Sensors andand Materials,Materials, Vol.
Vol. 17,17, No.
No. 77 (2005)(2005) 391– 395
Sensors
MYU Tokyo391

S & M 0616

Gamma Band Oscillations and Real-Time Breath
Gas Monitoring Using Artificial Noses
in An Intravenous Olfaction Test
Tadashi Ishimaru*
Department of Otorhinolaryngology, Nanto General Hospital,
2007-5 Umeno, Nanto, Toyama 939-1724, Japan(Received December 1, 2004; accepted May 9, 2005)
Key words:

olfaction, gamma band, artificial nose, Alinamin, intravenous olfaction test

Most clinical olfactometry is a psychological test, and electrophysiological tests arerare. To develop clinically objective olfactometry, the applicability of intravenous olfactory-elicited gamma band oscillation (GBO) was investigated. The GBO was elicited byintravenous olfactory activation by thiamine propyldisulphide (Alinamin, Takeda Pharmaceutical Company, Osaka, Japan). Intravenous olfaction occurred because of odorous
breath gas caused by an intravenously administrated odorant. The breath gas was monitored by an odor meter using artificial noses (FPO-II, Futaba Electric, Yokohama, Japan).
Odorant intensity in the breath gas was increased after the administration of Alinamin.
GBO was also observed after the administration of alinamin. The change in GBO
amplitude was similar to the change in odorant intensity until the first peak of odorantintensity after the administration of Alinamin. After the first peak, GBO amplitude still
increased in one subject but decreased in another. Although GBO was thought to correlate
to the intensity of an odorant in breath gas (IOBG), the difference in olfactory fatigue
among subjects seemed to affect the difference in GBO. Measuring GBO combined withIOBG monitoring provides a method to analyze the relationship between olfactory response and for real-time odorant intensity in the nasal cavity. This seems a useful method
not only for basic but also for clinical research and even suggests ways to improve theartificial nose.

1.

Introduction

Most clinical olfactometry is conducted using psychological tests, and electrophysiological tests are rarely performed. When electrophysiological olfactometry has beenperformed, odorant concentration or intensity in the nasal cavity has generally remained*Corresponding author, e-mail address: taishimaru-alg@umin.ac.jp

391

392

Sensors and Materials, Vol. 17, No. 7 (2005)

unknown. In the study of human olfaction, it has been difficult to record an electrophysiological response combined with odorant concentration in the nasal cavity until theinvention of the artificial nose. Olfaction is composed of front and retro nasal olfaction. It
is possible to record the intensity of an odorant in the expired air, which simulates retro
nasal olfaction, using the artificial nose.
A unique method of clinical olfactometry, the intravenous olfaction test (IVO-test),
which is also called the “Alinamin test,” is a test of retro nasal olfaction that is widely usedin Japan. One of the weak points of the IVO-test is the unclear odorous intensity in thenasal cavity. Therefore, Nakashima(1,2) attempted to measure the intra nasal intensity of anodorant breathed from the lungs using the artificial nose during IVO-testing. In this study,
the electrophysiological response combined with the response of artificial noses wasrecorded during the IVO-test. The aim of this study is to provide a method for investigating
whether the electrophysiological response was linked to the odorant concentration in thenasal cavity in the IVO-test.

2.

Subjects and methods

2.1 Subjects
Two male volunteers, 58 and 37 years old, who have normal olfaction participated inthis study. The subjects gave their informed consent. The subjects were instructed torespond using a hand switch when odor was detected and this was labeled subjective
response (SR).

2.2 Stimulation
The IVO-tests were conducted according to the standard clinical protocol; thiamine
propyldisulphide (Alinamin, Takeda Pharmaceutical Company, Osaka, Japan) was intravenously administrated for 20 s.(3) The duration of Alinamin administration was marked by
the experimenter by stepping on a pedal switch.

2.3 Electrophysiological recordings
Olfactory elicited gamma band oscillation (GBO) recorded from the human frontal
scalp was amplified and filtered over a range from 28 to 200 Hz. This technique is same asin our previous report.(4)2.4 Artificial noses
The breath in the nasal cavity was monitored by an odor meter with artificial noses (FPO-II, Futaba Electric, Yokohama, Japan). Odorous air was aspirated by an air pump andlead to two artificial noses in an odor meter. The aspiration tube was located in the nasal
cavity 1 cm from the nostril. The odor meter was constructed of two different types ofartificial nose and their data were analyzed by a built-in microprocessor. These raw data
were translated to odorant intensity and character and saved on memory chips.(5)2.5 Capture and analysis of data
GBO data, SR, and the pedal switch signal for Alinamin administration were captured
using a personal computer with a 12-bit A/D converter. The odorant intensity saved on theSensors and Materials, Vol. 17, No. 7 (2005)

393

FPO-II was read using a personal computer via an RC232C port and was merged with thedata captured via the A/D converter (Fig. 1). GBO was rectified and sent through a band
pass filter to generate a pseudo-DC-response (GBO-DC, Fig. 2).

3.

Results

Odorant intensity in the breath gas increased after administration of Alinamin. GBO
was also observed after administration of Alinamin. Changes in GBO-DC were similar tothe changes in odorant intensity during Alinamin administration. In one subject, odorantintensity and GBO-DC decreased post administration of Alinamin but increased again after
a 120 s interval (Fig. 3(a)). In the other subject, odorant intensity increased following theadministration of Alinamin but GBO-DC decreased after the peak during Alinamin
administration (Fig. 3(b)).

4.

Discussion

GBO was thought to correspond to the intensity of odorant in the breath gas (IOBG).
Therefore, measuring GBO combined with IOBG monitoring provides a method todistinguish real olfactory response and is a breakthrough in clinical electrophysiologicalolfaction testing. When Alinamin is mixed with blood, propyl mercaptan is generated. The
odorized breath produced by intravenous administration of Alinamin was proven as theFig. 1. Block diagram of the system for this study. The amplified gamma band oscillation andswitch responses for SR and Alinamin administration were captured by a personal computer.

394Sensors and Materials, Vol. 17, No. 7 (2005)

Fig. 2. Procedure for generating GBO-DC. The gamma band oscillation is amplified (G = 100),filtered (28–200 Hz), and digitalized. A post A/D converter process was performed by a personalcomputer. The absolute value of the digitalized gamma band oscillation was filtered (0.01–0.5 Hz)
to eliminate DC drift and noise.

Fig. 3. GBO-DC and artificial nasal responses. Data from (a) a 58 years old man and (b) a 37years
old man are shown. Black and gray traces indicate GBO-DC and odor intensity (IOBG), respectively,measured by the artificial nose; an upper deflection is positive. Black and gray horizontal bars
indicate the periods of Alinamin administration, 20 s, and SR.

propyl mercaptan generated was measured using a gas chromatograph.(6) In this study,changes in IOBG were sometimes very similar to changes in GBO, but at other times they
were not. The human sense of smell often decreases when an odorant is delivered
continually and this phenomenon is known as olfactory fatigue. Until the first peak ofSensors and Materials, Vol. 17, No. 7 (2005)395

IOBG, GBO-DC of the two subjects showed similar increases, but after the peak, changes
in IOBG and GBO-DC differed between the two subjects. Individual differences exist
among subjects regarding odorous intensity and the tendency toward the occurrence ofolfactory fatigue. When a subject experiences olfactory fatigue easily despite sustained orincreased odorant intensity, the sense of smell decreases. Hatanaka(7) et al. investigated
GBO induced by intravenous administration of Alinamin on 179 subjects and reported
typical cases as follows. In one typical case, the GBO amplitude elicited by intravenous
olfactory stimulation was suppressed before the end of odordetection was reported.
Another typical case showing the GBO amplitude suppressed below the base line afteradministration of Alinamin was also reported. Multiple increases in GBO amplitude
despite the administration of Alinamin was also reported once. Nakashima measuredchanges in IOGB using the artificial nose and surmised that multiple increases in IOGB
were possibly produced because of the stimulation of generally circulated Alinamin byblood2). This may be an explanation for the differences between the response curves ofGBO-DC and IOBG. Olfactory fatigue is also called olfactory desensitization and it occurs
within the olfactory receptor neuron.(8) Pseudo-human olfaction modeled by the artificial
nose may need to simulate the olfactory desensitization phenomenon. In other words, inorder for the artificial nose to more close by approximate the human nose, the following
developments are necessary. 1) The time-series response of the artificial nose should
simulate the human nose. 2) The intensity response of the artificial nose should correspondto physiological responses such as those described by the Weber-Fechner law. Because acomputer simulation model of typical responses of the olfactory receptor neuron wasproposed,(9) it is possible that post-processing of information from the artificial noseemulates the computer model of the olfactory receptor neuron. When a more human-likeartificial nose is developed, differences between changes in GBO-DC and IOBG showed
become smaller.
In this way, acquisition of electrophysiological responses combined with the artificial
nose response many improve not only the clinical appreciation, but also may assist thedevelopment of a more human-like artificial nose.

References
1 T. Nakashima, J. Miyazaki, K. Kidera and A. Inokuchi: Jpn. J. Rhinol. 41 (2002) 251. (inJapanese)
2 T. Ishimaru: Aroma Research 5 (2004) 106. (in Japanese)
3 S. F. Takagi: Olfactory Tests, Human Olfaction (University of Tokyo Press, Tokyo, 1989) p.
35.
4 T. Ishimaru, S. Hatanaka, T. Yata, I. Horikawa, T. Tsukatani, T. Nishimura, T. Miwa andM. Furukawa: Chem. Senses 29 (2004) 247.
5 T. Okano: Keiso 43 (2000) 85. (in Japanese)
6 R. Kazama and H. Zusho: Nippon Jibiinnkouka Gakkai Kaiho 84 (1981) 400. (in Japanese)
7 S. Hatanaka, T. Ishimaru, T. Yata, T. Miwa and M. Furukawa: Acta Otolaryngol. Suppl. 553(2004) 65.
8 T. Kurahashi and A. Menini: Nature 385 (1997) 725.
9 N. Suzuki, M. Takahata and K. Sato: Chem. Senses 27 (2002) 789.