ABSTRACT
BACKGROUND: Abnormal synchronization of neuronal activity in dopaminergic circuits is related to motor impairment in Parkinson's disease (PD). Vibrotactile coordinated reset (vCR) fingertip stimulation aims to counteract excessive synchronization and induce sustained unlearning of pathologic synaptic connectivity and neuronal synchrony. Here, we report two clinical feasibility studies that examine the effect of regular and noisy vCR stimulation on PD motor symptoms. Additionally, in one clinical study (study 1), we examine cortical beta band power changes in the sensorimotor cortex. Lastly, we compare these clinical results in relation to our computational findings. METHODS: Study 1 examines six PD patients receiving noisy vCR stimulation and their cortical beta power changes after 3 months of daily therapy. Motor evaluations and at-rest electroencephalographic (EEG) recordings were assessed off medication pre- and post-noisy vCR. Study 2 follows three patients for 6+ months, two of whom received daily regular vCR and one patient from study 1 who received daily noisy vCR. Motor evaluations were taken at baseline, and follow-up visits were done approximately every 3 months. Computationally, in a network of leaky integrate-and-fire (LIF) neurons with spike timing-dependent plasticity, we study the differences between regular and noisy vCR by using a stimulus model that reproduces experimentally observed central neuronal phase locking. RESULTS: Clinically, in both studies, we observed significantly improved motor ability. EEG recordings observed from study 1 indicated a significant decrease in off-medication cortical sensorimotor high beta power (21-30 Hz) at rest after 3 months of daily noisy vCR therapy. Computationally, vCR and noisy vCR cause comparable parameter-robust long-lasting synaptic decoupling and neuronal desynchronization. CONCLUSION: In these feasibility studies of eight PD patients, regular vCR and noisy vCR were well tolerated, produced no side effects, and delivered sustained cumulative improvement of motor performance, which is congruent with our computational findings. In study 1, reduction of high beta band power over the sensorimotor cortex may suggest noisy vCR is effectively modulating the beta band at the cortical level, which may play a role in improved motor ability. These encouraging therapeutic results enable us to properly plan a proof-of-concept study.
ABSTRACT
OBJECTIVE: EVT is a refractory voice disorder that significantly affects quality of life. This work aims to conduct a multiparametric assessment of the effect of deep brain stimulation (DBS) of the thalamic ventral intermediate nucleus (VIM) on essential vocal tremor (EVT) and investigate the relation between DBS lead location and EVT outcomes. METHODS: Nine participants underwent DBS for essential tremor and were diagnosed with co-occurring EVT in this prospective cohort study. Objective measurements including acoustic evaluation of vocal fundamental frequency (F0) and intensity modulation and subjective measurements including physiologic evaluation of the oscillatory movement of the laryngeal muscles and vocal tract and perceptual ratings of tremor severity were collected PRE and POST DBS. Finally, we investigated the relation between DBS lead location and EVT outcomes. RESULTS: Acoustic modulations of F0 and intensity were significantly improved POST DBS. Physiologic assessment showed a POST DBS reduction of oscillatory movement in the laryngeal muscles and vocal tract, but not significantly. Listener and participant perception, of EVT severity was also significantly reduced. Finally, our results indicate better EVT control with increased distance to midline of left VIM thalamic stimulation. CONCLUSIONS: By employing a battery of objective and subjective measures, our study supports the benefit of DBS for the treatment of EVT and specifies the acoustic and physiologic mechanisms that mediate its positive effect. We further provide preliminary results on the relation between lead location and EVT outcomes, laying the foundation for future studies to clarify the optimal DBS target for the treatment of EVT.
