Early neuronal processing of basic tastes in healthy young adults and elderly, investigated with fMRI.

Previous studies indicate that the gustatory cortex (Insula & overlying
Operculum) plays an important role in taste processing. Manipulations in
pleasantness, taste identity, taste intensity or physiological state (hunger or
satiety) were all associated with activity changes within the gustatory cortex.
Where identification was recorded in the anterior insula and overlying frontal
operculum (AIFO), pleasantness was recorded in the mid insula and intensity was
associated with increased BOLD responses in the insula. Furthermore, the
physiological state of hunger also showed to increase activity in the insula,
compared to being satiated.
So far no study has shown a specific chemotopy within the gustatory cortex
for the different basic tastes in humans. Results from primate studies show
similar results. Single cell recordings in primates indicate that neurons in
the gustatory cortex are broadly tuned; they responded to more than one taste
stimulus. This could imply that rather a network of neurons is representing the
identity of a basic taste. In rodents this indeed seemed to be the case.
However, these activation patterns do not represent identification alone. It
was also shown that tastes with a similar hedonic value activate more common
regions in rodents. Furthermore it was shown that the activation pattern of
saccharin is plastic: by means of a conditioned taste aversion paradigm, the
activation pattern of saccharin changed and showed activity in regions that are
similar to the activity regions of unpleasant tastes.
By specifically zooming on the gustatory cortex we aim to investigate the
activity patterns that are associated with (interactions between) taste
identity, intensity and hedonic value with a higher spatial resolution. This in
order to build a better understanding on the functional organization of the
gustatory cortex of healthy people. Furthermore, we aim to indicate where the
differences are between both men and women and young adults and elderly. This
information is vital in order to further investigate the neuronal changes
induced by chemosensory disturbances such as disturbances caused by undergoing
chemotherapy or by aging.
With a higher spatial resolution and including different taste identities,
intensities and pleasantness, we hypothesize that we are able to find a more
specific functional organization in the gustatory cortex and specific
correlations with other regions within the brain stem, basal ganglia and
midbrain. Based on animal models we expect to find activity patterns that
overlap based on pleasantness. Furthermore, if the anterior insula and
overlying operculum can indeed be associated with taste identity we expect
correlations with memory regions such as the hippocampus. We also expect that
activity regions that can be associated with pleasantness show correlations
with activity with emotion regions such as the amygdala.

This study will form the basis for future studies that are planned to
investigate chemosensory disturbances in elderly and testicular cancer patients
who are undergoing cisplatin based chemotherapy within the University Medical
Center Groningen. Being able to investigate these changes requires insight in
how the neuronal activation behaves in healthy patients.
Together with the previously approved study METc2011.151; ABR:
Nl36783.042.11 we aim to model the different attributes of tastes based on the
measured brain activity and by employing machine learning techniques. This
model will constitute a second objective of this study.
Furthermore there is little known about the neuronal processing of taste
stimuli in elderly. Therefore we also aim to pinpoint the functional changes
during taste processing in elderly.

Participants will be subject to the following paradigms:

1) Participants who are interested in taking part in the study will first
undergo a screening by telephone. During the screening the inclusion and
exclusion criteria for both the experiment and MR compatibility will be
discussed. Furthermore the experiment will be discussed briefly and any
questions will be answered. The intake by telephone will end with arranging an
appointment for the first visit.

2) During the intake the experimental paradigm will be shown to the participant
in order to get familiar with it. Furthermore the participant will take place
in a dummy scanner to factor out any effects of claustrophobia. Participants
will also undergo 2 small tests, both consisting of ±10 minutes each. These are
a saliva test and a taste threshold test. The saliva test will indicate how
much saliva the participant produces during normal circumstances and during
chewing (stimulation). Also we will determine the amount of proteins that are
present in the saliva. The taste threshold test will involve tasting taste
strips and recognizing the taste of the strip. This test will ensure that the
participant is not experiencing abnormalities in his or her taste perception.
The outcomes of both these tests will contribute to the interpretation of the
results from the MRI experiment.
At the end of the intake visit an appointment will be made for the MRI
experiment. For this new appointment, young women will be asked to keep using
there hormonal anti conceptive, to ensure hormone levels will be constant.

3) During the MRI experiment the participant will be scanned in a 3 Tesla MR
scanner. During the fMRI experiment the participant will administer the
different tastes. These tastes are presented in liquid form with a volume of
2mL per administration. After receiving the taste, the participant is asked to
rate the pleasantness of the taste by means of a button box. When the
pleasantness is rated, a rinsing trial will commence to wash away the existing
taste in the mouth. Rinsing will be done with a solution of artificial saliva
in water, with a total volume of 2mL.

4) Scanning will take place in either the morning or at the end of the
afternoon. The participant will be asked to stop eating after at least two
hours before the experiment begins.

The complete dataset will be composed by behavioral data (the pleasantness and
intensity ratings) as well as by brain activity data (recorded MR images).
Additionally, an high-resolution anatomical MR scan will be used to match the
brain activity with brain structures at an individual level.

The analysis of the data will include:
- Standard preprocessing of the MR data. This will include realignment,
coregistration between functional and anatomical data, normalization and
spatial smoothing.
- Single subject analysis of brain activity by looking at the differences
between conditions (e.g. the difference between the basic tastes), as well as
the differences between the experience of a taste and the baseline activity of
the brain (i.e. looking at a fixation cross). The results of the behavioral
data will be included as covariates.
- Application of machine learning techniques and/or other cognitive modelling
techniques to the combined brain activity and behavioral response data.
- Group analysis of the results collected at single subject level, using both
parametric and non parametric techniques.

- The exposure to a Magnetic Resonance environment is not considered harmful
per se.
- The insurgence of a claustrophobic feeling is not uncommon; in order to
reduce this risk, we (a) ask the participant about being prone to
claustrophobia, and (b) when desired, we will put the participant in a dummy
scanner (a far lesser stressful environment) before to exposition to the real
MR environment.
- During the scanning sessions the participants receive small amount of liquids
in their mouths (2mL); this could provoke, in cases of mis-swallowing,
coughing. It is very unlikely that this will invoke a life threatening
situation. Furthermore an experimenter will stand next to the subject to
provide the taste stimuli and will constantly observe the well-being of the
participant. Besides, the participant will have the ability to control an
emergency button which will stop the scanning procedure.

We believe that for the present study the ratio between the possible increase
of knowledge on the one hand and the burden/risk on the other hand is
favorable. It is an acknowledged fact that Magnetic Resonance is an eminently
risk-free investigational tool.

This study promises to shed light on the inner mechanisms of how the human
brain reacts to basic tastes. Furthermore, this study will form the basis for
future studies that are planned to investigate chemosensory disturbances in
elderly and testicular cancer patients who are undergoing cisplatin based
chemotherapy within the University Medical Center Groningen. This study will
help understanding these problems and, ultimately, contribute to a healthy
diet, which is of vital importance for survival of these patient groups.

About the benefits for individual participants: there are no direct benefits.
However, they will benefit from an early detection if any structural
abnormalities are detected at the level of their brain.