Increasing Consistency of Evoked Response in Thalamic Nuclei During Repetitive Burst Stimulation of Peripheral Nerve in Humans

Objective. Peripheral nerve stimulation has been proposed as a noninvasive treatment for patients with movement disorders such as essential tremor, Parkinson's disease, and dystonia. While the outcomes have shown clinical effect, the mechanism behind the effect is not yet clear. The goal of this work was to study the brain's responses to peripheral stimulation bursts and explain the therapeutic results. Approach. We performed peripheral stimulation of the median nerve(s) in 12 pediatric patients undergoing deep brain stimulation for dystonia. Stimulation was given in bursts (50-200 Hz stimulation in blocks of 100 ms, separated by 100 ms without stimulation) and intracranial activity was simultaneously recorded from deep brain stimulation leads implanted in thalamic nuclei. After using a novel method to remove stimulus artifacts, sequences of neural responses during and after the bursts were analyzed. Results. Peripheral burst stimulation induced increasing consistency of successive evoked responses in thalamic nuclei. Significance. We propose that this phenomenon is due to progressive synchronization of small populations of thalamic neurons, so that over time there is phase locking of the response in an increasing number of neurons in the population. Clinical efficacy could thus be due to "synchronization blockade", in which the synchronized response of the population prevents transmission of intrinsic abnormal signals due to tremor or dystonia. Further studies are necessary to confirm this model of clinical effect. Enhanced understanding will increase the potential for use of peripheral stimulation as a noninvasive alternative or adjunct to deep brain stimulation.