"Schrödinger’s Rat”: Testing Consciousness Under Anesthesia Alters Brain State and Neuronal Responses in Auditory Cortex

Aaron J Krom,1– 6 Lottem Bergman,3,7 Yaniv Sela,8 Hanna Cattan-Hayat,3,9 Noa Regev,3 Yuval Nir2,3,8,10,111Department of Anesthesiology, Intensive Care, and Pain Management, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; 2Sagol Brain Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; 3Department of Physiology and Pharmacology, Faculty of Medicine and Health Sciences, Tel Aviv University, Tel Aviv, Israel; 4Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; 5Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel; 6Department of Anesthesiology and Critical Care Medicine, Hadassah Medical Center, Jerusalem, Israel; 7Department of Neurosurgery, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; 8Sagol School of Neurosciences, Tel Aviv University, Tel Aviv, Israel; 9Department of Biological Chemistry, University of California Los Angeles, Los Angeles, CA, USA; 10Department of Biomedical Engineering, Faculty of Engineering, Tel Aviv University, Tel Aviv, Israel; 11The Sieratzki-Sagol Center for Sleep Medicine, Tel Aviv Sourasky Medical Center, Tel Aviv, IsraelCorrespondence: Aaron J Krom, Department of Anesthesiology, Pain and Critical Care Medicine, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel, Tel +972 3 6974444, Email [email protected]: In anesthesia research and clinical practice, the level of consciousness is often assessed by stimulating subjects and observing their responses. It is possible that such stimulation alters the very state of consciousness being assessed. Whether this phenomenon is accompanied by specific cortical activities remains unknown. Here, we tested the effects of behavioral assessments on neuronal activity in the rat primary auditory cortex (A1) and perirhinal cortex (PrC).Methods: Neuronal spiking activity was recorded from microwire arrays targeting A1 and/or PrC in rats (n = 9), whilst presenting 40 Hz click-trains and gradually increasing infusion rates of propofol, remifentanil, ketamine or dexmedetomidine. We assessed righting reflex, pain withdrawal, whisking reflex, and corneal reflex every 12 minutes (every 360 auditory trials). We searched for significant changes in baseline firing rate and stimulus-evoked activities (where present) due to the behavioral assessments, by comparing 4 min intervals before and after the behavioral tests.Results: Out of 1004 units in 20 sessions, we found significantly elevated activity (p < 0.01) following behavioral tests in 32% and 20% of A1 auditory-responsive units and 8.6% and 5.3% of auditory-unresponsive units under propofol and dexmedetomidine, respectively, but not under remifentanil or ketamine. A higher proportion of units modulated their firing following behavioral tests in A1 compared to PrC, with median gains ranging from +0.23 to +1.06, depending on the specific response feature.Conclusion: Behavioral testing increases ongoing firing rate and responses to sounds in some cortical neurons. This increase is more prevalent in A1 than in PrC, mirroring clinical observations that patients exhibit basic responses under sedation, while complex processing, such as memory encoding, is impaired. The degree of neuronal modulation due to behavioral testing varies between anesthetic agents, mirroring their clinical phenotypes.Keywords: assessing consciousness, sedation, propofol, dexmedetomidine, remifentanil, ketamine