Spatiotemporal reconfiguration of large-scale brain functional networks during propofol-induced loss of consciousness

Abstract

Applying graph theoretical analysis of spontaneous BOLD fluctuations in functional magnetic resonance imaging (fMRI), we investigated whole-brain functional connectivity of 11 healthy volunteers during wakefulness and propofol-induced loss of consciousness (PI-LOC). After extraction of regional fMRI time series from 110 cortical and subcortical regions, we applied a maximum overlap discrete wavelet transformation and investigated changes in the brain's intrinsic spatiotemporal organization. During PI-LOC, we observed a breakdown of subcortico-cortical and corticocortical connectivity. Decrease of connectivity was pronounced in thalamocortical connections, whereas no changes were found for connectivity within primary sensory cortices. Graph theoretical analyses revealed significant changes in the degree distribution and local organization metrics of brain functional networks during PI-LOC: compared with a random network, normalized clustering was significantly increased, as was small-worldness. Furthermore we observed a profound decline in long-range connections and a reduction in whole-brain spatiotemporal integration, supporting a topological reconfiguration during PI-LOC. Our findings shed light on the functional significance of intrinsic brain activity as measured by spontaneous BOLD signal fluctuations and help to understand propofol-induced loss of consciousness.

Figures

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).

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.

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).