Increased Functional MEG Connectivity as a Hallmark of MRI-Negative Focal and Generalized Epilepsy

Abstract

Epilepsy is one of the most prevalent neurological diseases with a high morbidity. Accumulating evidence has shown that epilepsy is an archetypical neural network disorder. Here we developed a non-invasive cortical functional connectivity analysis based on magnetoencephalography (MEG) to assess commonalities and differences in the network phenotype in different epilepsy syndromes (non-lesional/cryptogenic focal and idiopathic/genetic generalized epilepsy). Thirty-seven epilepsy patients with normal structural brain anatomy underwent a 30-min resting state MEG measurement with eyes closed. We only analyzed interictal epochs without epileptiform discharges. The imaginary part of coherency was calculated as an indicator of cortical functional connectivity in five classical frequency bands. This connectivity measure was computed between all sources on individually reconstructed cortical surfaces that were surface-aligned to a common template. In comparison to healthy controls, both focal and generalized epilepsy patients showed widespread increased functional connectivity in several frequency bands, demonstrating the potential of elevated functional connectivity as a common pathophysiological hallmark in different epilepsy types. Furthermore, the comparison between focal and generalized epilepsies revealed increased network connectivity in bilateral mesio-frontal and motor regions specifically for the generalized epilepsy patients. Our study indicated that the surface-based normalization of MEG sources of individual brains enables the comparison of imaging findings across subjects and groups on a united platform, which leads to a straightforward and effective disclosure of pathological network characteristics in epilepsy. This approach may allow for the definition of more specific markers of different epilepsy syndromes, and increased MEG-based resting-state functional connectivity seems to be a common feature in MRI-negative epilepsy syndromes.

The Effectiveness of Vagus Nerve Stimulation in Drug-Resistant Epilepsy Correlates with Vagus Nerve Stimulation-Induced Electroencephalography Desynchronization

“…In other studies, the intraindividual and even interindividual comparisons of functional connectivity assessment with PLI had similar amplitudes (Douw et al, 2010;Geraedts et al, 2018;Stam et al, 2009;Wang and Meng, 2016). A small difference is explained in part by numerous cofactors that influence interictal functional connectivity such as age (Smit et al, 2012(Smit et al, , 2016, cognitive and psychiatric coexisting conditions (Yoo et al, 2018), epilepsy types (Li Hegner et al, 2018) and treatments (Clemens et al, 2014;Haneef et al, 2015). Furthermore, the decrease in functional connectivity between ON and OFF periods does not need to be high to be relevant.…”

Dynamical Mechanisms of Interictal Resting-State Functional Connectivity in Epilepsy

“…Various contradictory findings were reported, such as globally increased/decreased connectivity (Pereira et al, 2010;Pittau et al, 2012;Wirsich et al, 2016), or concomitantly increased and decreased connectivity in neighboring networks (Bettus et al, 2009(Bettus et al, , 2010Liao et al, 2010;Su et al, 2015). In contrast, most RS-FC studies using magnetoencephalographic (MEG) and electroencephalographic (EEG) recordings indicate predominantly increased connectivity between the regions found to be less connected in fMRI (Bettus et al, 2008;Bartolomei et al, 2013a,b;Schevon et al, 2007;Lagarde et al, 2018;Li Hegner et al, 2018). These discrepancies could be attributed to the different functional aspects captured by each modality or the different RS-FC estimates applied (Ridley et al, 2017).…”

Network Perspectives on Epilepsy Using EEG/MEG Source Connectivity

“…Epilepsy is commonly considered an archetypical network disease (1), with seizures and interictal activity generated and spreading in networks involving one or both hemispheres. There is a growing body of imaging evidence suggesting that epilepsy affects both structural (2, 3) and functional brain network properties (4–7). Interestingly, even in idiopathic/genetic generalized epilepsy, there is a certain level of focality both in resting-state imaging (7) as well as for generators of epileptiform activity (8) and seizures (9, 10).…”