Stimulation to probe, excite, and inhibit the epileptic brain

Abstract

Direct cortical stimulation has been applied in epilepsy for nearly a century and has experienced a renaissance, given unprecedented opportunities to probe, excite, and inhibit the human brain. Evidence suggests stimulation can increase diagnostic and therapeutic utility in patients with drug‐resistant epilepsies. However, choosing appropriate stimulation parameters is not a trivial issue, and is further complicated by epilepsy being characterized by complex brain state dynamics. In this article derived from discussions at the ICTALS 2022 Conference (International Conference on Technology and Analysis for Seizures), we succinctly review the literature on cortical stimulation applied acutely and chronically to the epileptic brain for localization, monitoring, and therapeutic purposes. In particular, we discuss how stimulation is used to probe brain excitability, discuss evidence on the usefulness of stimulation to trigger and stop seizures, review therapeutic applications of stimulation, and finally discuss how stimulation parameters are impacted by brain dynamics. Although research has advanced considerably over the past decade, there are still significant hurdles to optimizing use of this technique. For example, it remains unclear to what extent short timescale diagnostic biomarkers can predict long‐term outcomes and to what extent these biomarkers add information to already existing biomarkers from passive electroencephalographic recordings. Further questions include the extent to which closed loop stimulation offers advantages over open loop stimulation, what the optimal closed loop timescales may be, and whether biomarker‐informed stimulation can lead to seizure freedom. The ultimate goal of bioelectronic medicine remains not just to stop seizures but rather to cure epilepsy and its comorbidities.

The time-evolving epileptic brain network: concepts, definitions, accomplishments, perspectives

“…Considering the recent promising developments of centrality concepts and metrics to characterize properties of edges as well as the edges’ time-varying role in the larger network ( Bröhl and Lehnertz, 2019 ; Bröhl and Lehnertz, 2022 ; Contisciani et al, 2022 ; Altafini et al, 2023 ), adopting an edge-centric perspective (cf. Faskowitz et al, 2022 ; Novelli and Razi, 2022 ) could lead to a further improved understanding of the time-evolving epileptic brain network and its control ( Sinha et al, 2022 ; Lehnertz et al, 2023 ; Frauscher et al, 2023 ).…”

Unearthing the mechanisms of responsive neurostimulation for epilepsy

“…RNS stimulation parameters are typically adjusted every few months, remaining constant in the interim. Thus, observed outcomes may underestimate the potential impact of RNS therapy by being the compositive of potentially opposing effects during network state cycling 49 .…”