Phase Coherent Currents Underlying Neocortical Seizure-Like State Transitions

Breton, Vanessa L.; Bardakjian, Berj L.; Carlen, Peter L.

doi:10.1523/eneuro.0426-18.2019

Cited by 8 publications

(6 citation statements)

References 75 publications

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“…Interestingly, our study is the first to demonstrate that even focal seizures that do not generalize can coactivate the ANT at the onset. Phases of slower oscillations are reported to be associated with increased neural excitability (Vanhatalo et al, 2004)(Alvarado-Rojas et al, 2011) (Breton et al, 2019). Similarly, our observation from power spectra, spectral exponents, and PAC suggests increased thalamic intrinsic excitability at seizure onset.…”

Section: Discussionsupporting

confidence: 76%

Anterior Nucleus of Thalamus Gates Progression of Mesial Temporal Seizures by Modulating Thalamocortical Synchrony

Chaitanya

Ilyas

Tóth

et al. 2020

Preprint

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The anterior nucleus of the thalamus (ANT) mediates cortical-subcortical interactions between the limbic system and is hypothesized to facilitate the early organization of temporal lobe seizures. We set out to investigate the dynamic changes in synchronization parameters between the seizure onset zone (SOZ) and ANT during seizure stages (pre-onset to post-termination) in seven patients (n=26 seizures) with drug-resistant nonlesional temporal lobe epilepsy. Using local field potentials recorded directly from the limbic system and the ANT during stereoelectroencephalography, we confirm that the onset of mesial temporal lobe seizure is associated with increased thalamocortical network excitability and phase-amplitude coupling. The increase in thalamocortical phase synchronization preceded seizure onset, thereby suggesting that the early organization of temporal lobe seizures involves the integration of the ANT within the epileptic network. Towards seizure termination, there is a significant decrease in thalamic excitability, thalamocortical synchronization, and decoupling, thereby suggesting a breakdown in thalamocortical connectivity. A higher disease burden is significantly correlated with increased synchronization between the ANT and epileptic networks. Collectively, the results elucidate mechanistic insights and provide the temporal architecture of thalamocortical interactions that can be targeted in the rational designing of closed-loop seizure abortive interventions.HighlightsAnterior nucleus of thalamus is coactivated at the onset of temporal lobe seizuresIncrease thalamocortical synchronization and excitability is observed at seizure onsetSeizure termination is characterized by a breakdown in thalamocortical connectivityIncreased seizure burden affects thalamocortical synchronization

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Section: Discussionsupporting

confidence: 76%

Anterior Nucleus of Thalamus Gates Progression of Mesial Temporal Seizures by Modulating Thalamocortical Synchrony

Chaitanya

Ilyas

Tóth

et al. 2020

Preprint

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“…To classify the post-ictal state, a first-order hidden Markov model (HMM) was applied as per Breton et al (2019) . We adapted the features for application to a 4-state model with two Gaussians used to fit each state (as depicted in Supplementary Fig.…”

Section: Methodsmentioning

confidence: 99%

“…A similar approach for significance calculation was used for connectivity analysis. The method of surrogate data testing was adapted from Guirgis et al (2015) and Breton et al (2019) . A 200-surrogate test with 5% significance threshold was used on a sample patients’ iEEG data, to determine whether the PAC observed was significant.…”

Section: Methodsmentioning

confidence: 99%

Delta-gamma phase-amplitude coupling as a biomarker of postictal generalized EEG suppression

Grigorovsky

Jacobs

Breton

et al. 2020

Brain Communications

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Phase-amplitude coupling analysis shows that a state of postictal generalized EEG suppression has increased delta-gamma coupling. These coupling features, used with an unsupervised hidden Markov model, reliably differentiated four substates in seizure episodes. A sudden unexpected death in epilepsy case study showed coupling activity similar to a postictal state. Postictal generalized EEG suppression is the state of suppression of electrical activity at the end of a seizure. Prolongation of this state has been associated with increased risk of sudden unexpected death in epilepsy, making characterization of underlying electrical rhythmic activity during postictal suppression an important step in improving epilepsy treatment. Phase-amplitude coupling in EEG reflects cognitive coding within brain networks and some of those codes highlight epileptic activity; therefore, we hypothesized that there are distinct phase-amplitude coupling features in the postictal suppression state that can provide an improved estimate of this state in the context of patient risk for sudden unexpected death in epilepsy. We used both intracranial and scalp EEG data from eleven patients (six male, five female; age range 21–41 years) containing 25 seizures, to identify frequency dynamics, both in the ictal and postictal EEG suppression states. Cross-frequency coupling analysis identified that during seizures there was a gradual decrease of phase frequency in the coupling between delta (0.5-4 Hz) and gamma (30+ Hz), which was followed by an increased coupling between the phase of 0.5-1.5 Hz signal and amplitude of 30-50 Hz signal in the postictal state as compared to the pre-seizure baseline. This marker was consistent across patients. Then, using these postictal-specific features, an unsupervised state classifier – a hidden Markov model – was able to reliably classify four distinct states of seizure episodes, including a postictal suppression state. Furthermore, a connectome analysis of the postictal suppression states showed increased information flow within the network during postictal suppression states as compared to the pre-seizure baseline, suggesting enhanced network communication. When the same tools were applied to the EEG of an epilepsy patient who died unexpectedly, ictal coupling dynamics disappeared and postictal phase-amplitude coupling remained constant throughout. Overall, our findings suggest that there are active postictal networks, as defined through coupling dynamics, that can be used to objectively classify the postictal suppression state; furthermore, in a case study of sudden unexpected death in epilepsy, the network does not show ictal-like phase-amplitude coupling features despite the presence of convulsive seizures, and instead demonstrates activity similar to postictal. The postictal suppression state is a period of elevated network activity as compared to the baseline activity which can provide key insights into the epileptic pathology.

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“…The phase amplitude cross frequency coupling (PAC) analysis was computed as previously described ( Breton et al, 2019 ). The instantaneous phase of the low frequency oscillations (1-12 Hz) and amplitude of the high frequency oscillations (30-250 Hz) were computed by convolution of the filtered LFP signal with the complex Morlet wavelet.…”

Section: Signal Processingmentioning

confidence: 99%

Altered neocortical oscillations and cellular excitability in an in vitro Wwox knockout mouse model of epileptic encephalopathy

Breton

Aquilino

Repudi

et al. 2021

Neurobiology of Disease

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Summary Loss of function mutations of the WW domain-containing oxidoreductase ( WWOX ) gene are associated with severe and fatal drug-resistant pediatric epileptic encephalopathy. Epileptic seizures are typically characterized by neuronal hyperexcitability; however, the specific contribution of WWOX to that hyperexcitability has yet to be investigated. Using a mouse model of neuronal Wwox -deletion that exhibit spontaneous seizures, in vitro whole-cell and field potential electrophysiological characterization identified spontaneous bursting activity in the neocortex, a marker of the underlying network hyperexcitability. Spectral analysis of the neocortical bursting events highlighted increased phase-amplitude coupling, and a propagation from layer II/III to layer V. These bursts were NMDAR and gap junction dependent. In layer II/III pyramidal neurons, Wwox knockout mice demonstrated elevated amplitude of excitatory post-synaptic currents, whereas the frequency and amplitude of inhibitory post-synaptic currents were reduced, as compared to heterozygote and wild-type littermate controls. Furthermore, these neurons were depolarized and demonstrated increased action potential frequency, sag current, and post-inhibitory rebound. These findings suggest WWOX plays an essential role in balancing neocortical excitability and provide insight towards developing therapeutics for those suffering from WWOX disorders.

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Phase Coherent Currents Underlying Neocortical Seizure-Like State Transitions

Cited by 8 publications

References 75 publications

Anterior Nucleus of Thalamus Gates Progression of Mesial Temporal Seizures by Modulating Thalamocortical Synchrony

Anterior Nucleus of Thalamus Gates Progression of Mesial Temporal Seizures by Modulating Thalamocortical Synchrony

Delta-gamma phase-amplitude coupling as a biomarker of postictal generalized EEG suppression

Altered neocortical oscillations and cellular excitability in an in vitro Wwox knockout mouse model of epileptic encephalopathy

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