Single pulse TMS: variability and reproducability of MEP and EEG responses in healthy subjects.

The diagnostic process in epilepsy is often time-consuming due to the limited
sensitivity and the nature of standard EEG recordings. TMS-EEG is a candidate
tool to significantly improve the diagnostic efficiency in epilepsy. In this
study, we will perform initial measurements in healthy volunteers to evaluate
the presence of a circadian rhythm in TMS-EEG responses. Clearly, the presence
or absence of a circadian rhythm is relevant for subsequent measurements in
patients, as this may interfere with variations due to epilepsy.

The primary objective of this study is to evaluate if there exists a circadian
variability of the MEP and EEG response to single pulse TMS in healthy
subjects.

Secondary objectives are to:
- investigate the accuracy of coil placement and the overall reproducibility of
the MEP and EEG measurements performed with our equipment.
- explore additional signal analysis techniques for characterizing the EEG
response.
- evaluate the TMS-EEG protocol for future studies in epilepsy patients.
- collect TMS-MEP and TMS-EEG data in healthy subjects to use as control data
for future studies in epilepsy patients.

This study is an interventional study that will run from July - September 2010.

Before subjects will be included, they will fill out the screening
questionnaire for TMS candidates and the Dutch Handedness Questionnaire to
determine if they are right-handed. All subjects will receive an MRI of the
head prior to the TMS experiments.

At the day of the TMS experiments, subjects will undergo five sessions of
single pulse TMS between 8 AM and 19 PM. During the administration of TMS
pulses, MEP and EEG measurements take place. Single pulse TMS is applied to 3
different parts of the brain, in both hemispheres. Five subjects will be asked
to return for an additional session, one week after their whole day of TMS
experiments. This session will be used to examine the reproducibility of our
measurements. There will be no invasive procedures. None of the procedures is
part of a medical treatment.

TMS (transcranial magnetic stimulation).
The TMS equipment has a maximum output of 1.5 Tesla. The puls duration is 400
microsec. 50 Single TMS pulses will be given to 6 different brain areas (3 in
each hemisphere), while the EMG and EEG are registrated. There are 5 TMS
sessions, at 8:00 AM, 10:30 AM, 13:00 PM, 15:30 PM and 18:00 PM.

First, the hot spot and motor threshold of the right abductor digiti minimi
(ADM) are determined. Then, the 3 brain areas in the left hemisphere are
stimulated on 110% of motor threshold. Measurements are then repeated in the
right hemisphere. Pulses are given with a frequency of ~0.25 Hz (single pulse
TMS).

The MRI scan of the head takes ~ 20 minutes. The single pulse TMS experiment
consists of 5 experimental sessions of ~ 50 minutes during 1 day. Applying the
EEG cap and EMG electrodes takes 30 minutes and takes place prior to the first
TMS session. During the TMS experiments, the subject will be seated in a
comfortable chair. The MRI, EEG and EMG measurements will only produce minor
discomfort and do not have associated risks. Single pulse TMS is generally well
tolerated. Possible side-effects and risks are described in section 9.4 in the
protocol.