ABSTRACTÂ
Despite great progress in neuroscience, there are still fundamental unanswered questions about the brain, including the origin of subjective experience and consciousness. Some answers might rely on new physical mechanisms. Given that biophotons have been discovered in the brain, it is interesting to explore if neurons use photonic communication in addition to the well-studied electro-chemical signals. Such photonic communication in the brain would require waveguides. Here we review recent work [S. Kumar, K. Boone, J. Tuszynski, P. Barclay, and C. Simon, Scientific Reports 6, 36508 (2016)] suggesting that myelinated axons could serve as photonic waveguides. The light transmission in the myelinated axon was modeled, taking into account its realistic imperfections, and experiments were proposed both in vivo and in vitro to test this hypothesis. Potential implications for quantum biology are discussed.
INTRODUCTIONÂ
Over the past decades a substantial number of facts has been discovered in the field of brain research. However, the fundamental question of how neurons, or more specifically all particles involved in the biological processes in the brain, contribute to mental abilities such as consciousness is still unanswered. The true explanation to this question might rely on physical processes other than those that have been discovered so far. One interesting candidate to focus on is biophotons, which might serve as supplementary information carriers in the brain in addition to the well established electro-chemical signals. Biophotons â which are photons ranging from near-IR to near-UV frequency and emitted without any enhancement or excitationâ have been observed in many organisms such as bacteria (1), fungi (2), germinating seeds (3), plants (4), animal tissue 1 arXiv:1708.08887v1 [physics.bio-ph] 23 Aug 2017 Are there optical communication channels in the brain? cultures (5), and different parts of the human body (6â9), including the brain (10â15). These biophotons are produced by the decay of electronically excited species which are created chemically during oxidative metabolic processes (16, 17) and can contribute to communication between cells (18). Moreover, several experimental studies show the effects of light on neuronsâ and, generally, the brainâs function (19â21). The existence of biophotons and their possible effects on the the brain along with the fact that photons are convenient carriers of information raises the question whether there could be optical communication in the brain. For the sources and detectors of the optical communication process in the brain, mitochondrial respiration (22, 23) or lipid oxidation (24), and centrosomes (25) or chromophores in the mitochondria (26) have been proposed, respectively. It has also been observed that opsins, photoreceptor protein molecules, exist in the brains of birds (27, 28), mammals (29â32), and more general vertebrates (33) and even in other parts of their bodies (34, 35) as well. Another essential element for this optical communication, which is not well established yet, is the existence of physical links to connect all of these spatially separated agents in a selective way. In the dense and (seemingly) disordered environment of the brain, waveguide channels for traveling photons would be the only viable way to achieve the targeted optical communication processes. Mitochondria and microtubules in neurons have been introduced as the candidates for such waveguides (36â39). However, they are not suitable in reality due to their small and inhomogeneous structure for light guidance over proper distances in the brain. Ref. (40) proposed myelinated axons as potential biophoton waveguides in the brain. The proposal is supported by a theoretical model and numerical results taking into account real imperfections. Myelin sheath (formed in the central nervous system by a kind of glia cell called oligodendrocyte) is a lamellar structure surrounding the axon and has a higher refractive index (41) than both the inside of the axon and the interstitial fluid outside (see Fig. 1a) which let the myelin sheath to guide the light inside itself for optical communications. This compact sheath also increases the propagation speed of an action potential (via saltatory conduction) based on its insulating property (42). There has been a few indirect experimental evidence for light conduction by axons (12, 43, 44). Another related and interesting experiment has shown that a certain type of glia cells, known as Muller cells, ¨ guide light in mammalian eyes (45, 46). Ref. (40) also proposed experiments to test the existence of the optical waveguides in the brain. One interesting property of optical communication channels is that they can also transmit quantum information. Quantum effects in biological systems are being studied in different areas such as photosynthesis (47, 48), avian magnetoreception (49, 50), and olfaction (51, 52). There is an increasing number of conjectures about the role of quintessential quantum features such as superposition and entanglement (53) in the brain (15, 38, 54â56). The greatest challenge when considering quantum effects in the brain or any biological system in general is environmentally induced decoherence (57), which leads to the suppression of these quantum phenomena. However, some biological processes can be fast and may show quantum features before they are destroyed by the environment. Moreover, nuclear spins can have coherence times of tens of milliseconds in the brain (58, 59). A recent proposal on âquantum cognitionâ suggests even longer coherence times of nuclear spins (56), but relies on quantum information transmission via molecule transport, which is very slow. In contrast, photons are the fastest and most robust carriers for quantum information over long distances, which is why currently man-made quantum networks rely on optical communication channels (typically optical fibers) between spins (60, 61).
ResultsÂ
To show that myelinated axons could serve as the waveguides for traveling biophotons in the brain, Ref. (40) solved the three dimensional electromagnetic field equations numerically in different conditions, using Lumericalâs software packages FDTD (Finite Difference Time Domain) Solutions and MODE Solutions. These software packages solve Maxwellâs equations numerically, allowing the optical properties of dielectric structures defined over a mesh with subwavelength resolution to be simulated. The refractive indices of the fluid outside of the axon, the axon, and the myelin sheath were taken close to 1.34, 1.38 and 1.44 respectively (see Fig. 1a), which are consistent with their typical values (41, 62, 63). These indexes let the myelin sheath guide the light inside itself. The ratio of the radius of the axon, r to the outer radius of the myelin sheath r 0 (g-ratio) is taken equal to 0.6 for the most of the simulations, close to the experimental values (64). In reality, the radius of the myelinated axons in the brain changes from 0.2 microns to close to 10 microns (65). For the purpose of guiding light inside the myelin sheath, Ref. (40) considered the wavelength of the observed biophotons in the brain which is from 200 nm to 1300 nm. Since several proteins in the environment of the axons strongly absorb at wavelengths close to 300nm, a wavelength range of the transmitted light from the shortest permissible wavelength, Îťmin = 400nm, to the longest one, Îťmax, was chosen to avoid the absorption and confine the light well in the myelin sheath. Îťmax is chosen to the upper bound of the observed biophoton wavelength (1300 nm) or the thickness of the myelin sheath (denoted by d), whichever is smaller. Besides Îťmin and Îťmax, an intermediate wavelength was considered, denoted by Îťint , corresponding to the central permissible frequency (mid-frequency of the permissible frequency range) in the simulations. In the following section we discuss the guided modes in the myelinated axons and their transmissions in nodal and paranodal regions and even in the presence of the imperfections such as bends, varying cross-sections, and non-circular cross-sections.
Optical transmission in myelinated axonsÂ
Within the neuron, one can identify numerous intra-cellular structures that can function as potential scatterers, i.e. sources of waveguide loss. They are located both inside the axon and outside of the axon. Intra-cellular structures include cell organelles, for example, mitochondria, the endoplasmic reticulum, lipid vesicles, as well as the many filaments of the cytoskeleton, namely microtubules, microfilaments and neurofilaments. Extra-cellular structures include microglia, and astrocytes. However, the electromagnetic modes which are spatially confined within the myelin sheath, should not be affected by the presence of these structures. These biophoton modes considered here would be able to propagate in a biological waveguide provided its dimension is close to or larger than the wavelength of the light. Fig. 1b shows the numerically calculated magnitude of the electric field of a cylindrically symmetric eigenmode of an axon with radius r = 3Âľm and myelin sheath radius r 0 = 5Âľm for the wavelength 0.612Âľm. This electric field is azimuthally polarized as depicted is Fig. 1c and it is similar to the TE01 mode of a conventional fiber (66) which has higher refractive index of the core than that of the cladding. It is important to note that azimuthal polarization would prevent modal dispersion in the birefringent myelin sheath. Importantly, its optical axes are oriented radially (67). It can be readily established that there are hundreds of potential guided modes allowed to exist given the thickness of myelin sheath. Consequently, biophotons that could be generated by a source in the axons (e.g. mitochondria or recombination of reactive oxygen species) could readily interact with these modes as determined by mode-specific coupling coefficients. While we lack detailed knowledge of the particulars for these interactions, for the sake of simplicity and ease of illustration we select a single mode and examine its transmission. It is interesting to analyze transmission in the presence of optical imperfections such as discontinuities, bends and varying cross-sectional diameters. In this connection, we simulated short axonal segments due to computational limitations and extrapolated the results for the full length of an axon.
Transmission in nodal and paranodal regionsÂ
A myelinated axon has periodically unmyelinated segments, called Nodes of Ranvier, which are approximatly 1Âľm long (68) (while the whole axon length varies from 1 mm to the order of a meter). Here, we discuss the transmission in the Ranvier nodes and at the edges of the nodes, the paranodes. The configuration of myelin sheath is special in the paranodal regions (see Fig. 2a). There are many layers making up the compact myelin sheath and at the edge of each node, almost all of the layers are in contact with the core (bared axon) with a small pocket of cytoplasm. Thatâs because each layer moving from the innermost outward is longer than the one below. However, for thick myelin sheaths, many cytoplasmic pockets cannot reach the surface of the bare axon, but end on inner layers. Thus, the length of paranodal regions is dependent on the thickness of the myelin sheath. We call the ratio of the length of paranode, lparanode, to the thickness of the myelin sheat, d, p-ratio and take its value close to 5 in our simulations based on the realistic values (69). Fig. 2a displays the model of Ref. (40) for two adjacent paranodal regions with the node in between, and Fig. 2b shows the magnitude of the electric field profile in the longitudinal direction (along the length of the axon), EFPL, as a cylindrically symmetric input mode crosses this region. Fig. 2c shows the power transmission in the guided modes as a function of p-ratio for three wavelengths, 0.40 Âľm, 0.61 Âľm, and 1.30 Âľm. For the transmission, there are two main losses: divergence or scattering of the light beam. Shorter wavelengths scatter more but diverge less. Thus, in Fig. 2c, for small p-ratios, shorter wavelengths have higher transmission and as the effect of divergence is dominant in this region and the shorter wavelengths diverge less. However, for the large p-ratios, the effect of scattering is dominant and since the higher wavelengths scatter less, and have a higher transmission. Fig. 2dâf compares the transmission percentage for different axon radii, wavelengths, and pâratios. Although in Fig. 2d, the behavior of the transmission as a fuction of axon radius is independent of pâratios for the longest permissible wavelength, it can be concluded that for the most loosely confined modes (Îťmax) transmission increases in thicker axons. Itâs also possible that for long wavelengths, a fraction of the light diverging into the axon comes back into the myelin sheath at the end of the paranodal region and not all the light that diverges is lost. This can be an explanation for not well-defined dependency of the transmission on the paranodal lengths (see Fig. 2d). In, Fig. 2e, and Fig. 2f, for p-ratio = 2.5, based on our intuition from Fig. 2c, the divergence is dominant. Here, the thickness of the axon plays a role in the transmission such that the thicker the axon the divergence is less and the light is transmitted more. However, for larger pâratios, the scattering is dominant and the light scatters more in thick axons. To summarize, for small pâratios (âź2.5), the well confined modes (shorter wavelengths) transmit better while for large pâratios (âź5 or greater), the loosely confined ones (longer wavelengths) transmit better. Thicker axons yield higher transmission for all wavelengths with small pâratios while itâs inverse only for the shorter wavelengths with large pâratios. The transmission after several paranodal regions can be roughly estimated by following the intuition of exponentiating the transmission through one (see Supplementary Information of Ref (40))...
DiscussionÂ
In this review of Ref. (40) we have discussed how light conduction in a myelinated axon is feasible even in the presence of realistic imperfections in the neuron. We have also described future experiments that could validate or falsify this model of biophoton transmission (40). It is also worth addressing a few related questions. It is of interest to identify possible interaction mechanisms between biophotons and nuclear spins within the framework of quantum communication. Spin chemistry research (87) determined effects whereby electron and nuclear spins affect chemical reactions. These effects can also involve photons. In particular, a class of cryptochrome proteins can be photo-activated resulting in the production of a pair of radicals per event, with correlated electronic spins. This effect has been hypothesized to explain bird magnetoreception (49). It has been recently shown by theoretical considerations that interactions between electron and nuclear spins in cryptochromes are of critical importance to the elucidation of the precision of magnetoreception effects (50). Importantly for this topic, cryptochrome complexes are found in the eyes of mammals and they are also magnetosensitive at the molecular level (88). Therefore, if similar proteins can be found in the inner regions of the human brain, this could provide the required interface between biophotons and nuclear spins. However, for individual quantum communication links to form a larger quantum network with an associated entanglement process involving many distant spins, the nuclear spins interfacing with different axons must interact coherently. This, most likely, requires close enough contact between the interacting spins. The involvement of synaptic junctions between individual axons may provide such a proximity mechanism. We should also address the question of the potential relevance of optical communication between neurons with respect to consciousness and the binding problem. A specific anatomical question that arises is whether brain regions implicated in consciousness (89) (e.g. claustrum (90, 91), the thalamus, hypothalamus and amygdala (92), or the posterior cerebral cortex (89)) have myelinated axons with sufficient diameter to allow light transmission. A major role of the myelin sheath as an optical waveguide could provide a better understanding of the causes of the various diseases associated with it (e.g. multiple sclerosis (93)) and hence lead to a design and implementation of novel therapies for these pathologies. Let us note that, following Ref. (40), we have focused our discussion here on guidance by myelinated axons. However, light guidance by unmyelinated axons is also a possibility, as discussed in more detail in the supplementary information of Ref. (40). Finally, with the advantages optical communication provides in terms of precision and speed, it is indeed a wonder why biological evolution would not fully exploit this modality. On the other hand, if optical communication involving axons is harnessed by the brain, this would reveal a remarkable, hitherto unknown new aspect of the brains functioning, with potential impacts on unraveling fundamental issues of neuroscience.
Source:Â https://arxiv.org/pdf/1708.08887.pdf
