Chem. Senses 28: 565-572,
2003
© Oxford University Press 2003
Activation of the Anterior Cingulate Gyrus by ‘Green Odor’: A Positron Emission Tomography Study in the Monkey
1 Department of Oral Physiology 2 Department of Oral and Maxillofacial Surgery, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka 565-0871 3 BF Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-0873 4 Department of Psychology, Tokyo Metropolitan Institute for Neuroscience, 2-6 Musashidai, Fuchu, Tokyo 183-8526 5 Department of Physiology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585 6 Central Research Laboratory, Hamamatsu Photonics KK, 5000 Hirakuchi, Hamakita, Shizuoka 434-8061 7 Department of Investigative Radiology, National Cardio-Vascular Center, Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-0873 8 Soda Aromatic Co., Ltd, Soda Bldg, 4-15-9 Nihonbashi Honcho, Chuo-ku, Tokyo 103-0023 9 Department of Applied Biological Chemistry, Yamaguchi University, Yamaguchi 753-8511, Japan
Correspondence to be sent to: Yasuyoshi Watanabe, Department of Physiology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan. e-mail: yywata{at}med.osaka-cu.ac.jp
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and methodsResultsDiscussionReferences |
|---|
The equivalent mixture of cis-3-hexenol and trans-2-hexenal (hexenol/hexenal), ‘green odor’, is known to have a healing effect on the psychological damage caused by stress. Behavioral studies in humans and monkeys have revealed that hexenol/hexenal prevents the prolongation of reaction time caused by fatigue. In the present study, we investigated which brain regions are activated by the odor of hexenol/hexenal using positron emission tomography with alert monkeys. Regional cerebral blood flow (rCBF) in the prepyriform area (the primary olfactory cortex) was commonly increased by the passive application of odor: acetic acid, isoamylacetate or hexenol/hexenal. We observed rCBF increases in the orbitofrontal cortex (the secondary olfactory cortex) by these olfactory stimuli in two of three monkeys, and found no predominance of laterality of the activated hemisphere. Furthermore, rCBF increase in the cerebellum was observed in two of three monkeys, and the odor of acetic acid increased rCBF in the substantia innominata in all monkeys. In addition to these olfactory related regions, the anterior cingulate gyrus was activated by the odor of hexenol/hexenal. These findings suggest that the increase of rCBF in the anterior cingulate gyrus by the odor of hexenol/hexenal may contribute the healing effects of this mixture observed in the monkey.
Key words: laterality, olfaction, PET, primate
|
Introduction |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
Hexenol and hexenal, which mixed together produce the so-called ‘green odor’, are plant origin compounds from the chloroplast membrane (Hatanaka, 1996
). They have various effects on the biological function: plant-to-plant messengers in allelopathy, insect-attracting pheromone-like action and bactericidal-like action (Hatanaka, 1999). Recently, green odor has been found to have various physiological actions on the mammalian brain. Stress-induced hyperthermia was attenuated by the green odor in rats (Akutsu et al., 2002). Sano et al. (2002) reported that the mixture of hexenol and hexenal was accepted as a pleasant odor, and it decreased the amplitude of an event-related potential (P300). However, the neural mechanisms of the effect of hexenol and hexenal are almost completely unknown.
Positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) are non-invasive functional brain-imaging techniques, which have been used to elucidate the neural mechanisms of olfaction in the human (reviewed by Zald and Pardo, 2000; Savic, 2002). By using PET, Zatorre et al. (1992) first reported that olfactory stimuli increase regional cerebral blood flow (rCBF) in the bilateral pyriform cortex and right orbitofrontal cortex in the human. The finding of activation in the pyriform and orbitofrontal cortices has been replicated in other PET (Zald and Pardo, 1997; Qureshy et al., 2000; Savic et al., 2000, 2002) and fMRI studies (Yousem et al., 1997; Sobel et al., 1998a; Francis et al., 1999; Poellinger et al., 2001). The results of these imaging studies are consistent with the clinical findings that patients with temporal lobe epilepsy and patients that underwent temporal or frontal lobectomy have difficulty in discriminating and detecting odors (Abraham and Mathai, 1983; Eskenazi et al., 1986; Jones-Gotman and Zatorre, 1988; Zatorre and Jones-Gotman, 1991). Imaging studies have also demonstrated that other regions considered to be irrelevant to olfactory processing, such as the cerebellum, claustrum, anterior cingulate gyrus and visual cortex, are activated by odors using PET (Small et al., 1997; Zald and Pardo, 1997; Qureshy et al., 2000; Savic et al., 2000, 2002; Royet et al., 2001) and fMRI (Yousem et al., 1997; Sobel et al., 1998b; Francis et al., 1999; Poellinger et al., 2001).
To investigate precise mechanisms of olfactory function, we need to bridge the gap between human PET studies described above and electrophysiological studies in the monkey (Tanabe et al., 1975a,b; Rolls and Baylis, 1994). Recently, we have developed a system for imaging the monkey brain using PET (Onoe et al., 1994, 2001; Takechi et al., 1994; Kondoh et al., 2002), and elucidated the mechanisms of olfactory processing in the alert monkey (Kobayashi et al., 2002). Although there are not a few advantages of fMRI over PET, we chose the latter because of: (i) easier presentation of odors and ventilation to the alert monkey; (ii) clear visualization of the skull base areas especially the prepyriform area and orbitofrontal cortex; and (iii) no dose limitation of radioisotope. In the present study we used the PET systems in alert monkeys to address the question: which brain regions are activated by passive odor application of hexenol and hexenal? We compared the activated brain regions by hexenol and hexenal with those activated by acetic acid or isoamylacetate. We found that rCBF in the prepyriform area is commonly increased by these odors, and rCBF in the anterior cingulate gyrus was increased by hexenol and hexenal.
|
Materials and methods |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
Animals
Three male adult rhesus monkeys (Macaca mulatta), weighing 4.8, 6.5 and 9.0 kg, were used for this experiment. The monkeys were maintained and handled in accordance with the National Institute of Health Guide for the Care and Use of Laboratory Animals. The experimental protocol was approved by the animal research committee of Hamamatsu Photonics and BF Research Institute. The surgical protocol for implantation of a head holder is the same as reported previously (Kobayashi et al., 2002). Briefly, after initial anesthesia with ketamine–HCl (10 mg/kg i.m.; Sankyo, Japan) and atropine (0.05 mg/kg; Tanabe Seiyaku, Japan), pentobarbital (20 mg/kg; Dainippon Pharmaceutical, Japan) was administered to maintain the animal at a deep surgical level of anesthesia. During surgery pentobarbital was injected intravenously as needed to maintain a deep surgical level of anesthesia. A custom-made stainless steel head holder was implanted to which the positioner could be fitted during PET imaging. Antibiotics were administered for a week after surgery.
Olfactory stimulation
All monkeys were trained to sit on a monkey chair that was equipped with the instrument for olfactory stimulation. During the PET scan, the unanesthetized monkey sat on the chair, and its head was fixed in the center of the PET scanner gantry. A bundle of tubes for each odor stimulus was set just upon the nostrils. Tubes were connected to closed glass bottles which contained the following solutions: propylene glycol solvent, 5% acetic acid, 98% isoamylacetate, and an equivalent mixture of 0.03% cis-3-hexenol and 0.03% trans-2-hexenal (hexenol/hexenal; Soda Aromatic, Japan) diluted with triethyl citrate. Acetic acid and isoamylacetate have a vinegar-like and a banana-like smell, respectively. As control, we applied pure air (80% nitrogen and 20% oxygen) at 540 ml/min through propylene glycol solvent to remove odor. We applied an odor by aerating the solution by pure air at 540 ml/min. The intensity of the odor was chosen to be easily identifiable by humans. To prevent the odor from contaminating the scanner room, an outlet was set behind the monkey and connected to the outlet of the room fan. Breathing was recorded with the aid of a thermo-probe in front of the nostril.
PET scan
The rCBF was measured by the bolus injection of [15O]water with PET (Raichle et al., 1983). PET Scanners (EXACT HR, Siemens, Germany, for monkey A; or SHR7700, Hamamatsu Photonics KK, Japan, for monkeys B and C) were used. A transaxial resolution of EXACT HR in high sensitivity three-dimensional mode and SHR7700 in enhanced two-dimensional mode was 3.8 mm full width at half maximum and 2.6 mm, respectively. The effects of radiation self-attenuation were corrected by an initial transmission scan for 30 min using an external positron emitting isotope (68Ge). The [15O]water (5 mCi in 2.5 ml saline in EXACT HR and 60 mCi in SHR7700) was injected through a venous cannula placed into a sural vein at 0.2 ml/s, and the emission scan started 30 s after the injection, when the radioactivity reached the brain. An odor stimulus was delivered for 30 s just after the scan started. Three scans with 30 s time frames for 90 s were used for analysis. We performed 20 randomized trials in a day, and the interscan was set at 10–15 min. The number of PET scans for each odor stimulus is 10 in monkey A, 14 in monkey B and 16 in monkey C. The number of control scans was 30 in monkeys A and B, and 32 in monkey C. Scans were obtained within a 5-week period.
Data analysis
The data were analyzed with statistical parametric mapping (SPM99, MRC Cyclotron Unit, UK) implemented in Matlab (MathWorks, USA). Adjusted rCBF values were analyzed using statistical parametric mapping (SPM96, MRC Cyclotron Unit, UK) implemented in Medx (Sensor Systems, USA). The scans were filtered by a Gaussian filter set at 4 mm full width at half-maximum. Global activity was set as a confounding covariate. The mean global cerebral blood flow was normalized to a level of 50 ml/100 ml/min. We subtracted images of pure air from those of each odor to detect the activated region by the odor. In addition, we made the images of hexenol/hexenal subtracted by those of isoamylacetate or acetic acid. The threshold for significance was set at t = 3.00, corresponding to an uncorrected probability of P < 0.0025. To identify the anatomical localization of the activated area, T1-weighted, high-resolution (256 x 256 matrix, 1.2 mm thickness; 60 slices) magnetic resonance image (MRI) scans were obtained using a 3 Tesla scanner (Signa VH/I, GE Medical Systems, USA) or 0.5 Tesla scanner (MRT-50A/II, Toshiba, Japan) under deep pentobarbital anesthesia before surgery. Structural MRIs from each subject were co-registered to the PET data following realignment of the PET time series using a software program (3D Brain Station, Loats Associates, USA). To identify the activated regions, we referred to stereotaxic coordinates of a monkey brain atlas (Paxions et al., 2000).
To estimate rCBF increase quantitatively, we measured the relative change of rCBF in the prepyriform area and anterior cingulate gyrus. We set the region of interest (ROI; 1.2 x 1.2 x 3.6 mm) in the activated regions showing the highest t-value during hexenol/hexenal application, and the same ROIs were set in the other sessions. Adjusted rCBF values during control and odor application were compared by one-way ANOVA with post-hoc Scheffé’s test for multiple comparisons. To compare rCBF values between the left and right orbitofrontal cortex, we subtracted images of pure air from those of all odors and measured adjusted rCBF values in the ROIs set in the orbitofrontal region showing the highest t-value. Statistical comparisons were performed by one-way ANOVA with post-hoc Scheffé’s test for multiple comparisons. All statistical values are presented as mean ± standard deviation. The level of P < 0.05 was considered statistically significant in the ROI-based analysis.
|
Results |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
Detection of activated regions by odor application
As shown in Figure 1 and Table 1, the subtraction images of pure air from each odor, hexenol/hexenal, isoamylacetate and acetic acid, revealed a similar increase of rCBF in the prepyriform area in all monkeys as reported previously (Kobayashi et al., 2002). In two out of three monkeys, rCBF in the cerebellum was significantly increased by hexenol/hexenal, isoamylacetate and acetic acid. In one of the monkeys, rCBF in the orbitofrontal cortex was consistently increased by all odor stimuli. Application of hexenol/hexenal increased rCBF in the anterior cingulate gyrus (anterior portion) in all monkeys (Figure 2). Increase of rCBF in the anterior cingulate gyrus was also observed during isoamylacetate application in one of the three monkeys, though the activation site is posterior to those by hexenol/hexenal application. Acetic acid application did not increase rCBF in the anterior cingulate gyrus. Application of acetic acid increased rCBF in the substantia innominata of all three monkeys (Figure 1, Table 1). There was no common activated region by isoamylacetate outside of the prepyriform area.
|
|
|
Subtraction of hexenol/hexenal minus isoamylacetate or acetic acid only demonstrated subthreshold rCBF increase (t < 3.00) in the anterior cingulate gyrus.
Quantitative analysis of rCBF increase in the prepyriform area and anterior cingulate gyrus
Figure 3 shows an example of the relative value of rCBF change (see Materials and methods) in monkey C. All odors significantly increased rCBF in the right prepyriform area, and there was no significant difference in rCBF increase among the odors (Figure 3A). Monkeys A and B also showed significant increase of rCBF in the left or right prepyriform area without a difference in rCBF increase among the odors (data not shown). On the other hand, only hexenol/hexenal caused significant increase of rCBF in the right anterior cingulate gyrus (P < 0.001; Figure 3B). rCBF values in the anterior cingulate gyrus of monkeys A and B were also increased by hexenol/hexenal application compared to those of control (P < 0.001 and P < 0.015, respectively).
|
Laterality of activation in the orbitofrontal cortex by odor stimuli
There is a hypothesis that the right orbitofrontal cortex predominantly processes the olfactory information (Zatorre et al., 1992; Savic et al., 2000, 2002). To test the hypothesis we measured adjusted rCBF values of the left and right orbitofrontal cortex. Figure 4 shows adjusted rCBF values in monkey C. Although rCBF values during odor application were significantly higher than those of control in both hemispheres (P < 0.001), rCBF value of odors in the left orbitofrontal cortex was almost similar to that in the right. Taken together with the finding that only the left orbitofrontal cortex was activated by isoamylacetate in monkey A (Table 1), we conclude that there is no obvious laterality of rCBF increase in the orbitofrontal cortex during passive olfactory stimulation.
|
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
Prepyriform and orbitofrontal cortices
Olfactory information is conveyed from the olfactory bulb to the pyriform cortex, the primary olfactory cortex in the monkey (Tanabe et al., 1975a). Several human PET studies are consistent with this anatomical finding (Zatorre et al., 1992; Small et al., 1997; Qureshy et al., 2000; Savic et al., 2000, 2002). However, Zald and Pardo (1997) reported only subthreshold activation is observed in the pyriform cortex by odor stimulation, and Dade et al. (1998) reported the absence of increased rCBF in the pyriform cortex during olfactory encoding. The lack of activation in the pyriform cortex by odor is also observed in human fMRI studies (Yousem et al., 1997, 1999; Sobel et al., 1998a). In terms of the monkey, our previous (Kobayashi et al., 2002) and the present studies confirmed that a passive odor stimulation increases rCBF in the prepyriform area. This finding is consistent with electrophysiological results in the alert monkey (Tanabe et al., 1975a,b). On the other hand, rCBF in the orbitofrontal cortex is not constantly activated among monkeys by odor stimulation in the present study as reported previously (Kobayashi et al., 2002), though most of human PET studies have reported the increase of rCBF in the orbitofrontal cortex (Zatorre et al., 1992; Small et al., 1997; Zald and Pardo, 1997; Qureshy et al., 2000; Savic et al., 2000, 2002; see the discussion in Kobayashi et al., 2002).
Interestingly, Zatorre et al. (1992) reported that in humans the right, but not the left, orbitofrontal cortex processes the olfactory information. This hypothesis is supported by later PET studies (Savic et al., 2000, 2002). However, some studies reported that rCBF increase in the left orbitoforntal cortex is predominant to the right during odor perception (Zald and Pardo, 1997; Qureshy et al., 2000). Thus, dominance of hemisphere during odor processing seems to be controversial in the human. In the present study using alert monkeys, we observed rCBF increase in the bilateral orbitofrontal cortex of monkey C by hexenol/hexenal or acetic acid, and isoamylacetate increased rCBF in the left orbitofrontal cortex of monkeys A and C (Table 1). The quantitative analysis in monkey C shows no significant difference of rCBF increase between the left and right orbitofrontal cortex. Thus, there may be no apparent laterality of activation in the monkey orbitofrontal cortex by passive olfactory stimulation, rather the laterality might depend on the properties of odors and/or additional meanings of odors.
Cerebellum and substantia innominata
Previous PET and fMRI studies have revealed that there is a large difference in activated regions except for the pyriform and orbitofrontal cortices. There are several explanations for the discrepancy. First, the activation pattern in the brain by odor depends on the kind of odors (Yousem et al., 1997). Second, Sobel et al. (1998a,b) reported that the way of sensing the odor—sniffing and smelling—is a critical factor that determines what regions are activated. Third, olfactory-related tasks are also an important factor for the pattern of activated brain regions (Royet et al., 2001; Savic et al., 2000). In the present study, the cerebellum and substantia innominata were activated by passive olfactory stimulation. Human PET studies have shown that complex and specific tasks using odors increased rCBF in the human cerebellum (Qureshy et al., 2000; Savic et al., 2000; Royet et al., 2001). However, the precise role of the cerebellum during odor simulation is still unclear in the human. The present results show that the monkey may be a suitable model for elucidating the precise role of these olfactory-related regions during odor stimuli.
The activation of the substantia innominata is consistent with the finding obtained from a tracing study that used horseradish peroxidase in the monkey, which showed that the substantia innominata receives afferents from the prepyriform cortex (Naito et al., 1984). However, there are few human PET studies that reported substantia innominata activation.
Anterior cingulate gyrus
Subtraction images of pure air from each odor demonstrate that isoamylacetate and acetic acid stimuli activated no common brain region except for the prepyriform area, but that hexenol/hexenal application increased rCBF in the anterior cingulate gyrus in all monkeys (Figure 2, Table 1). However, the subtraction images of hexenol/hexenal minus isoamylacetate or acetic acid only revealed the subthreshold increase of rCBF in the anterior cingulate gyrus, and the ROI-based analysis showed no significant difference of rCBF increase between hexenol/hexenal and other odors. The reason for this discrepancy is that isoamylacetate or acetic acid also increased rCBF in the anterior cingulate gyrus though it did not reach the threshold level (Figure 3). Then one question arises: why does hexenol/hexenal increase rCBF more than the other odors in the anterior cingulate gyrus?
In the monkey brain, the anterior cingulate gyrus (area 24) receives projections from the orbitofrontal cortex (area 13) (Vogt and Pandya, 1987), which receives afferents from the primary olfactory cortex (Barbas, 1993; Carmichael et al., 1994). These anatomical findings suggest that olfactory stimulation may influence the neural activity in the anterior cingulate gyrus. Human imaging studies have revealed controversial results concerned with the activation in the anterior cingulate gyrus by olfactory stimulation. Although several human imaging studies using PET (Francis et al., 1999; Savic et al., 2000, 2002; Royet et al., 2001) and fMRI (Sobel et al., 1998a,b; Poellinger et al., 2001) have revealed that passive olfactory stimuli activate the anterior cingulate gyrus, Zatorre et al. (1992) and Small et al. (1997) have not reported the activation of the anterior cingulate gyrus by odor stimuli. The anterior cingulate gyrus is involved in the limbic circuit (Martin, 1989), which is considered to process emotion or affective behavior (reviewed by Bush et al., 2000; Cardinal et al., 2002). A recent imaging study using PET reveals a decrease of rCBF in the anterior cingulate gyrus in major depressive patients (Bench et al., 1992; Chua et al., 1996; Kennedy et al., 1997). In addition, an electrophysiological study in the alert monkey showed that reward expectancy related activities were observed for several neurons in the anterior cingulate gyrus (Shidara and Richmond, 2002). These findings suggest that the anterior cingulate gyrus may play a key role for motivation for tasks, and might be activated by odors that stimulate the limbic system. Taken together with the findings that hexenol/hexenal causes pleasantness (Sano et al., 2002), hexenol/hexenal may simultaneously activate both the olfactory and limbic systems, which may activate the anterior cingulate gyrus effectively.
Recent studies using hexenol/hexenal have revealed various biological functions in mammals. Akutsu et al. (2002) reported that hexenol/hexenal attenuates hyperthermia caused by autonomic stress response to novel environment in the rat. In addition, there is a report that a low concentration (0.03%) of hexenol/hexenal was accepted as a pleasant odor by humans, and decreased the amplitude of an event-related potential (P300) (Sano et al., 2002). Our behavioral study in the alert monkey also revealed the improvement of delay time observed during a long-lasting performance of a continuous task by a passive application of hexenol/hexenal (Onoe et al., 2003). In addition, hexenol/hexenal prevented the prolongation of response time caused by fatigue in the mental loaded task, the advanced trail making test, which can estimate the function of the frontal cortex in the human (unpublished observation). Therefore, the activation in the anterior cingulate gyrus by the odor of hexenol/hexenal may correlate with the improvement of response time during a long continuous task.
In summary, we investigated the brain regions activated by the odor of hexenol/hexenal in alert rhesus monkeys. In addition to the olfactory-related regions (prepyriform area, substantia innominata and orbitofrontal cortex), odor application of hexenol/hexenal activated the anterior cingulate gyrus, which was not commonly activated by odors of isoamylacetate or aceteic acid. This action of hexenol/hexenal may contribute to its physiological effect of stress release.
|
Acknowledgements |
|---|
We thank Dr Paul S. Buckmaster for critical reading of the manuscript. We also thank Mrs N. Ejima, K. Watanabe, H. Imori (BF Research Institute) and D. Fukumoto (Hamamatsu Photonics) for their technical support. This study was supported in part by the Special Coordination Funds of the Ministry of Education, Culture, Sports, Science, and Technology, Japanese Government, and by Research for the Future Program JSPS-RFTF 98L00201 from the Japan Society for the Promotion of Science to Y.W.
|
References |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
Abraham, A. and Mathai, K.V. (1983) The effect of right temporal lobe lesions on matching of smells. Neuropsychologia, 21, 277–281.[CrossRef][Web of Science][Medline]
Akutsu, H., Kikusui, T., Takeuchi, Y., Sano, K., Hatanaka, A. and Mori, Y. (2002) Alleviating effects of plant-derived fragrances on stress-induced hyperthermia in rats. Physiol. Behav., 75, 355–360.[CrossRef][Medline]
Barbas, H. (1993) Organization of cortical afferent input to orbitofrontal areas in the rhesus monkey. Neuroscience, 56, 841–864.[CrossRef][Web of Science][Medline]
Bench, C.J., Friston, K.J., Brown, R.G., Scott, L.C., Frackowiak, R.S. and Dolan, R.J. (1992) The anatomy of melancholia-focal abnormalities of cerebral blood flow in major depression. Psychol. Med., 22, 607–615.[Web of Science][Medline]
Bush, G., Luu, P. and Posner, M.I. (2000) Cognitive and emotional influences in anterior cingulate cortex. Trends Cogn. Sci., 4, 215–222.[CrossRef][Web of Science][Medline]
Cardinal, R.N., Parkinson, J.A., Hall, J. and Everitt, B.J. (2002) Emotion and motivation: the role of the amygdala, ventral striatum, and prefrontal cortex. Neurosci. Biobehav. Rev., 26, 321–352.[CrossRef][Web of Science][Medline]
Chua, P., Morris, P.L.P., Egan, G.F., Saling, M., Pipingas, A., Berlangieri, S.U., Fitt, G., Schweitzer, I. and Burrows, G.D. (1996) A positron emission tomography (PET) activation study of major depression. Eur. Neuropsychopharmacol., 6, 73.
Carmichael, S.T., Clugnet, M.C. and Price, J.L. (1994) Central olfactory connections in the macaque monkey. J. Comp. Neurol., 346, 403–434.[CrossRef][Web of Science][Medline]
Dade, L.A., Jones-Gotman, M., Zatorre, R.J. and Evans, A.C. (1998) Human brain function during odor encoding and recognition. A PET activation study. Ann. N. Y. Acad. Sci., 855, 572–574.[CrossRef][Web of Science][Medline]
Eskenazi, B., Cain, W.S., Novelly, R.A. and Mattson, R. (1986) Odor perception in temporal lobe epilepsy patients with and without temporal lobectomy. Neuropsychologia, 24, 553–562.[CrossRef][Web of Science][Medline]
Francis, S., Rolls, E.T., Bowtell, R., McGlone, F., O’Doherty, J., Browning, A., Clare, S. and Smith, E. (1999) The representation of pleasant touch in the brain and its relationship with taste and olfactory areas. Neuroreport, 25, 453–459.
Hatanaka, A. (1996) The fresh green odor emitted by plants. Food Rev. Int., 12, 303–350.
Hatanaka, A. (1999) Biosynthesis of so-called ‘green odor’ emitted by green leaves. In Barton, D. and Nakanishi, K. (eds), Comprehensive Natural Products Chemistry, Vol. 1, Elsevier Science, New York, pp. 83–116.
Jones-Gotman, M. and Zatorre, R.J. (1988) Olfactory identification deficits in patients with focal cerebral excision. Neuropsychologia, 26, 387–400.[CrossRef][Web of Science][Medline]
Kennedy, S.H., Javanmard, M. and Vaccarino, F.J. (1997) A review of functional neuroimaging in mood disorders: positron emission tomography and depression. Can. J. Psychiatry, 42, 467–475.[Web of Science][Medline]
Kobayashi, M., Sasabe, T., Takeda, M., Kondo, Y., Yoshikubo, S., Imamura, K., Onoe, H., Sawada, T. and Watanabe, Y. (2002) Functional anatomy of chemical senses in the alert monkey revealed by positron emission tomography. Eur. J. Neurosci., 16, 975–980.[CrossRef][Web of Science][Medline]
Kondoh, Y., Yoshikubo, S., Ejima, N., Takeda, M., Kobayashi, M., Onoe, H., Watabe, H., Watanabe, Y., Iida, H. and Sawada, T. (2002) Development of a PET system for cognitive activation studies in conscious monkeys. In Senda, M., Kimura, Y. and Herscovitch, P. (eds), Brain Imaging Using PET. Academic Press, San Diego, pp. 253–258.
Martin, J.H. (1989) Neuroanatomy. Elsevier Science, New York, pp. 376–395.
Naito, J., Kawamura, K. and Takagi, S.F. (1984) An HRP study of neural pathways to neocortical olfactory areas in monkeys. Neurosci. Res., 1, 19–33.[CrossRef][Medline]
Onoe, H., Inoue, O., Suzuki, K., Tsukada, H., Itoh, T., Mataga, N. and Watanabe, Y. (1994) Ketamine increases the striatal N-[11C]methylspiperone binding in vivo: positron emission tomography study using conscious rhesus monkey. Brain Res., 663, 191–198.[CrossRef][Web of Science][Medline]
Onoe, H., Komori, M., Onoe, K., Takechi, H., Tsukada, H. and Watanabe, Y. (2001) Cortical networks recruited for time perception: a monkey positron emission tomography (PET) study. Neuroimage, 13, 37–45.[Web of Science][Medline]
Onoe, H., Yokoyama, C., Aou, S., Tsukada, H. and Watanabe, Y. (2003) Evaluation of the fatigue in macaque monkeys. J. Chronic Fatigue Synd., in press.
Paxions, G., Huang, X.F. and Toga, A.W. (2000) The Rhesus Monkey Brain in Stereotaxic Coordinates. Academic Press, San Diego.
Poellinger, A., Thomas, R., Lio, P., Lee, A., Makris, N., Rosen, B.R. and Kwong, K.K. (2001) Activation and habituation in olfaction: an fMRI study. Neuroimage, 13, 547–560.[Web of Science][Medline]
Qureshy, A., Kawashima, R., Imran, M.B., Sugiura, M., Goto, R., Okada, K., Inoue, K., Itoh, M., Schormann, T., Zilles, K. and Fukuda, H. (2000) Functional mapping of human brain in olfactory processing: a PET study. J. Neurophysiol., 84, 1656–1666.
Raichle, M.E., Martin, W.R., Herscovitch, P., Mintun, M.A. and Markham, J. (1983) Brain blood flow measured with intravenous H215O. II. Implementation and validation. J. Nucl. Med., 24, 790–798.
Rolls, E.T. and Baylis, L.L. (1994) Gustatory, olfactory, and visual convergence within the primate orbitofrontal cortex. J. Neurosci., 14, 5437–5452.[Abstract]
Royet, J.P., Hudry, J., Zald, D.H., Godinot, D., Gregoire, M.C., Lavenne, F., Costes, N. and Holley, A. (2001) Functional neuroanatomy of different olfactory judgments. Neuroimage, 13, 506–519.[Web of Science][Medline]
Sano, K., Tsuda, Y., Sugano, H., Aou, S. and Hatanaka, A. (2002) Concentration effects of green odor on event-related potential (P300) and pleasantness. Chem. Senses, 27, 225–230.
Savic, I. (2002) Imaging of brain activation by odorants in humans. Curr. Opin. Neurobiol., 12, 455–461.[CrossRef][Web of Science][Medline]
Savic, I., Gulyas, B., Larsson, M. and Roland, P. (2000) Olfactory functions are mediated by parallel and hierarchical processing. Neuron, 26, 735–745.[CrossRef][Web of Science][Medline]
Savic, I., Gulyas, B. and Berglund, H. (2002) Odorant differentiated pattern of cerebral activation: comparison of acetone and vanillin. Hum. Brain Mapp., 17, 17–27.[CrossRef][Web of Science][Medline]
Shidara, M. and Richmond, B.J. (2002) Anterior cingulate: single neuronal signals related to degree of reward expectancy. Science, 296, 1709–1711.
Small, D.M., Jones-Gotman, M., Zatorre, R.J., Petrides, M. and Evans, A.C. (1997) Flavor processing: more than the sum of its parts. Neuroreport, 8, 3913–3917.[Web of Science][Medline]
Sobel, N., Prabhakaran, V., Desmond, J.E., Glover, G.H., Goode, R.L., Sullivan, E.V. and Gabrieli, J.D. (1998a) Sniffing and smelling: separate subsystems in the human olfactory cortex. Nature, 392, 282–286.[CrossRef][Medline]
Sobel, N., Prabhakaran, V., Hartley, C.A., Desmond, J.E., Zhao, Z., Glover, G.H., Gabrieli, J.D. and Sullivan, E.V. (1998b) Odorant-induced and sniff-induced activation in the cerebellum of the human. J. Neurosci., 18, 8990–9001.
Takechi, H., Onoe, H., Imamura, K., Onoe, K., Kakiuchi, T., Nishiyama, S., Yoshikawa, E., Mori, S., Kosugi, T., Okada, H., Tsukada, H. and Watanabe, Y. (1994) Brain activation study by use of positron emission tomography in unanesthetized monkeys. Neurosci. Lett., 182, 279–282.[CrossRef][Web of Science][Medline]
Tanabe, T., Iino, M. and Takagi, S.F. (1975a) Discrimination of odors in olfactory bulb, pyriform-amygdaloid areas, and orbitofrontal cortex of the monkey. J. Neurophysiol., 38, 1284–1296.
Tanabe, T., Yarita, H., Iino, M., Ooshima, Y. and Takagi, S.F. (1975b) An olfactory projection area in orbitofrontal cortex of the monkey. J. Neurophysiol., 38, 1269–1283.
Vogt, B.A. and Pandya, D.N. (1987) Cingulate cortex of the rhesus monkey: II. Cortical afferents. J. Comp. Neurol., 262, 271–289.[CrossRef][Web of Science][Medline]
Yousem, D.M., Williams, S.C., Howard, R.O., Andrew, C., Simmons, A., Allin, M., Geckle, R.J., Suskind, D., Bullmore, E.T., Brammer, M.J. and Doty, R.L. (1997) Functional MR imaging during odor stimulation: preliminary data. Neuroradiology, 204, 833–838.
Yousem, D.M., Maldjian, J.A., Siddiqi, F., Hummel, T., Alsop, D.C., Geckle, R.J., Bilker, W.B. and Doty, R.L. (1999) Gender effects on odor-stimulated functional magnetic resonance imaging. Brain Res., 818, 480–487.[CrossRef][Web of Science][Medline]
Zald, D.H. and Pardo, J.V. (1997) Emotion, olfaction, and the human amygdala: amygdala activation during aversive olfactory stimulation. Proc. Natl Acad. Sci. USA, 94, 4119–4124.
Zald, D.H. and Pardo, J.V. (2000) Functional neuroimaging of the olfactory system in humans. Int. J. Psychophysiol., 36, 165–181.[CrossRef][Web of Science][Medline]
Zatorre, R.J. and Jones-Gotman, M. (1991) Human olfactory discrimination after unilateral frontal or temporal lobectomy. Brain, 114, 71–84.[Web of Science][Medline]
Zatorre, R.J., Jones-Gotman, M., Evans, A.C. and Meyer, E. (1992) Functional localization and lateralization of human olfactory cortex. Nature, 360, 339–340.[CrossRef][Medline]
Accepted June 25, 2003
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Aou, M. Mizuno, Y. Matsunaga, K. Kubo, X.-L. Li, and A. Hatanaka Green Odor Reduces Pain Sensation and Fatigue-like Responses Without Affecting Sensorimotor Function Chem Senses, January 1, 2005; 30(suppl_1): i262 - i263. [Full Text] [PDF]
|
|
|
|
|
|
Y. Watanabe, T. Sasabe, K. Yamaguti, M. Kobayashi, S. Yamamoto, H. Kuratsune, K. Sano, A. Hatanaka, H. Tsukada, and H. Onoe Prevention and/or Recovery Effects by Green Odor(s) on Fatigue and Green-odor-responsible Brain Regions as Revealed by PET Chem Senses, January 1, 2005; 30(suppl_1): i268 - i269. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||