Talk:Neural correlates of consciousness
Regarding the line about the cerebellar role in consciousness (or lack thereof), I am not convinced that any part of the human brain can necessarily be ruled out due to its classically understood role. Specifically regarding the cerebellum, a review in NN by Ramnani (2006) cites possible evidence for a higher cognitive role in the human cerebellum. Perhaps the current language should be modified to reflect the debate on this matter. --Slee 23:05, 18 November 2007 (EST)
Reply: We are emphatically not stating that the cerebellum does not have any function in cognitive processing. Rather, we advance a standard locationist argument common in biology both for theoretical reasons - having to do with the decoupled, local circuitry of the cerebellum - as well as based on any lack of evidence that lesions of the cerebellum has a discernible effect on perceptual consciousness. Of course, there is plenty of evidence implicating the cerebellum in fine sensory-motor control. To make this clear, we’ve added the italic sentence to read “For instance, it is likely that neural activity in the cerebellum not underlie any conscious perception, and thus is not part of the NCC. That is, trains of spikes in Purkinje cells (or their absence) will not induce a sensory percept although they may ultimately affect some behaviors (such as eye movements).”.
Comments of Reviewer A
1. I agree that progress in solving the mind-body problem will ultimately come from empirical work and not from "eristic" philosophical arguments.But this does not mean that theory and the philosophy of mind are unnecessary.The search for neuronal correlates cannot be accomplished without any -explicit or implicit- theoretical assumptions that aim at an explanation of the relationship between the conscious mind and its physiological basis.Otherwise we would end up with an enumeration of countless necessary conditions.Most of them would be meaningless and irrelevant.The problem consists in identifying those causal factors that are specific and close to the explanans.The only possibility to decide upon the relevance or irrelevance of a correlate is within a theoretical framework which aims at a -reductionistic- explanation.Hence the seach for NCCs as an empirical research strategy is highly problematic.It may lead to nowhere.The authors should -at least- make a brief comment on that.
2.The authors claim to "review(!)empirical approaches that shed light on the neuronal basis of consciousness" and "summarize what has been learnt". This is not unpretentious.What follows is not really a review. Many important empirical data are not mentioned.And it remains unclear what has been learned from the data mentioned. For instance: focal disturbances of consciousness (such as unilateral neglect)are not mentioned.Or:there is not much on the pharmacology of altered states of consciousness. Or:sleep and what is known about it is not sufficiently covered.Or: anesthesia and the mechanism of action of general anesthetics are not dealt with.In particular the important observation that selective NMDA-antagonist like ketamin are anesthetics and the hypotheses based on that ( Flohr,H., An information processing theory of anaesthesia.Neuropsychologia 33:1169-1180,(1995)) are not mentioned.
3.I do not think that the chapter on quantum mechanics is necessary.These speculations have not lead to any empirical observation.
4.Many of the references cited in the text do not occur in the reference list.
5.The recommended reading list is too small.I suggest to include:
Baars,DJ, Banks,WP,Newman,JB (eds) Essential sources in the scientific study of consciousness. Cambridge(Mass.),London 2003; Metzinger,T (ed.)Neural correlates of consciousness.Cambridge(Mass.)(2000) Schulte am Esch,J, Scholz,J, Tonner PH, Molecular Pharmacology of anaesthesia.Lengerich.(2000) Hobson,JA Sleep and dreaming. The Journal of Neurosciences,10,371-382,(1990)
Reply to Reviewer A
(1) We do not state anywhere in this entry that philosophy, or, in particular, that philosophy of mind, are not necessary for studying consciousness. On the contrary, at the end of the section “The Neural Correlates of Consciousness” we write:
“It should be noted that discovering and characterizing the NCC in brains is not the same as a theory of consciousness. Only the latter can tell us why particular systems can experience anything, why they are conscious, and why other systems - such as the enteric nervous system or the immune system - are not. However, understanding the NCC is a necessary step toward such a theory.”
To make this point even clearer we have modified our concluding sentence to
“It is the combination of such fine-grained neuronal analysis in animals with ever more sensitive psychophysical and brain imaging techniques in humans, complemented by the development of a robust theoretical predictive framework and coupled to a more refined philosophical analysis, that will hopefully lead to a rational understanding of consciousness, one of the central mysteries of life.
(2) In principle, the reviewer is correct that we should have written something about anesthesia and consciousness. Unfortunately, so far, surprisingly little has been learned about the NCC from studying anesthetic agents.
General anesthetics are a very diverse collection of chemicals, ranging from inert gases like xenon, to nitrous oxide, chloroform and other haloalkanes, diethyl ether and other ethers, phencyclidine, barbiturates, cholinergic agents, and opioids. The majority of anesthetics boost the potency of inhibitory synapses; many others interfere with cholinergic transmission. And then there are the NMDA-targeted ones that the referee refers to.
Two intravenous dissociative drugs, ketamine and phencyclidine (PCP), do not bind to inhibitory synapses, targeting instead NMDA receptors. At low doses, both ketamine and PCP induce hallucinations, distortions of body image, and disorganized thought. At high doses, they cause anesthesia. Flohr has postulated that the peculiar properties of NMDA synapses, particularly their propensity to strengthen links among simultaneously active neurons, play a pivotal role in assembling the network of neurons necessary for consciousness. Flohr argues that complete inhibition of NMDA-dependent processes prevents formation of large-scale assemblies of cortical neurons, causing a loss of consciousness, as in anesthesia, while partial inhibition leads to altered states of consciousness, as in psychotic states. Flohr may well be right that consciousness ceases without NMDA receptor activation. The same can also be said, however, of the other excitatory synapses sensitive to glutamate (e.g., Bonhomme, 2001). Furthermore, NMDA synapses are found throughout the brain, so blocking them affects a myriad of processes, including the communication of sensory information to the cortico-thalamic system.
A handful of relevant experiments suggest that cortical cells in anesthetized animals fire less vigorously and less selectively, and that they lack some of their contextual, non-classical receptive field properties. These effects are compounded when ascending the cortical hierarchy, leading to weaker, delayed, and less specific neuronal responses in the upper stages of cortex. Of course, the direct comparison of neuronal responses between awake and anesthetized states is technically demanding because the monkey must be rapidly and safely put to sleep and awakened again without perturbing the electrophysiological setup (Lamme, Zipser and Spekreijse, 1998; Tamura and Tanaka, 2001; Leopold, Plettenberg and Logothetis, 2002). Functional imaging provides an alternative to chart differences between the awake and the anesthetized brain (Alkire et al., 1999; and Logothetis et al., 1999 and 2001) but has, so far, not led to any breakthrough insight.
The trouble is that anesthetics bind to receptor and channel proteins throughout much of the brain. So far, they have proven to be too blunt a tool to help in our quest, though that may change in the future.
Regarding the neurobiology of sleep and its relation to consciousness, we would like to refrain from covering this topic in more depth than we do in the section “States of Consciousness and Conscious States” since the Scholarpedia category “Consciousness” has already four full articles focused on this topic, namely “Dreaming”, “Functions of Sleep”, “Neurobiology of Sleep and Wakefulness” and “REM (Paradoxical) Sleep”.
In response to the query by the referee, we have added a short section on split-brain studies and spatial hemineglect.
(3) While speculations concerning quantum mechanics (QM) have so far not lead to any empirical insights, they are widespread and date back to the inception of QM. Recently, they have been popularized by Roger Penrose. Furthermore, there is a widespread, and usually unreflective bias, among brain and cognitive scientists – often due to unfamiliarity with quantum concepts such as non-locality – that QM cannot possibly be of relevance to the brain. Upon mature reflection we tend to agree with this evaluation (Koch and Hepp 2006, 2008). However, it is important to be explicit about this.
(4) We are sorry about the missing references and have fixed these.
(5) We thank the referee for these additional suggested ‘reading material’ and have added a number of these to our list.
Alkire MT, Pomfrett CJD, Haier RJ, Gianzero MV, Chan CM, Jacobsen BP, and Fallon JH, Functional brain imaging during anesthesia in humans. Anesthesiology 90: 701-709, 1999.
Bogen JE, The callosal syndromes. In: Clinical Neurosychology. 3rd ed., Heilman KM, and Valenstein E, eds., pp. 337-407. Oxford University Press: New York, 1993.
Bonhomme V, Hans P, Mechanisms of unconsciousness during general anaesthesia. Curr. Anaesth. Crit. Care 12: 109-13, 2001.
Gazzaniga MS, Principles of human brain organization derived from split-brain studies. Neuron 14: 217-228, 1995.
Lamme VAF, Zipser K and Spekreijse H, Figure-ground activity in primary visual cortex is suppressed by anesthesia. Proc. Natl. Acad. Sci. USA 95: 3263-3268, 1998.
Leopold DA, Plettenberg HK and Logthetis NK, Visual processing in the ketamine-anesthetized monkey. Exp. Brain Res. 143: 359-372, 2002.
Logothetis NK, Guggenberger H, Peled S, and Pauls J, Functional imaging of the monkey brain. Nature Neurosci. 2: 555-562, 1999.
Logothetis NK, Pauls J, Augath M, Trinath T and Oeltermann A, Neurophysiological investigation of the basis of the fMRI signal. Nature 412: 150-157, 2001.
Koch C and Hepp K, Quantum mechanics and higher brain functions: Lessons from quantum computation and neurobiology. Nature 440: 61161-2, 2006.
Koch C and Hepp K, The relation between quantum mechanics and higher brain functions: Lessons from quantum computation and neurobiology. In: Amazing Light: Visions for Discovery: New Light on Physics, Cosmology and Consciousness. Chiao RY, Cohen LM, Leggett AJ, Phillips WD, and Harper Jr. CL, eds., Cambridge University Press.
Tamura H and Tanaka K, Visual response properties of cells in the ventral and dorsal parts of the macaque inferotemporal cortex. Cerebral Cortex 11: 384-399, 2001.
New comments of Reviewer A
1.The modification of the concluding sentence has definitely improved the article.
2.I can also accept that sleep is covered elsewhere.
3.If the authors think that"little has been learned about the NCC from studying anesthetic agents the authors should say that and give reasons for that judgement.I disagree. In particular I think that the observations that suggest that the cortical NMDA-synapses are the common final pathway for anesthetics and halluciogens are relevant. 4 Why doe the authors not include Baars/Banks/Newman: Essential sources in the scientific study of consciousness in the reading list?
Reply to New comments of Reviewer A
We have followed the reviewer's suggestion and have added this following paragraph to our article after the second paragraph (ending with “compatible with clinical exigencies”) in the Global Disorders of Consciousness paragraph
“While anesthetics may, in principle, be useful for the study consciousness, they have as yet failed to provide breakthrough insights about the NCC. This is mainly due their diverse mechanisms of molecular action targeting receptors throughout large parts of the brain. As our ability increases to differentiate subreceptor variation and target them with molecular tools by means of genetic in vivo studies (Rudolph & Antkowiak 2004), this is likely to change. “
Regarding the common final pathway for anesthetics and hallucinogens, this depends on what is meant by “common final pathway”. For instance, hallucinogens, such as LCD, mescaline, magic mushroom etc., specifically bind to serotonin receptor subtype 5-HT2A on layer 5 cortical pyramidal cells (see the very recent elegant knock-in study on this subject in mice: J. González-Maeso, N. Weisstaub, M. Zhou, P. Chan, L. Ivic, R. Ang, A. Lira, M. Bradley-Moore, Y. Ge, Q. Zhou, S. Sealfon, J. Gingrich (2007) "Hallucinogens Recruit Specific Cortical 5-HT2A Receptor-Mediated Signaling Pathways to Affect Behavior" Neuron 53(3): 53, 439-452). Of course, subsequent to this NMDA-current mediated effects may also play a role as well as direct effects of the serotonin on intrinsic excitability (for example, 5HT enhances a TTX-sensitive persistent Na+ current in prefrontal cortex pyramidal neurons, and increased Na+ current can increase intrinsic excitability).
Many popular agents used for general anesthesia predominantly potentiate inhibitory ligand-gated ion channels, such as GABA-A, glycine receptors or benzodiazepines. For instance, the widely used intravenous anaesthetic propofol (see U. Rudolph, B. Antkowiak (2004) "Molecular and neuronal substrates for general anaesthetics" Nature Reviews Neuroscience 5(9): 709-720). The hypnotic and sedative effects of GABA-A agonists are likely mediated specifically by cortical GABA-A receptors containing the beta2 or beta3 subunit. Again, while it is in principle conceivable that subsequent NMDA receptor activation may play a general role in the mechanisms of anesthesia, the primary effect of these anesthetics is mediated by non-NMDA receptor activation.
We have added the reprint collection of Baars et al. to the Recommended Reading list. We also added the above mentioned general review on anesthetics by Rudolph and Antkowiak (2004).
Comments of Reviewer B
This is a very good introduction to one of the most challenging problems in neuroscience, namely, understanding how brain activity can lead to what people usually describe as "The Mind". As emphasized by the authors, this is a complex yet unsolved problem. The authors discuss the main research directions in the field and provide ample references for aficionados to learn further about this topic.
1- The section on "Quantum Mechanics" takes a prominent position as one of the initial subtitles. This is more of a side esoteric line of research and very few neuroscientists seem to find this to be a prominent line of research. Of course, maybe everybody is wrong about this. But right now, the article seems to emphasize this as an important idea/research direction. I would suggest removing this form the text or mentioning this within a section entitled "Other directions".
2- Similarly, free-will is a very intersting problem but it could be discussed later in the article rather than at the beginning before discussing more basic issues.
3- There is a brief comment about "meditative practices". This remains a rather controversial theme in neuroscience and I doubt that the weight of the evidence clearly shows that meditation can lead to "another state of consciousness". At the very least, this should be re-written in a more cautious way (or removed).
4- Ventral "what" / dorsal "where" pathways are mentioned without a clear definition. While this is standard nomenclature in vision research, the authors may want to add a sentence to describe the two main pathways and why they are called "what" and "where" pathways.
5- I was surprised not to see the important book by one of the authors "The Quest for Consciousness" in the list of references.
6- "... by the human cortex within 130-150 ms, far too slow for eye movements ...". --> "too fast"?
Gabriel Kreiman, Assistant Professor, Children's Hospital, Harvard Medical School, firstname.lastname@example.org
Reply to Reviewer B
(1+2) We have followed the Reviewer's suggestion and moved these sections further to the end of the article as subsections under "Other Aspects of Consciousness".
(3) We re-phrased the sentence but decided to keep it since it links to the Scholarpedia article on Meditation in the Consciousness category. It now reads "Yet another state of consciousness has been reported to occur during certain meditative practices, when conscious perception and insight are assumed to be enhanced compared to the normal waking state."
(4) These terms are linked to the Scholarpedia article "What And Where Pathways". One of the key features of Scholarpedia is that definitions can be given by using such links.
(5) We added the book to the reference list since it is referenced in several figure captions.
(6) Oops, we fixed this typo.
User 6: "The classical mind-body problem"
Regarding this sentence:
"This is the heart of the classical mind-body problem: What is the nature of the relationship between the immaterial, conscious mind and its physical basis in the electro-chemical interactions in the body?"
The classical mind-body problem did not presuppose that the mind had a "physical basis" in the body. For example, the standard account has it that Descartes believed that the mind interacted with the body via the pineal gland, not that the mind had a physical basis in the pineal gland or anywhere else. Further, the classical formulation of the mind-body problem was not given in terms of "electro-chemical interactions." The brain was not yet conceived in this way.