Generators of the frequency-following response in the subthalamic nucleus: implications for non-invasive deep brain stimulation

While Deep Brain Stimulation (DBS) is effective treatment for several movement disorders, non-invasive stimulation modes have major clinical relevance. We report on a novel method holding potential for non-invasive subthalamic nucleus (STN) stimulation. We used an auditory frequency-following response task (FFR), a popular tool for studying the auditory brainstem as the neural response in the cortical and midbrain generator, as it precisely reflects the ongoing dynamics of a speech or non-speech sound. We recorded EEG and DBS electrodes from 5 patients, in 4 from the STN, and one from the anterior thalamus and a number of cortical and subcortical areas located in the hippocampus and frontal regions, during an FFR at a frequency higher than the upper limit of phase-locking in the cortex (333Hz). Our results revealed a neural response local to the STN, but not other structures. This finding is novel. Auditory perception in the basal ganglia is rather unexplored, and the STN generator of the FFR has likely gone unseen due to the limitations of our tools and research focus. The potential clinical implications are far-reaching. Future research should investigate whether auditory stimuli at common electrical stimulation frequencies and waveforms of electrical DBS stimulation can induce clinical improvement.