02 / Theoretical neuroscience · Peer-reviewed research
Conscious
active inference.
I co-authored two theoretical reviews with Michael C. Wiest in 2025. They examine quantum dynamics as a possible implementation of planning and perceptual cycles in active inference.
- Role
- Co-author
- Publication
- Computational and Structural Biotechnology Journal
- Papers
- Two companion reviews · 2025
- Framework
- Active inference × quantum dynamics × Orch OR
Argument arc objection → perturbation → mechanistic hypothesis → discriminating experiment
Active inference specifies belief updating and policy selection under variational free-energy minimization.
The papers evaluate quantum dynamics and Orch OR as candidate physical implementations, not prerequisites of active inference itself.
A quantum account must outperform viable classical alternatives on discriminating, reproducible intervention predictions.
00 / From process to mechanism
Computational objectives, neural processes, and physical mechanisms
The project begins by separating three levels of explanation. Active inference supplies a normative objective. Process theories map belief updating onto neuronal populations and message passing. Mechanistic models must still explain how real biophysics realizes those computations.
Scientific basis: Ma et al. 2006; Friston et al. 2006, 2017; Friston 2018; Parr, Pezzulo & Friston 2022. [3] [4] [5] [6] [7]
Normative
Active inference
Process
Neural message passing
Mechanistic
Biophysics
01 / The decoherence challenge
Decoherence estimates and the neural timescale
Tegmark calculated extremely short decoherence times for candidate neural quantum states, roughly 10−13 to 10−20 seconds, compared with neural dynamics on roughly 10−3 to 10−1 second scales. The calculation became a central physical objection to quantum models of cognition. [1]
Modeled decoherence for the candidate neural superpositions he analyzed.
Recalculation for a different proposed microtubule superposition. Longer values require further model assumptions.
Reference range used to frame the biological timing problem.
One physical model
Environmental interactions rapidly decohere the superpositions he modeled, leaving a large separation from neural processing times.
Primary source ↗A different model
They argued that Tegmark had modeled a different superposition from the Orch OR proposal and obtained longer estimates under altered assumptions.
Primary source ↗Model dispute: calculation alone could not determine which physical description, if either, applies in living neurons.
02 / Anesthesia as a perturbation
Microtubule stabilization and anesthetic sensitivity
Volatile anesthetics act through multiple targets. Microtubules are one candidate. The cited experiments tested whether microtubule stabilization changes loss-of-righting-reflex latency.
Mean delay in loss of righting reflex after epothilone B under 4% isoflurane.
- Animals
- Male rats
- Endpoint
- Loss of righting reflex
- Effect size
- Cohen's d ≈ 1.9
Within-subject increase in loss-of-righting-reflex latency reported after 8 mg/kg epothilone B.
- Animals
- Male and female mice
- Endpoint
- Loss of righting reflex
- Effect size
- Cohen's d ≈ 0.8
Endpoint note: loss of righting reflex is a standard rodent behavioral proxy for anesthetic-induced unconsciousness. It is not a direct measurement of phenomenal consciousness.
Microtubule stabilization changes anesthetic sensitivity.
The rat and mouse experiments report delayed loss of righting reflex after epothilone B. [11] [16]
A functional microtubule contribution to anesthetic action.
The reported effects are consistent with a microtubule contribution. Classical molecular explanations remain possible.
A quantum mechanism of consciousness.
The experiments do not by themselves demonstrate quantum coherence, entanglement, objective reduction, or a microtubular substrate of phenomenal consciousness.
03 / Our contribution
Our reviews: planning and perceptual cycles
The two companion reviews connect temporally deep active inference to a candidate physical implementation. Paper I focuses on integration over possible future trajectories. Paper II focuses on discrete perceptual cycles and evaluates Orch OR as a proposed mechanism.
o₁, o₂, … oₜ
s₁, s₂, … sₜ
π₁ · π₂ · π₃ · … · πₙ
Alternative trajectories weighted under the generative model.
Planning across possible futures
We argued that temporally deep active inference requires integration over alternative future trajectories and that quantum path-integral dynamics offer a natural candidate implementation of that computation.
Read Paper I ↗Discrete perceptual cycles
We evaluated Orch OR as a candidate physical mechanism for temporally structured conscious updating. The paper proposes a mechanistic correspondence; it does not experimentally establish objective reduction in neurons.
Read Paper II ↗Where Orch OR enters the argument
Orch OR as a proposed mechanism
Paper II evaluates Orch OR as one candidate physical mechanism for discrete perceptual cycles. It is not a requirement of active inference and is not presented as an established substrate of consciousness.
04 / A disputed signal
The disputed MRI interpretation
A 2022 MRI study interpreted multiple-quantum-coherence measurements as possible evidence of a non-classical mediator associated with brain function. A published 2023 comment argued that the measurements did not justify an entanglement claim. The original authors published a reply.
Possible non-classical mediator
Kerskens and López Pérez reported an MRI signal they interpreted as consistent with a non-classical mediator and entanglement-related behavior.
Original paper ↗Classical alternatives remain
Warren argued that multiple-quantum-coherence MRI can arise through classical spin dynamics and that the reported result did not establish entanglement.
Published comment ↗05 / Evidence
Established findings, contested interpretations, and hypotheses
Frameworks and biology
- Active inference provides a formal framework for perception, action, learning, and planning.
- Neuronal population activity can encode probability distributions and support approximate Bayesian computations.
- Quantum coherence can occur in some biological or biomolecular systems under specific physical conditions; that fact alone does not imply quantum consciousness.
- Microtubules are intracellular cytoskeletal structures with established structural, transport, and signaling roles.
- Volatile anesthetics act through multiple molecular and circuit-level targets.
Perturbation results
- Epothilone B delayed isoflurane-induced loss of righting reflex in a 2024 rat experiment.
- A 2026 mouse study reproduced the direction of the microtubule-stabilization effect.
- These results support a functional microtubule contribution to anesthetic action without identifying that contribution as quantum mechanical.
Physical interpretation
- Whether the 2022 MRI result warrants an entanglement or non-classical-mediator interpretation remains disputed.
- Whether biologically relevant microtubule states preserve quantum coherence for the required duration remains unresolved.
- Classical molecular explanations remain viable for the anesthetic perturbation results.
Mechanistic proposal
- Orchestrated objective reduction as a generator of conscious moments.
- Collective microtubule quantum states as a substrate of consciousness.
- Quantum path-integral dynamics as the physical implementation of temporally deep active inference.
06 / Falsifiability
Proposed experiments to distinguish quantum and classical models
A useful experiment would separate a specifically quantum mechanism from conventional microtubule biology and classical network dynamics.
Directly measure a candidate microtubule quantum degree of freedom in living neural tissue at a behaviorally relevant timescale.
Perturb that degree of freedom while preserving conventional microtubule structure and transport as far as experimentally possible.
Demonstrate a reproducible change in a prespecified conscious-state measure or tightly defined neural correlate.
Show that a quantum model predicts the intervention effect better than competing classical molecular and dynamical models.
Replicate the result independently under preregistered conditions with explicit negative controls.
A quantum account should earn explanatory status only if it predicts intervention outcomes that viable classical models do not, and those predictions replicate.
Visual appendix / Figure atlas
Conceptual figure appendix
Switch between diagrams of the three explanatory levels, possible policy trajectories, the Orch OR proposal, and experimental requirements.
NORMATIVE
What should be computed?
Variational free-energy minimizationPROCESS
How is it computed?
Neural message passing / population codesMECHANISTIC
What is the physical substrate?
Candidate physical implementationQuantum active inference concerns a proposed mechanistic implementation, not a requirement of active inference itself.
Normative, process, and mechanistic levels are kept distinct; the quantum proposal enters only at the mechanistic level.
07 / Published work
Published reviews
Conscious active inference I: A quantum model naturally implements the path integral needed for real-time planning and control
Computational and Structural Biotechnology Journal, 30, 108–121 · 2025
A theoretical review proposing quantum dynamics as a possible implementation of path integration in temporally deep active inference. It does not demonstrate that implementation in neurons.
- Role
- Co-author
- DOI
- 10.1016/j.csbj.2025.09.017
Conscious active inference II: Quantum orchestrated objective reduction among intraneuronal microtubules naturally accounts for discrete perceptual cycles
Computational and Structural Biotechnology Journal, 30, 94–107 · 2025
A companion theoretical review arguing that Orch OR microtubule dynamics could provide discrete perceptual cycles for conscious active inference. It does not constitute experimental proof of a quantum mechanism for consciousness.
- Role
- Co-author
- DOI
- 10.1016/j.csbj.2025.09.016
Correction record: 2025 corrigendum correcting equations on page 102 ↗
References / Primary record
Sources behind the argument.
- 1Tegmark M. Importance of quantum decoherence in brain processes. Physical Review E. 2000;61:4194. ↗
- 2Hagan S, Hameroff SR, Tuszyński JA. Quantum computation in brain microtubules: Decoherence and biological feasibility. Physical Review E. 2002;65:061901. ↗
- 3Ma WJ, Beck JM, Latham PE, Pouget A. Bayesian inference with probabilistic population codes. Nature Neuroscience. 2006;9:1432–1438. ↗
- 4Friston K, Kilner J, Harrison L. A free energy principle for the brain. Journal of Physiology-Paris. 2006;100:70–87. ↗
- 5Friston K, FitzGerald T, Rigoli F, Schwartenbeck P, Pezzulo G. Active Inference: A Process Theory. Neural Computation. 2017;29:1–49. ↗
- 6Friston K. Am I Self-Conscious? (Or Does Self-Organization Entail Self-Consciousness?). Frontiers in Psychology. 2018;9:579. ↗
- 7Parr T, Pezzulo G, Friston KJ. Active Inference: The Free Energy Principle in Mind, Brain, and Behavior. MIT Press; 2022. ↗
- 8Kerskens CM, López Pérez D. Experimental indications of non-classical brain functions. Journal of Physics Communications. 2022;6:105001. ↗
- 9Warren WS. Comment on: Experimental indications of non-classical brain function. Journal of Physics Communications. 2023;7:038001. ↗
- 10Kerskens CM, López Pérez D. Reply to Comment on: Experimental indications of non-classical brain function. Journal of Physics Communications. 2023;7:038002. ↗
- 11Khan S et al. Microtubule-Stabilizer Epothilone B Delays Anesthetic-Induced Unconsciousness in Rats. eNeuro. 2024;11(8). ↗
- 12Wiest MC. A quantum microtubule substrate of consciousness is experimentally supported and solves the binding and epiphenomenalism problems. Neuroscience of Consciousness. 2025;2025(1):niaf011. ↗
- 13Wiest MC, Puniani AS. Conscious active inference I: A quantum model naturally implements the path integral needed for real-time planning and control. Computational and Structural Biotechnology Journal. 2025;30:108–121. ↗
- 14Wiest MC, Puniani AS. Conscious active inference II: Quantum orchestrated objective reduction among intraneuronal microtubules naturally accounts for discrete perceptual cycles. Computational and Structural Biotechnology Journal. 2025;30:94–107. ↗
- 15Corrigendum to Conscious active inference II. Computational and Structural Biotechnology Journal. 2025. ↗
- 16Huang Y et al. Brain-penetrant microtubule-stabilizer epothilone B delays isoflurane-induced unconsciousness in mice. Neuropharmacology. 2026;287:110834. ↗
- 17Lambert N et al. Quantum biology. Nature Physics. 2013;9:10–18. ↗
- 18Goodson HV, Jonasson EM. Microtubules and Microtubule-Associated Proteins. Cold Spring Harbor Perspectives in Biology. 2018;10:a022608. ↗
- 19Hemmings HC Jr et al. Towards a Comprehensive Understanding of Anesthetic Mechanisms of Action: A Decade of Discovery. Trends in Pharmacological Sciences. 2019;40:464–481. ↗
The references include the original studies, published critiques and replies, both reviews, and the Paper II corrigendum.