Identification of epileptiform networks using functional MRI: model- vs data-driven approaches

EEG-correlated functional MRI (EEG-fMRI) has been evaluated as a non-invasive
technique for the pre-operative work-up. EEG-fMRI is unique, because it is able
to visualize the activity of multifocal and deeply situated cortical areas. The
results are promising: most studies report good concordance between activated
BOLD areas and the presumed epileptiform focus. Despite many methodological
improvements, the sensitivity of the method ranges between 50 and 80%. The most
important reason is an insufficient number of interictal epileptiform
discharges (IEDs) during the limited time scope of the recording. To deal with
this limitation, data-driven techniques that analyze the fMRI data without the
use of EEG, might be an additional tool or even an alternative for EEG-fMRI.
However, these techniques need to be validated before they can be used for
clinical application.

The primary objective of this study is to investigate whether a data-driven
fMRI procedure enables the identification of the epileptiform network that can
be used in the pre-operative work-up of patients with localization related
epilepsy.

The first part of the study is a *proof-of-concept* study aimed at the
methodological development of the data-driven fMRI technique. For that purpose,
we will study patients with idiopathic generalized epilepsy (IGE) characterized
by bilateral synchronized spike-and-wave discharges (SWDs) in the EEG which is
typical for absence epilepsy, because the underlying networks of these
discharges are reported to be robust and reproducible with EEG-fMRI and
data-driven approaches. The EEG-fMRI data of these patients will be acquired
within one recording session, while they are on maintenance doses of their
habitual antiepileptic drugs. In the second phase (the clinical study), the
added value of the data-driven approach will be evaluated by applying the two
methods (EEG-fMRI and data-driven fMRI) to the simultaneously recorded EEG and
fMRI of patients with localization related epilepsy who are candidates for
epilepsy surgery (n=13). According to the standard clinical procedures the
medication of these patients will be minimized during their pre-surgical
video-EEG examination. EEG-fMRI data will be acquired before and at the end of
the video-EEG session, such that we will obtain data of two situations: before
and after medication withdrawal. For each situation, the data will be analyzed
with the model- and data-driven approach.

Several safety issues are involved with the simultaneous recording of EEG and
fMRI. Special MR-compatible EEG equipment is required that includes an EEG
amplifier and EEG cap without ferrous materials, current limited resistors for
each electrode on the cap and twisted electrode leads. We will use the
equipment of MicroMed (Treviso, Italy) that has been used in a previous
EEG-fMRI study as well (METC Utrecht, registration number 07-146/E). In
addition, a second EEG cap is available, that has additional wired loops
attached to the cap to record small movements of the electrode leads. Safety
tests were performed to test the equipment (for further information we refer to
the safety report included in appendix A of the research protocol).
The additional risk of seizures occurring during scanning that may increase in
case of medication withdrawal will be handled as usual by specially trained
personnel: the scan will be aborted immediately and the safety of the patient
will be assured.
All the patients who participate in this study will learn, especially, more
about the underlying mechanisms or networks of their epilepsy. The results of
the EEG-fMRI will, however, not influence the diagnosis and treatment on an
individual basis, but the gain of knowledge certainly will be of importance for
a better understanding and probably in the end a better surgical treatment of
patients with complex partial epilepsy.