Mobbs

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Neuron, Vol. 40, 1041–1048, December 4, 2003, Copyright
2003 by Cell Press
Humor Modulates the Mesolimbic Reward Centers
Dean Mobbs,
1,2
Michael D. Greicius,
1,2,3
modulate humor appreciation is of both social and clini-
Eiman Abdel-Azim,
1,2
Vinod Menon,
1,2,4,5
cal relevance.
and Allan L. Reiss
1,2,4,5,
*
Recent advances in functional neuroimaging have en-
1
Stanford Psychiatry Neuroimaging Laboratory
abled researchers a clear avenue from which to explore
2
Department of Psychiatry and Behavioral Sciences
this critical human attribute. Figuring prominently in the
3
Department of Neurology and Neurological
semantic and linguistic aspects of humor comprehen-
Sciences
sion are the temporo-occipital junction, middle/inferior
4
Program in Neuroscience
temporal cortex, and inferior frontal gyrus (IFG), includ-
5
Stanford Brain Research Institute
ing Broca’s area (Goel and Dolan, 2001; Ozawa et al.,
Stanford University School of Medicine
2000). Moreover, stimuli that provoke laughter (i.e., the
Stanford, California 94305
motor response to humor) have been shown to modulate
activity in the supplementary motor area (SMA) proper,
a somatatopically mapped region involved in multiple
motor operations (e.g., Toyokura et al., 2002), including
Summary
motor components of expressive laughter (Iwase et al.,
2002; Osaka et al., 2003). One preliminary fMRI study of
Humor plays an essential role in many facets of human
joke-induced humor implicated the right medial ventral
life including psychological, social, and somatic func-
prefrontal cortex (MVPFC) in the amusing, or rewarding,
tioning. Recently, neuroimaging has been applied to
feeling that accompanies a joke, although this has yet
this critical human attribute, shedding light on the af-
to be replicated (Goel and Dolan, 2001). Despite this
fective, cognitive, and motor networks involved in hu-
sequence of discoveries, investigations have failed to
mor processing. To date, however, researchers have
conclusively demonstrate the subcortical correlates of
failed to demonstrate the subcortical correlates of the
the most fundamental feature of humor—reward.
most fundamental feature of humor—reward. In an
Important clues about the neurological systems in-
effort to elucidate the neurobiological substrate that
volved in regulating reward have come from a recent
subserves the reward components of humor, we un-
flurry of fMRI studies using a myriad of primary and
dertook a high-field (3 Tesla) event-related functional
secondary rewarding tasks, including monetary reward
MRI study. Here we demonstrate that humor modu-
paradigms, the perception of aesthetically attractive
lates activity in several cortical regions, and we pres-
faces, and objects signifying wealth/dominance (Aharon
ent new evidence that humor engages a network of
et al., 2001; Breiter et al., 2001; Erk et al., 2002; Knutson
subcortical regions including the nucleus accumbens,
et al., 2001). These studies have convergently docu-
a key component of the mesolimbic dopaminergic re-
mented increased hemodynamic signal in the mesolim-
ward system. Further, the degree of humor intensity
bic dopaminergic reward system, a system known to
was positively correlated with BOLD signal intensity
play a pivotal role in drug reward and motivational be-
in these regions. Together, these findings offer new
haviors (for review, see Schultz, 2002). This system en-
insight into the neural basis of salutary aspects of
compasses a variety of distinct, but interconnected,
humor.
dopamine-enriched structures, including the ventral stri-
atum/nucleus accumbens (NAcc), the ventral tegmental
area (VTA), and the amygdala. Although our understand-
Introduction
ing of the anatomical organization and function of the
mesolimbic dopaminergic reward system is relatively
Without humor, life would undeniably be less exhilarat-
advanced, our understanding of this system’s role in
ing. Indeed, the ability to comprehend and find a joke
humor, a powerful endogenous reward, remains remark-
funny plays a defining role in the human condition, es-
ably poor.
sentially helping us to communicate ideas, attract part-
In the experiment reported here, we used event-
ners, boost mood, and even cope in times of trauma
related fMRI (efMRI) to seek hemodynamic increases in
and stress (Dixon, 1980; Gavrilovic et al., 2003; Martin,
regions associated with cartoons considered to be
2001; Neuhoff and Schaefer, 2002; Nezlek and Derks,
funny. While in the scanner, each subject was presented
2001). These beneficial manifestations are compli-
with 42 cartoons previously rated, by a separate group
mented at the physiological level where humor (i.e., the
of matched subjects, as being funny and 42 nonfunny
perception that something is funny; McGhee, 1971) is
cartoons (i.e., cartoons with funny cues omitted). Sub-
thought to have numerous salutary effects, including
jects were explicitly asked to respond with a press of a
acting as a natural stress antagonist and possibly en-
button if they found the cartoon funny (Figure 1A) or not
hancing the cardiovascular, immune, and endocrine
(Figure 1B). Our rationale for the present efMRI design
systems (Bennett et al., 2003; Berk et al., 1989; Fred-
was 3-fold: (1) the unpredictable nature of random efMRI
rickson and Levenson, 1998; Fry, 1992; Lefcourt et al.,
designs allowed us to look at pure reward, rather than
1990). It is therefore apparent that developing a sophisti-
anticipatory rewards (cf. Braver and Brown, 2003); (2)
cated understanding of the discrete neural systems that
because of the subjective quality of humor appreciation,
we parsed out activation on a subject-by-subject and
cartoon-by-cartoon basis, thus allowing us to take into
*Correspondence: reiss@stanford.edu
Neuron
1042
Figure 1. Example of a Funny Cartoon and
the Same Cartoon with Funny Cues Omitted
(A) Funny cartoon. (B) Nonfunny cartoon.
Stimuli were presented in an event-related
fMRI paradigm, with each cartoon being pre-
sented in random order for 6000 ms. A jittered
interstimulus interval (ISI) was used, varying
randomly between 2000, 4000, and 6000 ms
and counterbalanced, a priori, across funny
and nonfunny events. Analysis was limited
to the blood-oxygenation level-dependent
(BOLD) signal acquired during stimulus pre-
sentation (Figure 1C). Data were collected in
one 15 min and 4 s session consisting of 84
events using a TR of 2000 ms (see Experimen-
tal Procedures for more details).
consideration individualistic differences in humor; and
ject and cartoon-by-cartoon basis) preferred funny car-
toons to those considered not funny (see Figures 1A
(3) ultimately, this design allowed us, using postscan
ratings by each volunteer, to parametrically examine the
and 1B). The primary voxel-based analysis revealed a
network of cortical and subcortical regions involved in
association between humor intensity (and presumably
the degree of reward) and blood-oxygen level-depen-
humor appreciation (Figure 2). Significantly higher BOLD
dent (BOLD) signal magnitude.
signal was identified in three cortical areas. One cluster
In accordance with previous neuroimaging studies of
was centered in the left temporo-occipital junction ex-
humor, laughter, and reward, we hypothesized that
tending into the fusiform gyrus (Brodmann area [BA] 37).
funny cartoons, in comparison to nonfunny cartoons,
A second cluster was observed in Broca’s area of the
would elicit increased activation in several language and
left lateral IFG (BA 44/45). This cluster also extended
semantic regions, including the left anterior and poste-
ventrally to include a subcluster in the temporal pole
rior temporal regions and IFG, including Broca’s area.
(BA 38). The third cortical cluster was observed in the
We also predicted that motor aspects of humor would
SMA proper (BA 6) contiguously extending to the pre-
be expressed in the SMA (i.e., laughter and smiling).
SMA and dorsal anterior cingulate (dACC; BA 32). A
Ultimately, we hypothesized, several structures within
significant activation cluster was also found encapsulat-
the mesolimbic dopaminergic reward system, including
ing the anterior thalamus, ventral striatum/NAcc, ventral
the NAcc, would become active as subjects interpreted
tegmental area (VTA), hypothalamus, and amygdala.
cartoons they subjectively considered funny.
These results are summarized in Table 1.
A post hoc covariate analysis examining the associa-
Results
tion between humor intensity (i.e., degree of funniness
as rated by each experimental subject) and BOLD signal
Behavioral Results
magnitude revealed a striking concordance with whole-
Examination of response latencies showed a robust,
brain activation. This analysis showed humor intensity
albeit nonsignificant, trend [
t
(15)
1.8, p
.093]
to be associated with increased activation in several
for subjects to respond faster to nonfunny cartoons
regions also detected in our primary analysis including
(mean
standard deviation: 3645.1
691.1) than to
the left temporo-occipital junction, IFG, temporal pole,
funny cartoons (3859.1
438.4). Of the funny cartoons,
SMA proper, and the mesolimbic dopaminergic reward
subjects rated an average of 61.5%
6.9% as subjec-
system (see Figure 3 and Experimental Procedures for
tively funny. These findings parallel those of a prior ef-
more details).
MRI study of humor appreciation (Goel and Dolan, 2001).
fMRI Results
Time-Series Analysis: Nucleus Accumbens
We used a random-effects model to identify residual
activation patterns for subjectively (i.e., subject-by-sub-
To further probe the hemodynamic response of the NAcc
to humor, we raised the height threshold and isolated
Humor and Reward
1043
0.05) corrected at the whole-brain level. Results revealed activation in the left temporo-occipital junction
(Brodmann area [BA] 37), inferior frontal gyrus (IFG; BA 44/45) extending ventrally to include a subcluster in the temporal pole (BA 38), and
supplementary motor area (SMA proper; BA 6/32) extending to the pre-SMA and dorsal anterior cingulate (dACC). A subcortical cluster also
was observed encompassing the ventral striatum/NAcc, anterior thalamus, ventral tegmental area (VTA), hypothalamus, and amygdala (see
Results and Experimental Procedures for more details).
the caudal aspect of this structure as a 10 voxel subclus-
nonfunny cartoons activated the temporo-occipital
junction, IFG/temporal pole, and SMA/dACC, all in the
ter (at p
0.0001; peak stereotaxic coordinate at: 6, 2,
4) within the larger subcortical cluster. Using this 10
left hemisphere. This distinct pattern of left-lateralization
has been observed in monetary and video-game reward
voxel region of interest (ROI), we extracted the average
time courses for funny and nonfunny cartoons across
tasks, in addition to event-related potential (ERP) and
clinicopathological studies of humor appreciation, signi-
all 16 subjects (Figure 4). This analysis emphasizes the
prominent increase in BOLD signal in the NAcc during
fying that this hemisphere plays a distinct role in the
processing of reward and positive emotional stimuli
funny cartoons, compared to negligible BOLD signal
decreases in response to those that were not funny.
(Breiter et al., 2001; Coulson and Kutas, 2001; Gardner
et al., 1975; Koepp et al., 1998).
Activation of the temporo-occipital junction (BA 37),
Discussion
a division of the ventral-stream of visual cortical pro-
cessing (Ungerleider and Haxby, 1994), has previously
The results reported here provide the first evidence that
humor engages a network of subcortical structures, in-
been implicated in the semantic processing of jokes
needing holistic coherence (Goel and Dolan, 2001), de-
cluding the VTA, NAcc, and amygdala—key components
of the mesolimbic dopaminergic reward system. With
tection of incongruity (Iwase et al., 2002), and the identifi-
cation of emotionally important visual cues (Geday et al.,
respect to cortical components of humor appreciation,
our results are in good agreement with previous studies.
2003). Intriguingly, this activation cluster encompassed
the left fusiform gyrus, a region which, when electrically
We found that funny cartoons when contrasted with
Table 1. Brain Areas in Which Stimuli-Related BOLD Signal Was Significant for Funny Cartoons over and above Nonfunny Cartoons
Cluster Size
Talairach Coordinates
Regions
Right/Left
Brodmann’s Area
p Value
(Voxel)
z Score
(x, y, z)
Temporo-occipital junction
a
L
37
0.001
587
5.63
(
44,
60, 12)
IFG,
a
temporal pole
L
44/45/38
0.001
1457
4.73
(
50, 16, 20)
SMA proper,
a
pre-SMA, dACC
L
6/32
0.017
218
3.47
(
2, 5, 62)
Ventral striatum,
a
NAcc,
L/R
–
0.001
1406
4.71
(
10,
2, 4)
anterior thalamus, VTA,
hypothalamus, and amygdala
Only clusters with an extent threshold of p
0.05 corrected for whole brain are reported. Stereotaxic coordinates and Brodmann areas as
in Talairach and Tournoux (1988) atlas space.
Abbreviations: SMA, supplementary motor area; NAcc, nucleus accumbens; VTA, ventral tegmentum area; dACC, dorsal anterior cingulate
cortex; IFG, inferior frontal gyrus.
a
Denotes peak activation.
Figure 2. Functional Topographical Map of Funny Minus Nonfunny Cartoons
mricro.html). Significant clusters of activation were determined using the joint expected probability distribution (Poline et al., 1997) with height
(p
0.01) and extent threshold (p
Neuron
1044
Figure 3. Composite Montage Showing Activated Regions Covarying with Degree of Humor Intensity
Significant clusters of activation were determined using the joint expected probability distribution (Poline et al., 1997), with height (p
0.05)
and extent threshold (p
0.01) corrected at the whole-brain level. Results showed activation in the left temporo-occipital junction: peak
Talairach coordinates: x, y, z;
46,
65,
14; Z
5.73, BA 19/37; left IFG:
51, 9, 27; Z
4.92; BA 9/44/45. Again this cluster extended
ventrally to the temporal pole (TP) (BA 38). A cluster was also found in the medial SMA proper:
2, 18, 51; Z
4.22; BA 6/8. A final cluster
was also observed encompassing the mesolimbic doperminergic system:
8,
33,
7; Z
4.01. This clusters also extended to the right IFG
(BA 44).
stimulated, induces laughter accompanied by a feeling
cognitive functions somewhat of an enigma (Cabeza and
Nyberg, 2000), it is thought that this region is involved in
of mirth (i.e., positive emotion) (Arroyo et al., 1993). In
view of these observations, this region may be involved
lexical retrieval and is a major storehouse for semantic
knowledge (Damasio et al., 1996; Mummery et al., 2000).
in the incongruent, or surprising (Brownell et al., 1983),
elements of a joke, and thus may play a pivotal role in
One interpretation is that these regions may constitute
a frontal-temporal network involved in integrating lan-
the early stages of the humor network.
The largest area of cortical activation occurred in the
guage and long-term memory (Goel, 2003). Such a net-
work would presumably be needed to comprehend and
left lateral IFG (BA 44), including Broca’s area, possibly
reflecting the language-based decoding of the stimuli.
find the cartoon jokes funny.
Collectively, the temporo-occipital junction, IFG, and
The vast amount of literature has implicated the IFG in
word perception and production (e.g., Price et al., 1996),
temporal pole are of particular theoretical interest as
they fit well with Suls’ influential
incongruity-resolution
although it is now commonly believed that the IFG is a
polymodal language region, involved in numerous as-
model
of joke appreciation, which posits that a cartoon
is found funny via a two-stage process. First, the joke
pects of language processing, including semantic and
sentence processing (for review, see Gernsbacher and
recipient finds their expectation is incongruous with the
cartoon caption. Second, the joke recipient revises their
Kaschak, 2003). This cluster also proceeded ventrally
to the temporal pole (BA 38). Although the temporal pole
initial interpretation to accommodate the caption and
the rest of the cartoon, thus establishing coherence
is highly prone to susceptibility artifact and resultant
signal loss (Ojemann et al., 1997), leaving its role in
(Suls, 1972). It is an appealing conceptualization that
Figure 4. Averaged Time Series for Funny
Compared to Nonfunny Activity in the Right
NAcc
Stereotaxic coordinates: x, y, z; 6, 2,
4;
p
0.0001.
Humor and Reward
1045
the temporo-occipital junction detects incongruence as
induced euphoria in humans (Breiter and Rosen, 1999;
suggested in previous studies of humor and laughter
Drevets et al., 2001), it is reasonable to conclude that
(Goel and Dolan, 2001; Iwase et al., 2002), while more
the NAcc activation observed in the present study re-
anterior regions, including Broca’s area and the tempo-
flects the hedonic feeling that accompanies humor. Fur-
ral pole, ascertain linguistic coherence.
ther investigations, however, are needed to unravel the
Engagement of the left SMA proper (BA 6) and pre-
discrete nexus between NAcc activation and rewarding
SMA are likely to reflect motor aspects of expressive
aspects of humor.
laughter. Intraoperative electrical stimulation of the left
The presence of left amygdala activation also pre-
pre-SMA has been shown to elicit smiles and laughter
sents a compelling finding. The amygdala is an integral
(Fried et al., 1998). Recent neuroimaging studies also
component of the dopamine reward system, providing
have shown increased activation in the bilateral SMA
excitatory innervation to the NAcc (Price and Amaral,
proper to be correlated with laughter (Iwase et al., 2002;
1981). Comparative studies have demonstrated that dis-
Osaka et al., 2003). In the present study, the SMA proper
crete ablation of the amygdala produces conspicuous
cluster also extended to the adjacent dACC, a multifac-
impairments in stimulus-reward learning (for review, see
eted structure implicated in reward-based decision
Baxter and Murray, 2002). In humans, the amygdala,
making, attention allocation, and laughter (Arroyo et al.,
while classically associated with negative emotions, has
1993; Bush et al., 2002; Osaka et al., 2003; Procyk et
also been implicated in reward magnitude (Pratt and
al., 2000). Particularly compelling is that ictal laughter
Mizumori, 1998), laughter (Iwase et al., 2002), and pro-
(i.e., gelastic seizures) has been shown to arise from a
cessing of pleasurable emotions (Yang et al., 2002). Fur-
circumscribed region encompassing the SMA and dACC
thermore, the finding of amygdala activation is of clinical
(Chassagnon et al., 2003). It is also intriguing to note
interest, as this region has been implicated in the patho-
that both SMA proper and dACC receive rich dopamine
logical features of many affective disorders. Diminished
input via ascending mesocortical projections from the
dopaminergic tone in the amygdala has been implicated
ventral striatum (Bates and Goldman-Rakic, 1993; Dum
in the emotional memory dysfunction and anhedonia
and Strick, 1993), suggesting that these regions play
observed in depression (Nestler et al., 2002) and the
an extended role in the dopaminergic reward network
“affective flattening” seen in Parkinson’s disease (Tessi-
associated with humor appreciation.
tore et al., 2002). Conceptually, connections between
A novel finding of this study relates to the detection
the amygdala and ventral striatum may provide new
of a humor-specific cluster that encompassed several
insight into the symptomatology of psychiatric disorders
subcortical structures, including the amygdala, ventral
with hypodopaminergic underpinnings.
striatum/NAcc, ventral tegmental area (VTA), anterior
In summary, our results provide compelling new evi-
thalamus, and the subadjacent hypothalamus (see Table
dence that subcortical, dopaminergic structures may
1 and Figure 2). These regions constitute the core of the
play a key role in the hedonic aspects of humor. We
subcortical dopaminergic reward network, beginning in
also, in part, replicate previous findings related to the
the VTA, where cell bodies of dopamine neurons are
cortical, presumably cognitive and motor, aspects of
located, and projecting rostrally to striatal, limbic, and
humor and laughter. These findings also make modest
frontal lobe terminal fields (Schultz, 2000). Functional
steps toward elucidating the neural basis of salutary
connectivity within this network of subcortical regions
aspects of humor that may lead to a better understand-
has been demonstrated in oral amphetamine (Devous et
ing of the putative psychological and physiological ben-
al., 2001) and cocaine (Breiter and Rosen, 1999) infusion
efits of a good sense of humor.
studies, reflecting the prominent role of dopaminergic
signaling in drug rewards.
Experimental Procedures
Of these several components of the reward system,
the NAcc has been consistently implicated in psycho-
Subjects
logically and psychopharmalogically driven rewards
Sixteen young, healthy, adult subjects (mean age, 22.4
1.8; range,
20–26 years; 7 males, 9 females) participated in this study. All sub-
(Breiter et al., 2001; Breiter and Rosen, 1999; Knutson
jects spoke native English, were right-handed (as measured by the
et al., 2001). In the present study, the time series analysis
Edinburgh Handedness Inventory; Oldfield, 1971), and were
revealed a pronounced increase in activation during
screened for history of psychiatric or neurological problems using
funny cartoons, when compared to nonfunny cartoons
the Symptom Checklist-90-R (Derogatis, 1977). Subjects were
(see Figure 4). Modulation of the NAcc by funny cartoons
deemed eligible only if scores were within one standard deviation
of the mean normative standardized sample. All experimental proce-
was also confirmed in the post hoc covariate analysis
showing that activity in this region increases with the
dures complied with the guidelines of the human subjects committee
degree of humor intensity (see Figure 3). In addition,
at Stanford University School of Medicine. Written informed consent
was obtained from each subject.
humor-elicited NAcc activation converges with findings
from fMRI studies across a number of psychologically
Stimuli: Rating of Cartoons
rewarding tasks, suggesting that this structure is in-
Subjects, similar in age and background to the experimental sub-
volved in the processing of a diverse number of stimuli
jects, chose 42 of the funniest cartoons from a portfolio of approxi-
mately 130 cartoons. In addition, each cartoon was rated for simplic-
with rewarding characteristics (Aharon et al., 2001;
Breiter et al., 2001; Breiter and Rosen, 1999; Erk et al.,
ity (i.e., how easy the jokes were to comprehend) and visual clarity.
2002; Goel and Dolan, 2001; Rilling et al., 2002). Although
Of the final 42 cartoons, 36 of the funny cartoons were captioned,
compared to 37 of the nonfunny stimuli. The majority of the cartoons
we cannot exclude other intervening factors (e.g., nov-
were of the violation-of-expectation type (cf. Herzog and Larwin,
elty), in light of prior fMRI and physiological studies
1988). The final 42 funny cartoons were compared to 42 nonfunny
implicating NAcc modulation in self-reported happiness
cartoons (i.e., funny cues omitted) in the scanner. Nonfunny car-
toons were also matched to funny cartoons for luminance and visual
(Knutson et al., 2001) and cocaine/amphetamine-
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