Largest scale dissociation of brain activity at propofol-induced loss of consciousness

Abstract

The brain is a functional unit made up of multi-level connected elements showing a pattern of synchronized activity that varies in different states. The wake-sleep cycle is a major variation of brain functional condition that is ultimately regulated by subcortical arousal- and sleep-promoting cell groups. We analyzed the evolution of functional MRI signal in the whole cortex and in a deep region including most sleep- and wake-regulating subcortical nuclei at loss of consciousness induced by the hypnotic agent propofol. Optimal data were obtained in 21 of the 30 healthy participants examined. A dynamic analysis of functional MRI time courses on a time-scale of seconds was conducted to characterize consciousness transition, and functional connectivity maps were generated to detail the anatomy of structures showing different dynamics. Inside the magnet, loss of consciousness was marked by the participants ceasing to move their hands. We observed activity synchronization after loss of consciousness within both the cerebral cortex and subcortical structures. However, the evolution of functional MRI signal was dissociated, showing a transient reduction of global cortico-subcortical coupling that was restored during the unconscious state. An exception to cortico-subcortical decoupling was a brain network related to self-awareness (i.e., the default mode network) that remained connected to subcortical brain structures. Propofol-induced unconsciousness is thus characterized by an initial, transitory dissociated synchronization at the largest scale of brain activity. Such cortico-subcortical decoupling and subsequent re-coupling may allow the brain to detach from waking activity and reorganize into a functionally distinct state.

Neuropsychopharmacological effects of midazolam on the human brain

“…These results provide strong evidence that reductions in rCBF in the thalamus and precuneus/PCC is functionally related to decreased level of consciousness independently of nonspecific effects of anesthetic agents. Then, several recent fMRI studies have suggested that propofol decreased cortico-cortical connectivity in higher-order [88,[100][101][102]. In contrast, functional connectivity in lowlevel sensory cortices (e.g., sensorimotor network, visual and auditory networks) is preserved, consistent with the studies with midazolam reviewed above [88].…”

Temporal changes in resting state networks induced by propofol anesthesia

“…Specifically, the superior parietal lobule (SPL, BA7), dorsolateral prefrontal cortex (DLPFC, BA9, 46), and inferior parietal lobule (SMG, BA40) that started to change earlier in the present study are involved in conscious awareness (17,18), including attention, sensory perception, and integrating inputs from unimodal sensory regions (19)(20)(21)(22). The DMN is the crucial network of self-awareness and internal awareness (23). Therefore, the external awareness would be disrupted with the decreased activity of the FPN during the loss of consciousness induced by general anesthesia.…”

“…Previous EEG studies indicated that with increasing propofol concentration, the power spectrum shifts from a high-frequency, low-amplitude activity to a low-frequency, high-amplitude activity (5,7). However, power changes in beta of (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) Hz and low gamma of (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) Hz frequency during propofol induction were inconsistent with previous studies (5,(8)(9)(10). In the present study, we found that in the transition from awake state to unconscious state, power in the global ECoG channels increased at lower frequency (< 46 Hz), and decreased at high gamma frequency.…”

Structural and functional connectivity of the ascending arousal network for prediction of outcome in patients with acute disorders of consciousness

“…In the last decade, multiple efforts have been made to characterize AAN, aiming to provide information to predict neurological outcomes in patients with severe brain injury and consequent DOCs 8 , 14 , 16 , 19 . The advancement of MRI techniques has allowed analysis of the anatomic and functional connectivity of the human brain 4 , 12 , 23 , 24 . In combination with the information acquired from DTI and BOLD, analysis of the AAN has revealed bidirectional connectivity between AAN nuclei in the brainstem and diencephalon and other multiple areas over the brain cortex 12 .…”