Enhanced thalamo‐hippocampal synchronization during focal limbic seizures

Aracri, Patrizia; Curtis, Marco de; Forcaia, Greta; Uva, Laura

doi:10.1111/epi.14521

Cited by 19 publications

(9 citation statements)

References 41 publications

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“…The thalamus plays an important role during synchronization, as evidenced by various animal studies and human imaging studies. 36,37 This notion may be further supported by the finding that thalamic stimulation can be used to control seizures. 38 Since intracranial recording from thalamus is uncommon in epileptic patients, it was not possible to investigate the differences between thalamic and cortical termination activity in our study.…”

Section: Variability Of Patterns At Termination Implies Differences Imentioning

confidence: 87%

Quantification of seizure termination patterns reveals limited pathways to seizure end

Salami

Borzello

et al. 2021

Preprint

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Seizures result from a variety of pathologies and exhibit great diversity in their dynamics. Although many studies have examined the dynamics of seizure initiation, few have investigated the mechanisms leading to seizure termination. We examined intracranial recordings from patients with intractable focal epilepsy to differentiate seizure termination patterns and investigate whether these termination patterns are indicative of different underlying mechanisms. Seizures (n=710) were recorded intracranially from 104 patients and visually classified as focal or secondarily generalized. Only two patterns emerged from this analysis: (a) those that end simultaneously across the brain (synchronous termination), and (b) those whose ictal activity terminates in some regions but continues in others (asynchronous termination). Finally, seizures ended with either an intermittent bursting pattern (burst suppression pattern), or continuous activity (continuous bursting). These findings allowed for a classification and quantification of the burst suppression ratio, absolute energy and network connectivity of all seizures and comparison across different seizure termination patterns. We found that different termination patterns can manifest within a single patient, even in seizures originating from the same onset locations. Most seizures terminate with patterns of burst suppression regardless of generalization but that seizure that secondarily generalize show burst suppression patterns in 90% of cases, while only 60% of focal seizures exhibit burst suppression. Interestingly, we found similar absolute energy and burst suppression ratios in seizures with synchronous and asynchronous termination, while seizures with continuous bursting were found to be different from seizures with burst suppression, showing lower energy during seizure and lower burst suppression ratio at the start and end of seizure. Finally, network density was observed to increase with seizure progression, with significantly lower densities in seizures with continuous bursting compared to seizures with burst suppression. Our study demonstrates that there are a limited number of seizure termination patterns, suggesting that, unlike seizure initiation, the number of mechanisms underlying seizure termination is constrained. The study of termination patterns may provide useful clues about how these seizures may be managed, which in turn may lead to more targeted modes of therapy for seizure control.

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Section: Variability Of Patterns At Termination Implies Differences Imentioning

confidence: 87%

Quantification of seizure termination patterns reveals limited pathways to seizure end

Salami

Borzello

et al. 2021

Preprint

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“…Moreover, many other mechanisms such as acidosis (Ziemann et al, 2008), the upregulation of inhibitory neurons (Wen et al, 2015), glutamate depletion (Lado & Moshé, 2008), the depolarization block of neurons mediated by K + release from astrocytes (Bragin et al, 1997), after-hyperpolarization due to K + channels (Timofeev & Steriade, 2004), postburst depression (Boido et al, 2014), increased synchrony (Schindler et al, 2007) and the release of adenosine (During & Spencer, 1992; Uva & de Curtis, 2020) have been suggested to play a role in seizure termination. The abrupt termination of a seizure across the entire brain requires long-range communication which may involve thalamocortical interactions (Aracri et al, 2018; Evangelista et al, 2015), travelling waves (Martinet et al, 2017; Proix et al, 2018) and ephaptic interactions (Jefferys, 1995; Shivacharan et al, 2019). Multiple neuromodulatory, ionic, synaptic and neuronal components likely cooperate to terminate a seizure.…”

Section: Discussionmentioning

confidence: 99%

Focal seizures are organized by feedback between neural activity and ion concentration changes

Gentiletti

Gnatkovsky

et al. 2021

Preprint

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Human and animal EEG data demonstrate that focal seizures start with low-voltage fast activity, evolve into rhythmic burst discharges and are followed by a period of suppressed background activity. This suggests that processes with dynamics in the range of tens of seconds govern focal seizure evolution. We investigate the processes associated with seizure dynamics by complementing the Hodgkin-Huxley mathematical model with the physical laws that dictate ion movement and maintain ionic gradients. We show that the disturbance of K+ and Cl− homeostasis by the fast discharge of inhibitory interneurons is sufficient to initiate seizures, which are maintained by positive feedback between ion concentration changes and neuronal activity. Gradual Na+ accumulation increases the rate of the Na+/K+-pump, creating negative feedback which slows down and terminates ictal discharges and contributes to the postictal state. Our results emphasize ionic dynamics as elementary processes behind seizure generation and indicate targets for new therapeutic strategies.

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“…It can eventually lead to neuronal dysfunction and apoptosis by activating the calpain and caspase-3 pathways (Baudry and Bi, 2016; Hoque et al, 2016; Izumida et al, 2017; Deng et al, 2019). On the other hand, synchronous discharge, neuronal injury, and even neuronal loss are the typical electroencephalogram and pathological features of epilepsy (Aracri et al, 2018; Bumanglag and Sloviter, 2018; Chang et al, 2018). For example, apoptosis is known to be involved in the formation of hippocampal sclerosis in the patients with medial temporal lobe epilepsy (Danis et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Mode-Dependent Effect of Xenon Inhalation on Kainic Acid-Induced Status Epilepticus in Rats

Zhang

et al. 2019

Front. Cell. Neurosci.

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Previous studies have reported the possible neuroprotective effects of xenon treatment. The purpose of this study was to define the range of effective xenon ratio, most effective xenon ratio, and time-window for intervention in the kainic acid (KA) – induced status epilepticus (SE) rat model. Different ratios of xenon (35% xenon, 21% oxygen, 44% nitrogen, 50% xenon, 21% oxygen, 29% nitrogen, 70% xenon, 21% oxygen, and 9% nitrogen) were used to treat the KA-induced SE. Our results confirmed the anti-seizure role of 50 and 70% xenon mixture, with a stronger effect from the latter. Further, 70% xenon mixture was dispensed at three time points (0 min, 15 min delayed, and 30 min delayed) after KA administration, and the results indicated the anti-seizure effect at all treated time points. The results also established that the neuronal injury in the hippocampus and entorhinal cortex (EC), assessed using Fluoro-Jade B (FJB) staining, were reversed by the xenon inhalation, and within 30 min after KA administration. Our study, therefore, indicates the appropriate effective xenon ratio and time-window for intervention that can depress seizures. The prevention of neuronal injury and further reversal of the loss of effective control of depress network in the hippocampus and EC may be the mechanisms underlying the anti-seizure effect of xenon.

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Enhanced thalamo‐hippocampal synchronization during focal limbic seizures

Abstract: As suggested by clinical studies performed during pre-surgical intracranial monitoring, our data confirm a role of the midline thalamus in leading the synchronous bursting activity at the end of focal seizures in the mesial temporal regions.

Cited by 19 publications

References 41 publications

Quantification of seizure termination patterns reveals limited pathways to seizure end

Quantification of seizure termination patterns reveals limited pathways to seizure end

Focal seizures are organized by feedback between neural activity and ion concentration changes

Mode-Dependent Effect of Xenon Inhalation on Kainic Acid-Induced Status Epilepticus in Rats

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