Modeling the neurophysiology of tremor to develop a peripheral neuroprosthesis for tremor suppression

Abstract

Pathological tremor is an involuntary oscillation of the body parts around joints. Pharmaceu- ticals and surgical treatments are approved approaches for tremor management; however, their side effects limit their usability. The main objective of this study is, therefore, to design a closed-loop non-invasive electrical stimulation system that could suppress tremor without serious side effects. We started our system design by investigating motor unit (MU) behaviors during postural tremor via decomposition of high-density surface electromyography (EMG) recordings of antagonist pairs of wrist muscles of essential tremor (ET) patients. The common input strength that influences voluntary and tremor movements and the phase difference between activation of motor neurons in antagonist pairs of muscles were assessed to find the correlation of the motor unit activity during different tasks. We observed that, during postural tremor, the motor units in antagonist pairs of muscles were activated with a phase difference that varies over time. An online EMG decomposition method and a phase-locked-loop system were, therefore, implemented in our tremor suppression system to real-timely discriminate motor unit discharge timings, track the phase of the motor unit activity and use that real-time phase estimation to control the stimulation timing. We applied sub-threshold stimulation to the muscle pairs in an out-of-phase manner. The system was validated offline with the data recorded from 13 ET patients before it was tested with an ET patient to prove the concept. Since the spinal cord is the termination of the afferent neurons from the peripheral nervous system and connection to the central nervous system and motor neurons, we hypothesized that electrical stimulation at the spinal cord could also modulate tremor-related neural commands. Russian currents with a 5 kHz-carrier frequency modulated with a slow burst at tremor frequencies were used with sub-threshold intensity to stimulate at C5-C6 cervical spine of 9 ET patients. The reduction of the tremor power was observed via an analysis of the wrist angle recorded using an accelerometer. We present, in this thesis, two electrical stimulation approaches for tremor suppression via the peripheral nerves and spinal cord, providing options for patients to utilize based on their preference.