*3.4. Interrater Reliability*

SUs were identified and sorted by hand which is an inevitably subjective process (Figure 1). To test whether the effects we report were robust, every recording was inspected by at least two individuals (every site was inspected A.M.A.S. and one of M.J.B., M.J.R. or R.B.). We repeated the linear regression analysis for SU data (spikes/seconds and CV) using data for units identified by M.J.B., M.J.R. or R.B., including the sorter ID as an additional categorical variable. All main effects we report on were replicated in this analysis (supplementary material Table S2).

### *3.5. Dose-Dependent E*ff*ect of DEX*

Our analysis showed that DEX had a significant impact on electrophysiological measures. To test whether these effects were dose-dependent, we conducted further analysis focused only on patients who received DEX during surgery. We first performed a simple correlation analysis between each measure and DEX dose (Figure 4). The correlations were significant, but the correlation coefficient was low for all measures. For illustration, we extrapolated the regression line to include 0 dose and plotted the data for the 0 dose patients (not included PSA discontinued group). For both firing rate and CV the regression line passed close to the mean of the 0 dose data, while this was not the case for MUA. This may indicate a non-linear effect of DEX on MUA whereby even a small dose leads to strong suppression. This interpretation would be in line with our finding that discontinuation of DEX, 20 min before recordings MUA also had a large impact. One interesting point is that the analysis of firing rate was significant, showing a decrease in firing rate with increased dose. This might mean that the trend observed in the *t*-test and linear regression analysis is a true effect.

**Figure 4.** Correlation analysis on the dose of DEX for the electrophysiological measures. Correlations were significant. Data of the no PSA drug group is shown in black for comparison but was excluded from the regression analysis. DEX: dexmedetomidine.
