title: The effect of dexmedetomidine on the firing properties of STN neurons in Parkinson's disease.
abstract: Dexmedetomidine (an alpha-2 adrenergic agonist) sedation is commonly used during subthalamic nucleus (STN) deep-brain stimulation (DBS). Its effects on the electrophysiological characteristics of human STN neurons are largely unknown. We hypothesised that dexmedetomidine modulates the firing rates and bursting of human STN neurons. We analysed microelectrode recording (MER) data from patients with Parkinson's disease who underwent STN DBS. A 'Dex bolus' group (dexmedetomidine bolus prior to MER; 27 cells from seven patients) was compared with a 'no sedation' group (29 cells from 11 patients). We also performed within-patient comparisons with varying dexmedetomidine states. Cells were classified as dorsal half or ventral half based on their relative location in the STN. Neuronal burst and oscillation characteristics were analysed using the Kaneoke-Vitek methodology and local field potential (LFP) oscillatory activity was also investigated. Dexmedetomidine was associated with a slight increase in firing rate (41.1 ± 9.9 vs. 34.5 ± 10.6 Hz, P = 0.02) but a significant decrease in burstiness (number of bursts, P = 0.02; burst index, P < 0.001; percentage of spikes in burst, P = 0.002) of dorsal but not ventral STN neurons. This was not associated with modulation of beta oscillations in the spike-oscillations analysis(beta peak, P = 0.4; signal-to-noise ratio in the beta range for spikes and bursts, P = 0.3 and P = 0.5, respectively) and LFP analysis (Beta power, P = 0.17). As bursting pattern is often used to identify STN and guide electrode placement, we recommend that high-dose dexmedetomidine should be avoided during DBS surgery.
authors.affiliation: Division of Neurosurgery, Toronto Western Hospital, University of Toronto, 399 Bathurst Street, Toronto, ON M5T2S8, Canada.
authors.forename: Vibhor
authors.initials: V
authors.lastname: Krishna
authors.affiliation: Division of Neurosurgery, Toronto Western Hospital, University of Toronto, 399 Bathurst Street, Toronto, ON M5T2S8, Canada.
authors.forename: Gavin
authors.initials: G
authors.lastname: Elias
authors.affiliation: Division of Neurosurgery, Toronto Western Hospital, University of Toronto, 399 Bathurst Street, Toronto, ON M5T2S8, Canada.
authors.forename: Francesco
authors.initials: F
authors.lastname: Sammartino
authors.affiliation: Department of Physiology, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada.
authors.forename: Diellor
authors.initials: D
authors.lastname: Basha
authors.affiliation: Division of Neurosurgery, Toronto Western Hospital, University of Toronto, 399 Bathurst Street, Toronto, ON M5T2S8, Canada.
authors.forename: Nicolas K K
authors.initials: NK
authors.lastname: King
authors.affiliation: Morton and Gloria Shulman Movement Disorders Centre and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, Toronto, ON, Canada.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Fasano
authors.affiliation: Morton and Gloria Shulman Movement Disorders Centre and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, Toronto, ON, Canada.
authors.forename: Renato
authors.initials: R
authors.lastname: Munhoz
authors.affiliation: Division of Neurosurgery, Toronto Western Hospital, University of Toronto, 399 Bathurst Street, Toronto, ON M5T2S8, Canada.
authors.forename: Suneil K
authors.initials: SK
authors.lastname: Kalia
authors.affiliation: Division of Neurosurgery, Toronto Western Hospital, University of Toronto, 399 Bathurst Street, Toronto, ON M5T2S8, Canada.
authors.forename: Mojgan
authors.initials: M
authors.lastname: Hodaie
authors.affiliation: Department of Anesthesiology, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada.
authors.forename: Lashmi
authors.initials: L
authors.lastname: Venkatraghavan
authors.affiliation: Division of Neurosurgery, Toronto Western Hospital, University of Toronto, 399 Bathurst Street, Toronto, ON M5T2S8, Canada.
authors.forename: Andres M
authors.initials: AM
authors.lastname: Lozano
authors.affiliation: Department of Physiology, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada.
authors.forename: William D
authors.initials: WD
authors.lastname: Hutchison
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D046690:Deep Brain Stimulation / Q000379:methods; D020927:Dexmedetomidine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008839:Microelectrodes; D008875:Middle Aged; D009474:Neurons / Q000187:drug effects*; D010300:Parkinson Disease / Q000473:pathology* / Q000628:therapy; D018709:Statistics, Nonparametric; D020531:Subthalamic Nucleus / Q000166:cytology* / Q000502:physiology
chemical_list: D018712:Analgesics, Non-Narcotic; D020927:Dexmedetomidine
keywords: alpha-2 adrenergic agonist; beta oscillations; burst pattern; deep brain stimulation; intra-operative sedation; microelectrode recording