bioRxiv (Cold Spring Harbor Laboratory)
Shawn. M. Aarde, Pai-Kai Huang, Michael A. Taffe
1 citation
preprint
In rats, high ambient temperature (30°C) increases the acquisition of intravenous self-administration of MDMA more than low temperature (20°C). Initially, MDMA caused similar hypothermia in both temperature groups, but this effect diminished over training in the hot group. Activity levels, initially lower in the hot group, became similar by the end of training. When temperature conditions were swapped, rats trained in the hot condition increased MDMA intake under cold, while those trained in the cold modestly decreased intake under hot. Rats with higher MDMA intake showed blunted hypothermia after non-contingent MDMA. High temperature alone raised brain reward thresholds, and MDMA lowered thresholds below baseline only at low temperature. The findings suggest that high temperature enhances MDMA self-administration acquisition through an aversive effect rather than thermoregulatory motivation.
bioRxiv (Cold Spring Harbor Laboratory)
Iga Adamska, Karolina Finc
1 citation
preprint
Listening to music while under the influence of LSD alters the brain's moment-to-moment patterns of activity, particularly in networks linked to attention and task performance. In a study of 15 participants who underwent functional MRI scans after taking LSD or a placebo, the combination of music and LSD changed how long the brain stayed in a task-positive state. LSD alone, regardless of music, affected the dynamics of a state involving the default mode, somatomotor, and visual networks. Music itself appeared to have a lingering effect on resting-state brain activity, especially on networks associated with tasks. These findings suggest that music, as part of the setting, can shape the psychedelic experience at a neural level.
bioRxiv (Cold Spring Harbor Laboratory)
Kathleen A. Trychta, Brandon K. Harvey
1 citation
preprint
Hyperthermia—elevated body temperature—triggers the abnormal secretion of proteins normally retained inside the endoplasmic reticulum (ER), a process called ER exodosis. The club drugs MDMA (ecstasy) and caffeine, alone or combined, worsen this protein leakage in a cellular model. Hyperthermia also activates the unfolded protein response (UPR), a cellular stress pathway, but the drugs do not alter most UPR-related gene expression despite increasing ER exodosis of UPR proteins. One exception: MDMA raised BiP/Grp78 mRNA levels under hyperthermia. These results suggest that using club drugs in hot environments disrupts ER protein balance, potentially increasing cell toxicity.
bioRxiv (Cold Spring Harbor Laboratory)
Lucas Dwiel, Angela Henricks, Elise Bragg et al.
1 citation
preprint
Lysergic acid diethylamide (LSD) acutely reduces low-frequency electrical activity across the brain in rats, an effect that returns to normal after 24 hours. However, brain stimulation applied during a window of heightened neuroplasticity 24 hours after LSD produces larger and distinct changes in brain activity compared to stimulation after a placebo. This proof-of-concept finding suggests that psychedelic drugs may work in combination with brain stimulation to achieve enhanced effects on brain activity, with future work needed to assess impacts on behavior.
bioRxiv (Cold Spring Harbor Laboratory)
July 20, 2026
Neil K. Savalia, Ling-Xiao Shao, Cory A. Knox et al.
Psilocybin transiently increases calcium event rates in apical dendritic tufts of pyramidal tract neurons in the mouse medial frontal cortex, an effect that parallels the drug's brain pharmacokinetics. This acute effect occurs selectively during quiet wakefulness and depends on the 5-HT2A receptor. Under normal conditions, dendritic calcium signaling predicts subsequent spine formation, but psilocybin disrupts this relationship. The findings suggest that the mechanisms linking acute dendritic activity to long-term structural plasticity differ between physiological and psychedelic-induced plasticity.
bioRxiv (Cold Spring Harbor Laboratory)
July 17, 2026
Priyamvada Modak, Joshua W. Brown
During a risky decision-making task, participants reported how much free will they experienced. Brain regions in the mid-cingulum and middle frontal gyrus showed a positive association with self-reported free will, while the hippocampus and parahippocampal gyrus showed a negative association. Requiring participants to report their free will experience increased BOLD signal in the striatum during decisions. Behaviorally, reaction time showed a positive trend with free will. The small sample size limits conclusions, but the results offer a proof-of-concept for studying the neural and behavioral mechanisms of the subjective experience of free will.
bioRxiv (Cold Spring Harbor Laboratory)
July 17, 2026
Yoko Nagai
Mental imagery vividness is linked to cardiovascular physiology. Elevated diastolic blood pressure during an autonomic challenge predicted reduced vividness of mental images, especially for disgust and neutral scenes. Acute autonomic changes from a tilt table did not alter imagery vividness overall. The findings support the idea that mental imagery emerges from interactions between neural and bodily systems, and suggest cardiovascular function as a potential contributor to altered imagery experiences.
bioRxiv (Cold Spring Harbor Laboratory)
July 16, 2026
Filip Novický, Nikola Jajcay, Jaroslav Hlinka
Neural avalanches—bursts of coordinated brain activity—are typically studied using scale-free statistics, but their detailed spatiotemporal structure and recurrence have been difficult to analyze due to variability in duration and spatial extent. A new method using flexible alignment with unbalanced optimal transport and subsequence dynamic time warping allows comparison of events of different lengths and configurations. Applied to 64-channel EEG data from 63 participants in the PsiConnect psilocybin study, hierarchical clustering revealed 12 recurring propagation patterns. Under psilocybin, oscillating sequences—those with alternating polarity and spatial propagation—were reduced relative to stable sequences, shifting the balance toward stable patterns. This effect was confirmed by a permutation test and largely driven by one cluster, indicating specific neural dynamics temporally affected by psilocybin.
bioRxiv (Cold Spring Harbor Laboratory)
July 13, 2026
Natasha L. Mason, Eline Chm Haijen-Bongers, Kim P. C. Kuypers et al.
Female participants reported more intense subjective effects from psilocybin, 2C-B, and LSD than male participants, including feeling more strongly under the drug's influence, reduced vigilance, and impaired control and cognition, with medium-to-large effects consistent across the three drugs. No sex differences were found in empathy measures or peak drug concentrations in blood. These findings suggest pharmacodynamic mechanisms—how the body responds to the drug—rather than pharmacokinetic differences in drug exposure explain the sex differences. The results have implications for dosing, informed consent, and safety monitoring in psychedelic research.
bioRxiv (Cold Spring Harbor Laboratory)
July 10, 2026
Joseph Giorgio, Thomas Morin, Hsiang-Yu Chen et al.
In cognitively normal older adults, β-amyloid (Aβ) buildup in the default mode network impairs learning independently of tau, but higher dopamine synthesis capacity in the dorsolateral striatum can recover that learning performance. Aβ-positive individuals show reduced default mode network activity in response to error feedback, which relates to poorer learning. Computational modeling indicates that Aβ disinhibits the default mode network during error processing, and dopamine synthesis capacity in the dorsolateral striatum rebalances effective connectivity between the default mode network and frontostriatal network, counteracting Aβ-related disruption. These findings suggest that dopaminergic function can partially compensate for Aβ-related learning deficits through network rebalancing, offering a candidate mechanism for cognitive resilience in preclinical Alzheimer's disease.
bioRxiv (Cold Spring Harbor Laboratory)
July 3, 2026
Anastasia Tyulmenkova, Robert W. Stackman
The 5-HT2A receptor antagonists MDL 11,939 and MDL 100,907 produce different effects on fear extinction in adult C57BL/6J mice. Acute administration of either antagonist increased freezing to the first conditioned stimulus, indicating enhanced fear expression. Repeated MDL 11,939 impaired extinction, increasing freezing across trials and the number of trials to reach criterion, while MDL 100,907 did not significantly alter extinction. Selective 5-HT2C antagonism with SB 242084 did not affect fear expression or extinction. These results suggest ligand-specific and dose-dependent effects of 5-HT2A receptor antagonism on fear extinction, possibly through distinct intracellular signaling pathways.
bioRxiv (Cold Spring Harbor Laboratory)
July 3, 2026
Sébastien Czajko, Jelle Zorn, Oussama Abdoun et al.
Nondual meditation, specifically Open Presence (OP) practice, is associated with reduced bodily self susceptibility and increased large-scale integration of functional brain networks. Expert meditators with over 10,000 hours of practice showed lower global network eccentricity during OP compared to novices, particularly in dorsal attention, ventral attention, and frontoparietal networks, indicating greater integration. These neural patterns correlated positively with measures of bodily self illusion and negatively with cognitive defusion, a construct reflecting reduced self-grasping toward thoughts. The findings suggest that nondual awareness involves alterations in self-representation and large-scale functional brain integration.
bioRxiv (Cold Spring Harbor Laboratory)
July 2, 2026
Marco S. Fabus, Stephen Zerfas, Alex Gruver et al.
Jhana meditation produces states of self-reinforcing bliss that may be useful in clinical and scientific settings, but research has been limited by scarce data and few expert practitioners. To address this, the authors release the largest open-access dataset of electroencephalographic and physiological recordings from expert Jhana meditators, comprising over 100 hours of data from 26 subjects across three retreats. The dataset includes example analysis code. This resource aims to enable broader collaboration and advance understanding of internally generated altered states of consciousness.
bioRxiv (Cold Spring Harbor Laboratory)
July 1, 2026
Fernando Lehue, Iván Mindlin, Carlos Coronel-Oliveros et al.
Disorders of consciousness are linked to large-scale changes in brain dynamics, but the structural factors behind these changes are unclear. Using a whole-brain computational model constrained by diffusion MRI-derived connectivity, the authors show that a node's integration within the structural connectome, measured by a spectral integration metric, strongly predicts its impact on global brain dynamics. Lesions to highly integrative hubs, especially in posterior medial regions like the precuneus and posterior cingulate cortex, drive the system toward low-complexity dynamical regimes resembling disorders of consciousness. Increasing excitability in these regions restores healthy-like dynamics in silico. Perturbations to weakly integrated regions have limited global effects, explaining why damage to specific hubs disproportionately disrupts conscious brain activity.
bioRxiv (Cold Spring Harbor Laboratory)
June 30, 2026
Blake A Fordyce, Yi-Ting Chiu, Nicholas A. Wright et al.
Activation of mGluR2, the primary presynaptic autoreceptor for glutamate in the brain, attenuates the behavioral and electrophysiological effects of psychedelics. The mechanisms behind this are debated, with two competing hypotheses: direct actions via mGluR2/5-HT2A heterodimers, or presynaptic inhibition of glutamate release. In mice expressing tagged receptors, mGluR2 agonist pretreatment reduced the head twitch response induced by the psychedelic DOI. Multiple orthogonal in vivo and in vitro approaches found no evidence for receptor colocalization or oligomerization under basal or agonist-exposed conditions, nor for mGluR2-mediated modulation of 5-HT2A ligand binding. The findings support models where mGluR2 signaling modulates 5-HT2A receptor activity in layer V pyramidal neurons rather than requiring mGluR2/5-HT2A multimers.
bioRxiv (Cold Spring Harbor Laboratory)
June 26, 2026
Paulina Clara Dagnino, Irene Acero-Pousa, Robin Carhart-Harris et al.
A central challenge in neuroscience is understanding how the human brain is organised to support optimal functioning and adaptability. One approach to characterise complex brain dynamics is by artificially perturbing whole-brain models. Here, we asked whether whole-brain organisation under perturbation in major depressive disorder (MDD) changes after intervention with psilocybin and escitalopram. First, we built whole-brain models of pre- and post-treatment resting-state functional magnetic resonance imaging (fMRI) and obtained an initial generative effective connectivity (GEC) matrix for each individual.
bioRxiv (Cold Spring Harbor Laboratory)
June 23, 2026
Deysha Poyser, Eugenio Rodríguez
Intense aesthetic experiences involve distinct neural states rather than simply stronger versions of ordinary responses. Electroencephalography recordings from 22 Chilean participants viewing 113 artworks revealed threshold-specific neurodynamics: beta-band power and its interaction with the aperiodic 1/f exponent predicted the transition to the most intense response during viewing, while the aperiodic exponent alone predicted the shift from very low to higher intensity after viewing. Individual differences in alpha and gamma activity improved predictive performance, indicating meaningful neural variability in aesthetic processing. These findings support the hypothesis that being intensely moved constitutes a qualitatively distinct neural state.
bioRxiv (Cold Spring Harbor Laboratory)
June 22, 2026
Julie Boyer, Nathan Beraud, Benoît Béranger et al.
Conscious perception is linked to all-or-none late brain activations that exhibit bifurcation dynamics, even without a task. Using fMRI and near-threshold auditory stimulation, this study identified the brain networks producing these bifurcations and how they differ depending on task context. Stimulus intensity modulated activity across broad networks including sensory and extra-sensory regions like the prefrontal cortex in both task and no-task contexts. These networks had both shared and distinct components. Single-trial modeling revealed bifurcation dynamics beyond primary sensory cortices and allowed prediction of conscious perception on individual trials in both contexts, resolving previous conflicting results and showing common networks and dynamics underlying conscious perception regardless of task.
bioRxiv (Cold Spring Harbor Laboratory)
June 12, 2026
Nikola Jajcay, Čestmír Vejmola, Jakub Korčák et al.
Psilocybin accelerates the temporal dynamics of large-scale brain activity while preserving access to the normal repertoire of brain states. In a double-blind, placebo-controlled crossover study of 15 healthy volunteers, EEG microstate analysis revealed that psilocybin increased the number of global field power peaks and reduced microstate lifespan while increasing their frequency of occurrence during peak intoxication (50–100 minutes after administration), indicating faster transitions between brain states. Microstate coverage was largely unchanged except for a transient difference in the 2–20 Hz bandwidth. Individual differences in these microstate dynamics correlated with both acute subjective experience intensity and self-reported psychological changes 28 days later, suggesting EEG microstates as candidate neural markers linking acute psychedelic effects to longer-term outcomes.
bioRxiv (Cold Spring Harbor Laboratory)
June 9, 2026
Morten L. Kringelbach, Gustavo Deco
Brain dynamics can be described in three mathematical languages—connectome harmonics, turbulence, and complex harmonics (CHARM)—which are unified as a single self-adjoint operator and its spectral measure. The connectome Laplacian carries this measure; harmonics are its spectral projections, the turbulence smoothing kernel is its resolvent, and CHARM form is its unitary propagator. A shared control parameter, the spectral gap, yields cortical hierarchy, turbulent information cascade, and structured interference. Testing this with a pharmacological perturbation by LSD showed that one scalar coupling simultaneously predicts multi-scale turbulence shifts and macroscale harmonic energy redistribution, supporting the unified operator structure.
bioRxiv (Cold Spring Harbor Laboratory)
May 22, 2026
Somayeh Ataei, Mahdad Jafarzade Esfahani, Nikolai Axmacher et al.
Dream recall varies greatly between people and from night to night. Nocturnal awakenings are thought to help encode and retrieve dreams, but it was unclear whether the frequency, duration, sleep stage, or timing of awakenings matters most. Analyzing two cohorts (708 adults across three waves and 124 adults with high dream recall across multiple nights), trait-level dream recall was associated with a specific pattern: more habitual long REM awakenings and short NREM awakenings. State-level analysis showed that nights with more short and medium REM awakenings increased the likelihood of morning dream recall, while more long REM awakenings increased the likelihood of recalling dream content. Findings support arousal-retrieval and functional state-shift models with important nuances.
bioRxiv (Cold Spring Harbor Laboratory)
May 19, 2026
Saqib Hayat, Francesco Goretti, Rachele Fabbri et al.
EEG-based machine learning can reliably distinguish between three meditation styles (Shamatha, Vipassana, and Metta) and mind-wandering in experienced meditators when models are trained on an individual's own data, achieving high intra-subject accuracy. However, performance drops substantially when models are applied across different people, especially for distinguishing meditation styles, due to large inter-individual variability in meditation-related EEG patterns. Neural distinctions between meditation states become more pronounced over time. These findings support personalized EEG-based assessment of meditative states but highlight the difficulty of creating generalizable, subject-independent classification systems.
bioRxiv (Cold Spring Harbor Laboratory)
May 18, 2026
Vinod Jiani, Ankan Biswas, Supratim Ray
Meditation produces a broad-frequency (15–200 Hz) state-dependent decrease in functional connectivity (phase consistency) between brain regions, while simultaneously enhancing power spectral density (PSD) across the same range. Visual gratings, which boost narrow-band gamma power, reduced gamma FC in both meditators and controls. Aging and gender affected FC only in narrow alpha (8–12 Hz) and high-beta (20–36 Hz) bands. Average referencing severely distorted FC estimates, yielding uninterpretable results. These findings indicate distinct neural mechanisms for meditation, healthy aging, and vision, and caution against using average referencing in phase-based connectivity studies.
bioRxiv (Cold Spring Harbor Laboratory)
May 14, 2026
Shiva Khoshnoud, Federico Alvarez Igarzábal, Marc Wittmann
During flow, a state of full immersion in an activity, brain networks linked to self-referential thinking become less active. Using EEG microstate analysis of 43 people playing a video game, researchers found that two brain states associated with the default mode network (DMN) were shorter and occurred less often during flow compared to boredom or frustration. This suggests that flow reduces self-awareness by dampening DMN activity, similar to effects seen in meditation and psychedelic states.
bioRxiv (Cold Spring Harbor Laboratory)
April 24, 2026
Stephanie Nelli, Pachaya Sailamul, Waraset Wongsawat et al.
Mindful breathing meditation rapidly reduces stress-related brain activity in a context-dependent manner, with effects shaped by prior cognitive state and whether the eyes are open or closed. A factorial experiment manipulated cognitive state (mental arithmetic stress vs. passive viewing), recovery strategy (mindful breathing vs. mind-wandering), and sensory context (eyes open vs. closed). Mental arithmetic increased subjective stress, midline frontal theta power, and posterior beta and gamma power while suppressing posterior alpha power. Eyes-closed mindful breathing produced the greatest stress reduction. Around-ear EEG detected these neural signatures as reliably as full-coverage scalp recordings, supporting wearable neurotechnology for real-world stress monitoring and personalized mindfulness guidance.