Multiscale recordings reveal the dynamic spatial structure of human seizures

Schevon, Catherine A.; Tobochnik, Steven; Eissa, Tahra L.; Merricks, Edward M.; Gill, Brian J A; Parrish, R. Ryley; Bateman, Lisa M.; McKhann, Guy M.; Emerson, Ronald G.; Trevelyan, Andrew J.

doi:10.1016/j.nbd.2019.03.015

Cited by 55 publications

(59 citation statements)

References 121 publications

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“…Both in vivo and in vitro 4AP models have been used to good effect in tandem with optogenetic stimulation of specific subpopulations of neurons, indicating how in this special case, interneurons may drive ictogenesis (Shiri et al, 2015;Yekhlef et al, 2015;Chang et al, 2018;Magloire et al, 2018). This is hypothesized to happen through a sequence involving chloride-loading of pyramidal cells and secondary rises in extracellular K + via the potassium chloride cotransporter (KCC2) (Viitanen et al, 2010;Gonzalez et al, 2018;de Curtis et al, 2019;Schevon et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Divergent paths to seizure‐like events

et al. 2019

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Much debate exists about how the brain transitions into an epileptic seizure. One source of confusion is that there are likely to be critical differences between experimental seizure models. To address this, we have compared the evolving activity patterns in two widely used in vitro models of epileptic discharges. Brain slices from young adult mice were prepared in the same way and bathed either in 0 Mg2+ or 100 µmol/L 4AP artificial cerebrospinal fluid. We have found that while local field potential recordings of epileptiform discharges in the two models appear broadly similar, patch‐clamp analysis reveals an important difference in the relative degree of glutamatergic involvement. 4AP affects parvalbumin‐expressing interneurons more than other cortical populations, destabilizing their resting state and inducing spontaneous bursting behavior. Consequently, the most prominent pattern of transient discharge (“interictal event”) in this model is almost purely GABAergic, although the transition to seizure‐like events (SLEs) involves pyramidal recruitment. In contrast, interictal discharges in 0 Mg2+ are only maintained by a very large glutamatergic component that also involves transient discharges of the interneurons. Seizure‐like events in 0 Mg2+ have significantly higher power in the high gamma frequency band (60–120Hz) than these events do in 4AP, and are greatly delayed in onset by diazepam, unlike 4AP events. We, therefore, conclude that the 0 Mg2+ and 4AP models display fundamentally different levels of glutamatergic drive, demonstrating how ostensibly similar pathological discharges can arise from different sources. We contend that similar interpretative issues will also be relevant to clinical practice.

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Section: Introductionmentioning

confidence: 99%

Divergent paths to seizure‐like events

et al. 2019

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“…This simulation illustrates the fact that two dynamical regimes can emerge in a single seizure: whilst the ictal wave front is often characterised by fast frequency rhythms -that slowly recruit more cortical areas over time -ictal spikes later in an established seizure can propagate at near synchronous speeds in the areas of cortex that have already been recruited (Smith et al, 2016;Schevon et al, 2019). These different types of propagation mechanisms can be described in different models, such as propagation in excitable media (ictal onset), or coupled oscillator dynamics (for ictal spike and wave discharges).…”

Section: Coupled-oscillator Dynamics Support Both Ictal-and Ied Dynamicsmentioning

confidence: 77%

Interictal discharges spread along local recurrent networks between tubers and surrounding cortex

Tumpa

Thornton

Tisdall

et al. 2019

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The presence of interictal epileptiform discharges on electroencephalography (EEG) may indicate increased epileptic seizure risk and on invasive EEG are the signature of the irritative zone. In highly epileptogenic lesions -such as cortical tubers in tuberous sclerosis -these discharges can be recorded with intracranial stereotactic EEG as part of the evaluation for epilepsy surgery. Yet the network mechanisms that underwrite the generation and spread of these discharges remain poorly understood, limiting their current diagnostic use. Here, we investigate the dynamics of interictal epileptiform discharges using a combination of quantitative analysis of invasive EEG recordings and mesoscale neural mass modelling of cortical dynamics. We first characterise spatially organised local dynamics of discharges recorded from 36 separate tubers in 8 patients with tuberous sclerosis. We characterise these dynamics with a set of competing explanatory network models using dynamic causal modelling. Bayesian model comparison of plausible network architectures suggests that the recurrent coupling between neuronal populations within -and adjacent to -the tuber core explains the travelling wave dynamics observed in these patient recordings. Our results -based on interictal activity -unify competing theories about the pathological organisation of epileptic foci and surrounding cortex in patients with tuberous sclerosis. Coupled oscillator dynamics have previously been used to describe ictal activity, where fast travelling ictal discharges are commonly observed within the recruited seizure network. The interictal data analysed here add the insight that this functional architecture is already established in the interictal state. This links observations of interictal EEG abnormalities directly to pathological network coupling in epilepsy, with possible implications for epilepsy surgery approaches in tuberous sclerosis. Significance StatementInterictal epileptiform discharges (IEDs) are clinically important markers of an epileptic brain. Here we link local IED spread to network coupling through a combination of clinical recordings in paediatric patients with tuberous sclerosis complex, quantitative EEG analysis of interictal discharges spread, and Bayesian inference on coupled neural mass model parameters. We show that the kinds of interictal discharges seen in our patients require recurrent local network coupling extending beyond the putative seizure focus and that in fact only those recurrent coupled networks can support seizurelike and interictal dynamics when run in simulation. Our findings provide a novel integrated perspective on emergent epileptic dynamics in human patients.

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“…Recent studies have shown the relevance of PAC to detect epileptic seizures Ibrahim et al (2014); Edakawa et al (2016); Frauscher et al (2015); Amiri et al (2016) and it has been also hypothesized that ictal PAC, compared to interictal PAC, could provide more direct information to delineate the brain regions responsible for generation of habitual seizures Ibrahim et al (2014); Motoi et al (2018). More important, retrospective studies based on the postoperative surgical outcome of epilepsy surgery patients, have shown the clinical relevance of ictal PAC as a biomarker to improve the spatial delineation of resection boundaries associated to the ictal core from iEEG recordings with macroelectrodes Weiss et al (2013, 2015); Schevon et al (2012, 2019). Using invasive recordings with macro and microelectrodes in epilepsy patients, these studies demonstrated that repetitive transient increases in the amplitude of the high frequency band (80 Hz - 150 Hz), phase-locked to the slow ictal rhythm (1 Hz - 25 Hz), the so called phase-locked high gamma (PLHG), correlated with strong multi-unit firing bursts synchronized across the core territory of the seizure Weiss et al (2013).…”

Section: Discussionmentioning

confidence: 99%

Spectral harmonicity distinguishes two types of ictal phase-amplitude cross frequency couplings in patients candidate to epilepsy surgery

Dellavale

Urdapilleta

Cámpora

et al. 2020

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Objective: Spectral harmonicity of the ictal activity was analyzed regarding two clinically relevant aspects, (1) as a confounding factor producing 'spurious' phase-amplitude couplings (PAC) which may lead to wrong conclusions about the underlying ictal mechanisms, and (2) its role in how good PAC is in correspondence to the seizure onset zone (SOZ) classification performed by the epileptologists. Methods: PAC patterns observed in intracerebral electroencephalography (iEEG) recordings were retrospectively studied during seizures of seven patients with pharmacoresistant focal epilepsy. The time locked index (TLI) measure was introduced to quantify the degree of harmonicity between frequency bands associated to the emergence of PAC during epileptic seizures. Results: (1) Harmonic and non harmonic PAC patterns coexist during the seizure dynamics in iEEG recordings with macroelectrodes. (2) Harmonic PAC patterns are an emergent property of the periodic non sinusoidal waveform constituting the epileptiform activity. (3) The TLI metric allows to distinguish the non harmonic PAC pattern, which has been previously associated with the ictal core through the paroxysmal depolarizing shifts mechanism of seizure propagation. Conclusions: Our results suggest that the spectral harmonicity of the ictal activity plays a relevant role in the visual analysis of the iEEG recordings performed by the epileptologists to define the SOZ, and that it should be considered for the proper interpretation of ictal mechanisms. * Corresponding authors. Highlights 1 • Harmonic and non harmonic phase-amplitude couplings coexist in epilep-73 nusoidal waveform constituting the seizure activity as a mechanism originating 74 PAC, referred as 'harmonic PAC'. Implications of the coexistence of harmonic 75 and non harmonic PAC patterns during epileptic seizures regarding underlying 76 neural mechanisms and improved therapy are also discussed.77 3 2. METHODS 78 2.1. Patients 79 The seven patients with pharmacoresistant focal epilepsy included in this 80 retrospective study were consecutively selected from the candidates for surgi-81 cal treatment between 2012 and 2015 at the Epilepsy Center -"Ramos Mejía" 82 Hospital and El Cruce "N. Kirchner" Hospital -Universidad Nacional Arturo 83 Jauretche, Argentina. The patients underwent chronic invasive EEG procedure 84 guided by clinical criteria to help identify the epileptogenic zone (EZ) for sub-85 sequent resection. The characteristics of the patients are provided in Table 1 86 and the schematic view of the SOZ, as identified by the epileptologists (NC and 87 SK), is shown in Figure 1. 88 * No, Number of implanted unipolar electrode contacts; * * Number of seizures analyzed in this study; 5 6 2.2. Localization of electrode sites and imaging for three-dimensional reconstruc-89 tion 90 Electrode placement considered not only the final target but also the pre-91 cise trajectory. Surgical planning of electrode placement in specific anatomical 92 structures was thus dependent on the pre-established hypotheses of p...

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Multiscale recordings reveal the dynamic spatial structure of human seizures

Cited by 55 publications

References 121 publications

Divergent paths to seizure‐like events

Divergent paths to seizure‐like events

Interictal discharges spread along local recurrent networks between tubers and surrounding cortex

Spectral harmonicity distinguishes two types of ictal phase-amplitude cross frequency couplings in patients candidate to epilepsy surgery

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