Embracing Diversity: Sedative effects vary across drug chemistry and frequency domains

Moderate sedation can balance patients' comfort and preserve brain activities during deep brain stimulation neurosurgical procedures; however, the sub-cortical effects of different sedatives are rarely explored. We simultaneously recorded EEG, local field potential (LFP), and spikes (multi- and single-unit) from the dorsolateral frontal cortex and external globus pallidus (GPe), the central nucleus of the basal ganglia, of two female non-human primates. These recordings were carried out after titration of each drug and animal to achieve moderate sedative effects. The recording sessions included three 1-h epochs before, during, and after a continuous infusion of sedative drugs. We tested four sedative drugs (ketamine, propofol, remifentanil, and dexmedetomidine) that mainly affect glutamate, GABA, opiate, and noradrenaline neuromodulation, respectively. These sedative drugs modulate cortical and GPe activity across unique frequency bands. Ketamine increased EEG/LFP power in the beta/gamma bands and decreased theta band power. Propofol, remifentanil, and dexmedetomidine increased the power of the delta band and decreased theta, beta, and gamma bands’ power, respectively. GPe activity often aligns with cortical activity. The inter- and intra-area correlations show similar patterns to the spectrograms. The pattern and synchronization of spiking activity exhibited trends similar to those observed in EEG/LFP signals, although the effects were less pronounced. These results suggest that, similar to sleep, the thalamic-cortical network, plays a crucial role in shaping basal ganglia activity during moderate sedation. EEG activity may, therefore, serve as a reference for selecting sedation protocols in deep brain stimulation procedures.