AJCN Tufts Nutrition Symposium, Boston Sept 24-26
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American Journal of Clinical Nutrition, Vol. 70, No. 5, 806-810, November 1999
© 1999 American Society for Clinical Nutrition

Original Research Communications

Regions of the human brain affected during a liquid-meal taste perception in the fasting state: a positron emission tomography study1,2

Jean-François Gautier, Kewei Chen, Anne Uecker, Daniel Bandy, Jennifer Frost, Arline D Salbe, Richard E Pratley, Michael Lawson, Eric Ravussin, Eric M Reiman and P Antonio Tataranni

1 From the Clinical Diabetes and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ; the Positron Emission Tomography Center, Good Samaritan Regional Medical Center, Phoenix, AZ; and the Department of Psychiatry, University of Arizona, Tucson, AZ.

2 Address reprint requests to PA Tataranni, Clinical Diabetes and Nutrition Section, NIDDK/NIH, 4212 North 16th Street, Phoenix, AZ 85016. E-mail: antoniot{at}mail.nih.gov.


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: The sensation of taste provides reinforcement for eating and is of possible relevance to the clinical problem of obesity.

Objective: Positron emission tomography (PET) was used to explore regions of the brain that were preferentially affected during the taste perception of a liquid meal by 11 right-handed, lean men in the fasting state.

Design: After subjects had fasted for 36 h, 2 measurements of regional cerebral blood flow (rCBF) obtained immediately after subjects retained and swallowed 2 mL of a flavored liquid meal (the taste condition) were compared with 2 measurements of rCBF obtained immediately after subjects retained and swallowed 2 mL of water (the baseline condition).

Results: Compared with the baseline condition, taste was associated with increased rCBF (P < 0.005) in the left dorsolateral prefrontal cortex and superior temporal gyrus; the right ventrolateral prefrontal cortex, supramarginal gyrus, and anterior thalamus; and bilaterally in the hippocampal formation, posterior cingulate, midbrain, occipital cortex, and cerebellum. Taste was also associated with decreased rCBF (P < 0.005) in the right dorsolateral prefrontal cortex, superior temporal gyrus, and supplementary motor area, and bilaterally in the medial prefrontal cortex and inferior parietal lobule.

Conclusions: This exploratory study provides additional evidence that the temporal cortex, thalamus, cingulate cortex, caudate, and hippocampal formation are preferentially affected by taste stimulation. The asymmetric pattern of activity in the dorsolateral prefrontal cortex and superior temporal gyrus may contribute to the taste perception of a liquid meal perceived as pleasant. Additional studies are required to determine how these regions are affected in patients with obesity or anorexia.

Key Words: Taste • positron emission tomography • PET • human brain • cortex • thalamus • cingulate gyrus • caudate • cerebral blood flow • men


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Sensory stimulation provided by food results in cephalic responses affecting cardiovascular and gastrointestinal functions, exocrine and endocrine pancreatic secretions, thermogenesis, and, more generally, food selection (1). Of possible relevance to the clinical problem of obesity, the sensation of taste provides reinforcement for eating; moreover, differences in taste preference have been described between lean and obese subjects (2). Evidence from animal studies suggests that the perception of taste is mediated by a multisynaptic neuronal pathway that involves peripheral taste nerves (facial, glossopharyngeal, and vagus nerves), neurons arising in the nucleus of the solitary tract (brainstem), neurons arising in the ventral posteriomedial nucleus of the thalamus, neurons arising in the primary gustatory cortex (frontal opercular and anterior insular cortex), and neurons arising anteriorly in the secondary gustatory cortex (orbitofrontal cortex) and posteriorly in the amygdala (3, 4). In turn, the orbitofrontal cortex and amygdala have reciprocal connections with the lateral hypothalamus (4).

Human studies provide additional information about brain regions that participate in the sensation of taste. Henkin et al (5) and Small et al (6) reported that epileptic patients in whom the anterior temporal lobe had been surgically excised had a deficit in the recognition of gustatory stimuli. Using positron emission tomography (PET), Kinomura et al (7) showed that the perception of salty taste (0.18% saline) affected the superior and middle temporal gyri, insular cortex, thalamus, hippocampal region, lingual gyrus, cingulate gyrus, and caudate. The perception of an aversive saline concentration (5%) has been shown to affect the amygdala, orbitofrontal cortex, and cingulate (8). Small et al (6) found increased activity in the anteromedial temporal lobe and orbitofrontal cortex during taste perception of citric acid. Lastly, piriform and orbitofrontal cortex activities have been reported in response to odor stimulation (9), which commonly accompanies taste stimulation by food.

In this study, we used PET measurements of regional cerebral blood flow (rCBF), a marker of local neuronal activity, to investigate whether these paralimbic and limbic areas and the temporal lobe of the human brain are preferentially affected during the taste perception of a liquid meal. Unlike earlier human studies, we investigated how the brain responds to such a stimulus in the context of extreme hunger.


   SUBJECTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Baseline patient characteristics, experimental procedures, brain imaging procedures, and analyses were similar to those described elsewhere (10) with the differences described below. Briefly, 11 right-handed, white, male volunteers with body mass indexes (in kg/m2) <25 (35 ± 8 y, 73 ± 9 kg, 19 ± 6% body fat; x ± SD) were admitted for {approx}1 wk to the Clinical Research Unit of the National Institutes of Health in Phoenix, AZ, where they were restricted to the metabolic ward during the screening and fasting procedures. After the subjects had fasted for 36 h, magnetic resonance imaging of the brain was first performed. Next, 2 PET scans were performed during the baseline condition and 2 PET scans were performed during the taste condition. This procedure was part of a previously reported study in which 2 additional PET scans were performed after inducing satiation (10).

Two and 3 d before the imaging session, each subject participated in a dress rehearsal of the study to become familiarized with the behavioral tasks. For the dress rehearsal and subsequent PET sessions, subjects rested in the supine position. Customized foam molds were used to immobilize the head; a plastic extension tube (4 mm in diameter) was inserted into the mouth to reach the middle region of the tongue and secured on the chin with tape. During the baseline condition, subjects were asked to retain and swallow 2 mL of water administered from a syringe immediately before each scan (<30 s) to control for the potentially confounding effects of oropharyngeal somatosensation and swallowing. For the subsequent taste condition, subjects were asked to retain and swallow 2 mL of a flavored liquid-formula meal [Ensure-Plus, 6.2 MJ/L (1.5 kcal/mL); Ross Products Division, Abbott Laboratories, Columbus, OH] immediately before each scan (<30 s). The flavor of the liquid meal (chocolate, vanilla, or strawberry) was chosen by each subject before the PET study. Subjects were asked to rate the pleasantness and palatability of the flavored liquid meal on a 0–100-mm visual analogue scale. The protocol was approved by the Institutional Review Boards of the National Institute of Diabetes and Digestive and Kidney Diseases and Good Samaritan Regional Medical Center, and informed, written consent was obtained from all subjects.

Imaging procedures
Magnetic resonance imaging was performed with a 1.5-T Signa system (General Electric, Milwaukee) to rule out gross anatomical abnormalities and to facilitate comparisons between brain structure and function. For the PET procedure, a transmission scan using a 68Ge-68Ga ring source was performed to correct subsequent emission images for radiation attenuation. During each scan, subjects rested quietly in the supine position without moving and were asked to keep their eyes closed and pointing forward. PET images of regional brain activity (counts·pixel-1·min-1) were obtained for each subject by using an ECAT 951/31 scanner (Siemens, Knoxville, TN). For each scan, a 1.85-GBq intravenous bolus of [15O]water was injected. Two 1-min scans were obtained at baseline and 2 were obtained after taste stimulation, with intervals of 10–15 min between scans.

Image processing and statistical analysis
As described previously (10), automated algorithms were used to align each subject's sequential PET images, to transform PET images into spatial coordinates of a standard brain atlas, to investigate increases in rCBF independent of variations in whole-brain measurements by using analysis of covariance, and to generate normalized t value (ie, z score) maps of increases in rCBF (average of the 2 images in the taste condition minus the average of the 2 images in the baseline condition) and decreases in rCBF (average of the 2 images in the baseline condition minus the average of the 2 images in the taste condition) during taste stimulation. To reduce type I errors, a critical z score >=2.58 (P < 0.005 uncorrected for multiple comparisons) was used to characterize significant changes in regional brain activity.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Using the visual analogue scales, all subjects reported that the liquid formulation was pleasant (64 ± 18 mm) and palatable (65 ± 16 mm). Relative to the baseline control condition, the taste perception of a liquid meal in the fasting state was associated with increased rCBF in the left dorsolateral prefrontal cortex and superior temporal gyrus; the right ventrolateral prefrontal cortex, supramarginal gyrus, and anterior thalamus; and bilaterally in the hippocampal formation, posterior cingulate, midbrain (posterior to the hypothalamus), occipital cortex, and cerebellum (Table 1Go, Figure 1Go). Taste perception of a liquid meal in the fasting state was also associated with decreased rCBF in the vicinity of the right dorsolateral prefrontal cortex, superior temporal gyrus, and supplementary motor area, and bilaterally in the medial prefrontal cortex and inferior parietal lobule (Table 2Go, Figure 1Go).


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  		TABLE 1. Regions with increased regional cerebral blood flow in the pleasant taste condition relative to the control condition in 11 right-handed, lean men in the fasting state
 


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  		FIGURE 1. Significant differences in regional cerebral blood flow (rCBF) between the fasting taste stimulation and the fasting control condition in 11 right-handed, lean men. Compared with the control condition, regions with increased and decreased rCBF in the taste condition are shown in yellow and blue, respectively. Images were generated by using positron emission tomography and magnetic resonance imaging (MRI) data. Color-coded images are superimposed onto an average of the subjects' brain MRI scans (gray scale image); horizontal brain sections correspond to the coordinates of the Talairach and Tournoux brain atlas (11). The number under each section reflects the distance in mm superior (+) or inferior (-) to a horizontal plane between the anterior and posterior commissures; the right hemisphere in each section is on the reader's right. Taste perception was associated with significantly greater rCBF (P < 0.005 uncorrected for multiple comparisons) in the vicinity of the left dorsolateral prefrontal cortex (dlpf), ventrolateral prefrontal cortex (vlpf), hippocampal formation (hi/ph/ca), anterior thalamus (th), posterior cingulate (pc), left superior temporal gyrus (stg), supramarginal gyrus (smg), midbrain (mb), and occipital cortex and cerebellum (ce/oc). Lower rCBF (P < 0.005 uncorrected for multiple comparisons) was observed in the vicinity of the medial prefrontal cortex (mpf), anterior cingulate (ac), right dorsolateral prefrontal cortex (dlpf), right superior temporal gyrus (stg), inferior parietal cortex and angular gyrus (ip/a), and supplementary motor area (sma). The location and magnitude of the maximal differences are shown in Tables 1 and 2GoGo.

 

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  		TABLE 2. Regions with decreased regional cerebral flow in the pleasant taste condition relative to the control condition in 11 right-handed, lean men in the fasting state1
 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Although our findings must be considered exploratory, they support recent evidence that the anterior temporal cortex, thalamus, cingulate cortex, caudate, and hippocampal formation are preferentially involved in the perception of taste. They also raise the possibility that asymmetrical changes in brain activity in the vicinity of the lateral prefrontal and temporal cortex (ie, increases in the left and decreases in the right) are preferentially involved in the taste perception of a liquid meal in the fasting state.

Previous studies in humans indicated activation of the superior temporal gyrus, insular cortex, orbitofrontal cortex, amygdala, thalamus, hippocampal formation, lingual gyrus, cingulate, and caudate in response to salty taste (7, 8) and activation of the anteromedial temporal lobe and orbitofrontal cortex in response to acidic taste (6). As in these investigations, we also found rCBF changes in the anterior temporal cortex, thalamus, hippocampal formation, caudate, and cingulate. In addition, we found rCBF changes in the vicinity of the prefrontal cortex, supramarginal gyrus, inferior parietal lobule, supplementary motor area, midbrain, occipital cortex, and cerebellum. We postulate that these additional regions could be at least partly related to interactions between the subjects' underlying state of extreme hunger and the emotional valence of the taste perception.

Although our hypotheses did not include activation of the prefrontal cortex during taste stimulation, we retained this region because of the high z score obtained in the left dorsolateral prefrontal cortex (3.72, P < 0.0005). Previous studies (12, 13) suggested that asymmetric activity in the frontal and temporal lobes participates in emotional valence, ie, the extent to which an emotion is pleasant or unpleasant. According to these studies, pleasant emotions are associated with higher activity in the left hemisphere, whereas unpleasant emotions are associated with higher activity in the right hemisphere. In our study, the taste perception of the liquid meal in the unpleasant state of extreme hunger was associated with increased dorsolateral prefrontal cortex and superior temporal gyrus activity in the left hemisphere and decreased dorsolateral prefrontal cortex and superior temporal gyrus activity in the right hemisphere. We postulate that this asymmetric pattern of brain activity is related to the perception of the taste as pleasant. Although we cannot rule out the possibility that the prefrontal cortex is activated as a result of cognitive factors such as anticipation, this region was not reported previously to have activity in response to food exposure in the fasting condition (14).

Previous studies raised the possibility that the anterior cingulate cortex participates in the experience of unpleasant emotions and that the dorsomedial prefrontral cortex participates in the inhibition of excessive emotion (15). Because these regions were associated with greater activity in the fasting state, we speculate that the anterior cingulate region might participate in the attenuation of the relatively unpleasant state of hunger rather than the relatively pleasant taste sensation and that the adjacent medial prefrontal region inhibits excessively unpleasant emotions, helping to restrain subjects from the urge to consume food during the study.

In contrast with previous studies (6–8), we did not find the taste condition to be associated with increased activity in the primary gustatory (ie, insular) cortex, the amygdala, or the orbitofrontal cortex. We also did not find any activation in the vicinity of the hypothalamic areas (4). Possible explanations for these findings include limitations in statistical power, previous observations that the insular cortex and amygdala may be involved in unpleasant rather than pleasant emotions and sensory stimuli (8, 13, 16), and the interaction between our unpleasant baseline state involving hunger and our taste state involving a mixture of unpleasant hunger and pleasant taste sensations. It is possible that the insular and orbitofrontal cortex, which are both affected during hunger (10), were not activated in our study because of the pixel-wise subtraction analyses between the taste and hunger conditions. Indeed, these regions were activated when we compared the taste condition with the satiation condition described previously (10).

Although our study generates hypotheses that can be tested in future studies, several limitations prevent us from determining how the implicated regions contribute to particular aspects of taste, hunger, and their interaction. These limitations have largely been addressed previously (10). Briefly, they include 1) limitations in spatial resolution, contrast resolution, and the accuracy of the image deformation algorithm used to compute the statistical maps that prevent detection of significant state-dependent changes in regional brain activity in small regions such as hypothalamic or brainstem nuclei; 2) the choice of the critical z score of 2.58; and 3) the effect of scan order, because the taste condition routinely followed the control condition. We acknowledge that the scan order is a major concern of the study. However, subjects were familiarized with the experimental setting before the actual testing and we did not observe order effects in the regions affected by taste stimulation when subjects were repeatedly studied in a resting baseline condition (10). Still, our results were not statistically corrected for multiple comparisons and, thus, should be considered preliminary. Additional studies are needed to replicate the observed changes in regional brain activity associated with taste stimulation. Whether pleasant taste perception after an overnight fast instead of during an extreme state of hunger would elicit similar responses remains to be determined.

In conclusion, the present study provides additional evidence that the temporal cortex, thalamus, cingulate, caudate, and hippocampal formation are preferentially affected by taste stimulation. Our results raise the possibility that an asymmetric pattern of activity in the dorsolateral prefrontal cortex and superior temporal gyrus contributes to the taste perception of a liquid meal perceived as pleasant in the context of extreme hunger. Additional studies are required to clarify how the neuroanatomical correlates of taste might be involved in the pathophysiology of the hyperphagia associated with obesity or other eating disorders.


   ACKNOWLEDGMENTS
 
We thank Lang Sheng Yun, Sandy Goodwin, Leslie Mullen, Tricia Giurlani, David Stith, and Frank Gucciardo for technical assistance; Manish Amin and Vaishali Patel for their logistic help; and the nursing, dietary, and technical staffs of the Clinical Research Center.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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Received for publication February 9, 1999. Accepted for publication April 27, 1999.




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