Habituation to pain in healthy subjects: An fMRI-EEG study using a multilevel approach

Habituation to pain is a phenomenon that generally occurs after repeated
painful stimulation. However, its neural mechanisms are still largely unknown.
It is important to investigate the healthy process of habituation to pain
before further studies can investigate chronic pain patients. Research has
shown that individuals with chronic pain may have impaired habituation to pain,
which may underlie the chronic pain condition. Therefore, this study will serve
as a first step into investigating the neural mechanism of habituation to pain
using functional magnetic resonance (fMRI) combined with electroencephalography
(EEG).

The current study investigates which brain areas are related to habituation of
pain (using fMRI) and enables a direct coupling with concurrent EEG. We will
test the hypothesis that activation of areas in the brain show changes over
time as correlate of the psychophysical habituation process.

Single session experimental study with repetitive painful stimulation while
measuring fMRI and EEG responses. Questionnaire measures will be obtained
before and after the experiment.

From this experiment, brain regions will be identified which participate in the
mechanism of habituation to pain. With these insights, habituation to pain in
healthy participants can be compared with chronic pain patients in a later
study. This will give insights into the mechanisms of habituation to pain and
its disruption in chronic pain, and may serve as a starting point future
real-time neurofeedback treatment of chronic pain complaints. There are no
direct benefits for the subjects in participation in the experiment besides a
monetary compensation or course credits.

Habituation and intensity protocol
Participants will receive up to 200 very brief (10 milliseconds) painful
electrical intracutaneous stimuli during an fMRI-EEG protocol. A similar
habituation and intensity protocol will be used as in earlier research in EEG
which has been approved by this METC board (ABR 40284). In EEG research,
subjects generally evaluated the burden of the experiment as low. The painful
stimulation will be close to the pain threshold and will thus not cause extreme
pain. The pain threshold will be determined before the scanning procedure. This
will be in a controlled setting where subjects can stop the experiment at any
time.

MRI-EEG
All MRI guidelines will be strictly followed ensuring a safe procedure. No
long-term negative health effects of 3T MRI have been reported. Participants
will be routinely screened for any MRI contraindications (e.g., pacemaker,
metal implants). Participants can only take part if they agree that incidental
findings will be evaluated by a qualified radiologists who will inform their
general practitioner to invite them for follow-up tests if needed. Participants
are asked to lie still while measuring BOLD fMRI and EEG. There will be short
breaks between the scans to allow participants to relax, and the participant
can communicate with the researcher between scans. During the scans the
participant has the possibility to stop the experiment by pressing an alarm
bell. The scanning process results in loud noises for which the participants
receive hearing protection in the form of earplugs. We will use standard
procedures for fMRI-EEG, thus patient discomfort will not be higher than in
other similar studies performed at Scannexus.

Questionnaires
Questionnaires related to anxiety, depression and pain are to be completed.