Brain (1997), 120, 1675–1684
Regional cerebral blood flow during food exposure
in obese and normal-weight women
L. J. Karhunen,1,3 R. I. Lappalainen,2 E. J. Vanninen,4 J. T. Kuikka4 and M. I. J. Uusitupa1,3
1Department
of Clinical Nutrition and 2A. I. Virtanen
Institute, University of Kuopio, and 3Department of
Clinical Nutrition and 4Department of Clinical Physiology
and Nuclear Medicine, Kuopio University Hospital,
Kuopio, Finland
Correspondence to: Leila Karhunen, Department of
Clinical Nutrition, University of Kuopio, PO Box 1627
FIN-70211 Kuopio, Finland
Summary
The cerebral responses elicited by the sight of food and foodrelated cues are poorly known in humans. Therefore, regional
cerebral blood flow (rCBF) was measured during food
exposure in 11 obese and 12 normal-weight women. The
rCBF was mapped while the subject was looking at a picture
of a landscape (control) or at a portion of food (food
exposure), and was measured by 99mTc-ethyl-cysteine-dimer
single photon emission computed tomography. In the obese
women, the rCBF was higher in the right parietal and
temporal cortices during the food exposure than in the control
condition. In addition, in the obese women the activation of
the right parietal cortex was associated with an enhanced
feeling of hunger when looking at food. No such changes or
associations were seen in the normal-weight women. In
conclusion, exposure to food is associated with increases in
the rCBF of right parietal and temporal cortices in obese
women, but not in normal-weight women.
Keywords: cerebral blood flow; food; hunger; obesity; SPECT
Abbreviations: rCBF 5 regional cerebral blood flow; SPECT 5 single photon emission tomography
Introduction
Environmental as well as internal physiological cues can
control emotional and physiological responses associated
with food intake (Wardle, 1990). These responses preceding
eating, called cephalic phase responses (Powley, 1977), may
play an important anticipatory role by preparing the organism
for food ingestion (Powley and Berthoud, 1985). They can
also be seen as classically conditioned responses to cues that
have come to predict food intake, for example the sight,
smell or thought of food (Wardle, 1990; Lappalainen and
Sjödén, 1992). Some authors have attributed the development
and maintenance of human obesity and eating disorders to
inappropriately conditioned cephalic phase responses
(Storlien and Bruce, 1989; Jansen, 1994).
Recently, much interest has been devoted to the theoretical
basis and clinical applications of cue exposure in addictive
behaviours based on classical conditioning theory
(Drummond et al., 1995). Accordingly, it is supposed that
the response a subject makes to the cue is dependent on the
previous experience he/she has had with that cue. A cue
that has been repeatedly paired with eating (unconditioned
© Oxford University Press 1997
stimulus) can be viewed as a conditioned stimulus (e.g.
seeing food) which, when a subject is exposed to it (the cue
alone), can elicit a conditioned response (e.g. salivation or
insulin release). Reactivity to food-related cues has been
repeatedly observed in humans (Rodin, 1985; Lappalainen
et al., 1994). Moreover, some promising results have been
reported in binge eating when a conditioned stimulus–
unconditioned stimulus bond has been broken by prolonged
exposure with response prevention (Jansen et al., 1992). This
is in accordance with the experiences of the cue-exposure
treatment in alcohol (Rohsenow et al., 1995), and opiate and
cocaine dependence (Dawe and Powell, 1995). Methods
based on the cue-reactivity phenomena may, therefore, be
useful in the treatment of obesity and eating disorders.
There is evidence for anticipatory neural activity associated
with cues predicting food. There are populations of neurons
in the hypothalamus, amygdala and orbitofrontal cortex of
the nonhuman primates which respond to the sight of food
and are influenced by learning (Rolls, 1994). In addition, the
amygdala is involved in the causation of the conditioned
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L. J. Karhunen et al.
cephalic phase insulin response (Roozendaal et al., 1990),
and the projections from the hypothalamus to the brainstem
autonomic motor nuclei may provide a route by which foodrelated cues generate the conditioned autonomic responses,
such as salivation and insulin release (Rolls, 1994). The
striatum, in turn, may provide a route for learned stimuli
to influence behavioural responses by bringing together
information from many parts of the limbic system and the
cerebral cortex. Furthermore, the cortical areas, critical to
the control of sophisticated intentions and emotions in human
subjects, are expected to contribute to the control of eating
(Booth, 1994). The cortical areas, such as orbitofrontal,
prefrontal, frontal and temporal cortices, have also been
shown to be involved in human classical conditioning
(Hugdahl et al., 1995).
Advances in the understanding of eating and obesity require
multiple analysis of eating behaviour, and as pointed out by
Drummond et al. (1995), it is a scientific challenge to explain
the cue-reactivity phenomena. However, only a limited
information is available concerning the cerebral responses
related to eating in human subjects. Furthermore, the cerebral
responses during the cephalic phase of eating and their
associations with the emotional and peripheral physiological
responses, are not known. Therefore, the purpose of the
present study was to examine rCBF, and emotional and
peripheral physiological responses simultaneously, in obese
and normal-weight women, during exposure to food and
food-related cues.
Methods
Subjects
Eleven women with long-lasting obesity, duration of
obesity (mean 6 SD) 18 6 9 years (range 5–30 years),
with a current body mass index of 32.7 6 4.0 kg/m2 (24.7–
39.1 kg/m2) and 12 women of normal weight, i.e. 22.2 6
1.6 kg/m2 (20.3–24.6 kg/m2) kg/m2, who had never been
obese, participated in the study. The mean ages of the subjects
were 45.0 6 10.0 (28–56) years and 39.8 6 9.7 (25–53)
years, respectively. All subjects were right-handed and healthy
as established by medical and psychiatric history, and routine
laboratory tests, and they did not have any eating disorders
as established by the clinical interview and from their
response to the bulimia questionnaire BITE (Henderson and
Freeman, 1987). The group of obese women was studied
first, and then the group of normal-weight women. The obese
subjects were recruited from the participants of a weightreduction programme carried out at the University of Kuopio,
and at the time of the study, they had completed an active
weight loss period of the programme. The mean weight
change from the beginning of this programme to the present
study (i.e. over a 1.5–2.5-year period) was –5.5 6 8.9
(–25.1 to 13.8) kg. All obese subjects had participated
in our former studies on cephalic phase insulin secretion
(Karhunen et al., 1996, 1997). The normal-weight subjects
Fig. 1 The study design, where: ↑ 5 blood sampling; H 5
assessment of feeling of hunger; D 5 assessment of desire to eat;
T 5 injection of tracer; and SPECT 5 single photon emission
computed tomography scan. The study design was the same in the
control and food-exposure experiments, except that feeling of
hunger (H) and desire to eat (D) were assessed only during the
food-exposure experiment.
were recruited into the study from the university staff. After
complete description of the study to the subjects, written
informed consent was obtained. The study was approved by
the Ethics Committee of the University of Kuopio and was
in accordance with the Helsinki declaration.
Procedure
The study consisted of two experiments: the control and the
food exposure. Based on the current thinking of Pavlovian
conditioning, that the conditioned associations are formed
not just between the primary events presented, but with the
whole context in which they are presented (Rescorla, 1988),
all subjects experienced the control stimulus first, in order to
avoid conditioned anticipatory responses during the control
experiment.
The experiments were performed after an overnight fast
on two separate days between 09.00 and 12.00 hours. The
time between the control experiment and the food-exposure
experiment was ~20.6 6 21.5 days (range 3–72 days), i.e.
20.8 6 20.6 days (range 6–62 days) in obese women and
20.4 6 23.3 days (range 3–72 days) in normal-weight women.
The exceptionally long time period (.30 days) between the
two experiments in two normal-weight and two obese women
were due to technical problems and a hospital strike during
the time of the study, respectively. However, there had been
no weight changes between the two experiments.
Both the control and food-exposure experiments consisted
of two parts: a baseline (8 min) and exposure to a stimulus
(12 min) (Fig. 1). The rCBF was mapped at the beginning
of the exposure period while the subject was sitting in front
of a table and was looking at a control or food stimulus at a
distance of 50 cm. During the injection of the tracer, the
subject was advised to remain silent and relaxed, and to
concentrate on looking at the stimulus. Blood samples were
taken at 2-min intervals during the baseline and exposure
periods. In addition, during the food-exposure experiment,
the feeling of hunger and desire to eat were assessed three
times: before, at the beginning and at the end of food
exposure (Fig. 1). They were not assessed during the control
experiment in order to keep it totally free from food cues.
At the end of both experiments, the subject rated the
pleasantness of the experiment and the food she had eaten.
Cerebral responses to food
Control stimulus
A colourful picture of a landscape (41 cm wide and 31.5 cm
high) was used as a stimulus in the control experiment. It
was placed on the table in front of the subject just before
the injection of the tracer. The control exposure and the
baseline periods of both experiments were performed at
the hospital in a room free from food-related cues.
Food stimulus
A warm lunch, consisting of a self-selected warm main
course, a salad, bread, a beverage and a dessert, was used as
a stimulus in the food-exposure experiment. The foodexposure period was performed in a kitchen, adjacent to the
room where the baseline test had taken place. The food was
on the table in front of the subject during the injection of
the tracer and for the whole duration of the food-exposure
period. To confirm that the subject really liked the food, and
had also had a prior experience of eating it in that particular
situation, the subject was allowed to choose and eat a similar
lunch after the control experiment. However, she was not
told then, that the lunch would be a part of the second
experiment.
Blood samples
Blood samples for the determination of serum insulin and
plasma glucose concentrations were taken five times during
the baseline period and five times during the exposure periods
(Fig. 1). In addition, plasma noradrenalin concentrations were
determined from samples taken at the end of each period.
The blood samples were taken through an intravenous
cannula inserted into the subject’s antecubial vein 15 min
before the first samples were taken. The samples were
placed in pre-chilled tubes, and centrifuged and stored without
delay at –70°C until analysed. Blood samples could not be
obtained from one obese subject due to technical difficulties.
Emotional responses
The feeling of hunger and desire to eat were determined
with 10-cm visual analogue scales ranging from ‘absent’ to
‘extreme’, and the pleasantness of the experiment and of the
lunch eaten were determined with nine-point category scales.
The feeling of hunger was defined as a general feeling with
no specific food item in mind, and the desire to eat as a
specific desire to eat the exposed food when looking at or
thinking of it. Due to the technical difficulties in the blood
sampling (see above) the assessments of feeling of hunger
and desire to eat were not available for one obese subject.
1677
Kastrup, Denmark) was intravenously injected into the
subject’s antecubital vein. The SPECT scan was carried out
45 min later with a three-head Siemens MultiSPECT 3
gamma camera equipped with fan beam collimators (Siemens
Medical Systems, Hoffman Estates, Ill., USA) (Kuikka et al.,
1993). The subject’s head was positioned similarly in both
scans using positioning lasers in a head-holder specifically
built for the Siemens MultiSPECT 3. In total, 5–7 million
counts were acquired for the entire head using an angular
step of 3° over 360° (matrix size 1283128 and 120
projections). The imaging resolution was 7–8 mm. The
radiation load on the subject from the two experiments was
moderate, being 6–8 mSv (effective dose equivalent).
Transaxial (oriented in orbitomeatal line), sagittal and
coronal slices (3 mm thick) were reconstructed using the
Chang attenuation correction with a uniform attenuation
coefficient of 0.1 per cm. In addition, three-dimensional
surface shaded plots were used in preliminary visual
evaluations and for illustrative purposes (Fig. 2). Two
consecutive transaxial slices were combined in order to obtain
a slice thickness of 6 mm, and saved onto a hard disk for a
further analysis.
A semi-automatic brain quantification program of
Siemens was used to analyse the regions of interest (Fig. 3).
First, the slices were rotated and realigned so that transaxial
(x-direction), sagittal (y-direction) and coronal (z-direction)
ones were at right angles to each other. Secondly, the regions
of interest were drawn onto aligned transaxial slices on the
right and then mirrored on the left. The following regions
were used: cerebellum, amygdala (certainly including some
other parts of the temporal lobe, e.g. hippocampus),
hypothalamus, prefrontal cortex, temporal cortex, occipital
cortex, basal ganglia, thalamus, frontal cortex and parietal
cortex (Fig. 3). The average regional counts were normalized
relative to the mean cerebellar counts. It was reasoned that
the normalization of the regional counts with the mean
cerebellar counts would take into account any uncontrollable
non-specific stimulation, if any, between the experiments,
unrelated to the manipulated stimuli. The cerebellum was
used as a reference region because the reactivity of the
cerebellum to the sight of food or a picture was expected to
be minimal and not different from each other.
Biochemical analyses
Plasma glucose was measured by a glucose oxidase method
(Glucose Auto and Stat, Model GA-110, Daiici, Kyoto,
Japan), a radioimmunoassay method was used for the
measurement of serum insulin (Phadeseph Insulin RIA 100,
Pharmacia Diagnostics, Uppsala, Sweden), and plasma
noradrenalin concentrations were determined with a high
pressure liquid chromatography.
Single photon emission computed tomography
(SPECT)
Statistical analyses
For determining the rCBF, a dose of 550 MBq of 99mTc-ethylcysteine-dimer (Neurolite, DuPont Pharma/Durham APS,
The differences in the rCBF between the control and foodexposure experiments were analysed using the Wilcoxon
1678
L. J. Karhunen et al.
Fig. 2 An example of three-dimensional 99mTc-ethyl-cysteine-dimer SPECT surface-shaded image sets
in the control (lower panels) and food-exposure (upper panels) experiments, in a 54-year-old obese
subject. Note the increased uptake in her right parietal cortex as well as in the right temporal cortex
(upper panel, left).
matched-pairs test. The Friedman one-way analysis of
variance and the Wilcoxon matched-pairs tests were used to
analyse the changes in the peripheral physiological and
subjective measurements during the experiment. Spearman
rank correlation coefficients were used to analyse the
relationship of the emotional and peripheral physiological
responses to the rCBF in the cerebral regions showing
significant changes between the control and food-exposure
experiments. All the analyses were performed separately
in the obese and normal-weight groups. The differences
between the obese and normal-weight groups were analysed
using the Mann–Whitney U test. The results are expressed
as mean 6 SD. A value of P , 0.05 was set as the criterion for
statistical significance. All statistical analyses were performed
with the SPSS for Windows statistic program (SPSS, Chicago,
Ill., USA).
Results
The control and the food-exposure experiments were carried
out in comparable situations (Table 1). The cerebellar CBF
results (total counts) were also comparable in both
experiments (215 6 50 versus 208 6 42 counts/voxel in
obese subjects with P 5 0.53, and 235 6 40 versus 221 6
31 counts/voxel in normal-weight subjects with P 5 0.09;
control versus food exposure, respectively). There were no
significant differences in cerebellar CBF between the obese
and normal-weight groups either; in the control experiment
P 5 0.39 and in the food-exposure experiment P 5 0.18.
The rCBF results are all normalized relative to cerebellum
CBF counts.
The obese subjects had significantly lower rCBF in the
temporal and parietal cortices bilaterally during the control
experiment, as well as in the left parietal cortex during the
food-exposure experiment as compared with the normalweight subjects (Table 2). Furthermore, the obese subjects
had greater rCBF on the right side than on the left of the
parietal cortex and thalamus compared with the normalweight subjects during the food exposure; for parietal cortex
rCBF (right/left) 5 1.04 6 0.05 versus 0.99 6 0.04 with
P 5 0.02, and for thalamus rCBF (right/left) 5 1.05 6 0.05
Cerebral responses to food
1679
Fig. 3 Regions of interest used in the measurement of rCBF: cerebellum (upper panel, left); amygdala (upper panel, middle);
hypothalamus (upper panel, right); prefrontal, temporal and occipital cortex, basal ganglia and thalamus (lower panel, left); frontal and
parietal cortex (lower panel, right).
versus 1.00 6 0.04, P 5 0.03, obese versus normal-weight
subjects, respectively).
The rCBF of the right parietal and right temporal cortices
increased significantly from the control to the food-exposure
experiment in the obese women (Table 2, Fig. 2). No
significant changes in the rCBF were observed between the
two experiments in the normal-weight women.
In the obese women, the rCBF of the right parietal cortex,
as mapped during the food exposure, correlated positively
with the change in the feeling of hunger on seeing food
(r 5 0.66, P 5 0.04, n 5 10) (i.e. the change from H1 to
H2 in Fig. 1). Thus, the greater the increase in the feeling
of hunger in response to seeing food, the higher the rCBF
in the right parietal cortex during the food exposure. The
normal-weight women did not show any significant
associations between the rCBF and the emotional responses
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L. J. Karhunen et al.
Table 1 The experimental conditions in the control and food-exposure experiments
Obese subjects
Normal-weight subjects
Control
Time experiment started (h)
Dose of the tracer (MBq)
Duration of the fast (h)
Pleasantness of the experiment*
Pleasantness of the lunch*
*A
10.2
554
14.4
7.0
8.5
6
6
6
6
6
0.6
12
1.1
0.8
0.5
Food exposure
Control
10.3 6 0.7
558 6 15
14.6 6 1.2
6.4 6 0.9
8.5 6 0.7
10.3
546
13.8
6.8
8.3
6
6
6
6
6
Food exposure
0.8
39
1.0
1.5
0.8
10.2
559
13.7
6.1
7.8
6
6
6
6
6
0.8
17
0.9
1.2
1.1
nine-point category scale. Values are means 6 SD.
Table 2 Control and food-exposure experiments in obese and normal-weight women: rCBF normalized to cerebellar CBF
Cerebral region
Prefrontal
Right
Left
Frontal
Right
Left
Temporal
Right
Left
Parietal
Right
Left
Occipital
Right
Left
Thalamus
Right
Left
Basal ganglia
Right
Left
Amygdala
Right
Left
Hypothalamus
rCBF in obese women
rCBF in normal-weight women
Control
Food exposure
P-value†
Control
Food exposure
P-value†
0.93 6 0.06
0.90 6 0.06
0.94 6 0.08
0.88 6 0.07
0.86
0.48
0.91 6 0.05
0.89 6 0.06
0.93 6 0.10
0.90 6 0.10
0.39
0.69
0.99 6 0.05
0.96 6 0.04
0.99 6 0.06
0.96 6 0.05
0.48
0.79
1.00 6 0.05
0.96 6 0.04
1.01 6 0.07
0.97 6 0.08
0.39
0.86
0.99 6 0.04
0.97 6 0.04
1.02 6 0.06
1.00 6 0.09
0.04
0.13
1.04 6 0.06*
1.03 6 0.06**
1.05 6 0.08
1.03 6 0.09
0.81
0.75
0.93 6 0.05
0.93 6 0.05
0.97 6 0.06
0.94 6 0.08
0.01
0.37
1.05 6 0.07***
1.06 6 0.08****
1.05 6 0.11
1.07 6 0.13*
0.88
0.88
1.21 6 0.08
1.16 6 0.10
1.24 6 0.10
1.19 6 0.11
0.15
0.21
1.23 6 0.09
1.18 6 0.09
1.22 6 0.12
1.19 6 0.10
0.88
0.69
1.14 6 0.08
1.11 6 0.09
1.17 6 0.08
1.11 6 0.08
0.53
0.93
1.15 6 0.07
1.16 6 0.06
1.16 6 0.07
1.17 6 0.11
0.64
0.48
1.16 6 0.04
1.16 6 0.06
1.18 6 0.06
1.18 6 0.05
0.37
0.21
1.17 6 0.05
1.19 6 0.06
1.18 6 0.10
1.20 6 0.09
0.69
1.00
0.88 6 0.07
0.88 6 0.07
0.88 6 0.09
0.89 6 0.09
0.88 6 0.08
0.92 6 0.07
0.79
0.72
0.11
0.84 6 0.06
0.82 6 0.08
0.89 6 0.05
0.84 6 0.08
0.83 6 0.10
0.89 6 0.05
0.81
0.64
0.75
Means 6 SD are shown. †Difference between control and food-exposure experiment. *P 5 0.01;
****P 5 0.0003 (differences between the obese and normal-weight subjects).
during the food exposure. However, both the feeling of
hunger and the desire to eat did increase significantly in both
groups during the exposure to food (Table 3).
As would be expected, the concentrations of serum insulin
and plasma glucose were higher in the obese than in the
normal-weight subjects (Table 3). Neither the serum insulin
nor the plasma glucose concentrations changed significantly
during the two experiments in either group.
The baseline plasma noradrenalin concentrations were not
significantly different between the control and food-exposure
experiments in the obese or normal-weight groups (Table 3).
Instead, both obese and normal-weight subjects showed a
significant increase in the plasma noradrenalin concentration
**P
5 0.02; ***P 5 0.0009;
during the food exposure, whereas there were no significant
changes in the plasma noradrenalin concentrations during the
control experiment (Table 3).
Examples of the individual cerebral, peripheral and
emotional responses in the obese group are shown in Fig. 4.
Discussion
In the obese women, the exposure to food was associated
with increased rCBF in the right parietal and right temporal
cortices compared with the exposure to the non-food cues.
The obese women also had greater rCBF on the right side
of the parietal cortex and the thalamus than on the left during
Cerebral responses to food
1681
Table 3 The emotional and peripheral physiological responses during baseline and exposure periods in control and foodexposure experiments
Obese women
Normal-weight women
Control
Feeling of hunger†
Desire to eat†
Noradrenalin (nmol/l serum)
Insulin‡ (pmol/l serum)
Glucose‡ (nmol/l plasma)
Food exposure
Baseline
Exposure
Baseline
–
–
2.44 6 0.88
55.8 6 24.6
5.6 6 0.4
–
–
2.77 6 0.48
52.2 6 22.2
5.6 6 0.4
3.9
4.2
2.15
55.8
5.4
6
6
6
6
6
2.2
2.5
0.57
39.0
0.6
Control
Exposure
5.8
6.7
2.62
56.4
5.4
6
6
6
6
6
2.2**
2.2***
0.72****
45.6
0.6
Food exposure
Baseline
Exposure
Baseline
–
–
2.81 6 1.22
38.4 614.4*
4.9 6 0.3*
–
–
3.09 6 1.24
35.4 6 12.6*
4.9 6 0.4*
4.0
5.4
2.58
35.4
5.0
6
6
6
6
6
2.4
2.4
1.04
9.0*
0.3*
Exposure
6.1
7.1
2.94
33.6
5.0
6
6
6
6
6
2.8**
2.2***
1.34****
9.6*
0.2*
Means 6 SD are shown. †On a 10-cm visual analogue scale. ‡The values are means of five measurements from each period. *P , 0.05 for all obese versus normal
group comparisons. **Changes from baseline to beginning of food exposure: P 5 0.03 (obese group) and P 5 0.002 (normal group). ***Changes from baseline to
beginning of food exposure: P 5 0.009 (obese group) and P 5 0.01 (normal group). ****Changes from baseline to end of food exposure: P 5 0.007 (obese group)
and P 5 0.03 (normal group).
Fig. 4 Summary of results from individual obese subjects.
Changes, from the control to the food-exposure experiment, in the
rCBF of (A) right parietal and (B) right temporal cortex. Changes
during the food-exposure experiment, from the baseline to foodexposure, in (C) serum insulin (calculated from the means of five
samples taken during each of the baseline and food-exposure
periods), (D) plasma noradrenalin, (E) feeling of hunger and (F)
desire to eat. VAS 5 visual analogue scale.
food exposure, compared with the normal-weight subjects.
Interestingly, in the obese group, the rCBF of the right
parietal cortex was, in addition, associated with the enhanced
feeling of hunger.
The right hemisphere is known to be specialized for the
recognition and control of emotional expressions and related
behaviours (Silberman and Weingartner, 1986), as well as
for learning of the conditioned associations (Johnsen and
Hugdahl, 1994). Furthermore, glucose metabolism in the
right parietal cortex, as examined by PET, has been found
to correlate positively with the frequency of binge-eating
episodes in bulimic patients (Andreason et al., 1992).
Accordingly, although the obese women of the present study
were not binge eaters, it is possible that the increase in the
rCBF of the right parietal cortex due to exposure to food
could be associated with the difficulties in the control of
eating, and in that way even in the development of obesity.
On the other hand, all women in the obese group had sought
treatment for their obesity, and had had to pay attention to
their eating. The significance of food could therefore be
different for the obese and normal-weight women, thus
possibly explaining the different cerebral responses to food
in these two groups. In fact, the responses of cortical neurons
in the parietal and temporal regions to a given visual stimulus
have been shown to depend on the behavioural significance
of that stimulus to the observer (Maunsell, 1995). Yet, the
question whether the increase in rCBF of the right parietal
and temporal regions in response to exposure to food was a
cause or an effect of obesity, cannot be answered on the
basis of this study.
However, a point not to be overlooked was that the obese
subjects had lower rCBF on both sides of temporal and
parietal cortices during the control experiment compared with
the normal-weight subjects. Thus, the increase in the rCBF
of right parietal and temporal cortices could, alternatively,
be due to an initially low rCBF in these cerebral regions
during the control experiment. However, even in that case,
the finding of increased rCBF in the right side of the parietal
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L. J. Karhunen et al.
and temporal regions and, moreover, the association of the
rCBF of the right parietal cortex with the increased feeling
of hunger among the obese subjects during food exposure is
interesting. Thus, despite the potential rCBF defect in these
cerebral regions in the obese group, the role of right parietal
cortex in the presence of food cues among these subjects
was especially emphasized in the present study.
Paradoxically, hypometabolism of cortical, especially left
parietal, regions has also been observed in patients with
anorexia nervosa (Nozoe et al., 1995; Delvenne et al.,
1995, 1996). Although weight gain has been associated with
increased rCBF in the cortical regions, a trend toward relative
hypometabolism in the parietal cortex does remain in anorexic
patients, even after weight gain (Delvenne et al., 1996). The
obese subjects in the present study did not have any eating
disorders, but they had controlled their eating for a quite
long period of time. Anorexic patients do continuously control
their eating, and these ‘similarities’ in eating histories might
explain the similarity of the rCBF results in the anorexic
patients and our obese subjects. In line with this, the
differences in the eating and weight histories between the
obese and the normal-weight women (who had never been
obese) could explain the different rCBF in these two groups.
However, due to the study design the comparisons between
the obese and normal-weight groups have to be interpreted
with caution.
The right middle occipital gyrus, close to the area we
found to be involved in the sight of food in the obese
subjects, has recently been found to be speciliazed for picturespecific processing (Vandenberghe et al., 1996). However,
in the present study, the influence of the picture-specific
processing on rCBF was obtained in the control experiment
and subtracted from the ‘food cue’ results, so that the
increased rCBF in the right parietal region near the occipital
gyrus can therefore considered to be representative of the
food-related characteristics of the stimulus. Moreover,
the increase in rCBF in the parietal and temporal regions of
the obese women was not explained by the different arousal
levels between the experiments. The frontal lobe is the
cortical region having the most intimate connections with
the arousal system (Nauta, 1971). However, there were no
differences in the rCBF of the frontal regions between the
two experiments either in the obese or normal-weight groups.
Finally, parietal and temporal cortices are known to be
specialized for the processing of characteristics related, for
example, to colour, texture or shape, of the visual objects
(Maunsell, 1995). The differences in the rCBF between
the experiments could, therefore, be argued to be due to
characteristic differences between the food and control
stimuli. However, the absence of the food-elicited increase
in the rCBF of those cortical regions in the normal-weight
women does not support this view.
Nevertheless, although the cerebral responses to food
exposure were different in the obese and normal-weight
women, both groups showed comparable emotional responses
to the food. Subjective perceptions, e.g. wanting and liking
of food, are products of active reconstructions by cognitive
mechanisms of sensory, affective and memory processes
(Berridge, 1996). Accordingly, it has been suggested that
the subjective reports could contain false assessments of
underlying cerebral processes. This might explain the
apparent discrepancy between differing cerebral responses
and comparable emotional responses in the obese and normalweight subjects, in response to food.
The absence of cephalic phase insulin secretion during the
food exposure was unexpected. However, immediate affective
or cognitive alterations can determine conditioned cephalic
phase responses, and many factors associated with the
procedure are likely to interfere with, and modify, the
peripheral responses, for example stress experienced during
the experimental situation (Bellisle et al., 1983). In fact, in
the present study the plasma noradrenalin levels increased
during the food-exposure experiment, both in the obese and
normal-weight subjects, providing a plausible explanation
for the absence of cephalic phase insulin secretion (Teff
et al., 1993). On the other hand, the elevated noradrenalin
levels during the cephalic phase of eating have been suggested
to be mediated by the sensory stimulation associated with
the palatability of food (Diamond and LeBlanc, 1988;
LeBlanc et al., 1991). Therefore, the increased noradrenalin
concentrations during food exposure could also be induced
by the food-related characteristics of the stimulus used in the
present study.
The control and food-exposure experiments were not
performed in a random order; this was to avoid the anticipation
of food during the control condition, since the current view
that Pavlovian conditioning is associated with the whole
context in which the conditioned events are presented
(Rescorla, 1988). Furthermore, we had observed in our
earlier study that conditioning of cephalic phase responses
to delicious food stimuli can occur on a single occasion
(Lappalainen et al., 1994). Moreover, expectations can
modulate responses. Cephalic phase insulin responses have
been found to be altered when subjects have been informed
that they are to have nothing to eat in a situation where they
have expected something to eat (Bellisle et al., 1985), as
would have been the case in the present study if the
experiments had been performed in the random order.
Therefore, we cannot rule out the possibility that the responses
in the second experiment (food exposure) may have been
influenced by familiarity with the procedure. Nevertheless,
both experiments were carried out in comparable situations
with both obese and normal-weight subjects and the possible
effect of the unrandomized order could be expected to be
the same in both groups.
In conclusion, exposure to food is associated with an
increase in the rCBF of right parietal and temporal cortices
in obese women, but not in normal-weight women.
Furthermore, in obese women, right parietal cortex activation
was associated with an enhanced feeling of hunger with
exposure to food. Increased rCBF in these cortical regions
in the presence of food in obese women could, thus, be due
Cerebral responses to food
to a greater cerebral reactivity to food, but alternatively could
also be affected by initially low rCBF in these regions.
The significance of these findings regarding human eating
behaviour and obesity needs to be examined further.
Acknowledgements
The authors wish to thank Drs Jari Tiihonen, Asla Pitkänen
and Jouni Sirviö for their valuable comments on this study
and manuscript, and Kaija Kettunen for her excellent technical
assistance. This study was supported by grants from F.
Hoffman-La Roche to the University of Kuopio, Kuopio
University Hospital, the Academy of Finland, Research
Council for Health, the Yrjö Jahnsson Foundation, the Juno
Vainio Foundation and the Finnish Cultural Foundation.
References
Andreason PJ, Altemus M, Zametkin AJ, King AC, Lucinio J,
Cohen RM. Regional cerebral glucose metabolism in bulimia
nervosa [published erratum appears in Am J Psychiatry 1993; 150:
174]. Am J Psychiatry 1992; 149: 1506–13.
Bellisle F, Louis-Sylvestre J, Demozay F, Blazy D, Le Magnen J.
Reflex insulin response associated to food intake in human subjects.
Physiol Behav 1983; 31: 515–21.
Bellisle F, Louis-Sylvestre J, Demozay F, Blazy D, Le Magnen J.
Cephalic phase of insulin secretion and food stimulation in humans:
a new perspective. Am J Physiol 1985; 249: E639–45.
Berridge KC. Food reward: brain substrates of wanting and liking.
[Review]. Neurosci Biobehav Rev 1996; 20: 1–25.
Booth DA, editor. Psychology of nutrition. London: Taylor and
Francis, 1994.
Dawe S, Powell JH. Cue exposure treatment in opiate and cocaine
dependence. In: Drummond DC, Tiffany ST, Glautier S, Remington
B, editors. Addictive behaviour: cue exposure theory and practice.
Chichester: John Wiley, 1995: 197–209.
1683
Baker DP, et al. Brain mechanisms in human classical conditioning:
a PET blood flow study. Neuroreport 1995; 6: 1723–8.
Jansen A. The learned nature of binge eating. In: Legg CR, Booth
D, editors. Appetite: neural and behavioural bases. Oxford: Oxford
University Press, 1994: 193–211.
Jansen A, Broekmate J, Heymans M. Cue-exposure vs self-control
in the treatment of binge eating: a pilot study. Behav Res Ther
1992; 30: 235–41.
Johnsen BH, Hugdahl K. Brain asymmetry and autonomic
conditioning: sensitization control. Integr Physiol Behav Sci 1994;
29: 395–405.
Karhunen LJ, Lappalainen RI, Niskanen LK, Turpeinen AK,
Uusitupa MI. Determinants of the cephalic-phase insulin response
in obese nondiabetic subjects. Metabolism 1996; 45: 168–73.
Karhunen L, Lappalainen R, Tammela L, Turpeinen A, Uusitupa
M. Subjective and physiological cephalic phase responses in obese
women with binge eating. Int J Eat Disord 1997; 21: 321–8.
Kuikka JT, Tenhunen-Eskelinen M, Jurvelin J, Kiiliänen H. Physical
performance of the Siemens MultiSPECT 3 gamma camera. Nucl
Med Commun 1993; 14: 490–7.
Lappalainen R, Sjödén P-O. A functional analysis of food habits.
Scand J Nutr 1992; 36: 125–33.
Lappalainen R, Sjödén P-O, Karhunen L, Gladh V, Lesinska D.
Inhibition of anticipatory salivation and craving in response to food
stimuli. Physiol Behav 1994; 56: 393–8.
Le Blanc J, Diamond P, Nadeau A. Thermogenic and hormonal
responses to palatable protein and carbohydrate-rich food. Horm
Metab Res 1991; 23: 336–40.
Maunsell JHR. The brain’s visual world: representation of visual
targets in cerebral cortex. [Review]. Science 1995; 270: 764–9.
Nauta WJH. The problem of the frontal lobe: a reinterpretation.
[Review]. J Psychiatr Res 1971; 8: 167–87.
Nozoe S-I, Naruo T, Yonekura R, Nakabeppu Y, Soejima Y, Nagai
N, et al. Comparison of regional cerebral blood flow in patients
with eating disorders. Brain Res Bull 1995; 36: 251–5.
Delvenne V, Lotstra F, Goldman S, Biver F, De Maertelaer V,
Appelboom-Fondu J, et al. Brain hypometabolism of glucose in
anorexia nervosa: a PET scan study. Biol Psychiatry 1995; 37: 161–9.
Powley TL. The ventromedial hypothalamic syndrome, satiety, and
a cephalic phase hypothesis. [Review]. Psychol Rev 1977; 84:
89–126.
Delvenne V, Goldman S, De Maertelaer V, Simon Y, Luxen A,
Lotstra F. Brain hypometabolism of glucose in anorexia nervosa:
normalization after weight gain. Biol Psychiatry 1996; 40: 761–8.
Powley TL, Berthoud HR. Diet and cephalic phase insulin responses.
Am J Clin Nutr 1985; 42 (5 Suppl): 991–1002.
Diamond P, LeBlanc J. A role for insulin in cephalic phase of
postprandial thermogenesis in dogs. Am J Physiol 1988; 254:
E625–32.
Drummond DC, Tiffany ST, Glautier S, Remington B. Cue exposure
in understanding and treating addictive behaviours. In: Drummond
DC, Tiffany ST, Glautier S, Remington B, editors. Addictive
behaviour: cue exposure theory and practice. Chichester: John
Wiley, 1995: 1–17.
Henderson M, Freeman CPL. A self-rating scale for bulimia. The
‘BITE’. Br J Psychiatry 1987; 150: 18–24.
Hugdahl K, Berardi A, Thompson WL, Kosslyn SM, Macy R,
Rescorla RA. Pavlovian conditioning. It’s not what you think it is.
Am Psychol 1988; 43: 151–60.
Rodin J. Insulin levels, hunger, and food intake: an example of
feedback loops in body weight regulation. Health Psychol 1985; 4:
1–24.
Rohsenow DJ, Monti PM, Abrams DB. Cue exposure treatment in
alcohol dependence. In: Drummond DC, Tiffany ST, Glautier S,
Remington B, editors. Addictive behaviour: cue exposure theory
and practice. Chichester: John Wiley, 1995: 169–196.
Rolls ET. Neural processing related to feeding in primates. In: Legg
CR, Booth D, editors. Appetite: neural and behavioural bases.
Oxford: Oxford University Press, 1994: 11–53.
1684
L. J. Karhunen et al.
Roozendaal B, Oldenburger WP, Strubbe JH, Koolhaas JM, Bohus
B. The central amygdala is involved in the conditioned but not in
the meal-induced cephalic insulin response in the rat. Neurosci Lett
1990; 116: 210–5.
Silberman EK, Weingartner H. Hemispheric lateralization of
functions related to emotion. [Review]. Brain Cogn 1986; 5: 322–53.
Storlien LH, Bruce DG. Mind over metabolism: the cephalic phase
in relation to non-insulin-dependent diabetes and obesity. [Review].
Biol Psychol 1989; 28: 3–23.
Teff KL, Levin BE, Engelman K. Oral sensory stimulation in men:
effects on insulin, C-peptide, and catecholamines. Am J Physiol
1993; 265: R1223–30.
Vandenberghe R, Price C, Wise R, Josephs O, Frackowiak RSJ.
Functional anatomy of a common semantic system for words and
pictures [letter]. Nature 1996; 383: 254–6.
Wardle J. Conditioning processes and cue exposure in the
modification of excessive eating. [Review]. Addict Behav 1990; 15:
387–93.
Received February 6, 1997. Accepted May 6, 1997