Coordinated Reset Vibrotactile Stimulation Induces Sustained Cumulative Benefits in Parkinson's Disease.

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.

A Single Case Feasibility Study of Sensorimotor Rhythm Neurofeedback in Parkinson's Disease.

Electroencephalographic activity over the sensorimotor cortex has been one of the best studied targets for neurofeedback therapy. Parkinson's disease patients display abnormal brain rhythms in the motor cortex caused by increased synchrony in the basal ganglia-cortical pathway. Few studies have examined the effects of sensorimotor-based neurofeedback therapy in humans with PD. In this pilot study, one patient, diagnosed with Parkinson's disease 10 years prior, participated in two consecutive days of EEG neurofeedback training to increase sensorimotor rhythm (SMR) power over the motor cortex. Using a visual display connected to ongoing EEG, the patient voluntarily manipulated SMR power, and he/she was awarded with points to positively reinforce successful increases over a predefined threshold. Recorded EEG data were source localized and analyzed for the occurrence of high amplitude bursts of SMR activity as well as bursts in the beta frequency band in the precentral cortex. The rate of SMR bursts increased with each subsequent training session, while the rate of beta bursts only increased on the final session. Relative power in the beta band, a marker of PD symptom severity, decreased over the motor cortex in the later session. These results provide first evidence for the feasibility of SMR neurofeedback training as a non-invasive therapy for reducing Parkinson's disease related activity and upregulating SMR in the human motor cortex.

EEG Correlates of Involuntary Cognitions in the Reflexive Imagery Task.

The Reflexive Imagery Task (RIT) reveals that the activation of sets can result in involuntary cognitions that are triggered by external stimuli. In the basic RIT, subjects are presented with an image of an object (e.g., CAT) and instructed to not think of the name of the object. Involuntary subvocalizations of the name (the RIT effect) arise on roughly 80% of the trials. We conducted an electroencephalography (EEG) study to explore the neural correlates of the RIT effect. Subjects were presented with one object at a time in one condition and two objects simultaneously in another condition. Five regions were defined by electrode sites: frontal (F3-F4), parietal (P3-P4), temporal (T3-T4), right hemisphere (F4-P4), and left hemisphere (F3-P3). We focused on the alpha (8-13 Hz), beta (13-30 Hz), delta (0.01-4 Hz), and theta (4-8 Hz) frequencies.