TMS timed to interictal epileptiform discharges

Abstract Interictal epileptiform discharges (IEDs) are pathological hypersynchronous bursts of electrical brain activity that occur between seizures in patients with epilepsy. IEDs are caused by transient brain states that are difficult to predict, making them a challenging neurophysiological and technological case for brain-state-dependent stimulation. Administering stimulation at IED onset may provide insight into the epileptic network and optimize neurostimulation therapies. Here, we assessed the feasibility of IED-triggered transcranial magnetic stimulation (TMS) in two children with self-limited epilepsy with centrotemporal spikes (SeLECTS), a common pediatric epilepsy in which IEDs emerge from the motor cortex. A convolutional neural network (CNN) was trained on the participants’ pre-recorded electroencephalography (EEG) data with IEDs annotated by an epileptologist. The CNN was integrated into an EEG-processing pipeline that classified EEG segments as “IED” or “non-IED” in real time. With this pipeline, TMS pulses were administered during IED or non-IED periods in an interleaved, randomized design. We stimulated both the motor cortex generating the IEDs and the contralateral motor cortex and tested the impact of IEDs on TMS-evoked potentials (TEPs). Our study demonstrated that TMS can be timed to IEDs and that there is a site-specific increase in TEP amplitude when stimulating during IEDs. Out of the TMS pulses aimed at an IED, 39% and 19% were successfully delivered during an IED for the two participants, respectively. For future research, we propose ways to address the methodological challenges of IED-timed TMS, enabling brain-state-dependent TMS for epilepsy research and treatment. Competing Interest Statement RJI has patents on TMS technology, is a co-founder of Cortisys Inc and consultant to Nexstim Plc. PL is a consultant to Nexstim Plc. for TMS-EEG applications and speech cortical mapping. Footnotes ↵* Shared last authorship