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Ryan Smith

Laureate Institute for Brain Research, University of Tulsa, Tulsa Oklahoma, OK, USA.

10 papers in the library · 122 citations · publishing 2020-2026

Papers

From Generative Models to Generative Passages: A Computational Approach to (Neuro) Phenomenology.

Review of philosophy and psychology January 1, 2022 Maxwell J D Ramstead, Anil K Seth, Casper Hesp et al. 75 citations

A version of neurophenomenology is presented that uses generative modelling techniques from computational neuroscience and biology to formally model descriptions of lived experience from the phenomenological tradition (e.g., Husserl, Merleau-Ponty). The approach, called computational phenomenology, is situated within the broader project of naturalizing phenomenology. Philosophical objections to that project are evaluated, and the generative modelling framework is reviewed. The approach differs from previous uses of generative modelling for consciousness by constructing computational models of inferential or interpretive processes that best explain particular kinds of lived experience.

An active inference model of conscious access: How cognitive action selection reconciles the results of report and no-report paradigms.

Current research in neurobiology January 1, 2022 Christopher J. Whyte, Jakob Hohwy, Ryan Smith 21 citations

Cognitive theories of consciousness link frontoparietal circuits to conscious access, but no-report paradigms challenge this by showing conscious accessibility without prefrontal cortex (PFC) activation. This paper presents a computational model based on active inference, treating working memory gating as a cognitive action. Simulating a visual masking task, the model shows that late P3b-like event-related potentials and increased PFC activity arise from the working memory demands of self-report generation. Removing reporting demands eliminates these late potentials and reduces PFC activity, reproducing no-report paradigm results. However, even without reporting, simulated PFC activity on visible trials still crosses the threshold for reportability, maintaining the link between PFC and conscious access. Thus, no-report paradigm evidence does not necessarily contradict cognitive theories.

Psilocybin increases optimistic engagement over time: computational modelling of behaviour in rats.

Translational psychiatry September 30, 2024 Elizabeth L Fisher, Ryan Smith, Kyna Conn et al. 14 citations

Psilocybin treatment in rats performing a reversal learning task led to more rewards through increased task engagement, driven by changes in forgetting rates and reduced loss aversion. Computational modeling suggests psilocybin may induce an optimism bias by altering how beliefs are updated, which could have implications for clinical conditions marked by pessimism.

On the minimal theory of consciousness implicit in active inference.

Physics of life reviews March 1, 2026 Christopher J Whyte, Andrew W Corcoran, Jonathan Robinson et al. 5 citations

Subjective experience is multifaceted, making it hard for traditional neuroscientific theories of consciousness to be compared because each focuses on different aspects like perceptual awareness or global states. This work instead starts from active inference, a first-principles framework that models behavior as approximate Bayesian inference, and builds a minimal theory of consciousness from shared features of computational models derived under active inference. By reviewing studies that apply active inference models to consciousness, the authors identify a small set of theoretical commitments implicit in these models, pointing toward a minimal and testable theory of consciousness.

Ketamine treatment effects on DNA methylation and Epigenetic Biomarkers of aging

medRxiv Preprint Server September 10, 2024 Kristin Dawson, Athena May Jean M. Carangan, Jessica Klunder et al. 4 citations preprint

Depression and PTSD are linked to poor health outcomes similar to aging. Ketamine infusions rapidly reduce symptoms of treatment-resistant depression and PTSD. In 20 participants with moderate to severe depression or trauma, a 2-3 week course of 0.5 mg/kg ketamine infusions reduced depression and PTSD scores. Epigenetic age, measured by OMICmAge, GrimAge V2, and PhenoAge biomarkers, decreased after treatment. Changes in underlying epigenetic biomarker proxies and surrogate protein markers were also observed. The findings align with prior research on ketamine's epigenetic effects and suggest these biomarkers capture signals related to clinical improvement and biological aging.

Psilocybin increases optimistic engagement over time: computational modelling of behavior in rats

bioRxiv (Cold Spring Harbor Laboratory) May 17, 2024 Elizabeth L. Fisher, Ryan Smith, Andrew W. Corcoran et al. 2 citations preprint

Rats treated with psilocybin achieved more rewards in a decision-making task, driven by increased task engagement, altered forgetting rates, and reduced loss aversion. Computational modeling of the rats' behavior revealed that psilocybin may induce an optimism bias through changes in how beliefs are updated. This finding has potential relevance for clinical populations characterized by a lack of optimism, such as those with depression.

Brain-epigenome wide association study (BEWAS) on the effects of two emerging psychedelics: ketamine & MDMA

bioRxiv Preprint Server July 3, 2025 Moira G. Semple, Sarah E. Mennenga, Ryan Smith et al. 1 citation preprint

Psychedelic compounds like ketamine and MDMA induce widespread DNA methylation changes in brain-enriched genes, with ketamine altering 1,210 CpG sites and MDMA affecting 2,074 CpG sites. These changes occur in genes involved in neuroplasticity, immune regulation, and mental processes, with overlapping effects in genes such as PTPRN2 and SHANK2. The findings suggest shared epigenetic mechanisms through which psychedelics may drive increased neuroplasticity and produce lasting molecular changes relevant to neuroimmune function and psychiatric health.

Brain-targeted epigenetic effects of two emerging psychoplastogens: ketamine & MDMA

Translational Psychiatry July 11, 2026 Moira G. Semple, Sarah E. Mennenga, Ryan Smith et al.

Ketamine and MDMA, compounds known as psychoplastogens, show therapeutic potential for mood and trauma-related disorders, but their molecular mechanisms are not fully understood. In a study analyzing blood samples from 20 ketamine-treated participants and saliva samples from 16 MDMA-treated participants, DNA methylation changes were examined using a Brain-Epigenome-Wide Association Study targeting brain-relevant genes. Ketamine was associated with 405 significantly altered genes and 169 functional networks, while MDMA was linked to 346 altered genes and 183 networks. Both compounds converged on pathways related to neuroplasticity and neuroimmune regulation, suggesting they induce peripheral epigenetic changes that engage molecular pathways relevant to psychiatric health.

On the Minimal Theory of Consciousness Implicit in Active Inference

arXiv Preprint Archive October 9, 2024 Christopher J. Whyte, Andrew W. Corcoran, Jonathan Robinson et al.

Subjective experience is multifaceted, making consciousness hard to study because traditional theories often focus on isolated aspects like perception or wakefulness and are difficult to compare. This work starts from active inference—a first-principles framework that models behavior as approximate Bayesian inference—and builds toward a minimal theory of consciousness derived from shared features of computational models under active inference. Reviewing models applied to consciousness, the authors argue that these models imply a small set of theoretical commitments pointing to a minimal, testable theory of consciousness.

The Predictive Global Neuronal Workspace: A Formal Active Inference Model of Visual Consciousness

bioRxiv Preprint Server February 11, 2020 Christopher J. Whyte, Ryan Smith preprint

A new computational model called the 'predictive global workspace' combines ideas from the global neuronal workspace (GNW) theory of consciousness with Active Inference, a framework that treats brain activity as Bayesian inference. The model reproduces electrophysiological and behavioral results from studies of inattentional blindness and a four-way taxonomy linking consciousness, attention, and sensory signal strength. It also reconciles conflicting findings, extends the taxonomy to include prior expectations, and suggests new experimental paradigms. The model addresses limitations of current GNW research by enabling precise, testable predictions at both behavioral and neural levels.