Seizure forecasting by tracking cortical response to electrical stimulation

Background Seizure unpredictability is a significant burden in the lives of people with epilepsy. Previously published approaches to seizure forecasting analysed intracranial electroencephalographic recordings (iEEG) and showed that seizures can be forecast above chance levels. Although passive observation of the brain might provide some insights, repeated active perturbation of the cortex and measuring the cortical response may provide more direct information about time-varying cortical excitability. Objective The aim of this study is to investigate whether seizures can be forecast by stimulating the cortex via intracranial electrodes and measuring cortical response from the iEEG. Methods We studied a cohort of eight patients with treatment-resistant epilepsy who were admitted to King’s College Hospital for presurgical evaluation with iEEG. During their stay, they underwent prolonged single pulse electrical stimulation for approximately one day. Stimuli were delivered every 5 minutes to a constant pair of electrodes and all patients experienced at least one clinical seizure during the period of stimulation. We extracted quantitative features from the iEEG post-stimulus response and developed a logistic regression algorithm to estimate the seizure likelihood at each stimulus. To evaluate the algorithm’s performance, we used improvement over chance (IoC), sensitivity, time spent in warning and Brier Skill score. We also compared performance with seizure prediction based on passive observation of iEEG. Results In seven out of eight patients, seizures could be forecast using the post-stimulus response above chance levels (average IoC: 0.74). In comparison, the seizure forecasting performance based on passive (unstimulated) iEEG was less good (average IoC: 0.54). Conclusions These results suggest that cortical response to electrical stimulation may aid in the development of seizure forecasting algorithms as well as in the design of novel implantable devices that deliver electrical stimulation to control seizures. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the MRC IAA award held by Kings College London (MR/X502923/1). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the ethics committee of Kings College Hospital (Reference number: 06/Q0703/117) and all patients gave written informed consent to participate in the study. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The analysed data are available from the corresponding authors upon reasonable request.