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 [Formula: see text] 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.