A control-theoretic system identification framework and a real-time closed-loop clinical simulation testbed for electrical brain stimulation

Objective. Closed-loop electrical brain stimulation systems may enable a precisely-tailored treatment for neurological and neuropsychiatric disorders by controlling the stimulation based on neural activity feedback in real time. Developing model-based closed-loop systems requires a principled system identification framework to quantify the effect of input stimulation on output neural activity by learning an input-output (IO) dynamic model from data. Further, developing these systems needs a realistic clinical simulation testbed to design and validate the closed-loop controllers derived from the IO models before testing in human patients. Approach. First, we design a control-theoretic system identification framework to build dynamic IO models for neural activity that are amenable to closed-loop control design. To enable tractable model-based control, we use a data-driven linear state-space IO model that characterizes the effect of input on neural activity in terms of a low-dimensional hidden neural state. To learn the model parameters, we design a novel input waveform-a pulse train modulated by stochastic binary noise (BN) parameters-that we show is optimal for collecting informative IO datasets in system identification and conforms to clinical safety requirements. Second, we further extend this waveform to a generalized BN (GBN)-modulated waveform to reduce the required system identification time. Third, to enable extensive testing of system identification and closed-loop control, we develop a real-time closed-loop clinical hardware-in-the-loop (HIL) simulation testbed using the Neuro Omega (TM) microelectrode recording and stimulation device, which incorporates stochastic noises, unknown disturbances and stimulation artifacts. Using this testbed, we implement both the system identification and the closed-loop controller by taking control of mood in depression as an example. Results. Testbed simulation results show that the closed-loop controller designed from IO models identified with the BN-modulated waveform achieves tight control, and performs similar to a controller that knows the true IO model of neural activity. When system identification time is limited, performance is further improved using the GBN-modulated waveform. Significance. The system identification framework with the new BN-modulated waveform and the clinical HIL simulation testbed can help develop future model-based closed-loop electrical brain stimulation systems for treatment of neurological and neuropsychiatric disorders.