Sunday 8 July 2012

Gilles Plourde: General Anesthetics for the Study Consciousness


    Abstract: Although general anesthetics have been used for more than 150 years and suppress consciousness in a predictable manner, their mechanisms of action are not fully elucidated. Numerous studies have been devoted to understanding how general anesthetics impair consciousness in human subjects using either functional brain imaging or electrophysiology. These studies have obvious relevance for the study of consciousness, particularly for consciousness as a waking state and in regard to self-awareness. They have revealed the critical involvement of the thalamus and offered evidence supporting the hypothesis that the anesthetized state is associated with loss of connectivity and attenuation neuronal oscillations in the high-gamma range. In this lecture, I will first review the aspect of the pharmacology of general anesthetic that are essential to appreciate the possibilities that these drugs offer to study consciousness as well as their limitations. In the second part, I will summarize the main findings that emerge from the literature.

    Alkire MT, Hudetz AG, Tononi G. Consciousness and anesthesia. Science 2008; 322: 876-80 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743249/
    Franks NP. General anaesthesia: from molecular targets to neuronal pathways of sleep and arousal. Nat Rev Neurosci 2008; 9: 370-86http://hopecenterdev.wustl.edu/training/bio5663/Documents/FRANKS_NATNEUROSCI_rev.pdf
    Critical involvement of the thalamus and precuneus during restoration of consciousness with physostigmine in humans during propofol anaesthesia: a positron emission tomography study http://bja.oxfordjournals.org/content/106/4/548.full

Comments invited

18 comments:

  1. The way G. Plourde conceives unconsciousness makes me wonder if his definition would also include sleep as being an unconscious state? Most people know that sleep stages are not unconscious states (e.g., dreaming). If one person is not answering back after being asked to close his eyes, would it really mean that they person is unconscious, knowing now that she just can be asleep?

    What if anaesthesia, through all the substances, was a more profound state of sleep? This would mean that anaesthesia wouldn't be an unconscious state at all. On the other hand, the cerebral blood flow studies presented suggest that anaesthesia and sleep present with different patterns of metabolism.

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    1. People actually respond to stimuli in sleep. Besides, do you think all of sleep is conscious? Sure, when you dream, you are, but what about dreamless sleep? General anesthesia certainly is dreamless.

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    2. Dr. Plourde presented an interesting dissociation between long-term memory and consciousness. His anecdote about talking the whole time (thus seeming conscious) while he was under sub-anaesthesia and not remembering any of this episode afterwards is similar to the situation of patient HM who was clearly conscious (feeling/thinking/talking) but could not remember afterwards what he felt/thought/said. In the memory literature, it is widely thought that the hippocampus is required for long-term memory consolidation. That would suggest that the hippocampus is somehow knocked out first before the cortex during sub-anaesthesia! I will be interested to see brain-imaging during such a state to see if this is indeed true. Same goes for hypnosis that leads to spontaneous amnesia.

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    3. I think Dr. Plourde's anecdote (and Carey's description of HM) provide us with a pretty strong argument that consciousness need not require anything like long-term memory or even -- something that was suggested by some students before -- a capacity to create an autobiographical narrative of the moments during which you are conscious.

      It seems to me that people who make claims that consciousness requires such things do so often because they want to undermine the feeling/doing distinction. Their argument would be that because it is so intrinsically related to memory (and memory is a kind of doing), consciousness is also kind of doing. But, as these examples show, their argument clearly cannot work.

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    5. There are many similarities between (slow wave) sleep and anesthesia, and that includes cerebral blood flow changes (see N Franks' review in Nature Neuroscience). The main difference between sleep and anesthesia is that you cannot be aroused back to consciousness from adequate general anesthesia by sensory stimulation.

      By the criterion of response to commands, I think that subjects are unconscious during slow wave sleep and that they become progressively conscious of their environment as they emerge from sleep following sensory stimulation. This applies only to slow-wave sleep.

      There have been reports of dreams during general anesthesia, usually during emergence at the end of the procedure. See K Leslie, Dreaming during Anesthesia and Anesthetic Depth in Elective Surgery Patients: A Prospective Cohort Study, Anesthesiology 2007, 106pp 33-42

      Finally, I think that consciousness can occur in the absence of long-term memory.

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    6. This kind of approach to consciousness raises the interesting question of how felt experience is related to long-term memory. Indeed, Doctor Plourde’s anecdote seems to hint toward the possibility that phenomenal consciousness need not be linked to long-term memory. It does illustrate, however, that a coherent sense of a narrative self does necessarily involve long-term memory.

      Perhaps using a distinction such as the “I” of felt perception versus the “me” of continuous, lived experience might be helpful for understanding such anecdotes. Indeed, if dreams can occur during anesthesia, then perhaps such processes do not actually turn consciousness "off", as it were, as much as they tamper with higher-order memory and information integration. Studies of anesthesia in particular might help shed light into the ongoing construction of the sense of self in relation to memory and conscious experience.

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    7. I thought Dr. Plourde's talk was fascinating. I did a little research on the topic, to see what the literature might have to say. I came across the following article : Sanders, R. D., Tononi, G., Laureys, S., & Sleigh, J. W. (2012). Unresponsiveness ≠ unconsciousness. Anesthesiology, 116(4), 946-959.

      The authors draw a distinction between responsiveness, consciousness and connectedness. One, naturally, is all three when awake. During REM sleep, one can have disconnected consciousness (through dream), but be unresponsive. An individual who is sleepwalking can be disconnected, but show spontaneous responsiveness to environmental/sensory stimulation. Following anesthesia, but preceding administration of the paralysis-inducing neuromuscular blockade (Dr. Plourde, please correct me if I misunderstood this), one can prevent paralysis of a specific body part (e.g. by using an inflated cuff on the arm). Patients undergoing anesthesia with the so-called 'isolated fore-arm technique' show no spontaneous responsiveness, but do obey to goal oriented commands (e.g. squeeze my hand - I assume, in contrast, that they would be unable to open their eyes). In such instances, the authors deem that the person, despite being spontaneously unresponsive, is still consciously "connected".

      I thought these were useful distinctions for better understanding 'consciousness'.

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    8. There might be several similarities between slow-wave sleep and anaesthesia. However, in comparison to REM sleep (where most of our bizarre dreams occur), anaesthesia is very much different. Anaesthesiologists' definition of consciousness is too much linked to language abilities (whether in oral expression to say that you are conscious or in oral comprehension to understand someone asking if you are conscious). REM sleep is not an unconscious state because people cannot say that they are conscious (and thus respond to external stimuli: in REM sleep dreamers do not respond to external stimuli, unlike in slow-wave sleep): the brain is fully activated, the person is dreaming (vividly, more imaginatively than in any other circumstances, etc.). The person is indeed under some kind of consciousness.

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  2. Consciousness as presented by Gilles Plourde was really interesting because is asked the question "what does it really mean to be conscious".
    According to Gilles, an individual is considered to be conscious as long as he/she responds to an external stimulus such as "open your eyes". But, he also mentioned that the time following the anesthesia was often a period of confusion for the patient and it seemed to me that consciousness could not be considered as black or white and should rather be considered as a continuum with a kind of "semi-conscious state" where consciousness is still there but the individual cannot be really considered as fully conscious. In that situation, what does really matter? what you feel when you are fully conscious or what you fell when you are in any stae of consciousness? and if we can more or less distinguish between several levels of consciousnes, what about other cases of altered consciousness such as being drunk, or under drug's effects? are these people really "conscious of what they do"?

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  3. I thought it was very interesting to distinguish, in imaging studies, what is the unconscious state and what is the consequence of this unconscious state. The thalamus is a very important structure for the relay of information to other structures. Thus, if it is affected by anesthetic drugs, it will affect indirectly other structures.
    It is something to take into account in all brain imaging studies and espacially when we study consciousness since it involves many brain areas.

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  4. Dr. Plourde mentioned that in fMRI studies general anaesthetics result in an overall reduction of activity, with significant reductions in the occipital, parietal and particularly in the thalamus. I was curious if there is any connection between damage to these regions, particularly the thalamus, and coma patient who never regain consciousness?

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  5. I think Plourde's definition of consciousness is too simple, even if probably really useful in the anesthetics world. If we define consciousness as "being able to respond to external commands" where does the locked in syndrome stands? (in the brain signal, yes, but such criterion was not included in the scale presented in the talk). Also, the period of confusion that seems overlaps Plourde's barrier of consciousness is quite puzzling to me. Even if the content of consciousness isn't properly articulated during this period and memory of it can be brittle, it seems to me as it is conscious. It is not a gray zone.
    "Being able to report, or acknowledge to oneself" is to me, the definition of consciousness. It doesn't involve memory, it doesn't involve fully articulated language, it might involve feeling (yet to which extend, I am not sure) but it extirpates what consciousness is.

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    1. During the talk, I actually wondered about the importance of memory and expression.

      You say: "Even if the content of consciousness isn't properly articulated during this period and memory of it can be brittle, it seems to me as it is conscious."

      In a situation where the person feels, but is not able to report, and doesn't remember having felt when he/she IS able to report, how can we ever know it was a conscious experience?

      In a way memory is a way to report to yourself what has happened to you in the past, and it is also required to report to others. So are they required to measure consciousness if not to actually be conscious?

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  6. I was wondering the same thing about locked in syndrome! where would that fit in? As well, on the other end of the spectrum, couldn't there be things that are not conscious but are ‘able to respond to external commands’, such as robots?
    It is also very interesting to examine the link between memory and consciousness (as Carey mentioned HM). It seems long-term memory is not necessary for consciousness. (I don’t think anyone is claiming that HM was unconscious) If memory is not necessary, would one need the sense or recognition of the self to be conscious? Does a cat know it is a cat? Even if a cat didn’t know it was a cat, it seems to me it would still ‘feel’ like something to be a cat. What is necessary to attribute consciousness to an organism other than to ourselves?

    Izabo Deschênes

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  7. Xavier Dery ‏@XavierDery

    Sleep-like state with inability to respond to verbal stimuli... I hope Plourdes only uses this definition of consc. in the clinic! #TuringC

    11:26 AM - 9 Jul 12 via Twicca Twitter app

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  8. Xavier Dery ‏@XavierDery

    Seems that Plourdes' rain analogy for the neural correlates of anasthesy could elegantly fit many other neural correlates cases... #TuringC

    11:44 AM - 9 Jul 12 via Twicca Twitter app

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  9. Now you make it easy for me to understand and implement the concept. Thank you for the post.
    WHAT IS CONSCIOUSNESS

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