Online Tracking of the Phase Difference Between Neural Drives to Antagonist Muscle Pairs in Essential Tremor Patients

Transcutaneous electrical stimulation has been applied in tremor suppression applications. Out-of-phase stimulation strategies applied above or below motor threshold result in a significant attenuation of pathological tremor. For stimulation to be properly timed, the varying phase relationship between agonist-antagonist muscle activity during tremor needs to be accurately estimated in real-time. Here we propose an online tremor phase and frequency tracking technique for the customized control of electrical stimulation, based on a phase-locked loop (PLL) system applied to the estimated neural drive to muscles. Surface electromyography signals were recorded from the wrist extensor and flexor muscle groups of 13 essential tremor patients during postural tremor. The EMG signals were pre-processed and decomposed online and offline via the convolution kernel compensation algorithm to discriminate motor unit spike trains. The summation of motor unit spike trains detected for each muscle was bandpass filtered between 3 to 10 Hz to isolate the tremor related components of the neural drive to muscles. The estimated tremorogenic neural drive was used as input to a PLL that tracked the phase differences between the two muscle groups. The online estimated phase difference was compared with the phase calculated offline using a Hilbert Transform as a ground truth. The results showed a rate of agreement of 0.88 +/- 0.22 between offline and online EMG decomposition. The PLL tracked the phase difference of tremor signals in real-time with an average correlation of 0.86 +/- 0.16 with the ground truth (average error of 6.40 degrees +/- 3.49 degrees). Finally, the online decomposition and phase estimation components were integrated with an electrical stimulator and applied in closed-loop on one patient, to representatively demonstrate the working principle of the full tremor suppression system. The results of this study support the feasibility of real-time estimation of the phase of tremorogenic neural drive to muscles, providing a methodology for future tremor-suppression neuroprostheses.