Nature Communications
July 18, 2016
Erez Simony, Christopher J Honey, Janice Chen et al.
689 citations
The default mode network (DMN) reconfigures moment by moment to encode information about a changing environment, as shown by a new method called inter-subject functional correlation (ISFC). ISFC isolates stimulus-dependent correlations between brains exposed to the same stimulus, separating them from intrinsic neural processes and noise. In an fMRI experiment, subjects listened to an auditory narrative or temporally scrambled versions. ISFC revealed DMN correlation patterns locked to each narrative segment and specific to its meaning. These patterns were highly replicable across groups, and DMN coupling strength predicted memory of narrative segments, linking brain network dynamics to stimulus features and behavior.
Nature Communications
June 3, 2019
Farhan Ali, Danielle M. Gerhard, Katherine Sweasy et al.
201 citations
A subanesthetic dose of ketamine suppresses somatostatin-expressing (SST) interneurons in the medial prefrontal cortex of awake mice, leading to deficient dendritic inhibition. This causes greater synaptically evoked calcium transients in the apical dendritic spines of pyramidal neurons. By manipulating NMDAR signaling via GluN2B knockdown, the authors show that this dendritic inhibitory mechanism affects frontal cortex-dependent behaviors and cortico-cortical connectivity. The results demonstrate dendritic disinhibition and elevated calcium levels in dendritic spines as key local-circuit alterations driven by subanesthetic ketamine.
Nature Communications
September 25, 2020
Peter Lush, Vanessa Botan, R. B. Y. Scott et al.
136 citations
Hypnotisability—a normally distributed, stable trait—predicts experiential changes like hallucinations in response to imaginative suggestion, which feel involuntary. Such experiences can also be triggered by implicit suggestion outside hypnosis. In three large samples (156, 404, and 353 participants), substantial relationships were found between hypnotisability and experiential change in mirror-sensory synaesthesia and the rubber hand illusion, comparable to relationships with individual hypnosis scale items. The control of phenomenology to meet expectancies from perceived task requirements may explain experiential change in psychological experiments.
Nature Communications
April 29, 2019
Cirong Liu, Cecil Chern-Chyi Yen, Diego Szczupak et al.
127 citations
The default mode network (DMN) in humans is characterized by strong connections among the medial prefrontal cortex, posterior parietal cortex, and posterior cingulate cortex. In common marmosets, however, the dorsolateral prefrontal cortex shows robust functional and anatomical connections with the posterior DMN regions, while the medial prefrontal cortex has weak connections. This pattern differs markedly from the human DMN, suggesting that the medial prefrontal cortex may support brain functions that are more developed in humans than in other primates.
Nature Communications
February 25, 2022
Minji Lee, Leandro Sanz, Alice Barra et al.
120 citations
A deep-learning-based explainable consciousness indicator (ECI) uses EEG responses to transcranial magnetic stimulation and resting-state EEG to separately quantify arousal and awareness. Tested during sleep (n=6), general anesthesia (n=16), and severe brain injury (n=34), ECI distinguishes states such as ketamine-induced anesthesia and rapid eye movement sleep, which combine low arousal with high awareness. Parietal brain regions are most relevant for these measurements. The indicator offers a way to disentangle the two components of consciousness across physiological, pharmacological, and pathological conditions.
Nature Communications
May 12, 2022
Radhika Rawat, Elif Tunc-Ozcan, Tammy L. Mcguire et al.
69 citations
Activation of adult-born immature granule neurons (ABINs) in the mouse hippocampal dentate gyrus is both necessary and sufficient for the rapid antidepressant effects of ketamine. Ketamine activates ABINs in stressed and unstressed mice. Chemogenetic inhibition of ABIN activity blocks ketamine's antidepressant effects, while chemogenetic activation of ABINs mimics both the cellular and behavioral effects of ketamine without changing neuron numbers. These findings identify ABINs as a specific cell population mediating ketamine's antidepressant actions, suggesting that targeting ABINs could preserve therapeutic efficacy while limiting side effects.
Nature Communications
March 29, 2023
Fangyun Tian, Laura D. Lewis, David W. Zhou et al.
63 citations
Ketamine produces different brain oscillations in distinct regions: gamma oscillations in prefrontal cortex and hippocampus, linked to antidepressant effects, and a 3 Hz oscillation in posteromedial cortex, linked to dissociative effects. By analyzing intracranial recordings from humans and comparing effects with propofol, the authors identified that these frequency-dependent patterns arise from distinct neural circuits, potentially guiding development of biomarkers and treatments for depression.
Nature Communications
March 28, 2024
Jesse Hudspeth, Kai Rogge, Sebastian Dörner et al.
24 citations
Psilocybin, the natural hallucinogen in magic mushrooms, is produced in a final biosynthetic step where the enzyme PsiM adds two methyl groups to norbaeocystin. Atomic-resolution crystal structures (0.9 Å) of PsiM at different reaction stages reveal its detailed methylation mechanism. Structural and phylogenetic evidence indicates PsiM evolved from METTL16-family RNA methyltransferases, and its bound substrates mimic RNA. Limitations inherited from its ancestral scaffold prevent efficient psilocybin assembly and block trimethylation to aeruginascin. These insights will aid bioengineering efforts to create psilocybin variants with improved therapeutic properties.
Nature Communications
September 9, 2024
Zirui Huang, George A. Mashour, Anthony G. Hudetz
23 citations
Anesthesia-induced unconsciousness involves a shift in the functional geometry of thalamocortical circuits, moving from a normal unimodal-transmodal pattern to a transmodal-deficient one. This alteration is linked to spatial variations in matrix cell composition within the thalamus, suggesting that disrupted connectivity of matrix cells plays a key role in the loss of consciousness. The study used functional magnetic resonance imaging in healthy volunteers during conscious baseline, deep sedation, and recovery, applying a functional gradient mapping technique to delineate these changes. The findings bridge cellular and systems-level understanding of consciousness.
Nature Communications
October 19, 2023
Laura M Hack, Xue Zhang, B. Heifets et al.
20 citations
Ketamine rapidly induces altered states of consciousness, but the neural mechanisms are unclear. In a randomized, placebo-controlled study with nonclinical adults, functional neuroimaging examined brain activity during emotional tasks under placebo, low-dose (0.05 mg/kg), and high-dose (0.5 mg/kg) ketamine. Different dissociative experiences had opposing effects on right anterior insula activity: depersonalization reduced task-evoked activity by 0.39 standard deviations, while dissociative amnesia increased it by 0.32 standard deviations. These findings suggest that specific dissociative states may influence how ketamine affects brain activity, potentially informing treatment responses in depression.
Nature Communications
February 12, 2025
Farid Aboharb, Pasha A. Davoudian, Ling-Xiao Shao et al.
19 citations
A machine-learning pipeline using light sheet fluorescence microscopy to measure immediate early gene expression in mouse brain tissues classified psychoactive drugs with 67% accuracy across eight conditions, significantly above the 12.5% chance level. Psilocybin was discriminated from 5-MeO-DMT, ketamine, MDMA, or acute fluoxetine with over 95% accuracy. Shapley additive explanation identified brain regions driving predictions, suggesting a novel approach for characterizing and validating psychoactive drugs with psychedelic properties.
Nature Communications
January 22, 2026
Nicholas Gregory, Tyler Girard, Akila Ram et al.
5 citations
Psilocybin, a psychedelic compound, was tested for direct pain-relieving effects in mice with inflammatory, nerve injury, and muscle pain. Across a range of doses (0.3, 2, and 10 mg/kg) in both sexes, using multiple sensory and functional pain tests, psilocybin showed no analgesic effect except for reduced cold sensitivity. That reduction likely resulted from psilocybin-induced hypothermia rather than true pain relief. The findings suggest that any lasting therapeutic benefits of psilocybin for chronic pain are not due to direct analgesic action.
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
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
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
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
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
January 15, 2019
Brendan D. 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.