bioRxiv (Cold Spring Harbor Laboratory)
December 11, 2025
Caroline L. Alves, Fernanda Palhano-Fontes, Thaise G. L. de O. Toutain et al.
Ayahuasca alters conscious experience, and this study identifies EEG markers of its network-level effects using machine learning and complex-network analysis. In a randomized, double-blind, placebo-controlled trial with naïve ayahuasca users, resting-state EEG was recorded before dosing, 2 hours after, and 4 hours after. Connectivity was estimated with sliding windows; optimal classification performance occurred at 60–70 seconds (AUC and accuracy = 0.93). Network analysis revealed a bilateral decrease in eigenvector centrality (weaker hub influence), increased degree heterogeneity in the right hemisphere, and reduced global efficiency in the left. Posterior-left connections weakened acutely, while right temporal–central coupling transiently strengthened. The findings suggest that hub-centric shortcuts weaken, routing communication through more distributed, less efficient pathways with right-lateralized expression.
bioRxiv (Cold Spring Harbor Laboratory)
November 21, 2025
Joseph C. C. Chen, Gabriella Mace, Avery Ostrand et al.
preprint
Awe, a positive emotion linked to well-being and social behavior, was studied using EEG and autonomic physiology in 23 healthy older adults watching a nature film. Awe was the dominant emotion reported, though joy was also common. During awe events, skin conductance decreased, and EEG alpha and theta power decreased—changes associated with low arousal and positive emotion. Awe also increased Lempel Ziv Complexity (LZC), a measure of neural signal entropy linked to richer conscious experience. LZC correlated positively with awe intensity and negatively with skin conductance. Three additional datasets using different induction methods (video clips and DMT) showed similar occipital LZC increases, suggesting LZC may be a generalizable neurophysiological marker of awe.
bioRxiv (Cold Spring Harbor Laboratory)
November 7, 2025
Gabrielle Allohverdi, Milad Soltanzadeh, André Schmidt et al.
preprint
Ketamine and psilocybin, two hallucinogenic compounds being explored as treatments for major depressive disorder, affect sensory learning in the brain differently. By combining computational modeling with electroencephalography (EEG) data from a prior experiment, researchers analyzed how these drugs alter the brain's processing of unexpected sounds during an auditory task. Ketamine produced a larger reduction in the influence of sensory precision between 207 and 316 milliseconds after a sound, peaking at 277 milliseconds in frontal central brain regions, while psilocybin showed no significant effect in that measure. Both drugs reduced the expression of belief precision between 160 and 184 milliseconds, peaking at 172 milliseconds.
bioRxiv (Cold Spring Harbor Laboratory)
October 15, 2025
Sheida Shadani, Erika Greaves, Zane B. Andrews et al.
preprint
A single dose of psilocybin did not alter sociability in female mice exposed to activity-based anorexia, food restriction, or exercise, but increased preference for familiarity in control mice. Novelty-seeking behavior rose in both anorexia-model and exercise mice, with distinct social patterns. Psilocybin elevated the inflammatory marker interleukin-6 in exercised mice, which correlated with novelty preference; no such link appeared in other groups. These context-dependent effects on social behavior and inflammation underscore the need to study psilocybin's mechanisms across sexes and disease models.
bioRxiv (Cold Spring Harbor Laboratory)
October 2, 2025
D. Samuel Schwarzkopf, Xinran A Yu, Ecem Altan et al.
preprint
Vividness ratings, though lacking an objective reference, are a robust measure of mental visual imagery. They explain individual differences in subjective experiences such as the detail of mental imagery, the propensity for internally generated visual experiences, and the vividness of visual dreams. Simple vividness ratings can replace longer questionnaires, reducing methodological issues. Vividness is closely linked to the experience of seeing mental images or projecting them externally; people who report seeing mental images with eyes shut are more likely to experience externally projected imagery. However, many people report having mental depictions without seeing. The results suggest redefining visual aphantasia to distinguish those with faint or unseen images from those completely lacking pictorial representation.
bioRxiv (Cold Spring Harbor Laboratory)
September 17, 2025
Matheus Gallas‐lopes, Dagobert Müller, Thailana Stahlhofer-Buss et al.
preprint
Ketamine, an NMDA receptor antagonist, produced concentration-dependent behavioral changes in adult zebrafish. Acute exposure reduced social interaction and increased swimming activity and rotational behavior. These effects did not intensify with repeated daily dosing over five days and were not present 48 hours after the final treatment, indicating no behavioral sensitization or lasting disruption. The findings support zebrafish as a model for acute schizophrenia-like behavioral phenotypes induced by NMDA receptor blockade, but the lack of sustained effects differs from rodent studies.
bioRxiv (Cold Spring Harbor Laboratory)
September 12, 2025
Navid Shams Masjedi, Adeel Razi
preprint
The claustrum, a brain region with extensive connections to both cortical and subcortical areas, may help synchronize brain networks. Psychedelics like psilocybin appear to disrupt this synchrony by altering claustral signaling. Using brain scans from the Human Connectome Project and PsiConnect datasets, this work provides the first in vivo description of how the claustrum communicates with key brain networks in humans, both at rest and under psilocybin. The claustrum showed widespread bidirectional connections and a strong inhibitory influence on target regions. Psilocybin increased this inhibition on cortical networks while reducing it on subcortical areas, partly linked to subjective psychedelic effects, supporting a role for claustro-cortical inhibition in regulating network synchrony.
bioRxiv (Cold Spring Harbor Laboratory)
September 9, 2025
Ratna Jyothi Kakumanu, Ajay Kumar Nair, Arun Sasidharan et al.
preprint
A novel approach using four EEG-based biomarkers—potentials, their first-order derivatives, and phase slip rates derived from each—distinguished novice Vipassana meditators from non-meditator controls. Phase slip rates, discontinuities in instantaneous phase representing cortical phase transitions, were computed from 128-channel EEG data collected during a visual oddball task. Eight novice Vipassana subjects and eight non-meditator controls each completed 50 trials; 44 artifact-free trials per subject were averaged. Spatiotemporal profiles of all four biomarkers differed significantly between groups, and the novice Vipassana subjects showed faster object recognition. The findings suggest phase slip rates offer a promising set of biomarkers for quantitative task-based EEG analyses.
bioRxiv (Cold Spring Harbor Laboratory)
September 8, 2025
Adriana Michalak, Davide Marzoli, Francesco Pietrogiacomi et al.
preprint
Perceived sleep depth, a key factor in subjective sleep quality, is traditionally linked to unconsciousness and reduced brain activity. Using high-density EEG and a serial awakening paradigm during NREM sleep, researchers found that deeper sleep corresponded to lower high-to-low frequency power ratio, indicating reduced cortical activation. However, this relationship weakened when dreaming occurred, suggesting immersive conscious experiences can counteract the effect of cortical activation on perceived depth. Perceived sleep depth was lowest during states with a mere sense of presence and highest during immersive dreaming or deep unconsciousness. As the night progressed, physiological sleep pressure and subjective sleepiness declined, but perceived sleep depth increased alongside rising dream immersiveness. These findings challenge the view that deep sleep stems solely from reduced brain activity.
bioRxiv (Cold Spring Harbor Laboratory)
September 1, 2025
Jean-Baptiste Maranci, Pierre Champetier, Delphine Oudiette et al.
preprint
Dreams during REM sleep are emotionally fluid and fast-changing, with positive and negative emotions alternating frequently. In a study of 24 lucid dreamers with narcolepsy who reported emotional valence in real-time using facial codes during daytime naps monitored with polysomnography, 62 of 126 naps contained at least one emotional code during REM sleep, yielding 191 codes total. Positive and negative codes were evenly balanced per nap, and over half of naps with at least two codes showed opposite valences. The average duration of a given emotional valence was about one minute, with positive emotions emerging earlier than negative ones. These findings suggest that the emotional dynamics of REM sleep dreams may contribute to understanding how dreams help regulate emotions.
bioRxiv (Cold Spring Harbor Laboratory)
August 22, 2025
Matthew D. Greaves, Tamrin Barta, Leonardo Novelli et al.
preprint
Psilocybin reorganizes directed influences between brain regions while preserving the underlying structural connectivity, according to fMRI data analyzed with a dynamic causal model. Across four contexts—rest, guided meditation, music listening, and movie viewing—effects converged on outgoing influences from the left hippocampus, a hub linking memory and association systems with the default-mode network and thalamus. The left-hippocampus-to-thalamus pathway showed a sign-reversed association with mystical-experience scores: downregulation during guided meditation and upregulation during music listening. Left-hippocampal efferents predicted individual differences in mystical-experience intensity in cross-validation, and a simpler measure of hippocampal signal variability showed modest associations.
bioRxiv (Cold Spring Harbor Laboratory)
July 29, 2025
May Kung Sutherland, Christopher R. Nicholas, Richard C Lennertz et al.
preprint
Psilocybin, a serotonergic psychedelic, induces neural plasticity and alters consciousness, while midazolam, a benzodiazepine, blunts plasticity and causes sedation and amnesia. In an open-label pilot study, 25 mg of oral psilocybin was given alongside intravenous midazolam at doses that allowed a full psychedelic experience but reduced memory of it. EEG recordings showed that 15-30 minutes after dosing, when midazolam was at its target concentration, beta power increased and the spectral exponent decreased. As psilocybin's effects emerged over the next six hours, Lempel-Ziv complexity and spectral exponent increased while broadband power decreased. These findings suggest psilocybin's effects persist even with midazolam, supporting its use in mechanistic studies.
bioRxiv (Cold Spring Harbor Laboratory)
July 15, 2025
Dominic Standage, Yuki Hori, Joseph Y. Nashed et al.
preprint
Using fMRI in awake and anesthetized marmosets, the study shows that the anesthetic isoflurane weakens functional brain networks, making them more fragmented and more closely resembling anatomical structure. In contrast, wakefulness is characterized by coordinated network reconfiguration and distinct subnetworks. The authors argue that consciousness emerges from the dynamics of functional brain networks and that anesthetics reduce these dynamics by impairing synaptic transmission.
bioRxiv (Cold Spring Harbor Laboratory)
June 8, 2025
Anna Onisiforou, Morfeas Koumas, Andria Michael et al.
preprint
A single dose of (2R,6R)-hydroxynorketamine (HNK) reverses some but not all gene expression changes in the hippocampus of mice after three weeks of opioid abstinence, while also normalizing their behavior. Transcriptomic analysis identified 206 differentially expressed genes in untreated abstinent mice compared to controls; after HNK treatment, 55 of those genes were reversed, including Transthyretin and Cd5. However, 186 residual differentially expressed genes remained, enriched for immune and fear regulation pathways, indicating an intermediate molecular state despite behavioral recovery. Machine learning highlighted Il1rapl1 and Ctla2b as top predictors of treatment response. HNK did not alter behavior in opioid-naive mice, showing its context-dependent effects.
bioRxiv (Cold Spring Harbor Laboratory)
May 30, 2025
Pavel Osten, K Sunny Joseph, Jane Collins et al.
preprint
Ketamine relieves depression within a day, whereas standard monoaminergic antidepressants take weeks. In mice, whole-brain mapping of the activity marker c-fos after treatment with monoaminergic antidepressants, ketamine, and psilocybin revealed a shared limbic circuit involving subcortical and frontal cortical regions. Ketamine and high-dose psilocybin acutely activated the prelimbic and infralimbic frontal cortex—areas linked to depression—while the selective serotonin reuptake inhibitor fluoxetine and psilocybin microdosing activated these regions only after chronic dosing. This suggests a common limbic subcortico-cortical circuit underlies antidepressant efficacy, explains the delay of monoaminergic drugs, and shows that monoaminergic antidepressants and psilocybin microdosing evoke similar brain activity.
bioRxiv (Cold Spring Harbor Laboratory)
March 10, 2025
Shaun K.l. Quah, Cameron C. Glick, Leor Roseman et al.
preprint
People with major depression who responded to either psilocybin or escitalopram showed distinct changes in brain network connectivity compared to non-responders. Responders had increased linear connectivity within the ventral attention network and greater nonlinear connectivity within the default mode and ventral attention networks. Psilocybin responders showed enhanced coordination between higher-order networks, while escitalopram responders showed reduced connectivity within networks linked to self-referential thought and salience processing. These patterns suggest the two antidepressants work through different mechanisms, with nonlinear connectivity analyses revealing effects not captured by traditional linear measures.
bioRxiv (Cold Spring Harbor Laboratory)
February 14, 2025
Emma Peters, Kathrin Fischer, Daniel Erlacher
preprint
Lucid dreaming, where the dreamer is aware they are dreaming, could be used for motor practice, well-being, and nightmare therapy, but such applications require dream control. This investigation tested whether eight healthy participants (aged 24-50) could juggle—a complex motor skill—within a lucid dream. Four participants had lucid dreams, and two successfully juggled, demonstrating high dream control. Trait differences, including belief, motivation, and self-efficacy, appeared to influence dream control abilities. The small sample limits conclusions, but the findings suggest psychological traits play a role in dream control, laying groundwork for future research to optimize lucid dreaming applications in therapy, sports training, and cognitive science.
bioRxiv (Cold Spring Harbor Laboratory)
January 14, 2025
Alexia L Zylko, Ryan J. Rakoczy, Brianna F Roberts et al.
preprint
Psilocybin, the psychedelic compound in magic mushrooms, produced head twitch responses in adult rats but not in adolescent rats. Adult female rats in diestrus showed more head twitches after psilocybin than those in proestrus, indicating that hormonal phase influences the response. Adolescent exposure to psilocybin did not cause lasting changes in anxiety-like behavior or behavioral flexibility. No age- or estrous-related differences were found in 5-HT2A receptor expression in the medial prefrontal cortex. These results show age- and sex-dependent differences in psychedelic effects and emphasize the need for inclusive research that accounts for age, sex, and hormonal status.
bioRxiv (Cold Spring Harbor Laboratory)
January 2, 2025
Marcel Socoró-garrigosa, Yonatan Sanz Perl, Morten L. Kringelbach et al.
preprint
Using whole-brain models guided by the Thermodynamics of Mind framework, the authors estimated the brain hierarchy of specific brain states and simulated transitions between states. Applying this to major depressive disorder, they built models of depressed patients before and after psilocybin and escitalopram treatments. Dynamic sensitivity analysis showed that susceptibility to change was on average reduced by escitalopram and increased by psilocybin, and both treatments promoted healthier transitions. These results align with the post-treatment plasticity window opened by serotonergic psychedelics and with the similar clinical efficacy of both drugs observed in clinical trials.
bioRxiv (Cold Spring Harbor Laboratory)
November 28, 2024
T. Ben Tal, Ilana Pogodin, Alexaner Botvinnik et al.
preprint
Combining psilocybin with NMDAR modulators D-serine or D-cycloserine reduces hallucinogenic-like effects and enhances neuroplasticity in mice. Psilocybin alone increased head twitch response, a surrogate for hallucinogenic effects, which was dose-dependently reduced by either modulator. The combinations also decreased MK-801-induced hyperactivity, modeling antipsychotic effects. The psilocybin-D-serine combination increased GAP43 expression across all four brain regions examined and overall synaptic protein expression in the hippocampus, while psilocybin-D-cycloserine elevated PSD95 levels in all four regions, indicating synaptogenic synergy. These results suggest that pairing serotonergic psychedelics with NMDAR modulators may improve therapeutic efficacy and safety.
bioRxiv (Cold Spring Harbor Laboratory)
November 3, 2024
Ling-Xiao Shao, Clara Liao, Pasha A. Davoudian et al.
preprint
A single dose of psilocybin increased the density of dendritic spines in both subcortical-projecting pyramidal tract (PT) and intratelencephalic (IT) cell types in the mouse medial frontal cortex. Silencing PT neurons eliminated psilocybin's ability to ameliorate stress-related phenotypes, whereas silencing IT neurons had no detectable effect. In PT neurons only, psilocybin boosted synaptic calcium transients and elevated firing rates acutely after administration. Targeted knockout of 5-HT2A receptors abolished psilocybin's effects on stress-related behavior and structural plasticity. These results identify a pyramidal cell type and the 5-HT2A receptor in the medial frontal cortex as essential for psilocybin's long-term drug action.
bioRxiv (Cold Spring Harbor Laboratory)
September 29, 2024
Sabrina Zequeira, Emely A. Gazarov, Alara A. Güvenli et al.
preprint
Acute cannabis smoke enhanced working memory accuracy in aged male rats but impaired it in aged females, with no effects in young adults of either sex. The same smoke had minimal effects on a hippocampus-dependent memory task regardless of age or sex. Chronic oral Δ9-tetrahydrocannabinol (Δ9THC) enhanced working memory in aged rats of both sexes while not affecting young adults, and did not affect spatial learning or memory in either age group. Minimal age differences in Δ9THC pharmacokinetics were observed. Cannabis and Δ9THC can attenuate working memory impairments that emerge in aging without exacerbating age-associated hippocampus-dependent cognitive decline.
bioRxiv (Cold Spring Harbor Laboratory)
September 23, 2024
Michal Lazar, Michal Brownstien, Alexander Botvinnik et al.
preprint
Juvenile mice lacking the SAPAP3 gene, a model of obsessive-compulsive disorder (OCD), show anxiety-like behaviors before they develop the excessive self-grooming that mimics OCD compulsions. Compared to normal mice, these knockout mice spent less time in open areas, buried fewer marbles, and found fewer hidden objects. A single dose of psilocybin (4.4 mg/kg) did not reduce these anxiety-like behaviors. In adult but not juvenile male knockout mice, levels of several synaptic proteins (GAP43, synaptophysin, SV2A) were elevated across brain regions, suggesting compensatory plasticity changes that emerge with age. The findings parallel the clinical observation that anxiety often precedes OCD in humans and indicate that psilocybin's therapeutic effects may be age-dependent.
bioRxiv (Cold Spring Harbor Laboratory)
July 22, 2024
Irina Topchiy, Bernat Kocsis
preprint
Activating the cannabis-1 receptor fundamentally alters brain network activity during sleep. In rats, the CB1-R agonist disrupted the normal structure of intermediate sleep and rapid eye movement sleep episodes, lengthening intermediate sleep six-fold and intruding into REM sleep, where ongoing theta rhythm was drastically reduced. Sleep spindle architecture was also affected: spindle amplitude increased and peak frequency shifted down into the theta range. These results may help explain cannabis's dual effect on cognitive states and the role of network oscillations in psychiatric pathology.
bioRxiv (Cold Spring Harbor Laboratory)
March 31, 2024
David Martin, Á.v. Delgado, Donna J. Calu
preprint
Psychedelics may help treat neuropsychiatric disorders by disrupting entrenched associations and promoting new learning. In rats performing a Pavlovian task where sequential cues predict rewards, the psychedelic DOI (a 5-HT2A/2C agonist) increased dopamine signaling in the nucleus accumbens core to rewards and to cues immediately preceding them, but not to more distal predictive cues. This elevated dopamine occurred independently of changes in reward value and supports increased prediction error signaling. The findings suggest psychedelics could engage error-driven learning mechanisms to disrupt or form new associations.