Timing- and Frequency-Specific Effects of Dentate Nucleus Deep Brain Stimulation on Somatosensory Evoked Potentials in People with Post-Stroke Hemiparesis

Deep brain stimulation (DBS) of the dentate nucleus (DN) is being investigated as a therapy to enhance perilesional cortical excitability and promote motor recovery for individuals with chronic, post-stroke motor deficits. Given that acute motor changes are not anticipated, DBS optimization would benefit from surrogate markers of stimulation‘s effect on cortical excitability. Here, we evaluate whether continuous and paired DN stimulation modulates somatosensory evoked potentials (SSEPs), providing first-in-human insight into their candidacy as a tool for device programming. SSEPs were collected from participants in a phase I DN DBS clinical trial to characterize the effects of continuous and paired stimulation on SSEP response characteristics. Continuous low frequency DBS did not yield significant changes in short latency peak-to-peak amplitude, though high frequency stimulation yielded significantly lower peak-to-peak amplitude during double, but not single, pulse SSEP (64% of baseline, p < 0.05). As interstimulus interval (ISI) between SSEP and DBS was increased, short-latency power decreased (p < 0.005), with greatest power at an ISI of 0 ms (156% of baseline, p < 0.05). Our results support involvement of DN output in both early and late SSEP components. Modulation was modest and variable across subjects, limiting its potential role in therapeutic programming. Further work is required to elucidate the effects of lesion size and DBS lead placement.