Brain areas with epileptic high frequency oscillations are functionally isolated in MEG virtual electrode networks.
Previous studies have associated network hubs and epileptiform activity, such as spikes and high frequency oscillations (HFOs), with the epileptogenic zone. The epileptogenic zone is approximated by the area that generates interictal epileptiform activity: the irritative zone. Our aim was to determine the relation between network hubs and the irritative zone.



Interictal resting-state MEG recordings of 12 patients with refractory epilepsy were analysed. Beamformer-based virtual electrodes were calculated at 70 locations around the epileptic spikes (irritative zone) and in the contralateral hemisphere. Spikes and HFOs were marked in all virtual electrodes. A minimum spanning tree network was generated based on functional connectivity (phase lag index; PLI) between all virtual electrodes to calculate the betweenness centrality, an indicator of hub status of network nodes.



Betweenness centrality was low, and PLI was high, in virtual electrodes close to the centre of the irritative zone, and in virtual electrodes with many spikes and HFOs.



Node centrality increases with distance from brain areas with spikes and HFOs, consistent with the idea that the irritative zone is a functionally isolated part of the epileptic network during the interictal state.



A new hypothesis about a pathological hub located remotely from the irritative zone and seizure onset zone opens new ways for surgery when epileptogenic areas and eloquent cortex coincide.
Department of Clinical Neurophysiology and MEG Center, Neuroscience Campus Amsterdam, VU University Medical Center, Postbus 7057, 1007 MB Amsterdam, The Netherlands. Electronic address: i.nissen@vumc.nl.
Ida A
IA
Nissen
Brain Center Rudolf Magnus, Department of Neurology and Neurosurgery, University Medical Center Utrecht, Postbus 85500, 3508 GA Utrecht, The Netherlands. Electronic address: N.vanKlink-2@umcutrecht.nl.
Nicole E C
NE
van Klink
Brain Center Rudolf Magnus, Department of Neurology and Neurosurgery, University Medical Center Utrecht, Postbus 85500, 3508 GA Utrecht, The Netherlands; SEIN - Stichting Epilepsie Instellingen Nederland, Heemstede, Postbus 540, 2130 AM Hoofddorp, The Netherlands. Electronic address: mzijlmans@hotmail.com.
Maeike
M
Zijlmans
Department of Clinical Neurophysiology and MEG Center, Neuroscience Campus Amsterdam, VU University Medical Center, Postbus 7057, 1007 MB Amsterdam, The Netherlands. Electronic address: cj.stam@vumc.nl.
Cornelis J
CJ
Stam
Department of Clinical Neurophysiology and MEG Center, Neuroscience Campus Amsterdam, VU University Medical Center, Postbus 7057, 1007 MB Amsterdam, The Netherlands. Electronic address: a.hillebrand@vumc.nl.
Arjan
A
Hillebrand
D000293:Adolescent; D000328:Adult; D001921:Brain / Q000503:physiopathology; D058256:Brain Waves; D002648:Child; D004827:Epilepsy / Q000503:physiopathology*; D006801:Humans; D015225:Magnetoencephalography
Beamformer virtual electrodes; Betweenness centrality; Epileptogenic zone; High frequency oscillations; Irritative zone; MEG; Network hub