**4. Discussion**

In this retrospective analysis, we studied the influence of the non-GABAergic drugs DEX, CLONI and REMI on the firing rate and CV of single neuron activity, as well as the power of MUA in the STN of PD patients undergoing DBS surgery. The results of the present study demonstrated that, even when PSA was discontinued around 20 min prior to MER, this still had significant effect on MUA. A trend was observed for a reduced firing rate by DEX, which was significant on the correlation analysis. Both DEX and REMI showed an increase in CV, but only DEX showed a decrease in MUA. The effect of DEX was dose-dependent. CLONI showed no effect on all measures. Lastly, several patient-dependent variables, such as age, disease duration and left or right hemisphere influenced MUA and CV.

### *4.1. E*ff*ect of Procedural Sedation and Analgesia on Micro-Electrode Recordings*

The use of PSA agents and their effects on neuronal activity has been debated since the initiation of DBS surgery. Traditionally, the anesthetic managemen<sup>t</sup> approach comprised local anesthesia with monitored care to facilitate MER. However, recent work has shown that 40% of patients suffer from pain, severe OFF-symptoms and intolerable exhaustion during the hours of awake surgery [5]. To improve patient acceptance, sedation is thus commonly administered. Propofol, a GABAergic agent, has been most frequently used when sedation is required. As stated before, several clinical reports showed a dose-dependent effect of propofol on STN neuronal activity in patients with PD [7–9,20]. Propofol reduces neuronal activity by enhancing inhibitory neurotransmission and reducing excitatory neurotransmission [21]. Although some studies showed good quality MER with low-dose propofol, potent GABAergic agents such as propofol should not be the first choice for PSA during DBS surgery [22–24].

Alternatively, <sup>α</sup>2-agonists (non-GABAergic) are useful in this regard. Currently, two different <sup>α</sup>2-agonists are commonly used in clinical practice: CLONI and DEX. While both drugs have anxiolytic, sedative and analgesic properties, DEX is a more selective <sup>α</sup>2-receptor agonist than CLONI. Since central <sup>α</sup>1-receptor activation counteracts sedative α2 effects, DEX has a more profound sedative effect [25]. The sedative effects of <sup>α</sup>2-agonists are mediated through activation of pre- and postsynaptic <sup>α</sup>2-receptors in the locus coeruleus which has noradrenergic afferent connections with the STN [26,27]. This route provides a plausible mechanism for the effects observed in the current study, since it has been shown that noradrenergic modulation with α1 and <sup>α</sup>2-agonists change firing rate and firing patterns of STN neurons, in line with our findings [28,29].
