at 4 h after extubation, the intervention group had a significantly better anxiety effect than the control group [SMD = −3.42 (95% CI: −4.11, −2.73)]. The patients’ sleep was analyzed for a total of about 18 weeks of follow-up, and it was found that as the duration of the intervention increased, the patients’ overall sleep showed significant improvement compared to the control group, which showed a trend of further improvement as the duration of the intervention increased. Patients’ long-term quality of life was evaluated using PRI scores (long-term prognosis), and the results indicated that music therapy patients showed superior outcomes compared to the control group at 2 weeks [WMD = −1.52, 95% CI: −2.48 to −0.57], 4 weeks [WMD = −1.62, 95% CI: −2.57 to −0.57], and 6 weeks [WMD = −1.27, 95% CI: −1.96 to −0.58]. Moreover, the benefits of music therapy were sustained over the long term. In a 12-month follow-up study, music therapy patients were consistently more likely to report better quality of life scores than those in the control group. Conclusion: The use of music therapy for cancer surgery patients can significantly improve postoperative pain and anxiety and help patients improve their sleep and long-term prognosis.

Art and creativity in Parkinson's disease: the mysterious effects of dopamine

Article

May 2025
ZH NEVROL PSIKHIATR

The article is devoted to the phenomenon of the emergence or enhancement of creative abilities during therapy in some patients with Parkinson’s disease (PD). The article discusses the possible pathogenetic causes of this phenomenon, the connection with impulsive-compulsive disorders (ICD). All PD patients who are addicted to one type of creativity are characterized by increased motivation, forcing them to spend hours doing what they love, the time of which coincided with the start of dopaminergic therapy. There is a fine line between the emerging «passion» for art and CAVIAR, which is determined by the dose of Antiparkinsonian drugs, genetic characteristics, and personal characteristics. The issue of the emergence of creativity in the work of patients with PD remains controversial, and most studies indicate a deterioration in divergent thinking, which is a criterion for creativity. The results of the observation of artists suffering from PD showed changes in the style of their work against the background of the disease, the appearance of an emphasis on color, changing the brightness and spectrum of the color palette, moving to more abstract images. Among the factors that can influence creative activities, such as pre—existing skills or abilities in relation to a particular type of art, taking dopaminergic drugs, their dose, the preservation of cognitive functions, family support, and the social environment are discussed.

The Unique Autonomic Signatures of Savoring Meditation for Anxiety Reduction: A Pilot Randomized Controlled Trial

Article

May 2025
J ANXIETY DISORD

The right sound at the right time: Cerebellar and ventral striatal involvement in imitating pitch and timing

Article

May 2025
J NEUROLINGUIST

Analyzing Functionalized Carbon Quantum Dots in Electrode Engineering for the Precise Electrochemical Detection of a Neurotransmitter: Achieving Laboratory Accuracy with Portable Sensors

Article

Apr 2025

Threefold relationship between ideal humanity and sublime beauty in Chinese art forms

Article

Full-text available

Apr 2025

In Chinese thought, the concept of the “sublime” is closely intertwined with “beauty,” the two concepts merging to form a sublime beauty that seeks the continuous development of universal life amid change. This paper explores the multifaceted relationship between the Chinese artistic mind and sublime beauty through three dimensions of the research model: potential, processes, and goals. In terms of potential, Chinese artistic thought places full trust in the inherent potential of an individual’s ideal humanity, emphasizes the awakening of the sublime beauty within each person through specific art forms, and cultivates different perspectives to understand the connection between the mind and the sublime beauty of our world. In terms of process, Chinese artistic thought is characterized by the focused sincerity of the creative mindset; creative thinking that balances the “degree” of rational expression of emotions and the “qi” cultivated through daily spiritual practice; and the cognition of the sublime, which combines the gradual enlightenment gained from daily experiences of embodied cognition with the sudden enlightenment triggered by creative talent. In terms of artistic goals, ideal humanity in pursuit of sublime beauty is divided into three states: the “self state” that manifests the style of the individual subject, the “no-self state” that transcends the limitations of the self, and the “empty state” that surpasses even the cognitive notion of “transcending the self.” The threefold relationship between ideal humanity and sublime beauty in Chinese art can provide contemporary psychology with research model and unique perspectives on being aware of one’s self-potential, understanding their emotions and other aspects of the mind, and constructing multiple value goals.

Musical Expectancy and Thrills

Article

Full-text available

Jul 1993

Intense emotional responses to music: A test of the physiological arousal hypothesis

Article

Full-text available

Oct 2004
Psychol Music

Nikki Rickard

A consistent theme across general theories of emotion is that intense emotions are accompanied by increased levels of physiological arousal. The aim in the current study was to determine whether music which elicited intense emotions produced higher levels of physiological arousal than less emotionally powerful music. Twenty-one participants (9 females, 12 males) were exposed to relaxing music, arousing (but not emotionally powerful) music, an emotionally powerful film scene, and a music piece selected by participants as 'emotionally powerful'. A range of physiological and subjective measures of arousal was recorded before and during the treatments. The emotionally powerful music treatment elicited significantly greater increases in skin conductance and number of chills than the other treatments. The findings are discussed in terms of the sensitivity of skin conductance and chills as measures of emotional intensity, and it is suggested the study offers some support for the emotivist thesis of musical emotions. Copyright

Investigating emotion with music: An fMRI study

Article

Jun 2003

The present study uses music as a tool to induce emotion, and functional magnet resonance imaging (fMRI) to determine neural correlates of emotion processing. We found that listening to pleasant music activated the larynx representation in the rolandic operculum. The larynx is the source of vocal sound, and involved in the production of melody, rhythm, and emotional modulation of the vocal timbre during vocalization. The activation of the larynx is reminiscent of the activation of premotor areas during the observation of grasping movements and might indicate that a system for the perception-action mediation which has been reported for the visual domain also exists in the auditory domain.

A simplified reference tissue model for PET receptor studies

Article

Jan 1996

A unified statistical approach for determining significant voxels in images of cerebral activation

Article

Jan 1996
HUM BRAIN MAPP

We present a unified statistical theory for assessing the significance of apparent signal observed in noisy difference images. The results are usable in a wide range of applications, including fMRI, but are discussed with particular reference to PET images which represent changes in cerebral blood flow elicited by a specific cognitive or sensorimotor task. Our main result is an estimate of the P-value for local maxima of Gaussian, t, χ2 and F fields over search regions of any shape or size in any number of dimensions. This unifies the P-values for large search areas in 2-D (Friston et al. [1991]: J Cereb Blood Flow Metab 11:690–699) large search regions in 3-D (Worsley et al. [1992]: J Cereb Blood Flow Metab 12:900–918) and the usual uncorrected P-value at a single pixel or voxel.

An exploratory study of musical emotions and psychophysiology

Article

Jan 1997
CAN J EXP PSYCHOL

Carol L. Krumhansl

A basic issue about musical emotions concerns whether music elicits emotional responses in listeners (the 'emotivist' position) or simply expresses emotions that listeners recognize in the music (the 'cognitivist' position). To address this, psychophysiological measures were recorded while listeners heard two excerpts chosen to represent each of three emotions: sad, fear, and happy. The measures covered a fairly wide spectrum of cardiac, vascular, electrodermal, and respiratory functions. Other subjects indicated dynamic changes in emotions they experienced while listening to the music on one of four scales: sad, fear, happy, and tension. Both physiological and emotion judgments were made on a second-by-second basis. The physiological measures all showed a significant effect of music compared to the pre-music interval. A number of analyses, including correlations between physiology and emotion judgments, found significant differences among the excerpts. The sad excerpts produced the largest changes in heart rate, blood pressure, skin conductance and temperature. The fear excerpts produced the largest changes in blood transit time and amplitude. The happy excerpts produced the largest changes in the measures of respiration. These emotion-specific physiological changes only partially replicated those found for non-musical emotions. The physiological effects of music observed generally support the emotivist view of musical emotions.

A general statistical analysis for fMRI data

Article

May 2000

Animal: Validation and Applications of Nonlinear Registration-Based Segmentation

Article

Nov 2011

Magnetic resonance imaging (MRI) has become the modality of choice for neuro-anatomical imaging. Quantitative analysis requires the accurate and reproducible labeling of all voxels in any given structure within the brain. Since manual labeling is prohibitively time-consuming and error-prone we have designed an automated procedure called ANIMAL (Automatic Nonlinear Image Matching and Anatomical Labeling) to objectively segment gross anatomical structures from 3D MRIs of normal brains. The procedure is based on nonlinear registration with a previously labeled target brain, followed by numerical inverse transformation of the labels to the native MRI space. Besides segmentation, ANIMAL has been applied to non-rigid registration and to the analysis of morphometric variability. In this paper, the nonlinear registration approach is validated on five test volumes, produced with simulated deformations. Experiments show that the ANIMAL recovers 64% of the nonlinear residual variability remaining after linear registration. Segmentations of the same test data are presented as well. The paper concludes with two applications of ANIMAL using real data. In the first, one MRI volume is nonlinearly matched to a second and is automatically segmented using labels, predefined on the second MRI volume. The automatic segmentation compares well with manual labeling of the same structures. In the second application, ANIMAL is applied to seventeen MRI data sets, and a 3D map of anatomical variability estimates is produced. The automatic variability estimates correlate well (r =0.867, p = 0.01) with manual estimates of inter-subject variability.

Learning and Motivation?

Article