Understanding the mechanisms underlying general anesthesia would be a key step towards understanding consciousness. The process of xenon-induced general anesthesia has been shown to involve electron transfer, and the potency of xenon as a general anesthetic exhibits isotopic dependence. We propose that these observations can be explained by a mechanism in which the xenon nuclear spin influences the recombination dynamics of a naturally occurring radical pair of electrons. We develop a simple model inspired by the body of work on the radical-pair mechanism in cryptochrome in the context of avian magnetoreception, and we show that our model can reproduce the observed isotopic dependence of the general anesthetic potency of xenon in mice. Our results are consistent with the idea that radical pairs of electrons with entangled spins could be important for consciousness.

It is known that bipolar disorder and its lithium treatment involve the modulation of oxidative stress. Moreover, it has been observed that lithium’s effects are isotope-dependent. Based on these findings, here we propose that lithium exerts its effects by influencing the recombination dynamics of a naturally occurring radical pair involving oxygen. We develop a simple model inspired by the radical-pair mechanism in cryptochrome in the context of avian magnetoreception and xenon-induced anesthesia. Our model reproduces the observed isotopic dependence in the lithium treatment of hyperactivity in rats. It predicts a magnetic-field dependence of the effectiveness of lithium, which provides one potential experimental test of our hypothesis. Our findings show that Nature might harness quantum entanglement for the brain’s cognitive processes.

Hundreds of studies have found that weak magnetic fields can significantly influence various biological systems. However, the underlying mechanisms behind these phenomena remain elusive. Remarkably, the magnetic energies implicated in these effects are much smaller than thermal energies. Here, we review these observations, and we suggest an explanation based on the radical pair mechanism, which involves the quantum dynamics of the electron and nuclear spins of transient radical molecules. While the radical pair mechanism has been studied in detail in the context of avian magnetoreception, the studies reviewed here show that magnetosensitivity is widespread throughout biology. We review magnetic field effects on various physiological functions, discussing static, hypomagnetic and oscillating magnetic fields, as well as isotope effects. We then review the radical pair mechanism as a potential unifying model for the described magnetic field effects, and we discuss plausible candidate molecules for the radical pairs. We review recent studies proposing that the radical pair mechanism provides explanations for isotope effects in xenon anaesthesia and lithium treatment of hyperactivity, magnetic field effects on the circadian clock, and hypomagnetic field effects on neurogenesis and microtubule assembly. We conclude by discussing future lines of investigation in this exciting new area of quantum biology.

Drosophila’s circadian clock can be perturbed by magnetic fields, as well as by lithium administration. Cryptochromes are critical for the circadian clock. Further, the radical pairs in cryptochrome also can explain magnetoreception in animals. Based on a simple radical pair mechanism model of the animal magnetic compass, we show that both magnetic fields and lithium can influence the spin dynamics of the naturally occurring radical pairs and hence modulate the circadian clock’s rhythms. Using a simple chemical oscillator model for the circadian clock, we show that the spin dynamics influence a rate in the chemical oscillator model, which translates into a change in the circadian period. Our model can reproduce the results of two independent experiments, magnetic field and lithium effects on the circadian clock. Our model predicts that stronger magnetic fields would shorten the clock’s period. We also predict that lithium influences the clock in an isotope-dependent manner. Furthermore, our model also predicts that magnetic fields and hyperfine interactions modulate oxidative stress. The findings of this work suggest that the quantum nature of radical pairs might play roles in the brain, as another piece of evidence in addition to recent results on xenon anesthesia and lithium effects on hyperactivity.

It is known that bipolar disorder and its lithium treatment involve the modulation of oxidative stress. Moreover, it has been observed that lithium's effects are isotope-dependent. Based on these findings, here we propose that lithium exerts its effects by influencing the recombination dynamics of a naturally occurring radical pair involving oxygen. We develop a simple model inspired by the radical-pair mechanism in cryptochrome in the context of avian magnetoreception and xenon-induced anesthesia. Our model reproduces the observed isotopic dependence in the lithium treatment of hyperactivity in rats. It predicts a magnetic-field dependence of the effectiveness of lithium, which provides one potential experimental test of our hypothesis. Our findings show that Nature might harness quantum entanglement for the brain's cognitive processes.

Exposures to a hypomagnetic field can affect biological processes. Recently, it has been observed that hypomagnetic field exposure can adversely affect adult hippocampal neurogenesis and hippocampus-dependent cognition in mice. In the same study, the role of reactive oxygen species (ROS) in hypomagnetic field effects has been demonstrated. However, the mechanistic reasons behind this effect are not clear. This study proposes a radical pair mechanism based on a flavin-superoxide radical pair to explain the modulation of ROS production and the attenuation of adult hippocampal neurogenesis in a hypomagnetic field. The results of our calculations favor a singlet-born radical pair over a triplet-born radical pair. Our model predicts hypomagnetic field effects on the triplet/singlet yield of comparable strength as the effects observed in experimental studies on adult hippocampal neurogenesis. Our predictions are in qualitative agreement with experimental results on superoxide concentration and other observed ROS effects. We also predict the effects of applied magnetic fields and oxygen isotopic substitution on adult hippocampal neurogenesis.

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The exact mechanism behind general anesthesia remains an open question in neuroscience. It has been proposed that anesthetics selectively prevent consciousness and memory via acting on microtubules (MTs). It is known that the magnetic field modulates MT organization. A recent study shows that a radical pair model can explain the isotope effect in xenon-induced anesthesia and predicts magnetic field effects on anesthetic potency. Further, reactive oxygen species are also implicated in MT stability and anesthesia. Based on a simple radical pair mechanism model and a simple mathematical model of MT organization, we show that magnetic fields can modulate spin dynamics of naturally occurring radical pairs in MT. We propose that the spin dynamics influence a rate in the reaction cycle, which translates into a change in the MT density. We can reproduce magnetic field effects on the MT concentration that have been observed. Our model also predicts additional effects at slightly higher fields. Our model further predicts that the effect of zinc on the MT density exhibits isotopic dependence. The findings of this work make a connection between microtubule-based and radical pair-based quantum theories of consciousness.