Sedative drugs modulate the neuronal activity in the subthalamic nucleus of parkinsonian patients

Abstract

Microelectrode recording (MER) is often used to identify electrode location which is critical for the success of deep brain stimulation (DBS) treatment of Parkinson's disease. The usage of anesthesia and its' impact on MER quality and electrode placement is controversial. We recorded neuronal activity at a single depth inside the Subthalamic Nucleus (STN) before, during, and after remifentanil infusion. The root mean square (RMS) of the 250-6000 Hz band-passed signal was used to evaluate the regional spiking activity, the power spectrum to evaluate the oscillatory activity and the coherence to evaluate synchrony between two microelectrodes. We compare those to new frequency domain (spectral) analysis of previously obtained data during propofol sedation. Results showed Remifentanil decreased the normalized RMS by 9% (P < 0.001), a smaller decrease compared to propofol. Regarding the beta range oscillatory activity, remifentanil depressed oscillations (drop from 25 to 5% of oscillatory electrodes), while propofol did not (increase from 33.3 to 41.7% of oscillatory electrodes). In the cases of simultaneously recorded oscillatory electrodes, propofol did not change the synchronization while remifentanil depressed it. In conclusion, remifentanil interferes with the identification of the dorsolateral oscillatory region, whereas propofol interferes with RMS identification of the STN borders. Thus, both have undesired effect during the MER procedure.Trial registration: NCT00355927 and NCT00588926.

Conflict of interest statement

AR is a consultant for Medtronic (unrelated to the current manuscript), HB is a consultant for Alpha Omega and had received travel honoraria from Medtronic and Boston Scientific (unrelated to the current manuscript). None of the other authors reported any conflict of interest.

Figures

Figure 1

Effects of sedation on the global spiking activity in the STN. A: Raw data examples from a single trajectory. Top: before STN entry (presumably in white matter). Second line: inside the STN, before remifentanil administration. Third line: inside the STN, at the same location during remifentanil administration (patient sedated to the desired level). Bottom: inside the STN, at the same location, after remifentanil administration stopped, patient awake and responsive. All traces are 30 s long and presented with the same y scale. B–C: Examples of normalized root mean square (RMS) changes during propofol (B) and remifentanil (C) administration. X-axis = time (min); Y-axis = normalized RMS. Gray bars above the graphs indicates duration of drug administration. D–E: Population normalized. RMS. Aligned to the beginning of propofol (D) or remifentanil (E) administration. X-axis = time (min); Y-axis = normalized RMS. Subplots B and D are modified from Raz et al. Anesth Analg 2010; 111:1,285–9 for easy comparison of propofol and remifentanil effects.

Figure 2

Effects of sedation on oscillatory activity in the STN. Green and red frames (A, B) represent two cells which are also depicted in figures C and D for propofol and remifentanil, respectively. A: Raw data examples from two distinct cells. Top row: First cell, before propofol administration. Second row: Second cell, before propofol administration. Third row: First cell, during propofol administration (patient sedated to the desired level). Bottom row: Second cell, during propofol administration (patient sedated to the desired level). All traces are 10 s long and presented with the same y scale. B: The same as A, for remifentanil administration. C: Average power spectrum (left) and coherence (right) of 30 s of neural (multi-unit) activity in a single location measured from one patient before (top) and during (bottom) administration of propofol. It can be seen that no reduction of the beta power oscillations or coherence was observed. D: Same as C but with administration of remifentanil, measured from a different patient. It can be seen that one of the cells lost its’ oscillatory behavior, and the previously robust synchronization disappeared. E: Power spectrum of the multi-unit activity recorded by a single electrode measured around the time of propofol administration. It can be seen oscillatory activity in the beta power increased during propofol sedation. F: Same as E, but around the time of remifentanil administration. It can be seen that significant reduction in the beta power was observed during remifentanil administration. G: Coherence of the mutli-unit activity of two simultaneously recorded electrodes measured around the time of propofol administration. It can be seen that there is a significant coherence between the two electrodes which is maintained under sedation with propofol. H: Same as G but during administration of remifentanil. It can be seen that there is a significant coherence between the two electrodes which is depressed after remifentanil administration. For E–H, x-axis = time (min); y-axis = frequency (Hz) and color code represents power (E, F) or coherence (G, H). Time of sedative drug administration (propofol—left column, remifentanil—right column) is marked by a vertical line.