Dynamic Information Flow based on EEG and Diffusion MRI in Epilepsy: An explorative study

Epilepsy is a complex neurological disorder characterised by recurrent
seizures. It is the most common serious neurological disorder worldwide, but
there are still no reliable biomarkers. Recently renewed interest for the
coupling of transcranial magnetic stimulation (TMS) with EEG (TMS-EEG) has
grown among researchers to use it as an additional tool for epilepsy
diagnostics and therapy evaluation. Recent studies have shown that epileptiform
discharges are connected with changes in the dynamics of the brain and possible
alterations in connectivity between inter-connected areas of the brain. The
"Variational Bayesian Multimodal Encephalography" methode provides a way to
analyse the dynamic information flow between cortical sources, this can provide
information about among other things the seizure, the interictal state and
change in the brain network connectivity. TMS in combination with
electroencephalogram (EEG) is a non-invasive method. TMS induces an electrical
field in the brain, causing a depolarization and generation of action
potentials. TMS-evoked EEG responses can be used to analyse the brain's
excibatility and the brain network connectivity. Visual stimulation evoked EEG
responses might serve as an alternative method to study changes in brain
connectivity.

Exploration and possibly chaniging of the VBMEG method to analyse dynamic
changes in the connectivity network in epilepsy patients. This study is a
prerequisite to apply the VBMEG method to a larger dataset to possibly identify
a quantitative biomarker in epilepsy patients.

This might eventually serve three goals:
1. Serving as a biomarker which can be used to define the phenotype of the
disease.
2. Objective evaluation of the effectiveness of the treatment
3. Regain more insight in the pathophysiology of the epileptic brain

Een side objective is an exploration if visual stimulation, as being part of
routine EEG recordings, might serve as an alternative stimulation method to
study VBMEG changes in brain connectivity.

We aim to design an explorative study to investigate the differences in the
brain network connectivity in epileptic patients and healthy people, secondly
to investigate the influence of medication on the brain network connectivity.
Participation will consist of two session with an EEG registration with TMS and
photic stimulation for the TLE participants.The first measurement will be a
week before the admission to the EMU or observational unit. The second
measurement will be when the medication is tapered. This will be either just
before or directly after their stay on to the EMU. Both the healthy
participants and GGE participants will only schedule one appointment. Lastly, a
MRI-scan will be made of all participants.

Participation for the TLE participants will consists of a total of 2 EEG
registrations. The first TMS-EEG measurement shall be performed during an extra
appointment, scheduled prior the admission to the EMU/observation unit. The
second measurement shall be performed just before or directly after the regular
EMU stay for EEG-videoregistration. The admission to the EMU unit shall not be
lengthened due to participation in this study. Each session will have a total
duration of 120 minutes and will consist of explanation of the study, filling
out questionnairs, the TMS-EEG stimulation protocol and lastly photic
stimulation protocol. For both the GGE participants and healthy controls,
participation will only consist of one EEG registration with TMS and photic
stimulation. Furthermore, all participants will schedule an appointment to make
a MRI-scan.

TMS is non-invasive. TMS stimulation itself can be experiene as a small shock
with an accompanying muscle twitch. Furthermore, there is a small chance of
dizzyness and headache. The sitmulaiton protocol will be given with continuous
patient feedback to determine comfort, tolerability and effects of the
stimulation trials.The risk that it triggers a seizure in people with epilepsy
is reported to be max. 2.6%. In healthy subjects, TMS-related seizures have
been reported in seven cases in literature to our knowledge, and doubt was
expressed as to whether the events were seizures as no EEG was available at the
moment of occurence.The EMU or observation unit, where the TMS-EEG registration
will be performed, is a setting designed for optimal safety of patients in case
of seizure events. The goal of an EEG-videoregistration is the registration of
seizures, this is also the reason for the tapering of the medication which
increases the chance of capturing a seizure during the patients' admission. The
TMS evoked seizure may give valuable clinical information that influences the
decision-making process for that
patient.