Recovery of consciousness and cognition after general anesthesia in humans
- Center for Consciousness Science, Department of Anesthesiology, University of Michigan Medical School, United States
- Department of Anesthesiology, Washington University School of Medicine, United States
- Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, United States
- Department of Mathematics and Statistics, Washington University, United States
Figures
Figure 1
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.
Figure 2
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.
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Figure 2—source data 1
Source data supporting Figure 2.
- https://cdn.elifesciences.org/articles/59525/elife-59525-fig2-data1-v2.zip
Figure 3
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.
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Figure 3—source data 1
Source data supporting Figure 3.
- https://cdn.elifesciences.org/articles/59525/elife-59525-fig3-data1-v2.zip
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).
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Figure 4—source data 1
Source data for Figure 4A, B.
- https://cdn.elifesciences.org/articles/59525/elife-59525-fig4-data1-v2.zip
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Figure 4—source data 2
Source data for Figure 4C.
- https://cdn.elifesciences.org/articles/59525/elife-59525-fig4-data2-v2.zip
Figure 4—figure supplement 1
Confirmatory results of permutation entropy (PE) with different settings of embedding dimension () 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).
Figure 5
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.
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Figure 5—source data 1
Source data supporting Figure 5.
- https://cdn.elifesciences.org/articles/59525/elife-59525-fig5-data1-v2.xlsx
Figure 6
Summary of the study findings.
Author response image 1
Author response image 2
Tables
Table 1
Neurocognitive battery, associated cognitive domains, and neuroanatomy.
| Test | Cognitive domains assessed | Brain regions primarily recruited |
|---|---|---|
| Motor Praxis | Sensorimotor speed | Sensorimotor cortex |
| Visual Object Learning | Spatial learning and memory | Medial temporal cortex, hippocampus |
| Fractal 2-Back | Working memory | Dorsolateral prefrontal cortex, cingulate, hippocampus |
| Abstract Matching | Abstraction, concept formation | Prefrontal cortex |
| Digit Symbol Substitution | Complex scanning and visual tracking, working memory | Temporal cortex, prefrontal cortex, motor cortex |
| Psychomotor Vigilance | Vigilant attention | Prefrontal 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.
| Speed | Accuracy | |||||
|---|---|---|---|---|---|---|
| Estimate | p-value | CI | Estimate | p-value | CI | |
| MP | 0.3562 | 0.1101 | (−0.2437, 0.9561) | 0.0366 | 0.8721 | (−0.5824, 0.6556) |
| VOLT | 0.7666 | 0.0720 | (−0.3757, 1.9089) | 0.3915 | 0.0847 | (−0.2184, 1.0015) |
| NBCK | 1.2803 | <0.0001 | (0.6642, 1.8964) | 0.0089 | 0.9664 | (−0.5679, 0.5857) |
| AM | 0.6336 | 0.0023 | (0.09021, 1.1770) | 0.3692 | 0.0709 | (−0.1791, 0.9176) |
| PVT | 0.7986 | 0.0026 | (0.1052, 1.4921) | 1.0916 | 0.0557 | (−0.4359, 2.6191) |
| DSST | 1.0184 | <0.0001 | (0.4420, 1.5949) | 0.5454 | 0.0931 | (−0.3279, 1.4188) |
Author response table 1
| Test | Cognitive Domains Assessed | Brain Regions Primarily Recruited |
|---|---|---|
| Motor Praxis | Sensory-motor speed | Sensorimotor cortex |
| Visual Object Learning | Spatial learning and memory | Medial temporal cortex, hippocampus |
| Fractal 2-Back | Working memory | Dorsolateral prefrontal cortex, cingulate, hippocampus |
| Abstract Matching | Abstraction, concept formation | Prefrontal cortex |
| Digit Symbol Substitution | Complex scanning and visual tracking, working memory | Temporal cortex, prefrontal cortex, motor cortex |
| Psychomotor Vigilance | Vigilant attention | Prefrontal cortex, motor cortex, inferior parietal and some visual cortex |
Author response table 2
| Control | Experimental | ||||
|---|---|---|---|---|---|
| Variable | Average BL | SD BL | Average BL | SD BL | p-value |
| MP Average RT [ms] | 962.4 | 155.1 | 1049.5 | 172.3 | 0.0440 |
| MP Accuracy | 28.8% | 9.3 | 30.0% | 10.3% | 0.6527 |
| VOLT Average RT [ms] | 2067.0 | 390.6 | 2088.8 | 381.7 | 0.8271 |
| VOLT Correct | 80.3% | 13.5% | 83.7% | 10.6% | 0.2919 |
| NBCK Average RT [ms] | 605.8 | 92.4 | 589.3 | 89.1 | 0.4847 |
| NBCK Correct | 85.9% | 7.4% | 85.7% | 6.3% | 0.9040 |
| AM Average RT [ms] | 2116.4 | 661.7 | 1895.0 | 504.3 | 0.1504 |
| AM Correct | 68.3% | 13.6% | 68.8% | 11.5% | 0.8918 |
| PVT Speed [1/s] | 5.6 | 0.3 | 5.7 | 0.3 | 0.3889 |
| PVT Accuracy | 93.6% | 4.2% | 93.1% | 4.6% | 0.6922 |
| DSST Average RT [ms] | 1417.5 | 272.9 | 1419.6 | 234.6 | 0.9752 |
| DSST Correct | 95.7% | 7.6% | 97.2% | 3.2% | 0.3331 |
Additional files
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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
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Transparent reporting form
- https://cdn.elifesciences.org/articles/59525/elife-59525-transrepform-v2.docx
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Recovery of consciousness and cognition after general anesthesia in humans
eLife 10:e59525.
https://doi.org/10.7554/eLife.59525
