Subthalamic nucleus deep brain stimulation evokes resonant neural activity

Abstract

Deep brain stimulation (DBS) is a rapidly expanding treatment for neurological and psychiatric conditions; however, a target-specific biomarker is required to optimize therapy. Here, we show that DBS evokes a large-amplitude resonant neural response focally in the subthalamic nucleus. This response is greatest in the dorsal region (the clinically optimal stimulation target for Parkinson disease), coincides with improved clinical performance, is chronically recordable, and is present under general anesthesia. These features make it a readily utilizable electrophysiological signal that could potentially be used for guiding electrode implantation surgery and tailoring DBS therapy to improve patient outcomes.

Proceedings of the Seventh Annual Deep Brain Stimulation Think Tank: Advances in Neurophysiology, Adaptive DBS, Virtual Reality, Neuroethics and Technology

“…DBS LFP recordings stimulate from the two inferior contacts and record from the two superior contacts of the depth lead. They show a response with a latency of 350 µs, as well as ERNA (Sinclair et al, 2018). As the CS and TS approach become more proximate, there is evidence of relative and absolute refractory periods as the latency increases and amplitude decreases, with the evoked response and ERNA disappearing as the two stimuli converge.…”

“…Unlike beta oscillations, ERNA is an active signal created by stimulation, and cannot be recorded from resting-state activity. ERNA localizes to the STN (Supplementary Figure S4A) and is present under general anesthesia ( Supplementary Figure S4D), suggesting a role to guide electrode implantation with patients asleep without intraoperative imaging (Sinclair et al, 2018). ERNA amplitude varies even within the STN, being maximal in the dorsal subregion where DBS is reported to achieve the greatest benefit (Horn et al, 2017;Sinclair et al, 2018;Supplementary Figure S4B) and electrodes that record larger ERNA amplitudes have been found to produce greater clinical benefit (Supplementary Figure S4C).…”

“…However, these oscillations are small (<15 µV), and can be difficult to detect in and across certain conditions. In this light, we propose a new biomarker, evoked resonant neural activity (ERNA), which is significantly larger than the beta band (>100 µV) and can be reliably recorded across all conditions (Sinclair et al, 2018(Sinclair et al, , 2019. ERNA is evoked and recorded from within the STN itself and is generated by a train of square biphasic pulses.…”

“…During DBS, modulation of ERNA frequency correlates with the amplitude of beta oscillations (a useful surrogate of the clinical state of the patient; Supplementary Figure S4F; Sinclair et al, 2019). During programming, the ERNA could facilitate optimization of more precise settings, especially given that there is a larger amplitude in the dorsal motor region of the STN (Sinclair et al, 2018). This raises the possibility that ERNA frequency could be investigated as a biomarker to trigger adaptive STN DBS in PD.…”

“…Unlike thalamic DBS EPps , sEPs were polyphasic and highly stereotyped Sinclair et al, 2018). Implementing a 3-dimensional biophysical model of the STN-GPe subcircuit enabled the determination of the origin of sEPs.…”