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    Where forward thinking terrestrials share ideas and information about the state of the species, their planet and the universe, living the lives of science fiction. Introduction
    Featuring Powers of Ten by Charles and Ray Eames, based on an idea by Kees Boeke.
    What follows is a paper by Klaus M. Stiefel which summarizes the latest studies into the mechanisms of the salvia divinorum induced hallucinogenic experience. This paper is reproduced here in full WITHOUT permission or knowledge of the original author.

    [begin paper : ]

    The consciousness-altering effects of Salvia Divinorum are likely due to its action on the claustrum and cortex.

    Klaus M. Stiefel

    Theoretical and Experimental Neurobiology Unit, Okinawa Institute of Science and Technology,
    Uruma, Okinawa, Japan. Tel. +81-98-921-3927 Fax. +81-98-921-4021

    This theoretical article aims to bring together three findings and ideas relevant for the understanding of human consciousness: (1) Crick's and Koch's ideas on the central role of the claustrum as a directing center crucial for subjective conscious experience. (2) The wealth of subjective reports describing the severely consciousness-altering effects of salvinorin A, a κ- opioid receptor agonist and the active ingredient of the plant Salvia divinorum. (3) The high density of κ-opioid receptors in the claustrum. Taken together, these facts lead me to hypothesize that the consciousness-altering effects of salvinorin A, the main active compound of Salvia divinorum, are due to a κ-opioid receptor mediated inhibition of primarily the claustrum and, additionally, the deep layers of the (mainly prefrontal) cortex. The high consciousness-altering potency of salvinorin A and the high density of its target, the κ-opioid receptors, in the claustrum give added weight to the ideas emphasizing the role of this brain area in human consciousness. I discuss opportunities for experimental consciousness research arising from the proposed role of salvinorin A in modulating claustral function.

    Keywords: Claustrum, consciousness, Salvia divinorum, salvinorin A, κ opioid receptor

    Introduction and Results
    Crick and Koch's ideas on the role of the claustrum
    The late Francis Crick proposed the idea that human subjective consciousness is brought about by the activity of a limited number (~105) of neurons (Crick, 1995). These neurons need to fulfill a number of criteria: 1. They must be central in the connection-scheme of the human brain, not to close to primary sensory or motor areas. 2. They must involve a number of sensory areas, since consciousness integrates several sensory modalities. 3. Their activity must be correlated with conscious experience, even in situations where it is dissociated from direct sensory input (for instance during the perception of visual illusions). The identity of these neural populations will change with changing contents of the conscious experience. Possibly a brain region acting as a “director” of this process is needed. In Crick's very last paper, he and Koch argued that the claustrum is an ideal candidate for this role (Crick & Koch, 2005). The claustrum, is a layered brain region in-between the insular cortex, piriform cortex and the caudate-putamen (Crick & Koch, 2005; Franklin & Paxinos, 2007). It is highly connected to a number of cortical areas in a non-trivial, mostly reciprocal manner. This strong and complex interconnectivity with the cortex makes it a prime candidate for the role of the “director” of the “conscious field” (Searle, 2004), “dynamical core” (Tononi & Edelman, 1998a; Tononi & Edelman, 1998b) or “neuronal workspace” (Dehaene & Changeux, 2004). Ways to test this hypothesis fall in two groups: One would be to conduct recordings of claustral activity in conscious humans. This possible, but challenging due to the small size of the claustrum, which presents difficulties for interpreting the results obtained with non-invasive imaging methods (functional magnetic resonance imaging, positron emission tomography). Invasive recordings in non-human primates and other mammals are possible, but in this case it is impossible to obtain verbal reports of the subjects’ experiences during the recordings.
    An alternative approach would be a selective pharmacological manipulation of the claustrum. I argue that salvinorin A, the active compound of the psychoactive plant Salvia divinorum, provides the opportunity for such a manipulation.

    Consciousness-altering effects of salvinorin A

    Salvia divinorum is a plant native to the Oxaca region in southern Mexico which is traditionally used in the Mazatec culture as inebriate in religious and spiritual contexts (Cheyene, 2006; Siebert, 2008). It is smoked or orally ingested. Its active compound, salvinorin A, is the substance with the lowest known effective concentration for mind-altering effects (Siebert, 1994). Salvinorin A is a κ-opioid receptor agonist (Ansonoff et al., 2006; Chavkin et al., 2004; Roth et al., 2002). Subjective effects at low doses are described as disorienting, confusing, even frightening or alternatively also as subtly calming and meditative. The unpredictability of the effects is one of their prominent and most interesting features. Subjective effects at higher doses are often described as dissociative to an extreme degree. Subjects often report a loss of the awareness of their current surroundings and, while fully conscious, believe that they are in different locations which they remember, sometimes from decades in the past. Space is often distorted and subject sometimes experience states which are described as complete non-spatial
    existence. These experiences are described as interesting, even life-altering, but typically as unpleasant. They are clearly distinct from the experiences brought about by classical, serotroninergic, psychedelics like LSD and psilocybin. In general, verbal reports of experiences induced by the consumption of high doses of Salvia divinorum describe a most profound alteration of consciousness, even more fundamental than those induced by these classical psychedelics (Arthur, 2008; Siebert, 2008). How does this effect arise from the action of salvinorin A in the brain?

    The effects of κ-opioid receptors and their distribution in the primate brain
    The κ-opioid receptor, the target of salvinorin A, is a g-protein coupled neurotransmitter receptor. Upon agonist binding, it activates phospholipase C, which then sets off an intracellular IP3 and cAMP based 2nd messenger cascade (Law et al., 2000). This second messenger cascade couples the agonist binding to downstream cellular effects (Law et al., 2000). Known effects are the reduction of presynaptic neurotransmitter release, via a reduction in N-type calcium current (Tallent et al., 1994), and a decrease of cellular excitability, via an increase of the inward rectifier potassium currents (Henry et al., 1995). The effects of κ-opioid receptors are thus inhibitory, both by reducing the amount of input a neuron is receiving and by reducing the response to that input.
    In human brains, κ-opioid receptor expression was measured by mRNA in situ hybridization (Peckys & Landwehrmeyer, 1999). High densities were found in the striatum, hippocampal dentate gyrus, deep cortical layers (V and VI, with more expression in the prefrontal than in the occipital cortex) and, especially, in the claustrum. The claustrum was the only brain region in which nearly all cells were labeled with dense to very dense labeling density. In the macaque monkey brain, κ-opioid receptor activity was measured by monitoring the agonist- induced binding of a radioactively labeled GTP-analogue ([35S]GTPγS). Strong activity was found in the limbic and association cortex, ventral striatum, caudate, putamen, globus pallidus, claustrum, amygdala, hypothalamus and substantia nigra (Sim-Selley et al., 1999). The authors report that “A very high level of κ1-stimulated [35S]GTPγS binding was observed in the claustrum, with an area of especially high stimulation in the ventral claustrum, adjacent to the amygdala.”. While there was evidence for κ-opioid receptor activity in other brain regions as well, the densities were significantly higher in the afro mentioned regions.

    This presents us with a number of candidate brain regions for the consciousness-altering effects of salvinorin A. The inhibition of each of these brain regions alone, or in any combination, could be responsible for its consciousness-altering effects. While all brain regions are important for brain function, and ultimately the survival of the animal, not the activity of all of them might be neural correlates of consciousness. Excluding some regions will be somewhat speculative due to the still incomplete characterization of the complex functions of these brain regions. There is nevertheless a sizeable body of work available in systems neuroscience which makes it possible to narrow the candidate list down. The striatum, caudate, putamen, substantia nigra and globus pallidus are commonly considered to be part of an integrated system involved in action selection, reinforcement learning and motor control, and are not likely neural correlates of consciousness (Wilson, 2004). The hypothalamus is considered to be responsible for the regulation of metabolic processes as part of the autonomous nervous system. It is also an unlikely candidate for a role in consciousness. The amygdala is a brain region thought to be involved in emotional processing, such as fear and fear conditioning (Phelps & LeDoux, 2005). While many subjects report a component of fear in their Salvia divinorum evoked experiences, this is separate from the consciousness-altering effects I am discussing here.
    This leaves us with the deep layers of the (mainly prefrontal) cortex and the claustrum as relevant salvinorin A target areas. Most likely, these are the brain areas which, when inhibited by salvinorin A, give rise to the intense consciousness-altering experiences reported by users of Salvia divinorum. The unusually high κ-opioid receptor density in the claustrum makes it a particularly good candidate target area.

    I hypothesize that the consciousness-altering effects of salvinorin A, the main active compound of Salvia divinorum, are due to a κ-opioid receptor mediated inhibition of primarily the claustrum and, additionally, the deep layers of the (mainly prefrontal) cortex. This hypothesis supports the role of the claustrum in human consciousness as proposed by Crick and Koch. It is a testable hypothesis, by non-invasive and invasive recordings in humans and non-human primates under the influence of salvinorin A, respectively. Furthermore, it opens new avenues for experimental consciousness research. One open question is the exact role of the inhibition of the claustrum and the cortex in bringing about the changes experienced under the influence of salvinorin A. Other open questions are the time course of its action and the difference in neural activity between high and low doses which are experienced in a qualitatively different way. Lastly, if the hypothesis about the claustrum’s role as a “director” of cortical activity is correct, then claustral inhibition by salvinorin A should lead to a massive alteration of cortical synchronization patterns.
    I thank Drs. Charles F. Stevens, Gordon W. Arbuthnott and John Jacobson for helpful discussion and critically reading the manuscript.


    * Ansonoff, M. A., Zhang, J., Czyzyk, T., Rothman, R. B., Stewart, J., Xu, H., Zjwiony, J., Siebert, D. J., Yang, F., Roth, B. L. & Pintar, J.E. (2006). Antinociceptive and hypothermic effects of Salvinorin A are abolished in a novel strain of kappa-opioid receptor-1 knockout mice. J Pharmacol Exp Ther, 318, pp. 641-648.
    * Arthur, J.D. (2008). Peopled Darkness: Perceptual Transformation through Salvia divinorum: iUniverse.
    * Chavkin, C., Sud, S., Jin, W., Stewart, J., Zjawiony, J. K., Siebert, D. J., Toth, B. A., Hufeisen, S. J. & Roth, B.L. (2004). Salvinorin A, an active component of the hallucinogenic sage salvia divinorum is a highly efficacious kappa-opioid receptor agonist: structural and functional considerations. J Pharmacol Exp Ther, 308, pp. 1197-1203.
    * Cheyene, S. (2006). Salvia Divinorum: Shamanic Plant Medicine: Aardvark.
    * Crick, F. C. (1995). The astonishing hypothesis: Scribner.
    * Crick, F. C. & Koch, C. (2005). What is the function of the claustrum? Philos Trans R Soc Lond B Biol Sci, 360, pp. 1271-1279.
    * Dehaene S, C. J. & Changeux, J-P. (2004). Neural mechanisms for access to consciousness. In Gazzaniga (Ed.), The cognitive neurosciences: MIT Press.
    * Franklin KBJ, P. G. (2007). The Mouse Brain in Stereotaxic Coordinates: Academic Press.
    * Henry, D. J., Grandy, D. K., Lester, H. A., Davidson, N. & Chavkin, C. (1995). Kappa-opioid receptors couple to inwardly rectifying potassium channels when coexpressed by Xenopus oocytes. Mol Pharmacol, 47, pp. 551-557.
    * Law, P. Y., Wong, Y. H. & Loh, H.H. (2000). Molecular mechanisms and regulation of opioid receptor signaling. Annu Rev Pharmacol Toxicol, 40, pp. 389-430.
    * Peckys, D. & Landwehrmeyer, G.B. (1999). Expression of mu, kappa, and delta opioid receptor messenger RNA in the human CNS: a 33P in situ hybridization study. Neuroscience, 88, pp. 1093-1135.
    * Phelps, E. A. & LeDoux, J.E. (2005). Contributions of the amygdala to emotion processing: from animal models to human behavior. Neuron, 48, pp. 175-187.
    * Roth, B. L., Baner, K., Westkaemper, R., Siebert, D.J., Rice, K. C., Steinberg, S., Ernsberger, P. & Rothman, R.B. (2002). Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist. Proc Natl Acad Sci U S A, 99, pp. 11934-11939.
    * Searle, J. (2004). Mind: a brief introduction: Oxford University Press.
    * Siebert, D. J. (1994). Salvia divinorum and salvinorin A: new pharmacologic findings. J Ethnopharmacol, 43, pp. 53-56.
    * Siebert, D.J. (2008). Retrieved from
    * Sim-Selley, L. J., Daunais, J. B., Porrino, L. J. & Childers, S.R. (1999). Mu and kappa1 opioid-stimulated [35S]guanylyl-5'-O-(gamma-thio)-triphosphate binding in cynomolgus monkey brain. Neuroscience, 94, pp. 651-662.
    * Tallent, M., Dichter, M. A., Bell, G. I. & Reisine, T. (1994). The cloned kappa opioid receptor couples to an N-type calcium current in undifferentiated PC-12 cell. Neuroscience, 63, pp. 1033-1040.
    * Tononi, G. & Edelman, G.M. (1998a). Consciousness and the integration of information in the brain. Adv Neurol, 77, p. 245-79.
    * Tononi, G. & Edelman, G.M. (1998b). Consciousness and complexity. Science, 282, pp. 1846-1851.
    * Wilson, C.J. (2004). Basal Ganglia. In Shepherd, G. (Ed.), The Synaptic Organization of the Brain: Oxford University Press. pp. 361-414.
    Sat, Feb 21, 2009  Permanent link

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    "In retrospect, it was a natural progression. The counterculture was rapidly exhausting existing intoxicants, and the creation of new drugs took a considerable amount of expertise and luck. Even then the compounds were course, imperfect, and not without side effects. Ultimately, the desire for increasingly novel experiences drove the use of neuroscience toward recreational purposes. Those individuals who would have formed roving bands of homeless hippies in the 60s now form rouge "research groups," largely outside the reach of law or even rigorous science, who's subject of investigation is of course entirely their own minds, and who's objective is undefined."
    Fri, Feb 13, 2009  Permanent link
    Categories: [transmitted from the future]
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    I built some goggles to experiment with strobe light induced hallucinations. At the moment they are driven by an arduino. Each eye has a single very bight 3 channel LED inside a diffusor ( well, cut up and glued back together ping pong ball ). Each eye has a 24 bit color range, courtesy of the arduino PWM output pins. The arduino program can load a series of strobe light patches, which are stored in the arduino EEPROM memory, and played back as a sequence. It entertains me. My friends have reported rather complex hallucinations under the influence of this device. I however have only been able to experience simple geometric hallucinations.

    Sat, Jan 17, 2009  Permanent link

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    less beautiful than the nebula itself, which was considerable fracture structure on its own

    Wed, Dec 3, 2008  Permanent link

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    Once conscious systems are virtualized, we will have the ability to do some unusual things, for example : separate two halves of the brain and putting them on different tasks, or turning off inhibition at will. Such events happen already, and are caused by damage to or sugical manipulation of the human brain. For a virtual conscious system ( or a heavily modified biological neural system ), we should be able to recreate these events reliably and reversibly.

    Furthermore, it may be possible to swap bits of different individuals. I am not sure if I mean individuals in the human sense or individuals as conscious software entities. A mature human consciousness would not take well to having its frontal lobe swapped out for that of another person, but it may be able to handle, with practice, swapping out sensory-motor modules. If you train modules from the start (from birth, or from first awakening for a software entity) to be able to be swapped, we could create a set of self assembling processing modules that could instantly adapt to new problems. However, If you try to use bits of "people" in this framework they might go insane rather quickly.

    What might be more feasible would be extremely high bandwidth communication between normal humans, using implantable electrode arrays. It would be like using a language more expressive than any spoken language. Depending on exactly how you link together separate individuals, you may get radically different results. For instance, wiring one man's motor cortex to another man's frontal lobe would seem like a very bad thing, since having your super-ego controlled by your friend's left toe is never a good idea. A person would probably be able to use a direct sensory-motor link though, since this would more closely resemble normal communication, like speech.

    It is also possible that strong, human level, artificial intelligence will first emerge from such a modular framework. I am not extremely familiar with the state of the art in software AI, but I believe that as the field progresses the training of a software solution for a task will become a significant part of the development process. I can imagine the day that someone takes a group of pre-trained software AIs and links them together under a common executive module, and accidentally creates something we might call conscious.

    Tue, Nov 18, 2008  Permanent link

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    This model more closely reproduces some of the results in this paper (Bressloff et al, 2000). However, some of the vision people I have talked with have said that there is no compelling evidence for the type of lateral connections assumed by the model in this paper.

    and just for fun,

    Fri, Aug 29, 2008  Permanent link

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    This is another toy (it is unclear if such things belong here). However, I thought the emergent complexity resulting from multiple interacting automata was worth showing.

    you will need the latest version of java to view this

    ( click and drag things )

    if you in an empty area a moth appears
    ......on a moth it turns into a light
    ......on a light it goes away
    ...drag a moth it follows
    ......a light the string appears
    ...tie the string to a moth the light will follow

    ( for some reason it stopped working ? )
    Sun, Aug 24, 2008  Permanent link

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    ( you probably need the latest version of Java to run this )

    Mon, Aug 18, 2008  Permanent link

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    This is the same algorithm as in the last post, but I played around with the color scheme and rendered a longer video.

    note : I would like to embed applets in these posts, however I don't have another web hosting service. Is it possible to host applets and other content besides text and images directly on spacecollective ?
    Sat, Aug 16, 2008  Permanent link

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    This video expands upon the model from my previous post. It now incorporates connections between orientation selective cells in the visual cortex. If I made this right ( and I'm not sure I did ), cobweb like lattices of lines should be stabilized. I couldn't generate a proper map of the orientation selectivity in visual cortex, so I just seeded random orientation selectivity. This is not physically realistic and probably changes the results. The equations are the same as in my previous post, but with a new term Eorient added into du/dt which accounts for input from other orientation selective cells.

    The degree of excitation from orientation selective connections at some point r is proportional to the sum over the activation of all cells in the neighborhood of r, where input is weighted as a Gaussian function of distance, and is strongest when both cells are tuned to the same orientation, and cell r lies along the direction of the preferred orientation of cell r' . U and Theta are fields ( represented at floating point matrices in the code ). The bold subscripts represent particular points in the filed. U represents the synaptic activation ( correlated to neuron firing rate ), and Theta represents the preferred stimulus orientation for a cell.
    Tue, Aug 12, 2008  Permanent link

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