Flavour processing in healthy males, investigated with fMRI.

The neural processing of a food is influenced by various factors including but
not exclusively to the perceived intensity, perceived pleasantness, tactile
sensations, complexity, how it looks and possibly caloric content. How these
attributes influence the activation patterns of the brain when we taste a
flavour is not yet fully clear. Here, we refer to flavour being a taste
stimulus, which contains both a taste and an odor. Although taste experiments
often used basic tastes (e.g. sweet, salty, sour or bitter), we encounter
flavours more often in daily life.

In recent studies we have isolated activation patterns in the insula specific
to valence and intensity of basic taste processing and have found separate
networks for pleasure and disgust in complex flavours. The regions involved in
both disgust and reward processing show similarities with regions found that
respond to human facial expressions, emotions and visual stimuli. In the
upcoming study we hope to separate intensity and valence coding on a whole
brain level in complex flavours. In addition we expect to be able to show that
the disgust and reward networks we have identified are not specific to food but
universal processing networks for disgust and reward.

Investigating the neural mechanisms underlying the intensity and pleasantness
coding of flavours in healthy volunteers would provide 1) dissociation of the
brain activity patterns related to flavour intensity and pleasantness and 2)
insight into how food reward and disgust processing relates to the processing
pictures containing emotional content.

This study will combine fMRI and behavioral measurements. Subjects will undergo
one fMRI scanning session in which they will be shown various images from the
International Affective Picture System (IAPS) set, which is a frequently used
method to study emotion, and they will also experience four repetitions of
lemonade solutions; one pleasant and one unpleasant. The unpleasant stimulus
will be created by diluting the lemonade with fish sauce. We will balance the
lemonade that will be assigned as unpleasant over participants. The stimulus
solutions exist of five intensities ranging from not intense at all to
extremely intense of two kinds of lemonade. The lemonades will be diluted in
tap water. Furthermore tap water will be used for rinsing. Each lemonade flavor
will be presented in a run containing 5 consecutive trials with an increasing
intensity. These flavor runs will be pseudo-randomized as well as balanced and
counter-balanced between subjects. Each individual flavor trial will include
both a flavor stimulus and a rinsing stimulus. The behavioral measurement will
include subjective pleasantness- and intensity ratings from the participant for
each administered flavor during the fMRI experiment. The analysis of the fMRI
data will take into account the behavioral data as a covariate. The
pleasantness rating will show what brain activation can be associated with
liked and disliked stimuli for each participant individually. Using the
intensity ratings the whole brain response to varying degrees of intensity can
be determined. The IAPS dataset will be used to determine whether responses to
rewarding and disgusting drinks are food specific or whether these responses
are universal to disgusting and rewarding stimuli. Furthermore, heart rate and
respiratory data will be logged. This data is used to remove any heart rate and
respiratory induced artifacts. The design of this study is single-blind; at the
moment of the flavor administration, the healthy volunteers do not know which
taste he or she is experiencing. The subjects will be informed about the nature
of the stimuli, before inclusion into this study.

Functional MRI is an eminently safe technique; there are no risks that have
been associated with the acquisition of fMRI data per se. Above certain limits,
warming and/or an itching/tingling feeling (stimulation of peripheral nerve
terminations) are possible. However, the magnetic intensities used in this
research are amply below these limits. Subjects will be exposed to a magnetic
field of 3 Tesla and rapidly alternating gradients and radio frequency fields.
This field and gradients' changes are routinely used in fMRI and MRI research.
It is worth to mention that scanners supporting a magnetic field that is more
than twice as powerful (7 Tesla) are used in The Netherlands for research
purposes. Also, no harmful side effects have been reported there.
The data collected during the functional and anatomical MRI scans will be used
for research purposes only. However, if evident abnormalities in the brain are
noticed, then the General Practitioner, who is indicated by the subject, will
be notified.

The strong magnetic fields used by fMRI can dislocate ferromagnetic particles
inside the brain and the eyes, interfere with the functioning of electronic
devices implanted inside a person's body (pacemakers, insulin pumps, etc.), as
well as induce heating in artificially metal-rich regions (red tattoos,
metallic supports to previously fractured bones, prosthetic implants). In order
to stave off the risks involved with such possible conditions, subjects will be
required to complete a questionnaire and only if none of the exclusion criteria
is met the subject will be allowed to participate in our experiment.

The environmental conditions of being inside an MR scanner and of being
partially restrained can induce claustrophobic feelings. Three steps will be
taken to reduce this risk: 1) the subject will be explicitly asked about being
claustrophobic, 2) the subject will experience a training moment in a dummy
scanner and 3) prior to the beginning of the actual experiment, and during
pauses between scans, subject will be asked about their well being.
Additionally, they will receive an alarm trigger that they will be able to use
at any moment to interrupt the scanning. Finally, an experimenter will be in
close proximity of the participant during the session, for the primary reason
to present the aforementioned small amounts of liquids. Such proximity will
allow a close monitoring of the subject*s well being.

The subject's burden is as follows, regarding time: a screening moment by
telephone, to ensure that all the requirements are met and to determine the
individual intensity/pleasantness curve needed for the scanning session. Before
each scanning session the subject will be required to fill and sign a
safety-specific questionnaire.

The scanning sessions will be between 8:00 and 18:00 hours; we will ask the
subjects to stop eating at least three hours before the scan to ensure a
sufficient state of hunger to induce a stronger BOLD response to the stimuli.

To undergo a fMRI scan involves: exposure to loud noise (addressed with ear
protection, by means of both ear plugs and headphones), a moderate amount of
physical restraint (the head is inside a fMRI coil; the feeling is similar to
wearing a motorbike helmet), as well as to a strong constant magnetic field
(3Tesla), and small variable electromagnetic fields (see question E9).

During the scanning sessions the subjects will receive beverages. The
individual administrations are the equivalent of small sips (approx. 2 ml), and
the total amount of liquid ingested in one scanning session (approx. 30 min) is
the equivalent to little more than half a can of cola (180ml). The current
study design is largely based on earlier approved study (METc2012/090 and
METc2011/151). In this previous study, 80 subjects participated and showed no
problems with regard to the 2 ml. taste administrations or with the horizontal
position of the body while swallowing. Based on this experience we do not
expect the paradigm to be problematic for the current subject group.

The subjects will receive two flavours of lemonade, one with a pleasant taste
and one with an unpleasant taste. The solutions are made from consumer grade
lemonade and will pose no threat to their health. The caloric content of the
solutions will be kept stable by addition of a non-sweet carbohydrate
(Fantomalt), this is an over the counter food supplement. Assuming an intake of
maximum 100ml of lemonade, the total amount of Fantomalt ingested will not
exceed the advised intake of 100g daily. In addition to the lemonade solutions
the participants will view images of the IAPS picture set. These pictures range
from regularly encountered experiences such as household items to images meant
to elicit disgust and pleasure. This set of images is frequently used in
experiments studying emotional processing and attention.

No immediate benefits for the subjects are expected from their participation in
this study.