Biomarkers for the ictogenesis of absence seizures – The role of cortical 5-9 Hz oscillations.
Final Report Abstract
Absence epilepsy is one of the most common forms of idiopathic generalized epilepsies and its etiology is poorly understood. With the current pharmacological treatment approaches up to 30% of patients remain refractory and 60% of them show substantial neurological side effects. Neurophysiologically, absence epilepsy is characterized by spike and wave discharges (SWD), which can be recorded in the electroencephalogram of patients. A recent study of our group revealed that the spike- and the wave component of the SWD are generated at different locations within the thalamo-cortical system and that the wave component forms the basic rhythm of the SWD in the form of 5-9 Hz oscillations. At the same time however, cortical 5-9 Hz oscillations can not only be seen before an SWD (preictal) but also during seizure free periods (interictal). This project investigated and compared spectral characteristics, the level of excitability and the degree of communication between brain regions (coupling) for pre- and interictal 5-9 Hz oscillations as well as during seizure free periods without 5-9 Hz oscillations. We found that pre-ictal 5-9 Hz oscillations have a unique spectral and coupling profile that can be used to improve SWD prediction. Nonetheless, we could causally proof that also interictal 5-9 Hz oscillations are high risk moments for SWD generation as low frequency electrical double pulse stimulation of the cortical seizure onset zone carried a significantly higher risk for the induction of epileptic afterdischarges (AD) compared to stimulation during periods without 5-9 Hz oscillations. By comparing excitability and coupling for stimulations that either induced or not induced an AD as well as 5-9 Hz oscillations that were followed or not followed by a spontaneous SWD, it could be established that an intermediate level of coupling between the seizure onset zone in S1 and the centromdedian thalamic nucleus (CM) is most favorable for the generation of an SWD. Interestingly, while no overall differences in cortical excitability were revealed between conditions, more dynamic changes in excitability were detected during 5-9 Hz oscillations. More specifically, a significantly higher excitability was present during the ascending phase of the oscillation compared to the descending phase of the oscillation. The latter supports the idea that cortical 5-9 Hz oscillations provide adequate time windows of heightened excitability in which thalamic input provided by the CM can superimpose the spike component on the ascending phase of the 5-9 Hz oscillation to compose the rhythmic stereotypic SWD pattern. Lastly, while low frequency cortical stimulation carried a high risk for the induction of afterdischarges, closed loop high frequency stimulation during 5-9 Hz oscillations were found to have the potential to prevent SWD. This project therefor deepened our understanding on network mechanisms of SWD generation and paves the way for the development of a closed loop SWD prediction and prevention system.
Publications
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Biomarkers for the ictogenesis of absence seizures - The role of cortical 5-9 Hz oscillations. Society for Neuroscience annual Meeting. Chicago, IL: Poster Abstract
Lüttjohann A. & Nikalexi E.
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Exploring the dynamics of 5–9 Hz oscillations: Implications for absence epilepsy and seizure prediction. Abstract. Epilepsia, 65(S1), 1-508.
Nikalexi E., Budde T., Seidenbecher T., Pape H.C. & Lüttjohann A.
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Unique frequency and excitability characteristics seen for 5-9 Hz oscillations preceding absence seizures. FENS Forum 2024, Vienna, Austria
Nikalexi E., Budde T., Seidenbecher T., Pape H.C. & Lüttjohann A.
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Precursor activity in 24 hours EEG recordings of children with childhood absence epilepsy. Poster Abstract 2.63; 25th Dutch Neuroscience Meeting, Tiel, The Netherlands
Lüttjohann A., Seiger M., Ossenblok P., van Luijtelaar G., van Blooijs D., Bourez-Swart M. & Dietze C.
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Spectral and coupling characteristics of somatosensory cortex and centromedian thalamus differentiate between pre- and inter-ictal 5–9 Hz oscillations in a genetic rat model of absence epilepsy. Neurobiology of Disease, 205, 106777.
Nikalexi, Eleni; Maksimenko, Vladimir; Seidenbecher, Thomas; Budde, Thomas; Pape, Hans-Christian & Lüttjohann, Annika
