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Towards Closed-Loop Neuromodulation with Wireless Biomimetic Circuits and Systems

Abstract

Conventional functional electrical stimulation for neuromodulation delivers regular and periodic electrical pulses in an open-loop fashion. However, with advances in neuroscience, emerging applications require an electrical stimulation delivered in a non-conventional form. For example, electroceuticals and brain-machine interface (BMI) need a closed-loop modulation scheme such that the stimulation protocol can be dynamically adjusted in response to the subject’s physiological state. Furthermore, it has been recently shown that a stimulation pattern that mimics the biological signal (i.e. biomimetic stimulation) outperforms periodic pulses in some applications including retina stimulation to regain eyesight and spinal cord stimulation to restore motor function. Despite increasing interests in closed-loop neuromodulation and biomimetic stimulation, existing implantable neuromodulation devices have limited capability in supporting those sophisticated stimulation schemes.

We have developed two wireless biomimetic systems—an implantable stimulation and recording system and a biomimetic stimulation system, aiming to support closed-loop neuromodulation and biomimetic stimulation. In this dissertation, system design and circuit implementation of both systems are presented. Both systems were validated in bench-top tests and in-vivo experiments. The implantable system was used to conduct intestinal stimulation that facilitated the intestinal transit in chronic porcine experiments. The implant is an order lighter and 7.7 times smaller than commercialized GI stimulators, and the delivered electrical charge is smaller than most existing protocols, thus safer and more energy-efficient. The system was also used to conduct acute epidural stimulation in rat models and selectively activate desired muscles through targeting different motor neurons, laying the foundation for the future development of the control algorithms for closed-loop epidural stimulation. On the other hand, the biomimetic stimulation system was also validated in acute experiments using spinally transected rats. The system that delivered a protocol mimicking electromyography (EMG) signal lowered the excitation threshold of the spinal network, showing its potential of accelerating the rate of functional recovery after spinal cord injury. The development of these two biomimetic systems along with the future implementation of the closed-loop control algorithm using the in-vivo data acquired by both systems will make an implantable device that supports closed-loop biomimetic stimulation a reality.

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