Neural substrates of anticipatory food reward in healthy males and cancer survivors, investigated with fMRI.

This study is part of a TI Food and Nutrition project, which aims to understand
food choice in cancer survivors and other populations (e.g., elderly).
Perceived pleasantness while consuming a food product must be translated into
motivation in order to influence subsequent food choice. Such motivation is
also known as anticipatory food reward. Visual features that motivate people to
choose a specific food product induce anticipatory reward, and are a strong
predictor of food choice. Increased Body Mass Index and increased risk of
cardiovascular disease are frequently observed as a side effect after treatment
with cisplatin-based chemotherapy in testical cancer. Therefore, in the current
study we aim to investigate the neural mechanisms behind the anticipation of
reward from food products in these cancer survivors.

Investigating the neural mechanisms underlying the anticipation of food reward
induced by visual cues related to different food
characteristics in healthy males would provide 1) brain activity patterns that
can be associated with the anticipation of food reward
and 2) a baseline to further investigate if and how these brain activity
patterns differ between healthy males and cancer
survivors.

This study will combine fMRI and behavioral measurements. Participants will
undergo one fMRI scanning session in which they will
perform a computer-based paradigm consisting of visual (anticipatory) food
stimuli. All stimuli will vary along two dimensions - taste
(sweet or salty) and calorie (high or low). The anticipatory reward to each
visual food stimulus will be assessed by a two-alternative
forced choice methodology (i.e. an established controlled measure of choice
which is widely used to test choice behavior), designed
and executed using Matlab. In this task, the participants will be instructed to
select the food they *would most like to eat now* in a
series of trials in which a visual food stimulus from one of the four food
categories will be paired with a stimulus from either the same
or another category. Each choice, made via key-press on the keyboard, triggers
the next pair of stimuli and so on until all possible
combinations (i.e. 10 combinations) are presented 16 times in order to acquire
a reliable brain response. The total amount of 160
trials will be divided over four task blocks of 40 trials. The order of all
combinations of visual food stimuli will be randomized across
all four block as well as balanced and counter-balanced between participants.

A behavioral and neural measure of *anticipated reward* is derived in two ways.
First, the brain response derived during each choice
can convey information about the degree (on a continuous, interval unit of
measurement) to which a chosen visual food stimulus is
anticipated to be rewarding relative to an alternative. Second, the analysis of
the fMRI data will take into account the reaction times
when choices are made to each food category respectively as a covariate. This
might show what brain activation can be associated
to anticipated food reward for each food category for each participant
individually.

The design of this study is single-blind; at the moment of presenting the
visual food stimulus, the participants do not know which food
category they are experiencing. However, the participants 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: filling in a safety questionnaire before intake
(to ensure that all the inclusion requirements are met), Before each scanning
session the subject will be required to fill and sign a safety-specific
questionnaire. During the intake session, participants will fill in a reward
questionnaire and rate the food images used during the fMRI session on
pleasantness and calorie density. The scanning sessions will be between 16:00
and 19:00 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).