**1. Introduction**

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established procedure for the treatment of refractory Parkinson's disease (PD) [1]. The clinical outcome of the surgery largely depends on correct positioning of the stimulating electrode in the sensorimotor region of the STN [2,3]. Microelectrode recordings (MER) of single-cell and multi-unit neuronal activity are commonly used to verify the borders of the STN [4]. To obtain reliable MER, DBS surgery is traditionally performed under local anesthesia alone, as the sedative and anesthetic agents may interfere with neural activity. However, patients may experience pain, anxiety or other forms of discomfort. To improve patient comfort and tolerance of the DBS implantation procedure, procedural sedation and/or analgesia (PSA) may be applied [5].

Propofol is commonly used for sedation during DBS implantation. It exerts its clinical e ffect through an agonist e ffect on the gamma-aminobutyric acid type A (GABA A) receptor [6]. Several studies have shown that GABAergic agents alter STN activity in a dose-dependent manner [7–9]. In the past decade experience has been gained with non-GABA-mediated agents, including the <sup>α</sup>2-agonists clonidine (CLONI) and dexmedetomidine (DEX), which possess sedative and mild analgesic e ffects, and the ultrashort acting opioid, remifentanil (REMI) which provides potent analgesia and mild sedation. Since the pharmacokinetic e ffects of these drugs are not mediated by GABA A receptors, their influence on STN neuronal activity is postulated to be less pronounced than of GABAergic agents. However, the available literature on non-GABA-mediated PSA e ffects on STN neuronal activity is sparse and consists largely of small uncontrolled retrospective case series with poor control over heterogeneity in patient cohorts [10–16].

The primary aim of this study was to determine the e ffect of the non-GABAergic PSA agents DEX, CLONI and REMI on MER in patients with PD during DBS electrode implantation surgery. In addition to PSA-related e ffects on MER, we analyzed patient characteristics such as age, disease severity and disease duration to control for heterogeneity in the sample.

### **2. Materials and Methods**
