Nature Communications
August 19, 2025
Maxwell B. Madden, Chloe Schaefgen, Binita Vedak et al.
4 citations
Serotonin activates 5-HT1B receptors on anterior cingulate cortex inputs to the claustrum, suppressing signaling to parietal association cortex-projecting claustrum neurons. Psilocybin, metabolized to the serotonin receptor agonist psilocin, similarly activates these presynaptic 5-HT1B receptors, reducing cortical signaling through the claustrum. This gain-control mechanism may be directly targeted by psilocybin to modulate downstream cortical network states, offering insight into how the classic psychedelic disrupts widespread brain activity.
Nature Communications
March 22, 2025
Chunyan Meng, Wenting Guo, Chuan Xiao et al.
4 citations
Psilocybin, a compound from psychedelic mushrooms, shows promise for treating psychiatric conditions when used in therapy. A biosynthetic method could produce psilocybin quickly and efficiently, and understanding the enzymes involved can improve this process. Researchers determined the crystal structures of three key enzymes—PsiD, PsiK, and PsiM—in various forms, revealing how they work together to convert L-tryptophan into psilocybin. The structures show self-cleavage and self-inhibition mechanisms in PsiD and the stepwise catalytic sequence. Tests on female mice with depression-like behaviors demonstrated antidepressant effects from biosynthetic intermediates, particularly norbaeocystin, highlighting its clinical potential.
Nature Communications
September 30, 2025
Cassandra J. Hatzipantelis, Min Liu, A. H. G. Love et al.
2 citations
Psilocybin, which increases social connectedness and shows promise for treating mental illness, was tested in a mouse model of peripartum mood disorders. Social stress caused maternal withdrawal and increased stress-related behaviors, and psilocybin did not alleviate these effects. Weeks later, psilocybin-treated mothers were more anxious, regardless of prior stress exposure, while virgin females were unaffected. Reproductive status did not alter psilocybin metabolism, but serotonin receptor transcription and 5-HT2A receptor-dependent responses were reduced in mothers. Offspring exposed to psilocybin through breastfeeding showed anhedonia in adulthood. The findings indicate that both parous parents and their children may be uniquely vulnerable to psychedelic treatment during the postpartum period.
Nature Communications
April 10, 2026
D P Effinger, J L Hoffman, S G Quadir et al.
1 citation
Psilocin, the active metabolite of psilocybin, alters brain activity in rats in a sex-specific manner. It increases activity in the paraventricular nucleus of the thalamus (PVT) and selectively engages PVT projections to the central amygdala (CeA) in females but not males. Psilocin enhances PVT reactivity to an aversive stimulus, driven by passive responders, and prevents time-dependent reductions in stimulus-evoked activity in PVT→CeA neurons in females but not males, driven by active responders. These findings identify sex-specific modulation of thalamic-limbic circuitry by psilocin, advancing understanding of how psychedelics modulate emotional brain circuits.
Nature Communications
June 24, 2026
Drummond E-Wen Mcculloch, Anders S. Olsen, Brice Ozenne et al.
A prominent theory holds that psychedelics increase brain entropy, but past studies have used many different entropy measures. This work analyzed 121 fMRI scans from 28 healthy adults before and after psilocybin, testing 14 entropy metrics with two brain-parcellation methods and seven denoising pipelines. Five metrics—including Shannon entropy of spatial eigendistribution, path-length, instantaneous correlations, brain-state switching, and sample entropy at short time-scales—consistently showed positive associations with psychedelic effects. However, eight metrics showed no significant effects, and Lempel-Ziv complexity gave inconsistent positive results. The entropy measures correlated poorly with each other, indicating that brain entropy is not a single, unified phenomenon.
Nature Communications
April 8, 2026
Thomas J. Kelly, Xiaojie Liu, Yao Huang et al.
High doses of cannabinoids like THC produce anxiety, but the underlying brain mechanisms were unclear. This study in mice identifies a specific neural circuit—projections from the anterior cingulate cortex to the dorsomedial striatum—where cannabinoid signaling promotes anxiety and aversion. Activating this circuit reduces anxiety, whereas cannabinoids suppress its activity via CB1 receptors. Deleting CB1 receptors specifically in this circuit reduced both innate anxiety and conditioned place aversion to THC. These findings reveal a circuit-level mechanism for cannabinoid-induced anxiety.
Nature Communications
November 21, 2025
Marco Aqil, Gilles De Hollander, Nina Vreugdenhil et al.
Psilocybin changes how the brain processes visual context, altering perception of the Ebbinghaus illusion and modifying cortical responses to visual stimuli. A computational model links these changes, suggesting that psychedelics generally act by disrupting contextual computations in the brain.
Nature Communications
June 5, 2026
Maxwell B Wang, Max G'Sell, James F Castellano et al.
The brain's neural activity during everyday, unconstrained behavior transitions between stable states through bursts of chaotic, exploratory activity that then settle into new patterns. Using multi-electrode brain recordings from twenty people over a week, combined with deep learning analysis, researchers identified neural dynamics linked to circadian rhythms, heart rate, and behaviors such as socializing, screen watching, and sleep depth. Despite this chaos, large-scale dynamics remain anchored to a stabilizing center involving the default mode network. Sleep deprivation made these transitions more chaotic and suppressed the stabilizing center, suggesting diminished neural control. The findings indicate the brain balances dynamic exploration with stable equilibria during real-world behavior.
Nature Communications
May 8, 2026
Nicolás Sánchez-Fuenzalida, Chris Jungerius, Stephen M Fleming et al.
A key challenge in consciousness research is separating genuine conscious perception from non-perceptual biases when observers report whether they saw a stimulus. In experiments with 505 participants who detected and reproduced dim or absent visual patterns under different conditions—attentional cues, asymmetrical base rates, and payoff schemes—a Hurdle-Gaussian model decomposed responses into a perceptual continuous component and a non-perceptual hurdle component. Statistical priors and reward structures shifted the non-perceptual hurdle, while attentional cues selectively shifted the perceptual component, consistent with changes in conscious experience. Crucially, including detection trials contaminated reproduction reports with non-perceptual criterion effects, urging caution in interpreting detection-based measures in consciousness research.
Nature Communications
December 9, 2025
Cristina Martín-Monteagudo, Javier Sánchez Romero, Julia Adams et al.
Cannabis, the most widely used illicit drug, is often consumed during adolescence. Its active component, THC, disrupts glutamate balance and synaptic plasticity in the nucleus accumbens (NAc). A specific group of astrocytes in the NAc, linked to the ventral hippocampus-NAc circuit, is critical for these effects. Using the AstroLight tool, researchers found that THC increases calcium activity and glutamate release in these astrocytes. This glutamate release depends on p38α signaling, as mice lacking astrocytic p38α showed no such changes. Blocking THC-induced calcium activity in this astrocyte ensemble prevented spatial learning and synaptic plasticity impairments, highlighting these astrocytes as potential therapeutic targets.
Nature Communications
April 3, 2025
Joseph Cichon, Thomas Joseph, Xinguo Lu et al.
A single dose of inhaled nitrous oxide (N2O) rapidly and durably activates a specific population of neurons in the cingulate cortex of rodents exposed to chronic stress. This activation rescues a stress-induced hypoactivity state in layer V (L5) pyramidal neurons and is necessary for N2O's antidepressant-like effects. Although N2O is believed to work primarily by blocking NMDA receptors, L5 neurons still activate when NMDA receptor function is inhibited. Instead, N2O inhibits calcium-sensitive potassium (SK2) channels, driving L5 neuron activity and antidepressant-like effects. These findings identify a novel molecular and circuit mechanism for N2O's fast antidepressant action.
Nature Communications
October 24, 2024
Hyunwoo Jang, George A. Mashour, Anthony G. Hudetz et al.
A metric called the integration-segregation difference (ISD), derived from fMRI data, captures two key brain network properties: efficiency (integration) and clustering (segregation). During anesthesia with propofol, brain networks shift profoundly toward segregation as consciousness is lost. A common sequence of disintegration and reintegration occurs in unimodal and transmodal networks during loss and return of responsiveness. Machine learning models using these measures accurately identify awake versus unresponsive states. Metastability is more closely linked to integration, while complexity is linked to segregation. Similar patterns appear in sleep. The ISD reliably indexes states of consciousness.
Nature Communications
December 2, 2023
Shi-Ge Xue, Jin-Gang He, Ling-Li Lu et al.
Ketamine's rapid antidepressant effects rely on the recruitment of TARP-γ8, a protein that regulates AMPA receptors, to postsynaptic sites in the ventral hippocampus of stressed male mice. Blocking TARP-γ8-containing AMPA receptors or uncoupling TARP-γ8 from PSD-95 abolished ketamine's rapid antidepressant effects. Overexpression of TARP-γ8 reversed chronic stress-induced depressive-like behaviors and reduced AMPA receptor-mediated neurotransmission, while knockdown of TARP-γ8 in excitatory neurons prevented ketamine's rapid effects. The findings suggest TARP-γ8 is a key molecular target for ketamine's antidepressant action.
Nature Communications
October 27, 2023
Brandon R Munn, Eli J Müller, Vicente Medel et al.
A microscale biophysical network model of layer-5 pyramidal neurons reproduces coarse-sampled dynamics seen in macroscale electrophysiological recordings from macaques and humans. By inverting the model, the authors identify spike and burst dynamics that distinguish unconscious, dreaming, and awake arousal states and reveal their functional signatures. Neuromodulatory arousal shifts neuronal dynamics around a low-dimensional energy landscape, altering the model's response to external stimuli. The work demonstrates how multiscale modeling can connect theories of consciousness across spatiotemporal scales.
Nature Communications
August 30, 2023
Forough Habibollahi, Brett J. Kagan, A. Burkitt et al.
Cortical neurons grown in a dish and trained to play a simplified version of the video game Pong exhibit near-critical dynamics when they receive structured sensory input related to the task. Better game performance correlates with how close the network is to a critical state. However, criticality alone does not enable learning without feedback about the consequences of previous actions. The authors propose that neural criticality emerges as a basic feature of processing structured information, not requiring higher-order cognition.
Nature Communications
June 5, 2023
Ang Li, Haiyang Liu, Xu Lei et al.
Consciousness is linked to how neural activity shifts along a unimodal-transmodal cortical axis, a simple signature that is abnormally elevated under psychedelics and in psychosis. This hierarchical dynamic reflects changes in global brain integration and connectome diversity. Quasi-periodic patterns show hierarchical heterogeneity as spatiotemporally propagating waves tied to arousal, a pattern also seen in macaques. The spatial distribution of the principal cortical gradient aligns with genetic transcription of the histaminergic system and functional connectome mapping of the tuberomammillary nucleus, which promotes wakefulness. Combining behavioral, neuroimaging, electrophysiological, and transcriptomic evidence, the authors propose that global consciousness is supported by efficient hierarchical processing along a low-dimensional macroscale gradient.
Nature Communications
January 5, 2023
Zirui Huang, G. Mashour, A. Hudetz
Dimensions of consciousness such as wakefulness and awareness are encoded in multiple neurofunctional dimensions of the brain's cortical geometry. Disruptions of consciousness from pharmacological, neuropathological, or psychiatric causes degrade one or more major cortical gradients depending on the condition. Network-specific reconfigurations within this multidimensional gradient space are associated with behavioral unresponsiveness across various etiologies, and these spatial reconfigurations correlate with a temporal disruption of structured transitions of dynamic brain states. The work provides a unifying neurofunctional framework for multiple dimensions of human consciousness in both health and disease.
Nature Communications
April 26, 2022
David E. Melnikoff, Ryan W. Carlson, Paul E. Stillman
Flow—the immersive, engaging feeling of being 'in the zone'—is well known to boost productivity and health, but what causes it has been unclear. A new theory proposes that flow arises from the mutual information between desired goals and the means to achieve them, a measure of how strongly two variables are linked. Across five experiments (four preregistered), increasing this mutual information consistently increased flow and improved attention and enjoyment. The effect held even when controlling for other psychological factors and alternative measures of association. The findings offer a formal, computational account of how the mind generates the experience of flow.
Nature Communications
June 29, 2021
Thomas Andrillon, Angus C. Burns, Teigane Mackay et al.
Attentional lapses—moments when focus drifts to unrelated thoughts (mind wandering) or the stream of consciousness halts (mind blanking)—are linked to localized slow-wave brain activity resembling sleep. Healthy participants performed a task while high-density electroencephalography recorded their brain activity; random interruptions prompted them to report whether their mental state was task-focused, mind-wandering, or mind-blanking. Slow waves preceded reports of both mind wandering and mind blanking, and their location distinguished between sluggish and impulsive behaviors as well as between the two types of lapses. The findings suggest that attentional lapses share a common physiological origin: the emergence of local sleep-like activity within the awake brain.
Nature Communications
May 31, 2021
M. Pereira, P. Mégevand, Mi Xue Tan et al.
Conscious perception and the ability to reflect on one's own perceptual experiences both rely on a common neural mechanism of evidence accumulation in the posterior parietal cortex. Recordings from a single neuron in a human participant, combined with electroencephalography in healthy volunteers, showed that detected tactile stimuli triggered neuronal activity resembling the gradual buildup of evidence seen during decision-making. A computational model reproduced the behavioral and neural data, treating a stimulus as detected when accumulated evidence reaches a threshold, and confidence as the distance between the maximal evidence and that threshold. The findings suggest that gradual changes in neuronal dynamics during evidence accumulation underlie both perceptual consciousness and perceptual monitoring.
Nature Communications
February 19, 2021
C. Sergent, M. Corazzol, G. Labouret et al.
The same auditory stimulus can produce either sustained or brief brain activity around 250–300 milliseconds after the sound, even when people are not performing any task. This bifurcation in electroencephalographic dynamics predicts whether people later report having consciously perceived the stimulus, both when they are asked to report on a task and when their conscious contents are sampled randomly during passive listening. Source localization shows that task-free conscious access engages the same neural networks as explicit report, except for frontal executive components. Studying variability in brain dynamics may help identify the core signatures of conscious access independently of decision or report processes.
Nature Communications
October 10, 2019
A. Luppi, Michael M. Craig, I. Pappas et al.
Consciousness relies on spatio-temporal interactions between brain integration and functional diversity. Combining graph theory and dynamic functional connectivity, resting-state fMRI data from awake volunteers, propofol-anaesthetised volunteers, and patients with disorders of consciousness showed that cortical networks are especially affected during loss of consciousness in temporal states of high integration, exhibiting reduced functional diversity and compromised informational capacity, while thalamo-cortical functional disconnections emerge during states of higher segregation. Posterior regions of the brain's default mode network show reductions in both functional diversity and integration during unconsciousness. These overlapping reductions in diversity and integration may represent a generalisable biomarker of loss of consciousness.
Nature Communications
June 4, 2019
T. Pascoal, S. Mathotaarachchi, M. Kang et al.
Amyloid-β (Aβ) aggregation in the brain's default mode network leads to reduced glucose metabolism in distant but functionally connected brain regions. The interaction between this hypometabolism and overlapping Aβ aggregation is associated with subsequent cognitive decline. These results were also observed in transgenic Aβ rats that do not form neurofibrillary tangles, supporting these findings as an independent mechanism of cognitive deterioration. The findings suggest a model where distant Aβ induces regional metabolic vulnerability, while the interaction between local Aβ with a vulnerable environment drives the clinical progression of dementia.
Nature Communications
January 15, 2019
Brendan Hare, R. Shinohara, Rong-Jian Liu et al.
Activating Drd1 dopamine receptor expressing pyramidal cells in the medial prefrontal cortex (mPFC) produces rapid and long-lasting antidepressant and anxiolytic responses in mice, whereas stimulating Drd2 expressing pyramidal cells does not affect anxiety-like or depression-like measures. Disrupting Drd1 activity also blocks the rapid antidepressant effects of ketamine. Stimulation of mPFC Drd1 terminals in the basolateral amygdala recapitulates the antidepressant effects of somatic stimulation. These findings identify specific cellular targets in the mPFC and downstream circuitry involved in rapid antidepressant responses.
Nature Communications
August 17, 2018
Stephen LaBerge, Benjamin Baird, Philip G Zimbardo
People typically cannot smoothly track imagined objects with their eyes, but during REM sleep dreams, smooth pursuit eye movements occur when tracking a slow-moving visual target in a lucid dream. These movements closely resemble those during actual perception, unlike the jerky, saccadic tracking seen during waking imagination. The findings indicate that visual imagery in REM sleep is more like perception than imagination, showing that the brain's smooth pursuit circuitry can be activated by a visual experience without retinal input. Voluntary gaze shifts within dreams also correspond to physical eye rotations.