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Functional MRI and Sensory Perception of Food

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Functional MRI and Sensory Perception
of Food

J.M. Bonny, C. Sinding, and T. Thomas-Danguin

Abstract
Nowadays, human brain activity in response to complex paradigms can be
extensively mapped. Though introduced relatively recently, functional magnetic
resonance imaging (fMRI) based on blood-oxygen-level-dependent contrast has
developed dramatically. It is a noninvasive and exploratory approach which
provides in a relatively direct way a differentiated measure of each processing
step within the brain, the complete network giving access to cognitive mecha-
nisms. Compared with the other functional imaging methods, fMRI offers high
spatial and temporal resolution, and so can detail cognitive tasks both in space
and in time by following the time course of the operations. This review deals with
how this detailed breakdown is achieved. A further aim is to show how and why
fMRI can be used to study sensory perceptions that might, at first sight, seem hard
to address by this method, namely perceptions during eating. The processing of
stimuli from food by the brain is one determinant of food representation, but also
of food liking and wanting, which in turn control appetite, and ultimately food
intake. Food consumption also activates the reward system, which thus helps to
control food intake. fMRI experiments conducted with human subjects have
largely helped to gain a fuller understanding of these intricate brain processes.
Among the sensations triggered by food, visual, olfactory, gustatory, and somato-
sensory cues are the most salient. Accordingly, we focus here on these sensory
systems and on the integration of the two senses necessary to produce flavor
perception: namely olfaction and gustation.

J.M. Bonny (*)

AgroResonance – UR370 Qualité des Produits Animaux, INRA, Saint-Genès-Champanelle, France
e-mail: jean-marie.bonny@inra.fr
C. Sinding • T. Thomas-Danguin
Centre des Sciences du Goût et de l’Alimentation, INRA, AgroSup Dijon, CNRS, University of
Bourgogne Franche-Comté, Dijon, France
e-mail: charlotte.sinding@inra.fr; thierry.thomas-danguin@inra.fr

# Springer International Publishing AG 2017 1

G.A. Webb (ed.), Modern Magnetic Resonance,
DOI 10.1007/978-3-319-28275-6_132-1
2 J.M. Bonny et al.

Keywords
Functional • Magnetic resonance imaging • Human brain mapping • Blood-
oxygen-level-dependent (BOLD) • Olfaction • Gustation • Somatosensory •
Vision • Chemical senses • Integration

Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
fMRI Techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Olfaction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
Gustation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
Somatosensory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Exploration of Taste and Odor Integration in the Human Brain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
Vision . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
Conclusion and Perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

Introduction

Though introduced relatively recently, functional magnetic resonance imaging

(fMRI) has developed at lightning pace on two main fronts: acquisition methods
and analytical approaches. For human investigations, fMRI offers considerable
advantages in being both noninvasive and exploratory. The pulse response of the
vascular system to stimuli is about 20 s. In this time, it is possible to return to a
baseline and then apply further stimuli. In this way, brain responses induced by
complex paradigms can be studied in the course of a single experiment, while
integrating the necessary control conditions.
Functional neuroimaging is not, as sometimes alleged, a sophisticated form of
phrenology that identifies the cerebral location of cognitive functions whose exis-
tence and functional organization have already been independently established.
fMRI studies enable to analyze the internal organization of mental representations.
By examining activity in a brain structure, it provides in a relatively direct way a
differentiated measure of each processing step, the complete network giving access
to cognitive mechanisms. Compared with the other functional imaging methods
(PET, EEG, MEG), fMRI offers high spatial and temporal resolution, and so can
detail cognitive tasks both in space (decomposition of network activation schemes at
brain region scale, though not at neuron scale) and in time by following the time
course of the operations. This review deals with how this detailed breakdown is
achieved.
A further aim is to show how and why fMRI can be used to study sensory
perceptions that might, at first sight, seem hard to address by this method, namely
perceptions during eating. The processing of stimuli from food by the brain is one
determinant of food representation, but also of food liking and wanting, which in
turn control appetite, and ultimately food intake. Food consumption also activates
the reward system, which thus helps to control food intake. fMRI experiments
Functional MRI and Sensory Perception of Food 3

conducted with human subjects over the last 20 years have largely helped to gain a
fuller understanding of these intricate brain processes. Among the sensations trig-
gered by food, visual, olfactory, gustatory, and somatosensory (trigeminal) cues are
the most salient. Accordingly, we focus here on these sensory systems and on the
integration of the two senses necessary to produce flavor perception: namely olfac-
tion and gustation.

fMRI Techniques

When neurons are activated, local demand for oxygen and glucose causes an array of
cascading physiological events. Briefly, these result in dilation of vessels, and in
changes in cerebral blood flow and oxygen consumption by the neurons, leading to
variations in the concentration of deoxyhemoglobin and oxyhemoglobin. Owing to
the paramagnetism of deoxyhemoglobin (oxyhemoglobin is diamagnetic), trans-
verse (T2) relaxation is influenced by its concentration, so that variations in concen-
tration can be captured by MRI and used as an indirect measure of neuron activity.
The overwhelming majority of fMRI studies dedicated to food-related cues are based
on this blood-oxygen-level-dependent (BOLD) contrast. In essence, it is an indirect
method based on the coupling between activity and hemodynamics. The BOLD
signal is only a surrogate signature of neural activations, a feature that distinguishes
it from methods for measuring the neural electrical activity itself, for instance by
means of multichannel electrodes (EEG) or by optical imaging methods. It is thus
essential to examine the relationship between neural activity and the corresponding
hemodynamic response in terms of shape and other variables in amplitude, time, and
space.
First, the hemodynamic response to stimulation is much longer than the timescale
of neural spikes. The response to a short stimulus lasts approximately 20 s before
return to baseline. Although this rules out studying spiking frequency, it leaves
enough time to sample the BOLD response by imaging, several times, and through-
out the brain. This is mostly done using echoplanar imaging (EPI) fast sequences.
The major drawback of EPI is its sensitivity to the spatial inhomogeneities of the
magnetic field, originating from susceptibility differences near the interfaces
between different tissues or other components of the brain. The susceptibility
differences between air and soft tissues, and between soft tissues themselves, suffice
to produce magnetic field inhomogeneities in the human brain, especially at high
static magnetic fields. These macroscopic inhomogeneities are too weak to induce a
force inside the head, but are a source of various image artifacts (e.g., signal loss,
blurring, geometrical distortion, streaks), depending on the k-space trajectory. Such
susceptibility artifacts are especially salient in temporal and frontal regions, because
of the proximity of air and cortex near the sinus and ear canal. These magnetic field
gradients can modulate the BOLD sensitivity spatially, giving rise to different
amplitudes of BOLD response for the same underlying variation in transverse
relaxation due to hemodynamic changes. The examples most often given are those
of the primary olfactory cortex and the orbitofrontal cortex (OFC), involved in
4 J.M. Bonny et al.

particular in the reward coding, in which the gradients are so steep that it is not
always possible to detect activation. The experiment described by Mathiak et al. [1]
illustrates the misleading consequences of these local gradients. On presenting
emotional pictures of human facial expressions, they reported a lateralization of
amygdala responses depending on the phase-encoding polarity. This shows that
BOLD sensitivity is spatially variable, and depends in a complex manner on the
interaction between the susceptibility gradients and the encoding gradients of the
image.
At weak-to-moderate magnetic fields (<4 T), the EPI sequences used are gener-
ally based on a gradient echo to detect variations in T2*. T2* is a transverse
relaxation time resulting from the sum of a reversible component T20 (reversible in
that its effect can be eliminated with a spin echo) and an irreversible component T2
(T2  1 = T21 + T20  1). By cumulating the variations due to T2 and T20 , the
gradient echo-EPI approach allows better detection of low BOLD contrast values.
However, the combination of moderate magnetic field and gradient echo-EPI is
sensitive to signals from large vessels, and thus prone to localization errors. To
limit these errors and achieve a higher degree of spatial localization, spin echo-EPI
can be used, albeit with a marked loss of sensitivity. The use of this T2 contrast is
especially justified at higher field (>4 T), which reduces signals from large vessels
and enhances those from small ones. A further utility of spin echo-EPI is that it limits
the impact of susceptibility losses. This is only partly true owing to the EPI coding:
the static variations of T20 distort the k-space trajectory and significantly modify
BOLD sensitivity. The best demonstration of this effect was obtained at 7 T by
Goerke et al. [2] using a color-word matching Stroop task. They compared the
activations in the OFC detected from acquisitions by gradient echo-EPI, spin
echo-EPI, and RASER, a nonstandard encoding approach that leads to pure T2
weighting (i.e., with no T20 effect). Fig. 1 shows that only the maps obtained from
the pure T2-weighted time series show significant activations in the OFC. There is
also a small difference in BOLD sensitivity between gradient echo-EPI and spin-
echo-EPI.
For reasons of cost and availability, the great majority of fMRI studies dedicated
to the analysis of food-induced signals are conducted at medium-strength fields
(most often 1.5–3 T), with spatial resolutions of several millimeters (e.g., a voxel
volume of (3 mm)3 = 27 μl) and temporal resolutions of 2–3 s to have time to cover
the whole brain. However, there are many advantages to be gained from increasing
the spatial resolution. First, because standard spatial resolutions are far distant from
the intrinsic limit given by the hemodynamic point spread function, which is well
below 200 μm in width [3], and second, because it is obviously desirable to have
more spatially precise information. For example, Schoenfeld et al. [4] investigated
the neural representation of the four basic tastes by fMRI. They found spatially
different but overlapping activations for all the tastes investigated, subject to con-
siderable interindividual variability (see Fig. 4). In addition, we know that key
regions for food-induced signal processing, such as the insula, possess an extremely
complex functional topography [5, 6]. Hence, an excellent spatial resolution facili-
tates interpretation of the results. Methodologically, the expected benefits of
Functional MRI and Sensory Perception of Food 5

Fig. 1 t-Maps corresponding to GE-EPI, SE-EPI, and RASER acquisition schemes at 7 T. The
color code corresponds to congruent versus neutral and incongruent versus neutral condition of the
Stroop test. The t-maps are superimposed on a T1-weighted anatomical scan (Reprinted from
Goerke et al. [2], with permission from Elsevier)

reducing voxel volume are threefold. First, it is a straightforward solution to mitigate

BOLD-sensitivity modulations due to susceptibility artifacts; when voxel size is
reduced isotropically, its efficiency is furthermore immune to the orientation of static
magnetic field gradients, known to change rapidly over the brain. Second, it may be
advantageous to acquire images with a reduced voxel volume, in which thermal
noise dominates the physiological noise [7]. Third, the images are routinely spatially
smoothed in the analysis workflow of fMRI data, mainly to improve signal-to-noise
ratio and thus detection. A high resolution offers a greater possibility of adapting the
width of the smoothing kernel to the true size of activation and to its contrast-to-
noise ratio, both being unknown, which allows a higher percent signal change to be
obtained by a reduced partial volume effect, and thus stronger activations. Evidence
supporting high spatial resolution as a valuable solution for human BOLD fMRI at
3 T, especially for studying food-related stimuli, is given in [8].
6 J.M. Bonny et al.

However, desirable though it may be, improved spatial resolution is often

achieved at the expense of temporal resolution, simply because a greater k-space
demands a longer sampling time. To maintain temporal resolution without changing
the sequence, the simplest solution is to reduce the number of sections acquired and
so target certain regions of interest rather than the whole brain. For imaging larger
volumes at a high spatial resolution, several solutions have been developed, e.g.,
echo shifting, parallel acquisition, partial Fourier, or multiplexed EPI sequences, to
name the most popular. By combining the last two solutions, Feinberg et al. made
EPI acquisitions covering the whole brain (64 slices), with a voxel volume of
(2 mm)3 obtained in less than 500 ms at 3 T [9]. By operating in this way, the
simultaneous increase in spatial and temporal resolutions improves the BOLD
sensitivity, and not only at ultra-high field. However, these approaches are clearly
still under-exploited.
The postprocessing step is equally decisive for making use of information from
fMRI datasets. The conventional approach is based on a priori modeling of the signal
variations to optimize detection sensitivity. This requires a reliable hemodynamic
response model. Most studies assume an invariant hemodynamic model across brain
regions and subjects, despite much reported evidence for substantial variability in its
shape [10]. In the most popular approach, the signal time course obtained in each
voxel is modeled as a weighted sum of predefined models, each model being
obtained by convolving the on-off stimulation regressor with the hemodynamic
response function. This general linear model approach (GLM) has proved extremely
fruitful, although it has some drawbacks (see, e.g., [11] for a review). In practice, it is
well known that the inferences based on such statistical parametric modeling are
prone to false positives because the same (possibly misspecified) model has to be
repeatedly tested, i.e., voxelwise. These false detections should be controlled to infer
activations with more confidence (e.g., using family-wise error or false discovery
rate corrections). We note that these last have recently been criticized for being still
too permissive to make statistical inferences at cluster scale [12].
All these provisos tell us that BOLD fMRI needs to be handled with the greatest
caution because of its propensity to yield not only false positives but also false
negatives. Emphasizing this point, Gonzalez-Castillo et al. [10] have highlighted that
over 95% of the brain responds to repetitive visual stimulation, neatly suggesting
that the sparsity of activation maps obtained by BOLD fMRI is not a result of
localized brain function but stems instead from a lack of statistical power of the
whole chain (i.e., stimulation paradigm, acquisition, and statistical analysis). It is
likely that this conclusion also holds for the chemical senses elicited by food cues.
Because the response shapes have been shown to vary substantially across regions,
the model needs to be suitably adapted, i.e., less strictly specified than is often the
case using the canonic hemodynamic model. Data-driven methods are credible
solutions for this purpose, because they avoid a priori modeling of BOLD responses
to tasks. Of the different options, independent component analysis (ICA) is probably
the most popular. ICA splits the fMRI data into several independent sources, each
Functional MRI and Sensory Perception of Food 7

composed of a map showing its spatial distribution and a signal depicting its time
course. The statistical independence criterion can be applied either in time or in
space. Less computationally demanding, the most widely-used method is spatial
ICA (even though temporal independence might seem more natural). Recently,
Dalenberg et al. [13] used spatial ICA to analyze the brain responses to flavor stimuli
in young adult men. This approach both allowed artifacts due to swallowing to be
discarded and the functional brain data during flavor processing to be assigned to
spatially independent functional brain networks. Finally, the different time courses
were related to flavor pleasantness scores using linear mixed models. At the group
level, one component was significantly associated with pleasantness scores, which
showed a broad spatial overlap with the ventral emotion network (consisting of the
ventral prefrontal cortex, ventral striatum, amygdala, insula, and parahippocampal
gyrus). This work offers an elegant illustration of the utility of ICA to denoise and
analyze fMRI data without an a priori model. We add that such data-driven
approaches are useful not only for improving functional sensitivity, but also for
estimating the average shapes of the different BOLD responses, which may hold
important information about brain function.
Because BOLD fMRI is an indirect hemodynamic method, it naturally raises the
question of the quantitative value of the observed effect sizes. Although the spatial
extents between BOLD responses and the neural field potentials are well correlated
in early sensory areas [14], the relationship between neural and BOLD signals is
more complicated [15]. The Hoge power law [16] is, however, useful for under-
standing how the percentage BOLD contrast is scaled. It is modeled by:
"

 #
ΔBOLD CMRO2 β CBF αβ
ΔBOLDð%Þ ¼ ¼M 1
BOLD0 CMRO2, 0 CBF0
h i
¼ M 1  ð1 þ CMRO2 ð%ÞÞ ð1 þ ΔCBFð%ÞÞαβ ,
β

where CBF is the cerebral blood flow, CMRO2 the cerebral metabolic rate of oxygen
consumption, α Grubb’s coefficient, M the maximum value for the relative BOLD
contrast, and β a scaling exponent. The parameters with and without subscript “0”
represent the basal and activated states, respectively. This expression illustrates the
inability of BOLD fMRI alone to disentangle the respective contributions of CBF
and CMRO2 in the contrast measured. It also shows that the contrast depends on the
baseline, i.e., it depends on CBF and CMRO2 variations relative to their values at the
basal state within the voxel of interest. In calibrated experiments, some have
advocated replacing percentage change in BOLD signal by percentage change in
CMRO2 during the stimulation as a quantitative probe of brain function. This
appealing option requires combining BOLD and CBF measurements and estimating
the unknown baseline state variables [17, 18].
8 J.M. Bonny et al.

Olfaction

In everyday life, olfaction is not specific to food perception. As regards food odors,
volatile components (odorants) can be perceived through the direct orthonasal route
or, when food is in the mouth, through the retronasal pathway. The odorants then
activate olfactory sensory neurons located in the olfactory mucosa in the upper nose
[19]. The axons of the sensory neurons project to the olfactory bulb, the first relay of
olfactory information in the brain. Several fMRI studies have focused on the
subsequent relay of olfactory information, the primary olfactory cortex, to investi-
gate the role of this cortex, and especially the piriform cortex, in odor processing.
Activations in the piriform cortex were found to be correlated with odor intensity and
quality. An fMRI cross-adaptation experiment in humans thus showed that odor
coding was functionally dissociable in the piriform cortex. Anterior regions of the
piriform cortex encode the chemical structure of odorants, while posterior regions
encode odor quality [20]. This result was obtained using odorants found in citrus
fruits or vegetables. Using an MRI-compatible olfactometer, the subjects were
stimulated sequentially with odorants that contained the same chemical functional
group, which resulted in decreased or cross-adapting responses in anterior regions of
the piriform cortex. Conversely, in the posterior regions, cross-adaptation was
observed after sequential presentation of odorants that had similar perceptual qual-
ities, i.e., that evoked either citrus-like or vegetable-like odors regardless of their
chemical features. The authors concluded that the presence of chemical structure-
based codes suggested fidelity of sensory information coming from the olfactory
bulb, while quality-based codes did not depend on a chemical structural feature,
implying that configural processing of odor information may take place in posterior
regions of the piriform cortex, thus sustaining the object-oriented functioning of
olfaction [21]. The olfactory information, once processed in the piriform cortex, is
projected to multisensory integrative areas such as the amygdala and orbitofrontal
cortex (Fig. 2). Whether in terms of intensity, extent, or location, fMRI activations in
response to odorant stimuli showed high interindividual variability in the main
olfactory areas, on contrary to the patterns observed for vision [22]. This variability
may arise from methodologic limits and also from intrinsic physiological differ-
ences, human olfactory perception being known to be affected and even totally
modified by several non-olfactory inputs.

Gustation

Unlike olfaction, gustation is specific to food perception. It participates in the

detection of potential nutrients and toxins. Taste includes the sensations of salty,
sour, sweet, bitter, and umami, and possibly fat, which originate from taste receptors
located in the oral cavity, especially at the surface of the tongue. Taste information is
Functional MRI and Sensory Perception of Food 9

Fig. 2 Schematic diagram showing some of the gustatory, olfactory, visual, and somatosensory
pathways to the orbitofrontal cortex in primates (Reprinted from Rolls [23], with permission from
Elsevier)

conveyed by three cranial nerves (VII, IX, and X) to the nucleus of the solitary tract,
which directly projects to the taste thalamus in the ventral posterior medial nucleus
[24] (Fig. 3). Several fMRI studies have explored cortical representation of taste, and
have shown that taste stimuli activate an area of the anterior insula/frontal opercu-
lum, which appears to be the first relay after the thalamus nucleus, and is accordingly
considered the primary taste cortex in humans [25]. Taste stimuli also activate the
OFC (Fig. 2), which is probably the secondary taste cortex, but is also a highly
integrative area of the brain [23]. Interestingly, fMRI studies have contributed to
provide a better insight into the functional architecture of the central taste system: the
anterior insula is found to respond to unimodal taste, but also to unimodal olfactory
stimuli, whereas the anterior frontal operculum is activated only by unimodal taste
stimuli [26].
10 J.M. Bonny et al.

Gustatory cortex
(anterior insula-
frontal operculum)

Ventral posterior
medial nucleus of
thalamus
Chorda Geniculate
tympani ganglion

N, VII

Tongue Nucleus of
N, IX solitary tract
Petrosal
Glossopharyngeal ganglion
N, X Gustatory
area

Nodose
ganglion

Pharynx

Fig. 3 Taste information is transmitted from the taste buds to the cerebral cortex via synapses in the
brain stem and thalamus. Signals carried by fibers that innervate the taste buds travel through
several different nerves to the gustatory area of the nucleus of the solitary tract, which relays
information to the thalamus. The thalamus transmits taste information to the gustatory cortex
(Reprinted from Buck [27], Fig. 32-17, with permission from McGraw-Hill Companies, Inc.)

As previously mentioned, Schoenfeld et al. [4] (Fig. 4) highlighted the large

interindividual variability found with fMRI in activations of the insula in response to
each tastant evoking salt, sweet, sour, bitter, and umami. They developed an
unfolding method that offers the possibility of studying the precise anatomical
locations of each activation in the insula. As the insula is a large area, activations
to different tastants do not overlap across subjects, and activations vanish in group
analysis. This finding reveals the importance of individual analysis in gustatory
fMRI studies.
The hedonic value of taste may also be encoded within the cingulate cortex where
activations correlate with the subjective pleasantness of taste: glucose (pleasant
sweet taste) was found to activate the pregenual cingulate cortex, and monosodium
glutamate (less pleasant umami taste) activated a more dorsal part of the anterior
cingulate cortex [23]. Overall, fMRI experiments revealed that the anterior cingulate
cortex and the orbitofrontal cortex were involved in the reward value of taste, while
the identity and intensity of tastes was found to be encoded in the anterior insula,
where the BOLD signal was correlated with the subjective intensity of the taste.
Functional MRI and Sensory Perception of Food 11

Fig. 4 Individual activation maps elicited by five taste stimuli represented on the flattened cortical
surfaces of the insular/opercular cortex in six subjects (Reprinted from Schoenfeld MA, et al. [4],
with permission from Elsevier)

Somatosensory

Somatosensory nerves innervate the entire body surface including the epithelia
lining body orifices and especially mucosal membranes of the nose and the mouth
through cranial nerves V, IX, and X. The general somatosensory system mediates
several types of sensation, such as pain, temperature, texture, and chemesthesis
[28]. Several fMRI studies have focused on these last two types of sensation,
which are highly relevant to food perception. Food textures can be perceived, for
example, as soft, hard, viscous, or crisp; chemesthesis mediates sensations such as
pungent, tingling, stinging, cooling, or heating.
In the case of chemesthesis, owing to strong experimental constraints related to
in-mouth stimulations with irritant substances (long-lasting irritating sensations),
most experiments have compared olfactory and trigeminal stimulations in the nose.
In one study exploring the neural network involved in encoding stimulus intensity in
the trigeminal and olfactory systems [29], participants were given specific olfactory
(H2S) and trigeminal (CO2) stimuli. Brain responses to the trigeminal stimulus
revealed activation in a network including various subregions of the cingulate
cortex, suggesting separate but overlapping neural networks involved in encoding
12 J.M. Bonny et al.

the intensity of olfactory and trigeminal sensations. Overall, trigeminal stimulations

were found to activate the brainstem, thalamus, caudate nucleus, parts of the
orbitofrontal cortex, medial frontal gyrus, frontal operculum, superior temporal
gyrus, cingulate, and postcentral gyrus. Olfactory and trigeminal sensation encoding
have been shown to involve common brain areas such as the medial orbitofrontal
cortex, amygdala, parahippocampal gyrus, and cerebellum.
Concerning food texture, fMRI studies have been conducted using liquid or
semisolid food. Solid food needing mastication has very seldom been tested owing
to the dorsal decubitus position and artifacts induced by motion during image
acquisition. Using solutions of ranging viscosity, it has been shown that the repre-
sentation of oral texture involves the insular cortex posterior to the taste cortex in the
anterior insula [30]. Oral viscosity is also represented in the human orbitofrontal and
perigenual cingulate cortices. The latter area, in which many pleasant stimuli are
represented, is also strongly activated by the texture of fat in the mouth. High-fat
stimuli that included a pleasant flavor reinforced the coupled activations between the
orbitofrontal cortex and somatosensory cortex, arguing for a role of the somatosen-
sory cortex in processing the sensory properties of food in the mouth [31].

Exploration of Taste and Odor Integration in the Human Brain

Taste and olfaction are hidden senses, both by their location and by our tenuous
awareness of them. Food perception can be theorized as a “misfit” perception [32], as
in the course of a meal, we are fully conscious only of misfit olfactory and gustatory
perceptions; we process, integrate, and memorize the rest of the meal obliviously,
and most of our food choices are actually driven by implicit memory [13, 33, 34]. In
this light, fMRI offers a sound technique to highlight neurological substrates of food
representation and to gain further understanding of food choices. The identification
of neurobiological substrates of flavor perception has been addressed by fMRI for a
decade, but results are still controversial. Most dissension arises from similar
interpretations of results showing, on one side, the convergence between olfaction
and taste (i.e., interactions), and on the other side the integration of olfaction and
taste into a unitary object in memory areas.
Multisensory integration is the combination by the nervous system of perceptions
from different sensory modalities into a coherent unified representation of objects.
There is still debate on what sensory modalities constitute flavor perception, and how
to define flavor and flavor perception [35]. However, at least taste and olfaction are
necessary to create a flavor perception. To simplify the discussion, in this chapter we
will therefore mainly cover the binding of taste and odor. However, it is important to
keep in mind that flavor may be modulated, and can integrate other sensory modal-
ities such as trigeminal, somesthesic, visual, and auditory perceptions. Flavor per-
ception is our brain representation of food when we are eating. It can be shown by a
supra-additive activation of an area in response to food perception (containing
olfactory and gustatory stimulations), relative to the responses to independent
presentation of olfactory and gustatory constituents of the food. Interactions between
Functional MRI and Sensory Perception of Food 13

odor and taste consist in the modulation of the perception of a stimulus by the
presence of another (here tastants and odorants), and may occur at different levels of
the flavor integration processes. The neuronal substrates for interactions can be
shown by overlapping activations by independent olfactory and gustatory
stimulations.
Many fMRI studies have highlighted interactions between taste and odor percep-
tions, but not integration, mainly for methodological reasons. Flavor stimulation
requires presenting a textureless palatable liquid food, with controlled temperature
and time of delivery. Techniques to do this exist, but are costly and require special
expertise. The food must also be safely delivered in the scanner, and needs to be
presented either in small drops or as a light drizzle. Finally, masticatory movements
or swallowing must be reduced or controlled as fully as possible in order not to bias
brain responses. However, flavor perception mainly occurs after swallowing, as this
is when the velum (muscle at the back of the mouth that closes the nasal cavity
during liquid food consumption) will be open to allow volatile substances to reach
the olfactory epithelium. Therefore, most “flavor” studies actually show brain
responses to independent olfactory and gustatory stimulations (unimodal), and not
combined presentation of odor and taste (multimodal), in order to avoid swallowing
bias, favoring general misunderstanding of the mechanisms underlying true flavor
perception. Although these unimodal studies failed to show supra-additive responses
to congruent odor-taste stimulation, they nevertheless isolated a network of odor and
taste-responsive regions that could be responsible for flavor perception. Independent
presentation of tastants and odorants activated both regions in the insula and frontal
operculum, the OFC, and the anterior cingulate cortex [36]. Stimulation with food
images was also used to circumvent these methodological constraints. Although
these studies were not targeting flavor perception per se, they present interesting
overlapping regions, which may be involved in flavor perception coding. These
visual approach to “flavor perception” emphasized the functional contribution of the
anterior insula, the OFC, and amygdala [8] in the processing of visually presented
food. Animal electrophysiological studies were able to show the presence of bimodal
neurons in the previously exposed areas where olfactory and gustatory perceptions
converged. First evidence for bimodal neurons was found in highly integrative
centers such as OFC and amygdala [37, 38] (Fig. 2). However, recent studies also
show convergence between insula and piriform cortex (i.e., primary gustatory and
olfactory areas) such that taste perception modulated odor perception [39, 40]
(Fig. 5). These bimodal neurons can respond to independent taste and odor (or
taste and trigeminal, or taste and texture), but also responded to their combination.
However, these bimodal neurons alone cannot explain the flavor integration as
theorized by Small et al. [41]. It is likely that integration of taste and odor occurs
through configural learning [41, 42]. This learning involves the memory encoding of
the unified pattern of taste and odor perceptions resulting in flavor perception.
Rolls’ group was the first to demonstrate flavor integration, first in primates with
electrophysiological recordings [38], and then in humans with fMRI [26, 44,
45]. The results pinpointed integration in the OFC (Fig. 2). Interestingly, two studies
[45, 46] partly demonstrated the configural learning mechanisms for flavor
14 J.M. Bonny et al.

Fig. 5 Schematic diagram of taste and olfactory pathways and their convergence. NST nucleus of
the solitary tract, VPMpc ventral posterior medial nucleus (Reprinted from Small et al. [43], with
permission from Elsevier)

integration by comparing brain responses for congruent odorant-tastant stimulation

to an incongruent odorant-tastant stimulation. Using either salty or sweet stimuli,
they both showed activations in the insula, anterior cingulate cortex, and OFC. In the
literature, the amygdala is often cited as an integrative center. However, no supra-
additive activations have been found in amygdala. This region is involved in the
reward system, sodium appetite, and food pleasure and disgust [13, 26, 47]. It may
also be a key node structure for retention processes of odor-taste integration, as
shown in rats [48]. Finally, the OFC, a high-level area, appears in the literature as the
most consensual region for flavor integration. However, Seubert et al. [49] identified
flavor integration in the primary gustatory area, namely the insula. A supra-additive
activation was found in the dorsal mid-insula in response to an orange juice after
swallowing, relative to the independently presented olfactory and gustatory stimu-
lations (orthonasal presentation of the orange juice constituted the olfactory stimu-
lation, while holding the orange juice in the mouth with the olfactory pathway closed
constituted the gustatory stimulation). Insula and OFC could therefore be integrative
Functional MRI and Sensory Perception of Food 15

Fig. 6 Three stages of the swallowing process for liquid foods taken from a sagittal real-time MRI:
(a) swallow preparatory phase, (b) pharyngeal phase of swallowing, and (c) swallow breath with
aroma perception after swallowing (Reprinted from Buettner et al. [51], with permission from
Elsevier)

areas for flavor. Verhagen, however, postulated that the insula-OFC system evalu-
ated affects associated with flavor, while the insula and perirhinal system enabled the
object representation [50]. However, owing to difficulty detecting activation within
the limbic structures, because of their small size, no studies have shown any supra-
additive activation in this area. Progress in high-resolution recording and BOLD
signal analysis should, however, soon make it possible to identify such
responses [8].
To study flavor perception, specific designs and tools that eliminate swallowing
artifacts have to be developed. Swallowing is a necessary condition for flavor
perception, as the olfactory component of flavor is achieved maximally when the
velum is deliberately opened, as done by wine tasters (Fig. 6) [51]. However, this
16 J.M. Bonny et al.

deliberate opening is made possible only by placing no more than a small portion of
liquid in the oral cavity, or by bending the head forward so that no liquid can flow
into the pharynx. In many studies, it is assumed that motion artifacts are identical
across conditions and therefore that contrasting conditions will suffice to suppress
artifacts and emphasize activations. However, salivation and consequent swallowing
have been shown to differ across different tastes or even between different levels of
saltiness [52–55], which is a source of false detection in BOLD fMRI [13]. To avoid
such artifacts, we can opt to prevent swallowing by training subjects and removing
saliva and liquid from the mouth with a vacuum pump. In this situation, subjects
should be trained to breath with the velum opened. Another possibility is to
explicitly model the effect of swallowing on the image signal as a regressor of no
interest. This solution is challenging, because it probably depends on various factors
such as stimulus, position in the brain, and the way the subject swallows.
To achieve a better characterization of food perception, an important step would
be the stimulation of subjects with solid food. This hurdle will hopefully be
overcome in future studies, with a better identification of the brain flavor network,
by the development of food models that can isolate and combine the different
modalities involved in eating, and by the development of brain signal analysis. In
that respect, the seminal work of Sayer et al. [56] demonstrates, however, the
feasibility of measuring a consummatory response while eating a solid food,
whereby the insula response can be correlated with palatability ratings.

Vision

Vision has been mainly used to get around issues with chemosensory stimulation in
the magnet. Despite the fact that food images cannot pinpoint flavor brain mecha-
nisms, they have been widely used in order to investigate other food-related mech-
anisms such as reward processes, impact of satiety, exposure, learning, or culture on
food choices.
Numerous fMRI studies have investigated the brain processes associated with
appetite and food intake, especially in the case of deregulated feeding behaviors,
using images of food [8, 57]. For instance, it has been found that responses to visual
food cues are associated with increased activations in obese individuals in the reward
system and associated brain regions. These results could be obtained by comparing
obese and normal-weight subjects for brain activation in response to food and
nonfood images. Murdaugh et al. [58] investigated fMRI activations in the reward
system and other brain regions in response to visual stimulation with food versus
control pictures in obese subjects before and after a 12-week weight-loss treatment.
High-calorie food images consisted of an equal number of sweet foods, such as a
slice of chocolate cake or cheesecake, and savory foods, such as a cheeseburger or
french fries, whereas low-calorie food images consisted of low-fat foods, such as
broiled fish or salad; a set of control images consisted of pictures of cars that matched
the low-calorie food images in ratings of pleasantness. The results especially
revealed greater activation to food versus control pictures in brain regions involved
Functional MRI and Sensory Perception of Food 17

in the reward system processes (nucleus accumbens, anterior cingulate) and insula
during the pretreatment session for the subjects who were least successful in losing
weight during the treatment. Furthermore, less successful weight maintenance after
treatment was associated with greater posttreatment activation in such brain regions
as the insula, ventral tegmental area, putamen, and fusiform gyrus.

Conclusion and Perspectives

Despite its severe technical constraints, which still preclude normal eating condi-
tions, fMRI based on BOLD contrast has been used with success to elucidate many
mechanisms of coding and integration, mostly directly in the human eater. Further
progress is clearly needed, in particular to improve multisensory stimulations, and
increase the sensitivity and specificity of the activation maps obtained.
BOLD fMRI is a proven functional technique, but it is not quantitative, and its
sensitivity is relatively low. It is therefore subject to wide variability, which usually
goes unseen when an activation map is inferred from group responses; generally
very large cohorts would be required to show an irrefutable effect [59]. Even so, we
must emphasize that the processing of sensory stimuli involves an individual
component containing information that should not be systematically erased by
group analysis.
Several attempts have recently been made to detect neural currents associated
with brain activity, which produce weak transient magnetic fields that attenuate MR
signal intensity. The present MRI techniques are not sensitive enough to detect such
attenuation. BOLD fMRI thus needs to be extended by other experimental means, in
particular EEG, which is complementary in that it provides direct neural recordings
at a high temporal resolution. Devices exist that allow coupled measurements.
Although the measurement of deep, noise-clean electrical signals remains difficult,
this combination seems very promising to clarify mechanisms that include percep-
tion, action, and anticipation [60].

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