A brain-machine interface for control of burst suppression in medical coma

Burst suppression is an electroencephalogram (EEG) marker of profound brain inactivation and unconsciousness and consists of bursts of electrical activity alternating with periods of isoelectricity called suppression. Burst suppression is the EEG pattern targeted in medical coma, a drug-induced brain state used to help recovery after brain injuries and to treat epilepsy that is refractory to conventional drug therapies. The state of coma is maintained manually by administering an intravenous infusion of an anesthetic, such as propofol, to target a pattern of burst suppression on the EEG. The coma often needs to be maintained for several hours or days, and hence an automated system would offer significant benefit for tight control. Here we present a brain-machine interface (BMI) for automatic control of burst suppression in medical coma that selects the real-time drug infusion rate based on EEG observations and can precisely control the burst suppression level in real time in rodents. We quantify the burst suppression level using the burst suppression probability (BSP), the brain's instantaneous probability of being in the suppressed state, and represent the effect of the anesthetic propofol on the BSP using a two-dimensional linear compartment model that we fit in experiments. We compute the BSP in real time from the EEG segmented into a binary time-series by deriving a two-dimensional state-space algorithm. We then derive a stochastic controller using both a linear-quadratic-regulator strategy and a model predictive control strategy. The BMI can promptly change the level of burst suppression without overshoot or undershoot and maintains precise control of time-varying target levels of burst suppression in individual rodents in real time.