Abstract

Abnormally strong neuronal synchronization is a hallmark of Parkinson’s disease (PD). Standard deep brain stimulation (DBS) reduces specific symptoms during stimulus delivery in medically refractory PD patients. Coordinated Reset (CR)-DBS is a computationally developed technique that uses dedicated patterns of electrical stimuli to counteract abnormal neuronal synchronization by desynchronization specifically. CR stimulation aims to make neuronal populations unlearn abnormal synaptic connectivity patterns, inducing long-lasting relief. Long-lasting therapeutic and desynchronizing CR-DBS effects were demonstrated in Parkinsonian (MPTP) monkeys and externalized PD patients. We developed vibrotactile Coordinated Reset (vCR) fingertip stimulation to provide a non-invasive alternative to DBS. To this end, instead of administering electrical bursts through depth electrodes, we non-invasively deliver weak vibratory shots in a CR mode to patients’ fingertips. In a first-in-human study, vCR fingertip stimulation was administered to 5 idiopathic PD patients for 4 h per day on three consecutive days. Off-medication kinematic assessments revealed improved gait and bradykinesia during stimulation days and one month after cessation of stimulation. In a pilot study, six idiopathic PD patients were treated with vCR stimulation delivered 4 hours per day for three months. Patients’ conditions were evaluated after medication withdrawal (off medication) through MDS-UPDRS III scores and EEG recordings before and after three months of vCR. vCR therapy caused a statistically and clinically significant reduction of PD symptoms off medication together with a substantial decrease in high beta (21-30 Hz) power in the sensorimotor cortex (https://www.youtube.com/watch?v=dSjv6m4xLH0 ). Additionally, in a case series in 3 idiopathic PD patients, 6+ months of vCR therapy caused a significant motor improvement, where off-medication MDS-UPDRS III scores decreased linearly. The ultimate goal of vCR is to induce sustained symptom relief by non-invasively delivering weak vibratory stimulation patterns only regularly or occasionally.