Nature reviews. Neuroscience
July 5, 2021
Jonathan Smallwood, Boris C. Bernhardt, Robert Leech et al.
970 citations
The default mode network (DMN) is a set of brain regions in the parietal, temporal, and frontal cortex that typically reduce activity during attention-demanding tasks but increase activity during complex cognition linked to memory or abstract thought. These regions are located farthest from sensory and motor systems. The paper considers how knowledge of the DMN's topographic characteristics can be used to better understand its contributions to cognition and behavior.
iScience
February 2, 2021
Jonathan Smallwood, Adam Turnbull, Hao-ting Wang et al.
130 citations
The landscape of ongoing thought is heterogeneous and shaped by both personal traits and environmental context. Recent work shows that attention and control systems organize experience in response to changing demands, while the default mode network contributes not only to task-negative or episodic content but also to the vividness of experience in both task contexts and spontaneous self-generated states. Multiple neural systems reflect the landscape of ongoing thought, and it is important to distinguish processes that shape how experience unfolds from those that regulate it.
Sci Adv
March 16, 2022
Galen Ballentine, Samuel Freesun Friedman, Danilo Bzdok
66 citations
Psychedelics likely alter consciousness by disrupting the usual hierarchy between higher-level association cortex and incoming sensory signals. Analyzing 6,850 free-form testimonials about 27 drugs alongside 40 neurotransmitter receptor subtypes and their gene expression maps in the brain, the authors found that drug-induced changes in awareness correspond to cortex-wide distributions of receptor density. Each receptor-experience factor spanned a continuum from higher-level association to sensory input, possibly reflecting a collapse of hierarchical order among large-scale brain networks. The framework reveals the semantic structure underlying diverse drug experiences and links it directly to brain anatomy.
Nature Medicine
April 1, 2026
Manesh Girn, Manoj K. Doss, Leor Roseman et al.
8 citations
Psychedelic drugs are being studied again for their therapeutic potential, but how they change brain function is not well understood. By combining 11 brain-scanning datasets from five different psychedelics (psilocybin, LSD, mescaline, DMT, and ayahuasca) across three continents, researchers found a common pattern: increased communication between brain networks that handle high-level thinking (default, frontoparietal, and limbic) and those that handle sensory input (visual and somatomotor). Key deep-brain regions (thalamus, caudate, putamen) and the cerebellum also changed how they connect with sensorimotor networks. Contrary to some earlier studies, reductions in within-network connectivity were weak to moderate and varied by drug. These findings help resolve previous inconsistencies and provide a comprehensive map of how psychedelics alter large-scale brain organization.
bioRxiv (Cold Spring Harbor Laboratory)
July 14, 2021
Galen Ballentine, Sam Friedman, Danilo Bzdok
6 citations
preprint
Psychedelic drugs alter consciousness by disrupting how the brain's higher association cortex processes incoming sensory signals. Analyzing 6,850 free-form testimonials about 27 drugs and linking them to 40 neurotransmitter receptor subtypes via gene transcription maps, a pattern-learning approach revealed that specific changes in awareness—such as dissolving self-world boundaries or fractal visual distortions—correspond to distinct distributions of receptor densities across the cortex. Ego-dissolution-like experiences were tied to 5-HT2A, D2, KOR, and NMDA receptors in both deep hierarchical (associative higher-order cortex) and shallow hierarchical (visual cortex) brain regions. Emotional effects involved 5-HT2A and Imidazoline1 receptors, while auditory and visual sensations involved SERT, 5-HT1A, and 5-HT2A receptors. Each receptor-experience factor spanned between higher-level association and sensory input poles, potentially relating to a collapse of hierarchical order among large-scale brain networks.
Research Square
August 8, 2024
Danilo Bzdok, Robin Carhart-Harris, Chloe Savignac et al.
3 citations
Large language models can design, annotate, and evaluate experience dimensions from psychedelic reports, producing over 2 million automatic ratings that discriminate the unique mental effects of 30 psychoactive substances. This approach offers a bottom-up complement to legacy questionnaires for measuring changes in subjective awareness.
bioRxiv (Cold Spring Harbor Laboratory)
January 8, 2025
Delong Zhou, Heike Schuler, Vedrana Cvetkovska et al.
2 citations
preprint
A single dose of psilocybin increases synaptic transmission in the medial prefrontal cortex of mice. Single-cell RNA sequencing reveals that, 24 hours after administration, plasticity-related gene expression rises in excitatory neurons, with particularly robust changes in a deep-layer neuron type called L5/6 NP. This cell-type specificity aligns with 5-HT 2C receptor expression patterns, not 5-HT 2A. Multivariate analyses show that psilocybin-induced gene expression in L5/6 NP neurons predicts 5-HT 2C transcript levels. Blocking 5-HT 2C receptors with an antagonist attenuates the sustained effect on synaptic transmission, identifying 5-HT 2C signaling and L5/6 NP neurons as key mediators of psilocybin's lasting neuroplastic effects.
bioRxiv Preprint Server
June 7, 2026
Andrea I. Luppi, Dragana Manasova, Justine Y. Hansen et al.
preprint
Functional connectivity in the awake human brain is shaped primarily by cognitive co-activation—the tendency of brain regions to work together during mental tasks—more than by structural or molecular constraints. This predominance is systematically lost across five datasets involving pharmacological and pathological perturbations of consciousness (chronic disorders of consciousness; anesthesia with sevoflurane, propofol, or ketamine), when cognition is disconnected from the environment or abolished. During such states, the predictors of functional architecture shift away from cognitive co-activation and toward anatomical and molecular constraints.