bioRxiv
November 26, 2020
49 citations
preprint
The brain coordinates information from many sources to create a unified conscious experience. Combining network science and information theory, the authors identify a “synergistic global workspace” where gateway regions gather synergistic information from specialized brain modules, integrate it, and then broadcast it widely via broadcaster regions. Functional MRI shows that gateway regions correspond to the default mode network and broadcasters to the executive control network. Loss of consciousness from general anesthesia or disorders of consciousness reduces the workspace’s ability to integrate information, which is restored upon recovery. This work reconciles aspects of the Global Neuronal Workspace and Integrated Information Theory.
bioRxiv
August 21, 2023
7 citations
preprint
The brain's activity constantly reorganizes across space and time. A new framework called Harmonic Decomposition of Spacetime (HADES) was developed to track how spatial activity patterns (harmonic modes) change over time. As a proof-of-principle, HADES was applied to brain recordings from healthy participants under the psychedelic DMT and in a normal state. DMT significantly decreased contributions from most low-frequency harmonic modes. After normalizing by condition, a specific decrease appeared in the second functional harmonic, which represents the brain's hierarchy from unimodal to transmodal regions, supporting the hypothesis that psychedelics alter this functional hierarchy. Dynamic measures of fractional occupancy, lifetime, and latent space precisely described changes in the spacetime hierarchical organization of brain activity during the psychedelic state.
bioRxiv
March 20, 2024
5 citations
preprint
Intense positive emotional experiences induced by psychedelics, known as 'peak experiences', are strong predictors of positive outcomes in psychedelic-assisted therapy. This study investigated how the autonomic nervous system (ANS) relates to such experiences. Analyzing electrocardiogram data from 17 participants who received DMT or placebo, researchers found that coactivation of the sympathetic and parasympathetic branches of the ANS during the DMT experience was strongly correlated with ratings of 'Spiritual Experience' and 'Insightfulness', and also linked to improved wellbeing two weeks later. Additionally, the balance between these branches before DMT injection predicted 'Insightfulness' scores. These findings demonstrate the ANS's involvement in psychedelic-induced peak experiences and suggest potential for biofeedback tools to enhance therapy.
bioRxiv
December 15, 2022
5 citations
preprint
Psilocybin, the psychoactive compound in Psilocybe mushrooms, first evolved in that genus, with 4–5 possible horizontal gene transfers to other mushroom species occurring between 40 and 22 million years ago. Sequencing 71 fungarium specimens and analyzing 2,983 single-copy gene families produced a fully supported phylogeny, showing the stem lineage arose about 66 million years ago and diversified around 53 million years ago. Two distinct gene orders within the psilocybin biosynthetic gene cluster correspond to a deep split within Psilocybe, possibly indicating independent acquisition of the cluster. This may predict chemical differences between the two major clades, aiding development of novel therapeutics.
bioRxiv
August 29, 2022
5 citations
preprint
Using fMRI data from fifteen people who took LSD or a placebo, researchers modeled brain dynamics with an Ising spin model to test whether psychedelics push the brain into a more disordered state. LSD increased the Ising temperature of brain activity, moving it further away from a critical point (the edge between order and disorder) into a more disordered, paramagnetic phase. This shift was accompanied by a decrease in interhemispheric connectivity, especially between corresponding regions in the two hemispheres. Algorithmic complexity of brain signals also increased with LSD. The findings suggest LSD loosens homotopic connections, driving the brain into a more flexible, complex state, consistent with theories that psychedelics increase neural entropy.
bioRxiv
February 1, 2022
5 citations
preprint
Schizophrenia and drug-induced states from LSD and ketamine both increase neural signal diversity, but they differ in how information flows in the brain. In schizophrenia, transfer entropy from the front to the back of the brain is increased, whereas under both drugs it is reduced overall. These differences can be modeled by altering Bayesian inference within a predictive processing framework: drug effects correspond to reduced precision of prior beliefs, while schizophrenia corresponds to increased precision of sensory information. The findings clarify similarities and differences between these altered states, with potential implications for understanding consciousness and developing mental health treatments.
bioRxiv
February 8, 2025
4 citations
preprint
The psychedelic DMT shifts brain oscillations away from criticality—a state thought to support healthy brain function—in alpha and adjacent frequency bands, moving toward subcritical regimes. Entropy increases while complexity decreases during this shift. The magnitude of the criticality shift in alpha and theta bands correlates with the intensity of ego-dissolution, a core feature of the psychedelic experience. These results suggest that altered proximity to critical brain dynamics may underlie the neurological and subjective effects of psychedelics, with implications for understanding altered states of consciousness.
bioRxiv
July 18, 2019
4 citations
preprint
Intravenous DMT, a fast-acting psychedelic, markedly alters human brain activity. Compared with a placebo, DMT reduced oscillatory power in alpha and beta brainwaves and increased spontaneous signal diversity. Time-referenced analyses linked changes in subjective experience to changes in brain activity. Emergence of delta and theta frequency oscillations correlated with the peak of the experience, particularly its eyes-closed visual component. These findings advance understanding of the neurobiological underpinnings of immersive states of consciousness.
bioRxiv
March 24, 2025
3 citations
preprint
LSD profoundly alters consciousness by reorganizing brain networks in specific frequency bands. Analyzing MEG data from 14 healthy participants, the substance enhances high alpha (12.1, 13.3 Hz) activity across all conditions and high beta (25.3 Hz) in three conditions, while suppressing low beta (18.1, 19.3 Hz) and low alpha (8.5 Hz). LSD also shifts network spatial distributions: low alpha moves anteriorly toward the motor cortex, high alpha becomes more localized to the visual cortex, and low beta expands over temporal and occipital cortices. These frequency- and region-specific changes add nuance to theories of network disintegration under psychedelics.
bioRxiv
June 11, 2021
3 citations
preprint
During conscious states, the cortex's electrical activity operates near the edge-of-chaos critical point—the boundary between stability and chaos. Applying a new chaos test to ECoG and MEG recordings from humans and macaques across waking, seizure, anesthesia, and psychedelic states shows that unconsciousness shifts cortical dynamics away from this critical point, disrupting information processing. Psychedelics may enhance information-richness by tuning activity closer to this point. Analysis of EEG from patients with disorders of consciousness suggests that measuring proximity to the edge-of-chaos critical point could serve as a clinical biomarker of consciousness.
bioRxiv
July 4, 2025
2 citations
preprint
Long-term meditators show distinct patterns of directed brain connectivity depending on the type of meditation they practice. Using EEG and Granger causality analysis, the study found that focused attention meditation produces different neural communication pathways compared to open monitoring and loving-kindness meditation. Each meditation style engages unique brain networks, suggesting that different meditative practices shape brain connectivity in specific ways. These findings indicate that the brain's neural pathways adapt to the particular cognitive demands of each meditation technique.
bioRxiv
July 7, 2025
1 citation
preprint
Long-term meditation increases directed information flow from posterior to frontal brain regions and between the two frontal hemispheres. Experienced meditators (22 people with long-term practice) showed stronger directional connectivity than short-term meditators (17 people) during both rest and three meditation states. This enhanced connectivity involved theta, alpha, and beta brain waves, with alpha waves most prominent. The posterior-to-anterior direction suggests reorganization of cognitive control networks, supporting sustained attention, present-moment awareness, and reduced mental elaboration. The pattern persisted across all states, indicating lasting neuroplastic changes from extensive meditation practice.
bioRxiv
February 8, 2025
1 citation
preprint
LSD and MDMA, two psychoactive drugs being explored for psychiatric use, alter how the striatum—a brain region central to reward and motivation—communicates with other areas. In a resting-state fMRI study, neither drug changed connectivity within the striatum's own networks. However, MDMA reduced connectivity between the limbic striatum and the amygdala, while LSD increased connectivity between the associative striatum and frontal, sensorimotor, and visual cortices. These changes occurred mostly outside standard striatal networks, suggesting the drugs reduce the brain's usual network segregation, which may help explain their therapeutic potential for conditions like addiction, mood disorders, and PTSD.
bioRxiv
November 14, 2024
1 citation
preprint
People report dreaming most of the time when awakened from sleep, even during deep sleep. A review of 69 awakening studies from 2000 to 2024 found that how you wake up matters: being called by name leads to better dream recall than being woken by an alarm. Dream recall is higher at home than in a laboratory and decreases when participants are studied over multiple days. Personal characteristics beyond age and sex also affect recall. Null reports were similar in NREM stage 2 and stage 3 sleep. The findings suggest that both the awakening method and participant traits influence what people report, which can affect research on the neural correlates of consciousness.
bioRxiv
April 8, 2024
Zepeng Fang, Yuanyuan Dang, Xiaoli Li et al.
1 citation
preprint
Consciousness-related neural activity in the human brain can be separated into two processes: phenomenal consciousness (early, brief awareness) and access consciousness (later, reportable awareness). Using electrodes implanted in epilepsy patients, researchers found that visual awareness-related brain signals appeared at two distinct latencies—short and long—that originate from different brain regions, except in the lateral prefrontal cortex, where both types mix. Early activity was confined to the side of the brain opposite the visual stimulus, while late activity appeared on both sides. Information flowed from early to late sites, supporting a two-stage model of conscious perception and providing the first direct evidence from intracranial recordings for this division.
bioRxiv
July 9, 2026
Psilocybin can improve cognitive flexibility, but only when the impairment stems from a specific brain-circuit problem. In mice, psilocybin reversed deficits caused by abnormal signaling between the prefrontal cortex and the mediodorsal thalamus, but it did not help deficits caused by disrupted communication between brain hemispheres. The drug reduced overactivity in prefrontal-thalamic neurons during post-error exploration, an effect that lasted at least 24 hours. It also triggered lasting changes in those neurons, strengthening inputs from the thalamus while dampening afterdepolarizations that sustain aberrant signaling. These results suggest psilocybin's therapeutic effects are circuit-specific and point toward a precision-medicine approach for psychedelic treatments.
bioRxiv
July 1, 2026
A single dose of ketamine reduces anxiety for an extended period in female Wistar Kyoto rats, even though it increases oxidative stress in the brain. The anxiolytic effect persists long after the drug is cleared, suggesting that the initial oxidative stress does not prevent the lasting behavioral benefit.
bioRxiv
June 3, 2026
A metabolite of ketamine, (2R,6R)-hydroxynorketamine (HNK), selectively targets μ-δ opioid receptor heterodimers on astrocytes. This interaction activates Gs-coupled signaling, increases intracellular cAMP, and elevates phosphorylated CREB levels and calcium dynamics in astrocytes, restoring key astrocytic proteins and functions in depression models. Disrupting the assembly of these opioid receptor heterodimers or Gs signaling eliminates HNK's antidepressant effects both in cells and in animals. The findings indicate that astrocytic opioid receptor heterodimers are critical for antidepressant responses and suggest HNK as a prototype for targeting astrocyte dysfunction in brain disorders.
bioRxiv
May 29, 2026
LSD induces gene expression patterns that oppose the transcriptional signatures of brain aging and dementia. By comparing chronic LSD treatment in rodents with age- and dementia-related gene expression changes in the human prefrontal cortex, the authors show that LSD's effects are strongly anti-correlated with these disease programs, a reversal specific compared to other pharmacological perturbations and reproducible across datasets and species. LSD also counteracts amyloid-β-induced structural and molecular alterations in primary cortical neurons, linking transcriptomic opposition to functional rescue under neurodegenerative stress. These findings suggest LSD modulates molecular and cellular pathways associated with brain aging and neurodegeneration.
bioRxiv
May 18, 2026
A single dose of psilocybin (1.5 mg/kg) in female rats enhanced cognitive flexibility in several learning tasks by amplifying dopamine signals in the nucleus accumbens. The drug increased learning rates and reduced reliance on prior expectations, leading to faster reversal learning. However, calorie restriction and prior exposure to activity-based anorexia (ABA) reduced these benefits. Calorie restriction shifted the timing of psilocybin's effect on reversal learning and increased neural activity in the nucleus accumbens. Prior ABA exposure eliminated improvements in discrimination accuracy and trended toward worsening reversal learning, likely due to reduced cortical 5-HT2A receptor availability. The results show that nutritional state and history of anorexia-like behavior critically moderate psilocybin's cognitive effects.
bioRxiv
May 4, 2026
Inhalation of DMT, a serotonergic psychedelic, produces a brief surge in sympathetic nervous system activity—heart rate, skin conductance, and respiration—that closely tracks the intensity of the emotional experience. Nineteen participants received 20 or 40 mg of DMT under a semi-naturalistic blinded design. Higher doses caused heart rate and breathing to increase within the first two minutes, while skin conductance rose only later, indicating a prolonged autonomic response. As the drug's effects waned, feelings of pleasantness and bliss emerged. Combining simple physiological measures with moment-by-moment self-reports offers a way to objectively characterize psychedelic-induced emotional states, which may aid future clinical biomarker research.
bioRxiv
April 13, 2026
Psilocybin, a serotonergic drug, alters brain function and connectivity as measured with fMRI, but whether these effects are frequency-specific was unknown. In 28 healthy volunteers scanned after oral psilocybin (0.2–0.3 mg/kg), psilocin (the active metabolite) was associated with a selective reduction in low-frequency spectral power (0.01–0.06 Hz) and an increase in spectral entropy, with strongest effects in transmodal networks. Low-frequency connectivity energy explained by the unimodal/transmodal axis also decreased. These findings demonstrate that psilocin induces spatially distributed, frequency-dependent alterations, suggesting broadband fMRI analyses may obscure low-frequency dynamics and that frequency-resolved approaches offer greater sensitivity.
bioRxiv
November 26, 2025
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.
bioRxiv
September 29, 2025
preprint
A neurophenomenological study using EEG and experience tracing in 33 experienced Transcendental Meditation (TM) practitioners and matched controls (doing mental counting) found that TM reliably elicits reports of pure awareness—a minimal form of experience with little mental content. TM practitioners reported greater intensity and more variable timing of pure awareness, independent of years of practice. Distinct neural signatures separated TM from counting: temporal entropy and aperiodic brain activity best distinguished the two states, while phase-based connectivity was least informative. Comparing TM to its own baseline, low-frequency connectivity dominated and temporal entropy mattered little. These patterns were distributed across the brain, not localized. Counting, but not TM, showed lingering effects after the task. The results characterize pure awareness electrophysiologically and support neurophenomenology as a way to study minimal experience.
bioRxiv
September 25, 2025
preprint
Advanced concentrative absorption meditation (jhāna) produces a shift in brain dynamics toward near-criticality, a state of heightened flexibility and integration. Using 7T fMRI and whole-brain modeling, the study found that later absorption states, considered minimal phenomenal experiences, show increased large-scale functional integration and a shift of the default mode network from a noise-driven regime to near-critical dynamics. This near-critical regime is interpreted as a form of openness, where constrained brain activity gives way to greater flexibility, correlating with broader attention and reduced narrative thought. The trajectory of these states is non-linear, with major reconfigurations at key meditative milestones.