Standard drug visit activities: Participants were fitted with a saline gel EEG cap and a pre-sedation recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. Once the pre-sedation recording was collected, the faculty anesthesiologist began administering the study drug. A new EEG recording was started to monitor brain waves while all of the pre-sedation activities were repeated after the administration of the study drug.

Dexmedetomidine-specific activities: Rapid infusion of 3.0 mg kg-1 h-1 was administered over a 10 min period followed by a 0.5 mg kg-1 h-1 maintenance infusion to achieve the first drug step. The second drug step was similarly achieved by a 10 min infusion of 3.0 mg kg-1 h-1 followed by a 1.5 mg kg-1 h-1 maintenance infusion. Duration of drug exposure was limited to 4 hours.

Standard drug visit activities: Participants were fitted with a saline gel EEG cap and a pre-sedation recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. Once the pre-sedation recording was collected, the faculty anesthesiologist began administering the study drug. A new EEG recording was started to monitor brain waves while all of the pre-sedation activities were repeated after the administration of the study drug.

Ketamine-specific activities: Ketamine was titrated using up to a 4.5mg/kg bolus over 10 minutes followed by 0.1-0.5mg/min intravenous infusion with 5 minutes between increments and titrated to desired observed alertness/sedation level. This infusion rate may be slowed further or stopped for patient safety concerns. Infusion rates will be adjusted using information from the target-controlled infusion model clinical judgment. Short-lived emergence delirium (confusion on awakening) may occur on emergence from ketamine anesthesia and this will be managed through standard clinical practice including administration of midazolam (up to 4mg IV) if required. Duration of drug exposure was limited to 4 hours.

Standard drug visit activities: Participants were fitted with a saline gel EEG cap and a pre-sedation recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. Once the pre-sedation recording was collected, the faculty anesthesiologist began administering the study drug. A new EEG recording was started to monitor brain waves while all of the pre-sedation activities were repeated after the administration of the study drug.

Propofol-specific activities: A target-controlled infusion model used to predict plasma concentrations of propofol at 0.5 mcg/mL increments allowing 5-minutes to equilibrate between any step change. Dosing will be confined to FDA approved limits with up to a 2.5mg/kg bolus over 1 to 3 minute followed by an infusion of 50-200mcg/kg/min titrated to the desired observed alertness/sedation levels. Drug exposure was limited to 4 hours.

Standard drug visit activities: Participants were fitted with a saline gel EEG cap and a pre-sedation recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. Once the pre-sedation recording was collected, the faculty anesthesiologist began administering the study drug. A new EEG recording was started to monitor brain waves while all of the pre-sedation activities were repeated after the administration of the study drug.

Midazolam-specific activities: Initial boluses of up to 0.35mg/kg followed by doses up to 0.1mg/kg/h as a maintenance infusion. Duration of drug exposure was limited to 4 hours.

Participants were fitted with a saline gel EEG cap and a pre-sleep recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. After the pre-sleep recording, participants laid down within 30 minutes of their usual bedtime and were left to sleep for 2-3 hours. After this period, the participant was woken up every 15-30 minutes to answer standardized wake report form questions. After awaking a final time, the participant repeated 10 minutes of awake eyes open and eyes closed recordings as well as the predictive coding cognitive task on a computer.

Standard drug visit activities: Participants were fitted with a saline gel EEG cap and a pre-sedation recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. Once the pre-sedation recording was collected, the faculty anesthesiologist began administering the study drug. A new EEG recording was started to monitor brain waves while all of the pre-sedation activities were repeated after the administration of the study drug.

Dexmedetomidine-specific activities: Rapid infusion of 3.0 mg kg-1 h-1 was administered over a 10 min period followed by a 0.5 mg kg-1 h-1 maintenance infusion to achieve the first drug step. The second drug step was similarly achieved by a 10 min infusion of 3.0 mg kg-1 h-1 followed by a 1.5 mg kg-1 h-1 maintenance infusion. Duration of drug exposure was limited to 4 hours.

Standard drug visit activities: Participants were fitted with a saline gel EEG cap and a pre-sedation recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. Once the pre-sedation recording was collected, the faculty anesthesiologist began administering the study drug. A new EEG recording was started to monitor brain waves while all of the pre-sedation activities were repeated after the administration of the study drug.

Ketamine-specific activities: Ketamine was titrated using up to a 4.5mg/kg bolus over 10 minutes followed by 0.1-0.5mg/min intravenous infusion with 5 minutes between increments and titrated to desired observed alertness/sedation level. This infusion rate may be slowed further or stopped for patient safety concerns. Infusion rates will be adjusted using information from the target-controlled infusion model clinical judgment. Short-lived emergence delirium (confusion on awakening) may occur on emergence from ketamine anesthesia and this will be managed through standard clinical practice including administration of midazolam (up to 4mg IV) if required. Duration of drug exposure was limited to 4 hours.

Standard drug visit activities: Participants were fitted with a saline gel EEG cap and a pre-sedation recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. Once the pre-sedation recording was collected, the faculty anesthesiologist began administering the study drug. A new EEG recording was started to monitor brain waves while all of the pre-sedation activities were repeated after the administration of the study drug.

Propofol-specific activities: A target-controlled infusion model used to predict plasma concentrations of propofol at 0.5 mcg/mL increments allowing 5-minutes to equilibrate between any step change. Dosing will be confined to FDA approved limits with up to a 2.5mg/kg bolus over 1 to 3 minute followed by an infusion of 50-200mcg/kg/min titrated to the desired observed alertness/sedation levels. Drug exposure was limited to 4 hours.

Standard drug visit activities: Participants were fitted with a saline gel EEG cap and a pre-sedation recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. Once the pre-sedation recording was collected, the faculty anesthesiologist began administering the study drug. A new EEG recording was started to monitor brain waves while all of the pre-sedation activities were repeated after the administration of the study drug.

Midazolam-specific activities: Initial boluses of up to 0.35mg/kg followed by doses up to 0.1mg/kg/h as a maintenance infusion. Duration of drug exposure was limited to 4 hours.

Participants were fitted with a saline gel EEG cap and a pre-sleep recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. After the pre-sleep recording, participants laid down within 30 minutes of their usual bedtime and were left to sleep for 2-3 hours. After this period, the participant was woken up every 15-30 minutes to answer standardized wake report form questions. After awaking a final time, the participant repeated 10 minutes of awake eyes open and eyes closed recordings as well as the predictive coding cognitive task on a computer.

NIH Toolbox Card Sorting Score

3 degrees of freedom

Statistical significance defined by p < 0.05.

NIH Toolbox Card Sorting Score

Standard drug visit activities: Participants were fitted with a saline gel EEG cap and a pre-sedation recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. Once the pre-sedation recording was collected, the faculty anesthesiologist began administering the study drug. A new EEG recording was started to monitor brain waves while all of the pre-sedation activities were repeated after the administration of the study drug.

Dexmedetomidine-specific activities: Rapid infusion of 3.0 mg kg-1 h-1 was administered over a 10 min period followed by a 0.5 mg kg-1 h-1 maintenance infusion to achieve the first drug step. The second drug step was similarly achieved by a 10 min infusion of 3.0 mg kg-1 h-1 followed by a 1.5 mg kg-1 h-1 maintenance infusion. Duration of drug exposure was limited to 4 hours.

Standard drug visit activities: Participants were fitted with a saline gel EEG cap and a pre-sedation recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. Once the pre-sedation recording was collected, the faculty anesthesiologist began administering the study drug. A new EEG recording was started to monitor brain waves while all of the pre-sedation activities were repeated after the administration of the study drug.

Ketamine-specific activities: Ketamine was titrated using up to a 4.5mg/kg bolus over 10 minutes followed by 0.1-0.5mg/min intravenous infusion with 5 minutes between increments and titrated to desired observed alertness/sedation level. This infusion rate may be slowed further or stopped for patient safety concerns. Infusion rates will be adjusted using information from the target-controlled infusion model clinical judgment. Short-lived emergence delirium (confusion on awakening) may occur on emergence from ketamine anesthesia and this will be managed through standard clinical practice including administration of midazolam (up to 4mg IV) if required. Duration of drug exposure was limited to 4 hours.

Standard drug visit activities: Participants were fitted with a saline gel EEG cap and a pre-sedation recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. Once the pre-sedation recording was collected, the faculty anesthesiologist began administering the study drug. A new EEG recording was started to monitor brain waves while all of the pre-sedation activities were repeated after the administration of the study drug.

Propofol-specific activities: A target-controlled infusion model used to predict plasma concentrations of propofol at 0.5 mcg/mL increments allowing 5-minutes to equilibrate between any step change. Dosing will be confined to FDA approved limits with up to a 2.5mg/kg bolus over 1 to 3 minute followed by an infusion of 50-200mcg/kg/min titrated to the desired observed alertness/sedation levels. Drug exposure was limited to 4 hours.

Standard drug visit activities: Participants were fitted with a saline gel EEG cap and a pre-sedation recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. Once the pre-sedation recording was collected, the faculty anesthesiologist began administering the study drug. A new EEG recording was started to monitor brain waves while all of the pre-sedation activities were repeated after the administration of the study drug.

Midazolam-specific activities: Initial boluses of up to 0.35mg/kg followed by doses up to 0.1mg/kg/h as a maintenance infusion. Duration of drug exposure was limited to 4 hours.

Participants were fitted with a saline gel EEG cap and a pre-sleep recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. After the pre-sleep recording, participants laid down within 30 minutes of their usual bedtime and were left to sleep for 2-3 hours. After this period, the participant was woken up every 15-30 minutes to answer standardized wake report form questions. After awaking a final time, the participant repeated 10 minutes of awake eyes open and eyes closed recordings as well as the predictive coding cognitive task on a computer.

Predictive Coding Task Accuracy

17 degrees of freedom

Statistical significance defined by p < 0.05.

Predictive Coding Task Accuracy

Standard drug visit activities: Participants were fitted with a saline gel EEG cap and a pre-sedation recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. Once the pre-sedation recording was collected, the faculty anesthesiologist began administering the study drug. A new EEG recording was started to monitor brain waves while all of the pre-sedation activities were repeated after the administration of the study drug.

Dexmedetomidine-specific activities: Rapid infusion of 3.0 mg kg-1 h-1 was administered over a 10 min period followed by a 0.5 mg kg-1 h-1 maintenance infusion to achieve the first drug step. The second drug step was similarly achieved by a 10 min infusion of 3.0 mg kg-1 h-1 followed by a 1.5 mg kg-1 h-1 maintenance infusion. Duration of drug exposure was limited to 4 hours.

Standard drug visit activities: Participants were fitted with a saline gel EEG cap and a pre-sedation recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. Once the pre-sedation recording was collected, the faculty anesthesiologist began administering the study drug. A new EEG recording was started to monitor brain waves while all of the pre-sedation activities were repeated after the administration of the study drug.

Ketamine-specific activities: Ketamine was titrated using up to a 4.5mg/kg bolus over 10 minutes followed by 0.1-0.5mg/min intravenous infusion with 5 minutes between increments and titrated to desired observed alertness/sedation level. This infusion rate may be slowed further or stopped for patient safety concerns. Infusion rates will be adjusted using information from the target-controlled infusion model clinical judgment. Short-lived emergence delirium (confusion on awakening) may occur on emergence from ketamine anesthesia and this will be managed through standard clinical practice including administration of midazolam (up to 4mg IV) if required. Duration of drug exposure was limited to 4 hours.

Standard drug visit activities: Participants were fitted with a saline gel EEG cap and a pre-sedation recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. Once the pre-sedation recording was collected, the faculty anesthesiologist began administering the study drug. A new EEG recording was started to monitor brain waves while all of the pre-sedation activities were repeated after the administration of the study drug.

Propofol-specific activities: A target-controlled infusion model used to predict plasma concentrations of propofol at 0.5 mcg/mL increments allowing 5-minutes to equilibrate between any step change. Dosing will be confined to FDA approved limits with up to a 2.5mg/kg bolus over 1 to 3 minute followed by an infusion of 50-200mcg/kg/min titrated to the desired observed alertness/sedation levels. Drug exposure was limited to 4 hours.

Standard drug visit activities: Participants were fitted with a saline gel EEG cap and a pre-sedation recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. Once the pre-sedation recording was collected, the faculty anesthesiologist began administering the study drug. A new EEG recording was started to monitor brain waves while all of the pre-sedation activities were repeated after the administration of the study drug.

Midazolam-specific activities: Initial boluses of up to 0.35mg/kg followed by doses up to 0.1mg/kg/h as a maintenance infusion. Duration of drug exposure was limited to 4 hours.

Participants were fitted with a saline gel EEG cap and a pre-sleep recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. After the pre-sleep recording, participants laid down within 30 minutes of their usual bedtime and were left to sleep for 2-3 hours. After this period, the participant was woken up every 15-30 minutes to answer standardized wake report form questions. After awaking a final time, the participant repeated 10 minutes of awake eyes open and eyes closed recordings as well as the predictive coding cognitive task on a computer.

Null hypothesis is a 50% recall rate.

17 degrees of freedom

Statistical significance defined by p < 0.05.

Null hypothesis is a 50% recall rate.