Combined magnetoencephalography and electroencephalography in presurgical epilepsy evaluation

The goal of the proposed research project is the assessment of combined magneto- and electroencephalography in the presurgical evaluation of epilepsy patients. Magnetoencephalography (MEG) is a new technique which allows the measurement of the weak magnetic fields generated by neuronal activity of the human brain. Because the skull and scalp are essentially transparent to magnetic fields, MEG offers superior spatial resolution as compared to the traditional scalp-EEG and thus a new dimension for the investigation of brain pathophysiology. Epilepsy has been the main clinical application of MEG research, because only neurophysiological techniques like EEG and MEG provide specific information and have a temporal resolution in the order of milliseconds which is necessary to study the dynamical changes associated with human epilepsy. The recent introduction of whole-head MEG systems led to a major technological breakthrough and facilitates simultaneous recordings of spontaneous activity from the entire brain. Epilepsy surgery has become a valuable treatment option for medically refractory focal epilepsies rendering 70- 80% of patients seizure-free. Successful surgical treatment relies on a thorough presurgical work-up with coverging evidence from clinical seizure semiology, interictal and ictal EEG documented ruing intensive video-EEG monitoring, structural imaging with MRI as well as functional imaging with SPECT and PET. However, in a significant number of patients the seizure onset zone cannot be localized adequately with these methods. Therefore invasive electrodes (subdural grid or depth electrodes) have to be implanted which carry significant risks for the patient, require special facilities and are expensive in terms of personnel and equipment. Therefore, the improvement of non-invasive methods like MEG is warranted. Specifically, we will investigated the following research questions: 1. Localization of the irritative zone: We will record interictal epileptiform discharges in patients with well-defined temporal and extratemporal epileptic syndromes. We will assess the question whether different temporal lobe syndromes, e.g. mesial temporal lobe epilepsy, lesional temporal lobe epilepsy and non-lesional temporal lobe epilepsy and whether different seizure onset zones, e.g., mesial versus lateral, can be differentiated on the basis of interictal spike parameters. In exteratemporal lobe epilepsies we will assess the usefulness of combined MEG/EEG recordings for the localization of the irritative zone, for the placement of subdural grid electrodes, and for the assessment of supplementary sensorimotor motor area (SSMA) epilepsy. Finally, we will study propagation of interictal epileptic activity by spatiotemporal dipole modeling. 2. The relationship of MEG, scalp-EEG and electrocorticography (ECoG): We will investigate what area of cortex involved in synchronized epileptic activity is necessary to produce a detectable signal on scalp-EEG and MEG by simultaneous invasive EEG recordings. Furthermore, we will address the question whether and under which circumstances epileptic activity can be recorded from mesial temporal structures on scalp-EEG and MEG. 3. Ictal MEG recordings: We will record seizures on MEG in selected patients and systematically compare EEG and MEG localizations of the seizure onset zone. We will perform DC-MEG-recordings to clarify the mechanisms underlying the transition from the interictal to the ictal state. 4. Focal slow wave activity as a marker of the functional deficit zone: We will measure slow wave activity in patients with defined temporal and extratemporal lobe syndromes, quantify this activity by spectral analysis and compare the results with other tests of functional deficit like interictal SPECT and neuropsychological assessment. 5. Localization of essential brain regions using somatosensory evoked responses: We will record somatosensory evoked responses in order to localize central sulcus non-invasively which is important to avoid neurological deficits during neurosurgical procedures in the central region. During the 3-year period of the proposed research project we will study approximately 300 patients with well- defined epileptic syndromes with combined MEG/EEG recordings, 30-45 patients will also undergo invasive EEG measurements. We will apply novel biophysical modeling techniques including spatiotemporal dipole models and realistic head models. We anticipate that our research will provide new insights into the neurophysiologal basis of human epilepsy and improve non-invasive presurgical evaluation of epilepsy patients.

We investigated the role of the combined use of magnetoencephalography (MEG) and scalp- electroencephalography (EEG) for the presurgical evaluation of epilepsy patients with medically refractory seizures. MEG is a new neurophysiological technique which allows the measurement of the weak magnetic fields generated by neuronal activity of the human brain. Because magnetic fields are less distorted than electric fields by the skull and scalp, MEG offers superior spatial resolution as compared to the traditional scalp-EEG. The combined use of both techniques yielded valuable information on the localization of both the epileptogenic zone and essential brain areas. Our results should facilitate an improved non-invasive presurgical epilepsy evaluation and should be helpful for planning the most efficient and safest surgical procedure. Purpose: Epilepsy has a prevalence of 0.8% and thus represents one of most frequent neurological disorders. Although epilepsy can be treated successfully with antiepileptic drugs in 80% of patients, 20% of patients turn out to suffer from medically refractory seizures. Many of these patients can be rendered seizure-free by a neurosurgical operation removing the brain area where the seizures originate - the so-called epileptogenic zone. In Austria 4.000- 6.000 patients can be considered as potential candidates for epilepsy surgery. The goal of the operation is to remove the epileptogenic tissue while sparing essential brain regions like primary motor and speech cortex which have to be localized exactly during a thorough presurgical evaluation. The aim of the research project was the assessment of combined magnetoencephalography (MEG) and scalp-electroencephalography (EEG) in presurgical epilepsy evaluation. MEG is a new neurophysiological technique which allows the measurement of the weak magnetic fields generated by neuronal activity of the human brain. Because magnetic fields are less distorted than electric fields by the skull and scalp, MEG offers a superior spatial resolution as compared to the traditional scalp-EEG and therefore represents a promising tool for epilepsy evaluation. Results: Simultaneous MEG and scalp-EEG recordings were performed with a 143 channel whole-head MEG system in a large magnetically shielded room and from 23-40 gold-disk electrodes placed according the extended International 10-20 System. We applied novel biophysical modeling techniques including spatiotemporal dipole models and distributed source models with realistic head models and thus could correlate the neurophysiological information with anatomical structures in magnetic resonance images. The combined use of MEG and EEG was superior to either technique alone and provided valuable information for the exact localization of both the epileptogenic zone and essential brain areas. Combined MEG/EEG recordings therefore can further reduce the need for invasive electrophysiological procedures and are helpful for planning the most efficient and safest surgical procedure.