Multimodal wearable sensors inform cycles of seizure risk

Objective Seizure unpredictability is a major source of disability for people with epilepsy. Recent work using chronic brain recordings has established that for many individuals with epilepsy seizure risk is not random, but corresponds to circadian and multiday (multidien) cycles in brain excitability. Here, we aimed to evaluate whether multimodal wearable device recordings can characterize cycles of seizure risk, and compare wearables performance with concurrent chronic brain recordings. Methods Fourteen subjects underwent long-term ambulatory monitoring with a multimodal wrist worn device (measuring heart rate, heart rate variability, accelerometry, tonic and phasic electrodermal activity, temperature) and an implanted responsive neurostimulation system (measuring interictal epileptiform abnormalities (IEA) and electrographic seizures). Wavelet time-frequency analyses identified circadian and multiday cycles in wearable and brain recordings. Circular statistics assessed seizure phase locking to cycles in physiology. Results Ten subjects met inclusion criteria. The mean recording duration was 232 days. Seven subjects had reliable electrographic seizure detections (mean 76 seizures). Seizure phase locking to multiday cycles occurred in six (IEA), five (temperature), four (heart rate, phasic electrodermal activity), and three (accelerometry, heart rate variability, tonic electrodermal activity) subjects. Seizure phase locking to residual HR multiday cycles (HR after regression of correlated physical activity (ACC)) increased to six subjects. Interpretation Long timescale cyclical changes in wearable recordings are common in epilepsy, and seizures occur at preferred phases of these cycles for many individuals. Broadly accessible wearable technology can provide new insights into the chronobiology of epilepsy with implications for seizure forecasting. ### Competing Interest Statement G.A.W., and B.H.B. declare intellectual property licensed to Cadence Neuroscience. N.M.G. and G.A.W. are investigators for the Medtronic Deep Brain Stimulation Therapy for Epilepsy Post-Approval Study. E.S.N., P.J.K, M.J.C. and D.R.F. declare a financial interest in Seer Medical. ### Funding Statement This research was supported by the Epilepsy Foundation Epilepsy Innovation Institute My Seizure Gauge; NIH grants UH3-NS95495 & R01-NS09288203; American Epilepsy Society Research & Training Fellowship for Clinicians (N.M.G.); National Science Foundation grant CBET-2138378 (M.N.). ### 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 Institutional Review Board of Mayo Clinic gave ethical approval for this work. 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 and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Wearable data will be made available in 2023 on EpilepsyEcosystem.org. The analysis approach is described in detail above; MATLAB scripts are available from the author by reasonable request. * ACC : accelerometry ASD : amplitude spectral density BVP : blood volume pulse. EDAp : phasic electrodermal activity EDAt : tonic electrodermal activity HR : heart rate HRV : heart rate variability IBI : interbeat interval IEA : interictal epileptiform activity iEEG : intracranial EEG RNS : responsive neurostimulation TEMP : temperature