Brain Mechanisms of Propofol-Induced Loss of Consciousness in Humans: a Positron Emission Tomographic Study

Abstract

In the present study, we used positron emission tomography to investigate changes in regional cerebral blood flow (rCBF) during a general anesthetic infusion set to produce a gradual transition from the awake state to unconsciousness. Five right-handed human volunteers participated in the study. They were given propofol with a computer-controlled infusion pump to achieve three stable levels of plasma concentrations corresponding to mild sedation, deep sedation, and unconsciousness, the latter defined as unresponsiveness to verbal commands. During awake baseline and each of the three levels of sedation, two scans were acquired after injection of an H215O bolus. Global as well as regional CBF were determined and correlated with propofol concentrations. In addition, blood flow changes in the thalamus were correlated with those of the entire scanned volume to determine areas of coordinated changes. In addition to a generalized decrease in global CBF, large regional decreases in CBF occurred bilaterally in the medial thalamus, the cuneus and precuneus, and the posterior cingulate, orbitofrontal, and right angular gyri. Furthermore, a significant covariation between the thalamic and midbrain blood flow changes was observed, suggesting a close functional relationship between the two structures. We suggest that, at the concentrations attained, propofol preferentially decreases rCBF in brain regions previously implicated in the regulation of arousal, performance of associative functions, and autonomic control. Our data support the hypothesis that anesthetics induce behavioral changes via a preferential, concentration-dependent effect on specific neuronal networks rather than through a nonspecific, generalized effect on the brain.

Gamma Coherences in the Default Mode Resting State as a Measure of Consciousness Level

“…However, this study and also several other studies in anaesthesia or in the vegetative state (Fiset et al, 1999;Alkire et al, 2000;Laureys et al, 2000) showed that significantly greater reduction was seen in multiple regions of the prefrontal cortex, the superior frontal gyrus, the anterior cingulate gyrus, the parietal association areas, the insula and the thalamus. The majority of these areas constitute the DMRSN or have a close relationship to it.…”

Posterior cingulate, precuneal and retrosplenial cortices: cytology and components of the neural network correlates of consciousness

“…These include the thalamus and PCC/PrCC (Fiset et al, 1999;Kaisti et al, 2002). Although individual changes in rCBF did not correlate with propofol concentrations and the differences between three levels of propofol were not significant for any areas (Kaisti et al, 2002), this latter study did show that the lowest concentration of propofol assessed produced a profound average reduction in PCC/PrCC and Fiset et al, (1999) showed a strong negative correlation between rCBF in the thalamus and PCC/PrCC and propofol concentration. Furthermore, the close correlation of activity under propofol in the thalamus and midbrain in this latter study confirms the relevance of the reticular projections to thalamus as mediating arousal and initiation of consciousness.…”

The Action Sites of Propofol in the Normal Human Brain Revealed by Functional Magnetic Resonance Imaging

“…In the present study, we showed that in 5 of 10 subjects, the signals of thalamus were decreased during propofol anesthesia although the changes were weak and significantly different compared with the changes in hypothalamus, frontal lobe, and temporal lobe. However, most of the studies using PET reported that the thalamus was important in anesthesia (Fiset et al, 1999). We think that the probable reasons for these different results are the imaging methods and the doses of propofol used.…”