An individualized Neural Mass Model of ictal activity based on GABA-A pathology for personalization of brain stimulation protocols in epilepsy

Lopez-Sola, Edmundo; Sanchez-Todo, Roser; Lleal, Elia; Ersöz, Elif Köksal; Yochum, Maxime; Makhalova, Julia; Mercadal, Borja; Benquet, Pascal; Wendling, Fabrice; Ruffini, Giulio

doi:10.1016/j.brs.2021.10.282

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“…More specifically, large networks of 10 thousand neurons showed the longer-lasting effects on ED decrease, while small networks of 250 neurons only showed immediate effects. Recently, following the work of Wendling et al ( 2002 ) and Lopez-Sola et al ( 2021 ) provide a laminar NMM capable of realistically reproducing the electrical activity recorded by SEEG in the epileptogenic zone during interictal to ictal states. A novel element in the model is a physiologically motivated algorithm for chloride dynamics: the gain of GABAergic post-synaptic potentials is modulated by the pathological accumulation of chloride in pyramidal cells due to high inhibitory input and/or dysfunctional chloride transport.…”

Section: Resultsmentioning

confidence: 99%

Transcranial current stimulation in epilepsy: A systematic review of the fundamental and clinical aspects

Simula

Daoud

Ruffini³

et al. 2022

Front. Neurosci.

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PurposeTranscranial electrical current stimulation (tES or tCS, as it is sometimes referred to) has been proposed as non-invasive therapy for pharmacoresistant epilepsy. This technique, which includes direct current (tDCS) and alternating current (tACS) stimulation involves the application of weak currents across the cortex to change cortical excitability. Although clinical trials have demonstrated the therapeutic efficacy of tES, its specific effects on epileptic brain activity are poorly understood. We sought to summarize the clinical and fundamental effects underlying the application of tES in epilepsy.MethodsA systematic review was performed in accordance with the PRISMA guidelines. A database search was performed in PUBMED, MEDLINE, Web of Science and Cochrane CENTRAL for articles corresponding to the keywords “epilepsy AND (transcranial current stimulation OR transcranial electrical stimulation)”.ResultsA total of 56 studies were included in this review. Through these records, we show that tDCS and tACS epileptic patients are safe and clinically relevant techniques for epilepsy. Recent articles reported changes of functional connectivity in epileptic patients after tDCS. We argue that tDCS may act by affecting brain networks, rather than simply modifying local activity in the targeted area. To explain the mechanisms of tES, various cellular effects have been identified. Among them, reduced cell loss, mossy fiber sprouting, and hippocampal BDNF protein levels. Brain modeling and human studies highlight the influence of individual brain anatomy and physiology on the electric field distribution. Computational models may optimize the stimulation parameters and bring new therapeutic perspectives.ConclusionBoth tDCS and tACS are promising techniques for epilepsy patients. Although the clinical effects of tDCS have been repeatedly assessed, only one clinical trial has involved a consistent number of epileptic patients and little knowledge is present about the clinical outcome of tACS. To fill this gap, multicenter studies on tES in epileptic patients are needed involving novel methods such as personalized stimulation protocols based on computational modeling. Furthermore, there is a need for more in vivo studies replicating the tES parameters applied in patients. Finally, there is a lack of clinical studies investigating changes in intracranial epileptiform discharges during tES application, which could clarify the nature of tES-related local and network dynamics in epilepsy.

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Section: Resultsmentioning

confidence: 99%