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
August 23, 2019
Adam Turnbull, Hao-ting Wang, Charlotte Murphy et al.
197 citations
When a task is undemanding, people often let their minds wander to personally relevant thoughts. The dorsolateral prefrontal cortex (DLPFC), a brain region known for maintaining goal representations, also helps prioritize off-task thinking. Neural activity in the DLPFC was high both when people were on-task under demanding conditions and off-task during a non-demanding task. Individuals who increased off-task thought when external demands decreased showed weaker correlation between neural signals linked to external tasks and lateral default mode network regions within the DLPFC, and had less cortical grey matter in regions sensitive to those external signals. The findings suggest that humans use the DLPFC to align cognition with personal goals when environmental demands drop, prioritizing daydreaming.
Nature Communications
October 3, 2022
S Parker Singleton, Andrea I. Luppi, Robin Carhart-Harris et al.
156 citations
Psychedelics like LSD and psilocybin temporarily alter subjective experience by acting on serotonin 2a (5-HT2a) receptors, increasing the diversity (entropy) of brain activity. This increase may arise from a flattening of the brain's control energy landscape. Using fMRI data, the authors show that these compounds reduce the control energy needed for transitions between brain states compared to placebo. Across individuals, lower control energy correlates with more frequent state transitions and higher entropy. Incorporating PET data on 5-HT2a receptor distribution under non-drug conditions, the analysis links these receptors to reduced control energy. The findings demonstrate that receptor-informed network control theory can model how neuropharmacological manipulation affects brain dynamics.
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 R. D. 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
April 11, 2019
Ingvar R Möller, Marika Slivacka, Anne Kathrine Nielsen et al.
92 citations
The serotonin transporter (SERT) clears serotonin from the synapse, making it a key target for antidepressants and other drugs. Using hydrogen-deuterium exchange mass spectrometry, the authors mapped changes in SERT's shape and flexibility when it binds sodium and potassium ions, the neurotransmitter serotonin, and the drugs S-citalopram, cocaine, and ibogaine. Binding altered dynamics in specific structural regions: TM1, EL3, EL4, and TM12 for ions, and TM1, EL3, and EL4 for the other ligands. These results offer a direct view of how SERT responds to both natural substrates and pharmaceutical compounds, deepening understanding of its structure and function.
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 11, 2024
Andrea I. Luppi, Lynn Uhrig, Jordy Tasserie et al.
43 citations
Loss of consciousness under anesthesia increasingly constrains brain activity to follow the brain's physical structure, collapsing hierarchical cortical organization across scales. This effect was observed with three different anesthetics—propofol, sevoflurane, and ketamine—and was reversed by electrically stimulating the central thalamus, which also restored behavioral signs of arousal. Stimulating the ventral lateral thalamus did not produce these effects, showing specificity. The findings identify distributed brain signatures of consciousness that are orchestrated by particular thalamic nuclei.
Nature Communications
August 23, 2024
David H. Sarrazin, Wilf Gardner, Carole Marchese et al.
41 citations
Depression involves disrupted circadian rhythms, but the role of internal clocks in mood-regulating brain areas was unclear. In a mouse model of depression, the medial prefrontal cortex (mPFC) showed increased expression of circadian negative-loop genes and decreased positive-clock regulators, and the rapid antidepressant ketamine counteracted these changes. Removing the clock gene Bmal1 from excitatory neurons prevented both depression-like behavior and ketamine's effects. Silencing the clock gene Per2 in mPFC produced antidepressant-like effects, while activating REV-ERB worsened depression and blocked ketamine. Boosting the clock activator ROR had antidepressant-like effects, increasing plasticity-related proteins and synaptic receptors in mPFC. The mPFC molecular clock critically regulates depression-like behavior, and targeting it therapeutically may influence glutamatergic plasticity.
Nature Communications
May 9, 2024
Jacinthe Cataldi, Aurélie M Stephan, José Haba-Rubio et al.
32 citations
Incomplete awakenings from non-rapid eye movement sleep can produce sleepwalking and related behaviors, which sometimes involve conscious experience and later recall. Using high-density EEG and immediate interviews, the authors found that conscious experiences during these episodes (56% of cases) were preceded by high-amplitude slow waves in anterior brain regions and activation in posterior regions, patterns similar to those seen in dreaming. Recall of the experience (56% of cases) was linked to higher EEG activation in the right medial temporal area before movement. No conscious experience occurred in 19% of episodes, and no recall in 25%. These findings suggest that the brain activity underlying parasomnia experiences resembles that of dreams, pointing to core processes for sleep consciousness.
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
May 5, 2026
T Lyons, M Spriggs, L Kerkelä et al.
19 citations
A single high dose of psilocybin (25 mg) in 28 healthy, psychedelic-naive participants produced anatomical and functional brain changes lasting from one hour to one month. At one month, participants showed increased cognitive flexibility, psychological insight, and well-being. Diffusion tensor imaging revealed decreased axial diffusivity in prefrontal-subcortical tracts, correlating with reduced brain network modularity. Decreased modularity negatively correlated with increased well-being, consistent with depression findings. Increased cortical signal entropy one to two hours after dosing predicted improved well-being at one month, mediated by next-day psychological insight. No effects occurred with a 1 mg placebo dose.
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
September 20, 2024
Václav Havel, Andrew C Kruegel, Benjamin Bechand et al.
18 citations
A new class of iboga alkaloids, called oxa-iboga, was created by modifying the iboga molecular structure to replace a key component with a benzofuran ring. These compounds lack the heart rhythm risks (proarrhythmic effects) of ibogaine and noribogaine when tested on human heart cells. In male rats, oxa-iboga compounds were more effective than ibogaine at reducing opioid use. They act as potent kappa opioid receptor agonists but produce different behavioral effects than typical kappa agonists. A single dose or short treatment with oxa-noribogaine led to long-lasting reductions in morphine, heroin, and fentanyl intake, reversed persistent opioid-induced pain sensitivity, and suppressed drug-seeking behavior in relapse models. These compounds offer a mechanistically distinct approach to treating opioid use disorder.
Nature Communications
June 22, 2024
Devin P. Effinger, Jessica L Hoffman, Sarah E Mott et al.
15 citations
Psilocin, the psychoactive metabolite of psilocybin, increases activity in the paraventricular nucleus of the hypothalamus (PVN) in rats, a brain region central to stress response, autonomic function, and social behavior. In male rats, psilocin heightened PVN reactivity to an aversive air-puff stimulus, driven by active threat responders, while females showed no such increase. This effect was temporary, with reactivity returning to baseline 2 and 7 days after injection. Prior psilocin did not alter PVN reactivity during acute restraint stress. The findings identify the PVN as a key site of psychedelic action with implications for threat-related behavior.
Nature Communications
August 13, 2025
William Wong, Rubén Herzog, Kátia Cristine Andrade et al.
10 citations
A new open database, the DREAM database, combines standardized sleep magneto/electroencephalography (M/EEG) recordings with dream reports from 505 participants across 20 datasets, totaling 2,643 awakenings. Each awakening includes at least 20 seconds of high-resolution sleep EEG (≥100 Hz, ≥2 electrodes) and a classification of the sleeper's reported experience. Analyses showed that reports of conscious experiences during sleep can be predicted from objective EEG features in both REM and NREM sleep. The database aims to overcome limitations of small sample sizes and methodological variability in dream research, enabling larger-scale investigations of the neurocognitive basis of dreaming.
Nature Communications
November 20, 2025
Alaina M Jaster, Thomas M Hadlock, Belle Buzzi et al.
9 citations
A single dose of the psychedelic psilocybin reduces conditioned behavior and withdrawal caused by the opioid oxycodone in male mice but not in females. This sex-specific effect is mediated by the 5-HT2A receptor in frontal cortex pyramidal neurons that project to the nucleus accumbens. Psilocybin also alters epigenomic regulation after repeated oxycodone exposure and induces sex-specific structural plasticity in the nucleus accumbens independently of the 5-HT2A receptor. Female frontal cortex and nucleus accumbens show fewer changes at gene enhancer regions in response to psilocybin, repeated oxycodone, or their combination compared to males, with the frontal cortex displaying more pronounced sex differences at the epigenomic level.
Nature Communications
August 15, 2024
Davor Curic, Donovan M Ashby, Alexander McGirr et al.
9 citations
Brain activity during quiet wakefulness exhibits scale-free patterns of coordinated neuronal firing, thought to reflect a universal operating mechanism. This study examined how three common anesthetics—isoflurane, pentobarbital, and ketamine—at multiple doses alter these patterns in the mouse cortex using calcium imaging. Low doses largely preserved scale-free statistics, but surgical-plane anesthesia disrupted critical avalanche dynamics, producing multiple abnormal modes. The findings reveal distinct pathways away from the default critical state, depending on the anesthetic and individual responses, suggesting a complex relationship between criticality and consciousness.
Nature Communications
June 10, 2024
Andiara E Freitas, Bo Feng, Timothy Woo et al.
9 citations
A single low dose of ketamine produces both immediate and lasting antidepressant effects, linked to the repair of glutamatergic synapses in the medial prefrontal cortex. In a mouse model of chronic stress, ketamine altered multiple molecular pathways. Cell-cell communication analyses predicted that planar-cell-polarity (PCP) signaling decreased after chronic corticosterone treatment but increased after ketamine in most excitatory neurons. Similar PCP signaling reductions were predicted in the dorsolateral prefrontal cortex of people with major depressive disorder. Neurons connecting the infralimbic prefrontal cortex to the basolateral amygdala regulated immobility and food intake. Knocking out specific PCP proteins in these neurons blocked ketamine's synapse restoration and behavioral improvements, indicating that PCP proteins in this circuit mediate ketamine's effects.
Nature Communications
January 22, 2026
Nicholas Gregory, Tyler E. 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.