General anesthesia consists of
amnesia,
hypnosis,
analgesia, and areflexia. Of these, the mechanism of
hypnosis, or
loss of consciousness, has been the most elusive, yet a fascinating problem. How
anesthetic agents suppress human consciousness has been investigated with neuroimaging for two decades.
Anesthetics substantially reduce the global cerebral metabolic rate and blood flow with a degree of regional heterogeneity characteristic to the
anesthetic agent. The thalamus appears to be a common site of modulation by several
anesthetics, but this may be secondary to cortical effects. Stimulus-dependent brain activation is preserved in primary sensory areas, suggesting that unconsciousness cannot be explained by cortical deafferentation or a diminution of cortical sensory reactivity. The effect of
general anesthetics in functional and effective connectivity is varied depending on the agent, dose, and network studied. At an
anesthetic depth characterized by the subjects' unresponsiveness, a partial, but not complete, reduction in connectivity is generally observed. Functional connectivity of the frontoparietal association cortex is often reduced, but a causal role of this change for the
loss of consciousness remains uncertain. Functional connectivity of the nonspecific (intralaminar) thalamic nuclei is preferentially reduced by
propofol. Higher-order thalamocortical connectivity is also reduced with certain
anesthetics. The changes in functional connectivity during
anesthesia induction and emergence do not mirror each other; the recovery from
anesthesia may involve increases in functional connectivity above the normal wakeful baseline.
Anesthetic loss of consciousness is not a block of corticofugal information transfer, but a disruption of higher-order cortical information integration. The prime candidates for functional networks of the forebrain that play a critical role in maintaining the state of consciousness are those based on the posterior parietal-cingulate-precuneus region and the nonspecific thalamus.