Recovery of consciousness and cognition after general anesthesia in humans
- University of Michigan, United States
- Washington University, United States
- University of Pennsylvania, United States
- McGill University, Canada
Abstract
Understanding how the brain recovers from unconsciousness can inform neurobiological theories of consciousness and guide clinical investigation. To address this question, we conducted a multicenter study of 60 healthy humans, half of whom received general anesthesia for three hours and half of whom served as awake controls. We administered a battery of neurocognitive tests and recorded electroencephalography to assess cortical dynamics. We hypothesized that recovery of consciousness and cognition is an extended process, with differential recovery of cognitive functions that would commence with return of responsiveness and end with return of executive function, mediated by prefrontal cortex. We found that, just prior to the recovery of consciousness, frontal-parietal dynamics returned to baseline. Consistent with our hypothesis, cognitive reconstitution after anesthesia evolved over time. Contrary to our hypothesis, executive function returned first. Early engagement of prefrontal cortex in recovery of consciousness and cognition is consistent with global neuronal workspace theory.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting files. Source data have been provided for Figures 2-5.
Article and author information
Author details
Andrew R McKinstry-Wu
Funding
James S. McDonnell Foundation (Understanding Human Cognition)
- George A Mashour
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: The study received ethics committee approval from the University of Michigan, Washington University, and the University of Pennsylvania; written informed consent was obtained after careful discussion with each participant.
Copyright
© 2021, Mashour et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Recovery of consciousness and cognition after general anesthesia in humans
eLife 10:e59525.
https://doi.org/10.7554/eLife.59525
Further reading
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Background:
Individuals with Down syndrome (DS), the genetic condition caused by trisomy 21 (T21), display clear signs of immune dysregulation, including high rates of autoimmunity and severe complications from infections. Although it is well established that T21 causes increased interferon responses and JAK/STAT signaling, elevated autoantibodies, global immune remodeling, and hypercytokinemia, the interplay between these processes, the clinical manifestations of DS, and potential therapeutic interventions remain ill defined.
Methods:
We report a comprehensive analysis of immune dysregulation at the clinical, cellular, and molecular level in hundreds of individuals with DS, including autoantibody profiling, cytokine analysis, and deep immune mapping. We also report the interim analysis of a Phase II clinical trial investigating the safety and efficacy of the JAK inhibitor tofacitinib through multiple clinical and molecular endpoints.
Results:
We demonstrate multi-organ autoimmunity of pediatric onset concurrent with unexpected autoantibody-phenotype associations in DS. Importantly, constitutive immune remodeling and hypercytokinemia occur from an early age prior to autoimmune diagnoses or autoantibody production. Analysis of the first 10 participants to complete 16 weeks of tofacitinib treatment shows a good safety profile and no serious adverse events. Treatment reduced skin pathology in alopecia areata, psoriasis, and atopic dermatitis, while decreasing interferon scores, cytokine scores, and levels of pathogenic autoantibodies without overt immune suppression.
Conclusions:
JAK inhibition is a valid strategy to treat autoimmune conditions in DS. Additional research is needed to define the effects of JAK inhibition on the broader developmental and clinical hallmarks of DS.
Funding:
NIAMS, Global Down Syndrome Foundation.
Clinical trial number:
