Functional anatomy of taste perception in the human brain studied with positron emission tomography

BRAIN RESEARCH ELSEVIER

Brain Research 659 (1994) 263-266

Short communication

Functional anatomy of taste perception in the human brain studied with positron emission tomography Shigeo Kinomura a, Ryuta Kawashima a,,, Kenji Yamada a, Shuichi Ono a, Masatoshi Itoh b, Seiro Yoshioka a, Tatsuo Yamaguchi a, Hiroshige Matsui a, Hidemitsu Miyazawa a, Hiroshi Itoh a, Ryoui Goto a, Takehiko Fujiwara b, Kazunori Satoh a, Hiroshi Fukuda " a Department of Nuclear Medicine and Radiology, Institute of Development, Aging and Cancer, Tohoku Unil,ersio', 4-1 Seiryo-machi, Aobaku, Sendai 980-77, Japan h Dil~ision of Nuclear Medicine, Cyclotron and Radioisotope Center, Tohoku Unirersity, Aramaki, Aobaku, Sendai 980, Japan Accepted 12 July 1994

Abstract

Regional cerebral blood flow (rCBF) was measured with positron emission tomography (PET) in 10 normal volunteers with the purpose of measuring rCBF changes related to taste physiology. Discrimination of 0.18% saline from pure water was associated with significantly increased rCBF values in the thalamus, the insular cortex, the anterior cingulate gyms, the parahippocampal gyrus, the lingual gyrus, the caudate nucleus, and the temporal gyri. The results indicate that rCBF changes in these structures may reflect oral exposure to salt.

Keywords: Positron emission tomography; Regional cerebral blood flow; Taste stimulation; Insular cortex; Cingulate cortex; Parahippocampal gyrus; Human brain

Taste perception in the brain has been studied mainly in non-human animals. Electrophysiological studies in monkeys have indicated neurons in the frontal operculum and the insular cortex to function in relation to taste stimuli [8,12,13,15,17]. Recently, Rolls et al. [9] have reported that the orbitofrontal cortex is the secondary cortical taste area concerned with the quality of taste. An anatomical study of monkeys [3] has revealed that the taste pathway in the cerebral comprises the insula and the frontal operculum. However, little is known about the physiology of taste in the human brain. Y a m a m o t o et al. [19], using the evoked potential technique, did describe that evoked potentials in relation to taste stimuli can be recorded from the temporal region, but due to the nature of this method they could not identify which anatomical structures were involved. Recent developments in functional brain mapping techniques using P E T now allow precise study of the

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functional anatomy of the human brain related to cognitive functions. To our knowledge, however, there have been no previous studies using P E T methods with the aim of demonstrating which specific structures in the human brain are responsible for monitoring taste. The present investigation was, therefore, designed to determine anatomical structures participating in the discrimination of a salty taste. Ten healthy male volunteers (18 to 21 years) participated in this study. All subjects were strongly righthanded according to the H.N. Handedness Inventory [2]. Informed consent was obtained from each subject using forms approved by the Radioactive Drug Clinical Research Committee of Tohoku University. Each subject had two P E T runs for rCBF measurement: a control state and a taste discrimination state. During the control state, 0.2 ml of pure water was injected into the subject's mouth every 15 s through two plastic tubes (2 m m in diameter). The subjects were instructed to press a key button in their left hand with the first finger after every two injections. During the taste stimulation state, either 0.18% saline or pure water was injected randomly every 15 s. Subjects were

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instructed to press the key button only when they experienced a salty taste. During P E T measurements, subjects were laid in a supine position in the P E T scanner (Model 931/04; CTI, Knoxville, TN) with an in-plane resolution of 6.1 m m full width at half maximum. Reconstruction and filtering gave final image resolution of 8.5 × 8.5 × 7.0 mm [16]. Subject's eyes were closed and covered with cotton wool pads and the room was darkened and kept quiet for the duration of the study. Their heads were fixed into a head holder using Verculo strapping and the positron adjusted using 3-D P E T laser alignment beams. The orbitomeatal (OM) line was aligned with the horizontal beam, with the heads positioned symmetrically about the midsagittal plane. Subjects inhaled 150-labeled carbon dioxide (C~502) gas, which was mixed with air to deliver a concentration of 10 m C i / 1 0 0 m l / m i n . This was inhaled continuously for 7 min to produce an equilibrium state before PET measurements commenced. Two emission scans, each of 5 min, were obtained. C ~50 2 inhalation continued throughout the entire study. The order of scans was the control state (Control), followed by the taste discrimination state (Taste). T h e r e were 5 min between each emission scan. Seven P E T images were obtained on the plane parallel to the O M line from 24 to 72 mm, with 7-ram increments. In the present study, all P E T images were anatomically standardized using the computerized brain atlas system of Roland et al. [11]. After the anatomical standardization of the P E T images, % chan~e of relative rCBF between two globally normalized images (Taste and Control) were calculated for each subject on a voxel by voxel basis [1]. Then, a descriptive 3-D t image of Taste minus Control was calculated. In the descriptive t image, voxels having t > 3.58 and occurring in clusters of size 350 m m [3] and above were considered to represent significant activation [10]. The % correct responses were calculated from the receiver-operating characteristic for the taste discrimination task for each subject. The mean (S.D.) value for correct discrimination was 87.6% (6.1%), confirming that the subjects directed sufficient attention to the task. In the present study, 10 areas showed significant increases in rCBF during the taste discrimination task (Fig. 1). The locations of the centers of gravity of the

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Table l Regions demonstrating significant activation Anatomical location

Talairach coordinates (mm) X,

Y,

Z

-

13 36 10 11 16 8 - 26

39 6(I 76 - 55 11 -26 - 43

19 11 (/ 1 17 9 I

62 50 46

-27 24 6

13 12 12

Right hemisphere Cingulate gyrus Middle temporal gyrus Lingual gyrus Parahippocampal gyrus Caudate nucleus Thalamus Hippocampus

Left hemisphere Superior temporal gyrus Transverse temporal gyrus Insula

Talairach coordinates of the centers of gravity of each of the activations, X, Y and Z, are in ram, measured from the anterior commissure, corresponding to the atlas of Talairach and Tournoux [18]. The coordinates are given in the order X (width), Y (anterior-posterior) and Z (height).

activated fields in the Talairach coordinates [18] are summarized in Table 1. To our knowledge, this is the first human brain mapping study demonstrating the cerebral fields involved in specific taste discrimination. In the present case, the physics of tactile sensation to the tongue and the motor output (key pressing) were the same for Taste and Control states. Therefore, subtraction images of Taste minus Control can be considered to reflect synaptic activity related to a salty taste, and, therefore, to relate to sensory discrimination. However, since the Control task was done followed by the Taste task, the results could have been confounded by effects related to habituation [14]. The most striking finding was the activation of the left insula cortex. For humans, almost the same stereotaxic coordinates have been reported by Zatorre et al. [20] whose subjects inhaled an agent giving olfactory stimuli. Saline solution, the taste stimulus used in the present study, does not contain any odor. Therefore, our results, combined with the findings of Zatorre et al. [20], suggest the hypothesis that different sensory modalities, i.e., taste and olfaction, converge in a specific area in the insula cortex. Since different laboratories use different systems to transform their P E T data to their standard anatomical space, it is not possible, of

Fig. 1. a-c: horizontal sections of MRI of the standard shaped brain of the computerized brain atlas of Roland et al. [11]. White bright areas on the MRI show the fields of significant activation. Left hemisphere on the right side. a: this section is parallel to the AC-PC line [18] from 1 mm above. Fields of activation in the lingual gyrus, the parahippocampal gyrus and the hypocampus of the right hemisphere are shown, b: this section is parallel to the AC-PC line from 11 mm above. Fields of activation in the right middle temporal gyrus, the right thalamus, the left anterior part of the insula cortex, the left superior transverse temporal gyrus, and the left superior temporal gyrus are shown, c: this section is parallel to AC-PC line from 19 mm above. Fields of activation in the anterior part of the cingulate gyrus and the head of the caudate nucleus of the right hemisphere are shown.

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course, to make simple comparisons of results. However, there is a consistency between this hypothesis and the anatomical evidence from monkeys indicating that the anterior insula is related to both olfactory and gustatory behavior [6]. The fact of an area of activity in the thalamus may be related to the synaptic activity in the thalamic taste area. This latter has been demonstrated to have projections towards the frontal operculum and the insula cortex [7]. From neurophysiological studies of monkeys, both cortical areas have been concluded to be involved in taste perception [8]. Anatomical studies in monkeys have also shown that cortico-cortical connections exist between the insula cortex and the cingulate gyrus, the insula cortex and the frontal operculum [5], and the cingulate gyrus and the parahippocampal gyrus [4]. Our results, combined with these anatomical and physiological findings, may indicate that some of the cortical activations observed in the present study constitute part of a neuronal network involved in taste discrimination. Further human brain mapping studies are necessary to more clearly define the cortical response to taste stimuli.

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We wish to thank S. Watanuki and S. Seo for technical assistance. This research was supported by Grants 9136 and 92052 of the Salt Science Research Foundation, Research Grant for Aging and Health from the Japanese Ministry of Health and Welfare as well as Grants-in-Aid for Scientific Research 03670554 and 04670657 from the Japanese Ministry of Education, Science and Culture. [1] Grafton, S.T,, Mazziotta, J.C,, Woods, R.P. and Phelps, M.E., Human functional anatomy of visually guided finger movements, Brain, 115 (1992) 565-587. [2] Hatta, T. and Nakatsuka, Handedness inventory. In D. Ohno (Ed.), Papers on Celebrating 63rd Birthday of Prof. Ohnishi, Osaka City University, Osaka, 1975, pp. 224-245. [3] Ito, S. and Ogawa, H., Cytochrome oxidase staining facilities unequivocal visualization of the primary gustatory area in the fronto-operculo-insular cortex of macaque monkeys, NeuroscL Lett., 130 (1991) 61-64. [4] Morecraft, R.J., Geula, C. and Mesulam, MM., Cytoarchitec-

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