www.elsevier.com/locate/ynimg

NeuroImage 30 (2006) 1340 – 1346

A putative social chemosignal elicits faster cortical responses than

perceptually similar odorants

Johan N. Lundstrom,a,* Mats J. Olsson,b Benoist Schaal,c and Thomas Hummel d

aMontreal Nuerogical Institute, McGill University, 3801 University Street, Room 276 Montreal, Quebec, Canada H3A 2B4bDepartment of Psychology, Uppsala University, Box 1225, SE-751 42, Uppsala, SwedencCentre des Sciences du Gout, CNRS-Universite de Bourgogne, Dijon, FrancedSmell and Taste Clinic, Dept. of Otorhinolaryngology, University of Dresden Medical School, Dresden, Germany

Received 30 April 2005; revised 12 September 2005; accepted 31 October 2005

Available online 18 January 2006

Social chemosignals, so-called pheromones, have recently attracted

much attention in that effects on women’s psychophysiology and

cortical processing have been reported. We here tested the hypothesis

that the human brain would process a putative social chemosignal, the

endogenous steroid androstadienone, faster than other odorants with

perceptually matched intensity and hedonic characteristics. Chemo-

sensory event-related potentials (ERP) were recorded in healthy

women. ERP analyses indicate that androstadienone was processed

significantly faster than the control odorants. Androstadienone elicited

shorter latencies for all recorded ERP components but most so for the

late positivity. This finding indicates that androstadienone is processed

differently than other related odorants, suggesting the possibility of a

specific neuronal subsystem to the main olfactory pathway akin to the

one previously reported in Old-world monkeys and emotional visual

stimuli in humans.

D 2005 Elsevier Inc. All rights reserved.

Keywords: Pheromones; ERP; Olfaction; Androgens; Attention

Introduction

Specialized chemicals or chemical mixtures used for commu-

nication of social messages between conspecifics, so-called

pheromones, were described more than 50 years ago in insects

(Karlson and Luscher, 1959). Although several identified com-

pounds have been suggested to act as pheromonal signals among

non-primates (Melrose et al., 1971; Schaal et al., 2003), the

existence of a specific pheromonal compound in humans has so

far been supported only by indirect evidence. Among the first

reports on phenomena possibly explainable by pheromonal

mediation was the observation that women living in close

proximity synchronized their menstrual cycles (McClintock,

1971). However, although studies have shown that the complex

1053-8119/$ - see front matter D 2005 Elsevier Inc. All rights reserved.

doi:10.1016/j.neuroimage.2005.10.040

* Corresponding author. Fax: +1 514 398 1338.

E-mail address: jlunds@po-box.mcgill.ca (J. Lundstro m).

Available online on ScienceDirect (www.sciencedirect.com).

odor of axillary sweat carries biological signals (Preti et al., 2003;

Russell et al., 1980; Stern and McClintock, 1998) and specific

compounds have been suggested (Monti-Bloch and Grosser,

1991), no pheromonal compound in humans has been undisput-

edly identified so far (Schaal, 2001).

Several studies have investigated the psychobiological activity

of the endogenous human compound 4, 16-androstadien-3-one

(androstadienone) that can, among other places, be found in male

axillary secretion (Nixon et al., 1988). Androstadienone is also

found in women’s axillary hair, although generally at much smaller

concentrations (Brooksbank et al., 1972). Androstadienone has

been reported to influence women’s mood (Bensafi et al., 2004;

Jacob and McClintock, 2000; Lundstrom et al., 2003a; Lundstrom

and Olsson, 2005), psychophysiological variables (Bensafi et al.,

2003; Jacob et al., 2001a), and regional cerebral blood flow (rCBF;

Gulyas et al., 2004; Jacob et al., 2001b; Savic et al., 2001). Due to

the demonstrated sex-specific effects in several of these studies and

the higher prevalence of the compound in male secretions,

androstadienone has been proposed as a human pheromone (Sobel

and Brown, 2001).

In line with this notion, Savic et al. (2001, 2005) recently

demonstrated in two studies a sex-specific hypothalamic activation

to androstadienone exposure. When stimulated by androstadie-

none, the participating women, but not men, showed an increase of

rCBF in the hypothalamic area. Interestingly, this effect seems to

be dependent on sexual orientation in that heterosexual men

exhibited a hypothalamic activation, whereas their homosexual

counterparts did not (Savic et al., 2005). The authors discussed

whether a separate neuronal pathway could mediate the sex-

specific results: a separate pathway that processes social odorants.

Androstadienone has recently been suggested to be a putative

‘‘modulator pheromone’’ (Jacob and McClintock, 2000; McClin-

tock, 2000). Rather than eliciting a stereotypical response, such

stimulants are thought to modulate an ongoing psychobiological

state in relation to a specific social context, such as an

enhancement of attention to relevant stimuli in the environment.

Indeed, behavioral evidence indicates that androstadienone affects

J.N. Lundstrom et al. / NeuroImage 30 (2006) 1340–1346 1341

attention-related mechanisms (Lundstrom and Olsson, 2005;

Lundstrom et al., 2003a). Stimuli of high relevance for the

individual may have been selected to become triggers of attention

and hence processed faster (Tooby and Cosmides, 1990). From

these considerations, one would expect that androstadienone, if in

fact a human pheromone and in that a social odorant, would be

processed faster by a separate neuronal subsystem than other

common odorants.

Although androstadienone release effects hitherto not seen with

other odorants, no study has directly compared cortical responses of

androstadienone exposure with responses to other odorants that are

similar in both hedonic and intensity percept, two perceptual

dimensions that are known to significantly affect measures of mood

(Chen and Haviland-Jones, 1999; Knasko, 1995), psychophysio-

logical recordings (Bensafi et al., 2002), and rCBF (Royet et al.,

2001; Savic et al., 2000). To examine whether androstadienone is

processed differently by the human brain than other perceptually

similar but non-social odorants, we recorded chemosensory event-

related potentials (ERP) for androstadienone and two other odorants

matched for intensity and hedonic valence. ERP peak latencies are

considered to reflect the time at which certain subroutines in the

brain are activated (Kok, 1997), and the amplitude of these peaks is

thought to reflect the intensity of the activation (Hummel and

Kobal, 2001; Krauel et al., 1998). Olfactory ERPs are commonly

divided into the early, more exogenously or sensory evoked

potentials (P1 and N1) and the late, more endogenously or

psychologically evoked potential (P3), making distinctions between

sensory and psychological factors possible (Pause and Krauel,

2000). ERP recordings were selected before other imaging

techniques as measurements due to the inherent high temporal

resolution which makes the technique uniquely sensitive to the

differential information processing of sensory stimuli (Kok, 1997).

5alpha-androst-16en-3-one (androstenone) and hydrogen sul-

fide (H2S) were used in the present experiment as control odorants.

In the popular scientific literature, androstenone has repeatedly

been brought forward as a potential human pheromone (cf. Preti

and Wysocki, 1999) based on its well recognized pheromonal

effect among pigs (Melrose et al., 1971). However, although

several interesting psychophysical aspects of androstenone have

been reported, such as a high level of specific anosmia, to the best

of our knowledge, only one peer-reviewed article claiming meager

pheromonal effects has been published (Filsinger et al., 1990; but

see also a conference abstract: Kirk-Smith and Booth, 1980).

Androstenone was here selected as a control odorant as it is a

member of the same chemical group as androstadienone, thus

possessing a similarity in chemical structure and hedonic proper-

ties, being an odorant of endogenous origin (Gower and Ruparelia,

1993), and a lack of reported reliable pheromonal effects (Cornwell

et al., 2004; McClintock, 2003; Preti and Wysocki, 1999). H2S is

widely used in human olfactory research due to its lack of

trigeminal irritation (Kobal and Hummel, 1998) and is typically

rated to have an unpleasant odor, similar to the two androgen

odorants used. H2S is also found endogenously but has never been

suggested to be a human pheromone. The use of these two

chemically dissimilar control odorants further allows us to control

for potential effects on processing speed due to chemical structure

as previously hypothesized by others (Laing et al., 1994).

Based on these previous findings (e.g., Lundstrom and Olsson,

2005; Savic et al., 2001), we hypothesized that the sensory

processing of androstadienone, as measured by cortical responses,

would be differentiated from these perceptually similar odorants in

that androstadienone would be processed faster than both

androstenone and H2S.

Material and methods

Participants

Fifteen right-handed, reportedly heterosexual women with a

mean age of 28 years (SD = 7.8; range 20–45 years) provided

written consent to participate in the study. Inclusion criteria were

self-reported absence of major head trauma, nasal congestion,

pregnancy, lactation, and use of tobacco products. To exclude nasal

pathology, participants underwent a detailed otorhinolaryngologi-

cal examination including nasal endoscopy. Of the participating

women, 4 were within days 1–5 from menstrual onset, 4 were in

the follicular phase (days 6–14), and 7 in the luteal phase (days

15–30) of their menstrual cycle. Participants were instructed to

avoid food or beverages 1 h prior to testing. All aspects of the

study were performed in accordance with the declaration of

Helsinki and directions from the local ethics committee.

Stimuli

The steroid compounds were dissolved in propylene glycol

(purity � 99%; Sigma), a relatively odorless and non-toxic liquid.

To produce the stimuli, odorless air was bubbled through solutions

of 4 mM androstenone (Sigma, Deisenhofen, Germany) or 4 mM

androstadienone (Steraloids Inc., Newport, RI, USA), these odor-

saturated airstreams were then diluted to produce stimuli of 15% v/

v androstenone and 40% v/v androstadienone, respectively. H2S

was obtained from Air Liquide Deutschland GmbH (Krefeld,

Germany) and was presented at a concentration of 4 ppm. The

concentrations of the three compounds were chosen since they

produce a suprathreshold odor with very little or no trigeminal

stimulation (Kobal and Hummel, 1998; Lundstrom et al., 2003b;

Wysocki et al., 1987), and they were deemed to be iso-intense in a

pilot study where six participants rated intensities of different

concentrations of the three odorants in a side-by-side comparison

task.

Procedure

Prior to the electrophysiological measurements, participants

were screened for olfactory function using the ‘‘Sniffin’ Sticks’’

12-item screening test (Hummel et al., 2001). Ten or more correct

identifications were needed to fulfil the study’s inclusion criteria.

Since previous studies have demonstrated a high rate of specific

anosmia to androstenone (Amoore, 1977) and also, at a lesser rate,

to androstadienone (Lundstrom et al., 2003b), a three-alternative

forced-choice discrimination test was administered for both

androstenone and androstadienone, separately. Each discrimination

test consisted of seven trials during which the participants were

presented with three 50 ml glass jars, placed on the table in front of

them in a randomized order. One jar contained 4 ml of the odor in

the same concentration that was used for the ERP recordings for

that specific compound; the two other jars contained 4 ml of the

diluent only. The participants were then asked to sniff each jar once

and to identify the odd one. For inclusion in the study, five or more

correct identifications were needed on each test, corresponding to a

binomial probability of less than 0.04. After the initial psycho-

Table 1

Means and standard deviations (SD) for each peak’s amplitude (AV) andlatency (ms) at the Cz electrode

Androstadienone Androstenone H2S

Mean SD Mean SD Mean SD

Amplitude P1 1.26 2.97 1.94 2.62 2.58 2.07

N1 �3.48 3.17 �3.18 2.16 �1.94 2.77

P3 7.30 6.37 5.65 3.66 7.18 3.71

P1–N1 4.74 2.91 5.12 2.59 4.52 2.60

N1–P3 10.78 5.47 8.84 3.43 9.13 4.51

Latency P1 430 141 512 117 479 120

N1 522 158 609 135 559 129

P3 701 157 817 162 818 145

J.N. Lundstrom et al. / NeuroImage 30 (2006) 1340–13461342

physical screening tests, participants completed the Edinburgh

Handedness Inventory to ensure that only right-handed individuals

were included in the study (Oldfield, 1971). Only right-handed

women were included due to a previous report of cortical

asymmetries of olfactory processing between right- and left-

handed individuals (Royet et al., 2003).

Previous studies have indicated that the sex of the experimenter

could be a potential mediator of psychophysiological effects due to

androstadienone exposure (Jacob et al., 2001a; Lundstrom and

Olsson, 2005). To adhere with the logic of these findings and to

ensure consistency in experimenter behavior, the same 31-year-old

male experimenter performed all parts of the study, otorhinolaryn-

gological examination excluded, for all participants.

Electrophysiological recordings and perceptual ratings

Participants were seated comfortably in a secluded area. White

noise was used to mask any acoustical stimulation from the

switching valves of the olfactory stimulator. In order to keep the

participants in an awake and vigilant state during ERP recordings,

they were instructed to perform a tracking task on a video monitor

(Hummel and Kobal, 2001). Using a mouse, they had to keep a

small square inside a larger one that moved in an unpredictable

pattern across the screen. To examine participants’ percept of the

odors, the tracking task was briefly interrupted after each stimulus

presentation, and participants rated stimulus intensity by moving a

marker on a visual analogue scale that was presented on the screen

in front of them with Fvery weak_ as the left end point and Fveryintense_ as the right end point on the scale. Ratings were

automatically transformed to a scale ranging from 0.0 to 10.0.

For stimulus presentation, a dynamic olfactometer based on air-

dilution principles was used (OM6b; Burghart instruments, Wedel,

Germany). This delivery method allows the embedding of odorous

stimuli in a constant flow of odorless air (Kobal, 1981). For each

odorant, 20 stimulations grouped in blocks of four were presented

pseudo-randomized to prevent that the same odor block would be

presented twice in a row, comprising a total of 60 stimulations

within a session. The odorants were presented non-synchronously

to breathing with an average inter-stimulus interval of 40 s with

250 ms stimulus duration. Stimuli were presented monorhinally to

either the left or right nostril in a counterbalanced order.

Participants were instructed and trained to use the technique of

velopharyngeal closure during the whole session (Kobal, 1981).

Velopharyngeal closure restricts airflow to the oral cavity which

eliminates the need for presenting the stimuli synchronized to the

participant’s breathing; this procedure reduces potential expecta-

tion-related effects such as the contingent negative variation

(Loveless, 1983). After completion of the ERP recordings,

participants were once again stimulated with the three odorants

and asked to rate their hedonic valence by indicating how pleasant

or unpleasant they perceived each of them. Ratings were performed

on a visual analogue scale similar to the one described above with

the difference that the left end of the scale was marked Fveryunpleasant_, the middle of the scale as Fneutral_, and the right side

as Fvery pleasant_.ERPs were recorded at 3 midline scalp positions according to

the international 10–20 system (Fz, Cz, and Pz) using an 8-channel

amplifier (SIR, Rottenbach, Germany), referenced to linked

earlobes (A1 + A2). Vertical eye movements were monitored at

the Fp2 lead. The sampling frequency was 250 Hz; the pre-trigger

period was 500 ms with a recording time of 2048 ms (band pass

0.02–30 Hz). Recordings were additionally filtered off-line (low-

pass 15 Hz). Eye blink-contaminated recordings with artifacts

larger than 50 AV in the Fp2 lead were discarded. Recordings were

averaged off-line separately for each recording site, yielding late

near-field ERPs (Hummel and Kobal, 2001). Peaks of the ERP

were defined as P1, N1, and P3. Mean base-to-peak amplitudes,

peak latencies, and peak-to-peak amplitudes (P1–N1 and N1–P3)

were measured (software BOMPE 4.1; Kobal, Erlangen, Ger-

many). Means and standard deviations for the ERP at recording site

Cz for each compound are given in Table 1.

Statistical analyses

ERP data were submitted to repeated-measures analyses of

variance (repeated-measures (rm)-ANOVA) for each ERP peak

(P1, N1, and P3) separately, with Fodorant_ (androstadienone,

androstenone, and H2S) and Felectrodes_ (Fz, Cz, and Pz) as

within-subject factors. Differences in hedonic and intensity ratings

were analyzed with rm-ANOVAs with Fodorant_ (androstadienone,androstenone, and H2S) as a within-subject factor. Alpha values

below 0.05 are here reported as significant differences, and alpha

values below 0.10 are reported as statistical tendencies.

Results

Perception

Rm-ANOVAs with Fodorants_ as a within-subject factor indicat-ed that there were no significant differences in participants’ intensity

ratings, F(2,28) = 0.75, ns, or hedonic ratings among odorants

[ F(2,28) = 1.86, ns; see Fig. 1]. As indicated by Fig. 1,

androstadienone was nominally rated as more pleasant than the

two other odorants. To explore this potential difference further,

separate paired Student’s t tests were performed, demonstrating no

differences in the participant’s hedonic ratings between any of the

odorants, all P’s ns.

Cortical responses

There were significant differences among odorants for all peak

latencies as indicated by rm-ANOVAs with Fodorants_ and

Felectrodes_ as within-subject factors [P1, F(2,28) = 4.00, P <

0.05; N1, F(2,28) = 3.45, P < 0.05; P3, F(2,28) = 7.00, P < 0.01].

Fisher PLSD post-hoc tests, corrected for multiple comparisons,

showed that androstadienone was processed faster than both

Fig. 1. Perception of the odorants. Mean (TSEM) psychophysical ratings of the odorants’ stimulus intensity and hedonic value for androstadienone (ANDI),

androstenone (AND), and hydrogen sulfide (H2S). Units expressed as distances on a visual analogue scale. For intensity, zero represents Fvery weak_, and ten

represents Fvery intense_; for hedonic, zero represents Fvery unpleasant_, five represents Fneutral_, and ten represents Fvery pleasant_. (A) Rm-ANOVAs with

Fodorant_ as within-subject factor, (B) separate paired Student’s t test.

J.N. Lundstrom et al. / NeuroImage 30 (2006) 1340–1346 1343

androstenone and H2S in the P1 peak (all corrected P < 0.05). No

difference was found between H2S and androstenone (corrected P

ns). Although not significant, there were statistical tendencies for

androstadienone to be processed faster than both androstenone and

H2S in the N1 peak (all corrected P < 0.10). Again, no difference

was found between H2S and androstenone (corrected P ns). In the

P3 peak, no difference was found between H2S and androstenone

(corrected P ns). However, androstadienone was on average

processed over 100 ms faster than both androstenone and H2S

[all corrected P < 0.01, (see Fig. 2)].

There were no significant differences in base-to-peak amplitudes

among these odorants for any of the peaks as indicated by rm-

Fig. 2. Electrophysiological responses. Mean (TSEM) latencies of the averaged mea

* denotes a significant difference ( P < 0.05) and . denotes a statistical tendency (

indicates ERP components and electrode locations.

ANOVAs with Fodorants_ and Felectrodes_ as within-subject

variables [P1, F(2,28) = 0.33, ns; N1, F(2,28) = 0.80, ns; P3, F(2

28) = 0.77, ns]. Finally, there were no significant differences in peak-

to-peak amplitudes among these odorants for neither P1–N1 nor

N1–P3 as indicated by rm-ANOVAs with Fodorants_ and

Felectrodes_ as within-subject factors [P1–N1, F(2,28) = 0.52, ns;

N1–P3, F(2,28) = 1.75, ns].

A visual comparison of the participants’ ratings of odor

hedonics and the difference in P3 latencies between odorants

suggests a functional relationship. To investigate whether the large

difference in P3 latency between androstadienone and the two

control odors is dependent on the participants’ hedonic ratings of

ns of the Fz, Cz, and Pz electrodes separated by ERP components. In figure,

P > 0.10) as deemed by post-hoc tests with Bonferroni corrections. Cartoon

J.N. Lundstrom et al. / NeuroImage 30 (2006) 1340–13461344

androstadienone, participants were split into two groups based on

their hedonic ratings, forming the factor Fhedonic rating_ [Flowrater_ (n � 8); Fhigh rater_ (n � 7)]. An rm-ANOVA with

Fodorants_ and Felectrodes_ as within-subject factors and Fhedonicrating_ as between-subject factor indicated that there was no main

effect of Fhedonic rating_ on the P3 latencies [F(1,13) = 0.17, ns]

nor was there an interaction effect between Fodorants_ and Fhedonicrating_ on the P3 latencies [F(2,26) = 0.39, ns]. The nominal

difference in hedonic ratings between androstadienone and the two

control odors thus had no impact on the differences in latencies

between odorants.

Discussion

The odor of androstadienone was here processed faster than both

androstenone and H2S, although the participants rated the three

compounds as iso-intense and as having a similar hedonic tone. The

perceptual similarity among these odorants was supported by the

lack of differences in amplitudes among responses to the three

odorants. The large difference in processing speed between

androstadienone and the two other odorants presented in the current

study is unique. Androstadienone was here processed between 13

and 20% faster than the two control odorants in all ERP components.

Differences in chemosensory ERP have previously only been

demonstrated between perceptually very dissimilar compounds

(cf. Hummel and Kobal, 2001). This large difference in processing

speed between perceptually similar odorants has not previously been

reported and supports the hypothesis that androstadienone is

processed differently by the cortex than the other odorants.

Savic et al. (2001, 2005) recently proposed that androstadie-

none could be processed by a separate neuronal pathway. Such a

separate subcortical olfactory pathway has indeed previously been

demonstrated in Old-world monkeys (Takagi, 1989; Tazawa et al.,

1987) that, similar to humans, appear to miss a functional receptor

organ for an accessory olfactory system (Zhang and Webb, 2003).

Little is known about potential pheromonal pathways in humans

(Meredith, 2001) and the separate question of which specific

anatomical sensory system could be responsible for mediating the

above effects is beyond the scope of this study. However, the large

differences in latency between odors on both the early and late

positive components of the ERP indeed suggest that androstadie-

none may be processed by a separate neuronal subcortical circuit.

Such a separate circuitry has previously been demonstrated in the

visual system for both arousing emotional and social stimuli by

behavioral (Ohman et al., 2001a,b; Zihl and von Cramon, 1979),

imaging (Morris et al., 1999; Sahraie et al., 1997), and lesion

studies (Tomaiuolo et al., 1997). These stimuli are processed by a

separate subcortical pathway, rendering a faster and more

automatic processing than non-relevant stimuli (Morris et al.,

1999; Ohman and Mineka, 2001). If androstadienone is a human

pheromone in some sense, its relevance as a social signal should be

evident. It is thus conceivable that androstadienone is processed by

a similar subsystem of the main olfactory pathway as previously

demonstrated in the visual system, a subsystem that processes

emotional and social stimuli of high relevance. This preliminary

study sets the stage for further work on the differential processing

of putative social chemical signals. Future studies employing

connectivity analyses, possibly in relation with receptor organ

manipulation, will be helpful to establish the potential differences

in neural pathways.

As a putative human modulator pheromone, androstadienone is

expected to enhance attention to relevant stimuli (Jacob and

McClintock, 2000; McClintock, 2000). In the present study, the

latency of the P3 component showed the greatest difference

between androstadienone and the two other odorants. Previous

studies have demonstrated that latencies of the late component are

considerably reduced when subjects are performing automatic

processing of stimuli in comparison with non-automatic processing

(Hoffman et al., 1983; Kramer et al., 1986, 1991), a phenomenon

that may reflect an automatic attention response (Kok, 1997). It is

thus conceivable that this significant difference in response

latencies for the late positive component between androstadienone

and the two control odorants indicates that androstadienone

receives more rapid and more automatic processing, implying

pheromonal properties (Gulyas et al., 2004; Lundstrom and

Olsson, 2005; Lundstrom et al., 2003a).

One might argue that the difference in latencies among odorants

is due to a difference in speed of mucus absorption in the olfactory

mucosa as previously hypothesized for odorants in mixtures (Laing

et al., 1994). However, this is an unlikely explanation. Androsta-

dienone was processed faster than both the perceptually and

chemically similar androstenone and the perceptually similar but

chemically dissimilar H2S. If mucus transfer processes aremediating

the above-reported effects, androstadienone and androstenone

should be processed in a similar temporal fashion due to their

chemical similarity (Jinks et al., 2001; Schild and Restrepo, 1998).

In fact, when temporal differences in processing between odorants

have previously been demonstrated, less pleasant and more intense

stimuli are processed faster (Jinks and Laing, 1999; Kobal et al.,

1992; Laing et al., 1994). In this context, the participants’ hedonic

and intensity ratings of the odorants argue that androstadienone

should be processed slower rather than faster than the two control

odorants. However, we demonstrate here that the large difference in

processing speed for androstadienone is not dependent on differ-

ences in perception between the odorants. Moreover, since

comparisons to both a chemically similar and a chemically

dissimilar odorant were made, we argue that the large difference in

processing speed demonstrated here cannot be explained by a

difference in mucus transduction process. Of special interest is the

difference in latencies between androstadienone and androstenone.

These odorants are not only both endogenously produced with a

similar musky odor quality, the participating women could also be

expected to have similar lifetime exposure to both compounds. The

demonstrated difference in speed of processing between these

odorants could thus not readily be explained by amount of exposure

or learned responses.

In conclusion, this study demonstrates a difference in cortical

activity between odorants similar in intensity and hedonic value. The

participating women had shorter latencies on all ERP components

when exposed to androstadienone as compared to the perceptually

similar odors of androstenone and H2S. This difference in latencies

suggests that androstadienone is processed by a neural subsystem to

the main olfactory system which would make it unique among

odorants.

Acknowledgments

We thank Dr. Michael Knecht for help with the ENT

examinations and Julie Boyle and Dr. Marilyn Jones-Gotman

for helpful comments on previous versions of the manuscript.

J.N. Lundstrom et al. / NeuroImage 30 (2006) 1340–1346 1345

The authors declare that they have no competing financial

interest.

References

Amoore, J.E., 1977. Specific anosmia and the concept of primary odors.

Chem. Senses Flavor 2, 267–281.

Bensafi, M., Rouby, C., Farget, V., Bertrand, B., Vigouroux, M., Holley, A.,

2002. Autonomic nervous system responses to odours: the role of

pleasantness and arousal. Chem. Senses 27 (8), 703–709.

Bensafi, M., Brown, W.M., Tsutsui, T., Mainland, J.D., Johnson, B.N.,

Bremner, E.A., Young, N., Mauss, I., Ray, B., Gross, J., et al., 2003.

Sex-steroid derived compounds induce sex-specific effects on auto-

nomic nervous system function in humans. Behav. Neurosci. 117 (6),

1125–1134.

Bensafi, M., Brown, W.M., Khan, R., Levenson, B., Sobel, N., 2004.

Sniffing human sex-steroid derived compounds modulates mood,

memory and autonomic nervous system function in specific behavioral

contexts. Behav. Brain Res. 152 (1), 11–22.

Brooksbank, B.W., Wilson, D.A., MacSweeney, D.A., 1972. Fate of

androsta-4,16-dien-3-one and the origin of 3-hydroxy-5-androst-16-

ene in man. J. Endocrinol. 52 (2), 239–251.

Chen, D., Haviland-Jones, J., 1999. Rapid mood change and human odors.

Physiol. Behav. 68 (1–2), 241–250.

Cornwell, R.E., Boothroyd, L., Burt, D.M., Feinberg, D.R., Jones, B.C.,

Little, A.C., Pitman, R., Whiten, S., Perrett, D.I., 2004. Concordant

preferences for opposite-sex signals? Human pheromones and facial

characteristics. Proc. R. Soc. London, Ser. B Biol. Sci. 271 (1539),

635–640.

Filsinger, E.E., Braun, J.J., Monte, W.C., 1990. Sex differences in

response to the odor of alpha androstenone. Percept. Mot. Skills 70

(1), 216–218.

Gower, D.B., Ruparelia, B.A., 1993. Olfaction in humans with special

reference to odorous 16-androstenes: their occurrence, perception and

possible social, psychological and sexual impact. J. Endocrinol. 137 (2),

167–187.

Gulyas, B., Keri, S., O’Sullivan, B.T., Decety, J., Roland, P.E., 2004.

The putative pheromone androstadienone activates cortical fields in

the human brain related to social cognition. Neurochem. Int. 44 (8),

595–600.

Hoffman, J.E., Simons, R.F., Houck, M.R., 1983. Event-related potentials

during controlled and automatic target detection. Psychophysiology 20

(6), 625–632.

Hummel, T., Kobal, G., 2001. Olfactory event-related potentials. In: Simon,

S.A., Nicolelis, M.A.L. (Eds.), Methods in Chemosensory Research.

CRC Press, Boca Raton, pp. 429–464.

Hummel, T., Konnerth, C.G., 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 (10), 976–981.

Jacob, S., McClintock, M.K., 2000. Psychological state and mood

effects of steroidal chemosignals in women and men. Horm. Behav.

37 (1), 57–78.

Jacob, S., Hayreh, D.J., McClintock, M.K., 2001a. Context-dependent

effects of steroid chemosignals on human physiology and mood.

Physiol. Behav. 74 (1–2), 15–27.

Jacob, S., Kinnunen, L.H., Metz, J., Cooper, M., McClintock, M.K., 2001b.

Sustained human chemosignal unconsciously alters brain function.

NeuroReport 12 (11), 2391–2394.

Jinks, A., Laing, D.G., 1999. Temporal processing reveals a mechanism for

limiting the capacity of humans to analyze odor mixtures. Brain Res.

Cogn. Brain Res. 8 (3), 311–325.

Jinks, A., Laing, D.G., Hutchinson, I., 2001. A psychophysical study of the

relationship between temporal processing in odor mixtures and

transduction pathways. Brain Res. Cogn. Brain Res. 12 (2), 273–288.

Karlson, P., Luscher, M., 1959. FPheromones_: a new term for a class of

biologically active substances. Nature 183, 55–56.

Kirk-Smith, M.D., Booth, D.A., 1980. Effect of androstenone on choice of

location in others’ presence. In: Starre, H.V.D. (Ed.), IRL Press,

Noordwijkerhout, Netherlands, pp. 397–400.

Knasko, S.C., 1995. Pleasant odors and congruency: effects on approach

behavior. Chem. Senses 20 (5), 479–487.

Kobal, G., 1981. Electrophysiologische Untersuchungen des menschlichen

Geruchssinns. Thieme Verlag, Stuttgart.

Kobal, G., Hummel, T., 1998. Olfactory and intranasal trigeminal

event-related potentials in anosmic patients. Laryngoscope 108 (7),

1033–1035.

Kobal, G., Hummel, T., Van Toller, S., 1992. Differences in human

chemosensory evoked potentials and somatosensory chemical stimuli

presented to left and right nostril. Chem. Senses 17, 233–244.

Kok, A., 1997. Event-related-potential (ERP) reflections of mental

resources: a review and synthesis. Biol. Psychol. 45 (1–3), 19–56.

Kramer, A., Schneider, W., Fisk, A., Donchin, E., 1986. The effects of

practice and task structure on components of the event-related brain

potential. Psychophysiology 23 (1), 33–47.

Kramer, A.F., Strayer, D.L., Buckley, J., 1991. Task versus component

consistency in the development of automatic processing: a psychophys-

iological assessment. Psychophysiology 28 (4), 425–437.

Krauel, K., Pause, B.M., Mueller, C., Sojka, B., Mueller-Ruchholtz, W.,

Ferstl, R., 1998. Central nervous correlates of chemical communication

in humans. Ann. N. Y. Acad. Sci. 855, 628–631.

Laing, D.G., Eddy, A., Francis, G.W., Stephens, L., 1994. Evidence for the

temporal processing of odor mixtures in humans. Brain Res. 651 (1–2),

317–328.

Loveless, N.E., 1983. Event-related brain potentials and human perfor-

mance. In: Gale, A.D. (Ed.), Physiological Correlates of Human

Behavior. Academic Press, London, pp. 80–97.

Lundstrom, J.N., Olsson, M.J., 2005. Subthreshold amounts of social

odorant affect mood, but not behavior, in heterosexual women when

tested by a male, but not a female, experimenter. Biol. Psychol. (70),

197–204.

Lundstrom, J.N., Goncalves, M., Esteves, F., Olsson, M.J., 2003a.

Psychological effects of subthreshold exposure to the putative human

pheromone 4,16-androstadien-3-one. Horm. Behav. 44 (5), 395–401.

Lundstrom, J.N., Hummel, T., Olsson, M.J., 2003b. Individual differences

in sensitivity to the odor of 4,16-androstadien-3-one. Chem. Senses 28

(7), 643–650.

McClintock, M.K., 1971. Menstrual synchrony and suppression. Nature

229 (5282), 244–245.

McClintock, M.K., 2000. Human pheromones: primers, releasers, signalers,

or modulators? In: Wallen, K., Schneider, J.E. (Eds.), Reproduction in

Context: Social and Environmental Influences on Reproductive Phys-

iology and Behavior. MIT Press, Cambridge, pp. 355–420.

McClintock, M.K., 2003. Pheromones, odors, and vasanas: the

neuroendocrinology of social chemosignals in humans and animals.

In: Pfaff, D.W. (Ed.), Hormones, Brain, and Behavior. Academic Press,

pp. 797–870.

Melrose, D.R., Reed, H.C., Patterson, R.L., 1971. Androgen steroids

associated with boar odour as an aid to the detection of oestrus in pig

artificial insemination. Br. Vet. J. 127 (10), 497–502.

Meredith, M., 2001. Human vomeronasal organ function: a critical review

of best and worst cases. Chem. Senses 26 (4), 433–445.

Monti-Bloch, L., Grosser, B.I., 1991. Effect of putative pheromones on

the electrical activity of the human vomeronasal organ and olfactory

epithelium. J. Steroid Biochem. Mol. Biol. 39 (4B), 573–582.

Morris, J.S., Ohman, A., Dolan, R.J., 1999. A subcortical pathway to the

right amygdala mediating ‘‘unseen’’ fear. Proc. Natl. Acad. Sci. U. S. A.

96 (4), 1680–1685.

Nixon, A., Mallet, A.I., Gower, D.B., 1988. Simultaneous quantification

of five odorous steroids (16-androstenes) in the axillary hair of men.

J. Steroid Biochem. 29 (5), 505–510.

Ohman, A., Mineka, S., 2001. Fears, phobias, and preparedness: toward

J.N. Lundstrom et al. / NeuroImage 30 (2006) 1340–13461346

an evolved module of fear and fear learning. Psychol. Rev. 108 (3),

483–522.

Ohman, A., Flykt, A., Esteves, F., 2001. Emotion drives attention: detecting

the snake in the grass. J. Exp. Psychol. Gen. 130 (3), 466–478.

Ohman, A., Lundqvist, D., Esteves, F., 2001. The face in the crowd

revisited: a threat advantage with schematic stimuli. J. Pers. Soc.

Psychol. 80 (3), 381–396.

Oldfield, R.C., 1971. The assessment and analysis of handedness: the

Edinburgh inventory. Neuropsychologia 9 (1), 97–113.

Pause, B.M., Krauel, K., 2000. Chemosensory event-related potentials

(CSERP) as a key to the psychology of odors. Int. J. Psychophysiol. 36

(2), 105–122.

Preti, G., Wysocki, C.J., 1999. Human pheromones: releasers or primers—

Fact or myth. In: Johnston, R.E. (Ed.), Advances in Chemical Signals in

Vertebrates. Kluwer Academic, New York, pp. 315–331.

Preti, G., Wysocki, C.J., Barnhart, K.T., Sondheimer, S.J., Leyden, J.J.,

2003. Male axillary extracts contain pheromones that affect pulsatile

secretion of luteinizing hormone and mood in women recipients. Biol.

Reprod. 68 (6), 2107–2113.

Royet, J.P., Hudry, J., Zald, D.H., Godinot, D., Gregoire, M.C., Lavenne, F.,

Costes, N., Holley, A., 2001. Functional neuroanatomy of different

olfactory judgments. NeuroImage 13 (3), 506–519.

Royet, J.P., Plailly, J., Delon-Martin, C., Kareken, D.A., Segebarth, C.,

2003. fMRI of emotional responses to odors: influence of hedonic

valence and judgment, handedness, and gender. NeuroImage 20 (2),

713–728.

Russell, M.J., Switz, G.M., Thompson, K., 1980. Olfactory influences

on the human menstrual cycle. Pharmacol. Biochem. Behav. 13 (5),

737–738.

Sahraie, A., Weiskrantz, L., Barbur, J.L., Simmons, A., Williams, S.C.,

Brammer, M.J., 1997. Pattern of neuronal activity associated with

conscious and unconscious processing of visual signals. Proc. Natl.

Acad. Sci. U. S. A. 94 (17), 9406–9411.

Savic, I., Gulyas, B., Larsson, M., Roland, P., 2000. Olfactory functions

are mediated by parallel and hierarchical processing. Neuron 26 (3),

735–745.

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 (4), 661–668.

Savic, I., Berglund, H., Lindstrom, P., 2005. Brain response to putative

pheromones in homosexual men. Proc. Natl. Acad. Sci. U. S. A. 102

(20), 7356–7361.

Schaal, B., 2001. Olfactory exchanges in humans: information or

communication. Primatologie 4, 11–75.

Schaal, B., Coureaud, G., Langlois, D., Ginies, C., Semon, E., Perrier, G.,

2003. Chemical and behavioural characterization of the rabbit mamma-

ry pheromone. Nature 424 (6944), 68–72.

Schild, D., Restrepo, D., 1998. Transduction mechanisms in vertebrate

olfactory receptor cells. Physiol. Rev. 78 (2), 429–466.

Sobel, N., Brown, W.M., 2001. The scented brain: pheromonal responses in

humans. Neuron 31 (4), 512–514.

Stern, K., McClintock, M.K., 1998. Regulation of ovulation by human

pheromones. Nature 392 (6672), 177–179.

Takagi, S.F., 1989. Human Olfaction. University of Tokyo Press, Tokyo.

Tazawa, Y., Onoda, N., Takagi, S.F., 1987. Olfactory input to the

lateral hypothalamus of the old world monkey. Neurosci. Res. 4 (5),

357–375.

Tomaiuolo, F., Ptito, M., Marzi, C.A., Paus, T., Ptito, A., 1997. Blindsight

in hemispherectomized patients as revealed by spatial summation across

the vertical meridian. Brain 120 (Pt. 5), 795–803.

Tooby, J., Cosmides, L., 1990. The past explains the present—Emotional

adaptations and the structure of ancestral environments. Ethol. Socio-

biol. 11 (4–5), 375–424.

Wysocki, C.J., Beauchamp, G.K., Schmidt, H.J., Dorries, K.M., 1987.

Changes in olfactory sensitivity to androstenone with age and

experience. Chem. Senses 12 (4), 710.

Zhang, J., Webb, D.M., 2003. Evolutionary deterioration of the vomer-

onasal pheromone transduction pathway in catarrhine primates. Proc.

Natl. Acad. Sci. U. S. A. 100 (14), 8337–8341.

Zihl, J., von Cramon, D., 1979. The contribution of the Fsecond_

visual system to directed visual attention in man. Brain 102 (4),

835–856.