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Implantation of deep brain stimulation (DBS) electrodes in the subthalamic nucleus (STN) for the treatment of Parkinson disease is often performed using microelectrode recording (MER) of STN population spike activity. The extent to which sedative drugs interfere with MER is unknown. We recorded the population activity of STN neurons during propofol sedation and examined its effect on neuronal activity.The procedure was performed during DBS surgery for Parkinson disease. We administered propofol (50 μg/kg/min) at a constant electrode location in the STN until stable sedation was achieved. We recorded the electrical activity, and calculated its root mean square (RMS) before, during, and after the propofol infusions.The activity of 24 electrode trajectories was recorded in 16 patients. The RMS of STN activity decreased significantly after propofol administration in 18 of the 24 trajectories. The average normalized RMS decreased by 23.2%± 9.1% (mean ± SD) during propofol administration (P < 0.001), and returned to baseline 9.3 ± 4.0 minutes after it was stopped.Propofol administration leads to a significant decrease of STN neuronal activity. Thus, it may interfere with MER identification of the STN borders. However, activity returns to baseline shortly after administration stops. Therefore, propofol can be safely used until shortly before MER for DBS.