Reconstructing Consciousness and Cognition (RCC)

Currently it is unknown how the human brain reorganizes its network organization to generate conscious experience and cognitive activity after a period of unconsciousness. Therefore, the purpose of this study is to assess how cognitive activity is reconstructed after general anesthesia. The investigators hypothesize that the brain's transition from unconsciousness to consciousness and full cognition is a complex process that occurs over an extended period of time. Specifically, the investigators hypothesize the following order of cognitive reconstitution: responsiveness to command, attention, complex scanning and visual tracking, working memory, and executive function.

Volunteers will be healthy participants who are anesthetized with commonly used anesthetic drugs as well as a non-anesthetized group to control for circadian influences. A total of 60 subjects will be recruited for this study. All subjects (male and female) will perform basic tests for cognition on a laptop computer at 30-minute intervals during this study. The testing battery to be administered was assembled to assess multiple cognitive functions in order to determine whether and how cognitive processes return to baseline function. Electroencephalogram (measuring brain electrical activity) data will be monitored and recorded during both anesthesia and cognitive testing, for subsequent analysis.

This study is significant because it could lead to a better understanding of the neural correlates of human consciousness, as well as normal and abnormal conscious state transitions (including barriers to such transitions).

Study Overview

• Status: Completed
• Conditions: Postoperative Cognitive Dysfunction
• Intervention / Treatment: Other: Control Group: Cognitive Testing; Drug: ISOFLURANE- Experimental Arm

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University in St. Louis
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy 20-40 year old volunteers,
• American Society of Anesthesiologists Physical Status I or II (i.e., healthy),
• Body mass index < 30 kg/m2,
• Easily visualized uvula,
• With anticipated equal recruitment of males and females.

Exclusion Criteria:

• Physical signs suggestive of difficult airway (e.g., mouth opening <3cm, short distance between the chin and neck, poor mandibular subluxation, thick neck),
• History of obstructive sleep apnea,
• Reactive airway disease,
• Neuropsychiatric disorders,
• History or current use of psychotropic medications,
• Current tobacco and alcohol use,
• History of hypertension or current medication for blood pressure control, cardiovascular disease or arrhythmias,
• Positive urine toxicology screen,
• History of reflux,
• Pregnancy,
• Family history of problems with anesthesia (including but not limited to malignant hyperthermia),
• Sleep disorders,
• History of postoperative nausea/vomiting or motion sickness,
• Allergy to eggs, egg products or soy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control Group: Cognitive Testing; Control arm will receive cognitive testing only without undergoing general anesthesia	Other: Control Group: Cognitive Testing; The control group will undergo cognitive testing while connected to an EEG machine following a comparable rest period, but will not receive general anesthesia.
Experimental: ISOFLURANE- Experimental Arm; Experimental arm will receive cognitive testing before and after general anesthesia	Drug: ISOFLURANE- Experimental Arm; The experimental group will be given the anesthetic isoflurane for three hours, and will undergo cognitive tests immediately following emergence from general anesthesia while connected to an EEG machine.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurocognitive scores	Neurocognitive battery performed on computer	Three hours following emergence from general anesthesia

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain network connectivity	Functional brain networks will be reconstructed from EEG data.	Three hours following emergence from general anesthesia

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: University of Pennsylvania; Washington University School of Medicine; James S McDonnell Foundation
• Investigators: Principal Investigator: George A Mashour, MD, PhD, University of Michigan; Principal Investigator: Michael Avidan, MBBCh, Washington University School of Medicine; Principal Investigator: Mathias Basner, MD, PhD, MSc, University of Pennsylvania; Principal Investigator: Max Kelz, MD, PhD, University of Pennsylvania

Publications and helpful links

General Publications

• Mashour GA, Palanca BJ, Basner M, Li D, Wang W, Blain-Moraes S, Lin N, Maier K, Muench M, Tarnal V, Vanini G, Ochroch EA, Hogg R, Schwartz M, Maybrier H, Hardie R, Janke E, Golmirzaie G, Picton P, McKinstry-Wu AR, Avidan MS, Kelz MB. Recovery of consciousness and cognition after general anesthesia in humans. Elife. 2021 May 10;10:e59525. doi: 10.7554/eLife.59525.
• Labonte AK, Kafashan M, Huels ER, Blain-Moraes S, Basner M, Kelz MB, Mashour GA, Avidan MS, Palanca BJA; ReCCognition Study Group. The posterior dominant rhythm: an electroencephalographic biomarker for cognitive recovery after general anaesthesia. Br J Anaesth. 2023 Feb;130(2):e233-e242. doi: 10.1016/j.bja.2022.01.019. Epub 2022 Feb 17.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2013
• Primary Completion (Actual): February 9, 2015
• Study Completion (Actual): February 9, 2015

Study Registration Dates

• First Submitted: July 21, 2013
• First Submitted That Met QC Criteria: July 25, 2013
• First Posted (Estimated): July 30, 2013

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 14, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: cognition; General anesthesia; consciousness
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Postoperative Complications; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction; Postoperative Cognitive Complications; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, General; Anesthetics; Anesthetics, Inhalation; Isoflurane
• Other Study ID Numbers: McDonnell RCC

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No