Reorganization of rich-clubs in functional brain networks during propofol-induced unconsciousness and natural sleep

Abstract

Background: General anesthesia (GA) provides an invaluable experimental tool to understand the essential neural mechanisms underlying consciousness. Previous neuroimaging studies have shown the functional integration and segregation of brain functional networks during anesthetic-induced alteration of consciousness. However, the organization pattern of hubs in functional brain networks remains unclear. Moreover, comparisons with the well-characterized physiological unconsciousness can help us understand the neural mechanisms of anesthetic-induced unconsciousness.

Methods: Resting-state functional magnetic resonance imaging was performed during wakefulness, mild propofol-induced sedation (m-PIS), and deep PIS (d-PIS) with clinical unconsciousness on 8 healthy volunteers and wakefulness and natural sleep on 9 age- and sex-matched healthy volunteers. Large-scale functional brain networks of each volunteer were constructed based on 160 regions of interest. Then, rich-club organizations in brain functional networks and nodal properties (nodal strength and efficiency) were assessed and analyzed among the different states and groups.

Results: Rich-clubs in the functional brain networks were reorganized during alteration of consciousness induced by propofol. Firstly, rich-club nodes were switched from the posterior cingulate cortex (PCC), angular gyrus, and anterior and middle insula to the inferior parietal lobule (IPL), inferior parietal sulcus (IPS), and cerebellum. When sedation was deepened to unconsciousness, the rich-club nodes were switched to the occipital and angular gyrus. These results suggest that the rich-club nodes were switched among the high-order cognitive function networks (default mode network [DMN] and fronto-parietal network [FPN]), sensory networks (occipital network [ON]), and cerebellum network (CN) from consciousness (wakefulness) to propofol-induced unconsciousness. At the same time, compared with wakefulness, local connections were switched to rich-club connections during propofol-induced unconsciousness, suggesting a strengthening of the overall information commutation of networks. Nodal efficiency of the anterior and middle insula and ventral frontal cortex was significantly decreased. Additionally, from wakefulness to natural sleep, a similar pattern of rich-club reorganization with propofol-induced unconsciousness was observed: rich-club nodes were switched from the DMN (including precuneus and PCC) to the sensorimotor network (SMN, including part of the frontal and temporal gyrus). Compared with natural sleep, nodal efficiency of the insula, frontal gyrus, PCC, and cerebellum significantly decreased during propofol-induced unconsciousness.

Conclusions: Our study demonstrated that the rich-club reorganization in functional brain networks is characterized by switching of rich-club nodes between the high-order cognitive and sensory and motor networks during propofol-induced alteration of consciousness and natural sleep. These findings will help understand the common neurological mechanism of pharmacological and physiological unconsciousness.

Keywords: Brain network; Natural sleep; Propofol-induced sedation; Resting-state functional magnetic resonance images (rs-fMRI); Rich-club organization.

Fig. 1

The regions of interest (ROIs) in the Dos-160 template. The different colors represented different brain functional networks. DMN: the default mode network, FPN: the fronto-parietal network, CON: the cingulo-opercular network, SMN: the sensorimotor network, ON: the occipital network, CN: the cerebellum network.(For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 2

The rich-club organization and the distribution of rich-club regions of the PIS group. (A) Schematic diagram of a network with high-degree rich-club nodes (blue) that are also highly connected among one another. The connection among rich-club nodes is so-called rich-club connections (red), while connections linking rich-club nodes to non-rich-club nodes are labeled feeder connections (orange) and connections among non-rich-club nodes are local connections (yellow). (B) Rich-club coefficients normalized relative to random are shown in blue (wakefulness), green (m-PIS), red (d-PIS). The coefficients are plotted against degree, between 11 and 35. (C) Number and percent of rich-club regions during wakefulness (left), m-PIS (middle) and d-PIS (right). (D) The percent of rich-club regions in the different functional brain networks during wakefulness (left), m-PIS (middle) and d-PIS (right). (E) The distribution of rich-club regions in the whole brain network during wakefulness (left), m-PIS (middle) and d-PIS (right). The different colors represented different brain functional networks.(For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 3

The significant alteration in the number and strength of different categories of connections in the PIS group. (A) The significant alteration in the number of rich-club (left), feeder (middle) and local (right) connections. * represented the significant difference between the different states (p<0.05). Error bar represented a standard error of mean (SEM). (B) The significant alteration in the strength of rich-club (left), feeder (middle) and local (right) connections. (C) The distribution of different categories of connections in the group-averaged functional brain network during wakefulness (left), m-PIS (middle) and d-PIS (right). The different colors represented the different categories of connections (red: rich-club connection; orange: feeder connection; yellow: local connection).(For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 4

The rich-club organization and the distribution of rich-club regions in the sleep group. (A) Rich-club coefficients normalized relative to random are shown in blue (wakefulness), red (sleep). The coefficients were plotted against degree, between 11 and 35. (B) Number and percent of rich-club regions during wakefulness (left) and sleep (right). (C) The percent of rich-club regions in the different functional brain networks during wakefulness (left) and sleep (right). (D) The distribution of rich-club regions in the whole brain network during wakefulness (left) and sleep (right). The different colors represented different brain functional networks.(For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 5

The significant alteration in the number and strength of different categories of connections in the sleep group. (A) The significant alteration in the number of rich-club (left), feeder (middle) and local (right) connections. * represented the significant difference between the different states (p<0.05). Error bar represented SEM. (B) The significant alteration in the strength of rich-club (left), feeder (middle) and local (right) connections. (C) The distribution of different categories of connections in the group-averaged functional brain network during wakefulness (left) and sleep (right). The different colors represented the different categories of connections (red represented rich-club connection; orange: feeder connection; yellow: local connection).(For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 6

The significant alteration in the number and strength of different categories of connections between PIS and sleep. (A) The significant alteration in the number of rich-club (left), feeder (middle) and local (right) connections between m-PIS and sleep. (B) The significant alteration in the strength of rich-club (left), feeder (middle) and local (right) connections between d-PIS and sleep. * represented the significant difference between the different states (p<0.05). Error bar represented SEM.

Fig. 7

The significant alteration of the topological properties in the PIS group. (A) The significant alteration of nodal strength. (B) The significant alteration of nodal efficiency. Left: The distribution of the significantly altered brain region. The larger size of the ball represented the smaller p-value. The different colors represented different brain functional networks. As was shown in Fig. 1. Right: The detailed significant alteration of brain regions between the different states. * represented the significant difference between the different states (p<0.05, FDR correction for 160 nodes). Error bar represented SEM.(For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 8

The significant alteration of the topological properties in the sleep group. (A) The significant alteration of nodal strength. (B) The significant alteration of nodal efficiency. Left: The distribution of the significantly altered brain region. The larger size of the ball represented the smaller p-value. The different colors represented different brain functional networks. As was shown in Fig. 1. Right: The detailed significant alteration of brain regions between wakefulness and sleep. * represented the significant difference between the different states (p<0.05, FDR correction for 160 nodes). Error bar represented SEM.(For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 9

The significant alteration of the topological properties between PIS and sleep. (A) The significant alteration of nodal efficiency between m-PIS and sleep. (B) The significant alteration of nodal efficiency between d-PIS and sleep. Left: The distribution of the significantly altered brain region. The larger size of the ball represented the smaller p-value. The different colors represented different brain functional networks. As was shown in Fig. 1. Right: The detailed significant alteration of brain regions between wakefulness and sleep. * represented the significant difference between the different states (p<0.05, FDR correction for 160 nodes). Error bar represented SEM.