Microtubule-stabilizer epothilone B delays anesthetic-induced unconsciousness in rats

May combine two claims.

In the separate tolerance group, the 2-d-interval slope analysis resulted in a negative slope estimate of −11.5 s/d, not significantly different from zero (p = 0.1).

“In this case the 2-d-interval slope analysis resulted in a negative slope estimate of −11.5 s/d. This estimate also failed to be significantly different from zero but was a stronger trend [p = 0.1d; n = 36 session-pairs (i.e., intervals) in four rats]”

May combine two claims.

The 2-d interval slope estimate of tolerance in the main experimental group was 2.5 s/d, not significantly different from zero (p = 0.7).

“Averaging these latency differences (in seconds) across rats and dividing by the 2 d interval resulted in a 2 d interval slope estimate of 2.5 s/d [based on n = 20 session-pairs (i.e., intervals) in eight rats]. Although this slope estimate was not significantly different from zero slope (t test; n = 20 intervals; p = 0.7c; no significant tolerance effect)”

May combine two claims.

LORR latency was very weakly correlated with rat weight and age; R2 = 0.058 for weight fit and 0.029 for age fit.

“LORR latency was very weakly correlated with rat weight and age.”

• Also stated in: § Neither rat weight nor age predicts LORR latency · plain

  “Linear fits to these data resulted in correlation coefficient squared (R2) of 0.058 for the weight fit and 0.029 for the age fit.”

May combine two claims.

In the tolerance group after the 41 d pause, linear fit estimated a slope of 4.5 s/d, with sessions every 2.65 d on average.

“After the pause, the linear fit resulted in a slope of 4.5 s/d in the context of sessions taking place every 2.65 d on average (Table 3).”

Classified as probably not a substantial claim.

These sessions were repeated with an average interval of 3.3 d between sessions.

“These sessions were repeated with an average interval of 3.3 d between sessions.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Mice repeatedly exposed to 4% isoflurane for 45 min at 3-4 d intervals for 3 weeks did not display significant differences in nest building behavior, home cage activity, body weight, or corticosterone concentrations compared with control mice.

“On the other hand, mice repeatedly exposed to 4% isoflurane for 45 min at 3–4 d intervals for 3 weeks did not display significant differences in terms of nest building behavior, home cage activity, body weight, or corticosterone concentrations when compared with control mice (Hohlbaum et al., 2017).”

• cites Hohlbaum et al., 2017 sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Studies of mice with mutant GABAA receptors concluded that GABAA receptors contribute to LORR under isoflurane.

“studies of mice with mutant GABAA receptors concluded that GABAA receptors contribute to LORR under isoflurane (the standard proxy for loss of consciousness).”

May combine two claims.

Multiple competing processes of facilitation and depression of sensitivity to isoflurane with different characteristic time scales are active simultaneously, so complex nonlinear interactions may result if intersession interval varies.

“The fact that our slope estimate based only on pairs of sessions separated by 2 d was negative suggests that multiple competing processes of facilitation and depression of sensitivity to isoflurane with different characteristic time scales are active simultaneously, so that if intersession interval varies, complex nonlinear interactions may result.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Isoflurane potentiates inhibitory GABA receptor activity in vitro.

“Isoflurane potentiates inhibitory GABA receptor activity in vitro (Hall et al., 1994; Garcia et al., 2010)”

• cites Hall et al., 1994Not checked yet

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• cites Garcia et al., 2010Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

In mice, continuous exposure to 0.15-0.3% isoflurane for 2-3 weeks was not found to produce a tolerance effect based on time to LORR.

“In mice, continuous exposure to 0.15–0.3% isoflurane for 2–3 weeks was not found to produce a tolerance effect based on time to LORR (Smith et al., 1979).”

• cites Smith et al., 1979Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Isoflurane directly activates sleep-promoting neurons of the hypothalamic ventrolateral preoptic nucleus, and this contributes to causing unconsciousness.

“Isoflurane directly activates sleep-promoting neurons of the hypothalamic ventrolateral preoptic nucleus, and this contributes to causing unconsciousness (Moore et al., 2012; Kottler et al., 2013; Jiang-Xie et al., 2019).”

• cites Moore et al., 2012Not checked yet

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• cites Kottler et al., 2013Not checked yet

  Not checked in the free run.

• cites Jiang-Xie et al., 2019Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Exposure to 1% isoflurane once a day for 10 consecutive days may produce a tolerance effect in mice as shown by longer LORR latencies.

“Another study found that exposure to 1% isoflurane given once a day for 10 consecutive days may produce a tolerance effect in mice as shown by longer LORR latencies (Chalon et al., 1983).”

• cites Chalon et al., 1983Not checked yet

  Not checked in the free run.

May combine two claims.

The tolerance effect estimated in the main experimental group from the control period was negative, indicating greater sensitivity after repeated sessions rather than growing insensitivity.

“The tolerance effect we estimated in the main experimental group, from the control period of our epoB experiment, was negative, indicating a greater sensitivity after repeated sessions rather than a growing insensitivity (aka tolerance).”

Probably not a substantial claim: may not pass S3 (load-bearing).

Anesthetics may act on a unitary site, via relatively nonspecific physical interactions such as London/van der Waals forces between induced dipoles.

“Together these results suggest that anesthetics may act on a unitary site, via relatively nonspecific physical interactions (such as London/van der Waals forces between induced dipoles).”

Probably not a substantial claim: may not pass S3 (load-bearing).

Older rats took significantly longer to emerge from isoflurane-induced unconsciousness than younger rats.

“This contrasts with a study which found that older rats took significantly longer to emerge from isoflurane-induced unconsciousness than younger rats (Chemali et al., 2015).”

• cites Chemali et al., 2015Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Cytoskeletal microtubules have been considered as a candidate target of anesthetic action for over 50 years.

“Cytoskeletal microtubules (MTs) have been considered as a candidate target of anesthetic action for over 50 years (Allison and Nunn, 1968; S. Hameroff, 1998).”

• cites Allison and Nunn, 1968Not checked yet

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• cites S. Hameroff, 1998 sourceNot checked yet

  Not checked in the free run.

Classified as probably not a substantial claim.

Only male rats were used to avoid potentially confounding interactions with estrous phase in females.

“We used only male rats to avoid potentially confounding interactions with estrous phase in females.”

Classified as probably not a substantial claim. May combine two claims.

MTs have been proposed to process information, encode memory, and mediate consciousness.

“MTs have also been proposed to process information, encode memory, and mediate consciousness (S. R. Hameroff et al., 1982; S. Hameroff and Penrose, 1996; S. Hameroff, 2022).”

• cites S. R. Hameroff et al., 1982Not checked yet

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• cites S. Hameroff and Penrose, 1996 sourceNot checked yet

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• cites S. Hameroff, 2022Not checked yet

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May combine two claims.

Injections were given after isoflurane induction to avoid stressing rats before LORR measurements, which preserved LORR latency data but introduced large variability into emergence measurements, preventing firm conclusions from those data.

“To avoid stressing the rats before taking LORR measurements, which would likely introduce large uncontrolled variability into the data, we gave injections after isoflurane induction. This preserved the integrity of the LORR latency data but unfortunately did introduce large variability into the emergence (latency to regaining of righting response) measurements, which prevented our drawing any firm”

Probably not a substantial claim: may not pass S3 (load-bearing).

The possibility that general anesthesia might be explained by unitary action of all (or most) anesthetics on one target protein is supported by the Meyer-Overton correlation and the additivity of potencies of different anesthetics.

“The possibility that general anesthesia might be explained by unitary action of all (or most) anesthetics on one target protein is supported by the Meyer–Overton correlation and the additivity of potencies of different anesthetics (Eger et al., 2008).”

• cites Eger et al., 2008Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Emerson et al. used MT-stabilizing agents epothilone D and discodermolide to directly implicate MTs as a functional target of general anesthetics in tadpoles.

“Another study used MT-stabilizing agents epothilone D and discodermolide to directly implicate MTs as a functional target of general anesthetics in tadpoles (Emerson et al., 2013).”

• cites Emerson et al., 2013Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Craddock et al.'s modeling suggests possible unitary action of anesthetics in MTs.

“This suggests possible unitary action of anesthetics in MTs.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

This could occur if isoflurane remained in the animal's system long enough to contribute to hypnosis in subsequent anesthesia sessions after relatively short intervals without isoflurane exposure.

“This could occur, for example, if isoflurane remained in the animal's system long enough to contribute to hypnosis in subsequent anesthesia sessions after relatively short intervals without isoflurane exposure.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Griffin et al. measured brain concentrations of epoB over time and found sustained levels of epoB in the brain through the 16 d period of their measurements.

“Those authors also measured brain concentrations of epoB over time and found sustained levels of epoB in the brain through the 16 d period of their measurements.”

• cites Griffin et al., 2023 sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Recipients of taxane chemotherapy had a significantly elevated blood pressure response to incision during breast cancer surgery and required significantly more opioid analgesic compared with patients who did not receive taxane chemotherapy.

“Recipients of taxane chemotherapy had a significantly elevated blood pressure response to incision during surgery for breast cancer and required significantly more opioid analgesic, as compared with patients who did not receive taxane chemotherapy (Linganna et al., 2015).”

• cites Linganna et al., 2015 sourceNot checked yet

  Not checked in the free run.

May combine two claims.

The interval between sessions in the post-epoB period was 2 d (SD 0), more frequent than in the pre-epoB sessions.

“the interval between sessions in the post-epoB period was 2 d (SD, 0; Table 3), which is more frequent than in the pre-epoB sessions”

Probably not a substantial claim: may not pass S3 (load-bearing).

Researchers taking LORR measurements and administering injections were blind to the injection and drug condition of the animal.

“Researchers taking the LORR latency measurements and administering injections were blind to the injection and drug condition of the animal.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The Meyer-Overton correlation is the finding that anesthetic potency of chemically diverse anesthetic molecules is directly correlated with their solubility in lipids akin to olive oil.

“The Meyer–Overton correlation refers to the venerable finding that the anesthetic potency of chemically diverse anesthetic molecules is directly correlated with their solubility in lipids akin to olive oil (S. R. Hameroff, 2018; Kelz and Mashour, 2019).”

• cites S. R. Hameroff, 2018 sourceNot checked yet

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• cites Kelz and Mashour, 2019Not checked yet

  Not checked in the free run.

Classified as probably not a substantial claim.

Epothilones are distinguished from older MT-stabilizing drugs by their better ability to penetrate the blood-brain barrier and affect the brain and spinal cord.

“Epothilones are distinguished from older MT-stabilizing drugs by their better ability to penetrate the blood–brain barrier and affect the brain and spinal cord.”

• cites Varidaki et al., 2018Not checked yet

  Not checked in the free run.

May combine two claims.

Griffin et al. (2023) compared intraperitoneal versus subcutaneous injections and found greater concentrations of the drug in the brain with subcutaneous injections.

“(Griffin et al., 2023) compared with the effectiveness of intraperitoneal versus subcutaneous injections and found greater concentrations of the drug in the brain with subcutaneous injections.”

• cites Griffin et al., 2023 sourceNot checked yet

  Not checked in the free run.

Classified as probably not a substantial claim. May combine two claims.

MTs were not ruled out and remain a candidate for a unitary site of anesthetic action.

“However, MTs (composed of tubulin subunits) were not ruled out and remain a candidate for a unitary site of anesthetic action.”

Classified as probably not a substantial claim. May combine two claims.

All researchers were trained to use the identical procedure for determining LORR latency, and at least two blind researchers were present for every experiment.

“All researchers were trained to use the identical procedure for determining LORR latency, and at least two researchers (both blind) were present for every experiment.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

There was no significant change in heart rate or anesthetic delivery during surgery in the taxane group compared with controls.

“there was no significant change in the heart rate or anesthetic delivery during surgery in the taxane group as compared with controls.”

• cites Linganna et al., 2015 sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

MTs are the major components of the cytoskeleton in all cells, and in neurons they have additional specialized roles in intracellular transport and neural plasticity.

“MTs are the major components of the cytoskeleton in all cells, and they also play an essential role in cell reproduction—and aberrant cell reproduction in cancer—but in neurons, they have additional specialized roles in intracellular transport and neural plasticity (Kapitein and Hoogenraad, 2015).”

• cites Kapitein and Hoogenraad, 2015Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

The epoB condition came after the control condition for every rat.

“even though the epoB condition came after the control condition for every rat”

Classified as probably not a substantial claim.

To eliminate any possibility of experimenter bias, epoB and vehicle injections were prepared by two researchers so that researchers taking LORR measurements could not know whether injections were epoB or vehicle.

“To eliminate any possibility of experimenter bias, epoB and vehicle injections were prepared for each anesthesia session for each rat by two of us (Y.H. and M.C.W.) so that researchers taking the LORR latency measurements could not know whether the injections were epoB or vehicle.”

Classified as probably not a substantial claim.

Singh et al. (2021a) showed that MT activities do regulate axonal firing, for example, overriding membrane potentials.

“Singh et al. (2021a) showed that MT activities do regulate axonal firing, for example, overriding membrane potentials.”

• cites Singh et al. (2021a)Not checked yet

  Not checked in the free run.

Classified as probably not a substantial claim.

The orchestrated objective reduction (Orch OR) theory proposes that anesthesia directly blocks quantum effects in MTs necessary for consciousness.

“The orchestrated objective reduction (Orch OR) theory proposes that anesthesia directly blocks quantum effects in MTs necessary for consciousness (S. Hameroff and Penrose, 2014).”

• cites S. Hameroff and Penrose, 2014Not checked yet

  Not checked in the free run.

May combine two claims.

Known side effects of epoB include tiredness/weakness and fatigue, but not hyperarousal, so epoB would not be expected to cause resistance to anesthesia through an off-target effect on arousal.

“Note that known side effects of epoB include tiredness/weakness and fatigue (Sessa et al., 2007), but not hyperarousal, so epoB would not be expected to cause resistance to anesthesia through an off-target effect on arousal.”

• cites Sessa et al., 2007Not checked yet

  Not checked in the free run.

May combine two claims.

The 2-d slope estimate in the separate tolerance group was negative like the overall slope of the pre-epoB data, and the 2-d slope used to estimate a 40 s tolerance effect was not significantly different from zero, making the 40 s estimate conservative.

“We emphasize that this is our most conservative estimate, given that our 2 d slope estimate in the separate tolerance group was negative like the overall slope of the pre-epoB data and that the 2 d slope we used to estimate a 40 s tolerance effect was not significantly different from zero (i.e., zero slope meaning no tolerance effect).”

Classified as probably not a substantial claim.

The precise molecular mechanisms by which volatile anesthetics reversibly abolish consciousness remain elusive.

“the precise molecular mechanisms by which these molecules reversibly abolish consciousness remain elusive (Eger et al., 2008; Hemmings et al., 2019; Kelz and Mashour, 2019; Mashour, 2024).”

• cites Eger et al., 2008Not checked yet

  Not checked in the free run.

• cites Hemmings et al., 2019Not checked yet

  Not checked in the free run.

• cites Kelz and Mashour, 2019Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Detailed quantum chemical modeling found that anesthetic potency was predicted by the modeled disruption or failure to disrupt high-frequency vibrations inside MT protein subunits, and the latter study found a Meyer-Overton correlation for all eight anesthetics studied.

“detailed quantum chemical modeling of anesthetic and nonanesthetic molecules binding to the tubulin dimers that make up MTs found that anesthetic potency was predicted by the modeled disruption or failure to disrupt high-frequency vibrations inside MT protein subunits (Craddock et al., 2015, 2017). The latter study found a Meyer–Overton correlation for all eight anesthetics studied.”

• cites Craddock et al., 2015, 2017Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Researchers did not know when LORR measurements would stop or whether additional doses of epoB would be provided after the first.

“Moreover, they did not know when we would stop taking LORR latency measurements or whether we would provide additional doses of epoB after the first.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Tegmark calculated MT decoherence would occur at 10−13 s, too fast for functional effects.

“Criticizing the Penrose–Hameroff Orch OR theory, Tegmark (Tegmark, 2000) calculated MT decoherence would occur at 10−13 s, too fast for functional effects.”

• cites Tegmark, 2000Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Tegmark erred, using a key term for superposition separation distance of tens of nanometers (10−8 m) rather than femtometers (10−15 m) as stipulated in Orch OR.

“However, Tegmark erred, using a key term for superposition separation distance of tens of nanometers (10−8 m) rather than femtometers (10−15 m) as stipulated in Orch OR.”

• cites Hagan et al., 2002Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S4 (based). May combine two claims.

These experimental results corroborate the plausibility of the MT-based quantum physical model of consciousness and the hypothesis that isoflurane could contribute to abolishing consciousness by interacting with an entangled state of MTs.

“These experimental results corroborate the plausibility of the MT-based quantum physical model of consciousness and the hypothesis that isoflurane could contribute to abolishing consciousness by interacting with an entangled state of MTs.”

Classified as probably not a substantial claim.

Another class of quantum model understands consciousness in terms of physical vibrational states of MTs in neurons.

“In contrast, another class of quantum model understands consciousness in terms of physical vibrational states of MTs in neurons (S. Hameroff and Penrose, 1996, 2014; Craddock et al., 2017; S. Hameroff, 2022).”

• cites S. Hameroff and Penrose, 1996 sourceNot checked yet

  Not checked in the free run.

• cites Craddock et al., 2017 sourceNot checked yet

  Not checked in the free run.

• cites S. Hameroff, 2022Not checked yet

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May combine two claims.

The Orch OR MT-based consciousness theory was part of the Templeton World Charity Foundation program in Accelerating Research in Consciousness and produced the only confirmatory evidence among theories tested.

“The Orch OR MT-based consciousness theory was part of the Templeton World Charity Foundation program in Accelerating Research in Consciousness and produced the only confirmatory evidence among theories tested.”

• cites S. Hameroff, 2021 sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Isoflurane's effect reducing synaptic transmission has been shown to proceed primarily via its effect on syntaxin 1A or via its effect inhibiting mitochondrial function.

“In different studies, isoflurane's effect reducing synaptic transmission has been shown to proceed primarily via its effect on syntaxin 1A (Herring et al., 2009) or via its effect inhibiting mitochondrial function (Zimin et al., 2018).”

• cites Herring et al., 2009Not checked yet

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• cites Zimin et al., 2018Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

These results support that the MT vibrational state and resultant electromagnetic field can interact systematically with the membrane voltage and that this coupling can traverse the physical gap between neurons.

“Additionally, these results support that the MT vibrational state and resultant electromagnetic field can interact systematically with the membrane voltage that we know is closely related to mental function and behavior and again that this coupling can traverse the physical gap between neurons.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Their results support the conjecture that MTs can couple across neurons.

“Their results support the conjecture of Babcock et al. that MTs can couple across neurons.”

• cites Babcock et al., 2024 sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Our results are potentially consistent with classical models of consciousness, but they represent a more stringent test of MT-based models because MT-based models specifically predict that directly disrupting the physical state of MTs should contribute to loss of consciousness.

“Our results are potentially consistent with classical models of consciousness, but they represent a more stringent test of these MT-based models, because while the classical models are agnostic about MTs as a functional anesthetic target, the MT-based models specifically predict that directly disrupting the physical state of MTs should contribute to loss of consciousness.”

• AssumptionRests on an assumption: Classical models of consciousness are agnostic about MTs as a functional anesthetic target.

Probably not a substantial claim: may not pass S3 (load-bearing).

The prediction of quantum coherence in MTs at high temperatures (room temperature) has now been experimentally verified.

“The prediction of quantum coherence in MTs at high temperatures (i.e., room temperature) has now been experimentally verified (Saxena et al., 2020; Babcock et al., 2024).”

• cites Saxena et al., 2020 sourceNot checked yet

  Not checked in the free run.

• cites Babcock et al., 2024 sourceNot checked yet

  Not checked in the free run.

Classified as probably not a substantial claim. May combine two claims.

Anesthetics dampen the quantum dipole oscillations and cause unconsciousness.

“Anesthetics dampen the quantum dipole oscillations and cause unconsciousness.”

Probably not a substantial claim: may not pass S3 (load-bearing).

In classical models, consciousness is understood in terms of functional connectivity or classical integrated information among neurons, cortical areas, or parts of the system.

“because consciousness in these models is understood in terms of functional connectivity (Dehaene et al., 1998; Sergent and Dehaene, 2004; Tsuchiya et al., 2015; Mashour et al., 2020) or classical integrated information (Tononi, 2008; Tononi et al., 2016; Albantakis et al., 2023) among neurons, cortical areas, or parts of the system.”

• cites Dehaene et al., 1998Not checked yet

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• cites Tononi, 2008Not checked yet

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• cites Albantakis et al., 2023Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S1 (asserted). May combine two claims.

In this quantum model, quantum dipole vibrations in MTs inside neurons mediate consciousness, modulate functional connectivity, and regulate neuronal firing.

“In this picture, quantum dipole vibrations in MTs inside neurons mediate consciousness, modulate functional connectivity, and regulate neuronal firing.”

Classified as probably not a substantial claim. May combine two claims.

The predictions were that MT quantum effects would be shown at ambient temperature and they would be inhibited by anesthesia.

“The predictions were that (1) MT quantum effects would be shown at ambient temperature and (2) they would be inhibited by anesthesia (S. Hameroff, 2021).”

• cites S. Hameroff, 2021 sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

In humans, anesthetic sensitivity generally increases with age, as indicated by a ~6% per decade decrease in the minimum alveolar concentration of volatile anesthetics needed to abolish movement in response to a noxious stimulus.

“In humans, anesthetic sensitivity generally increases with age, as indicated, for example, by the decrease in the minimum alveolar concentration of volatile anesthetics needed to abolish movement in response to a noxious stimulus, by ∼6% per decade (Kanonidou and Karystianou, 2007).”

• cites Kanonidou and Karystianou, 2007Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Detailed quantum chemical modeling studies support that anesthetic potency is predicted by the modeled disruption or failure to disrupt high-frequency vibrational states of MT proteins.

“As we noted above, detailed quantum chemical modeling studies support that anesthetic potency is predicted by the modeled disruption or failure to disrupt high-frequency vibrational states of MT proteins (Craddock et al., 2015, 2017).”

• cites Craddock et al., 2015 sourceNot checked yet

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• cites Craddock et al., 2017 sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Anirban Bandyopadhyay and colleagues explored resonant responses of MTs at frequencies varying over many orders of magnitude in bare MTs and in cultured neurons.

“Anirban Bandyopadhyay and colleagues explored resonant responses of MTs at frequencies varying over many orders of magnitude in “bare” MTs and in cultured neurons (Saxena et al., 2020; Singh et al., 2021a,b).”

• cites Saxena et al., 2020 sourceNot checked yet

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• cites Singh et al., 2021aNot checked yet

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• cites Singh et al., 2021bNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

For a quantum MT-based model of consciousness to be viable, the putative conscious MT physical state must be able to interact with the membrane potential of neurons, and the quantum interaction must be able to span multiple neurons to solve the perceptual binding problem.

“In order for a quantum MT-based model of consciousness to be viable, (1) the putative conscious MT physical state must be able to interact with the membrane potential of neurons, where we know perceptual information is encoded and through which our actions (i.e., muscle activations) must be implemented, and (2) the quantum interaction must be able to span multiple neurons if it is to solve the Per”

• AssumptionRests on an assumption: Perceptual information is encoded in the membrane potential of neurons, and actions are implemented through it.

Probably not a substantial claim: may not pass S3 (load-bearing).

Those authors cited theoretical work in support of the possibility that the physiological arrangement of MTs in axons could magnify the collective interaction to an extremely long range.

“Those authors cited theoretical work (Solano et al., 2017) in support of the “tantalizing possibility” that the physiological arrangement of MTs in axons could magnify the collective interaction “to an extremely long range.””

• cites Solano et al., 2017 sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Hagan et al. (2002) corrected Tegmark and calculated 10−5-10−4 s MT coherence time, potentially sufficient for Orch OR to influence neural processing.

“Hagan et al. (2002) corrected Tegmark and calculated 10−5–10−4 s MT coherence time, potentially sufficient for Orch OR to influence neural processing.”

• cites Hagan et al., 2002Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

That would represent additional support for the alternative hypothesis that binding to MTs interferes with the physical substrate of consciousness directly rather than by (or in addition to) indirect effects on neural membrane voltage and spiking activity.

“That would represent additional support for the alternative hypothesis about how binding to MTs contributes to isoflurane-induced unconsciousness—that is, the hypothesis that binding to MTs interferes with the physical substrate of consciousness directly rather than by (or in addition to) indirect effects on neural membrane voltage and spiking activity.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

In humans, the surgically required concentration of inhalable anesthetics increases with body mass index, but the increase is small.

“In humans, the surgically required concentration of inhalable anesthetics increases with body mass index, but the increase is small (Lemmens et al., 2008).”

• cites Lemmens et al., 2008Not checked yet

  Not checked in the free run.

Classified as probably not a substantial claim.

These quantum models predict that volatile anesthetics interfere directly with the vibrational state of MTs, which are understood as the immediate substrate of consciousness.

“That is, these models predict that volatile anesthetics interfere directly with the vibrational state of MTs which are understood as the immediate substrate of consciousness.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Tegmark's paper supported widespread skepticism that macroscopic or mesoscopic quantum effects could persist long enough at biological temperatures to be functionally relevant.

“Nevertheless, Tegmark's paper supported widespread skepticism that macroscopic or mesoscopic quantum effects could persist long enough at biological temperatures to be functionally relevant.”

• cites Tegmark, 2000Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

In the Chemali et al. study, younger rats were 6-8 months old and older rats were 24-26 months old.

“The younger rats in that study were 6–8 months old, and the older group was 24–26 months old.”

• cites Chemali et al., 2015Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Classical theories of consciousness do not at present predict specific molecular targets of anesthetics.

“These theories do not at present predict specific molecular targets of anesthetics.”

Probably not a substantial claim: may not pass S3 (load-bearing).

A recent report describes theoretical predictions and experimental confirmation of superradiance from MTs at room temperature that was enhanced as they were joined into larger structures.

“A recent report describes theoretical predictions and experimental confirmation of superradiance—a fundamentally quantum effect (Dicke, 1954)—from MTs at room temperature that was enhanced as they were joined into larger structures (Babcock et al., 2024).”

• cites Babcock et al., 2024 sourceNot checked yet

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• cites Dicke, 1954Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Hagan et al. (2002) noted other inappropriate assumptions in Tegmark's analysis.

“That paper also noted other inappropriate assumptions in Tegmark's analysis.”

• cites Hagan et al., 2002Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

They reported that electromagnetic waves transmitted to the MTs at MT resonant frequencies resulted in systematic modulation of the electric potential difference between two neighboring neurons.

“They reported that electromagnetic waves transmitted to the MTs (acting like antennas) at MT resonant frequencies resulted in systematic modulation of the electric potential difference between two neighboring neurons.”

• cites Saxena et al., 2020 sourceNot checked yet

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• cites Singh et al., 2021aNot checked yet

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• cites Singh et al., 2021bNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Recent MRI studies appear to offer support for the general hypothesis that the physical substrate of consciousness in the brain must be a nontrivial macroscopic quantum state.

“Recent MRI (i.e., nuclear magnetic resonance imaging) studies appear to offer support for the general hypothesis that the physical substrate of consciousness in the brain must be a nontrivial macroscopic quantum state (C. M. Kerskens and Pérez, 2022; Pérez et al., 2023).”

• cites C. M. Kerskens and Pérez, 2022 sourceNot checked yet

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• cites Pérez et al., 2023 sourceNot checked yet

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Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing). May combine two claims.

Their response reaffirms their entanglement claim and provides further clarification of their argument.

“Their response reaffirms their entanglement claim and provides further clarification of their argument (C. Kerskens and Pérez, 2023).”

• cites C. Kerskens and Pérez, 2023Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Their work is not the first experimental indication of functionally relevant coupling between nuclear spins and consciousness-related brain processes.

“However, their work is not the first experimental indication of functionally relevant coupling between nuclear spins and consciousness-related brain processes.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

Under the quantum MT picture, nuclear spin can affect anesthetic potency because anesthetics couple to electron clouds by quantum dipoles.

“Under the quantum MT picture, nuclear spin can affect anesthetic potency because anesthetics couple to electron clouds by quantum dipoles.”

Probably not a substantial claim: may not pass S3 (load-bearing).

They have also developed a noninvasive extension of EEG, called DDG, for measuring very high-frequency electromagnetic signals emitted from the scalps of awake humans.

“They have also developed a noninvasive extension of EEG, called DDG (“dodecanogram”), for measuring very high-frequency electromagnetic signals—some putatively originating from MT resonances internal to neurons—emitted from the scalps of awake humans (Singh et al., 2023, 2024).”

• cites Singh et al., 2023 sourceNot checked yet

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• cites Singh et al., 2024Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Anesthesia experiments in mice demonstrated that isotopes of xenon with nuclear spin were less effective than isotopes without nuclear spin and that this difference could not be accounted for by other physical properties such as polarizability.

“Anesthesia experiments in mice demonstrated that isotopes of xenon with nuclear spin were less effective than isotopes without nuclear spin and that this difference could not be accounted for by other physical properties of the isotopes such as polarizability (Li et al., 2018).”

• cites Li et al., 2018Not checked yet

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• AssumptionRests on an assumption: Nuclear spin in normal circumstances would not directly influence the chemical properties of the molecule or atom.

Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based).

These experimental results may corroborate the MRI study above claiming the conscious brain process can interact with entangled nuclear spins.

“These experimental results may corroborate the MRI study above claiming the conscious brain process can interact with entangled nuclear spins.”

Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

The unknown brain process that mediates entanglement is itself an entangled quantum state.

“This implies the unknown brain process that mediates the entanglement is itself an entangled quantum state.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Anesthetic experiments in fruit flies show that anesthetics perturb electronic spin states and that these spin responses are altered in anesthetic-resistant mutants.

“Similarly, anesthetic experiments in fruit flies show that anesthetics perturb electronic spin states and that these spin responses are altered in anesthetic-resistant mutants (Turin et al., 2014), again supporting that a consciousness-related brain process can couple to spin degrees of freedom.”

• cites Turin et al., 2014Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Nuclear spin could actually promote electron entanglement by bosonic pair interactions.

“Nuclear spin could actually promote electron entanglement by bosonic pair interactions (S. R. Hameroff, 2018).”

• cites S. R. Hameroff, 2018 sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The interpretation in terms of entanglement has been challenged, but the challenger did not propose an alternative classical account of the signal.

“The interpretation in terms of entanglement has been challenged (Warren, 2023); however, that author did not propose an alternative classical account of the signal reported by Kerskens and Perez.”

• cites Warren, 2023 sourceNot checked yet

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May combine two claims.

Overall the Orch OR theory, in which MTs mediate anesthetic action, has more explanatory power, biological connection, and experimental validation than the classical theories.

“Overall the Orch OR theory, in which MTs mediate anesthetic action, has more explanatory power, biological connection, and experimental validation than the classical theories.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The Bandyopadhyay group has adapted methods from solid-state physics and quantum optics to noninvasively target known resonances of the MTs in living networks of neurons.

“Along these lines, the Bandyopadhyay group has adapted methods from solid-state physics and quantum optics to noninvasively target known resonances of the MTs in living networks of neurons (Singh et al., 2021a,b; Ghosh et al., 2022).”

• cites Singh et al., 2021aNot checked yet

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• cites Singh et al., 2021bNot checked yet

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• cites Ghosh et al., 2022 sourceNot checked yet

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May combine two claims.

Kalra et al. (2023) showed that tryptophan fluorescence lifetimes propagated and persisted due to quantum exciton mechanisms, and these were dampened by isoflurane and etomidate.

“Kalra et al. (2023) showed that tryptophan fluorescence lifetimes propagated and persisted due to quantum exciton mechanisms, and these were dampened by two types of anesthetic, isoflurane and etomidate.”

• cites Kalra et al., 2023 sourceNot checked yet

  Not checked in the free run.