1Department of Experimental Psychology, University of Oxford, Oxford OX1 3UD; 2Magnetic Resonance Centre, School of Physics and Astronomy, University of Nottingham, Nottingham NG7 2RD2; and 3Unilever Research, Port Sunlight Laboratory, Wirral L63, United Kingdom
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ABSTRACT |
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O'Doherty, J., E. T. Rolls, S. Francis, R. Bowtell, and F. McGlone. Representation of Pleasant and Aversive Taste in the Human Brain. J. Neurophysiol. 85: 1315-1321, 2001. In this study, the representation of taste in the orbitofrontal cortex was investigated to determine whether or not a pleasant and an aversive taste have distinct or overlapping representations in this region. The pleasant stimulus used was sweet taste (1 M glucose), and the unpleasant stimulus was salt taste (0.1 M NaCl). We used an ON/OFF block design in a 3T fMRI scanner with a tasteless solution delivered in the OFF period to control for somatosensory or swallowing-related effects. It was found that parts of the orbitofrontal cortex were activated (P < 0.005 corrected) by glucose (in 6/7 subjects) and by salt (in 6/7 subjects). In the group analysis, separate areas of the orbitofrontal cortex were found to be activated by pleasant and aversive tastes. The involvement of the amygdala in the representation of pleasant as well as aversive tastes was also investigated. The amygdala was activated (region of interest analysis, P < 0.025 corrected) by the pleasant taste of glucose (5/7 subjects) as well as by the aversive taste of salt (4/7 subjects). Activation by both stimuli was also found in the frontal opercular/insular (primary) taste cortex. We conclude that the orbitofrontal cortex is involved in processing tastes that have both positive and negative affective valence and that different areas of the orbitofrontal cortex may be activated by pleasant and unpleasant tastes. We also conclude that the amygdala is activated not only by an affectively unpleasant taste, but also by a taste that is affectively pleasant, thus providing evidence that the amygdala is involved in effects produced by positively affective as well as by negatively affective stimuli.
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INTRODUCTION |
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The aims of this study are to
investigate the representation of taste in the human brain and in
particular to compare and contrast the representations of a pleasant
and an aversive taste. The study of the affective representation of
taste is important as a means of advancing our understanding of the
neural mechanisms for the regulation of food intake as well as the
mechanisms underlying emotional processing in the brain (Rolls
1999). Particular issues of interest are whether areas of the
human brain such as the insula, orbitofrontal cortex, and amygdala
implicated in taste are activated by both a pleasant and an aversive
taste, or whether in contrast there is some specialization of different
brain regions. If particular areas are activated by both pleasant and
unpleasant tastes, it is then of interest to investigate whether the
regions activated show topological separation.
Experimental investigations in macaques have shown that there is a
primary taste cortical region in the anterior insula and adjoining
frontal operculum, with a taste area in the orbitofrontal cortex that
receives from this, and that is therefore defined as the secondary
taste cortex (Baylis et al. 1994; Rolls
1997
; Rolls et al. 1990
; Scott et al.
1986
). Neurons in this orbitofrontal secondary taste cortex
region have been found to be modulated by the motivational state of the
animal, responding to the sight or taste of food when the animal is
hungry and not responding when the animal is satiated (Rolls et
al. 1989
). Furthermore, electrical stimulation of this brain
region is rewarding when the animal is hungry and the reward value (as
shown by whether the monkey will work for the stimulation) decreases as
the animal is fed to satiety (Mora et al. 1979
). These
results suggest that the orbitofrontal cortex is involved in
representing the affective aspects of taste in nonhuman primates. In
addition, lesion studies and neuroimaging studies in humans have
implicated the human orbitofrontal cortex in affective processing
(Bechara et al. 1994
; Elliot et al. 2000
;
Francis et al. 1999
; Rolls et al. 1994
).
Consequently, it is suggested that the human orbitofrontal cortex is
one region in which the affective aspects of taste are represented.
Previous neuro-imaging studies of the representation of taste in the
human brain have found cortical areas activated to taste such as the
frontal operculum/insula and the orbitofrontal cortex (Francis
et al. 1999; Small et al. 1997
,
1999
; Zald et al. 1998
). With the
exception of Zald et al. (1998)
, the representations of
pleasant and aversive tastes have not been compared within the same
subject group. In the study by Zald et al. using positron emission
tomography (PET), it was found that a region of the left orbitofrontal
cortex was activated by aversive taste (salt solution). However, the
interpretation of that study was complicated by the lack of consistent
activation of the orbitofrontal cortex or other brain areas such as the
amygdala by the pleasant stimulus used (solid chocolate). This may have
been due to the fact that water was used as the control stimulus, a
substance that itself has a taste and is known to activate neurons in
the primate insular and orbitofrontal taste cortices (Rolls et
al. 1990
; Yaxley et al. 1990
). Further,
Zald et al. (1998)
acknowledge that water is a positive
reinforcer in its own right, so that it could have obscured activation
to the pleasant stimulus in a subtraction paradigm. Also, that study
was not designed to measure the effects of pleasant taste, in that the
positive stimulus used, chocolate, has taste, olfactory, and texture components.
The primate amygdala also receives gustatory inputs that activate
single neurons (Sanghera et al. 1979; Scott et
al. 1993
). Moreover, it is of potential interest as an area
containing an affect-related representation of taste, as its function
in fear conditioning and thus in negative affect has been emphasized
(LeDoux 1992
). Indeed, many imaging studies of emotion
reviewed by Davidson and Irwin (1999)
have found
amygdala activation related to negative affect. Further, there is
evidence that patients with amygdala lesions have difficulties with
identifying negative face expressions (Adolphs et al.
1994
), and with aversive conditioning (LaBar et al.
1995
). However, a few imaging studies have also found amygdala activation to affectively positive stimuli (Breiter et al.
1996
; Schneider et al. 1997
) and the amygdala
has also been implicated in memory encoding of affectively positive as
well as affectively negative events (Hamann et al.
1999
). Another way to obtain evidence on the role of the human
amygdala in affect is to measure its activation to tastes with
different affective value. In the study by Zald et al.
(1998)
, activation of the human amygdala was found to aversive
saline, but there was no consistent activation to the pleasant
chocolate stimulus, perhaps due to the reasons outlined above. However,
in neurophysiological recordings made in nonhuman primates, amygdala
neurons have been found that respond to rewarding tastes (such as
glucose), while other neurons respond to other tastes, such as salt or
sour (Scott et al. 1993
). This raises the possibility
that the amygdala is not only involved in processing affectively
negative tastes, but also affectively positive taste. Indeed, testing
whether the human amygdala is activated by affectively positive as well
as by affectively negative tastes, as described here, is one way to
obtain evidence on whether the human amygdala is involved only in
negative emotions, or in both positive and negative emotions.
In this experiment, we used functional magnetic resonance imaging (fMRI) to investigate brain activation to pleasant and unpleasant tastes. The pleasant taste used in this study was sweet taste (1 M glucose), and the aversive taste salt (0.1 M NaCl). The neutral control stimulus used was designed to be a tasteless solution by being formulated to include the main ionic components present in saliva, and thus to overcome the pitfalls of using water alone as a control stimulus (see above). The aims of the study are to investigate whether the orbitofrontal cortex is activated by the pleasant and unpleasant tastes, and, if so, to show whether there is a functional anatomical separation between regions of orbitofrontal cortex involved in processing the two tastes, and to determine whether or not the amygdala can be activated by pleasant as well as by aversive tastes.
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METHODS |
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Seven healthy human subjects participated in this experiment.
Imaging was conducted using a 3.0 Tesla fMRI scanner at the University
of Nottingham. Ten coronal T2* weighted EPI (Echo-planar imaging)
slices were acquired every 2 s with a slice thickness of 8 mm
(TR = 2 s). The matrix size was 128 × 64. The following parameters were carefully selected to minimize susceptibility and
distortion artifact in the orbitofrontal cortex. First, the data were
acquired in a coronal rather than axial slicing direction, as this
aligned the slices to be perpendicular to the predominant direction of
the intrinsic susceptibility-induced field gradients, and helped to
minimize through plane dephasing. Second, the in-plane voxel resolution
was set to 3 mm by 3 mm, which results in less phase cancellation than
would be produced by a lower voxel resolution. Third, a relatively low
TE of 23 ms was selected to decrease the signal dropout, as less phase
dispersion is created across the voxels. Fourth, each subject was
individually shimmed using both linear and second-order shimming to
minimize static field inhomogeneities in the orbitofrontal cortex.
Finally, geometric distortion was minimized by using a head insert
gradient coil with very high gradient switching frequency of 1.9 kHz.
The images were acquired beginning anteriorly at the orbitofrontal
cortex (Talairach Y = +50) and moving posteriorly (to Y = 30) taking care to include the putative primary taste cortex (frontal
operculum/insula). Anatomical localization was achieved by acquiring a
multislice echo-planar dataset for each subject with isotropic 3-mm
resolution using an inversion recovery (IR) sequence with the gray
matter nulled (TI = 1,200 ms). Taste stimuli were delivered
intra-orally by two polythene tubes held between the lips. The taste
stimuli consisted of 1 M glucose, and 0.1 M NaCl. In the experiment,
0.5 ml of the taste stimulus (either glucose or saline) was delivered at the start of an 8-s ON period. This was followed by 0.5 ml of a tasteless control solution (with the main ionic components of
saliva consisting of 25 mM KCl and 2.5 mM NaHCO3)
that was delivered at the start of an 8-s OFF period. This
OFF period thus enabled nontaste-related activations such
as swallowing or somatosensory effects to be subtracted out in the
subsequent analysis (the subject was instructed to move the stimulus
around the tongue and swallow once during each period). This protocol
was repeated 24 times. In five subjects each taste was delivered
separately in two separate runs. For the two additional subjects, an
interleaved design was employed whereby both taste stimuli and the
control stimulus were applied together in one imaging run using the
same ON/OFF design but interleaving the
application of the two taste stimuli. The subjects' subjective ratings
of the pleasantness of the taste stimuli were also measured just before
the imaging run using a rating scale ranging from +2 = very
pleasant, 0 = neutral,
2 = very unpleasant, which has been
validated in psychophysical experiments on the sensory factors that
control food intake (O'Doherty et al. 2000
;
Rolls et al. 1981
). The subjects were given practice in
the use of the scale so that they knew the range of stimuli to be rated
before the final ratings were taken.
Image analysis
The data were analyzed with MEDx (Sensor Systems). Motion
correction [using automatic image registration (AIR)]
(Woods et al. 1992), spatial smoothing (using a
Guassian kernel with full width at half-maximum of 5 mm), intensity
normalization (slice based ratio normalization), and temporal filtering
(using a low-pass filter width of 2.8 s and a high pass filter set
to twice the stimulus repetition period) were applied to the datasets.
Significant changes of voxel intensity between each taste stimulus and
the tasteless control condition were calculated by performing the following t-test comparisons using the standard Medx
statistics and the appropriate time window given the hemodynamic
response lags determined for this dataset as described previously
(Francis et al. 1999
): Glucose-Tasteless Control and
Salt-Tasteless Control. To enable a single subject analysis, the
thresholds in the resulting z-maps were then set at
P < 0.005 (resel corrected) with a minimum cluster
size of three contiguous voxels. For a more statistically sensitive
analysis of activation in the region of the amygdala, a region of
interest analysis (ROI) was also carried out, by defining two 84-voxel
cubic ROIs centered on each amygdala within the medial temporal lobes,
using the individual subjects' anatomical IR volume as a reference.
The z-scores in the amygdala were then corrected for
multiple comparisons (restricted to that region) at P < 0.025. The individual subjects' IR anatomical volumes were then
registered to a standard high resolution (1 mm isotropic) anatomical
volume, and the z-scores were rendered to that anatomical
volume for better visualization. A group analysis was also carried out
by setting the threshold for significance of the z-maps from
each subject for each of the two conditions at P < 0.01 (uncorrected) and identifying those voxels that were commonly
activated (after transformation into Talairach space) in a minimum of
six of seven subjects in each condition. The group analysis enabled
voxels that were commonly activated at a significance level of
P < 0.01 to be identified across subjects, and thus
provided a measure of the reliability of the activation of particular
voxels across subjects. Cluster sizes of <3 contiguous voxels in the
group combined image were excluded from the analysis.
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RESULTS |
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Pleasantness ratings
The average pleasantness rating (ranging from +2 = very
pleasant, 0 = neutral, 2 = very unpleasant) for the Glucose
condition, was +0.9 ± 0.49 (mean ± SE), whereas that for
the Salt condition was
1.5 ± 0.16 (paired t = 4.93, df = 6, P < 0.003).
Orbitofrontal cortex
The single subject analysis showed that the orbitofrontal cortex
was activated in six of seven subjects in the Glucose-Control condition
and in six of seven subjects in the Salt-Control condition. Within each
individual subject in the orbitofrontal cortex, different areas were
activated by the Glucose and Salt tastes (the results from a single
subject are presented in Fig. 1). The
group analysis revealed common areas of activation across subjects in
the orbitofrontal cortex for both glucose (pleasant) (Talairach
coordinates: X = 38, Y = 40, Z = 10; X = 47, Y = 38, Z =
6; X =
28,
Y = 36, Z =
7; X = 12, Y = 42, Z =
1) and salt
(aversive) tastes (Talairach coordinates: X = 13, Y = 36, Z =
8; X =
18, Y = 39, Z =
7), and that the
areas activated by each taste were nearby but showed little overlap
(see Fig. 3). Taken together, the analyses show that there is some
consistency of the areas activated across subjects, that the common
area across subjects for glucose is separate from that for saline, and
that in individual subjects the centers of mass of the activations were
even further apart.
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Insula and frontal operculum
The insula and frontal operculum were activated by the taste
stimuli. The single subject analysis showed that the insula was activated in five subjects to glucose, and in three subjects to salt;
the frontal operculum in five subjects to glucose, and three subjects
to salt. The results for a single subject are shown in Fig.
2. The common areas across subjects (as
revealed by the group analysis) showed that a considerable
anterior-posterior extent of the insula/operculum could be activated by
taste stimuli (Fig. 3). Some regions
showed overlap of the activations to glucose and salt (Talairach
coordinates: X = 42, Y = 28, Z = 10; X = 48, Y =
5, Z = 0), while other regions were activated by
glucose (Talairach coordinates: X = 46, Y = 11, Z = 17; X = 40, Y = 13, Z =
6; X =
33, Y = 17, Z = 2). Both the group
analysis and the single subject analysis did not provide clear evidence
for chemotopography (with respect to glucose vs. salt) in the
insular/opercular taste cortical areas.
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Amygdala
The ROI analysis showed that pleasant taste (glucose) activated
the left amygdala in five of the seven subjects (average Talairach coordinates: X = 20, Y =
5,
Z =
21). Activation was also found to the taste of
glucose in the right amygdala in two of the seven subjects (Talairach
coordinates: X = 25, Y =
4,
Z =
24). Figure 4 shows
not only the activations found in each subject, but also the median
value of the activated voxels across subjects within the amygdala in
the Glucose-Control condition. In the Salt-Control condition, the
amygdala was significantly activated in four subjects in total, two
subjects on the left side (Talairach coordinates: X =
24, Y =
5, Z =
21), and two
subjects on the right (Talairach coordinates: X = 18, Y =
4, Z =
14).
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Other areas
Activation was also found in the dorsal anterior cingulate (5 subjects to salt, 5 subjects to glucose). The Talairach coordinates of the areas with activation in the group analysis are shown in Table 1.
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DISCUSSION |
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The results from the single subject and the group analysis showed
that the orbitofrontal cortex could be activated by sweet (pleasant)
and salt (aversive) tastes. Moreover, the group analysis showed that
the regions of the orbitofrontal cortex reliably activated across
subjects by the sweet and salt tastes were adjacent. The separation
between the two areas was more pronounced within individual subjects,
as illustrated in Fig. 1. This is the first paper to investigate the
effects of both pleasant and aversive taste stimuli (glucose and NaCl)
against a tasteless control condition (as contrasted with previous
studies that used substances such as citric acid or water that can
activate neurons in the primate taste cortex) (Small et al.
1999) and thus provides clear evidence that pure gustatory
stimuli (with nongustatory effects controlled for) activate the
orbitofrontal cortex. We note that the sweet taste was rated as
pleasant (+0.9) and the salt taste as aversive (
1.5). Thus we
conclude that both a pleasant and an aversive taste are represented in
the orbitofrontal cortex, and it follows, with respect to taste hedonics, that the orbitofrontal cortex is not concerned exclusively with the representation of only pleasant or aversive tastes. Although the two tastes were rated as pleasant or aversive, the study described here does not show directly that it is explicitly the hedonic value of
the tastant that is represented in the orbitofrontal cortex. One way to
address this issue would be to investigate the effects on the
orbitofrontal cortex activation by glucose of feeding to satiety with
glucose, which decreases the pleasantness of the taste of glucose but
much less of its intensity (Rolls et al. 1983
). However,
we predict that this result would be found, because we have shown that
in a nearby region of the orbitofrontal cortex the activation produced
by a food odor is decreased by eating that food to satiety
(O'Doherty et al. 2000
). Given the results presented
here for taste, it will be of interest to investigate further whether
both pleasant and aversive stimuli in other modalities (including
somatosensory, olfactory, and visual) can activate the human
orbitofrontal cortex. Evidence on these issues is fundamental in
understanding the functions of the human orbitofrontal cortex in
emotion (Rolls 1999
).
Another novel finding of this study is that the human amygdala can be
activated by pleasant as well as by aversive tastes. The amygdala was
activated in five of seven subjects in the pleasant taste condition,
and in four of seven subjects in the unpleasant taste (salt) condition.
These results provide new evidence to support the argument that the
human amygdala is involved in pleasant as well as negative affect
(Rolls 1999).
It is of interest that in humans the region of the insula and operculum
that can be activated by taste does extend several millimeters back
from the front of the operculum and insula. Although quite extensive,
it is likely that this is the primary taste cortex of humans, with the
orbitofrontal cortex containing the secondary taste cortex as in
macaques (Baylis et al. 1994; cf. also Small et
al. 1999
). In previous neuroimaging studies of taste,
activation has been reported over quite a wide region of the anterior
insular/opercular (primary taste) cortex, but in most studies only one
taste stimulus was used or comparisons were not made between the
effects of different tastants (Small et al. 1999
). In
our study, in the group analysis, it was found that in some parts of
the anterior insula and frontal operculum there was overlap between the
sweet and salt taste representations, while in other regions only one
of the tastes produced activation. We know that in the primate
(macaque) primary taste cortex there is some intermingling of neurons
responsive to sweet and salt tastes (Rolls 1997
;
Scott et al. 1986
). The present findings in humans are
consistent with this but at the same time suggest that further
exploration of whether there is in addition some chemotopography would
be important.
To conclude, this study has shown that the orbitofrontal cortex can be
activated by taste stimuli that are affectively positive and
affectively negative, and there is some indication that the areas
activated by pleasant and aversive tastes are topographically separate.
Further, it was shown that the human amygdala can be strongly activated
by affectively positive stimuli (sweet taste) as well as by affectively
negative stimuli (salt taste). These stimuli are known to be positive
and negative primary reinforcers, and the findings help to provide a
basis for understanding the functions of the amygdala and the
orbitofrontal cortex in positive as well as negative emotions (see
further Rolls 1999, 2000a
,b
).
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ACKNOWLEDGMENTS |
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A studentship was provided by the Medical Research Council (MRC) and the Oxford McDonnell Pew Centre for Cognitive Neuroscience to J. O'Doherty. This research was supported by Unilever and MRC Special Project Grant G9302591 to the University of Nottingham, by MRC Programme Grant PG9826105 to E. T. Rolls, and by the MRC Interdisciplinary Research Centre for Cognitive Neuroscience at Oxford.
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FOOTNOTES |
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Address for reprint requests: E. T. Rolls, Dept. of Experimental Psychology, University of Oxford, South Parks Road, Oxford OX1 3UD, UK (E-mail: edmund.rolls{at}psy.ox.ac.uk).
Received 6 July 2000; accepted in final form 17 November 2000.
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REFERENCES |
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