Three methodological aspects in TMS-EEG: Noise masking, pulse intensity and need for accurate coil positioning

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
second study we perform measurements in healthy subjects and epilepsy patients
to investigate three methodological aspects.

The primary goal of this study is to develop a protocol for future studies in
patients after a first seizure. We investigate 3 methodological aspects.

- What is the effect on the auditory evoked potential of different types of
noise masking?
- What TMS intensity do we need to evoke TMS-EEG responses?
- How accurate do we need to position the TMS coil to evoke reproducible
TMS-EEG responses?


Secondary objectives are to:
- Investigate what the effect of noise masking is on the motor threshold
- Investigate whether single-pulse TMS has any effect on the presence of
epileptic abnormalities in spontaneous EEG recordings
- Investigate whether epilepsy patients show abnormal TMS-EEG responses
o Investigate which brain area shows abnormal TMS-EEG responses
o Investigate whether the abnormal TMS-EEG responses are reproducible
o Investigate whether the need for accurate positioning of the coil is
different for abnormal TMS-EEG responses
o Investigate whether the needed TMS intensity to evoke TMS-EEG responses
is different for abnormal TMS-EEG responses

This study is an interventional study that will run from May 2011 - April 2013.

Before subjects will be included, they will ifll out the screening
questionnaire for TMS candidates and the Dutch handedness questionnaire.

The healthy subjects will undergo 3 TMS sessions during 1 day. During the
administration of TMS pulses, EMG and EEG measurements take place. Single pulse
TMS is applied to the motor cortex in the left hemisphere. We assess 8
different ways of noise masking, 7 different intensities and 8 locations
surrounding a specific target.

The epilepsy patient will undergo 1 TMS session during day 1. If they show
abnormal responses, they will undergo 3 more TMS sessions during a second day.
During the administration of TMS pulses, EMG and EEG measurements take place.
TMS is applied to 6 different brain areas. In addition, we assess 7 different
intensitites and 8 locations surrounding a specific target.

TMS (transcranial magnetic stimulation).
The TMS equipment has a maximum output of 1.5 Tesla. The puls duration is 400
microsec. Pulses are given with a frequency of ~0.25 Hz (single pulse TMS).

First, the hot spot and motor threshold of the abductor digiti minimi muscle
(ADM) are determined on both sides. In healthy subjects, we stimulate the hot
spot in the left hemisphere, while applying 8 different types of noise masking.
After that, we stimulate at 7 different intensities and at 8 locations
surrounding the hot spot.

In patients, we stimulate 6 different brain areas (hot spot left/right,
Brodmann area 19 left/right, epileptic focus ipsilateral/contralateral). If
they show abnormal responses, patients return for a second day of measurements.
On that day we stimulate at 7 different intensities and at 8 locations
surrounding a specific target.

Applying the EEG cap and EMG electrodes takes 15 minutes, locating the hot spot
and determining the motor threshold takes 20 minutes, and calibrating the
equipment takes 10 minutes, these actions take place prior to the first TMS
session. The single-pulse TMS experiment consists of 3 or 4 sessions of varying
length (40 - 65 minutes). During the TMS experiments, the subject will be
seated in a comfortable chair. The EEG and EMG measurements and listening to
the noise sounds 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.