General anesthesia and the neural correlates of consciousness
Section snippets
Consciousness as the dependent variable
It was not long ago that the mere mention of the “c” word (i.e., consciousness) in a scientific report would cause the editor of a neuroscience journal to question the very sanity of the heretical researcher who dared mention it. Presently, the study of consciousness has come to the forefront of scientific inquiry. This interest has been propelled forward not only by numerous recent conferences and scholarly works on the subject, but also directly because of numerous significant technological
The anesthetic approach to the consciousness problem
If we start our investigations of the neural correlates of consciousness from the theoretical framework where we assert that anesthesia causes a loss of consciousness, we are in an excellent position to proceed with the study of consciousness as a dependent variable that can be directly manipulated using the power of anesthetic drugs (Alkire et al., 1998). Anesthetics can be used in this manner because they can be given in precise specific doses that allow one to achieve any particular desired
The definitive anesthetic study versus reality
This chapter will review those anesthesia related studies that move us toward an understanding of what might be the neural correlates of consciousness. It is important to state, however, that the definitive study remains to be done. The definitive study would investigate essentially all anesthetic agents, including those that are considered dissociative in nature, as well as look at other methods of inducing unconsciousness. It would use standardized anesthetic endpoints such that a similar
Neuroimaging studies of anesthesia in humans
From a neurobiology perspective, the state of “conscious awareness” is likely to be an emergent property of distributed neural networks involving the thalamus and cerebral cortex (Newman and Baars, 1993; Crick, 1994; Llinas et al., 1998; Edelman and Tononi, 2000; John, 2001; also see Baars, this volume; Tononi, this volume; Ribary, this volume, John, this volume). It has been hypothesized, and follows logically, that the loss of consciousness induced by general anesthetic agents may result, in
The basis for the original observation of anesthetic effects on the thalamus
For the anesthetic end-point of loss of consciousness in humans, a more recent case has been made for a common effect of most, if not all, agents on thalamic metabolism/blood flow and thalamocortical–corticothalamic connectivity (Alkire et al., 2000; White and Alkire, 2003). This commonality observation led to the development of the “thalamic consciousness switch” hypothesis of anesthetic-induced unconsciousness (Alkire et al., 2000). The fact that anesthetics have an ability to affect
Recent anesthesia studies continue to demonstrate the thalamic effect
Further additional study over the intervening years has remained consistent with the thalamic overlap effect and has shown replications of propofol's thalamic effects (Kaisti et al., 2003; Veselis et al., 2004), along with an overlapping thalamic effect for the additional inhalational anesthetic agent sevoflurane (Kaisti et al., 2002). Additionally, recent studies with another newer class of sedative anesthetics, the -adrenoreceptor agonists, dexmedetomidine (Prielipp et al., 2002), and
Is consciousness in the parietal cortex?
The second most consistent anesthetic-related regional overlap effect involves the posterior cingulate and medial parietal cortical areas. These posterior areas are of some interest as potential neural correlates of consciousness for five primary reasons. First, as noted above, and as seen in Fig. 1, a number of these anesthetic agents suppress activity in these posterior brain regions. Second, these posterior parietal regions have been noted to show a relative decrease in functioning during
Network activity, anesthetic-induced signal suppression or signal scrambling?
As stated by Tononi and Edelman (1998), “Activation and deactivation of distributed neural populations in the thalamocortical system are not sufficient bases for conscious experience unless the activity of the neuronal groups involved is integrated rapidly and effectively.” Following this logic, it is unlikely that a full characterization of the effects of anesthetic agents which ablate conscious awareness, can be made by observing only the regionally specific and global suppressive effects of
The dose-dependent effects of anesthetics, keys to future study
As one awakens from an anesthetic, consciousness emerges from the subjective perception of complete oblivion. Of course, it remains unknown if oblivion is actually experienced by those experiencing it. Nonetheless, essentially all people who emerge from the unconsciousness of general anesthesia claim to have no memory of the time when they were unconscious. Their last memory is usually of the anesthesiologist telling them they would be going to “sleep” and their next memory is usually of waking
Conclusions
It appears that a convergence of evidence points toward the thalamus, thalamocortical, and corticocortical interactions as being critically involved with mediating not only anesthetic induced unconsciousness, but also with mediating other forms of altered states of consciousness. The study of the effects of anesthetics on consciousness is only just beginning. Even at this early stage, however, the current results suggest pharmacological manipulations in humans coupled with brain imaging
Acknowledgments
Funded, in part, by grant # RO1-GM065212 from the National Institutes of Health, Bethesda, MD, USA.
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