Kin Foon Kevin Wong1, Anne C Smith2, Eric T Pierce3, P Grace Harrell4, John L Walsh3, Andrés Felipe Salazar-Gómez5, Casie L Tavares6, Patrick L Purdon3, Emery N Brown7. 1. Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA; Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, USA. Electronic address: wong@neurostat.mit.edu. 2. Department of Bioengineering, University of Illinois at Chicago, Chicago, IL, USA. 3. Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. 4. Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA; Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, USA. 5. Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA; Boston University, Boston, MA, USA. 6. Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA; School of Nursing, Regis College, Weston, MA, USA. 7. Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA. Electronic address: enb@neurostat.mit.edu.
Abstract
BACKGROUND: Accurate quantitative analysis of the changes in responses to external stimuli is crucial for characterizing the timing of loss and recovery of consciousness induced by anesthetic drugs. We studied induction and emergence from unconsciousness achieved by administering a computer-controlled infusion of propofol to ten human volunteers. We evaluated loss and recovery of consciousness by having subjects execute every 4s two interleaved computer delivered behavioral tasks: responding to verbal stimuli (neutral words or the subject's name), or less salient stimuli of auditory clicks. NEW METHOD: We analyzed the data using state-space methods. For each stimulus type the observation model is a two-stage binomial model and the state model is two dimensional random walk in which one cognitive state governs the probability of responding and the second governs the probability of correctly responding given a response. We fit the model to the experimental data using Bayesian Monte Carlo methods. RESULTS: During induction subjects lost responsiveness to less salient clicks before losing responsiveness to the more salient verbal stimuli. During emergence subjects regained responsiveness to the more salient verbal stimuli before regaining responsiveness to the less salient clicks. COMPARISON WITH EXISTING METHOD(S): The current state-space model is an extension of previous model used to analyze learning and behavioral performance. In this study, the probability of responding on each trial is obtained separately from the probability of behavioral performance. CONCLUSIONS: Our analysis provides a principled quantitative approach for defining loss and recovery of consciousness in experimental studies of general anesthesia.
BACKGROUND: Accurate quantitative analysis of the changes in responses to external stimuli is crucial for characterizing the timing of loss and recovery of consciousness induced by anesthetic drugs. We studied induction and emergence from unconsciousness achieved by administering a computer-controlled infusion of propofol to ten human volunteers. We evaluated loss and recovery of consciousness by having subjects execute every 4s two interleaved computer delivered behavioral tasks: responding to verbal stimuli (neutral words or the subject's name), or less salient stimuli of auditory clicks. NEW METHOD: We analyzed the data using state-space methods. For each stimulus type the observation model is a two-stage binomial model and the state model is two dimensional random walk in which one cognitive state governs the probability of responding and the second governs the probability of correctly responding given a response. We fit the model to the experimental data using Bayesian Monte Carlo methods. RESULTS: During induction subjects lost responsiveness to less salient clicks before losing responsiveness to the more salient verbal stimuli. During emergence subjects regained responsiveness to the more salient verbal stimuli before regaining responsiveness to the less salient clicks. COMPARISON WITH EXISTING METHOD(S): The current state-space model is an extension of previous model used to analyze learning and behavioral performance. In this study, the probability of responding on each trial is obtained separately from the probability of behavioral performance. CONCLUSIONS: Our analysis provides a principled quantitative approach for defining loss and recovery of consciousness in experimental studies of general anesthesia.
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