Download Functional Neuronal Processing of Body Odors

Cerebral Cortex June 2008;18:1466--1474
doi:10.1093/cercor/bhm178
Advance Access publication October 12, 2007
Functional Neuronal Processing of Body
Odors Differs from that of Similar Common
Odors
Johan N. Lundström1,2, Julie A. Boyle1,2, Robert J. Zatorre1,2 and
Marilyn Jones-Gotman1,2
Visual and auditory stimuli of high social and ecological importance
are processed in the brain by specialized neuronal networks. To
date, this has not been demonstrated for olfactory stimuli. By
means of positron emission tomography, we sought to elucidate the
neuronal substrates behind body odor perception to answer the
question of whether the central processing of body odors differs
from perceptually similar nonbody odors. Body odors were
processed by a network that was distinctly separate from common
odors, indicating a separation in the processing of odors based on
their source. Smelling a friend’s body odor activated regions
previously seen for familiar stimuli, whereas smelling a stranger
activated amygdala and insular regions akin to what has previously
been demonstrated for fearful stimuli. The results provide evidence
that social olfactory stimuli of high ecological relevance are
processed by specialized neuronal networks similar to what has
previously been demonstrated for auditory and visual stimuli.
(Wallace 1977). In fact, humans are able to use signals
conveyed in body odor to make accurate kin--nonkin judgments (Weisfeld et al. 2003) and to detect minute differences
in genetic composition of unknown individuals (Jacob et al.
2002). It has even been suggested that signals communicating
emotions are held within body odors (Chen and Haviland-Jones
1999). Together, these studies suggest that the complex
mixture constituting human body odors is a stimulus of high
ecological importance for humans. Moreover, due to their
complex signal contents, it seems likely that body odors are
processed differently than common odors. Although a substantial number of studies have investigated the underlying
mechanisms of olfactory processing of human body odor
behaviorally, only a few have tried to assess how the brain
processes body odors. Recent studies based on overall cortical
activation by electroencephalography have demonstrated that
our brains treat individual body odors differently depending on
their origin (Pause et al. 1999, 2006). Body odors originating
from oneself receive preferential processing compared with
those from others (Pause et al. 1999). Our brains seem so finetuned to body odors that even minute differences in
immunochemistry between individuals influence the processing of them (Pause et al. 2006). However, no study to date has
tried to map the neuronal substrates of body odor processing.
We sought to determine the neuronal substrates of body
odor processing using H2O15 positron emission tomography
imaging while women smelled body odors originating from
different individuals. Each subject and one of her close longtime friends slept alone for 7 consecutive nights in a t-shirt that
had cotton nursing pads sewn into the armpits, which
collected and preserved their body odors while shielding them
from external odor sources. The 15 participating women were
scanned while they smelled the body odors from themselves,
their friends, or a stranger; all women. In addition, they smelled
a mixture consisting of common odors not found in human
underarm sweat, but with similar perceptual characteristics,
and, in a baseline condition, a clean odorless nursing pad. This
constellation of stimuli allowed us to determine the neuronal
substrates of body odor processing and the influence that body
odors originating from specific individuals might have on this
processing. Further, it allowed us to determine whether odors
with high ecological and social importance are processed
differently than odors of lower importance.
Keywords: body odor, imaging, neural networks, odor identification
Introduction
Ever since early anatomists labeled humans as microsmatic
animals (Broca 1888; Zwaardemaker 1895), there has been
a common misconception among scientists and laymen alike
that humans have a poorly developed sense of smell.
Comparisons among species demonstrate that humans are
more sensitive than new world monkeys to an odorant derived
from the human body (Laska et al. 2006). This lends support to
the theory that the behavioral relevance of an odor may be an
important determinant of a species’ olfactory ability (Laska
et al. 2005). In other sensory modalities the behavioral
relevance of the stimulus in question has been demonstrated
to be an important determinant of specialized neuronal
processing. Stimuli that have high significance for the individual, by signaling recurrent threats or other important
behavioral factors, seem to be ‘‘tagged’’ for priority processing
(Ohman et al. 2001). Stimuli such as faces (Morris et al. 1998)
and the cries of infants (Seifritz et al. 2003) are processed
differently from perceptually comparable stimuli that are
considered by the individual to be of limited behavioral
relevance. These so-called evolutionary relevant stimuli recruit
additional cortical and subcortical areas that are not commonly
active in response to stimuli with low evolutionary relevance.
In line with this notion, behaviorally relevant olfactory stimuli,
such as our body odor, could be hypothesized to recruit
nonolfactory structures to a higher degree than comparable
and perceptually similar common odors.
That humans are highly accurate at identifying individuals
based solely on their body odors has been known for some time
Ó The Author 2007. Published by Oxford University Press. All rights reserved.
For permissions, please e-mail: [email protected]
1
Department of Psychology, McGill University, Montreal, QC,
H3A1B1, Canada and 2Montreal Neurological Institute and
Hospital, McGill University, Montreal, Quebec H3A 2B4 Canada
Materials and Methods
Participants
Fifteen healthy, right-handed, nulliparous, nonsmoking women (mean
age 23 years; standard deviation [SD] ± 2.9; range 18--28 years),
recruited from the university’s student body, with an absence of nasal
congestion, sinus infection, allergies, or decreased olfactory function,
underwent positron emission tomography (PET) imaging (see Supplementary Material for additional information). Only women who
described themselves as exclusively heterosexual participated in the
study, either as ‘‘full participants’’ or odor donors. This exclusion
criterion was used because preference for body odors is influenced by
both gender and sexual orientation (Martins et al. 2005), and including
men in the study would require a large number of participants. Detailed
written informed consent was obtained from all participants prior to
enrollment, and all aspects of the study were performed in accordance
with the Declaration of Helsinki for experimentation with human
subjects. Participants and odor donors were rewarded upon completion of the study with a total of $130 and $30, respectively, and the
experimental protocol was approved by the Montreal Neurological
Institute (MNI) and Hospital’s Research Ethics Board.
Odor Stimuli
Body odors were collected from each participant and her long-time
close friend (mean length of friendship, 60 months). To collect the
body odors, each participant and odor donor slept for 7 consecutive
nights in a tight cotton t-shirt with cotton nursing pads sewn into the
underarm area. The t-shirts were used to prevent the cotton pads from
being contaminated by external odor sources and to ensure a close fit
of the pads in the armpits. The t-shirts were stored in a closed ziplocked bag at all times when not worn in bed. All odor donors followed
strict instructions that regulated their personal hygiene and diet to
ensure that the pads were not contaminated (see Supplementary
Material for a detailed description). After behavioral testing, as
described below, the pads were sealed in individual odor-free freezer
bags and deep frozen (–80 °C) until the day of scanning to prevent
degradation of the stimuli. The odor control mixture consisted of
cumin oil, anise oil, and indole (see Supplementary Material for
a detailed description). A 10% v/v concentration of this mixture was
applied to identical nursing pads and subjected to the same storage
procedure as the pads containing body odors.
Behavioral Testing Session
Participants returned the t-shirts on the morning of the eighth day, and
the pads were removed from the shirts and used for behavioral testing
before being deep frozen. That all participants possessed a functional
olfactory sense was determined using a 5-item olfactory identification
test (Hummel et al. 2001). All subjects had 4 or more correct
identifications. The ability to identify individual body odors was
assessed in a counterbalanced order using a psychophysical testing
paradigm. A 3-alternative, no feedback forced-choice task with 9
repetitions for each body odor category, with body odors from
strangers as foils, was administered. In addition, the agreement between
participants’ conscious experience and behavioral performance in the
aforementioned task was tested using a confidence assessment task. On
each individual trial, participants rated their confidence that they had
selected the correct response, using a visual analog scale ranging from
30% (guessing) to 100% (totally sure). Olfactory sensitivity for phenyl
ethyl alcohol was assessed using the Sniffin’ Sticks threshold test
(Hummel et al. 1997) at the end of the behavioral session.
PET Scanning Session
The PET session consisted of 5 odor conditions (odor-free Baseline,
Odor control, Self [BO], Friend [BO], and Stranger [BO]), each
presented twice in a pseudo-randomized order, yielding a total of 10,
60-s scans. Participants were informed that all body odors within each
scan would originate from the same identity category. Special care was
taken to assert that body odors in the category Stranger had not been
presented to the participant during the aforementioned behavioral
testing to prevent familiarization with the odor. The cotton pads were
positioned inside large-mouth glass bottles and presented during
scanning by placing the bottle approximately 10 mm under the
participant’s nose. Stimulus onset was 10 s prior to bolus onset and
ended approximately 10 s after scanning termination. Stimuli were
presented for 3 s with 5 s interstimulus intervals, yielding a total of 10
stimulus presentations for each condition. Scanning was performed
with eyes open so that the participants could synchronize their
breathing with the onset of the stimulus presentation. Participants
were instructed to focus on a mark located inside the scanner directly
above their heads, and to breathe normally and consistently throughout
all scans regardless of the valence or intensity of the stimuli. To ensure
that they focused on the presented stimuli, participants indicated with
a mouse click after each presentation whether the stimulus was
perceived as stronger or weaker than the previous one. To prevent
sniffing behavior that might activate cortical areas associated with
olfactory search (Zelano et al. 2005), participants were informed when
a blank stimulus would be presented (odor-free Baseline) and were
instructed to respond with a random click during each stimulus
presentation in that condition. Breathing was monitored with breast
and abdominal respiratory belts. No significant differences in breathing
were observed between scans. Following each scan, subjects were
asked to rate the stimulus for perceived pleasantness and intensity
using a 10-point visual analog scale. A minimum of 10 min occurred
between each scan to allow for the preparation of the isotope by the
cyclotron and to prevent olfactory adaptation.
Acquiring of Images and Data Analyses
PET scans were obtained with a Siemens Exact HR+ tomograph
operating in 3-dimensional acquisition mode using H2O15 water bolus.
T1-weighted structural magnetic resonance imaging (MRI) scans (160,
1-mm slices) were obtained for each subject with a 1.5-T Siemens
Sonata scanner to provide anatomical detail. PET images were
reconstructed using a 14-mm Hanning filter and processed using
normal methods (Zatorre et al. 1999). Statistical imaging analyses were
done using the in-house program ‘‘DOT,’’ described in detail elsewhere
(Worsley et al. 1992). The presence of significant changes in cerebral
blood flow (CBF) was established on the basis of an exploratory search
for which the t value criterion was set at >3.5. This value corresponds
to an uncorrected P value of <0.0002 for a whole-brain search volume.
Due to the conservative nature of conjunction analyses (Nichols et al.
2005), we established the presence of significant changes of CBF in the
conjunction analysis based on a t value criterion of >3.0, corresponding
to an uncorrected P value of <0.001 for a whole-brain search volume.
Results
Behavioral Results
All participating women had a normal olfactory threshold, as
indicated by the Sniffin’ Sticks normative values. The mean
olfactory threshold was 11.52; higher numbers in this test (16
being the maximum value) indicate higher sensitivity. To
investigate whether the subjects were able to correctly identify
the individual body odors that would be used during scanning,
identification performance and individual sensitivity were
recorded prior to the scanning session. All participants who
were selected to proceed to the scanning experiment were
able to identify correctly both their friend’s (Friend), t(14) =
4.94, P < 0.01, and their own (Self), body odor, t(14) = 16.00,
P < 0.01, above chance in a 3-alternative, no feedback forcedchoice task with 9 repetitions for each category using body
odors from strangers as foils (Fig. 1A). Anecdotal evidence has
indicated that conscious awareness of identification performance of individual body odor is low, which has been taken as
indicative of nonconscious processing. To explore this issue,
our participants were asked to assess their confidence in the
accuracy of their identifications after each trial. To evaluate the
agreement between subjects’ conscious judgment and their
behavioral performance on the identification task, an Over or
Underconfidence score (O/U) was calculated. Confidence is
commonly measured as the relationship between the mean
subjective probability of being correct, P, to that of the actual
Cerebral Cortex June 2008, V 18 N 6 1467
Figure 1. Identification of individual body odors. (a) Average identification performance in each body odor category. The dotted line represents chance performance. The mean
correct identification of the Self and Friend body odors were 8.33 (SD 1.29) and 6.80 (SD 2.98), respectively, out of a maximum score of 9. Error bars represent standard error of
the mean (SEM). (b) Confidence judgments plotted against actual proportion of correct answers for the 2 body odor categories. The dotted line represents perfect calibration,
indicating that subjective experience is well matched to actual performance. Values above the line indicate underconfidence in performance, whereas values under the line
indicate overconfidence. Note the relationship between excellent identification performance and large underconfidence when subjects were identifying body odors from Self.
proportion of correct discriminations, C (Bjorkman et al. 1993).
This difference, P – C, is expressed as an O/U score. Responses
are said to be calibrated to the extent that the proportion of
correct choices matches the subjective probability. In this
experiment, there was a dissociation between participants’
confidence in the 2 body odor categories. They were largely
underconfident in their ability to discriminate the Self body
odor correctly, O/U = –0.21, whereas they were well calibrated
in their ability to identify the Friend body odor, O/U = –0.01
(Fig. 1B).
There were no significant differences between the grouped
body odors and the Odor control in either perceived
pleasantness (4.8, SD ± 0.30 and 4.4, SD ± 0.43, respectively),
t(14) = 0.73, P ns (nonsignificant), or intensity (5.0, SD ± 0.33
and 5.7, SD ± 0.45, respectively), t(14) = 1.48, P ns, indicating
that the 2 odor categories were perceptually similar. This was
further supported by the fact that only 5 participants were able
to correctly label the Odor control as a nonbody odor during
scanning. The body odors forming the category Strangers
originated from the body odors that were presented as Friend
or Self to other participants, that is, the Strangers odors were
chemically identical to the Friend and Self odors. This unique
design allowed us to infer whether subjective ratings of the
individual body odor categories could be influenced by
category origin of the odor alone rather than the chemical
structure. Interestingly, there were significant differences in
how the individual body odors were perceived. Repeatedmeasures analysis of variance with Bonferroni post hoc tests
indicated that the body odor from the Stranger (intensity 5.9,
SD ± 0.43; pleasantness 4.03, SD ± 0.34) was perceived as both
more intense (all ts > 2.84, all Ps < 0.01) and less pleasant (all
ts > 1.97, all Ps < 0.05) than the other 2 categories. There were,
however, no significant differences in either perceived intensity or pleasantness between Self (intensity 4.6, SD ± 0.40;
pleasantness 5.1, SD ± 0.39) and Friend (intensity 4.5, SD ± 0.44;
pleasantness 5.3, SD ± 0.44) body odors. We did not statistically
assess participants’ performance in identifying each type of
body odor inside the scanner due to the small number of
stimulus repetitions during scanning.
1468 Neuronal Processing of Body Odors
d
Lundström et al.
Body Odor Processing
To evaluate the neuronal substrates of body odor processing,
we contrasted all body odor conditions (Stranger, Friend, and
Self) with the Baseline condition (clean nursing pad). Increased
regional CBF (rCBF) was observed in posterior cingulate
cortex, posterior occipital gyrus, dorsal postcentral gyrus, and
bilaterally in the angular gyrus (Supplementary Table 1a).
Interestingly, although these stimuli had a clear olfactory
percept, no activation above threshold was observed in regions
commonly associated with olfactory processing, such as the
piriform or the orbitofrontal cortex (Zatorre et al. 1992; Savic
et al. 2000). In fact, Body odors deactivated (Baseline vs. Body
odors) anterior parts of the orbitofrontal cortex (Fig. 2).
However, when assessing rCBF activation of the perceptually
similar Odor control compared with the Baseline condition,
activations above threshold were observed in dorsal postcentral gyrus, the middle orbitofrontal cortex and a just below
threshold activation (P = 0.002 by global contrast) in the
piriform cortex (Supplementary Table 1b). The latter 2 regions
are often labeled as secondary and primary olfactory cortex,
respectively (Zatorre et al. 1992; Savic et al. 2000).
A common activation in the 2 previous contrasts was the
postcentral gyrus, an area that has been implicated in the
neuronal processing of odors that activate the trigeminal nerve
(Boyle et al. 2007). Because both odor categories were
perceived as slightly irritating by the pilot group (Supplementary Material) who initially helped us choose a suitable
concentration of the Odor control, one might postulate that
Body odors and the Odor control both activated the
somatosensory system by virtue of their pungent percept. To
control for this and to investigate more thoroughly the
processing differences between body odors and common
odors with a similar percept, 2 additional computations were
performed. First, we contrasted body odors against the odor
control, revealing that body odors activated the posterior
cingulate cortex, occipital gyrus, cuneus, angular gyrus, and the
presupplementary motor area (pre-SMA) to a greater extent
than did the odor mixture (Supplementary Table 1c). We then
Table 1
Significant peaks of increased rCBF
Area
MNI coordinates
x
y
z
t value
(A) Conjunction analyses
Posterior cingulate cortex
Occipital gyrus
Angular gyrus
Dorsal medial anterior cingulate cortexa
Angular gyrusa
1
24
31
9
31
37
98
64
17
54
30
15
37
36
40
4.24
4.09
3.72
2.97
2.71
(B) Body odor from Stranger versus Body
odor from friend
Precuneus
Ventral Insula
Inferior frontal gyrus, orbital part
Substantia innominata/amygdalaa
8
37
42
13
67
0
37
3
40
16
9
13
3.74
3.55
3.50
3.11
(C) Body odor from Friend versus Body odor
from stranger
Postcentral gyrus
Precentral gyrus
Occipital gyrus
Paraoccipital transition zone/retrosplenial cortex
pre-SMA
5
7
11
21
7
37
25
92
76
15
63
64
6
33
57
4.12
3.97
3.73
3.67
3.52
Note: Anatomical labels follow the nomenclature of the Mai atlas. Positive x values denote
a right-sided activation, whereas negative values denote a left-sided activation.
Denotes peak activations that just missed significance.
a
Figure 2. A statistical parametric map (t statistics as represented by the color scale)
showing group averaged rCBF response showed to the processing of body odors
(contrast Baseline vs. all Body odors) superimposed on group averaged anatomical
MRI. Yellow circles mark decreased rCBF in bilateral anterior orbitofrontal cortex
(x, y, z MNI coordinates: 27, 58, 11; t 5 4.1 and 25, 58, 13; t 5 3.9).
Coordinates denote slice expressed according to the MNI world coordinates system.
Left in figure represents left side (L).
performed a conjunction analysis to explore regions that were
commonly activated in the 2 body odor contrasts (Body odors
vs. Baseline + Body odors vs. Odor control). Conjunction
analyses yield activations that are consistently found in all
individually included images within contrasts, whereas subtraction analyses rely on the average contrast only (Nichols
et al. 2005); hence, a conjunction analysis is a more conservative measure of the variable of interest. Increased rCBF above
threshold was observed in the posterior cingulate cortex
extending into the retrosplenial cortex, occipital gyrus, and
angular gyrus. In addition, activation just below threshold was
present in the dorsal medial anterior cingulate cortex and the
contralateral angular gyrus (Fig. 3 and Table 1). To control for
the possibility that the activation in the occipital cortex
was mediated by visualization following correct identification
of the body odor, we examined specifically scans where the
participants were exposed to the body odor from their friends
and themselves. This analysis was performed under the
assumption that subjects would not try to visualize an
individual when smelling either a believed stranger or
a believed common odor. The normalized rCBF values from
the peak activation in the aforementioned occipital region
were extracted, and scans in which subjects had correctly
identified their friends and/or themselves were compared with
scans in which the odors were incorrectly identified as
strangers or nonbody odors. There was no significant difference in rCBF (Supplementary Fig. 1) when subjects correctly
identified the body odor compared with when they did not, as
assessed by a 2-tailed independent samples Student’s t-test,
t(28) = 1.11, P ns. Further, to investigate the consistency of this
activation, we explored how many participants demonstrated
an increase at the occipital gyrus coordinate in the contrast
Body odors versus Baseline using a 5 mm volume of interest
(VOI) search sphere. The location of the activation in the
occipital cortex was very consistent across individuals, and only
4 participants did not demonstrate a marked increase in rCBF
when smelling body odors. These 4 individuals did, however,
show a marked increase in rCBF at a location just anterior to
the group averaged coordinate.
Processing of Individual Body Odors
We also explored whether neuronal processing differed
according to the relationship categories of the individual body
odors. Contrasting each body odor category against Baseline
did not produce different results than the combined Body odor
analyses presented above (Supplementary Table 2a--c). We then
contrasted individual body odor categories with each other.
Contrasting the condition of smelling an unknown body odor
(Stranger) to that of smelling a known body odor (Friend)
yielded significant rCBF increases in the precuneus, ventral
insula, and the inferior frontal gyrus. Interestingly, there were
also subthreshold activations in the substantia innominata/
amygdala (Supplementary Fig. 2, Table 1b). Reversing the
contrast, that is, smelling Friend versus Stranger, yielded
a different pattern. A significant increase in rCBF was detected
in the postcentral gyrus and extended into the precentral
gyrus, occipital gyrus, transverse occipital sulcus extending
into the retrosplenial cortex, and the pre-SMA (Table 1c).
These latter regions have previously been implicated in studies
investigating imagery (Djordjevic et al. 2005). Thus, to explore
whether this activation pattern was mediated by degree of
familiarity, we regressed the length of friendship with the
activation of smelling Friend versus Baseline using a voxel-wise
whole-brain regression analyses. Duration of friendship was
correlated only with increased rCBF in the right anterior
occipitotemporal cortex (Fig. 4) in close proximity to the
extrastriate body area (EBA) (Downing et al. 2001). The EBA
has previously been implicated in processing information
related to the human body (Downing et al. 2001). One might
speculate that the longer the participant had known her friend,
the more likely she would be to recognize the friend’s body
odor, thus recruiting this area more. However, there was no
Cerebral Cortex June 2008, V 18 N 6 1469
Figure 3. Statistical parametric maps (t statistics as represented by the color scale) of group averaged rCBF responses to processing of body odors (contrast all Body odors vs.
Odor control) superimposed on group averaged anatomical MRI. Blue circles mark increased rCBF in the posterior cingulate cortex (PCC), green circles mark increased rCBF
response in the left angular gyrus, and yellow circles mark an increased rCBF response in the right occipital cortex. Coordinates denote center of activation and slice expressed
according to the MNI world coordinates system. Left in upper row of pictures represents posterior and middle figures represent left side (L). Graphs under each statistical
parametric map represent extracted baseline-corrected rCBF values within the activation peak in question, using a 5 mm VOI search sphere, in each odor category. Error bars
represent standard error of the mean (SEM). All statistical parametric maps are thresholded at t 5 2.5.
Figure 4. (a) rCBF responses correlating with duration of friendship, assessed by the contrast Friend versus Baseline using voxel-wise whole-brain regression analyses
(t statistics as represented by the color scale). Duration of friendship was correlated only with increased rCBF in the right anterior occipitotemporal cortex (x, y, z MNI coordinates:
40, 66, 3; t 5 3.3). (b) Individual rCBF values in relationship duration of friendship (months). Equation was obtained with a bivariate correlation analysis, and solid line represents
regression line. rCBF values were extracted from the normalized raw images using a 5 mm VOI search sphere from the center of activation. Please note that cluster on regression
line contains more than one value.
correlation between length of friendship and ability to detect
the friend’s body odor in the screening session, as assessed with
a 2-tailed Pearson correlation analyses, r(15) = 0.28, P ns. In
addition, when normalized rCBF values extracted from scans in
which the subjects were able to correctly identify their friends
were compared with scans in which they were not, no
significant difference was found between the levels of rCBF,
as shown by an independent samples Student’s t-test, t(28) =
0.35, P ns. Hence, the response was not dependent on
conscious awareness of stimulus identity. Lastly, we assessed
the neuronal processing of the odor of ‘‘Self’’ by contrasting the
1470 Neuronal Processing of Body Odors
d
Lundström et al.
scans in which participants smelled Self body odor to those
when smelling Friend—both known odors. Interestingly, no
above-threshold activations were found in this contrast.
Discussion
Neuronal Correlates of Body Odor Processing
It is known that visual stimuli with high behavioral relevance
for the individual receive preferential processing. Here, in
concordance with the emerging view that endogenous odors
are of high ecological relevance, we have demonstrated for the
very first time that body odors are processed differently than
perceptually similar common odors. Body odors activated
a network consisting of the posterior cingulate cortex,
occipital gyrus, angular gyrus, and the anterior cingulate
cortex, none of which is believed to be related to olfactory
processing. However, together they form an interesting
pattern. Posterior cingulate cortex is known to be active in
response to emotional stimuli (Maddock 1999; Cato et al.
2004), whereas the anterior cingulate cortex is believed to
regulate attentional efforts (Botvinick et al. 1999). It is thus
possible that the processing of body odors is similar to what
previously has been demonstrated for highly emotional stimuli,
such as visual images of snakes (Fredrikson et al. 1995), where
the posterior cingulate cortex works in concert with the
anterior cingulate cortex to determine and process these
emotional stimuli. Although we are not able to infer a causal
direction between these 2 emotions, it is possible that by virtue
of their emotional load (Chen and Haviland-Jones 1999), body
odors receive not only differential treatment compared with
common odors, but also heightened attention. Seen from an
evolutionary perspective, stimuli signaling important information or related to recurrent survival threats might have been
selected by evolutionary pressure to receive preferential
processing in a direct access to emotional and attentional
centers of the brain.
The angular gyrus is strongly linked to the creation of
a visual body construct. Disruption or enhancement of the
neuronal signal in the angular gyrus is known to either abolish
or alter the percept of a body (Blanke et al. 2002, 2004; Arzy
et al. 2006). We are not able to make inferences to other
sensory modalities based on this experiment alone; however,
based on the strong dissociation in activation of the angular
gyrus between the body odors and the perceptually similar
common odors, especially in comparison with what has
previously been demonstrated for visual stimuli (Blanke et al.
2002, 2004; Arzy et al. 2006), it is tempting to suggest that the
angular gyrus serves as an important node in a modalityindependent network responsible for forming the basic
percept of a human body in the present—the body construct.
Interestingly, there were no above-baseline activations of
areas traditionally viewed as olfactory regions (piriform cortex
and orbitofrontal cortex) when participants smelled body
odors. Although the orbitofrontal cortex was activated when
smelling the Odor control, the perceptually similar Body odors
strongly deactivated large areas of the anterior orbitofrontal
cortex, an area reported to process common odors (Sobel et al.
2000; Poellinger et al. 2001; De Araujo et al. 2003; Gottfried and
Dolan 2004; Sabri et al. 2005), without activating the middle
orbitofrontal cortex. Similarly, no activation above baseline was
seen in the piriform cortex, an area commonly viewed as the
primary olfactory cortex, when smelling body odors, although
this area was activated for the Odor control. It is not possible to
elucidate whether this latter result may be due to the negative
control (a clean cotton pad smelling weakly of cotton). As
previously postulated by Boehm et al. (2005), our data seem to
indicate that endogenous odors are not processed by the
secondary olfactory cortex. This is indicative of an early
separation of odor processing dependent on the odor’s
signaling value, similar to what has been demonstrated for
the visual system. It is important to note that in this study, we
are only able to demonstrate the neuronal substrates of women
smelling women’s body odors. Others have reported that
women smelling the male endogenous compound androstadienone activated only the hypothalamus and not the primary or
secondary olfactory areas (Savic et al. 2001). Although one
might assume that the basic neuronal processing of body odors
would not exhibit a vast sex difference, we are not inferring
that the results reported here are generalizable to men’s
processing of body odors. Whether endogenous odors are
processed primarily by other, nonolfactory, cortical areas
in humans, as indicated by the lack of activation, or whether
there are sex differences in these processes remains to be
determined.
The Odor control condition activated a region associated
with higher odor processing, the middle orbitofrontal cortex. A
recent study demonstrated that changing the labeling of
a binary mixture of common odors from ‘‘body odor’’ to
‘‘cheddar cheese’’ led to an increased activation due to the
labeling, rather than the individual odorants, primarily in
the middle orbitofrontal cortex (De Araujo et al. 2005). The
authors suggested that this activation was formed by the
judgment of perceived pleasantness, a conclusion that is
supported by previous studies (Royet et al. 1999). To determine whether the activation in this region was mediated by
a hedonic perception in the present study, we regressed
pleasantness ratings against the rCBF values in the global
contrast Odor control versus Baseline. There was, however, no
above threshold correlation between pleasantness ratings and
rCBF values in the orbitofrontal cortex. An alternate explanation to this activation might be mixture processing. A recent
study from our lab indicates that an area of the orbitofrontal
cortex in close proximity to what we report here is specifically
involved in the processing of binary odor mixtures (Boyle et al.
2006). This region was activated while subjects smelled an
odor mixture, but not while they smelled a single odorant,
indicating a mixture identification mechanism. Because the
Odor control in that study was a mixture consisting of 3
individual odors, one might speculate that parts of the
orbitofrontal cortex process mixtures per se, rather than
responding uniquely to binary mixtures. Although this remains
to be elucidated, the lack of correlation between pleasantness
and rCBF values lends support to the notion that the activation
in this area occurred as a response to the mixture that was used
as an odor control.
The occipital cortex, an area commonly associated with
visual processing, was activated in all body odor contrasts.
Subjects were scanned with their eyes open in all conditions,
and there were no visual differences in how the stimuli were
presented. In other words, the visual input for each trial should
have been essentially identical, which is supported by the
consistency of the finding across participants. The activation of
the occipital cortex is a common finding in olfactory neuroimaging studies (Small et al. 1997; Royet et al. 1999, 2001;
Qureshy et al. 2000; Zatorre et al. 2000; Cerf-Ducastel and
Murphy 2001, 2006; Gottfried et al. 2004; Djordjevic et al. 2005;
Plailly et al. 2005, 2006). This indicates that the activation of
the occipital cortex cannot be attributed to the processing of
body odors per se (or an attempt to visualize the stimuli, as
demonstrated in this experiment); rather, the activity probably
represents some additional processes elicited by the odorous
stimuli. A review of the aforementioned articles reporting
visual activation demonstrates no obvious common variable
other than the use of olfactory stimuli. Determining whether
Cerebral Cortex June 2008, V 18 N 6 1471
the recruitment of cortical areas commonly associated with
visual processing is mediated by the odor processing itself or is
dependent on higher cognitive processes should be the focus
of future studies.
Neuronal Correlates of Smelling a Stranger
Smelling a stranger’s body odor evoked cortical activations
similar to what previously has been reported when viewing
masked fearful faces (Whalen et al. 1998). Inferior frontal gyrus
and the amygdala have both been linked in several studies to
the processing of negative emotional stimuli (Morris et al. 1998;
Whalen et al. 1998; Yamasaki et al. 2002). The percept of
a novel body odor that has not been encountered before thus
seems to activate similar emotional processes that have been
previously demonstrated for visual stimuli. This finding
supports the view that amygdalar responses to emotional
stimuli are not modality specific (Calder et al. 2001). Further,
this lends additional support to the view that endogenous
odors, which have high social and ecological importance, are
processed differently than perceptually comparable common
odors.
That body odors from strangers seem to evoke more
negative emotions than those from friends was further
supported by the perceptual ratings. When functioning as
a Stranger, body odors were consistently rated as more intense
and less pleasant than when functioning as a Friend, that is,
a body odor was rated differently depending on its relationship
to the individual doing the rating. This is a particularly nice
feature of the design and indicates that the neuronal responses
reported above are not due to the chemical composition per se;
rather, the difference in ratings is most probably mediated by
the implicit threat produced by the presence of a stranger in
the immediate vicinity. Moreover, this difference in perceptual
ratings might explain the activation of the precuneus and the
insular regions. Although the insula has been implicated in
recognition of fearful stimuli (Morris et al. 1999), a recent study
demonstrated a dissociation between these 2 regions. In the
study by Morris et al., the amygdala responded selectively to
fearful visual stimuli, whereas the insula and the precuneus
responded selectively to stimuli evoking disgust (see also
Phillips et al. 2004). More importantly, the insula has been
reported to respond to disgusting, but not pleasant, odors
(Wicker et al. 2003). In light of this, we suggest that the act of
smelling a stranger’s body odor activates the separate, yet
interlinked, feelings of both fear and disgust, or possibly here,
loathing (Calder et al. 2001). This is a sensation that most of us
have experienced for sudden visual or auditory stimuli. When
exposed to a sudden and novel sound or sight, we experience
not only the increase in arousal induced by fear, but also the
familiar negative feeling in the gut, a sensation possibly evoked
by the extensive anatomical connections between the amygdala and the insula (Amaral et al. 1992).
Neuronal Correlates of Familiar Body Odors
Smelling a friend activated a network consisting of areas
surrounding the central sulcus, occipital cortex including
posterior parts of the retrosplenial cortex, and the pre-SMA.
These areas are not analogous to those commonly reported
when viewing familiar visual stimuli. However, Shah et al.
(2001) recently reported that the posterior retrosplenial
cortex was uniquely involved in coding modality-independent
1472 Neuronal Processing of Body Odors
d
Lundström et al.
processing of familiar voices and faces. An activation just below
significance was also observed in the premotor cortex. In light
of this, we suggest that the activations observed when participants were stimulated with a long-time friend’s body odor
represent a network coding for person familiarity akin to the
network previously suggested by Shah et al. (2001). Interestingly, duration of friendship was significantly correlated with
increased rCBF in the EBA, an area that has been implicated in
the processing of information related to the human body
(Downing et al. 2001). To the best of our knowledge, this is the
first nonvisual study demonstrating that the percept of a body
activates this area. This indicates that the EBA is responding to
body-related stimuli in a modality-independent manner.
Participants were able to identify correctly the body odors of
themselves and their friends outside the scanner. However, the
independence between rCBF values and the ability to identify
the body odor, the subjects’ large underconfidence in their
ability to identify their own body odor, and the independence
between identification of friend’s body odor and duration of
friendship supports the notion that part of this process is
nonconsciously mediated. It is important to clarify that we are
not of the opinion that body odor identification is entirely
driven by nonconscious processes, nor do we wish to suggest
that explicit learning does not play a role. The correspondence
between the length of exposure to a body odor, defined by
length of the relationship, and the degree of rCBF activation in
the EBA clearly indicates that learning does play a role.
However, the lack of correspondence between correct
identification and rCBF activation in the EBA supports the
notion that this is mediated, on some level, by nonconscious
processes.
Interestingly, the contrast Self versus Friend did not produce
any activations above threshold. The lack of activation for Self
in contrast to another individual’s body odor might originate
from the underlying mechanism of body odor recognition. It
has been demonstrated that rodents use self-referent phenotype matching, the so-called armpit effect, when identifying
individual body odors (Mateo and Johnston 2000). In other
words, the animal uses its own body odor as a template to
assess the identity of an unknown individual. Vogt et al. (2006)
recently proposed that the posterior and anterior cingulate
cortices are functionally connected. The main responsibility of
the posterior cingulate cortex seems to be the processing of
emotional stimuli via interaction with the anterior cingulate
cortex using ‘‘self’’ as reference frame. If this mechanism of
body odor identification is also at play in humans, it would
explain both the lack of activation in the aforementioned
contrast and would put the angular gyrus activation into an
interesting context. As previously stated, disruption of activity
in the angular gyrus is associated with a distorted selfreferential space. Patients with an epileptic focus in the
angular gyrus often report out-of-body experiences or that
their percept of other people’s bodies is distorted (Blanke et al.
2002, 2004). The demonstration by Pause et al. (1999) that
body odors originating from oneself receive preferential
treatment lends further supports to the notion of self-referent
phenotype matching. Future studies are needed to determine
whether humans identify body odors using self-referent
phenotype matching akin to the mechanism demonstrated in
other animals.
In conclusion, we demonstrate that body odors are
processed differently from perceptually similar common odors
by activating regions commonly associated with emotions and
with the creation of a basic percept of a human body in the
present. In addition to providing the neuronal substrates of
processing body odors, a class of olfactory stimuli of high
occurrence and ecological interest, this finding is important for
several reasons. First, we demonstrate that body odors are
indeed processed differently than perceptually similar common
odors. These 2 classes of odors are treated differently by the
olfactory system. We demonstrate for the first time that body
odors are not primarily processed by what are commonly
regarded as olfactory cortices, indicating a separation in the
processing of odor signals. Second, it seems that the processing
of body odors is mostly nonconscious in nature, with limited
involvement of explicit learning. This lends support to the
emerging view that identification of body odors is an ongoing
automatic process that uses self-referent matching with little
conscious involvement. Third, we demonstrate for the first
time that the amygdala responds to the body odors of a stranger,
akin to what has previously been demonstrated for visually
masked faces, and that this activation is dependent on the
identity of the odor donor rather than on the odor’s chemical
composition. This might indicate that the amygdala responds to
fearful stimuli in a modality-independent manner. Finally, the
present results provide evidence that olfactory stimuli of high
ecological relevance are processed by specialized neuronal
networks similar to what has previously been demonstrated for
auditory and visual stimuli.
Supplementary Material
Supplementary material
oxfordjournals.org/.
can
be
found
at:
http://www.cercor.
Funding
Canadian Institutes of Health Research grant (MOP 57846) to
M.J.-G. and R.J.Z.; and a Swedish Research Council postdoctoral
research grant (VR 2005-960) to J.N.L.
Notes
We wish to thank the personnel at the McConnell Brain Imaging Center
for all their valuable help. Conflict of Interest: None declared.
Address correspondence to Johan N. Lundström PhD, Monell
Chemical Senses Center, 3500 Market Street, Philadelphia, PA 191043308, USA. E-mail: [email protected]
References
Amaral DG, Price JL, Pitkanen A, Carmichael ST. 1992. Anatomical
organization of the primate amygdaloid complex. In: Aggleton JP,
editor. The amygdala: neurobiological aspects of emotion, memory
and mental dysfunction. New York: Wiley-Liss. p. 1--66.
Arzy S, Seeck M, Ortigue S, Spinelli L, Blanke O. 2006. Induction of an
illusory shadow person. Nature. 443:287.
Bjorkman M, Juslin P, Winman A. 1993. Realism of confidence in sensory
discrimination: the underconfidence phenomenon. Percept Psychophys. 54:75--81.
Blanke O, Landis T, Spinelli L, Seeck M. 2004. Out-of-body experience
and autoscopy of neurological origin. Brain. 127:243--258.
Blanke O, Ortigue S, Landis T, Seeck M. 2002. Stimulating illusory ownbody perceptions. Nature. 419:269--270.
Boehm U, Zou Z, Buck LB. 2005. Feedback loops link odor and
pheromone signaling with reproduction. Cell. 123:683--695.
Botvinick M, Nystrom LE, Fissell K, Carter CS, Cohen JD. 1999. Conflict
monitoring versus selection-for-action in anterior cingulate cortex.
Nature. 402:179--181.
Boyle JA, Heinke M, Gerber J, Frasnelli J, Hummel T. 2007. Cerebral
activation to intranasal chemosensory trigeminal stimulation. Chem
Senses. 32:343--353.
Boyle JA, Olsson MJ, Djordjevic J, Lundstrom JN, Jones-Gotman M. 2006.
Contribution of the lateral orbitofrontal cortex to processing of
binary odor mixtures. Chem Senses. 31:A29.
Broca P. 1888. Mémoires d’Anthropologie. Paris: Reinwald.
Calder AJ, Lawrence AD, Young AW. 2001. Neuropsychology of fear and
loathing. Nat Rev Neurosci. 2:352--363.
Cato MA, Crosson B, Gokcay D, Soltysik D, Wierenga C, Gopinath K,
Himes N, Belanger H, Bauer RM, Fischler IS, et al. 2004. Processing
words with emotional connotation: an FMRI study of time course
and laterality in rostral frontal and retrosplenial cortices. J Cogn
Neurosci. 16:167--177.
Cerf-Ducastel B, Murphy C. 2001. fMRI activation in response to
odorants orally delivered in aqueous solutions. Chem Senses.
26:625--637.
Cerf-Ducastel B, Murphy C. 2006. Neural substrates of cross-modal
olfactory recognition memory: an fMRI study. NeuroImage.
31:386--396.
Chen D, Haviland-Jones J. 1999. Rapid mood change and human odors.
Physiol Behav. 68:241--250.
De Araujo IE, Rolls ET, Kringelbach ML, McGlone F, Phillips N. 2003.
Taste-olfactory convergence, and the representation of the pleasantness of flavour, in the human brain. Eur J Neurosci.
18:2059--2068.
De Araujo IE, Rolls ET, Velazco MI, Margot C, Cayeux I. 2005. Cognitive
modulation of olfactory processing. Neuron. 46:671--679.
Djordjevic J, Zatorre RJ, Petrides M, Boyle JA, Jones-Gotman M. 2005.
Functional neuroimaging of odor imagery. NeuroImage. 24:791--801.
Downing PE, Jiang Y, Shuman M, Kanwisher N. 2001. A cortical area
selective for visual processing of the human body. Science.
293:2470--2473.
Fredrikson M, Wik G, Fischer H, Andersson J. 1995. Affective and
attentive neural networks in humans: a PET study of Pavlovian
conditioning. NeuroReport. 7:97--101.
Gottfried JA, Dolan RJ. 2004. Human orbitofrontal cortex mediates
extinction learning while accessing conditioned representations of
value. Nat Neurosci. 7:1144--1152.
Gottfried JA, Smith AP, Rugg MD, Dolan RJ. 2004. Remembrance of
odors past: human olfactory cortex in cross-modal recognition
memory. Neuron. 42:687--695.
Hummel T, Konnerth CG, Rosenheim K, Kobal G. 2001. Screening of
olfactory function with a four-minute odor identification test:
reliability, normative data, and investigations in patients with
olfactory loss. Ann Otol Rhinol Laryngol. 110:976--981.
Hummel T, Sekinger B, Wolf SR, Pauli E, Kobal G. 1997. ‘Sniffin’ sticks’:
olfactory performance assessed by the combined testing of odor
identification, odor discrimination and olfactory threshold. Chem
Senses. 22:39--52.
Jacob S, McClintock MK, Zelano B, Ober C. 2002. Paternally inherited
HLA alleles are associated with women’s choice of male odor. Nat
Genet. 30:175--179.
Laska M, Fendt M, Wieser A, Endres T, Hernandez-Salazar LT,
Apfelbach R. 2005. Detecting danger—or just another odorant?
Olfactory sensitivity for the fox odor component 2,4,5-trimethylthiazoline in four species of mammals. Physiol Behav. 84:211--215.
Laska M, Wieser A, Salazar LT. 2006. Sex-specific differences in olfactory
sensitivity for putative human pheromones in nonhuman primates. J
Comp Psychol. 120:106--112.
Maddock RJ. 1999. The retrosplenial cortex and emotion: new insights
from functional neuroimaging of the human brain. Trends Neurosci.
22:310--316.
Martins Y, Preti G, Crabtree CR, Runyan T, Vainius AA, Wysocki CJ.
2005. Preference for human body odors is influenced by gender and
sexual orientation. Psychol Sci. 16:694--701.
Cerebral Cortex June 2008, V 18 N 6 1473
Mateo JM, Johnston RE. 2000. Kin recognition and the ‘armpit effect’:
evidence of self-referent phenotype matching. Proc R Soc Lond B
Biol Sci. 267:695--700.
Morris JS, Ohman A, Dolan RJ. 1998. Conscious and unconscious
emotional learning in the human amygdala. Nature. 393:467--470.
Morris JS, Scott SK, Dolan RJ. 1999. Saying it with feeling: neural responses to emotional vocalizations. Neuropsychologia. 37:1155--1163.
Nichols T, Brett M, Andersson J, Wager T, Poline J-B. 2005. Valid
conjunction inference with the minimum statistic. NeuroImage.
25:653--660.
Ohman A, Flykt A, Esteves F. 2001. Emotion drives attention: detecting
the snake in the grass. J Exp Psychol Gen. 130:466--478.
Pause BM, Krauel K, Schrader C, Sojka B, Westphal E, MullerRuchholtz W, Ferstl R. 2006. The human brain is a detector of
chemosensorily transmitted HLA-class I-similarity in same- and
opposite-sex relations. Proc Biol Sci. 273:471--478.
Pause BM, Krauel K, Sojka B, Ferstl R. 1999. Body odor evoked
potentials: a new method to study the chemosensory perception of
self and non-self in humans. Genetica. 104:285--294.
Phillips ML, Williams LM, Heining M, Herba CM, Russell T, Andrew C,
Bullmore ET, Brammer MJ, Williams SC, Morgan M, et al. 2004.
Differential neural responses to overt and covert presentations of
facial expressions of fear and disgust. NeuroImage. 21:1484--1496.
Plailly J, Bensafi M, Pachot-Clouard M, Delon-Martin C, Kareken DA,
Rouby C, Segebarth C, Royet JP. 2005. Involvement of right piriform
cortex in olfactory familiarity judgments. NeuroImage. 24:1032--1041.
Plailly J, d’Amato T, Saoud M, Royet JP. 2006. Left temporo-limbic and
orbital dysfunction in schizophrenia during odor familiarity and
hedonicity judgments. NeuroImage. 29:302--313.
Poellinger A, Thomas R, Lio P, Lee A, Makris N, Rosen BR, Kwong KK.
2001. Activation and habituation in olfaction—an fMRI study.
NeuroImage. 13:547--560.
Qureshy A, Kawashima R, Imran MB, Sugiura M, Goto R, Okada K,
Inoue K, Itoh M, Schormann T, Zilles K, et al. 2000. Functional
mapping of human brain in olfactory processing: a PET study. J
Neurophysiol. 84:1656--1666.
Royet JP, Hudry J, Zald DH, Godinot D, Gregoire MC, Lavenne F,
Costes N, Holley A. 2001. Functional neuroanatomy of different
olfactory judgments. NeuroImage. 13:506--519.
Royet JP, Koenig O, Gregoire MC, Cinotti L, Lavenne F, Le Bars D,
Costes N, Vigouroux M, Farget V, Sicard G, et al. 1999. Functional
anatomy of perceptual and semantic processing for odors. J Cogn
Neurosci. 11:94--109.
Sabri M, Radnovich AJ, Li TQ, Kareken DA. 2005. Neural correlates of
olfactory change detection. NeuroImage. 25:969--974.
Savic I, Berglund H, Gulyas B, Roland P. 2001. Smelling of odorous sex
hormone-like compounds causes sex-differentiated hypothalamic
activations in humans. Neuron. 31:661--668.
Savic I, Gulyas B, Larsson M, Roland P. 2000. Olfactory functions are
mediated by parallel and hierarchical processing. Neuron.
26:735--745.
1474 Neuronal Processing of Body Odors
d
Lundström et al.
Seifritz E, Esposito F, Neuhoff JG, Luthi A, Mustovic H, Dammann G, von
Bardeleben U, Radue EW, Cirillo S, Tedeschi G, et al. 2003.
Differential sex-independent amygdala response to infant crying
and laughing in parents versus nonparents. Biol Psychiatry. 54:
1367--1375.
Shah NJ, Marshall JC, Zafiris O, Schwab A, Zilles K, Markowitsch HJ,
Fink GR. 2001. The neural correlates of person familiarity. A
functional magnetic resonance imaging study with clinical implications. Brain. 124:804--815.
Small DM, Jones-Gotman M, Zatorre RJ, Petrides M, Evans AC. 1997.
Flavor processing: more than the sum of its parts. NeuroReport.
8:3913--3917.
Sobel N, Prabhakaran V, Zhao Z, Desmond JE, Glover GH, Sullivan EV,
Gabrieli JD. 2000. Time course of odorant-induced activation in the
human primary olfactory cortex. J Neurophysiol. 83:537--551.
Vogt BA, Vogt L, Laureys S. 2006. Cytology and functionally correlated
circuits of human posterior cingulate areas. NeuroImage. 29:
452--466.
Wallace P. 1977. Individual discrimination of humans by odor. Physiol
Behav. 19:577--579.
Weisfeld GE, Czilli T, Phillips KA, Gall JA, Lichtman CM. 2003. Possible
olfaction-based mechanisms in human kin recognition and inbreeding avoidance. J Exp Child Psychol. 85:279--295.
Whalen PJ, Rauch SL, Etcoff NL, McInerney SC, Lee MB, Jenike MA.
1998. Masked presentations of emotional facial expressions
modulate amygdala activity without explicit knowledge. J Neurosci.
18:411--418.
Wicker B, Keysers C, Plailly J, Royet JP, Gallese V, Rizzolatti G. 2003.
Both of us disgusted in My insula: the common neural basis of seeing
and feeling disgust. Neuron. 40:655--664.
Worsley KJ, Evans AC, Marrett S, Neelin P. 1992. A three-dimensional
statistical analysis for CBF activation studies in human brain. J Cereb
Blood Flow Metab. 12:900--918.
Yamasaki H, LaBar KS, McCarthy G. 2002. Dissociable prefrontal brain
systems for attention and emotion. Proc Natl Acad Sci USA.
99:11447--11451.
Zatorre RJ, Jones-Gotman M, Evans AC, Meyer E. 1992. Functional
localization and lateralization of human olfactory cortex. Nature.
360:339--340.
Zatorre RJ, Jones-Gotman M, Rouby C. 2000. Neural mechanisms
involved in odor pleasantness and intensity judgments. NeuroReport. 11:2711--2716.
Zatorre RJ, Mondor TA, Evans AC. 1999. Auditory attention to space and
frequency activates similar cerebral systems. NeuroImage. 10:
544--554.
Zelano C, Bensafi M, Porter J, Mainland J, Johnson B, Bremner E,
Telles C, Khan R, Sobel N. 2005. Attentional modulation in human
primary olfactory cortex. Nat Neurosci. 8:114--120.
Zwaardemaker H. 1895. Die Physiologie des Geruchs. Leipzig: Germany
W. Engelmann.