Toward asleep DBS: cortico-basal ganglia spectral and coherence activity during interleaved propofol/ketamine sedation mimics NREM/REM sleep activity

Orilia Ben-Yishay Nizri,Zvi Israel,Vadim Kapuller,Hagai Bergman,Shimon Firman,Jing Guang,Halen Baker,Uri Werner-Reiss

doi:10.1038/s41531-021-00211-9

Abstract

Deep brain stimulation (DBS) is currently a standard procedure for advanced Parkinson’s disease. Many centers employ awake physiological navigation and stimulation assessment to optimize DBS localization and outcome. To enable DBS under sedation, asleep DBS, we characterized the cortico-basal ganglia neuronal network of two nonhuman primates under propofol, ketamine, and interleaved propofol-ketamine (IPK) sedation. Further, we compared these sedation states in the healthy and Parkinsonian condition to those of healthy sleep. Ketamine increases high-frequency power and synchronization while propofol increases low-frequency power and synchronization in polysomnography and neuronal activity recordings. Thus, ketamine does not mask the low-frequency oscillations used for physiological navigation toward the basal ganglia DBS targets. The brain spectral state under ketamine and propofol mimicked rapid eye movement (REM) and Non-REM (NREM) sleep activity, respectively, and the IPK protocol resembles the NREM-REM sleep cycle. These promising results are a meaningful step toward asleep DBS with nondistorted physiological navigation.

Highlights

It is estimated that 10 million people worldwide suffer from Parkinson’s disease (PD)
The experiments were performed on two female African green monkeys (Chlorocebus aethiops sabaeus, weight: ~4 kg)
We performed an exploration of the pair-wise synchronization of EEG, cortex, and basal ganglia LFP and spiking activity

Summary

Introduction

It is estimated that 10 million people worldwide suffer from Parkinson’s disease (PD). One of the most promising long-term treatments available is deep brain stimulation (DBS). The most common targets are the subthalamic nucleus (STN) and the internal segment of the globus pallidus (GPi). This results in a vast improvement in PD symptoms[1,2,3,4]. To accurately reach the target of the DBS lead, a neural navigation system that requires brain electrophysiological signals from the awake patient may be used[9,10]. Some patients avoid DBS therapy due to the fear of undergoing awake brain surgery[11], leaving a wide gap for therapeutic improvement

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