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Articles, Behavioral/Systems/Cognitive

Spatiotemporal Reconfiguration of Large-Scale Brain Functional Networks during Propofol-Induced Loss of Consciousness

Manuel S. Schröter, Victor I. Spoormaker, Anna Schorer, Afra Wohlschläger, Michael Czisch, Eberhard F. Kochs, Claus Zimmer, Bernhard Hemmer, Gerhard Schneider, Denis Jordan and Rüdiger Ilg
Journal of Neuroscience 12 September 2012, 32 (37) 12832-12840; https://doi.org/10.1523/JNEUROSCI.6046-11.2012
Manuel S. Schröter
1Max Planck Institute of Psychiatry, 80804 Munich, Germany,
2Department of Neurology,
3Department of Anesthesiology, and
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Victor I. Spoormaker
1Max Planck Institute of Psychiatry, 80804 Munich, Germany,
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Anna Schorer
2Department of Neurology,
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Afra Wohlschläger
4Department of Neuroradiology, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany, and
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Michael Czisch
1Max Planck Institute of Psychiatry, 80804 Munich, Germany,
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Eberhard F. Kochs
3Department of Anesthesiology, and
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Claus Zimmer
4Department of Neuroradiology, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany, and
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Bernhard Hemmer
2Department of Neurology,
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Gerhard Schneider
3Department of Anesthesiology, and
5Department of Anesthesiology, Witten/Herdecke University, HELIOS Clinic Wuppertal, 42283 Wuppertal, Germany
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Denis Jordan
3Department of Anesthesiology, and
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Rüdiger Ilg
2Department of Neurology,
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    Figure 1.

    Effects of PI-LOC on functional connectivity strength. A, Average regional connectivity strength S during wakefulness and after loss of consciousness (PI-LOC); yellow to red colors indicate increasing connectivity strength. B, Lower figure shows significant p values of between-condition decreases in connectivity strength S of left and right hemisphere (LH and RH); light to dark blue colors indicate increasing significance. The dotted line depicts the FDR threshold (q = 0.05; see Materials and Methods).

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    Figure 2.

    Effects of PI-LOC on brain topological properties. Figure shows topological changes of brain functional networks across wakefulness (black) and PI-LOC (gray). A–C, Summary statistics for clustering (C, Crandom, γ = C/Crandom) (A), path length (L, Lrandom, λ = L/Lrandom) (B), and small-worldness (σ = γ/λ) (C) were performed on MODWT scale 3 (0.03–0.07 Hz) throughout a range of 36–50% connection probability (Table 2). Error bars indicate 95% CI.

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    Figure 3.

    Changes in mean degree and short/long-range connections. A, Group average networks for wakefulness and loss of consciousness. During PI-LOC, brain functional networks decreased in mean degree; depicted at correlation threshold r = 0.3. B, Ratio of long- to short-range connections at PI-LOC compared with wakefulness (mean and SEM values of all long/short-range correlations). Both long- and short-range correlations decreased significantly during PI-LOC; * indicates significance of wakefulness versus PI-LOC for one-sample t test (p < 0.05, one-sided). The reduction in long-range connections was significantly stronger; * indicates significance of wakefulness versus PI-LOC for paired t test (p < 0.05).

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    Table 1.

    Physiological variables

    ParameterWakefulnessPI-LOC
    Pulse (beats/min)77.5 ± 18.671.6 ± 19.0
    BPSystolic (mmHg)†132.9 ± 14.0117.4 ± 13.1*
    BPDiastolic (mmHg)†70.5 ± 10.861.1 ± 12.8
    SpO2 (%)98.3 ± 1.495.3 ± 1.6*
    CO2 (%)†29.5 ± 11.735.3 ± 9.4
    RF (breaths/min)†11.3 ± 3.612.6 ± 4.1
    • Results are expressed as mean ± SD of the whole group (n = 15).

    • ↵*Significance of wakefulness versus PI-LOC (paired t test, p < 0.05).

    • ↵†BP data of one subject; CO2 and RF data of three subjects had to be excluded from analysis due to recording problems. BP (blood pressure), SpO2 (oxyhemoglobin saturation), CO2 (endexpiratory carbon dioxide), RF (respiratory rate).

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    Table 2.

    Changes in functional connectivity and topological metrics

    MetricWakefulnessPI-LOCt valuesp values
    Clustering coefficient, C*0.69 ± 0.030.65 ± 0.04−2.190.026
    Clustering ratio, γ*1.11 ± 0.031.19 ± 0.131.860.046
    Path length, L*1.42 ± 0.021.43 ± 0.050.270.393
    Path length ratio, λ*1.01 ± 0.011.00 ± 0.00−0.800.220
    Small-worldness, σ*1.10 ± 0.041.19 ± 0.131.900.043
    Connectivity strength, S†0.32 ± 0.090.22 ± 0.13−2.580.013
    Regional diversity, D†0.19 ± 0.020.20 ± 0.031.700.059
    Global integration, I†36.3 ± 8.9%27.4 ± 12.9%−2.350.039
    • ↵*Means (±SD), t and p values (one-sided) are provided. Metrics C, L, γ, λ, and σ were calculated on pooled graphs in the applied range of thresholds.

    • ↵†Metrics S, D, and I were tested on the unthresholded connectivity matrices. Both analyses were performed on correlation coefficients of MODWT scale 3 (0.03–0.07 Hz).

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    Table 3.

    Differences in subsystem connectivity

    SubsystemsWakefulnessPI-LOCt values
    Neocortical connections
        Association–association0.35 ± 0.090.23 ± 0.12−2.89*
        Association–primary0.40 ± 0.120.24 ± 0.17−2.62*
        Primary–primary0.50 ± 0.120.41 ± 0.15−1.21
    Neocortical/(para)limbic connections
        Limbic–primary0.24 ± 0.120.13 ± 0.17−2.33*
        Paralimbic–primary0.32 ± 0.100.24 ± 0.19−1.47
        Association–limbic0.20 ± 0.100.13 ± 0.13−1.82
        Association–paralimbic0.29 ± 0.100.23 ± 0.15−1.48
    Limbic/paralimbic connections
        Limbic–limbic0.20 ± 0.100.21 ± 0.140.31
        Limbic–paralimbic0.24 ± 0.110.23 ± 0.14−0.29
        Paralimbic–paralimbic0.31 ± 0.110.31 ± 0.14−0.04
    Connections including the subcortical subsystem
        Association–subcortical0.24 ± 0.120.12 ± 0.14−4.19**
        Limbic–subcortical0.24 ± 0.120.21 ± 0.16−0.38
        Paralimbic–subcortical0.25 ± 0.110.16 ± 0.15−2.46*
        Primary–subcortical0.32 ± 0.140.17 ± 0.18−2.87*
        Subcortical–subcortical0.36 ± 0.110.26 ± 0.14−1.84
    Whole-brain connectivity0.31 ± 0.100.22 ± 0.14−2.57*
    • Results are expressed as mean ± SD and t values of a paired t test.

    • ↵*Significant at p < 0.05;

    • ↵**significant at FDR-corrected p < 0.05.

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The Journal of Neuroscience: 32 (37)
Journal of Neuroscience
Vol. 32, Issue 37
12 Sep 2012
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Spatiotemporal Reconfiguration of Large-Scale Brain Functional Networks during Propofol-Induced Loss of Consciousness
Manuel S. Schröter, Victor I. Spoormaker, Anna Schorer, Afra Wohlschläger, Michael Czisch, Eberhard F. Kochs, Claus Zimmer, Bernhard Hemmer, Gerhard Schneider, Denis Jordan, Rüdiger Ilg
Journal of Neuroscience 12 September 2012, 32 (37) 12832-12840; DOI: 10.1523/JNEUROSCI.6046-11.2012

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Spatiotemporal Reconfiguration of Large-Scale Brain Functional Networks during Propofol-Induced Loss of Consciousness
Manuel S. Schröter, Victor I. Spoormaker, Anna Schorer, Afra Wohlschläger, Michael Czisch, Eberhard F. Kochs, Claus Zimmer, Bernhard Hemmer, Gerhard Schneider, Denis Jordan, Rüdiger Ilg
Journal of Neuroscience 12 September 2012, 32 (37) 12832-12840; DOI: 10.1523/JNEUROSCI.6046-11.2012
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