Spectral Topography of the Subthalamic Nucleus to Inform Next‐Generation Deep Brain Stimulation

Abstract

Background The landscape of neurophysiological symptoms and behavioral biomarkers in basal ganglia signals for movement disorders is expanding. The clinical translation of sensing‐based deep brain stimulation (DBS) also requires a thorough understanding of the anatomical organization of spectral biomarkers within the subthalamic nucleus (STN). Objectives The aims were to systematically investigate the spectral topography, including a wide range of sub‐bands in STN local field potentials (LFP) of Parkinson's disease (PD) patients, and to evaluate its predictive performance for clinical response to DBS. Methods STN‐LFPs were recorded from 70 PD patients (130 hemispheres) awake and at rest using multicontact DBS electrodes. A comprehensive spatial characterization, including hot spot localization and focality estimation, was performed for multiple sub‐bands (delta, theta, alpha, low‐beta, high‐beta, low‐gamma, high‐gamma, and fast‐gamma (FG) as well as low‐ and fast high‐frequency oscillations [HFO]) and compared to the clinical hot spot for rigidity response to DBS. A spectral biomarker map was established and used to predict the clinical response to DBS. Results The STN shows a heterogeneous topographic distribution of different spectral biomarkers, with the strongest segregation in the inferior‐superior axis. Relative to the superiorly localized beta hot spot, HFOs (FG, slow HFO) were localized up to 2 mm more inferiorly. Beta oscillations are spatially more spread compared to other sub‐bands. Both the spatial proximity of contacts to the beta hot spot and the distance to higher‐frequency hot spots were predictive for the best rigidity response to DBS. Conclusions The spatial segregation and properties of spectral biomarkers within the DBS target structure can additionally be informative for the implementation of next‐generation sensing‐based DBS. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Spike-phase coupling of subthalamic neurons to posterior opercular cortex predicts speech sound accuracy

“…For example, neurons displaying significant theta SPC with the STG do not necessarily oscillate in the theta-rhythm at the population level. Therefore, our frequency-wise STN SPC topographies during speech production would not necessarily align with STN power-based topographies based on local field potentials recorded at rest 33,55 .…”

“…For example, neurons displaying significant theta SPC with the STG do not necessarily oscillate in the theta-rhythm at the population level. Therefore, our frequency-wise STN SPC topographies during speech production would not necessarily align with STN power-based topographies based on local field potentials recorded at rest 33,57 . Third, phase-based time delays do not necessarily reflect synaptic transmission delays 58 , but likely reflect the combination of cortical and subcortical inputs to the STN that become transiently stable 21,41 .…”

“…Previous studies have shown that neural activity in the cortex and STN feature frequency-specific topographies during resting state 32,33 and movement execution 34,35 . We sought to delineate the cortical and STN spatio-frequency distribution of t-SPC events during syllable repetition (Figure 3).…”

Disentangling Bradykinesia and Rigidity in Parkinson's Disease: Evidence from Short‐ and Long‐Term Subthalamic Nucleus Deep Brain Stimulation

“…The sensorimotor region of the STN (usually targeted by DBS) may include independent "sweet spots" for bradykinesia and rigidity, as suggested by recent symptom-stimulation mapping studies. [34][35][36][37][38] In theory, because the intraoperative assessment of rigidity is a relevant maneuver in guiding the optimal placement of the macroelectrode (when patients are operated on under local anesthesia), a preferential targeting for rigidity sweet spots could be responsible for our findings. However, the intrinsic variability in DBS electrode placement in the STN and the high number of subjects enrolled in this study make the hypothesis of a preferential targeting for rigidity sweet spot rather weak.…”