June 30, 2022
Sandeep M. Nayak, Bilal A. Bari, David B. Yaden et al.
1 citation
preprint
A Bayesian reanalysis of a trial comparing psilocybin (COMP360) to escitalopram for major depressive disorder found that psilocybin outperformed escitalopram, but not by a clinically meaningful amount. The analysis also found extremely strong evidence that psilocybin is non-inferior to escitalopram. Evidence for psilocybin's superiority varied by depression scale: indeterminate for one, strong for two, and extremely strong for another. For a clinically meaningful difference, evidence was moderate against it on one scale, indeterminate on two, and moderate supporting it on one. These results provide a more nuanced interpretation and support further research.
December 11, 2020
Balázs Szigeti, Laura Kärtner, Allan Blemings et al.
1 citation
A self-blinding citizen science study tested whether psychedelic microdosing improves well-being and cognition beyond placebo. 191 participants who already planned to microdose were randomly assigned to receive four weeks of microdoses, placebos, or a mix. All psychological outcomes—including well-being, mindfulness, and life satisfaction—improved from baseline in the microdose group, but the placebo group also improved, and no significant differences emerged between groups. Small acute differences in mood, energy, and creativity were observed, but these could be explained by participants correctly guessing whether they took a microdose. The findings suggest that the anecdotal benefits of microdosing are likely due to the placebo effect.
May 13, 2026
Robin Carhart-Harris, Richard Zeifman, Lorenzo Pasquini et al.
preprint
The paper argues that the term 'plasticity' in neuroscience refers to induced changes in brain function or structure, which differs from the dictionary definition of plasticity as the ability to be shaped or molded. Many biomarkers of neuroplasticity actually index processes that bias phenotypic canalization, the opposite of phenotypic plasticity, creating a paradox. The authors question extrapolating from these biomarkers to improved mental health, as the relationship is context dependent. They propose a new construct, 'mediational and recalibrative plasticity' (MR-P), which aligns with plasticity proper and can describe and predict phenotypic changes relevant to mental health.
arXiv (Cornell University)
August 6, 2020
Rodrigo Cofré, Rubén Herzog, Pedro A. M. Mediano et al.
Altered states of consciousness provide a key opportunity to understand how global brain activity changes relate to different subjective experiences. This paper advocates a research program that bridges bottom-up generative models of whole-brain activity with top-down signatures proposed by theories of consciousness. It defines altered states, discusses relevant brain-activity signatures, and introduces whole-brain models to explore the mechanisms of altered consciousness from the bottom-up. The authors argue that systematic investigation of altered states via bottom-up modeling may help clarify the biophysical, informational, and dynamical foundations of consciousness.
arXiv Preprint Archive
April 13, 2026
Adam B. Barrett, Borjan Milinkovic, Pedro A. M. Mediano et al.
The integrated information theory of consciousness (IIT) proposes a mathematical formula, derived from fundamental properties of conscious experience, to describe the quantity and quality of consciousness for any physical system. This article clarifies common misunderstandings. A high value of the measure Φ does not mean 'more consciousness'; Φ might be replaced with a suite of quantities for a multidimensional characterization. IIT implies a distinct panpsychism where space and time are tiled with substrates of proto-consciousness, which the authors find unproblematic. Φ is not well-defined for real physical systems and has never been computed on one; only proxies have been computed, not approximations. For IIT to align with fundamental physics, a reformulation in continuous fields would be needed.
NeuroImage
February 11, 2023
Andrea I. Luppi, Pedro A.M. Mediano, Fernando E. Rosas et al.
High-level brain functions are thought to arise from coordinated activity across neural systems, but this has been hard to test empirically. Using a framework called Integrated Information Decomposition, which quantifies emergence in dynamical systems, the authors analyzed functional MRI data and found that emergent and hierarchical neural dynamics are significantly reduced in chronically unresponsive patients with severe brain injury. Emergence capacity was positively correlated with hierarchical organization in brain activity. Combining network control theory and whole-brain modeling, the authors show that reduced emergent and hierarchical dynamics in these patients can be explained by disruptions in the structural connectome. The results suggest that chronic unresponsiveness after severe brain injury may stem from structural damage to neural infrastructure needed for emergent brain dynamics.
arXiv Preprint Archive
August 6, 2020
Rodrigo Cofré, Rubén Herzog, Pedro A. M. Mediano et al.
Altered states of consciousness, such as those experienced during dreaming or meditation, offer a way to study how large-scale brain activity relates to different subjective experiences. This paper advocates a research program that combines bottom-up generative models of whole-brain activity, based on known properties of neural tissue, with top-down signatures proposed by theories of consciousness. The authors define altered states, discuss relevant brain-activity signatures, and introduce whole-brain models to explore the mechanisms behind these states. They argue that systematically investigating altered states through bottom-up modeling can clarify the biophysical, informational, and dynamical foundations of consciousness.