Chronobiology; Cortical excitability; Steroid hormones; ElectroEncephaloGraphy; Epilepsy; Optogenetics; Sleep-wake cycle
Baud Maxime O., Proix Timothée, Rao Vikram R., Schindler Kaspar (2020), Chance and risk in epilepsy, in Current Opinion in Neurology
Baud Maxime O., Ghestem Antoine, Benoliel Jean-Jacques, Becker Christel, Bernard Christophe (2019), Endogenous multidien rhythm of epilepsy in rats, in Experimental Neurology
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Epilepsy is a common neurological disorder defined by the seemingly random occurrence of seizures. Without the ability to anticipate seizure timing, patients are plagued by constant uncertainty. Clinical observations suggest that Seizure Risk (Sz-risk, the variable probability of a seizure) is not uniform over time but rather influenced by fluctuating, patient-specific factors, including stress, circadian time, sleep-wake cycles, and hormonal changes. Such factors likely determine dynamic Sz-risk by modulating Cortical Excitability (CE) - the variable cortical response to a probing stimulus. Recently, using chronic intracranial EEG for years (cEEG), I studied the timing of thousands of seizures in ambulatory patients, an unprecedented opportunity. I unraveled that Sz-risk and Interictal Epileptiform Activity (IEA, the rate of epilepsy-related transient EEG waveforms) are modulated by well-known circadian rhythms, but also by multidien rhythms (over multiple days). Thus, IEA is a biomarker for Sz-risk over long time-scales, and reflects fluctuating CE. As a logical next step, I propose to characterize systemic influences on Cortical excitability, IEA and Seizure risk. In a translational effort, I will explore two parallel aims in epilepsy patients and a mouse model of seizures. Identifying systemic modulators of CE has groundbreaking potential for novel pharmacological strategies with broad applications to chronic cyclical brain disorders (epilepsy, migraine, mood disorders, etc.). In epilepsy, reliable seizure forecasting remains a major goal that is achievable with modern technology and may enable adjunct therapy targeted to periods of heightened Sz-risk.