2006/07/25 by Stuart R. Hameroff · 1 citation
Neuroscience · Medicine · #Anesthesia and Neurotoxicity Research #Anesthesia and Sedative Agents #Neuroscience and Neuropharmacology Research #Medicine #Consciousness #Anesthesia #Neuroscience
paper · pdf · doi:10.1097/00000542-200608000-00024
openalex publication_date 2006/07/25 · openalex created_date 2016/06/24 · openalex updated_date 2026/07/30
THE mechanism by which general anesthetics prevent consciousness remains unknown largely because the mechanism by which brain physiology produces consciousness is unexplained. But the two mysteries seem to share a critical feature—both consciousness and actions of anesthetic gases are mediated through extremely weak London forces (a type of van der Waals force) acting in hydrophobic pockets within dendritic proteins arrayed in synchronized brain systems. Unraveling this common thread may reveal not only how anesthetics act, but also why we are conscious in the first place.What is anesthesia? Anesthesia provides immobility, amnesia, and loss of conscious awareness, although the latter—loss of consciousness—is often omitted from operational definitions.1In recent years, putative sites of anesthetic action for immobility (spinal cord2), amnesia (dorsolateral prefrontal cortex,3amygdala4), and loss of consciousness (networks involving thalamocortical and intracortical—corticocortical—loops, prefrontal cortex, and other areas5,6) have been discriminated both anatomically and in terms of sensitivity to anesthetics. Immobility is least sensitive to anesthetics, followed by loss of consciousness and then amnesia, which is most anesthetic sensitive.7(Implicit memory may occur without consciousness or movement, but at light levels of anesthetic.8) Therefore, lack of movement—even though mediated by spinal cord rather than brain—in the absence of muscle relaxants is a good indicator of both loss of consciousness and amnesia. Autonomic responses are even less anesthetic sensitive than immobility9and, in the absence of autonomic-blocking drugs, are thus useful (although not perfectly reliable) early warning indicators of changes in anesthetic depth.What is consciousness? Unlike other receptor-mediated pharmacologic targets, consciousness is ill-defined, cannot be measured, and generates heated debate about its very nature. Indeed, except for the “dark age” of behaviorism in psychology during most of the 20th century (in which consciousness was, almost literally, a dirty word), conscious awareness has been a prominent mystery in science and philosophy.10However, many articles promising to discuss consciousness avoid the issue, e.g. , using bait-and-switch techniques to describe memory, learning, sleep, or other related activities. Others deconstruct consciousness into a group of cognitive functions so that the essential feature—conscious awareness—gets lost in the shuffle.11In this article, consciousness will be considered equivalent to even minimal awareness, the ineffable phenomenon of pure subjective experience—our “inner life.” Thus, conscious awareness can exist irrespective of memory, cognition, or organizational sophistication (e.g. , reflective self-consciousness, higher-order thought, human—as opposed to animal—consciousness12). These more complex levels, although difficult to explain, are relatively straightforward compared with the issue of why or how even a slight glimmer of any form of conscious experience occurs at all.Anesthesia offers a unique and profound opportunity to understand consciousness because it is relatively selective—many brain activities (e.g. , evoked potentials, slower electroencephalography, and autonomic drives) continue during anesthesia while conscious awareness disappears. Thus, details of anesthetic mechanism may illuminate how the brain specifically produces consciousness and vice versa . This article reviews what is known about mechanisms of consciousness and anesthesia, finding that the “fine grain” of neuronal activities supporting consciousness and the molecular actions of anesthetic gases are one and the same—van der Waals London forces acting in hydrophobic pockets of coherently synchronized dendritic brain proteins. London forces are not chemical bonds but weak quantum interactions (in this regard, anesthetic gases differ in their actions from all other pharmacologic agents). Thus, the relative selectivity of anesthetic gases implies that the quantum nature of London forces may play an essential role in brain function leading to consciousness.Because consciousness is not directly measurable or observable, we begin with brain functional organization, systems, and activities known to correlate with consciousness.The particular brain systems and their functional activities related to consciousness are known as the neural correlate of consciousness (NCC). Depending on the level of detailed description, the NCC can be identified without necessarily addressing how consciousness is produced within or by the NCC.Functional frameworks for consciousness stem metaphorically from 17th century French philosopher Rene Descartes’“Theater of Consciousness” (hence “Cartesian theater”). Cognitive scientist Bernard Baars described this idea: “… consciousness acts as a ‘bright spot’ on the stage, directed there by the selective ‘spotlight’ of attention …”13Outside the spotlight are vast unconscious contents. But who or what is the audience, and who or what directs the spotlight? Despite these obvious problems, the theater metaphor has proven useful.In the 1970s, artificial intelligence computer models of brain function used a virtual “blackboard” on which specialized processors and knowledge sources could post their hypotheses about particular stimuli and then “vote” on which one was best. In the early 1980s, brain theorists combined this notion with the Cartesian theater metaphor and anatomical evidence about consciousness, resulting in “global workspace” theory.14The stage, blackboard, or workspace is associated with widely distributed (“global”) corticocortical neural networks and (in some versions) thalamocortical networks representing perceptual systems and memory. Particular content “on the stage” or workspace is spotlighted or chosen by attentional focusing via “bottom-up” thalamic and limbic inputs and “top-down” executive action from prefrontal cortex. Spotlighted networks become the NCC, which continually changes with dynamically shifting, temporary alliances/networks of neurons. Thus, global workspace models demonstrate a dynamical, functional architecture for the NCC.On the other hand, consciousness may apparently occur in neural networks within localized, selected brain regions. Excessive activity in any feature-selective region may be sufficient on its own for that feature to enter consciousness. Thus, activity in cortical visual “color” area V4 alone can result in the visual experience of color.15Other brain regions have been suggested as NCC candidates, e.g. , the brainstem and limbic system in Antonio Damasio’s and Jaak Panksepp’s (separate) views of emotional “core consciousness.”16So theoretically, consciousness can occur in what may be termed a global workspace (e.g. , for general surroundings, planning and processing—corticocortical and thalamocortical networks) but can also arise in more localized and perhaps separate regions, e.g. , overwhelming colors in a sunset (area V4), profound emotional feelings (brainstem, limbic system). The best scientific evidence for the NCC comes from brain imaging and electrophysiologic monitoring with loss of consciousness due to induction of general anesthesia.Functional brain imaging techniques (positron emission tomography and functional magnetic resonance imaging) show that anesthetic induction/loss of consciousness correlates with reduced metabolic and blood flow activity in brainstem, thalamus, and various regions of cortex, including thalamocortical and corticocortical networks.5However, the metabolic and hemodynamic decreases are delayed secondary effects of loss of consciousness rather than its cause. Electrophysiology provides a better correlate.Electrophysiologic brain monitors used in anesthesiology (e.g. , BIS Monitor®, Aspect Medical Systems, Inc., Newton, MA; Patient State Analyzer, Physiometrix, Inc., N. Billerica, MA; Narcotrend, MonitorTechnik, Bad Bramstedt, Germany) provide reasonably accurate correlates of anesthetic depth and presence or absence of consciousness.17They rely on spectral analyses and measures of synchrony in the electroencephalogram, particularly γ synchrony: approximately 30–70 Hz or higher, in various brain regions. Similar devices measure entropy in the electroencephalogram, or auditory-evoked γ synchrony.18,19A comprehensive electroencephalographic analysis of anesthetic-induced loss of consciousness was conducted by John and Prichep.6Using various anesthetic drugs and techniques, they found that loss of consciousness is a fairly abrupt transition (less than 20 ms) involving interruption of γ synchrony between frontal and posterior cortical regions. Similarly, Imas et al. 20showed that volatile anesthetics disrupt frontal–posterior cortical γ synchrony.Gamma electroencephalographic synchrony reflecting coherence among different brain regions is the best measurable correlate of consciousness, but is difficult to explain physiologically. Experiments show that γ synchrony is marked by “zero-phase-lag coherence,”21,22precisely synchronized voltage fluctuations occurring among varying regions of cortex and thalamus (and spinal cord23). Such precise coherence cannot be easily explained by neural networks involving thalamocortical pacing, recurrent feedback, reciprocal connections, propagating action potentials, and/or synaptic transmissions, which all convey significant delay or dephasing.21,24As will be discussed below, voltage potentials in cortical dendrites connected by electrotonic gap junctions apparently mediate γ synchrony, but even dendritic potentials introduce significant delay. Some collective be at and synchrony is that a type of quantum γ synchrony and synchrony is also in of conscious of and actions are in different cortical regions within (e.g. , visual among different (e.g. , and and at different from other by or conscious are into and any one there is only one NCC, and activities in different brain regions are to of consciousness into that anesthesia consciousness by neural by γ This consciousness, and the transition from unconscious to consciousness through γ transition from unconscious to consciousness is a that only a of the or so the NCC at any one although many more are the and networks are not and not to a particular of the brain consciousness In the theater the spotlight is shifting, with content of particular neural conscious selected by attentional and emotional why neural activity has the subjective of awareness remains consciousness to be a a of from unconscious activity to e.g. , or to approximately in γ apparently not all brain activity can become activity autonomic functions almost and during anesthesia, evoked potentials and some electroencephalographic activity continue in the absence of consciousness. can become , we and not occur during general anesthesia, it is that unconscious of conscious are by anesthetics. 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