Anesthesia reduces discharge rates in the human pallidum without changing the discharge rate ratio between pallidal segments

Abstract

Classical rate models of basal ganglia circuitry associate discharge rate of the globus pallidus external and internal segments (GPe, GPi respectively) solely with dopaminergic state and predict an inverse ratio between the discharge rates of the two pallidal segments. In contrast, the effects of other rate modulators such as general anesthesia (GA) on this ratio have been ignored. To respond to this need, we recorded the neuronal activity in the GPe and GPi in awake and anesthetized human patients with dystonia (57 and 53 trajectories respectively) and in awake patients with Parkinson's disease (PD, 16 trajectories) undergoing deep brain stimulation procedures. This triad enabled us to dissociate pallidal discharge ratio from general discharge modulation. An automatic offline spike detection and isolation quality system was used to select 1560 highly isolated units for analysis. The mean discharge rate in the GPi of awake PD patients was dramatically higher than in awake dystonia patients although the firing rate in the GPe was similar. Firing rates in dystonic patients under anesthesia were lower in both nuclei. Surprisingly, in all three groups, GPe firing rates were correlated with firing rates in the ipsilateral GPi. Thus, the firing rate ratio of ipsilateral GPi/GPe pairs was similar in awake and anesthetized patients with dystonia and significantly higher in PD. We suggest that pallidal activity is modulated by at least two independent processes: dopaminergic state which changes the GPi/GPe firing rate ratio, and anesthesia which modulates firing rates in both pallidal nuclei without changing the ratio between their firing rates.

In vivo electrophysiological validation of DREADD‐based modulation of pallidal neurons in the non‐human primate

“…Moreover, we recorded the pallidal activity in anesthetized animals. Earlier studies demonstrated that anesthesia reduces the discharge rate of the GPe neurons (e.g., Castrioto et al., 2016). Therefore, we cannot rule out the possibility that anesthesia regimen minimized the DREADD’s action/CNOs'effect on pallidal activity.…”

Effect of Anesthesia on Microelectrode Recordings During Deep Brain Stimulation Surgery: A Narrative Review

“…The potential impact of nitrous oxide on MER was not discussed. 26 In summary, the evidence on the effects of volatile anesthetics on MER consists of 8 clinical trials with small sample sizes in which different volatile anesthetic agents and different surgical targets were investigated. Because of this heterogeneity in disease states, targets, and anesthetic agents, it is difficult to draw definitive conclusions on the effects of volatile anesthesia on MER.…”

Bilateral Subthalamic Nucleus Deep Brain Stimulation under General Anesthesia: Literature Review and Single Center Experience

“…Chen et al also reported that there was no difference in the UPDRS III reduction rate and score 6 months after STN DBS surgery between the MER group and the non-MER group [42]. In addition to frequently used imaging sequences, direct targeting can be used with quantitative susceptibility mapping (QSM) and diffusion tensor imaging (DTI) [ GA with both volatile and intravenous anesthetics in PD and dystonia patients showed no significant difference compared with patients awake during the procedure [54,[88][89][90][91]. Notably, the neural activity of typical burst pattern disappeared when higher anesthetic doses were used.…”

“…The biggest concern with STN DBS surgery under GA for movement disorder is the possibility of diminution of MER signals. A few small-sized retrospective studies have reported that MER obtained from STN, GPi, substantia nigra in STN DBS surgery under GA with both volatile and intravenous anesthetics in PD and dystonia patients showed no significant difference compared with patients awake during the procedure [ 54 , 88 , 89 , 90 , 91 ]. Notably, the neural activity of typical burst pattern disappeared when higher anesthetic doses were used.…”