Recovery of consciousness and cognition after general anesthesia in humans

  1. George A Mashour  Is a corresponding author
  2. Ben JA Palanca
  3. Mathias Basner
  4. Duan Li
  5. Wei Wang
  6. Stefanie Blain-Moraes
  7. Nan Lin
  8. Kaitlyn Maier
  9. Maxwell Muench
  10. Vijay Tarnal
  11. Giancarlo Vanini
  12. E Andrew Ochroch
  13. Rosemary Hogg
  14. Marlon Schwartz
  15. Hannah Maybrier
  16. Randall Hardie
  17. Ellen Janke
  18. Goodarz Golmirzaie
  19. Paul Picton
  20. Andrew R McKinstry-Wu
  21. Michael S Avidan
  22. Max B Kelz
  1. Center for Consciousness Science, Department of Anesthesiology, University of Michigan Medical School, United States
  2. Department of Anesthesiology, Washington University School of Medicine, United States
  3. Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, United States
  4. Department of Mathematics and Statistics, Washington University, United States
8 figures, 4 tables and 2 additional files

Figures

Experimental design.

Participants were randomized to one of two groups for investigating recovery of consciousness and cognition after general anesthesia. Sleep-wake actigraphy data were acquired in the week leading up to the day of the experiment, which started with baseline cognitive testing followed by either a period of general anesthesia (1.3 age-adjusted minimum alveolar concentration of isoflurane) or wakefulness. Upon recovery of consciousness (or similar time point for controls), recurrent cognitive testing was performed for 3 hr. Actigraphy resumed for 3 days after the experiment.

Time course for recovery of (normalized) accuracy in cognitive task performance after general anesthesia (time 0 is just after recovery of consciousness in the group that was anesthetized).

AM, Abstract Matching; DSST, Digit Symbol Substitution Test; MP, Motor Praxis; NBCK, Fractal 2-Back; PVT, Psychomotor Vigilance Test; VOLT, Visual Object Learning Test. The six cognitive tests are all represented.

Time course for recovery of (normalized) speed of cognitive task performance after general anesthesia (time 0 is just after recovery of consciousness in the group that was anesthetized).

AM, Abstract Matching; DSST, Digit Symbol Substitution Test; MP, Motor Praxis; NBCK, Fractal 2-Back; PVT, Psychomotor Vigilance Test; VOLT, Visual Object Learning Test. The six cognitive tests are all represented.

Figure 4 with 6 supplements
Cortical dynamics before, during, and after general anesthesia.

(A) Scalp topographic maps of the group-level permutation entropy (PE; median average across N = 30 participants) at the ten studied epochs. (B) The box plots of average PE values in frontal (Fp1, Fp2, Fpz, F3, F4, and Fz) and posterior channels (P3, P4, Pz, O1, O2, and Oz) for the studied epochs. On each box, the central mark is the median, the edges are the 25th and 75th percentiles, the whiskers extend to the most extreme data points determined by the MATLAB algorithm to be non-outliers, and the points deemed by the algorithm to be outliers are plotted individually (red cross). (C) The box plots of LZC values for the studied epochs. EC = eyes closed resting state (EC1 is baseline consciousness, EC2-7 are post-emergence just prior to cognitive testing), LOC = loss of consciousness, Pre-ROC = 2 min epoch just before recovery of consciousness. *indicates significant difference relative to EC1, using linear mixed model analysis (Bonferroni-corrected p<0.05).

Figure 4—figure supplement 1
Confirmatory results of permutation entropy (PE) with different settings of embedding dimension (dE) and time delay (τ).

The description of the figure and statistical results are the same as those in Figure 4A-B.

Figure 4—figure supplement 2
Confirmatory results of Lempel-Ziv Complexity (LZC).

(A) Sensitivity of the LZC measure to the selection of threshold for binarization. (B) Confirmatory results of LZC by using spatial shuffling (top) and phase randomization (bottom) in the generation of surrogate data for normalization. The spatial shuffling method permutates the spatial order (at each time point) of the spatiotemporal matrix. The phase randomization method preserves the spectral profile of the signals and reflects the complexity changes beyond the power spectrogram. The description of the figure and the statistical results are same with those in Figure 4C.

Figure 4—figure supplement 3
Cortical dynamics as assessed by permutation (PE) and Lempel-Ziv complexity (LZC) for the non-anesthetized control group.

(A) Scalp topographic maps of the group-level PE at the seven resting-state eyes-closed (EC) epochs. (B) The box plots of average PE values in frontal and posterior channels for the studied epochs. (C) The box plots of LZC values for the studied epochs.

Figure 4—figure supplement 4
Associations between EEG measures during pre-anesthetic baseline (EC1) with the impairment of cognitive functions at emergence (just after recovery of consciousness).

The EEG measures do not appear to be related to the degree of performance impairment via Spearman’s rank correlation analysis. AM, Abstract Matching; DSST, Digit Symbol Substitution Test; MP, Motor Praxis; NBCK, Fractal 2-Back; PVT, Psychomotor Vigilance Test; VOLT, Visual Object Learning Test; RT, Response time; ACC, Accuracy.

Figure 4—figure supplement 5
Associations between EEG measures during maintenance with the impairment of cognitive functions at emergence.

Only significant correlations were indicated (Spearman’s rank correlation, p<0.05).

Figure 4—figure supplement 6
Associations between EEG measures during pre-ROC with the impairment of cognitive functions at emergence.

Only significant correlations are indicated (Spearman’s rank correlation, p<0.05).

Effects of anesthetic exposure on rest-activity rhythms.

(A) Rest activity plots are displayed in the week prior to the study day for volunteers that were subsequently randomized to anesthetized (purple) or control (black) conditions. (B) Rest-activity rhythms in the same participants are displayed on the evening of the study day and for the ensuing days. Time = 0 corresponds to midnight on the evening of the study day.

Summary of the study findings.
Author response image 1
Author response image 2

Tables

Table 1
Neurocognitive battery, associated cognitive domains, and neuroanatomy.
TestCognitive domains assessedBrain regions primarily recruited
Motor PraxisSensorimotor speedSensorimotor cortex
Visual Object LearningSpatial learning and memoryMedial temporal cortex, hippocampus
Fractal 2-BackWorking memoryDorsolateral prefrontal cortex, cingulate, hippocampus
Abstract MatchingAbstraction, concept formationPrefrontal cortex
Digit Symbol SubstitutionComplex scanning and visual tracking, working memoryTemporal cortex, prefrontal cortex, motor cortex
Psychomotor VigilanceVigilant attentionPrefrontal cortex, motor cortex, inferior parietal and some visual cortex
Table 2
Results of nonlinear mixed-effects models comparing cognitive trajectories at 3 hr post emergence between anesthetized and non-anesthetized cohorts.

AM, Abstract Matching; DSST, Digit Symbol Substitution Test; MP, Motor Praxis; NBCK, Fractal 2-Back; PVT, Psychomotor Vigilance Test; VOLT, Visual Object Learning Test. For speed and accuracy of each task, we report the Bonferroni corrected confidence intervals (CI) of the difference with an overall significance level 0.05. The p-values of testing difference between groups should be compared to the corrected level 0.05/6 = 0.0083.

SpeedAccuracy
Estimatep-valueCIEstimatep-valueCI
MP0.35620.1101(−0.2437, 0.9561)0.03660.8721(−0.5824, 0.6556)
VOLT0.76660.0720(−0.3757, 1.9089)0.39150.0847(−0.2184, 1.0015)
NBCK1.2803<0.0001(0.6642, 1.8964)0.00890.9664(−0.5679, 0.5857)
AM0.63360.0023(0.09021, 1.1770)0.36920.0709(−0.1791, 0.9176)
PVT0.79860.0026(0.1052, 1.4921)1.09160.0557(−0.4359, 2.6191)
DSST1.0184<0.0001(0.4420, 1.5949)0.54540.0931(−0.3279, 1.4188)
Author response table 1
TestCognitive Domains AssessedBrain Regions Primarily Recruited
Motor PraxisSensory-motor speedSensorimotor cortex
Visual Object LearningSpatial learning and memoryMedial temporal cortex, hippocampus
Fractal 2-BackWorking memoryDorsolateral prefrontal cortex, cingulate, hippocampus
Abstract MatchingAbstraction, concept formationPrefrontal cortex
Digit Symbol SubstitutionComplex scanning and visual tracking, working memoryTemporal cortex, prefrontal cortex, motor cortex
Psychomotor VigilanceVigilant attentionPrefrontal cortex, motor cortex, inferior parietal and some visual cortex
Author response table 2
ControlExperimental
VariableAverage BLSD BLAverage BLSD BLp-value
MP Average RT [ms]962.4155.11049.5172.30.0440
MP Accuracy28.8%9.330.0%10.3%0.6527
VOLT Average RT [ms]2067.0390.62088.8381.70.8271
VOLT Correct80.3%13.5%83.7%10.6%0.2919
NBCK Average RT [ms]605.892.4589.389.10.4847
NBCK Correct85.9%7.4%85.7%6.3%0.9040
AM Average RT [ms]2116.4661.71895.0504.30.1504
AM Correct68.3%13.6%68.8%11.5%0.8918
PVT Speed [1/s]5.60.35.70.30.3889
PVT Accuracy93.6%4.2%93.1%4.6%0.6922
DSST Average RT [ms]1417.5272.91419.6234.60.9752
DSST Correct95.7%7.6%97.2%3.2%0.3331

Additional files

Supplementary file 1

A reports the sample size of data epochs for electroencephalographic analysis and file 1B describes model selection for the statistical analysis of electroencephalographic measures.

https://cdn.elifesciences.org/articles/59525/elife-59525-supp1-v2.docx
Transparent reporting form
https://cdn.elifesciences.org/articles/59525/elife-59525-transrepform-v2.docx

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. George A Mashour
  2. Ben JA Palanca
  3. Mathias Basner
  4. Duan Li
  5. Wei Wang
  6. Stefanie Blain-Moraes
  7. Nan Lin
  8. Kaitlyn Maier
  9. Maxwell Muench
  10. Vijay Tarnal
  11. Giancarlo Vanini
  12. E Andrew Ochroch
  13. Rosemary Hogg
  14. Marlon Schwartz
  15. Hannah Maybrier
  16. Randall Hardie
  17. Ellen Janke
  18. Goodarz Golmirzaie
  19. Paul Picton
  20. Andrew R McKinstry-Wu
  21. Michael S Avidan
  22. Max B Kelz
(2021)
Recovery of consciousness and cognition after general anesthesia in humans
eLife 10:e59525.
https://doi.org/10.7554/eLife.59525