Humor and smiling: Cortical regions selective for cognitive, affective, and

volitional components
B. Wild Privatdozentin, F. A. Rodden, A. Rapp, M. Erb, W. Grodd and W. Ruch
Neurology 2006;66;887-893
DOI: 10.1212/01.wnl.0000203123.68747.02

This information is current as of April 4, 2006

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://www.neurology.org/cgi/content/full/66/6/887

Neurology is the official journal of AAN Enterprises, Inc. A bi-monthly publication, it has been
published continuously since 1951. Copyright 2006 by AAN Enterprises, Inc. All rights reserved.
Print ISSN: 0028-3878. Online ISSN: 1526-632X.

Downloaded from www.neurology.org at Universitaet Tuebingen on April 4, 2006

 Humor and smiling
Cortical regions selective for cognitive, affective, and
volitional components
B. Wild, Privatdozentin Dr Med; F.A. Rodden, PhD; A. Rapp, Dr Med; M. Erb, Dr Rer Nat;
W. Grodd, Prof Dr Med; and W. Ruch, Prof Dr Phil

AbstractBackground: The interrelationships among humor, smiling, and grinning have fascinated philosophers for
millennia and neurologists for over a century. A functional dissociation between emotional facial expressions and those
under voluntary control was suggested decades ago. Recent functional imaging studies, however, have been somewhat at
odds with older studies with respect to the role of the right frontal cortex in the perception of humor. Methods: Blood
oxygen level dependent (BOLD) activity was measured in 13 subjects during the presentation of funny vs nonfunny
versions of essentially the same cartoons and compared with BOLD activity associated with merely grinning at similar
nonfunny cartoons via fMRI. Results: Humor perception was correlated with BOLD activity in the left temporo-
occipitoparietal junction and left prefrontal cortex and humor-associated smiling (recorded with an MR-compatible video
camera) with bilateral activity in the basal temporal lobes. Unexpectedly, both conditions were also accompanied by a
decrease in BOLD activity in the right orbitofrontal cortex. Voluntary grinning in the absence of humorous stimuli was
accompanied by bilateral activity in the facial motor regions. Conclusions: These results confirm the clinically derived
hypothesis of separate cortical regions responsible for the production of emotionally driven vs voluntary facial expressions.
The right orbitofrontal decrease reconciles inconsistencies between clinical and functional imaging findings and may
reflect a disinhibition of facial emotional expression.
NEUROLOGY 2006;66:887893

Humor, smiling, and laughter are integral compo-
nents of humanity. Whereas they have been ana-
lyzed for over two millennia within the contexts of
philosophy, psychology, theology, and philology,1 our
knowledge of the neurophysiologic processes that un-
derlie these phenomena is thin.2
The existence of a clinical dissociation between
voluntary and emotionally driven facial expressions
has been known for over 150 years.2 Lesions induc-
ing a paresis of voluntary smiling were found in the
ventral mesencephalic pons and the internal capsule
or, if bilateral, in the operculum. Emotionally driven
smiling, on the other hand, was compromised by le-
sions in the tegmental brainstem, the frontal cortex,
the internal capsule and striatum, the basal ganglia,
and the posterior thalamus.
More recent studies of patients whose senses of
humor have been impaired owing to brain damage2-4
suggested that the right frontal cortex is necessary
for humor perception. This region, however, was not
activated in the functional imaging studies published
to date on humor perception (table 1). None of these
Additional material related to this article can be found on the Neurology
Web site. Go to www.neurology.org and scroll down the Table of Con-
tents for the March 28 issue to find the title link for this article.
studies separated the effects of humor perception
from the reactions to humor (i.e., smile).
In this event-related fMRI study, we sought to
separate 1) regions associated with purely voluntary
smiling and those associated with emotionally asso-
ciated smiling and 2) regions related to humor per-
ception and those related to humor-induced smiling
with particular interest in the right frontal cortex.
Methods. Overview. Thirteen right-handed men (ages 18 to
25) were paid to participate in the study. All were healthy and
free of neurologic or psychiatric symptoms. Written, informed con-
sent was obtained from each subject, and the experiment was
approved by the Medical Ethics Committee of the University of
Tubingen.
Stimuli consisted of nonverbal (i.e., no captions) cartoons by a
single cartoonist (Gary Larson) projected onto a screen that was
visible to the subjects from within the MR apparatus. These
funny cartoons were presented at random intervals during a
baseline state in which the subject was shown very similar non-
funny cartoons. These were created by digitally altering funny
cartoons, so that the visual punch line was blanked out, but
without otherwise changing the content of the picture, or by omit-
ting the caption of verbal cartoons. To induce a baseline of a
looking-at-this-particular-Gary-Larson-cartoon state, we used
sets of three variations of each cartoon. The first two were always
not funny but the third was sometimes the original funny car-
toon. Stimulus duration was 2 seconds each, without intervals.
The experiment consisted of two conceptually closely related
segments: The first was designed to examine humor-associated

From the Department of Psychiatry (B.W., A.R.) and Section for Experimental Magnetic Resonance of the CNS (B.W., F.A.R., A.R., M.E.,W.G.), Department
of Neuroradiology, University of Tubingen, Germany; and Department of Psychology (W.R.), University of Zurich, Switzerland.
Supported by a grant from Fortune (University of Tubingen).
Disclosure: The authors report no conflicts of interest.
Received May 13, 2005. Accepted in final form November 21, 2005.
Address correspondence and reprint requests to Dr. B. Wild, Zwingerweg 1, 72202 Nagold, Germany; e-mail: bawild@med.uni-tuebingen.de

Copyright 2006 by AAN Enterprises, Inc. 887

Downloaded from www.neurology.org at Universitaet Tuebingen on April 4, 2006
Table 1 Synopsis of existing studies
Facial
Imaging expressions
Ref. method measured Paradigm
20 fMRI No Listening to humorous/philosophical/
boring sentences
12 fMRI No Listening to phonologic and
semantic joke vs nonjokes
13 PET Yes Smile evoked by funny films vs
(EMG) voluntary smile
14 fMRI No Funny vs nonfunny verbal and
nonverbal cartoons
15 fMRI No Funny films
29 fMRI No Amusing/sad/neutral films
EMG electromyography; SMA supplementary motor area.
states and the second to examine states associated with affect-free
grinning. Due to limitations in information storage capacities,
the part of the experiment intended to induce the humor-
associated states (humor perception and humor-associated
smiling) was divided into three equivalent sessions. The part
studying grinning formed a fourth session. Sessions were shown
in random order with approximately 3 minutes of rest in between.
To evoke humor-associated states, subjects were shown 63 sets
with 2 nonfunny and one funny cartoon in random order inter-
spersed between 72 sets with 3 nonfunny cartoon variations (in
sum 63 funny and 342 nonfunny cartoons). To evoke humorless
grinning, a separate series of 45 sets of 3 nonfunny cartoons was
used. In 15 of those sets, the last was enclosed within a thin circle.
This was the signal for the subject to smile as though this cartoon
were funny.
Monitoring of facial movements. Subjects were requested to
avoid head movements during the fMRI measurements but were
told that they need not suppress their facial movements. To mini-
mize head movements, subjects heads were restrained in a frame
with bilateral padding. A specially designed nonferrous video cam-
era5 monitored facial expressions (smiles).
The events of smiling were determined from the video data by
two independent raters (interrater agreement with respect to the
instant that each smile began and ended was 95%). Smiles dur-
ing the humorless grinning part and in response to the visual
command to smile (encircled nonfunny cartoons) were defined as
events of humorless grinning. Smiles during the humor seg-
ment, irrespective of whether the subject saw a cartoon deemed
funny by the experimenters or not, were defined as events of
humor-associated smiling, because interest here was in the sub-
jects subjective, spontaneous reactions.
Humor perception. Humor perception events were deter-
mined without regard to the video data. Immediately upon exiting
from the MR apparatus, each subject was again shown each of the
cartoons he had just seen: nonfunny, funny, and circled, and
asked to rate it on a funniness scale of 0 to 5 (0 not funny; 5
very funny). No consideration was given to the subjects prior
exposure to the funny cartoons inasmuch as the subjects were told
to rate the funniness they experienced at the time of scanning, not
the funniness per se. When the data were later evaluated, the
instants when the subject had begun viewing a cartoon that he
later listed as having been at least slightly funny (i.e., a score of
1 or more) were defined as events of humor perception.
888 NEUROLOGY 66 March (2 of 2) 2006
Downloaded from www.neurology.org at Universitaet Tuebingen on April 4, 2006
Activated brain regions
Humorous sentences vs other: Broca area, left middle gyrus
Phonologic jokes: left posterior inferior temporal gyrus, left
inferior frontal gyrus; semantic jokes: left posterior
middle temporal gyrus, right posterior middle temporal
gyrus, cerebellum. Covarying with subjective funniness:
medial ventral prefrontal cortex
During humor-related laughter/smiledegree of funniness
not rated: bilaterally SMA, left putamen
Nucleus accumbens, left temporo-occipital junction, Broca
area, SMA, dorsal anterior cingulum, anterior thalamus,
ventral striatum, hypothalamus, and amygdalae
Humor detection: anterior and posterior left temporal lobe,
left inferior frontal lobe, right posterior middle temporal
lobe, right cerebellum. Humor appreciation: insula,
amygdalae bilaterally, left lateral parietal cortex, left
hippocampus, right inferior frontal lobe
Uniquely active during amusement: right caudate, right
putamen, left globus pallidus, and right hippocampus
fMRI scanning. With use of a 1.5 T scanner (SONATA; Sie-
mens, Erlangen, Germany), an anatomic T1-weighted data set
was acquired for each subject with a three-dimensional gradient
echo sequence (MPRAGE, 128 slices with 256 256 pixels in
sagittal orientation, 1 1 1.5 mm3, repetition time [TR] 9.7
milliseconds, echo time [TE] 4 milliseconds, inversion time
300 milliseconds, acquisition time 397.6 seconds, flip angle
8). Then, in four blocks of 95 measurements, separated by periods
of rest amounting to approximately 3 minutes, 380 T2*-weighted
echo-planar measurements were made, which covered the whole
brain (28 slices of 4-mm thickness in axial orientation, 1-mm gap,
64 64 pixels, 3 3 mm2 in-plane resolution, TE 39 millisec-
onds, TR 3 seconds, flip angle 90).
Statistical analysis. Image processing and statistical analysis
were performed using statistical parametric mapping (SPM99;
Wellcome Department of Cognitive Neurology, London, UK). All
volumes were realigned to the first image as correction for inter-
scan movements by means of a rigid body transformation with six
variables (three rotations and three translations). A coregistration
of the structural volume to the first T2* volume of each subject
ensured that the functional and anatomic data were in the same
coordinate system. The structural image was normalized into a
standard stereotactic space6 by estimating the numbers for an
appropriate nonlinear transformation. With use of a transforma-
tion with the same numbers, the T2* data were resampled to 3
3 3mm3 voxels. The functional scans were smoothed using a
Gaussian filter with 10-mm full width at half-maximum.
Stimulus presentation and fMRI measurements were time-
linked by the presentation program. Via a split screen technique,
the stimulus and the subjects face could be monitored simulta-
neously on the video film. Smile latency was measured by count-
ing the number of video frames (each 40-millisecond duration)
between presentation of the stimulus and the beginning of the
movement.
Data were analyzed by modeling the events as stick functions,
representing stimulus onset, convolved with the synthetic canoni-
cal hemodynamic response function as supplied by SPM99. This
resulted in using the times when the subjects did not smile as
baseline for the voluntary smile and the humorous smile
events. The times during which the subjects were watching car-
toons they later did not judge to be funny served as baseline for
the humor perception events, irrespectively whether these were
among the nonfunny versions of funny cartoons or the other non-
funny cartoons. If cartoons immediately following each other were
judged as funny, these were modeled as one event because the
postexperiment ratings of funniness were potentially problematic:
When seen after the experiment, a nonfunny version of a funny
cartoon might bring recollections of the funny version, and this
might generate a rating of mild funniness.
Group results were calculated with a fixed effect model, as for
a random effect model, the within-subject variance has to be equal
for each subject. Because of the widely varying number of events
among the different subjects (humor perception events: mean 35,
SD 21.5; humorous smile events: mean 15.4, SD 10.6; voluntary
grinning events: mean 14.7, SD 0.8), this assumption was not
fulfilled. This, however, makes the data nongeneralizable beyond
the cohort studied. In line with established functional imaging
conventions, we report blood oxygenation level dependent
(BOLD) responses seen at an uncorrected threshold of p 0.001
for regions about which we had an a priori hypotheses. We also
report effects in other regions if they survived a more stringent
threshold of p 0.05, corrected for multiple comparisons across
the whole-brain volume. We also used the masking procedure as
defined by SPM99. This results in isolating regions that were
activated in one contrast (i.e., humor perception) and not by the
other contrast (i.e., humorous smile). As level of significance for
masking, we used p 0.05 corrected for the first contrast and p
0.05 uncorrected for the mask.
An additional parametric analysis was performed using the
funniness ratings to determine which regions showed a pattern of
BOLD activity modulated with the degree of funniness. We con-
sidered the seven subjects who had generated at least 31 events
(i.e., subjects who found more than 30 cartoons as at least slightly
funny). This selection ensured a sufficient number of events and
variances of such a degree of similarity that an estimate of para-
metric variations was possible. A parametric analysis for the smil-
ing events was not feasible because although there were multiple
smiling events, these events exhibited only minute differences in
their intensities. BOLD responses seen at a threshold of p 0.05
corrected for multiple comparisons with an extent of at least 6
voxels are reported.
To estimate the correlation between head movements and the
hemodynamic activity, we calculated the correlation between each
stimulus regressor and the realignment regressors as calculated
by SPM. We calculated this for each session in the six directions
(translation x, y, z and rotation x, y, z). To average these data and
to search for significant differences, we performed a Fisher Z
transformation. The mean correlations in the six directions were
as follows: tx: 0.0544; ty: 0.1163; tz: 0.0580; rx: 0.0246; ry:
0.1035; rz: 0.0682.
Results. On average, subjects exhibited 17.6 spontane-
ous smiles in response to the set of 135 cartoons, of which
21 were the nonaltered originals and thus designed to be
funny. Subjects averaged 14.5 voluntary grins in re-
sponse to the 15 circled cartoons, thus showing a 97%
compliance with the instructions to smile as though this
cartoon were funny when these cartoons were shown. The
average number of cartoons the subjects rated as funny
(i.e., during which they had experienced some degree of
humor perception) was 40.1. Thus, only 43.9% of the
cartoons (i.e., 17.6/40.1) perceived as funny were funny
enough to elicit a smile. This is within the range reported
in other humor studies outside the scanner.7 The funny
ratings for cartoons with smiles were higher than those
without (3.6 [SD 1.4] vs 2.1 [SD 1.4]; p 0.01). But
there was also a time difference between the smile
events and the funny events. The funny events pre- an impairment of patients abilities to perceive or react to
ceded the smile events on average by 0.6 scan (SD 0.6),
that is, 1.8 seconds. Some of the nonfunny cartoons
were rated as funny too. The reasons the subjects gave
for this unexpected perceived funniness varied from
such statements as I thought that the way the cartoon-
ist drew the dog was funny to The cartoon reminded
me of something funny.
Downloaded from www.neurology.org at Universitaet Tuebingen on April 4, 2006
As was to be expected, during grinning on command,
that is, a predominantly motor task, the predominant
BOLD changes occurred in the primary sensorimotor corti-
ces bilaterally (more markedly on the left). Activity was
also seen in the supplementary motor area and in the
frontal operculae (Brodmann area [BA] 47, also more
pronounced on the left), the cuneus, the right basal tem-
poral lobe, and two regions in the cerebellum (figure 1A;
also see table E-1 on the Neurology Web site; go to
www.neurology.org).
During humor-induced smiling, in contrast, prominent
regions of activation were seen in the left frontal cortex
anterior to Broca area (BA 47), bilaterally in the temporal
poles, in the hippocampus and amygdala (all more pro-
nounced on the right), in lateral regions of the cerebellum
(more on the left), the thalamus bilaterally, the left poste-
rior temporal lobe (BA 39), and the border between the
superior and inferior parietal lobules (BA 7). As opposed to
the volitional smile condition, the primary sensorimotor
cortices exhibited only a very small cluster of activation on
the right (figure 1B; see also table E-1).
Humor perception events correlated significantly with
positive BOLD activity in a large region over the left
temporo-occipitoparietal junction, in the temporal poles
(predominantly right), the left anterior prefrontal cortex,
the right frontal operculum, the pallidum and putamen
bilaterally, the mesencephalon, the right occipitotemporal
junction (BA 39), and small clusters bilaterally in the sen-
sorimotor cortices and the right cerebellum (figure 1C; see
also table E-1).
Masking regions of activation during humorous smile
by humor perception revealed regions presumably more
involved with the facial expression of humor-induced smil-
ing than with the perception of humor (figure 2A; table 2).
This showed activations in both basal temporal poles, the
left and right hippocampus, amygdala and parahippocam-
pal gyrus, the left frontal operculum, the thalamus bilater-
ally, and the lateral cerebellum (right and left). By using
the opposite masking procedure, regions presumably more
involved in the perception of humor than in its expression
were displayed. This revealed predominantly activation in
the left temporoparieto-occipital junction with local max-
ima in BA 5/7/40/39 (figure 2B; table 2). Additional regions
of activation were in the left inferior frontal gyrus (BA
45/46), the left medial frontal gyrus (BA 6), and the right
medial temporal gyrus.
The parametric analysis, searching for regions where
activation during humor perception was positively cor-
related with the amount of funniness as rated by the
subjects afterward showed a significant parametric modu-
lation again in the left frontolateral cortex (BA 10/11/44),
in the right temporal pole (BA 20/21/38), in the left tempo-
ral lobe (57, 66, 6; BA 37/39), and in the left temporo-
occipital junction (BA 7) (figure 2C).
Damage to the right frontal cerebral cortex resulted in
humor.3,4 As expected, this region exhibited no BOLD ac-
tivity during volitional grinning. Surprisingly, however, it
also exhibited no positive BOLD changes either during
humor perception or humor-induced smiling. This region
did, however, show an unexpected negative BOLD effect
during humorous smile and, to a lesser degree, during
humor perception. Differentiating those regions with sig-
March (2 of 2) 2006 NEUROLOGY 66 889

nificant (p 0.05 corrected) deactivation during humor-
ous smile that were not significantly deactivated during
humor perception by masking revealed BOLD changes in
the right G. frontalis medius (p 0.004; 39, 57, 0; BA 10;
figure 2D). During volitional grinning, no negative BOLD
change occurred.
Discussion. This study revealed discrete, charac-
teristic patterns of cerebral BOLD activity during
nonhumorous voluntary smiles (grinning), during
humor-induced smiles, and during humor percep-
tion. It adds support for the existence of a dissocia-
tion between neural systems for voluntary and for
emotionally motivated facial expressions in healthy
subjects, as previously postulated on the basis of
clinical observations in neurologic patients.2,8-10 Vol-
untary grinning, as expected, seems to be controlled
by cortical regions also responsible for other volun-
tary facial movements. These findings also confirm
the postulated role of the operculae as premotor ar-
eas for facial movements and are consistent with the
clinical observations of isolated voluntary facial pa-
reses after bilateral opercular lesions (the so-called
FoixChavanyMarie syndrome or anterior oper-
cular syndrome).9,11
Before discussing the differences between humor-
induced smiles and humor perception in detail,
methodologic issues should be considered. The con-
trast for humorous smiling was based on fewer
events than for humorous perception. This could
make it more difficult for activation during humor-
induced smiles to reach the same level of significance
and would cause the maps of activation to appear in
the same general regions, but to be smaller. On the
890 NEUROLOGY 66 March (2 of 2) 2006
Downloaded from www.neurology.org at Universitaet Tuebingen on April 4, 2006
Figure 1. Activation maps for nonhu-
morous grin (A), humorous smile
(B), and humor perception (C). Events
compared with baseline as obtained by
SPM99 as maximal intensity projection
onto representations of standard stereo-
tactic space in (from left) sagittal, coro-
nal (viewed from behind), and
transverse (viewed from above) view.
All maps were created with a threshold
of p 0.05, corrected for multiple
comparisons.
other hand, the events of smiling occurred with car-
toons with higher ratings of funniness. This could
render the comparison between both a kind of simple
parametric analysis with larger activation expected
for the humor-induced smile than for the humor per-
ception. Both interpretations, however, do not ex-
plain why there were regions activated with humor
perception but not with humorous smiling (prefron-
tal bilaterally, at the left temporoparietal junction,
right temporal, putamen and pallidum, and the mes-
encephalon; see table E-1) and also regions only acti-
vated with humorous smiling (left parietal and
limbic: amygdale, hippocampus, and parahippocam-
pal). Furthermore, the humor perception events oc-
curred slightly earlier than the humorous smiling
events. This was to be expected: First one perceives a
joke and than reacts with facial movements. This
means that the two activation maps show not just a
parametric difference but also a timing difference.
Therefore, a better explanation, and fitting with data
from other studies as detailed below, is that the two
show overlapping but differing parts of a network
engaged in reactions to humorous stimuli.
Increased cerebral activity in the temporoparieto-
occipital junction associated with humor perception
has also been described in several previous
studies.12-15 and in one study interpreted as being
related to the verbal nature of the humorous stimu-
li.12 That these regions were activated by the nonver-
bal funny material in the our study and others,13,14
however, suggests a different, possibly humor-
associated function for this region. Other studies
have shown increased activation in nearby regions

Figure 2. Comparison between humor-induced smiling (A),
humor perception (B), areas with parametric modulation
related to humor perception (C), and negative blood oxy-
genation level dependent (BOLD) effect during humorous
smile (D). Activation maps superimposed on a surface-
rendered T1 template brain after masking (A) humorous
smile by humor perception and (B) humor perception by
humorous smile, both at p 0.05 (view from the left [top]
and below [bottom]). (C) Regions with parametric modula-
tion by the individually rated degree of funniness. (D)
Negative BOLD effect during humorous smile (top: view
from the right side, bottom: from below; threshold set at
p 0.05 corrected).
during such activities as viewing emotionally laden
visual stimuli,16 the attribution of intentions to oth-
ers,17 or the perception of causality.18 Just as the
recognition of music depends on hierarchical synthe-
ses of phenomena from purely acoustic tonal and
rhythmic elements through chordal structures to
emotional associations,19 the perception of humor
possibly depends on similar emergent constructions.
We propose, therefore, that when confronted with
the raw material of humor, the temporoparieto-
occipital region may be responsible for the task of
detecting the incongruity necessary for the synthesis
of the perception of humorand possibly also in the
Downloaded from www.neurology.org at Universitaet Tuebingen on April 4, 2006
resolution of that incongruity in later stages of hu-
mor perception.
The left lateral prefrontal cortex (BA 44/45/47)
also has been shown to be active during humor per-
ception in almost all of the existing studies, indepen-
dent of the protocol employed.12,14,15,20 An increasing
number of imaging studies confirms the key role this
brain region plays in directing semantic search21 and
in the resolution of incongruity.22,23 The activation
found in our study may likewise reflect this process.
The basal temporal activation seen in this study is
most likely related to emotional components of the
exhilarative reaction to humor24 and to the facial
expression of emotion,25 inasmuch as it was most
prominent when humorous smile was masked by
humor perception. This interpretation corresponds
well with clinical observations of patients with foci in
the temporal poles or the hippocampal region who
smile or laugh during epileptic seizures26-28 and with
the mirth-associated laughter observed during para-
hippocampal intraoperative electrical stimulation.28
It is also consistent with the reported activation in
this region including the amygdala for humor appre-
ciation.14,15 This region overlaps with the mesolimbic
reward system (as defined previously)14 and the re-
ported activation in the basal ganglia and the hip-
pocampus in amusing vs neutral films.29
Surprisingly, in most of the reported imaging
studies, no evidence was found for the participation
of the right frontal lobe. This lack of evidence for an
association between humor perception and frontal
lobe activity seemed inconsistent with studies in pa-
tients, almost all of which indicated a prominent in-
volvement of this region.3,30 Only one study12
reported activation of the medial ventral prefrontal
cortex bilaterally. The proposition15 that the right
frontal lobe may only be needed if an immediate
appraisal of the funniness is needed, as was the
case in the patient studies, is inconsistent with the
results of the study14 in which subjects had to imme-
diately judge the degree of funniness in their stimuli.
None of the published studies, however, reported
having searched for regions with a negative correla-
tion with humor detection or appreciation. A final
interpretation of the local decreases in oxygenated
blood observed in this study must await further clar-
ification of the neural concomitants of the negative
BOLD effect. This BOLD negativity, however, has
been suggested to reflect a reduction in neuronal
activity.31
The classic view of the right frontal cortexs role in
humor reactions, that is, integration of complex con-
textual linguistic or ideational information,3,30 has
already been challenged.4 Those authors pointed out
that it has functions important not only for humor
appreciation but also for emotional responsiveness.
In particular, they stressed the anatomic connections
between area 10 with the multimodal superior tem-
poral sulcus and its role in facial grimacing. This
temporal region was activated in our study as well.
They conclude that the right frontal damage is rele-
March (2 of 2) 2006 NEUROLOGY 66 891
Table 2 Regions with significant change of blood oxygenation level dependent signal

Region/side Coordinates Brodmann area

Humor perception masked by humorous smile

Sensorimotor cortex, R 54, 6, 39* 6
Frontal operculum, L 54, 15, 6 47
Supplementary motor area, R L 0, 3, 66* 6
Temporal poles
R 27, 6, 45 36/38
42, 18, 33 38
L 36, 6, 42 36/38
Amygdala/hippocampus/parahippocampus
R 18, 12, 15*
L 18, 12, 15
Thalamus, R L 0, 18, 9*
Cerebellum
R 27, 66, 21*
L 42, 60, 30*
Humorous smile masked by humor perception
Frontal operculum, L 54, 30, 15* 45/46
Prefrontal, L 39, 6, 54* 6
Temporo-occipitoparietal junction, L 57, 63, 30 39
63, 39, 36 40
42, 48, 60 5/7
Temporal, R 57, 60, 9* 21/37

The table shows all clusters of activation with p 0.05 corrected for multiple comparisons, giving the x, y, and z coordinates in the
MNI space provided by SPM99.

* A priori hypotheses predicting the activation of a region (based, e.g., on observations from previous studies), significant at the less
stringent level of p 0.001 uncorrected.
The cluster was 10 voxels.

vant to producing a dissociation between cognitive
and affective responses. Interestingly, a recent very
detailed patient study32 provided another argument
for this. They used the Gardner Right Hemisphere
Communication Battery, which includes all the hu-
mor tests on a large number of patients with ana-
tomically very well classified lesions. They found no
evidence for a selective involvement of the right fron-
tal cortex in humor appreciation.
We submit the hypothesis that the frontal deacti-
vation is related to the disinhibition of emotional
expression following the feeling of exhilaration, or,
as Gowers (1887)33 commented on laughter many
years ago: The will is needed not to effect it, but to
restrain it. There have been several reports of pa-
tients with prefrontal lesions who exhibited involun-
tary laughter,34,35 and those patients have also been
described as showing inadequate emotional expres-
sions. Another observation congruent with our inter-
pretation is that of the right frontal decrease of
neural activation described during transient happi-
ness in healthy volunteers using H2 15O PET.36
Laughing gas, an N-methyl-d-aspartate antagonist,
has been suggested to exert its influence via inhibi-
tion of neurons in the premotor and motor cortex.37
Goel and Dolan instructed their subjects not to
laugh out loud (V. Goel, personal communication,
2002) during the perception of humor, whereas our
892 NEUROLOGY 66 March (2 of 2) 2006
Downloaded from www.neurology.org at Universitaet Tuebingen on April 4, 2006
subjects, probably in contrast to those in all the
other studies except one,13 were permitted to smile
when they saw something funny. Thus, in most ex-
periments, facial reactions may have been sup-
pressed and a disinhibition could not be observed.
We propose a neural network associated with re-
actions to humorous material in which the left
temporo-occipitoparietal junction and the left lateral
prefrontal lobe are involved in its perception and
cognitive processing, the basal temporal lobes in the
generation of facial reactions to humor, and the or-
bitofrontal cortex in the disinhibition of spontaneous
facial movements. The latter two regions also are
likely candidates for regions involved in the feeling
of exhilaration.
The current study represents another step in dis-
tinguishing among those regions of the brain in-
volved in the perception of humor, those involved in
its display, and those involved in its enjoyment. Fur-
ther studies will be needed to validate the functional
relevance of these regions in the presence such con-
founding factors as surprise, problem solving, detec-
tion of incongruity, and presence of various moods. A
deeper understanding of the cerebral correlates of
humor will also depend on further refinements in
operational definitions of such key concepts as
funny, humor, exhilaration, and mirth and
the relationships of these concepts with the brains of
subjects from a broad spectrum of demographic
groups.
Acknowledgment
The authors thank Silke Anders for help with statistics, Franziska
Hosl and Hans-Jorg Mast for technical assistance, and Mathias
Bartels for providing a stimulating and helpful atmosphere for
research.
References
1. Martin R. Approaches to the sense of humor: a historical review. In:
Ruch W, ed. The sense of humor. New York: Mouton de Gryter, 1998:
1660.
2. Wild B, Rodden FA, Grodd W, Ruch W. Neural correlates of laughter
and humour: a review. Brain 2003;126:21212138.
3. Gardner H, Ling PK, Flamm L, Silverman J. Comprehension and ap-
preciation of humorous material following brain damage. Brain 1975;
98:399412.
4. Shammi P, Stuss DT. Humour appreciation: a role of the right frontal
lobe. Brain 1999;122:657666.
5. Wild B, Erb M, Lemke N, Scholz P, Bartels M, Grodd W. Video camera
and light system for application in magnetic resonance scanners. Magn
Res Imag 2000;18:893896.
6. Collins DL, Neelin P, Peters TM, Evans AC. Automatic 3D intersubject
registration of MR volumetric data in standardized Talairach space.
J Comput Assist Tomogr 1994;18:192205.
7. Ruch W. Die Emotion Erheiterung: Ausdrucksformen und Bedingun-
gen. Department of Psychology, University of Dusseldorf, 1990.
8. Magnus A. Fall von Aufhebung des Willenseinflusses auf einige Hirn-
nerven. In: Muller J, ed. Archiv fur Anatomie, Physiologie und Wissen-
schaftliche Medicin. Berlin: Verlag von W. Thome, 1837:258266.
9. Hopf HC, Muller FW, Hopf NJ. Localization of emotional and volitional
facial paresis. Neurology 1992;42:19181923.
10. Poeck K. Pathophysiology of emotional disorders associated with brain
damage. In: Vinken, PJ, Bruyn GW, eds. Handbook of clinical neurol-
ogy. Amsterdam: Elsevier, 1985:343367.
11. Weller M. Anterior opercular cortex lesions cause dissociated lower
cranial nerve palsies and anarthria but no aphasia: FoixChavany
Marie syndrome and automatic voluntary dissociation revisited. J
Neurol 1993;240:199208.
12. Goel V, Dolan RJ. The functional anatomy of humor: segregating cogni-
tive and affective components. Nat Neurosci 2001;4:237238.
13. Iwase M, Ouchi Y, Okada H, et al. Neural substrates of human facial
expression of pleasant emotion induced by comic films: a PET study.
Neuroimage 2002;17:758768.
14. Mobbs D, Greicius MD, Abdel-Azim E, Menon V, Reiss AL. Humor
modulates the mesolimbic reward centers. Neuron 2003;40:10411048.
15. Moran JM, Wig GS, Adams RB, Janata P, Kelley WM. Neural corre-
lates of humor detection and appreciation. Neuroimage 2004;21:1055
1060.
16. Karama S, Roch Lecours A, Leroux J-M, et al. Areas of brain activation
in males and females during viewing of erotic film excerpts. Hum Brain
Map 2002;16:113.
ALERT: NEUROLOGY NOW USING ONLINE PEER REVIEW AND
MANUSCRIPT SUBMISSION SYSTEM
Neurology is now using an online peer review and manuscript submission system called BenchPress.
Authors should upload all original submissions via the Neurology website (www.submit.neurology.org). The
Instructions to Authors detail the submission process and adjusted specifications.
Downloaded from www.neurology.org at Universitaet Tuebingen on April 4, 2006
17. Brunet E, Sarfati Y, Hardy-Bayle M-C, Decety J. A PET investigation
of the attribution of intentions with a nonverbal task. Neuroimage
2000;11:157166.
18. Blakemore SJ, Fonlupt P, Pachot Clouard M, et al. How the brain
perceives causality: an event-related fMRI study. Neuroreport 2001;12:
37413746.
19. Peretz I, Zatorre RJ. The cognitive science of music. Oxford: Oxford
University Press, 2003.
20. Ozawa F, Matsuo K, Kato C, et al. The effects of listening comprehen-
sion of various genres of literature on response in the linguistic area: an
fMRI study. Neuroreport 2000;11:11411143.
21. Bookheimer S. Functional MRI of language: new approaches to under-
standing the cortical organization of semantic processing. Annu Rev
Neurosci 2002;25:151188.
22. Martin A, Chao L. Semantic memory and the brain: structure and
processes. Curr Opin Neurobiol 2001;11:194211.
23. Rapp A, Leube D, Erb M, Bartels M, Grodd W, Kircher T. Neural
correlates of metaphor processing. Cogn Brain Res 2004;20:395402.
24. Phan KL, Wager T, Taylor SF, Liberzon I. Functional neuroanatomy of
emotion: a meta-analysis of emotion activation studies in PET and
fMRI. Neuroimage 2002;16:331348.
25. Wild B, Erb M, Eyb M, Bartels M, Grodd W. Why are smiles conta-
gious? An fMRI study of the interaction between perception of facial
affect and facial movements. Psychiatry Res Neuroimag 2003;123:17
36.
26. Molinuevo JL, Arroyo S. Ictal smile. Epilepsia 1998;39:13571360.
27. Coria F, Bahillo ME, Moral BM, Garcia GP, Ortiz SdSMR. Late-onset
isolated gelastic epilepsy secondary to entrapment of the right temporal
horn. Neurologia 2000;15:204207.
28. Arroyo S, Lesser RP, Gordon B, et al. Mirth, laughter and gelastic
seizures. Brain 1993;116:757780.
29. Goldin PR, Hutcherson CAC, Ochsner KN, et al. The neural basement
of amusement and sadness: a comparison of block contrast and subject-
specific emotion intensity regression approaches. Neuroimage 2005;27:
2536.
30. Wapner W, Hamby S, Gardner H. The role of the right hemisphere in
the apprehension of complex linguistic material. Brain Lang 1981;14:
1533.
31. Harel N, Lee S-P, Nagaoka T, Kim D-S, Kim S-G. Origin of negative
blood oxygenation level-dependent fMRI signals. J Cereb Blood Flow
Metab 2002;22:908917.
32. Zaidel E, Kasher A, Soroker N, Batori E. Effects of right and left
hemisphere damage on performance of the Right Hemisphere Commu-
nication Battery. Brain Lang 2002;80:510535.
33. Ironside R. Disorders of laughter due to brain lesions. Brain 1956;79:
589609.
34. Zeilig G, Drubach DA, Katz ZM, Karatinos J. Pathological laughter and
crying in patients with closed traumatic brain injury. Brain Injury
1996;10:591597.
35. Mendez MF, Nakawatase TV, Brown CV. Involuntary laughter and
inappropriate hilarity. J Neuropsychiatry Clin Neurosci 1999;11:253
258.
36. George MS, Ketter TA, Parekh PI, Horwitz B, Herscovitch P, Post RM.
Brain activity during transient sadness and happiness in healthy
women. Am J Psychiatry 1995;152:341351.
37. Franks NP, Lieb WR. A serious target for laughing gas. Nat Med
1998;4:383384.
March (2 of 2) 2006 NEUROLOGY 66 893
 Humor and smiling: Cortical regions selective for cognitive, affective, and
volitional components
B. Wild Privatdozentin, F. A. Rodden, A. Rapp, M. Erb, W. Grodd and W. Ruch
Neurology 2006;66;887-893
DOI: 10.1212/01.wnl.0000203123.68747.02
This information is current as of April 4, 2006

Updated Information including high-resolution figures, can be found at:

& Services
Supplementary Material
Subspecialty Collections
Permissions & Licensing
Reprints
http://www.neurology.org/cgi/content/full/66/6/887
Supplementary material can be found at:
http://www.neurology.org/cgi/content/full/66/6/887/DC1
This article, along with others on similar topics, appears in the
following collection(s):
All Neuropsychology/Behavior
http://www.neurology.org/cgi/collection/all_neuropsychology_beh
avior Neuropsychological assessment
http://www.neurology.org/cgi/collection/neuropsychological_asses
sment
Information about reproducing this article in parts (figures, tables)
or in its entirety can be found online at:
http://www.neurology.org/misc/Permissions.shtml
Information about ordering reprints can be found online:
http://www.neurology.org/misc/reprints.shtml

Downloaded from www.neurology.org at Universitaet Tuebingen on April 4, 2006