Physiology & Behavior 83 (2004) 13 – 19

Recording of the human electro-olfactogram

M. Knecht, T. Hummel*
Smell and Taste Clinic, Department of Otorhinolaryngology, University of Dresden Medical School, Fetscherstrasse 74, 01307 Dresden, Germany

Received 13 April 2004; accepted 26 July 2004

Abstract

Electro-olfactograms (EOG) are electrical potentials of the olfactory epithelium that occur in response to olfactory stimulation. The EOG
represents the sum of generator potentials of olfactory receptor neurons. While this response has been used extensively in animal research,
there are only a handful of papers describing the properties of the human EOG. In addition to a discussion of methodological issues related to
the EOG, this review summarizes the characteristics and uses of these recordings. Among other results, EOGs have been used to provide
evidence for the dominant role of the central nervous system in olfactory desensitization, for the functional characterization of the olfactory
epithelium, the specific topographical distribution of olfactory receptors, or the expression of olfactory receptor neurons in response to
exposure to odorants, and the characterization of certain odorants as olfactory receptor antagonists. In conclusion, in combination with nasal
endoscopy and air-dilution olfactometry, the EOG is a unique part of a large array of techniques used to provide a complete picture of the
processing of olfactory information in humans.
D 2004 Elsevier Inc. All rights reserved.

Keywords: Smell; Olfaction; Electrophysiology; Nose

1. Recording of electro-olfactograms (EOG)—historical
perspective
1.1. Recordings in insects and vertebrates
First electrophysiological investigations of the olfactory
epithelium were performed by Hosoya and Yoshida in 1937
[1]. In ex-vivo experiments they saw responses in the
olfactory epithelium of the dog following odorous stim-
ulation. They reported a positive correlation between
response magnitude and degree of pigmentation of the
epithelium. Years later, Ottoson [2,3] extensively studied the
frog’s olfactory epithelium to describe olfactory activation
in the periphery. Major conclusions from his work included:
(1) The amplitude of the EOG is proportional to the
logarithm of the concentration of the odorous stimulus. (2)
The EOG’s amplitude is different at different positions of
the olfactory epithelium. (3) Results indicated that the
* Corresponding author. Tel.: +49 351 458 4189; fax: +49 351 458
4326.
E-mail address: thummel@rcs.urz.tu-dresden.de (T. Hummel).
0031-9384/$ - see front matter D 2004 Elsevier Inc. All rights reserved.
doi:10.1016/j.physbeh.2004.07.024
longer the stimulation and the higher the concentration of
the odorant, the slower the return of the EOG to baseline. (4)
The EOG originates from olfactory receptor neurons
(ORN). (5) Odorants produce selective desensitization in
the olfactory epithelium. (6) Different odorants may produce
a similar increase of the EOG, but responses differ with
regard to the return of the potential to baseline.
Getchell et al. [4] extended Ottoson’s findings through
their excellent work in the salamander. Based on single
cell recordings they demonstrated that only ORNs, and not
sustentacular cells, increased their firing rate in response to
odorous stimulation. They also reported a relationship
between response frequency of ORNs and stimulus
concentration, and a relation between response frequency
of ORN and the shape of the EOG [5,6]. The amplitude of
the EOG was shown to decrease when the response was
recorded at different depths in the olfactory epithelium,
indicating that surface elements in the olfactory epithelium
function are responsible for generation of the response [5].
In addition, following section of the olfactory nerves, EOG
recordings disappeared as the olfactory receptor cell
population underwent retrograde degeneration [7]. This
14 M. Knecht, T. Hummel / Physiology & Behavior 83 (2004) 13–19
series of experiments strongly argued for the idea that the
EOG originate from ORNs following activation with
odorants [4].
It was also in the 1950s that Schneider recorded
summated generator potentials from the antennae of
butterflies and moths, the so-called electro-antenogram [8].
Consecutive work by Kaissling and others indicated that a
single odorous molecule can trigger an impulse in the
antennae of moths [9], and that certain neuronal cells
respond only to certain odorants [10]. In insects it was also
established that the termination of a response may be due to
effects of odor-binding-proteins [11]. Other work indicated
the significance of enzymatic processes in the antennas for
the perception of odorants [12,13].
1.2. EOG recordings in humans
In 1969, Osterhammel et al. [14] were the first to publish
EOG recordings in humans. Reporting measurements in two
subjects they emphasized that inherent difficulties of this
technique would render it too demanding to be successfully
applied in routine clinical practice. Obviously alerted
through this cautious advice, Bekiaroglou and Gisdakis
[15] reported recordings from the human olfactory epithe-
lium following extensive local anesthesia before electrode
placement. However, other than previous researchers they
only demonstrated positive recordings.
A major methodical concern in olfactory research was
solved by Kobal in developing an olfactometer based on
the principles of air-dilution olfactometry [16,17]. This
stimulator allows the administration of chemical stimuli of
known concentration, duration, and quasi-rectangular
shape of stimulus onset and offset. Most importantly,
presentation of stimuli is possible at relatively high
concentrations at a rise time of less than 20 ms without
eliciting mechanically induced sensations, which are
prerequisites for the reproducible recording of electro-
physiological responses. Based upon this technique Kobal
[16] performed numerous experiments in a small number
of subjects which laid the ground for future developments.
Among his major findings were the following: (1) EOG
amplitudes depend on odor concentration; (2) While
odorous stimulation produces only negative responses at
the level of the olfactory epithelium, positive responses
can also be obtained from the respiratory epithelium; (3)
EOG recordings are independent from changes in skin
conductance; (4) Pairwise stimuli presented at short
interstimulus intervals of only several seconds produce
responses with little or no decrease in amplitude, although
the simultaneously recorded olfactory event-related poten-
tials [18] exhibited a strong decrease in amplitudes. This
was interpreted such that the process of odor desensitiza-
tion appears to be more strongly related to central but to
peripheral processes. Thus, Kobal’s [16] extensive work
can be regarded as the basis for the use of EOG recordings
in human studies.
2. Methodological issues
2.1. EOG electrode—biological significance of the EOG
In 1962, Mozell [19] questioned the biological signifi-
cance of Ottoson’s recordings, as he was able to record
EOG-like potentials from non-biological systems. However,
it was demonstrated [20] that EOGs cannot be recorded
from an Agar-plate when using electrodes as they had been
introduced by Ottoson [3]. This electrode must be insulated,
e.g. through a Teflon tube. A so-called bagar-bridgeQ (1%
Ringer-Agar) ascertains that the odorant has no direct
contact with the electrode. A silver-chlorided silver-elec-
trode is typically used for recording; the reference is placed
at the bridge of the nose, contralateral to the recording site
[16]. Background noise in the EOG is believed to represent,
at least in part, the electroencephalogram [15,16]. In order to
minimize artefacts produced by muscular contractions or
eye movements, it is helpful to place the subjects as
comfortable as possible. First employed by Hummel and
colleagues, a frame similar to lensless glasses is typically
used to keep the EOG electrode in place (Figs. 1 and 2).
2.2. Responses from the respiratory epithelium
It is also possible to record potentials from the respiratory
epithelium [21]. The so-called negative mucosa potential
(NMP) is believed to represent peripheral trigeminal
activation [22–24]. It is similar to EOGs in terms of both
shape and response properties [16,21]. As the olfactory
epithelium is also innervated by the trigeminal nerve (e.g.
Refs. [25,26]), this emphasizes the importance of a set-up,
which excludes trigeminal activation when EOGs are to be
obtained [16]. It is clear that odorants cannot be puffed onto
Fig. 1. Recording of an EOG in a healthy subject. After the electrode (short
white arrow) has been placed on the olfactory epithelium using endoscopy,
it is kept in place by means of a frame similar to lensless glasses [36]. The
outlet of the stimulator (thin white arrow) is carefully brought into the
nostril. The reference electrode has been placed on the bridge of the nose;
EEG is recorded simultaneously. White noise is played to the subject
through headphones for acoustical shielding.
 M. Knecht, T. Hummel / Physiology & Behavior 83 (2004) 13–19
Fig. 2. Example of an EOG (thick, black line) superimposed on a
simultaneously recorded olfactory event-related potential (thin gray line).
Onset of the 1 s vanillin stimulus is marked with an arrow. Note the
different scaling of the two responses.
the epithelium as this would produce a mechanical sensation
and thus trigeminal activation. Further, odorants used to elicit
EOGs should be bpureQ olfactory stimuli which produce little
or no trigeminal activation, e.g. vanillin or H2S [27–29].
2.3. Administration of odorous stimuli
Another important point in EOG recording is that the
odorant has to reach the epithelium with a high concen-
tration gradient and that it has to be removed immediately at
the end of the stimulus. The gold standard for stimulation in
EOG recordings is the use of an olfactometer developed by
Kobal [16,17]. This olfactometer is based on the embedding
of an odorous stimulus in a constantly flowing air stream
with controlled temperature and humidity. Only the use of
an appropriate olfactometer and bpureQ olfactory stimulants
guarantees exclusive activation of ORNs.
2.4. Sources of artefacts
Apart from artefacts due to inadequate stimulus presen-
tation, or inadequate electrode placement, other sources of
artefacts need to be considered. (1) The eyeballs constitute
electric dipoles. This is why eye blinks with consecutive eye
movements cause potential differences in the EEG that are
biggest in the area of the forehead, but may also super-
impose recordings from the olfactory epithelium. Therefore,
eye blinks should be controlled when EOGs are obtained.
(2) During the experiments subjects should breathe in a
specific manner in order to avoid movement of respiratory
air in the nasal cavity. Gently pressing the base of the tongue
upwards causes bvelopharyngeal closureQ and avoids any
air-flow of the air stream in the nose during breathing
[16,30]. Effectiveness of this bvelopharyngeal closureQ can
easily be controlled by the subjects in a bio-feedback system
using a mirror placed beneath the nostril (allowing to
visualize condensation of respiratory air) or a thermistor
placed in front of the nostril (allowing to visualize changes
of air-flow on an oscilloscope) (Fig. 3).
2.5. Positive and negative EOG
While most authors described exclusively negative EOG
recordings with a phasic initial response followed by a tonic
15
potential (compare Fig. 4), others also described positive
EOGs or EOGs with both positive and negative components
[20]. It was hypothesized [20] that the EOG principally
consisted of negative and positive potentials and that the
recorded EOG would be the result of a superposition of the
two components. Following section of the olfactory nerve
[31,32] it was observed that the extinction of the negative
EOG was accompanied by the development of a positivity.
The authors hypothesized that the positive response was due
to activation of the Bowman glands or the sustentacular
cells (compare Refs. [33,34]).
2.6. Localization of EOG recording sites
Kobal and co-workers were the first to record EOGs
under endoscopical control. This technique allowed place-
ment of the electrode in the area of the olfactory cleft, which
is difficult to accomplish otherwise [35–37]. In this context
it is important to keep in mind that, on a macroscopical
level, the human olfactory epithelium cannot be distin-
guished from respiratory epithelium as it does not contain
yellow/brownish pigment typically seen, for example, in rat
olfactory epithelium.
Leopold et al. [37] used the EOG to functionally describe
the extent of the olfactory epithelium. They reported the
presence of EOG responses (and functionally mature
olfactory receptor neurons) at the level of the insertion of
the middle turbinate which contradicted classical views of
the extent of the human olfactory epithelium (compare Refs.
[38,39]). Von Brunn [40] described the olfactory epithelium
in the area beneath the cribriform plate, the superior
turbinate, and its corresponding area on the septum.
However, his observations were only based on experiments
in two decapitated criminals (35 and 45 years old). Read
[41] reported that the neuroepithelium was more extended.
He made his observation in the cadaver of a 1-year-old child
and an adult. However, in both publications the verbal
descriptions of the extent of the olfactory epithelium do not
correspond to diagrams in which the olfactory epithelium is
shown to extend until the middle turbinate and its opposite
Fig. 3. MR image of a subject breathing normally (left; velum open) and
practicing velopharyngeal closure (right, velum closed). Velopharyngeal
breathing prevents respiratory air-flow through the nasal cavity.
16 M. Knecht, T. Hummel / Physiology & Behavior 83 (2004) 13–19

Fig. 4. EOG recordings before and after several administration of a local anesthetic [l.a.] (20 mg of lidocaine sprayed to the olfactory epithelium; the subject’s
ratings of the vanillin stimuli are shown on the right (visual analogue scale ranging from 0 [no intensity] to 100 [maximum intensity] estimation units).
Immediately following stimulation only a faint intensity was left which gradually recovers over time. Correspondingly, the EOG is almost extinguished after
application of the local anesthetic; it gradually recovers over time. Stimulus onset/offset is indicated by the dotted lines.

site on the septum. A reason for these controversies may be
the irregular distribution of the olfactory epithelium which
von Brunn [40] described as bcontinents surrounded by
peninsulas and islandsQ. While the olfactory epithelium is
uniform in the fetus, respiratory bmetaplasiasQ appear in the
olfactory epithelium during the first years of life [42]. As
this respiratory epithelium contains cells with microvilli as
opposed to respiratory epithelium in other parts of the nose
it is assumed that this epithelium represents remnants of
olfactory epithelium which transformed to respiratory
epithelium [43]. The degeneration of olfactory epithelium
is typical in adults and occur especially beneath skull base
[44].
Other vertebrates seem to lack this irregular and patch-
like distribution of the olfactory epithelium [45]. Biopsies
taken from the olfactory cleft in humans contained ORNs in
47% of the cases [43]. This patchy distribution of the
olfactory epithelium may also explain the relatively low rate
of successfully recorded EOGs even under endoscopical
control [35–37].
The studies described above indicate that ORNs exist
outside of the regio olfactoria. Having said this, several
experiments indicate that EOG can be obtained from ORNs
the axons of which do not connect to the olfactory bulb.
Gesteland et al. [46] recorded EOG in the rat fetus before
synaptic connections between ORNs and mitral cells was
established. These neurons reacted unspecifically to all
presented odors and exhibited specific responsitivity only
after development of synaptic connections. In addition,
EOG were also recorded after section of the olfactory nerves
in rainbow trouts [47] or in pigs [33]. Finally, EOG
recordings were reported in two congenitally anosmic
subjects with aplasia/hypoplasia of the olfactory bulbs
[48]. Along the same line are reports on EOG recordings
in anosmic patients which were possible with the same
probability as in healthy subjects (68%) [49]. Thus, while
EOG recordings indicate the presence of functionally
mature ORNs in circumscribed epithelial areas, their
presence may not be seen as proof for connectivity of those
ORNs to the olfactory bulb.
3. Characteristics and uses of the EOG
3.1. Odor specificity of EOG recordings
All publications on human EOG mention difficulties in
terms of the success rate of the recordings (compare Ref.
[50]). This may, at least in part, be due to the specificity of
the responsiveness of ORNs. In fact, EOGs to hydrogen
sulfide been reported to occur in only a certain percentage of
the recording sites [35,36], while responses were obtained to
stimulation with vanillin, and vice versa. These findings
compare to reports by Ottoson [3], who observed a striking
variation of EOG amplitudes in different areas in the
olfactory epithelium in the frog. In addition, Edwards et
al. [51] recorded EOG with 4 different odors in 12 positions
in the olfactory epithelium of the rat. Each odor showed
different answers in the 12 positions indicating a different
distribution of olfactory receptor populations in the different
areas of the olfactory epithelium (compare Refs. [52,53]).
These experiments indicate on an electrophysiological level
 M. Knecht, T. Hummel / Physiology & Behavior 83 (2004) 13–19
that certain ORNs are expressed in certain areas of the
olfactory epithelium [54,55].
3.2. Differential EOGs to different odorants
Using different odorants, Ottoson [3] reported no major
differences between EOGs with regard to the onset, but with
regard to the termination of the responses to different odor
qualities. Similar observations were made in humans where
the return of potential changes to baseline was prolonged for
EOG to vanillin compared to responses to H2S [35]. It may
be hypothesized that theses differences in responses to
different odorants relates to the different fate of those
odorants at the receptor site, for example the differential
binding of odorants to proteins contained in the olfactory
mucus, so-called odorant-binding proteins [56,57]. Other
explanations of the differential EOG-response to odorants
may refer to the differential metabolisation of odorants in the
epithelium (e.g. through cytochrom P450 2G1 [58], or UDP-
glucuronyl-transferase [59]). These enzymes may be of
significance in the termination of an olfactory signal [60] or
in terms of liberation of olfactory receptor cells from odorant
molecules to enable their reactivation [11,61]. Other reasons
for the differences in EOG shape may include the different
binding times of the odorant to the receptor, which, in turn,
could produce differences in activation.
3.3. Relation of the EOG to odor concentration
Most researchers agree that the amplitude of the EOG’s
onset depends on the concentration of the odorant. Some of
them simply describe that this amplitude increases with
increasing concentration of the odorant [16,19,62], others
describe this relationship in more detail. Specifically, the
EOG amplitude has been reported (a) to be proportional to
the logarithm of the stimulus concentration [3,14], (b) to
exponentially increase in relation to stimulus concentration
[47], or (c) to exponentially increase in relation to a
logarithmic increase of the stimulus concentration [63]. In
addition, (d) the concentration-amplitude-function has been
reported to be of a sigmoidal shape [4].
With prolonged stimulation, similarly to what has been
observed in the frog [3], the EOG from human subjects has
also been shown to exhibit a tonic phase [16,35]. The
EOG’s latency has been found to shorten with stimulus
concentration [16,35] (compare Ref. [3]).
3.4. Relation of the EOG to repeated stimulation
Zwaardemaker [64] was among the first to recognize that
desensitization in response to prolonged exposition to odors
would be due to central-nervous mechanisms, rather than to
peripheral processes. Ottoson [3] was the first to use
electrophysiological data in experiments in the frog to
support this hypothesis. Specifically, application of two
odorous stimuli with a short interstimulus interval produced
17
two distinct EOG responses. While the amplitude of the
second EOG was smaller it almost reached the amplitude of
the first EOG. No bmeltingQ of the two EOGs was seen.
Similar results were seen for the human EOG [16,36] with
subjects rating the intensity of the second stimulus to be
much weaker than the intensity of the first stimulus. In
addition, the response amplitudes of correspondingly
recorded olfactory event-related potentials exhibited a
strong decrease with repeated stimulation.
3.5. Other studies employing the EOG
In addition to the studies already mentioned above, the
human EOG has been used to study activation of ORN at
peri-threshold levels [65], to look at odor-specific induc-
tion of sensitivity at receptor level [66], or to study
responses to stimuli applied through the ortho- or retro-
nasal route [67]. Interesting developments can also be
expected from the use of fresh cadaveric material to study
peripheral aspects of human olfaction [68]. Last but not the
least, the EOG has been applied to investigate how
peripheral detection and conscious perception of an odor-
ant can be specifically inhibited by prior exposure to an
antagonistic odor [69,70].
4. Conclusions and perspectives
In conclusion, the EOG allows to non-invasively address
questions related to peripheral olfactory activation in
humans. Among other results, EOGs have been used to
provide evidence for the dominant role of the central nervous
system in olfactory desensitization, for the functional
characterization of the olfactory epithelium, the specific
topographical distribution of olfactory receptor neurons, the
expression of olfactory receptor neurons in response to
exposure to odorants, or the characterization of certain
odorants as olfactory receptor antagonists. In combination
with nasal endoscopy and air-dilution olfactometry, the EOG
is a unique part of a large array of techniques used to provide
a complete picture of the processing of olfactory information
in humans. Together with the recording of olfactory event-
related potentials [18], magnetic source imaging [71],
functional magnetic resonance imaging [72,73], and appro-
priate psychophysical techniques [74], the human sense of
smell can be described in its many facets at many different
levels, starting at the olfactory receptor neuron.
Acknowledgements
We would like to thank Dr. Johannes Gerber for
providing the MR image of the subject practicing velophar-
yngeal closure. We also would like to thank Dr. Gerd Kobal
for his help with some of the recordings presented in this
manuscript. Support: DFG HU441-2.
18 M. Knecht, T. Hummel / Physiology & Behavior 83 (2004) 13–19
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