GABAA Circuit Level Mechanisms are Associated with Ether- induced Unconsciousness

Objective—An emerging paradigm for understanding how anesthetics induce altered arousal is relating receptor targeting in specific neural circuits to electroencephalogram (EEG) activity. We have previously found that enhanced gamma amino-butyric acid A (GABAA) inhibitory postsynaptic currents (IPSCs) manifest with large-amplitude slow (0.1–1 Hz) and frontally coherent alpha (8–12 Hz) oscillations. Therefore, we investigated the EEG signatures of modern day derivatives of ether (MDDE) to assess the extent to which we could obtain insights into MDDE anesthetic mechanisms Methods—We retrospectively studied cases from our database in which patients received isoflurane vs. isoflurane/ketamine (n=10 each) or desflurane vs. desflurane/ketamine (n = 9 each). We analyzed the EEG recordings with spectral power and coherence methods. Results—Similar to known GABAA circuit level mechanisms, we found that MDDE induced large amplitude slow and frontally coherent alpha oscillations. Additionally, MDDE also induced frontally coherent theta (4–8 Hz) oscillations. Reduction of GABAergic IPSCs with ketamine Corresponding Author: Oluwaseun Akeju, 55 Fruit Street, Jackson Building, Rm. 460, Boston, MA 02114. USA, Tel.: +1-617-724-7200, [email protected]. Disclosures The authors Oluwaseun Akeju, Emery N. Brown, and Patrick L. Purdon have submitted a provisional patent application describing the use of the EEG measures described in this manuscript for monitoring sedation and general anesthesia. All other authors declare no competing interests. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. HHS Public Access Author manuscript Clin Neurophysiol. Author manuscript; available in PMC 2017 June 01. Published in final edited form as: Clin Neurophysiol. 2016 June ; 127(6): 2472–2481. doi:10.1016/j.clinph.2016.02.012. A uhor M anscript