quantum aspects of neuroscience

Recently thought to cancel themselves out in the brain, quantum forces likely play a role in neurophysiology & biology. As neuro & cognitive sciences, classical and contemporary physics, art and philosophy merge, without hierarchy, fundamental truths regarding who and how are begin to reveal themselves

Quantum mechanics, not classical mechanics, rules the roost at (this) sensory outpost of the brain [the eye/its light sensing protein, rhodopsin]”– Werner Loewenstein

work & theories of Jedlicka, Markram, Lowenstein, Salari, Summhammer, Bernroider and others

sensory receptors

Sensory light, olfactory & magneto receptors

• Coherent quantum waves in the rhodopsin molecule were revealed using high-resolution spectroscopic and nuclear-magnetic resonance techniques (Wang et al., 1994; Loewenstein)

• Electron tunneling has been suggested to play an important role in the detection of odorants by olfactory receptors (Huelga and Plenio, 2013)

• Long-lived quantum entanglements in retinal cryptochromes seem to support the sensitivity of a bird’s eye to magnetic fields (avian magnetoreception) (Arndt et al., 2009; Ball, 2011; Huelga and Plenio, 2013)

• Quantum mechanical coherences in cryptochrome model simulations can account for the precision of the avian magnetic compass (Hiscock et al., 2016)

• Quantum tunneling has been observed in biomolecules, such as enzymes (Klinman and Kohen, 2013) and motor proteins (Hunter, 2006)

ion channel

Ion channels – ion selectivity & flow

How ion channels, proteins that span a cell’s membrane, selectively allow one type of ion (potassium, sodium, calcium) to very quickly pass through has long puzzled investigators. Classical thermodynamics often only approximated experimentally observed transition rates of ions through channel proteins, and has not fully explained ion channel selectivity

• Controversy – quantum effects in ion channel selectivity and ion translocation

  • In remarkably elegant calculations appearing in Nature, Salari, Naeij & Shafiee(2017) refute the role of quantum decoherence on ions’ behavior inside the KcsA ion channel’s selectivity filter. They report that the decoherence time inside the filter is about 100 ps, at least a hundred times shorter than the observed10–20 ns translocation time in the filter, making interference unlikely. They posit that molecular attractive forces within the selectivity filter (organic moieties/structure) overwhelm the quantum phenomena related to ions in movement

    • however, they also argue that, immediately outside of the channel, proximate water molecules may alter the coherence length of ions, and that water/ion (quantum-type) interference may occur immediately outside the channel

  • The following year, Summhammer, Sulyok and Bernroider(2018)(8) presented calculations (QM/MD) like those Salari calls for – comparing classical and quantum mechanical calculations of K+ ion motion (KcsA channel/its selectivity filter):

    • “It seems possible that initial, short (1ps), coherent ion transition states precede subsequent decoherence and an associated quantum-to-classical transition for permeating ions “ (8)

      It is found that short coherences are not just beneficial, but also necessary to explain the fast-directed permeation of ions through the potential barriers of the filter (8)

      Certain aspects of quantum dynamics and non-local effects appear to be indispensable to resolve the discrepancy between….classical thermodynamics, and experimentally observed transition rates of ions through channel proteins” (8)

    • They believe “that inserting quantum interference terms into classical [calculated] versions of action potential (AP) initiation reproduces the fast onset characteristic of experimental cortical neuron AP recordings”

    • They also believe they have “demonstrated evidence for different quantum oscillatory effects within the filter’s atomic environment, which discriminate intrinsic (e.g.,K+) from extrinsic (e.g.,Na+)” (8)

      That is, the quantum behavior of the (KcsA) ion channel selectivity filter (moiety) itself may prove to be part of the mechanism of specific ion selectivity

I’m in no position to judge the merits of these calculations, but, oh boy!, do I enjoy the handwaving. Ions channels were my first love…

neural networks

electric fields

Electric fields at molecular/ion channel, cellular and tissue levels

• Quantum events, e.g., at the level of ion channels, might affect and/or be affected by extracellular electric fields, which are generated at the level of neurons and their networks Jedlicka (4)

• Extracellular fields are able to influence membrane potential of neurons and their spiking activity by so called ephaptic coupling (Fröhlich and McCormick, 2010; Anastassiou et al., 2011; Anastassiou and Koch, 2015) (4)

  • Ephaptic coupling is a form inter-neuronal communication distinct from the direct communication systems of electrical and chemical synapses. Ephaptic coupling can influence the synchronization and timing of action potential firing between/among neurons by either:

    • intercellular ion exchange between adjacent neurons (gap junctions)

    • induction: local electric field(s) effect on a coupled neuron (wikipedia)

• “There is evidence for a causal loop between brain’s endogenous electrical fields and neuronal firing mediated by voltage-gated ion channels. Electrical fields may guide and synchronize firing of many neurons and thus affect cognition and behavior. Thus it is possible that…electrical fields are coupled to the level of quantum coherent events in many neurons, potentially affecting behaviorally relevant synchrony of neural firing (Al-Khalili and McFadden, 2014)” Jedlicka (4)

(Its hard not think of the alpha wave indiuction seen on EEGs master transcendtantl meditation practictionser

• Compared to eyes-closed rest, TM practice led to higher alpha1 frontal log-power, and lower beta1 and gamma frontal and parietal log-power; higher frontal and parietal alpha1 interhemispheric coherence and higher frontal and frontal-central beta2 intrahemispheric coherence. (Travis et al 2010))

stochasticity, signal/noise

Neural networks emerge through stochasticity/signal/noise

Do the classical forces at work in the “noisy, wet, warm” environmental conditions found in vivo overwhelm possible quantum influences at the atomic/molecular levels of neurons?

• “contrary to the long-held view, under some conditions, the strong coupling to the noisy and warm environment is able to promote rather than hinder long-lasting quantum coherence in biological systems” (Plenio and Huelga, 2008; Huelga and Plenio, 2013) Jedlicka (4)

• “Physicists thought the bustle of living cells would blot out quantum phenomena. Now they find that cells can nurture these phenomena—and exploit them” (Vedral, 2011) Jedlicka (4)

Blue Brain Project Founder and Director, Prof. Henry Markram:

• The thalamus pulls apart signal to noise

  “Thalamocortical stimuli can prompt reliable spike times with millisecond precision amid noise and chaos,” … “Surprisingly, we were able to demonstrate that this effect relies on the cortical neurons working as a team. Our model thus shows that noise and chaos in networks of cortical neurons are compatible with reliable spiking, allowing the brain to find order. This finding suggests that the highly fluctuating activity of cortical neurons in a live animal is reflecting order, not noise and chaos,” Markram (Markram & Muller, Nature Communications 2019)

Stochasticity in neurophysiology is postulated to scale up (from ion channels)

• “There ere are many stochastic neuronal mechanisms, which may be driven by quantum events. Although it is true that ‘the main sources of neural noise are forces that can be characterized as thermal and chaotic rather than quantum in nature’ (Sompolinsky, 2005), quantum physics is expected to shape at least some stochastic events in the brain, such as the opening of ion channels (Vaziri and Plenio, 2010). In this way microscopic quantum events might affect electrical signals in neurons, as proposed by Paul Glimcher:

  • “[T]hese data suggest that membrane voltage is the product of interactions at the atomic level, many of which are governed by quantum physics and thus are truly indeterminate events. Because of the tiny scale at which these processes operate, interactions between action potentials and transmitter release as well as interactions between transmitter molecules and post-synaptic receptors may be, and indeed seem likely to be, fundamentally indeterminate” (Glimcher, 2005) Jedlicka (4)

• Cognition

  • “Biological evolution is able to take advantage of non-trivial quantum events at the microscopic level….and even at larger-scale levels [by non-linear amplification…]…is not dependent on the plausibility or validity of quantum consciousness proposals” Jedlicka (4)

  • “Interestingly, a new quantum cognition model, based on entangled calcium phosphate molecules in neurons, has recently been suggested” (Fisher, 2015; Weingarten, 2016) Jedlicka (4)

connectomes, multidimensional neural topology, neuroplasticity

The brain as a complex non-linear system, capable of chaotic dynamics Markram/Blue Brain Project/EPFL (3); interview appearing in science alert/Signe Dean 2018

Connectomes are connected neural networks defined biologically (electron micrographs, patch clamping, MRI tractography etc) or computationally (mathematical models/simulations)

The Blue Brain Project/EPFL (Swizterland) identified multi-dimensional geometrical structures operating in up to11 dimensions using algebraic topology (mathematical, not spatial, dimensions) Markram (3)

• algebraic topology applies to both individual neurons and neural networks at all scales

• it considers the structural, directional and functional topology of the network

In simulations, they found two major things:

• Cliques of neurons form and bind together

• Cliques disintegrate – high-dimensional cavities form when high-dimensional (large) cliques bind together

Cliques are neuronal networks of directed structural/functional groups – nodes that are all-to-all connected

• the number of neurons in a clique determines its size, or rather, its dimension

• cliques orient around empty spaces (cavities) between them

• as or after cliques are activated/formed, the cavities around which they orientate increase, and cliques disintegrate

  • “Following a spatio-temporal stimulus to the network,…during correlated activity, active cliques form increasingly high-dimensional cavities (i.e., cavities formed by increasingly larger cliques). Moreover…while different spatio-temporal stimuli applied to the same circuit and the same stimulus applied to different circuits produced different activity patterns, they all exhibited the same general evolution, where functional relationships among increasingly higher-dimensional cliques form and then disintegrate.” Markram 2018 (3)

    • “Algebraic topology is like a telescope and microscope at the same time," "It can zoom into networks to find hidden structures, the trees in the forest, and see the empty spaces, the clearings, all at the same time." Kathryn Hess Blue Brain Project/EPFL, Dean 2018

    • "It is as if the brain reacts to a stimulus by building [and] then razing a tower of multi-dimensional blocks, starting with rods (1D), then planks (2D), then cubes (3D), and then more complex geometries with 4D, 5D, etc," Ran Levi Blue Brain Project/EPFL, Dean 2018

    • "The progression of activity through the brain resembles a multi-dimensional sandcastle that [materializes] out of the sand and then disintegrates."

They conclude this these structures may play a role in neuroplasticity & information coding for the CNS

• “Rewiring is readily triggered by stimuli as well as spontaneous activity (Le Be and Markram, 2006), which leads to a higher degree of organization (Chklovskii et al., 2004; Holtmaat and Svoboda, 2009) that is likely to increase the number of cliques” Markram 2018 (3)

• “We conjecture that a stimulus may be processed by binding neurons into cliques of increasingly higher dimension, as a specific class of cell assemblies, possibly to represent features of the stimulus … and by binding these cliques into cavities of increasing complexity, possibly to represent the associations between the features” Markram 2018 (3)

are the matter/voids reminiscent of the structure of space described in astrophysics?

does this allow us to consider multiple aspects/dimensions of thought at once: cogitate about ramifications, access the past, project a future, and add in emotional considerations?

summary

Summary from Jedlicka (4)

“The common view that minuscule fluctuations, including quantum events, cancel out in larger systems need not be true in highly non-linear systems like our brain. The nervous system can be seen as a nested hierarchy of non-linear complex networks of molecules, cells, microcircuits, and brain regions. In iterative hierarchies with non-linear dynamics (at the edge of chaos), small (even infinitesimal) fluctuations are not averaged out, but can be amplified. Quantum fluctuations on the lowest level of scale may influence the initial state of the next level of scale, while the higher levels shape the boundary conditions of the lower ones. This hierarchy of nested networks with many feedback loops exploits rather than cancels out the quantum effects as proposed by Jeffrey Satinover:

“[Q]quantum dynamics alters the final outcomes of computation at all levels – not by producing classically impossible solutions but by having a profound effect on which of many possible solutions are actually selected” (Satinover, 2001).” Jedlicka (4)

acupuncture &

signal propagation

Acupuncture, traditional asian medicine & neuroplasticity

Acupuncture, electricity, neuronal conduction and extracellular ionic flow

Much is known about the mechanism of acupuncture’s efficacy: neuroanatomic and neuroendricine/neurohumoral effects are in play, as well as gene expression, endocrine & immune modulation

Recently, elegant anatomic research demonstrated that nearly all somatic acupuncture points overlie peripheral nerve bifurcation points. Acupuncture needling these points:

• stimulates the peripheral nervous system – local current of injury

  • this in turn stimulates the CNS (fMRI, topology studies Harvard/Napadow Lab), most acupuncture studies

  • produces mild, controlled local foreign body/inflammatory responses, which have subsequent cellular & humoral effects

  • needling the pinna stimulates the ANS/vagus nerve (embryologic innervation (Nogier/Soliman 2008), and needling the scalp stimulates the CNS (Shunfa1971/1997, Hao 2011)

• produces non-neuronal local pico and microcurrents (from Helms 1995, chapters 2, 3)

  • acupuncture needles are composed of 2 different metals: one metal for a coiled handle and a different metal for the needle’s shaft

  • once inserted, the needle experiences a temperature differential between room air and the fascia/muscle

    • due to the bimetallic effect (bimetallic microbattery), an electrical potential is created along the temperature gradient (Seebeck effect)

      • when the handle is at room temperature, the needle tip is positive

      • the spiral handle acts as radiator, keeping a large surface area in contact with air, increasing the duration of the temperature gradient/electrical potential vs a simple shaft

      • spiraling the handle increases its electromagnetic effect on shaft’s metal

      • electron transfer from one metal to the next is affected by needle temperature variation (Peltier effect)

      • as the handle’s metal oxidizes over time, a “reservoir” or “electron exchange pool” is created between the two metals

  • due to the ionic composition of extracellular fluid, the positive needle tip starts to attract negative ions (electrolytes) until saturation

    • for a copper-handled, steel-shafted needle, saturation occurs after 15 minutes, which correlates neutral (non-manipulated) needling technique’s treatment duration

    • the potential difference across this type of needle results in a 2-3 microamp measured current

    • heating the air just above the skin or manually manipulating the needle (part of all acupuncture treatments) reverses the polarity of the needle–electrode

      • negative needle tip saturation (w/ positive ions) produces a 10-15 microamp current and occurs at 60-90 minutes, consistent with longer treatment durations for certain clinical conditions

  • thus, when 2 or more needles are placed in series, and one is manually manipulated or heated, and the other one is not, there is (lamellar) electron/ion flow via (wet) interstitial fluid

    • by in series, we mean along a classically defined acupuncture meridian. These are thought to correlate to certain fascial planes through which extracellular fluid (containing charged ions/electrolytes) flows relatively unimpeded. This correlates a certain extent to the lymphatic system

    • it is postulated that placing one non-manipulated needle in series with a manipulated one produces directed ionic flow within thees lamellae (cleavage planes between fascial tissues) – an electro-ionic model of current – with an “electron wave” directionality from negative–tipped to positive–tipped electrode

      • Helms does not consider that the electrolyte saturation ‘pool’ around the needle could actually render the needle tip functionally its opposite - so the flow could be from ‘negative saturation pool’ to ‘positive saturation pool’

      • in any case, electro-ionic flow that is non-neurologically mediated has been proposed as a mechanism of acupuncture’s effects

  • exogenous electrical stimulation can augment these microcurrents, (Helms 1995)

The proposed lamellar ion flow of interstitial ionic fluid would be far slower (and more lossy) than neuronal conduction. Could non-classical physics play a role in explaining messages propagated through non-neurologically–mediated acupuncture phenomena? Could the speeds with which needling effects occur represent a kind of binding problem, occurring more quickly than classical physics allows?

thalamic function

Thalamus for central homeostatic regulation and pain, acupuncture & bioelectronic medicine

According to Markram (3) (see above) “The thalamus pulls apart signal to noise”

“Thalamocortical stimuli can prompt reliable spike times with millisecond precision amid noise and chaos,” … “Surprisingly, we were able to demonstrate that this effect relies on the cortical neurons working as a team. Our model thus shows that noise and chaos in networks of cortical neurons are compatible with reliable spiking, allowing the brain to find order. This finding suggests that the highly fluctuating activity of cortical neurons in a live animal is reflecting order, not noise and chaos,” Markram (Markham & Muller, Nature Communications 2019)

Tusn Lee, proposed the Thalamic Neuron Theory (1977): he posited that the thalamus plays a role central in processing & physiologic homeostasis, and that acupuncture’s ability to modify painful stimuli and systemic conditions might be mediated through the thalamus.

The role of thalamus in processing pain from the periphery is well established

• CNS fMRI of nociceptive responses demostrate thalamic activation (Kuriowa 2005; Wallraven 2013)

• pain improvement correlates with excess and asynchronous CNS activity (order vs chaos) (Harvard/Napadow Lab) (see below)

  • Lee posits that the thalamus, as an evolutionarily earlier CNS structure, exerts humoral physiologic homeostasis via mechanisms similar to the hypothalamic/pituitary axis

CNS stimulation & autoantibody production

bioelectronic medicine

This concept may have implications for bioelectronic medicine, which seeks to map and then manipulate the CNS, ANS, and PNS for homeostatic regulation of various pathological conditions

Kristoffer Famm & Kevin Tracey (1) worked somewhat empirically at GlaxoSmithKline on the assumption that deep CNS (ANS/PNS) stimulation could resolve the pathologies of systemic diseases

• one of their most remarkable findings was that deep (central) vagus nerve stimulation down–regulated cytokine and autoantibody production in rheumatoid arthritis, resulting in clinical outcome improvements (1) (Nature Comment 2013)

• their plan for clinically delivering this therapy evolved into a plan to map the entire CNS and PNS. Subsequently, they plan to combine this information with implantable nanotechnology which will turn on/off various neurons and/or groups of neurons (in order to homeostatically re-regulate dysfunctional/pathological conditions)

Originally conceived as a public/private partnership, this project morphed into Galvani (private enterprise). As of this writing, I can no longer locate the detailed articles that reflected the various plans for moving forward on the mapping project. It is my understanding that this was biological, not simulated mapping, but I may be mistaken.

It is important to remember that we have ways of manipulating the vagus from the periphery, if we recall our developmental biology (the pinnae (Nogier/Soliman 2008). Simple bioelectronic devices with ear clips have been developed to address hypertension (related to autonomic instability) using this knowledge.

There has been 2000+ years of empiric research on stimulating human (and animal) peripheral nervous systems, which effectuate neurological and humoral improvements. It might be wise to review this collected knowledge to conceive of simpler means of CNS/PNS/ANS manipulation, upon which modern technology could possibly improve.

neuroplasticity

Acupuncture and neuroplasticity

Vitaly Napadow has made tremendous advances in topographically delineating neuroplastic changes related to pain and its improvement/absence. He has identified a somatosensory cortex subregion that clearly demonstrate somatotopic correlated with pain improvement – this reflect true re-wiring

• “As these primary somatosensory cortex subregions are distinctly targeted by local versus distal acupuncture electrostimulation, acupuncture at local versus distal sites may improve median nerve function at the wrist by somatotopically distinct neuroplasticity in the primary somatosensory cortex following therapy. Our study further suggests that improvements in primary somatosensory cortex somatotopy can predict long-term clinical outcomes for carpal tunnel syndrome.” (Napadow Brain 2017 and Brain 2014)

Since the thalamus relays painful stimuli to the somatosensory cortex, and the thalamus, according to Markram (3), “pulls apart signal to noise” – it is fun to consider that the thalamus may be playing a role in the somatorary cortex neuroplastic changes seen with pain, since it is the separator of signal/noise, and favors order

In traditional asian medicine, the term order could be correlated with the ideal therapeutic outcome we strive for balance

• also check out Napadow’s work on aberrant CNS firing patterns found in fibromyalgia who catastrophize/hear catastrophizing statements: pain signals in FM patients aberrantly loop into/through the affective portions of the CNS for processing, but do not in non-fibromyalgia patients (Journal of Pain 2017)