Dynamic Change of Global and Local Information Processing in Propofol-Induced Loss and Recovery of Consciousness

Abstract

Whether unique to humans or not, consciousness is a central aspect of our experience of the world. The neural fingerprint of this experience, however, remains one of the least understood aspects of the human brain. In this paper we employ graph-theoretic measures and support vector machine classification to assess, in 12 healthy volunteers, the dynamic reconfiguration of functional connectivity during wakefulness, propofol-induced sedation and loss of consciousness, and the recovery of wakefulness. Our main findings, based on resting-state fMRI, are three-fold. First, we find that propofol-induced anesthesia does not bear differently on long-range versus short-range connections. Second, our multi-stage design dissociated an initial phase of thalamo-cortical and cortico-cortical hyperconnectivity, present during sedation, from a phase of cortico-cortical hypoconnectivity, apparent during loss of consciousness. Finally, we show that while clustering is increased during loss of consciousness, as recently suggested, it also remains significantly elevated during wakefulness recovery. Conversely, the characteristic path length of brain networks (i.e., the average functional distance between any two regions of the brain) appears significantly increased only during loss of consciousness, marking a decrease of global information-processing efficiency uniquely associated with unconsciousness. These findings suggest that propofol-induced loss of consciousness is mainly tied to cortico-cortical and not thalamo-cortical mechanisms, and that decreased efficiency of information flow is the main feature differentiating the conscious from the unconscious brain.

Electroencephalogram reactivity to verbal command after dexmedetomidine, propofol and sevoflurane-induced unresponsiveness

“…In particular, the changes in non-specific thalamo-cortical connections seem to correlate with an altered state of consciousness. However, another study found that propofol preferably suppresses cortico-cortical connections [51], which is consistent with the present findings (Figs 3 and 4) of well preserved thalamo-cortical flow at UNRES within the pathways for auditory information processing. Thus, the primary site for the hypnotic effects of propofol seems to be the cerebral cortex followed by the suppression of deeper structures with higher doses [52].…”

Thalamo-frontal connectivity mediates top-down cognitive functions in disorders of consciousness

“…Furthermore, changes in thalamocortical connectivity have also been shown to underlie the dynamic reconfiguration of brain networks during loss of consciousness by anesthetic agent. 38 While we stress that because of the low sample the results should not be generalized beyond our cohort, these findings are consistent with the idea that functional or structural impairment (which we cannot distinguish in our dataset) within a cortico-striatopallidal-thalamo-cortical mesocircuit is characteristic of severe DOC. 23,35 In this work, we have shown that several levels of cognitive processing, including the ability to comprehend verbal information, maintain information through time, and adopt voluntary mindsets-a set of high-level cognitive processes thought to be crucial for consciousness 39 -can be maintained in patients with DOC.…”

Thalamic and extrathalamic mechanisms of consciousness after severe brain injury

“…28 On the one hand, the negative association between motor/communication scores and atrophy along the anterior and dorsomedial regions of thalamus is consistent with the mesocircuit theory according to which corticopetal projections from thalamus to prefrontal cortex are crucial for sustaining organized behavior 26 and integrating information across different regions of cortex. 29 These regions are known to be a target of secondary, nonmechanic, damage (eg, Wallerian degeneration) in acute moderate-to-severe brain injury, with the degree of atrophy correlating with long-term outcome. 10 Furthermore, the dorsomedial aspect of thalamus is known to be the main subcortical structure projecting to prefrontal cortex, 30 and to play a key role in the regulation of higher cognitive functions in DOC patients.…”