eLife
October 25, 2018
Katrin H. Preller, Joshua B. Burt, Jie Lisa Ji et al.
416 citations
Lysergic acid diethylamide (LSD) reduces associative brain connectivity while increasing sensory-somatomotor and thalamic connectivity. These neural effects, along with the subjective experience, are fully blocked by ketanserin, a selective 5-HT2A receptor antagonist. The spatial pattern of LSD's effects across the brain matches the distribution of 5-HT2A receptor gene expression in humans. These results strongly implicate the 5-HT2A receptor in LSD's neuropharmacology, informing the neurobiology of psychedelics and guiding development of psychedelic-based therapeutics.
eLife
April 13, 2015
202 citations
The default mode network, typically linked to internally-directed thoughts like mind wandering, shows reduced activity during many cognitive tasks. However, this network can become more active during a large and demanding switch in task set. Using multivoxel pattern analysis, the authors found that regions within the default mode network encode task-relevant information during task performance. Activity in this network may be driven by major revisions of cognitive context, whether internally or externally focused.
eLife
July 12, 2021
Joshua B. Burt, Katrin H. Preller, Murat Demirtaş et al.
49 citations
A computational model that simulates how LSD affects human brain activity shows that the drug alters communication between cortical areas by increasing the sensitivity of pyramidal neurons via the serotonin-2A receptor. The model accurately reproduced changes in functional connectivity observed in brain scans, and fitting it to individual participants captured personal differences in drug response related to altered consciousness. This approach links molecular drug actions to large-scale brain network changes, offering a path toward personalized medicine.
eLife
March 21, 2024
Yue Hu, Wenjie Du, Jiangtao Qi et al.
27 citations
Ketamine and isoflurane, two general anesthetics, produce unconsciousness through different neural mechanisms in mice. Ketamine activates many brain regions, especially cortical and subcortical areas involved in sensory, motor, emotional, and reward processing, with the temporal association areas acting as a strong hub, suggesting a top-down effect on consciousness by targeting higher-order cortical networks. Isoflurane primarily affects hypothalamic regions controlling neuroendocrine, autonomic, and homeostatic functions, with the locus coeruleus as a connector hub, indicating a bottom-up mechanism. Both anesthetics activate shared pathways for sensory processing, memory, cognition, reward, and autonomic control, revealing overlapping effects.
eLife
April 17, 2024
Flora Moujaes, Jie Lisa Ji, Masih Rahmati et al.
23 citations
Ketamine is a promising treatment for treatment-resistant depression, but why people respond differently is poorly understood. In a single-blind placebo-controlled study, 40 healthy participants received acute ketamine. Using data-driven global brain connectivity, the neural and behavioral effects of ketamine were found to be multi-dimensional, reflecting robust inter-individual variability. Ketamine's principal neural gradient matched somatostatin and parvalbumin cortical gene expression patterns, while the mean effect did not. Behavioral symptom variation mapped onto distinct neural gradients resolvable at the single-subject level. These results highlight the importance of individual variation for developing precise pharmacological biomarkers in psychiatry.
eLife
January 5, 2024
Daniel Toker, Eli Müller, Hiroyuki Miyamoto et al.
21 citations
Bidirectional communication between the cortex and thalamus via a specific cross-frequency channel is linked to conscious states. In humans, mice, and rats, low-frequency waves (1–13 Hz) sent from either the cortex or thalamus are consistently encoded by the other region using high gamma waves (52–104 Hz). This cross-frequency communication is diminished during propofol-induced unconsciousness and generalized spike-and-wave seizures, but enhanced by the psychedelic 5-MeO-DMT. Numerical simulations and neural recordings suggest these changes are mediated by shifts in thalamocortical electrodynamics toward or away from edge-of-chaos criticality, offering a mathematical framework for disrupted information transfer during unconsciousness.
eLife
January 24, 2024
Zepeng Fang, Yuanyuan Dang, Zhipei Ling et al.
16 citations
Saccadic latency is significantly shorter when people are aware of a visual stimulus than when they are unaware. Local field potential recordings from the prefrontal cortex of six patients show early awareness-related activity, including event-related potentials and high-gamma activity, between 200 and 300 milliseconds. The neural activity in the prefrontal cortex can reliably decode the awareness state from an early stage, and the neural pattern changes dynamically rather than remaining stable during awareness. Enhanced dynamic functional connectivity through low-frequency phase modulation between the prefrontal cortex and other brain regions in early awareness trials may explain the mechanism of conscious access. These results indicate that the prefrontal cortex is critically involved in the emergence of awareness.
eLife
May 28, 2025
Johannes Jacobus Fahrenfort, Philippa A Johnson, Niels A Kloosterman et al.
10 citations
Conservative response criterion placement unexpectedly inflates effect sizes in neural measures of both conscious and unconscious processing, while liberal criterion placement reduces them. Simulations and electroencephalography decoding analyses from two studies using common subjective awareness indicators confirm these confounding effects. The widely used Perceptual Awareness Scale (PAS) does not protect against criterion confounds. Follow-up simulations show that the experimental context determines whether the confounding effect is larger for conscious or unconscious neural measures. Criterion placement threatens the construct validity of neural measures of consciousness.
eLife
May 19, 2025
Makaela Nartker, Chaz Firestone, Howard Egeth et al.
9 citations
In inattentional blindness, people fail to report visible stimuli when their attention is elsewhere, famously missing a gorilla. However, the standard measure—asking if they noticed anything unusual—may be biased. In the largest set of inattentional blindness studies to date, participants who denied noticing a stimulus could still report its location, color, and shape, showing that perceptual information remains accessible. Introducing absent trials revealed that observers are biased to report not noticing, essentially playing it safe. These findings provide the strongest evidence yet of significant residual visual sensitivity in inattentional blindness and challenge the claim that awareness requires attention.
eLife
March 2, 2021
Lindsay P Cameron
5 citations
A citizen science approach to research indicates that the improvements in mood and cognition linked to psychedelic microdosing are probably attributable to a placebo effect.
eLife
March 27, 2026
Malin Schmidt, Anne Hoffrichter, Mahnaz Davoudi et al.
3 citations
Psilocin, the psychoactive metabolite of psilocybin, increases BDNF abundance in human cortical neurons derived from induced pluripotent stem cells via the 5-HT2A receptor. Transcriptomic profiling shows gene expression changes that prime neurons for neuroplasticity. Morphologically, psilocin enhances neuronal complexity and increases synaptic proteins, especially in the postsynaptic compartment. Functionally, it leads to increased excitability and enhanced synaptic network activity. These findings suggest psilocin induces a state of enhanced neuronal plasticity, which may explain its therapeutic potential in neuropsychiatric disorders involving synaptic dysfunction.
eLife
May 22, 2025
Michael Pereira, Nathan Faivre, Fosco Bernasconi et al.
3 citations
Neurons in the subthalamic nucleus and thalamus, subcortical brain regions traditionally linked to motor and cognitive control, also play a role in perceptual consciousness. Recording single-neuron activity in patients undergoing deep brain stimulation surgery, researchers found that a significant proportion of these neurons changed their firing rate while participants anticipated a weak vibrotactile stimulus. The firing rate of 23% of these neurons differed between detected and undetected stimuli. This direct neurophysiological evidence suggests that subcortical structures contribute to conscious detection, challenging the prevailing cortico-centric view of the neural correlates of consciousness.
eLife
June 18, 2025
Samuel Noorman, Timo Stein, Jasper Zantvoord et al.
2 citations
Perceptual inference—how the brain integrates visual features into a coherent whole—depends on recurrent processing, the back-and-forth communication between higher and lower cortical regions. Animal studies have implicated NMDA receptors in this process, but human evidence was lacking. In two double-blind, placebo-controlled experiments with healthy participants, the NMDA receptor antagonist memantine selectively improved the brain's ability to decode complex visual illusions (Kanizsa triangles) that require recurrent processing, while leaving simpler visual processing (contrast and collinearity) unaffected. This enhancement occurred only when stimuli were attended and consciously perceived. The findings suggest that blocking NMDA receptors can enhance recurrent processing for attended objects, linking animal and human research on the neural basis of conscious perception.
eLife
May 15, 2025
Tudor M Ionescu, Mario Amend, Rakibul Hafiz et al.
1 citation
A novel imaging technique called molecular connectivity (MC) combines functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) to map how specific molecules, such as the serotonin transporter, interact across brain regions. Using dynamic [11C]DASB PET scans in rats, the study examined changes in serotonin transporter distribution after a single dose of MDMA (ecstasy). Results showed clear alterations in molecular connectivity following MDMA, directly linking drug effects on serotonin transporter occupancy to changes in functional brain networks. This approach provides a comprehensive view of brain function at the molecular level and offers new ways to understand how drugs modulate brain activity.
eLife
December 12, 2014
Thu N Huynh, Eric Klann
1 citation
Ketamine can reduce depression symptoms by targeting NMDA receptors in the brain, as shown in experiments with genetically modified mice. The findings suggest a specific mechanism for the drug's rapid antidepressant effects.
eLife
March 31, 2026
Jessica L Maltman, Javier González-Maeso
Exposure to psilocin, the active metabolite of the psychedelic psilocybin, increases structural complexity and strengthens synaptic connections in human neurons derived from stem cells. These changes suggest enhanced neuroplasticity at the cellular level.
eLife
January 13, 2026
Colin Bredenberg, Fabrice Normandin, Blake Richards et al.
Classical psychedelics produce complex visual hallucinations that are coherent at low levels but surreal at high levels, resembling dream-like states. The oneirogen hypothesis proposes that these perceptual effects arise because psychedelics induce neural activity states similar to dreaming. By simulating psychedelics' effects on neural network models trained with the Wake-Sleep algorithm—which alternates between a perceptual (wake) phase and a generative (dream) phase—partially shifting the model to the 'Sleep' state (increasing top-down connections, consistent with effects on apical dendrites) captures observed phenomena: hallucinations, increased stimulus-conditioned variability, and large synaptic plasticity increases. The hypothesis offers testable predictions for validation.
eLife
May 28, 2025
Ling Liu
When researchers are overly cautious in how they report their analyses of brain activity, it can artificially inflate the apparent relationship between neural measures and conscious or unconscious experiences. This makes it harder to tell the difference between conscious and unconscious processing. The finding suggests that reporting practices can introduce bias that obscures the true distinctions between these two types of experiences.
eLife
May 3, 2024
Mariann Oemisch, Hyojung Seo
Ketamine, a rapid-acting antidepressant, reduces how aversive negative outcomes feel without changing how gains are evaluated, motivation, or other learning processes. In rhesus macaques making token-based decisions, ketamine lowered the impact of losses when given intramuscularly or intranasally. This effect was separate from side effects like fixation errors, which could be countered by strong motivation. The acute reduction in negative event impact may lead to longer-term antidepressant effects by preventing the cumulative buildup of negative memories. The findings suggest that disrupting affective memory could pose challenges in treating depression and invite further study across different mood states and time scales.