Scientific Reports
October 20, 2020
Rubén Herzog, Pedro A. M. Mediano, Fernando E. Rosas et al.
60 citations
Psychedelic drugs such as lysergic acid diethylamide, which activate the serotonin 2A receptor, produce profound changes in consciousness and increase entropy in spontaneous neural activity. This study provides the first model-based explanation for that entropy increase by extending a whole-brain model of serotonergic neuromodulation. The model reproduced the overall entropy rise seen in previous experiments. Entropy changes were not uniform: some brain regions showed increased entropy while others showed decreases, indicating a topographical reconfiguration driven by receptor activation. At the whole-brain level, this reconfiguration was not well explained by receptor density but was closely related to the brain's anatomical connectivity topology.
Scientific reports
April 17, 2023
Rubén Herzog, Pedro A M Mediano, Fernando E Rosas et al.
51 citations
Psychedelic drugs such as LSD, which activate the serotonin 2A receptor, produce profound changes in consciousness and are linked to increased entropy in spontaneous brain activity. This study provides the first model-based explanation for that entropy increase by extending a whole-brain model of serotonin neuromodulation. The model reproduced the overall rise in neural entropy seen in prior experiments. Entropy increased across all brain regions, with the largest effects in visuo-occipital areas. At the whole-brain level, this reconfiguration was not well explained by the density of serotonin 2A receptors but was closely related to the topological properties of the brain's anatomical connectivity.
Nature communications
March 11, 2024
Andrea I Luppi, Lynn Uhrig, Jordy Tasserie et al.
43 citations
Loss of consciousness under anesthesia increasingly constrains brain activity to follow the brain's physical structure, collapsing hierarchical cortical organization across scales. This effect was observed with three different anesthetics—propofol, sevoflurane, and ketamine—and was reversed by electrically stimulating the central thalamus, which also restored behavioral signs of arousal. Stimulating the ventral lateral thalamus did not produce these effects, showing specificity. The findings identify distributed brain signatures of consciousness that are orchestrated by particular thalamic nuclei.
Communications Biology
September 30, 2024
Pablo Castro, Andrea I. Luppi, Enzo Tagliazucchi et al.
21 citations
Brain activity during unconsciousness, whether from general anaesthesia or slow wave sleep, is dominated by a recurrent functional connectivity pattern primarily mediated by structural connectivity and with a reduced capacity to transition to other patterns. Conscious awareness is characterized by richer brain dynamics measured by entropy and a greater repertoire of connectivity states. These findings suggest that the dynamic exploration of functional connectivity states provides robust and generalizable markers for the state of consciousness across different conditions.
MDPI (MDPI AG)
September 10, 2020
Rodrigo Cofré
7 citations
Altered states of consciousness, which differ from ordinary wakefulness, offer a valuable opportunity to understand how global changes in brain activity relate to different subjective experiences. This paper advocates for 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 biophysics of altered consciousness from the bottom-up. The authors argue that systematically investigating altered states via such modeling can illuminate the biophysical, informational, and dynamical foundations of consciousness.
Research Square
October 26, 2022
Rubén Herzog, Pedro A.M Mediano, Fernando E. Rosas et al.
6 citations
Psychedelic drugs like LSD, which activate serotonin 2A receptors, dramatically alter subjective experience and offer a window into the neurobiology of consciousness. A key signature of these drugs is increased entropy—or randomness—in spontaneous brain activity, but why this occurs was unclear. Using a computational model of serotonin's effects on the whole brain, researchers reproduced the entropy increase seen in living brains, providing the first model-based explanation. Entropy rose across all brain regions but was most pronounced in visual and occipital areas. Surprisingly, this pattern was not tied to the density of serotonin receptors but instead linked to the brain's structural connectivity network. The findings clarify how psychedelics reconfigure brain activity.
Sci Rep
September 15, 2022
Rubén Herzog, Pedro A. M. Mediano, Fernando E. Rosas et al.
3 citations
A scientific paper was retracted because a typo in the script used to calculate differential entropy made the reported entropy estimations invalid. The corrected calculations no longer show the expected increase in brain signal diversity or complexity that the original analysis had claimed.
bioRxiv : the preprint server for biology
June 1, 2026
Panagiotis Fotiadis, Hyunwoo Jang, Rui Dai et al.
Brain waves coordinate neural communication and shape conscious perception. Analyzing blood oxygen level-dependent activity from the Human Connectome Project and other datasets across sleep, propofol anesthesia, and psychedelic states (LSD, DMT, psilocybin, nitrous oxide, ketamine), four dominant wave propagation motifs were identified: a global synchronized wave, an anti-correlated unimodal-transmodal wave, an anti-correlated task-positive/task-negative wave, and an anti-correlated visual-somatomotor wave.
bioRxiv
November 26, 2025
Rui Dai, Rodrigo Cofré, Christopher Timmermann et al.
preprint
Classical psychedelics (DMT, LSD, psilocybin) and non-classical ones (nitrous oxide, ketamine) all disrupt local synchrony in small brain regions (<1 cm³) in humans, as measured by functional magnetic resonance imaging. This disruption occurred extensively in cortical regions and sparsely in subcortical regions. As local synchrony declined, large-scale functional connectivity increased. For classical psychedelics, the disruption was most strongly associated with 5-HT receptors; for nitrous oxide and ketamine, it was most strongly associated with NMDA receptors. Both neuronal and non-neuronal cell types were linked to these changes. The findings suggest diverse molecular events converge on a common outcome of disrupted local synchrony, which then mediates drug-specific global connectivity changes.
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
July 11, 2022
Matthieu Gilson, Enzo Tagliazucchi, Rodrigo Cofré
Consciousness depends on complex, irreversible brain dynamics that produce entropy. By fitting a statistical model to fMRI data and calculating entropy production, researchers found a monotonic relationship: entropy production decreases as people move from wakefulness to deep sleep. This suggests that entropy production is a robust signature of consciousness, linking conscious states to the thermodynamic activity of the brain.
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.