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

Spike-wave-discharges (SWD) are the electrophysiological hallmark of absence epilepsy. SWD are generated in the thalamo-cortical network and a seizure onset zone was identified in the somatosensory cortex (S1). We have shown before that inhibition of the centromedian thalamic nucleus (CM) in GAERS r...

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Main Authors: Eleni Nikalexi, Vladimir Maksimenko, Thomas Seidenbecher, Thomas Budde, Hans-Christian Pape, Annika Lüttjohann
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:Neurobiology of Disease
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Online Access:http://www.sciencedirect.com/science/article/pii/S0969996124003796
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author Eleni Nikalexi
Vladimir Maksimenko
Thomas Seidenbecher
Thomas Budde
Hans-Christian Pape
Annika Lüttjohann
author_facet Eleni Nikalexi
Vladimir Maksimenko
Thomas Seidenbecher
Thomas Budde
Hans-Christian Pape
Annika Lüttjohann
author_sort Eleni Nikalexi
collection DOAJ
description Spike-wave-discharges (SWD) are the electrophysiological hallmark of absence epilepsy. SWD are generated in the thalamo-cortical network and a seizure onset zone was identified in the somatosensory cortex (S1). We have shown before that inhibition of the centromedian thalamic nucleus (CM) in GAERS rats resulted in a selective suppression of the spike component while rhythmic cortical 5–9 Hz oscillations remained present. Such oscillations are often seen to precede SWD activity in this well-validated genetic rat model of absence epilepsy, but are also seen in seizure-free periods. The present study characterizes the profile of 5–9 Hz oscillations in thalamo-cortical circuits during pre- and inter-ictal states.Here we recorded local-field-potentials in S1, CM and the secondary motor cortex of GAERS. Time-frequency analysis was used to assess spectral power and non-linear-association analysis was used to determine coupling strength and directionality between brain areas. Phase-specific electrical stimulation was used to compare cortical excitability and to assess the risk for epileptic afterdischarges.Coupling strength and spectral power were higher for the inter-ictal compared to the pre-ictal 5–9 Hz oscillations. However, coupling strength during pre-ictal oscillations was higher than during passive wakefulness. Double pulse stimulation during 5–9 Hz oscillations was more likely to induce epileptic afterdischarges compared to stimulation during passive wakefulness. While no overall differences in cortical excitability were revealed, phase-specific differences in excitability were noticed during the oscillation.Our findings indicate that intermediate coupling between S1 and CM favors SWD generation, thereby adding to the previous notion that 5–9 Hz oscillations represent high-risk periods for seizure generation. In general, pre-ictal oscillations display a unique electrophysiological profile in GAERS that might pave the way for qualification as biomarker for SWD generation and seizure prediction.
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spelling doaj-art-69a7fb2053e34008acdd4679892ffd4a2025-01-24T04:44:38ZengElsevierNeurobiology of Disease1095-953X2025-02-01205106777Spectral 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 epilepsyEleni Nikalexi0Vladimir Maksimenko1Thomas Seidenbecher2Thomas Budde3Hans-Christian Pape4Annika Lüttjohann5Institute of Physiology I, Münster University, Münster, GermanyDepartment of Civil and Environmental Engineering, National University of Singapore, SingaporeInstitute of Physiology I, Münster University, Münster, GermanyInstitute of Physiology I, Münster University, Münster, GermanyInstitute of Physiology I, Münster University, Münster, GermanyInstitute of Physiology I, Münster University, Münster, Germany; Corresponding author at: Institute of Physiology I (Neurophysiology), Münster University, Robert-Koch Str. 27a, D-48149 Münster, Germany.Spike-wave-discharges (SWD) are the electrophysiological hallmark of absence epilepsy. SWD are generated in the thalamo-cortical network and a seizure onset zone was identified in the somatosensory cortex (S1). We have shown before that inhibition of the centromedian thalamic nucleus (CM) in GAERS rats resulted in a selective suppression of the spike component while rhythmic cortical 5–9 Hz oscillations remained present. Such oscillations are often seen to precede SWD activity in this well-validated genetic rat model of absence epilepsy, but are also seen in seizure-free periods. The present study characterizes the profile of 5–9 Hz oscillations in thalamo-cortical circuits during pre- and inter-ictal states.Here we recorded local-field-potentials in S1, CM and the secondary motor cortex of GAERS. Time-frequency analysis was used to assess spectral power and non-linear-association analysis was used to determine coupling strength and directionality between brain areas. Phase-specific electrical stimulation was used to compare cortical excitability and to assess the risk for epileptic afterdischarges.Coupling strength and spectral power were higher for the inter-ictal compared to the pre-ictal 5–9 Hz oscillations. However, coupling strength during pre-ictal oscillations was higher than during passive wakefulness. Double pulse stimulation during 5–9 Hz oscillations was more likely to induce epileptic afterdischarges compared to stimulation during passive wakefulness. While no overall differences in cortical excitability were revealed, phase-specific differences in excitability were noticed during the oscillation.Our findings indicate that intermediate coupling between S1 and CM favors SWD generation, thereby adding to the previous notion that 5–9 Hz oscillations represent high-risk periods for seizure generation. In general, pre-ictal oscillations display a unique electrophysiological profile in GAERS that might pave the way for qualification as biomarker for SWD generation and seizure prediction.http://www.sciencedirect.com/science/article/pii/S0969996124003796Spike and wave dischargesGAERSSomatosensory cortexCentromedian thalamusNetwork analysisEvoked potentials
spellingShingle Eleni Nikalexi
Vladimir Maksimenko
Thomas Seidenbecher
Thomas Budde
Hans-Christian Pape
Annika Lüttjohann
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
Spike and wave discharges
GAERS
Somatosensory cortex
Centromedian thalamus
Network analysis
Evoked potentials
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Spike and wave discharges
GAERS
Somatosensory cortex
Centromedian thalamus
Network analysis
Evoked potentials
url http://www.sciencedirect.com/science/article/pii/S0969996124003796
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