General anesthesia and the neural correlates of consciousness.

The neural correlates of consciousness must be identified, but how? Anesthetics can be used as tools to dissect the nervous system. Anesthetics not only allow for the experimental investigation into the conscious-unconscious state transition, but they can also be titrated to subanesthetic doses in order to affect selected components of consciousness such as memory, attention, pain processing, or emotion. A number of basic neuroimaging examinations of various anesthetic agents have now been completed. A common pattern of regional activity suppression is emerging for which the thalamus is identified as a key target of anesthetic effects on consciousness. It has been proposed that a neuronal hyperpolarization block at the level of the thalamus, or thalamocortical and corticocortical reverberant loops, could contribute to anesthetic-induced unconsciousness. However, all anesthetics do not suppress global cerebral metabolism and cause a regionally specific effect on thalamic activity. Ketamine, a so-called dissociative anesthetic agent, increases global cerebral metabolism in humans at doses associated with a loss of consciousness. Nevertheless, it is proposed that those few anesthetics not associated with a global metabolic suppression effect might still have their effects on consciousness mediated at the level of thalamocortical interactions, if such agents scramble the signals associated with normal neuronal network reverberant activity. Functional and effective connectivity are analysis techniques that can be used with neuroimaging to investigate the signal scrambling effects of various anesthetics on network interactions. Whereas network interactions have yet to be investigated with ketamine, a thalamocortical and corticocortical disconnection effect during unconsciousness has been found for both suppressive anesthetic agents and for patients who are in the persistent vegetative state. Furthermore, recovery from a vegetative state is associated with a reconnection of functional connectivity. Taken together these intriguing observations offer strong empirical support that the thalamus and thalamocortical reverberant network loop interactions are at the heart of the neurobiology of consciousness.