Firing Thoughts: The binding problem might be a wrong assessment

According to  Vincent Di Lollo [2012], from Simon Fraser University, Canada, the feature-binding problem has defied solution because it is based on an erroneous premise: the notion of modular specificity and independence of neurons in the visual cortex. Such premise has been disconfirmed by advances in neuroanatomy and neurophysiology. Instead of coding for single features, neurons throughout the visual cortex are now known to code for multiple features. Therefore the validity of the binding question is arguable.

Di Lollo, Vincent. The feature-binding problem is an ill-posed problem. Trends in Cognitive Sciences June 2012, Vol. 16, No. 6

Constructive Neurophilosophy

Bennet and Hacker [2003] have discussed at large the regrettable state of the relationship between philosophy and neuroscience after Crick, Edelman and Zeki expressed, in different terms, their reticence to grant philosophy any competence in questions about conscience. While Edelman [2001,208] proposed the grounding of epistemology in neuroscience, Zeki [Bennet and Hacker, 2003, 398] went as far as to say that neuroscience will solve the problems of philosophy. Unfortunately, neuroscience has not been able to fulfill such an ambitious program, but its contributions to epistemology are certainly elucidating areas that for long remained obscure and contradictory.

A polemical situation like this is not new for the philosophy of science. The epistemological discussions raised by the Vienna Circle and their extensions and developments well through the XX century met similar objections, especially among physicists. But the problem has even deeper roots, and goes back to the distinction between philosophy and natural philosophy, or put in epistemological terms, the distinction between a philosophy based on metaphysical assumptions and which proceed exclusively by inference from those assumptions (pretty much like axiomatic mathematics, or like theology, or rational ethics), and an inductive philosophy based on experience and contrast of hypothesis by experiment. The monolithic concept of philosophy and philosophical argumentations used by Edelman and Zeki does not apply to philosophy more that it would apply to mathematics.

From a constructive point of view, mathematics and the rest of our epistemological thinking has its roots on biological grounds, a postulate that, although expressed by Kronecker [Bishop, 2012,2],  it took till the experimentations of Changeaux [Changeaux and Connes, 1995] and Dehaene [2001] to be widely accepted, and only among the different epistemological branches that spread from Brouwer’s intuitionism. If we understand by biology only neuroscience, Edelman’s thesis would be right, but it seems too narrow a definition, and highly imprecise, for not only neuroscience, but biology itself seems to be only understandable in a wider astrobiological conceptual frame. Such a frame has to include also the anthropological system, the emergent buffer introduced by human societies, so we find ourselves in a much more complex situation than the one devised by naïve neuroscience.

No doubt, neuroscience has very much to say in the psychological processes of the ego formation and the question of consciousness (and Edelman’s theory of global mappings is a proof of that), but its language lacks the expressive means to address it in a critically manner, i.e., neuroscience has not the means to investigate its own methodologies (ontoepistemological bases of the scientific method, protocols of valuation, etc.), and therefore, to give a meaningful theory of the processes of life. On the other hand, if neuroscience adopts other languages (like the language of epistemology) to express their theories and expand them in wider conceptual realms, such action would be philosophical, and the parochial distinctions of Crick, Edelman and Zeki would no longer have any meaning.

The epistemological reductionist seems to ignore the semantical implications of Tarski’s theorem, i.e., it ignores the notion of emergence of meaning. Theoretical terms do not have necesarilly the same meaning in theories which are sintactically reducible among them. To reduce one theory to another is to find a common symbolical representation for both of them, and that implies that both have the same capabilities of expression, and therefore that we are expressing basically the same thing in both theories, a realist ontology which ignores the historical dimension of our theories and which implies the belief in an underlying reality beyond human symbolization.

It does not have to be called philosophy, let us call it constructive neurophilosophy or systems biology, or any other name, but the epistemological work has to be done if we want to have meaningful argumentations. The process is double: axiomatic critique (of the principles and of the methods) and theoretical construction. The results and postulates of neuroscience are needed at both levels.

References

Bennet, M.R and Hacker, P.M.S. [2003]. Philosophical Foundations of Neuroscience. Blackwell Publishing. Malden, (MA-USA), Oxford (G.B) and Victoria (AUS).

Bishop, Errett. [2012] Foundations of Constructive Analysis. Ishi Press International. New York an Tokio.

Changeaux, J.P. and Connes, A. [1995] Conversations on Mind, Matter and Mathematics. Princeton University Press.

Dehaene, Stanislas.[2001]. The Number Sense: How the Mind Creates Mathematics. Oxford University Press. New York.

Edelman, Gerald M., and Tononi, Giulio. [2001]. Consciousness. Penguin Books. London et alliae.

Glia in Neuropathic Pain Research

In the last decade, the new understanding of the role played by neural plasticity and glial cells[1] over central and peripheral sensitization in chronic pain conditions has prompted a huge wave of research. Glia has been found to be crucial in the maintenance of neuronal homeostasis in the central nervous system.[2] Up to date, numerous studies have shown the critical role of glia in neuropathic and inflammatory pain due to glia’s interrelationship with neurons. As Ji R.R, Berta T., and Nedergaard M. suggest in their review article Glia and pain: is chronic pain a gliopathy? published in PAIN in 2013, glia can communicate with neurons by “listening” and “talking” to them. Thus, “nerve injury-induced chronic pain is associated not only with neuropathy but with gliopathy.”[3] It is increasingly being accepted that chronic pain can manifest not only by neural plasticity but by dysfunction of glial cells.

This new understanding can lead to non-symptomatic therapy intervention for “gliopathy,” however, as the article affirms, it is still not clear what type of drugs could be designed because it is difficult to target only glial cells without affecting neurons, and to eliminate glial cells with glia-selective toxins could cause adverse effects due to their supportive and protective roles. Theoretically, as the authors explain, it should be more effective for pain relief to target both neurons and glia; recent studies have shown that lipid mediators not only inhibit glial activation and inflammation but also TRP (Transient Receptor Potential) channels and reverse synaptic plasticity in neurons. As they propose, these endogenous lipid mediators, given their potency and safety, could be developed for preventing and treating chronic pain, via targeting both neuronal and non-neuronal (immune and glial) mechanisms.

Another important factor in relation to glia is the influence that the immune system has in the modulation of chronic pain. Glia produces immune factors (specifically microglia) which are thought to play an important role in nociceptive transmission. Hence, to Mika et al, “pain may now be considered a neuro-immune disorder, since it is known that the activation of immune and immune-like glial cells in the dorsal root ganglia and spinal cord results in the release of both pro- and anti-inflammatory cytokines, as well as algesic and analgesic mediators.”[4] Following this notion, they propose several pathways as new treatments for neuropathic pain. Firstly, they explain that it could be directed towards drugs that seek targets such as anti-inflammatory factors. Secondly, a novel alternative suggested is a pharmacological attenuation of glial and immune cell activation. Thirdly, they think that other way could be to decrease pro-nociceptive agents such as transcription factor synthesis, kinase synthesis and protease activation. Lastly they suggest that, since it is known that opioid-induced glial activation opposes opioid analgesia, some glial inhibitors, which are safe and clinically well tolerated, could be used as potential co-analgesic agents for opioid treatment of neuropathic pain.

As it can be seen form these proposals and the evidence on glia’s role in chronic pain, the stimulation and optimization of endogenous analgesics and anti-inflammatory factors seems to be a challenging although promising pathway for improving neuropathic conditions. Many of the studies that are currently focusing on endogenous and non-endogenous opioids and cannabinoids as well as lipid mediators for the treatment of chronic pain, will benefit from the research on glial cells addressed here. The way is open for a new era in the understanding and intervention of chronic pain that may move away from the solely symptomatic approach towards a more decisive and effective treatment of pain as a disease. Regardless of the original trigger agent, it has become widely accepted that pain can become a condition which outlives its original cause, and from being physiologically nociceptive can acquire a neuropathic quality. Whether it may be considered a gliopathy, a neuro-immune disorder, or some other, it is clear that due to the unusual characteristics of neuropathic pain, it demands different methods for management, whether pharmacological or non-pharmacological. Pain needs to be addressed for itself, and the alternatives proposed by the authors of the articles reviewed here are a further step in reversing the unsatisfactory results of its management.

The following video is a TED talk given by Elliot Krane called: The mystery of chronic pain, which I think captures the spirit of this new frontier in the neuroscience of pain.

TED2011 · 8:14 · Filmed Mar 2011

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[1] From the Central Nervous System (CNS): microglia, astrocytes, and oligodendrocytes; and from the Peripheral Nervous System (PNS): satellite glial cells in the dorsal root ganglia and trigeminal ganglia, and Schwann cells in peripheral nerves.

[2] Cf. Joanna Mika, Magdalena Zychowska, Katarzyna Popiolek-Barczyk, Ewelina Rojewska, Barbara Przewlocka (2013). Importance of glial activation in neuropathic pain. European Journal of Pharmacology 716. p.p.106–119.

[3] Ru-Rong Ji, Temugin Berta, Maiken Nedergaard (2013). Glia and pain: Is chronic pain a gliopathy?  PAIN 154 p.p.S10–S28.

[4] Ibid. Mika et al. Ed.Cit. p.106.