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Background: Anaesthetic-induced unresponsiveness and non-rapid eye movement (NREM) sleep share common neural pathways and neurophysiological features. We hypothesised that these states bear resemblance also at the experiential level. Methods: We compared, in a within-subject design, the prevalence and content of experiences in reports obtained after anaesthetic-induced unresponsiveness and NREM sleep. Healthy males (N=39) received dexmedetomidine (n=20) or propofol (n=19) in stepwise doses to induce unresponsiveness. Those rousable were interviewed and left unstimulated, and the procedure was repeated. Finally, the anaesthetic dose was increased 50%, and the participants were interviewed after recovery. The same participants (N=37) were also later interviewed after NREM sleep awakenings. Results: Most subjects were rousable, with no difference between anaesthetic agents (P=0.480). Lower drug plasma concentrations were associated with being rousable for both dexmedetomidine (P=0.007) and propofol (P=0.002) but not with recall of experiences in either drug group (dexmedetomidine: P=0.543; propofol: P=0.460). Of the 76 and 73 interviews performed after anaesthetic-induced unresponsiveness and NREM sleep, 69.7% and 64.4% included experiences, respectively. Recall did not differ between anaesthetic-induced unresponsiveness and NREM sleep (P=0.581), or between dexmedetomidine and propofol in any of the three awakening rounds (P>0.05). Disconnected dream-like experiences (62.3% vs 51.1%; P=0.418) and memory incorporation of the research setting (88.7% vs 78.7%; P=0.204) were equally often present in anaesthesia and sleep interviews, respectively, whereas awareness, signifying connected consciousness, was rarely reported in either state. Conclusions: Anaesthetic-induced unresponsiveness and NREM sleep are characterised by disconnected conscious experiences with corresponding recall frequencies and content. Clinical trial registration: Clinical trial registration. This st, CC BY 4.0© 2023 The AuthorsAvailable online 31 May 2023Corresponding author: E-mail: katval@utu.fiFundingAcademy of Finland, Helsinki, Finland (266467 and 266434); Jane and Aatos Erkko Foundation, Helsinki, Finland; VSSHP-EVO (13323 and L3824); Doctoral Program of Clinical Investigation, University of Turku Graduate School, Turku, Finland to LR and AS; The Paulo Foundation, Espoo, Finland to AS; The Finnish Medical Foundation, Helsinki, Finland to AS; The Orion Research Foundation, Espoo, Finland to AS; Signe and Ane Gyllenberg Foundation, Helsinki, Finland to KV.

Background: Anaesthetic-induced unresponsiveness and non-rapid eye movement (NREM) sleep share common neural pathways and neurophysiological features. We hypothesised that these states bear resemblance also at the experiential level. Methods: We compared, in a within-subject design, the prevalence and content of experiences in reports obtained after anaesthetic-induced unresponsiveness and NREM sleep. Healthy males (N=39) received dexmedetomidine (n=20) or propofol (n=19) in stepwise doses to induce unresponsiveness. Those rousable were interviewed and left unstimulated, and the procedure was repeated. Finally, the anaesthetic dose was increased 50%, and the participants were interviewed after recovery. The same participants (N=37) were also later interviewed after NREM sleep awakenings. Results: Most subjects were rousable, with no difference between anaesthetic agents (P=0.480). Lower drug plasma concentrations were associated with being rousable for both dexmedetomidine (P=0.007) and propofol (P=0.002) but not with recall of experiences in either drug group (dexmedetomidine: P=0.543; propofol: P=0.460). Of the 76 and 73 interviews performed after anaesthetic-induced unresponsiveness and NREM sleep, 69.7% and 64.4% included experiences, respectively. Recall did not differ between anaesthetic-induced unresponsiveness and NREM sleep (P=0.581), or between dexmedetomidine and propofol in any of the three awakening rounds (P>0.05). Disconnected dream-like experiences (62.3% vs 51.1%; P=0.418) and memory incorporation of the research setting (88.7% vs 78.7%; P=0.204) were equally often present in anaesthesia and sleep interviews, respectively, whereas awareness, signifying connected consciousness, was rarely reported in either state. Conclusions: Anaesthetic-induced unresponsiveness and NREM sleep are characterised by disconnected conscious experiences with corresponding recall frequencies and content. Clinical trial registration: Clinical trial registration. This st, CC BY 4.0© 2023 The AuthorsAvailable online 31 May 2023Corresponding author: E-mail: katval@utu.fiFundingAcademy of Finland, Helsinki, Finland (266467 and 266434); Jane and Aatos Erkko Foundation, Helsinki, Finland; VSSHP-EVO (13323 and L3824); Doctoral Program of Clinical Investigation, University of Turku Graduate School, Turku, Finland to LR and AS; The Paulo Foundation, Espoo, Finland to AS; The Finnish Medical Foundation, Helsinki, Finland to AS; The Orion Research Foundation, Espoo, Finland to AS; Signe and Ane Gyllenberg Foundation, Helsinki, Finland to KV.

Background: Anaesthetic-induced unresponsiveness and non-rapid eye movement (NREM) sleep share common neural pathways and neurophysiological features. We hypothesised that these states bear resemblance also at the experiential level. Methods: We compared, in a within-subject design, the prevalence and content of experiences in reports obtained after anaesthetic-induced unresponsiveness and NREM sleep. Healthy males (N=39) received dexmedetomidine (n=20) or propofol (n=19) in stepwise doses to induce unresponsiveness. Those rousable were interviewed and left unstimulated, and the procedure was repeated. Finally, the anaesthetic dose was increased 50%, and the participants were interviewed after recovery. The same participants (N=37) were also later interviewed after NREM sleep awakenings. Results: Most subjects were rousable, with no difference between anaesthetic agents (P=0.480). Lower drug plasma concentrations were associated with being rousable for both dexmedetomidine (P=0.007) and propofol (P=0.002) but not with recall of experiences in either drug group (dexmedetomidine: P=0.543; propofol: P=0.460). Of the 76 and 73 interviews performed after anaesthetic-induced unresponsiveness and NREM sleep, 69.7% and 64.4% included experiences, respectively. Recall did not differ between anaesthetic-induced unresponsiveness and NREM sleep (P=0.581), or between dexmedetomidine and propofol in any of the three awakening rounds (P>0.05). Disconnected dream-like experiences (62.3% vs 51.1%; P=0.418) and memory incorporation of the research setting (88.7% vs 78.7%; P=0.204) were equally often present in anaesthesia and sleep interviews, respectively, whereas awareness, signifying connected consciousness, was rarely reported in either state. Conclusions: Anaesthetic-induced unresponsiveness and NREM sleep are characterised by disconnected conscious experiences with corresponding recall frequencies and content. Clinical trial registration: Clinical trial registration. This st, CC BY 4.0© 2023 The AuthorsAvailable online 31 May 2023Corresponding author: E-mail: katval@utu.fiFundingAcademy of Finland, Helsinki, Finland (266467 and 266434); Jane and Aatos Erkko Foundation, Helsinki, Finland; VSSHP-EVO (13323 and L3824); Doctoral Program of Clinical Investigation, University of Turku Graduate School, Turku, Finland to LR and AS; The Paulo Foundation, Espoo, Finland to AS; The Finnish Medical Foundation, Helsinki, Finland to AS; The Orion Research Foundation, Espoo, Finland to AS; Signe and Ane Gyllenberg Foundation, Helsinki, Finland to KV.

Background: Anaesthetic-induced unresponsiveness and non-rapid eye movement (NREM) sleep share common neural pathways and neurophysiological features. We hypothesised that these states bear resemblance also at the experiential level. Methods: We compared, in a within-subject design, the prevalence and content of experiences in reports obtained after anaesthetic-induced unresponsiveness and NREM sleep. Healthy males (N=39) received dexmedetomidine (n=20) or propofol (n=19) in stepwise doses to induce unresponsiveness. Those rousable were interviewed and left unstimulated, and the procedure was repeated. Finally, the anaesthetic dose was increased 50%, and the participants were interviewed after recovery. The same participants (N=37) were also later interviewed after NREM sleep awakenings. Results: Most subjects were rousable, with no difference between anaesthetic agents (P=0.480). Lower drug plasma concentrations were associated with being rousable for both dexmedetomidine (P=0.007) and propofol (P=0.002) but not with recall of experiences in either drug group (dexmedetomidine: P=0.543; propofol: P=0.460). Of the 76 and 73 interviews performed after anaesthetic-induced unresponsiveness and NREM sleep, 69.7% and 64.4% included experiences, respectively. Recall did not differ between anaesthetic-induced unresponsiveness and NREM sleep (P=0.581), or between dexmedetomidine and propofol in any of the three awakening rounds (P>0.05). Disconnected dream-like experiences (62.3% vs 51.1%; P=0.418) and memory incorporation of the research setting (88.7% vs 78.7%; P=0.204) were equally often present in anaesthesia and sleep interviews, respectively, whereas awareness, signifying connected consciousness, was rarely reported in either state. Conclusions: Anaesthetic-induced unresponsiveness and NREM sleep are characterised by disconnected conscious experiences with corresponding recall frequencies and content. Clinical trial registration: Clinical trial registration. This st, CC BY 4.0© 2023 The AuthorsAvailable online 31 May 2023Corresponding author: E-mail: katval@utu.fiFundingAcademy of Finland, Helsinki, Finland (266467 and 266434); Jane and Aatos Erkko Foundation, Helsinki, Finland; VSSHP-EVO (13323 and L3824); Doctoral Program of Clinical Investigation, University of Turku Graduate School, Turku, Finland to LR and AS; The Paulo Foundation, Espoo, Finland to AS; The Finnish Medical Foundation, Helsinki, Finland to AS; The Orion Research Foundation, Espoo, Finland to AS; Signe and Ane Gyllenberg Foundation, Helsinki, Finland to KV.

Background: Anaesthetic-induced unresponsiveness and non-rapid eye movement (NREM) sleep share common neural pathways and neurophysiological features. We hypothesised that these states bear resemblance also at the experiential level. Methods: We compared, in a within-subject design, the prevalence and content of experiences in reports obtained after anaesthetic-induced unresponsiveness and NREM sleep. Healthy males (N=39) received dexmedetomidine (n=20) or propofol (n=19) in stepwise doses to induce unresponsiveness. Those rousable were interviewed and left unstimulated, and the procedure was repeated. Finally, the anaesthetic dose was increased 50%, and the participants were interviewed after recovery. The same participants (N=37) were also later interviewed after NREM sleep awakenings. Results: Most subjects were rousable, with no difference between anaesthetic agents (P=0.480). Lower drug plasma concentrations were associated with being rousable for both dexmedetomidine (P=0.007) and propofol (P=0.002) but not with recall of experiences in either drug group (dexmedetomidine: P=0.543; propofol: P=0.460). Of the 76 and 73 interviews performed after anaesthetic-induced unresponsiveness and NREM sleep, 69.7% and 64.4% included experiences, respectively. Recall did not differ between anaesthetic-induced unresponsiveness and NREM sleep (P=0.581), or between dexmedetomidine and propofol in any of the three awakening rounds (P>0.05). Disconnected dream-like experiences (62.3% vs 51.1%; P=0.418) and memory incorporation of the research setting (88.7% vs 78.7%; P=0.204) were equally often present in anaesthesia and sleep interviews, respectively, whereas awareness, signifying connected consciousness, was rarely reported in either state. Conclusions: Anaesthetic-induced unresponsiveness and NREM sleep are characterised by disconnected conscious experiences with corresponding recall frequencies and content. Clinical trial registration: Clinical trial registration. This st, CC BY 4.0© 2023 The AuthorsAvailable online 31 May 2023Corresponding author: E-mail: katval@utu.fiFundingAcademy of Finland, Helsinki, Finland (266467 and 266434); Jane and Aatos Erkko Foundation, Helsinki, Finland; VSSHP-EVO (13323 and L3824); Doctoral Program of Clinical Investigation, University of Turku Graduate School, Turku, Finland to LR and AS; The Paulo Foundation, Espoo, Finland to AS; The Finnish Medical Foundation, Helsinki, Finland to AS; The Orion Research Foundation, Espoo, Finland to AS; Signe and Ane Gyllenberg Foundation, Helsinki, Finland to KV.

To understand how anesthetics with different molecular mechanisms affect consciousness, we explored subjective experiences recalled after responsive and unresponsive sedation induced with equisedative doses of dexmedetomidine, propofol, sevoflurane, and S-ketamine in healthy male participants (N = 140). The anesthetics were administered in experimental setting using target-controlled infusion or vapouriser for one hour. Interviews conducted after anesthetic administration revealed that 46.9% (n = 46) of arousable participants (n = 98) reported experiences, most frequently dreaming or memory incorporation of the setting. Participants receiving dexmedetomidine reported experiences most often while S-ketamine induced the most multimodal experiences. Responsiveness at the end of anesthetic administration did not affect the prevalence or content of reported experiences. These results demonstrate that subjective experiences during responsive and unresponsive sedation are common and anesthetic agents with different molecular mechanisms of action may have different effects on the prevalence and complexity of the experiences, albeit in the present sample the differences between drugs were minute., CC BY 4.0© 2021 The AuthorsCorresponding author. E-mail address: liemra@utu.fi (L. Radek).

To understand how anesthetics with different molecular mechanisms affect consciousness, we explored subjective experiences recalled after responsive and unresponsive sedation induced with equisedative doses of dexmedetomidine, propofol, sevoflurane, and S-ketamine in healthy male participants (N = 140). The anesthetics were administered in experimental setting using target-controlled infusion or vapouriser for one hour. Interviews conducted after anesthetic administration revealed that 46.9% (n = 46) of arousable participants (n = 98) reported experiences, most frequently dreaming or memory incorporation of the setting. Participants receiving dexmedetomidine reported experiences most often while S-ketamine induced the most multimodal experiences. Responsiveness at the end of anesthetic administration did not affect the prevalence or content of reported experiences. These results demonstrate that subjective experiences during responsive and unresponsive sedation are common and anesthetic agents with different molecular mechanisms of action may have different effects on the prevalence and complexity of the experiences, albeit in the present sample the differences between drugs were minute., CC BY 4.0© 2021 The AuthorsCorresponding author. E-mail address: liemra@utu.fi (L. Radek).

What happens in the brain when conscious awareness of the surrounding world fades? We manipulated consciousness in two experiments in a group of healthy males and measured brain activity with positron emission tomography. Measurements were made during wakefulness, escalating and constant levels of two anesthetic agents (Experiment 1, n=39) and during sleep-deprived wakefulness and Non-Rapid Eye Movement sleep (Experiment 2, n=37). In Experiment 1, the subjects were randomized to receive either propofol or dexmedetomidine until unresponsiveness. In both experiments, forced awakenings were applied to achieve rapid recovery from an unresponsive to a responsive state, followed by immediate and detailed interviews of subjective experiences during the preceding unresponsive condition. Unresponsiveness rarely denoted unconsciousness, as the majority of the subjects had internally generated experiences. Unresponsive anesthetic states and verified sleep stages, where a subsequent report of mental content included no signs of awareness of the surrounding world, indicated a disconnected state. Functional brain imaging comparing responsive and connected vs. unresponsive and disconnected states of consciousness during constant anesthetic exposure revealed that activity of the thalamus, cingulate cortices and angular gyri are fundamental for human consciousness. These brain structures were affected independent from the pharmacologic agent, drug concentration and direction of change in the state of consciousness. Analogous findings were obtained when consciousness was regulated by physiological sleep. State-specific findings were distinct and separable from the overall effects of the interventions, which included widespread depression of brain activity across cortical areas. These findings identify a central core brain network critical for human consciousness. SIGNIFICANCE STATEMENT Trying to understand the biological basis of human consciousness is currently one of the greatest c, CC BY 4.0Corresponding Author: harry.scheinin@utu.fi

What happens in the brain when conscious awareness of the surrounding world fades? We manipulated consciousness in two experiments in a group of healthy males and measured brain activity with positron emission tomography. Measurements were made during wakefulness, escalating and constant levels of two anesthetic agents (Experiment 1, n=39) and during sleep-deprived wakefulness and Non-Rapid Eye Movement sleep (Experiment 2, n=37). In Experiment 1, the subjects were randomized to receive either propofol or dexmedetomidine until unresponsiveness. In both experiments, forced awakenings were applied to achieve rapid recovery from an unresponsive to a responsive state, followed by immediate and detailed interviews of subjective experiences during the preceding unresponsive condition. Unresponsiveness rarely denoted unconsciousness, as the majority of the subjects had internally generated experiences. Unresponsive anesthetic states and verified sleep stages, where a subsequent report of mental content included no signs of awareness of the surrounding world, indicated a disconnected state. Functional brain imaging comparing responsive and connected vs. unresponsive and disconnected states of consciousness during constant anesthetic exposure revealed that activity of the thalamus, cingulate cortices and angular gyri are fundamental for human consciousness. These brain structures were affected independent from the pharmacologic agent, drug concentration and direction of change in the state of consciousness. Analogous findings were obtained when consciousness was regulated by physiological sleep. State-specific findings were distinct and separable from the overall effects of the interventions, which included widespread depression of brain activity across cortical areas. These findings identify a central core brain network critical for human consciousness. SIGNIFICANCE STATEMENT Trying to understand the biological basis of human consciousness is currently one of the greatest c, CC BY 4.0Corresponding Author: harry.scheinin@utu.fi

What happens in the brain when conscious awareness of the surrounding world fades? We manipulated consciousness in two experiments in a group of healthy males and measured brain activity with positron emission tomography. Measurements were made during wakefulness, escalating and constant levels of two anesthetic agents (Experiment 1, n=39) and during sleep-deprived wakefulness and Non-Rapid Eye Movement sleep (Experiment 2, n=37). In Experiment 1, the subjects were randomized to receive either propofol or dexmedetomidine until unresponsiveness. In both experiments, forced awakenings were applied to achieve rapid recovery from an unresponsive to a responsive state, followed by immediate and detailed interviews of subjective experiences during the preceding unresponsive condition. Unresponsiveness rarely denoted unconsciousness, as the majority of the subjects had internally generated experiences. Unresponsive anesthetic states and verified sleep stages, where a subsequent report of mental content included no signs of awareness of the surrounding world, indicated a disconnected state. Functional brain imaging comparing responsive and connected vs. unresponsive and disconnected states of consciousness during constant anesthetic exposure revealed that activity of the thalamus, cingulate cortices and angular gyri are fundamental for human consciousness. These brain structures were affected independent from the pharmacologic agent, drug concentration and direction of change in the state of consciousness. Analogous findings were obtained when consciousness was regulated by physiological sleep. State-specific findings were distinct and separable from the overall effects of the interventions, which included widespread depression of brain activity across cortical areas. These findings identify a central core brain network critical for human consciousness. SIGNIFICANCE STATEMENT Trying to understand the biological basis of human consciousness is currently one of the greatest c, CC BY 4.0Corresponding Author: harry.scheinin@utu.fi

To understand how anesthetics with different molecular mechanisms affect consciousness, we explored subjective experiences recalled after responsive and unresponsive sedation induced with equisedative doses of dexmedetomidine, propofol, sevoflurane, and S-ketamine in healthy male participants (N = 140). The anesthetics were administered in experimental setting using target-controlled infusion or vapouriser for one hour. Interviews conducted after anesthetic administration revealed that 46.9% (n = 46) of arousable participants (n = 98) reported experiences, most frequently dreaming or memory incorporation of the setting. Participants receiving dexmedetomidine reported experiences most often while S-ketamine induced the most multimodal experiences. Responsiveness at the end of anesthetic administration did not affect the prevalence or content of reported experiences. These results demonstrate that subjective experiences during responsive and unresponsive sedation are common and anesthetic agents with different molecular mechanisms of action may have different effects on the prevalence and complexity of the experiences, albeit in the present sample the differences between drugs were minute., CC BY 4.0© 2021 The AuthorsCorresponding author. E-mail address: liemra@utu.fi (L. Radek).

To understand how anesthetics with different molecular mechanisms affect consciousness, we explored subjective experiences recalled after responsive and unresponsive sedation induced with equisedative doses of dexmedetomidine, propofol, sevoflurane, and S-ketamine in healthy male participants (N = 140). The anesthetics were administered in experimental setting using target-controlled infusion or vapouriser for one hour. Interviews conducted after anesthetic administration revealed that 46.9% (n = 46) of arousable participants (n = 98) reported experiences, most frequently dreaming or memory incorporation of the setting. Participants receiving dexmedetomidine reported experiences most often while S-ketamine induced the most multimodal experiences. Responsiveness at the end of anesthetic administration did not affect the prevalence or content of reported experiences. These results demonstrate that subjective experiences during responsive and unresponsive sedation are common and anesthetic agents with different molecular mechanisms of action may have different effects on the prevalence and complexity of the experiences, albeit in the present sample the differences between drugs were minute., CC BY 4.0© 2021 The AuthorsCorresponding author. E-mail address: liemra@utu.fi (L. Radek).

To understand how anesthetics with different molecular mechanisms affect consciousness, we explored subjective experiences recalled after responsive and unresponsive sedation induced with equisedative doses of dexmedetomidine, propofol, sevoflurane, and S-ketamine in healthy male participants (N = 140). The anesthetics were administered in experimental setting using target-controlled infusion or vapouriser for one hour. Interviews conducted after anesthetic administration revealed that 46.9% (n = 46) of arousable participants (n = 98) reported experiences, most frequently dreaming or memory incorporation of the setting. Participants receiving dexmedetomidine reported experiences most often while S-ketamine induced the most multimodal experiences. Responsiveness at the end of anesthetic administration did not affect the prevalence or content of reported experiences. These results demonstrate that subjective experiences during responsive and unresponsive sedation are common and anesthetic agents with different molecular mechanisms of action may have different effects on the prevalence and complexity of the experiences, albeit in the present sample the differences between drugs were minute., CC BY 4.0© 2021 The AuthorsCorresponding author. E-mail address: liemra@utu.fi (L. Radek).

What happens in the brain when conscious awareness of the surrounding world fades? We manipulated consciousness in two experiments in a group of healthy males and measured brain activity with positron emission tomography. Measurements were made during wakefulness, escalating and constant levels of two anesthetic agents (Experiment 1, n=39) and during sleep-deprived wakefulness and Non-Rapid Eye Movement sleep (Experiment 2, n=37). In Experiment 1, the subjects were randomized to receive either propofol or dexmedetomidine until unresponsiveness. In both experiments, forced awakenings were applied to achieve rapid recovery from an unresponsive to a responsive state, followed by immediate and detailed interviews of subjective experiences during the preceding unresponsive condition. Unresponsiveness rarely denoted unconsciousness, as the majority of the subjects had internally generated experiences. Unresponsive anesthetic states and verified sleep stages, where a subsequent report of mental content included no signs of awareness of the surrounding world, indicated a disconnected state. Functional brain imaging comparing responsive and connected vs. unresponsive and disconnected states of consciousness during constant anesthetic exposure revealed that activity of the thalamus, cingulate cortices and angular gyri are fundamental for human consciousness. These brain structures were affected independent from the pharmacologic agent, drug concentration and direction of change in the state of consciousness. Analogous findings were obtained when consciousness was regulated by physiological sleep. State-specific findings were distinct and separable from the overall effects of the interventions, which included widespread depression of brain activity across cortical areas. These findings identify a central core brain network critical for human consciousness. SIGNIFICANCE STATEMENT Trying to understand the biological basis of human consciousness is currently one of the greatest c, CC BY 4.0Corresponding Author: harry.scheinin@utu.fi

What happens in the brain when conscious awareness of the surrounding world fades? We manipulated consciousness in two experiments in a group of healthy males and measured brain activity with positron emission tomography. Measurements were made during wakefulness, escalating and constant levels of two anesthetic agents (Experiment 1, n=39) and during sleep-deprived wakefulness and Non-Rapid Eye Movement sleep (Experiment 2, n=37). In Experiment 1, the subjects were randomized to receive either propofol or dexmedetomidine until unresponsiveness. In both experiments, forced awakenings were applied to achieve rapid recovery from an unresponsive to a responsive state, followed by immediate and detailed interviews of subjective experiences during the preceding unresponsive condition. Unresponsiveness rarely denoted unconsciousness, as the majority of the subjects had internally generated experiences. Unresponsive anesthetic states and verified sleep stages, where a subsequent report of mental content included no signs of awareness of the surrounding world, indicated a disconnected state. Functional brain imaging comparing responsive and connected vs. unresponsive and disconnected states of consciousness during constant anesthetic exposure revealed that activity of the thalamus, cingulate cortices and angular gyri are fundamental for human consciousness. These brain structures were affected independent from the pharmacologic agent, drug concentration and direction of change in the state of consciousness. Analogous findings were obtained when consciousness was regulated by physiological sleep. State-specific findings were distinct and separable from the overall effects of the interventions, which included widespread depression of brain activity across cortical areas. These findings identify a central core brain network critical for human consciousness. SIGNIFICANCE STATEMENT Trying to understand the biological basis of human consciousness is currently one of the greatest c, CC BY 4.0Corresponding Author: harry.scheinin@utu.fi

Background herent alpha electroencephalogram (EEG) rhythms in the frontal cortex have been correlated with the hypnotic effects of propofol and dexmedetomidine, but less is known about frontal connectivity as a state-specific correlate of unresponsiveness as compared with long-range connectivity. We aimed to distinguish dose- and state-dependent effects of dexmedetomidine and propofol on EEG connectivity. thods rty-seven healthy males received either dexmedetomidine (n=23) or propofol (n=24) as target-controlled infusion with stepwise increments until loss of responsiveness (LOR). We attempted to arouse participants during constant dosing (return of responsiveness [ROR]), and the target concentration was then increased 50% to achieve presumed loss of consciousness. We collected 64-channel EEG data and prefrontal–frontal and anterior–posterior functional connectivity in the alpha band (8–14 Hz) was measured using coherence and weighted phase lag index (wPLI). Directed connectivity was measured with directed phase lag index (dPLI). sults efrontal–frontal EEG-based connectivity discriminated the states at the different drug concentrations. At ROR, prefrontal–frontal connectivity reversed to the level observed before LOR, indicating that connectivity changes were related to unresponsiveness rather than drug concentration. Unresponsiveness was associated with emergence of frontal-to-prefrontal dominance (dPLI: –0.13 to –0.40) in contrast to baseline (dPLI: 0.01–0.02). Coherence, wPLI, and dPLI had similar capability to discriminate the states that differed in terms of responsiveness and drug concentration. In contrast, anterior–posterior connectivity in the alpha band did not differentiate LOR and ROR. nclusions cal prefrontal–frontal EEG-based connectivity reflects unresponsiveness induced by propofol or dexmedetomidine, suggesting its utility in monitoring the anaesthetised state with these agents. inical trial registration, CC BY-NC-ND. 4.0

Background herent alpha electroencephalogram (EEG) rhythms in the frontal cortex have been correlated with the hypnotic effects of propofol and dexmedetomidine, but less is known about frontal connectivity as a state-specific correlate of unresponsiveness as compared with long-range connectivity. We aimed to distinguish dose- and state-dependent effects of dexmedetomidine and propofol on EEG connectivity. thods rty-seven healthy males received either dexmedetomidine (n=23) or propofol (n=24) as target-controlled infusion with stepwise increments until loss of responsiveness (LOR). We attempted to arouse participants during constant dosing (return of responsiveness [ROR]), and the target concentration was then increased 50% to achieve presumed loss of consciousness. We collected 64-channel EEG data and prefrontal–frontal and anterior–posterior functional connectivity in the alpha band (8–14 Hz) was measured using coherence and weighted phase lag index (wPLI). Directed connectivity was measured with directed phase lag index (dPLI). sults efrontal–frontal EEG-based connectivity discriminated the states at the different drug concentrations. At ROR, prefrontal–frontal connectivity reversed to the level observed before LOR, indicating that connectivity changes were related to unresponsiveness rather than drug concentration. Unresponsiveness was associated with emergence of frontal-to-prefrontal dominance (dPLI: –0.13 to –0.40) in contrast to baseline (dPLI: 0.01–0.02). Coherence, wPLI, and dPLI had similar capability to discriminate the states that differed in terms of responsiveness and drug concentration. In contrast, anterior–posterior connectivity in the alpha band did not differentiate LOR and ROR. nclusions cal prefrontal–frontal EEG-based connectivity reflects unresponsiveness induced by propofol or dexmedetomidine, suggesting its utility in monitoring the anaesthetised state with these agents. inical trial registration, CC BY-NC-ND. 4.0

Background herent alpha electroencephalogram (EEG) rhythms in the frontal cortex have been correlated with the hypnotic effects of propofol and dexmedetomidine, but less is known about frontal connectivity as a state-specific correlate of unresponsiveness as compared with long-range connectivity. We aimed to distinguish dose- and state-dependent effects of dexmedetomidine and propofol on EEG connectivity. thods rty-seven healthy males received either dexmedetomidine (n=23) or propofol (n=24) as target-controlled infusion with stepwise increments until loss of responsiveness (LOR). We attempted to arouse participants during constant dosing (return of responsiveness [ROR]), and the target concentration was then increased 50% to achieve presumed loss of consciousness. We collected 64-channel EEG data and prefrontal–frontal and anterior–posterior functional connectivity in the alpha band (8–14 Hz) was measured using coherence and weighted phase lag index (wPLI). Directed connectivity was measured with directed phase lag index (dPLI). sults efrontal–frontal EEG-based connectivity discriminated the states at the different drug concentrations. At ROR, prefrontal–frontal connectivity reversed to the level observed before LOR, indicating that connectivity changes were related to unresponsiveness rather than drug concentration. Unresponsiveness was associated with emergence of frontal-to-prefrontal dominance (dPLI: –0.13 to –0.40) in contrast to baseline (dPLI: 0.01–0.02). Coherence, wPLI, and dPLI had similar capability to discriminate the states that differed in terms of responsiveness and drug concentration. In contrast, anterior–posterior connectivity in the alpha band did not differentiate LOR and ROR. nclusions cal prefrontal–frontal EEG-based connectivity reflects unresponsiveness induced by propofol or dexmedetomidine, suggesting its utility in monitoring the anaesthetised state with these agents. inical trial registration, CC BY-NC-ND. 4.0

Background herent alpha electroencephalogram (EEG) rhythms in the frontal cortex have been correlated with the hypnotic effects of propofol and dexmedetomidine, but less is known about frontal connectivity as a state-specific correlate of unresponsiveness as compared with long-range connectivity. We aimed to distinguish dose- and state-dependent effects of dexmedetomidine and propofol on EEG connectivity. thods rty-seven healthy males received either dexmedetomidine (n=23) or propofol (n=24) as target-controlled infusion with stepwise increments until loss of responsiveness (LOR). We attempted to arouse participants during constant dosing (return of responsiveness [ROR]), and the target concentration was then increased 50% to achieve presumed loss of consciousness. We collected 64-channel EEG data and prefrontal–frontal and anterior–posterior functional connectivity in the alpha band (8–14 Hz) was measured using coherence and weighted phase lag index (wPLI). Directed connectivity was measured with directed phase lag index (dPLI). sults efrontal–frontal EEG-based connectivity discriminated the states at the different drug concentrations. At ROR, prefrontal–frontal connectivity reversed to the level observed before LOR, indicating that connectivity changes were related to unresponsiveness rather than drug concentration. Unresponsiveness was associated with emergence of frontal-to-prefrontal dominance (dPLI: –0.13 to –0.40) in contrast to baseline (dPLI: 0.01–0.02). Coherence, wPLI, and dPLI had similar capability to discriminate the states that differed in terms of responsiveness and drug concentration. In contrast, anterior–posterior connectivity in the alpha band did not differentiate LOR and ROR. nclusions cal prefrontal–frontal EEG-based connectivity reflects unresponsiveness induced by propofol or dexmedetomidine, suggesting its utility in monitoring the anaesthetised state with these agents. inical trial registration, CC BY-NC-ND. 4.0

Background herent alpha electroencephalogram (EEG) rhythms in the frontal cortex have been correlated with the hypnotic effects of propofol and dexmedetomidine, but less is known about frontal connectivity as a state-specific correlate of unresponsiveness as compared with long-range connectivity. We aimed to distinguish dose- and state-dependent effects of dexmedetomidine and propofol on EEG connectivity. thods rty-seven healthy males received either dexmedetomidine (n=23) or propofol (n=24) as target-controlled infusion with stepwise increments until loss of responsiveness (LOR). We attempted to arouse participants during constant dosing (return of responsiveness [ROR]), and the target concentration was then increased 50% to achieve presumed loss of consciousness. We collected 64-channel EEG data and prefrontal–frontal and anterior–posterior functional connectivity in the alpha band (8–14 Hz) was measured using coherence and weighted phase lag index (wPLI). Directed connectivity was measured with directed phase lag index (dPLI). sults efrontal–frontal EEG-based connectivity discriminated the states at the different drug concentrations. At ROR, prefrontal–frontal connectivity reversed to the level observed before LOR, indicating that connectivity changes were related to unresponsiveness rather than drug concentration. Unresponsiveness was associated with emergence of frontal-to-prefrontal dominance (dPLI: –0.13 to –0.40) in contrast to baseline (dPLI: 0.01–0.02). Coherence, wPLI, and dPLI had similar capability to discriminate the states that differed in terms of responsiveness and drug concentration. In contrast, anterior–posterior connectivity in the alpha band did not differentiate LOR and ROR. nclusions cal prefrontal–frontal EEG-based connectivity reflects unresponsiveness induced by propofol or dexmedetomidine, suggesting its utility in monitoring the anaesthetised state with these agents. inical trial registration, CC BY-NC-ND. 4.0

There are several different approaches to analyze event-related potentials (ERPs) at single-subject level, and the aim of the current study is to provide information for choosing a method based on its ability to detect ERP effects and factors influencing the results. We used data from 79 healthy participants with EEG referenced to mastoid average and investigated the detection rate of auditory N400 effect in single-subject analysis using five methods: visual inspection of participant-wise averaged ERPs, analysis of variance (ANOVA) for amplitude averages in a time window, cluster-based non-parametric testing, a novel Bayesian approach and Studentized continuous wavelet transform (t-CWT). Visual inspection by three independent raters yielded N400 effect detection in 85% of the participants in at least one paradigm (active responding or passive listening), whereas ANOVA identified the effect in 68%, the cluster-method in 59%, the Bayesian method in 89%, and different versions of t-CWT in 22–59% of the participants. Thus, the Bayesian method was the most liberal and also showed the greatest concordance between the experimental paradigms (active/passive). ANOVA detected significant effect only in cases with converging evidence from other methods. The t-CWT and cluster-based method were the most conservative methods. As we show in the current study, different analysis methods provide results that do not completely overlap. The method of choice for determining the presence of an ERP component at single-subject level thus remains unresolved. Relying on a single statistical method may not be sufficient for drawing conclusions on single-subject ERPs.

There are several different approaches to analyze event-related potentials (ERPs) at single-subject level, and the aim of the current study is to provide information for choosing a method based on its ability to detect ERP effects and factors influencing the results. We used data from 79 healthy participants with EEG referenced to mastoid average and investigated the detection rate of auditory N400 effect in single-subject analysis using five methods: visual inspection of participant-wise averaged ERPs, analysis of variance (ANOVA) for amplitude averages in a time window, cluster-based non-parametric testing, a novel Bayesian approach and Studentized continuous wavelet transform (t-CWT). Visual inspection by three independent raters yielded N400 effect detection in 85% of the participants in at least one paradigm (active responding or passive listening), whereas ANOVA identified the effect in 68%, the cluster-method in 59%, the Bayesian method in 89%, and different versions of t-CWT in 22–59% of the participants. Thus, the Bayesian method was the most liberal and also showed the greatest concordance between the experimental paradigms (active/passive). ANOVA detected significant effect only in cases with converging evidence from other methods. The t-CWT and cluster-based method were the most conservative methods. As we show in the current study, different analysis methods provide results that do not completely overlap. The method of choice for determining the presence of an ERP component at single-subject level thus remains unresolved. Relying on a single statistical method may not be sufficient for drawing conclusions on single-subject ERPs.

There are several different approaches to analyze event-related potentials (ERPs) at single-subject level, and the aim of the current study is to provide information for choosing a method based on its ability to detect ERP effects and factors influencing the results. We used data from 79 healthy participants with EEG referenced to mastoid average and investigated the detection rate of auditory N400 effect in single-subject analysis using five methods: visual inspection of participant-wise averaged ERPs, analysis of variance (ANOVA) for amplitude averages in a time window, cluster-based non-parametric testing, a novel Bayesian approach and Studentized continuous wavelet transform (t-CWT). Visual inspection by three independent raters yielded N400 effect detection in 85% of the participants in at least one paradigm (active responding or passive listening), whereas ANOVA identified the effect in 68%, the cluster-method in 59%, the Bayesian method in 89%, and different versions of t-CWT in 22–59% of the participants. Thus, the Bayesian method was the most liberal and also showed the greatest concordance between the experimental paradigms (active/passive). ANOVA detected significant effect only in cases with converging evidence from other methods. The t-CWT and cluster-based method were the most conservative methods. As we show in the current study, different analysis methods provide results that do not completely overlap. The method of choice for determining the presence of an ERP component at single-subject level thus remains unresolved. Relying on a single statistical method may not be sufficient for drawing conclusions on single-subject ERPs.

There are several different approaches to analyze event-related potentials (ERPs) at single-subject level, and the aim of the current study is to provide information for choosing a method based on its ability to detect ERP effects and factors influencing the results. We used data from 79 healthy participants with EEG referenced to mastoid average and investigated the detection rate of auditory N400 effect in single-subject analysis using five methods: visual inspection of participant-wise averaged ERPs, analysis of variance (ANOVA) for amplitude averages in a time window, cluster-based non-parametric testing, a novel Bayesian approach and Studentized continuous wavelet transform (t-CWT). Visual inspection by three independent raters yielded N400 effect detection in 85% of the participants in at least one paradigm (active responding or passive listening), whereas ANOVA identified the effect in 68%, the cluster-method in 59%, the Bayesian method in 89%, and different versions of t-CWT in 22–59% of the participants. Thus, the Bayesian method was the most liberal and also showed the greatest concordance between the experimental paradigms (active/passive). ANOVA detected significant effect only in cases with converging evidence from other methods. The t-CWT and cluster-based method were the most conservative methods. As we show in the current study, different analysis methods provide results that do not completely overlap. The method of choice for determining the presence of an ERP component at single-subject level thus remains unresolved. Relying on a single statistical method may not be sufficient for drawing conclusions on single-subject ERPs.

There are several different approaches to analyze event-related potentials (ERPs) at single-subject level, and the aim of the current study is to provide information for choosing a method based on its ability to detect ERP effects and factors influencing the results. We used data from 79 healthy participants with EEG referenced to mastoid average and investigated the detection rate of auditory N400 effect in single-subject analysis using five methods: visual inspection of participant-wise averaged ERPs, analysis of variance (ANOVA) for amplitude averages in a time window, cluster-based non-parametric testing, a novel Bayesian approach and Studentized continuous wavelet transform (t-CWT). Visual inspection by three independent raters yielded N400 effect detection in 85% of the participants in at least one paradigm (active responding or passive listening), whereas ANOVA identified the effect in 68%, the cluster-method in 59%, the Bayesian method in 89%, and different versions of t-CWT in 22–59% of the participants. Thus, the Bayesian method was the most liberal and also showed the greatest concordance between the experimental paradigms (active/passive). ANOVA detected significant effect only in cases with converging evidence from other methods. The t-CWT and cluster-based method were the most conservative methods. As we show in the current study, different analysis methods provide results that do not completely overlap. The method of choice for determining the presence of an ERP component at single-subject level thus remains unresolved. Relying on a single statistical method may not be sufficient for drawing conclusions on single-subject ERPs.

There are several different approaches to analyze event-related potentials (ERPs) at single-subject level, and the aim of the current study is to provide information for choosing a method based on its ability to detect ERP effects and factors influencing the results. We used data from 79 healthy participants with EEG referenced to mastoid average and investigated the detection rate of auditory N400 effect in single-subject analysis using five methods: visual inspection of participant-wise averaged ERPs, analysis of variance (ANOVA) for amplitude averages in a time window, cluster-based non-parametric testing, a novel Bayesian approach and Studentized continuous wavelet transform (t-CWT). Visual inspection by three independent raters yielded N400 effect detection in 85% of the participants in at least one paradigm (active responding or passive listening), whereas ANOVA identified the effect in 68%, the cluster-method in 59%, the Bayesian method in 89%, and different versions of t-CWT in 22–59% of the participants. Thus, the Bayesian method was the most liberal and also showed the greatest concordance between the experimental paradigms (active/passive). ANOVA detected significant effect only in cases with converging evidence from other methods. The t-CWT and cluster-based method were the most conservative methods. As we show in the current study, different analysis methods provide results that do not completely overlap. The method of choice for determining the presence of an ERP component at single-subject level thus remains unresolved. Relying on a single statistical method may not be sufficient for drawing conclusions on single-subject ERPs.

BACKGROUND Differentiating drug-related changes and state-related changes on the electroencephalogram during anesthetic-induced unconsciousness has remained a challenge. To distinguish these, we designed a rigorous experimental protocol with two drugs known to have distinct molecular mechanisms of action. We hypothesized that drug- and state-related changes can be separated. METHODS: Forty-seven healthy participants were randomized to receive dexmedetomidine (n = 23) or propofol (n = 24) as target-controlled infusions until loss of responsiveness. Then, an attempt was made to arouse the participant to regain responsiveness while keeping the drug infusion constant. Finally, the concentration was increased 1.5-fold to achieve presumable loss of consciousness. We conducted statistical comparisons between the drugs and different states of consciousness for spectral bandwidths, and observed how drug-induced electroencephalogram patterns reversed upon awakening. Cross-frequency coupling was also analyzed between slow-wave phase and alpha power. RESULTS: Eighteen (78%) and 10 (42%) subjects were arousable during the constant drug infusion in the dexmedetomidine and propofol groups, respectively (P = 0.011 between the drugs). Corresponding with deepening anesthetic level, slow-wave power increased, and a state-dependent alpha anteriorization was detected with both drugs, especially with propofol. Negative phase-amplitude coupling before and during loss of responsiveness frontally and positive coupling during the highest drug concentration posteriorly were observed in the propofol but not in the dexmedetomidine group. CONCLUSIONS: Electroencephalogram effects of dexmedetomidine and propofol are strongly drug- and state-dependent. Changes in slow-wave and alpha activity seemed to best detect different states of consciousness., Copyright © 2018, the American Society of Anesthesiologists, Inc. Wolters Kluwer Health, Inc. All Rights Reserved. The RightsLink Digital Licensing and Rights Management Service (including RightsLink for Open Access) is available (A) to users of copyrighted works found at the websites of participating publishers who are seeking permissions or licenses to use those works, and (B) to authors of articles and other manuscripts who are seeking to pay author publication charges in connection with the submission of their works to publishers.