<scp>GABA</scp>ergic networks jump‐start focal seizures

Curtis, Marco de; Avoli, Massimo

doi:10.1111/epi.13370

Cited by 123 publications

(87 citation statements)

References 61 publications

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“…Such inter‐dependence reinforces the pathophysiological significance of the marker. As we discuss in more detail in Grinenko et al (), this fits well with the model proposed by Avoli and de Curtis (Avoli & de Curtis, ; De Curtis & Avoli, ): progressive synchronized activation of pyramidal cells (low‐frequency component of the preictal spikes) that excites disinhibited fast somatic inhibitory interneurons (FSIN) (fast‐frequency component of the preictal spikes) leading to a sustained FSIN activation (ictal FAs) with pyramidal silencing as a consequence (suppression of low frequencies) (Avoli & de Curtis, ; Elahian, Yeasin, Mudigoudar, Wheless, & Babajani‐Feremi, ; Fujiwara‐Tsukamoto et al, ; Gnatkovsky, Librizzi, Trombin, & De Curtis, ; Truccolo et al, ; Weiss et al, ). At the end of the sustained FSIN discharge, rebound activation of pyramidal cells and interneurons occurs before the seizure stops.…”

Section: Discussionsupporting

confidence: 86%

Learning to define an electrical biomarker of the epileptogenic zone

Grinenko

Mosher

et al. 2019

Human Brain Mapping

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The role of fast activity as a potential biomarker in localization of the epileptogenic zone (EZ) remains controversial due to recently reported unsatisfactory performance.We recently identified a "fingerprint" of the EZ as a time-frequency pattern that is defined by a combination of preictal spike(s), fast oscillatory activity, and concurrent suppression of lower frequencies. Here we examine the generalizability of the fingerprint in application to an independent series of patients (11 seizure-free and 13 nonseizure-free after surgery) and show that the fingerprint can also be identified in seizures with lower frequency (such as beta) oscillatory activity. In the seizure-free group, only 5 of 47 identified EZ contacts were outside the resection. In contrast, in the non-seizure-free group, 104 of 142 identified EZ contacts were outside the resection. We integrated the fingerprint prediction with the subject's MR images, thus providing individualized anatomical estimates of the EZ. We show that these fingerprint-based estimates in seizure-free patients are almost always inside the resection. On the other hand, for a large fraction of the nonseizure-free patients the estimated EZ was not well localized and was partially or completely outside the resection, which may explain surgical failure in such cases. We also show that when mapping fast activity alone onto MR images, the EZ was often over-estimated, indicating a reduced discriminative ability for fast activity relative to the full fingerprint for localization of the EZ. K E Y W O R D Sepileptogenic zone, high-frequency oscillations, localization-related epilepsy, partial seizure, stereo-EEG

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Section: Discussionsupporting

confidence: 86%

Learning to define an electrical biomarker of the epileptogenic zone

Grinenko

Mosher

et al. 2019

Human Brain Mapping

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“…; Huberfeld et al . ; de Curtis and Avoli, ). Notably, for each issue, the SST population provides a complementary solution.…”

Section: Discussionmentioning

confidence: 99%

Feedforward inhibition ahead of ictal wavefronts is provided by both parvalbumin‐ and somatostatin‐expressing interneurons

Parrish

Codadu

Scott

et al. 2019

The Journal of Physiology

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Key points There is a rapid interneuronal response to focal activity in cortex, which restrains laterally propagating activity, including spreading epileptiform activity. The interneuronal response involves intense activation of both parvalbumin‐ and somatostatin‐expressing interneurons. Interneuronal bursting is time‐locked to glutamatergic barrages in the pre‐ictal period. Ca 2+ imaging using conditional expression of GCaMP6f provides an accurate readout of the evolving firing patterns in both types of interneuron. The activation profiles of the two interneuronal classes are temporally offset, with the parvalbumin population being activated first, and typically, at higher rates. Abstract Previous work has described powerful restraints on laterally spreading activity in cortical networks, arising from a rapid feedforward interneuronal response to focal activity. This response is particularly prominent ahead of an ictal wavefront. Parvalbumin‐positive interneurons are considered to be critically involved in this feedforward inhibition, but it is not known what role, if any, is provided by somatostatin‐expressing interneurons, which target the distal dendrites of pyramidal cells. We used a combination of electrophysiology and cell class‐specific Ca 2+ imaging in mouse brain slices bathed in 0 Mg 2+ medium to characterize the activity profiles of pyramidal cells and parvalbumin‐ and somatostatin‐expressing interneurons during epileptiform activation. The GCaMP6f signal strongly correlates with the level of activity for both interneuronal classes. Both interneuronal classes participate in the feedfoward inhibition. This contrasts starkly with the pattern of pyramidal recruitment, which is greatly delayed. During these barrages, both sets of interneurons show intense bursting, at rates up to 300Hz, which is time‐locked to the glutamatergic barrages. The activity of parvalbumin‐expressing interneurons appears to peak early in the pre‐ictal period, and can display depolarizing block during the ictal event. In contrast, somatostatin‐expressing interneuronal activity peaks significantly later, and firing persists throughout the ictal events. Interictal events appear to be very similar to the pre‐ictal period, albeit with slightly lower firing rates. Thus, the inhibitory restraint arises from a coordinated pattern of activity in the two main classes of cortical interneurons.

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“…Instead, paradoxically, accumulating evidence indicates that increased synchronised GABAergic interneuronal activity is sufficient to disrupt neuronal networks and initiate the transition from interictal to ictal activity resulting in focal seizures [69]. The recruitment of neighboring neurons and subsequent seizure progression is then hypothesized to be mediated by an elevation in extracellular potassium [70]. Adding to the complexity of network-based activity, both excitatory and inhibitory roles of GABA and glutamatergic neurons have been reported, and a range of extrasynaptic as well as synaptic neurotransmitter receptors and ion channels have been implicated in seizures, in addition to those traditionally implicated, such as NMDA and GABA A receptors [71].…”

Section: Inflammation In Epileptogenesismentioning

confidence: 99%

Inflammation in epileptogenesis after traumatic brain injury

Webster

Sun

Crack

et al. 2017

J Neuroinflammation

230

185

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BackgroundEpilepsy is a common and debilitating consequence of traumatic brain injury (TBI). Seizures contribute to progressive neurodegeneration and poor functional and psychosocial outcomes for TBI survivors, and epilepsy after TBI is often resistant to existing anti-epileptic drugs. The development of post-traumatic epilepsy (PTE) occurs in a complex neurobiological environment characterized by ongoing TBI-induced secondary injury processes. Neuroinflammation is an important secondary injury process, though how it contributes to epileptogenesis, and the development of chronic, spontaneous seizure activity, remains poorly understood. A mechanistic understanding of how inflammation contributes to the development of epilepsy (epileptogenesis) after TBI is important to facilitate the identification of novel therapeutic strategies to reduce or prevent seizures.BodyWe reviewed previous clinical and pre-clinical data to evaluate the hypothesis that inflammation contributes to seizures and epilepsy after TBI. Increasing evidence indicates that neuroinflammation is a common consequence of epileptic seizure activity, and also contributes to epileptogenesis as well as seizure initiation (ictogenesis) and perpetuation. Three key signaling factors implicated in both seizure activity and TBI-induced secondary pathogenesis are highlighted in this review: high-mobility group box protein-1 interacting with toll-like receptors, interleukin-1β interacting with its receptors, and transforming growth factor-β signaling from extravascular albumin. Lastly, we consider age-dependent differences in seizure susceptibility and neuroinflammation as mechanisms which may contribute to a heightened vulnerability to epileptogenesis in young brain-injured patients.ConclusionSeveral inflammatory mediators exhibit epileptogenic and ictogenic properties, acting on glia and neurons both directly and indirectly influence neuronal excitability. Further research is required to establish causality between inflammatory signaling cascades and the development of epilepsy post-TBI, and to evaluate the therapeutic potential of pharmaceuticals targeting inflammatory pathways to prevent or mitigate the development of PTE.

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GABAergic networks jump‐start focal seizures

Cited by 123 publications

References 61 publications

Learning to define an electrical biomarker of the epileptogenic zone

Learning to define an electrical biomarker of the epileptogenic zone

Feedforward inhibition ahead of ictal wavefronts is provided by both parvalbumin‐ and somatostatin‐expressing interneurons

Inflammation in epileptogenesis after traumatic brain injury

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