Brain
January 15, 2004
Olaf Blanke, Théodor Landis, Laurent Spinelli et al.
746 citations
Out-of-body experiences (OBE) and autoscopy (seeing one's body from outside) share common neurological mechanisms rooted in disrupted body perception. In six neurological patients, these experiences were linked to vestibular sensations (floating, flying, rotation), visual body-part illusions (shortening or moving limbs), and the sensation of seeing only part of one's body. Body position before the experience influenced both OBE and autoscopy. Brain damage or dysfunction localized to the temporo-parietal junction (TPJ) in five patients. The findings suggest OBE and autoscopy result from a failure to integrate proprioceptive, tactile, visual, and vestibular information about one's own body, combined with a vestibular dysfunction that disconnects personal space from extrapersonal space, caused by temporary TPJ dysfunction during impaired consciousness.
Brain
February 28, 2010
R. L. Carhart-Harris, K. J. Friston
580 citations
Freudian constructs may have neurobiological substrates. Descriptions of primary and secondary processes align with self-organized activity in hierarchical cortical systems, and descriptions of the ego align with functions of the default-mode network and its exchanges with subordinate brain systems. This account views the brain as a hierarchical inference machine that minimizes free-energy, a process formally similar to Freudian energy treatments. The synthesis is substantiated by showing that descriptions of the primary process are consistent with the phenomenology and neurophysiology of rapid eye movement sleep, early acute psychotic states, temporal lobe epilepsy auras, and hallucinogenic drug states.
Brain
April 9, 2013
234 citations
Large-scale brain networks coordinate human behavior, and their anatomy helps explain how neurodegenerative diseases progress. Alzheimer's disease targets the default mode network, while behavioral variant frontotemporal dementia targets the salience network. The default mode network is active when healthy people consider personal moral dilemmas, yet Alzheimer's patients respond normally to these dilemmas, whereas frontotemporal dementia patients give abnormally utilitarian responses. This discrepancy may arise because the salience network modulates default mode network activity.
Brain
March 6, 2021
Joel Frohlich, Daniel Toker, Martin M. Monti
204 citations
High amplitude delta waves (1–4 Hz) in EEG have long been considered a marker of unconsciousness, observed during deep sleep, anesthesia, seizures, and disorders of consciousness. However, recent studies report prominent delta activity during conscious states, including Angelman syndrome, epilepsy, propofol anesthesia with behavioral responsiveness, postoperative delirium, dreaming, and psychedelic states. Older clinical reports also describe awake, conscious patients with high amplitude delta in Rett syndrome, Lennox-Gastaut syndrome, schizophrenia, mitochondrial diseases, hepatic encephalopathy, and non-convulsive status epilepticus.
Brain
October 22, 2021
Manoj K Doss, Maxwell B Madden, Andrew Gaddis et al.
196 citations
Classic psychedelic drugs like psilocybin and LSD may help treat psychiatric disorders by altering brain circuits. Two existing models—the cortico-striatal thalamo-cortical (CSTC) model and the relaxed beliefs under psychedelics (REBUS) model—highlight different subcortical structures in mediating these effects. This paper introduces a third circuit-level model, the cortico-claustro-cortical (CCC) model, focusing on the claustrum, a thin strip of grey matter that densely expresses serotonin 2A receptors. The CCC model proposes that the claustrum entrains canonical cortical network states, and psychedelic drugs disrupt 5-HT2A-mediated coupling between claustrum and cortex, attenuating these networks. Together, the three models may explain many phenomena of the psychedelic experience.
Brain
January 1, 2024
25 citations
Serotonin 2A receptor (5-HT2AR) signaling drives both the evolutionary expansion and ongoing modulation of the human cerebral cortex's most complex cognitive centers. The cortex is organized along a gradient from simple sensory processing to high-level integration, with the transmodal cortex at the apex—a region disproportionately enlarged in humans and rich in 5-HT2AR expression. During early brain development, 5-HT2AR signaling on neural progenitor cells stimulates their proliferation, contributing to cortical expansion. In the adult brain, 5-HT2AR agonism promotes neuroplasticity, learning, and cognitive flexibility with therapeutic potential. The receptor thus plays a dual role in enabling cortical growth and sophisticated functioning.
Brain
May 4, 2024
Jérôme Jeanblanc, Romain Bordy, Grégory Fouquet et al.
10 citations
Psilocybin reduces alcohol self-administration in rats by 50% when injected 4 hours before a drinking session, either intraperitoneally (1 mg/kg) or directly into the left nucleus accumbens (0.15 μg), but not the right nucleus accumbens or left ventral tegmental area. The effect is blocked by a 5-HT2A receptor antagonist injected into the left nucleus accumbens. Psilocybin increases dopamine D2 receptor mRNA in the nucleus accumbens and prefrontal cortex of rats that self-administered alcohol, but not saccharin, and increases D1 receptor mRNA only in the prefrontal cortex. These findings suggest psilocybin acts through the 5-HT2A receptor in the left nucleus accumbens, potentially via increased D2 receptor expression, and reveal unexpected hemispheric lateralization of psychedelic effects.
Brain
December 12, 2025
2 citations
The entropic brain hypothesis, introduced in 2014 and revised in 2018, proposes that along a dimension of the size of phenomenal consciousness, expansive states—such as expert meditation, psychedelic drug states, and near-death-like experiences—reliably exhibit increased brain entropy, whereas states of reduced or no consciousness—including deep sleep, anesthesia, and disorders of consciousness—show low brain entropy. The hypothesis demonstrates convergent, correlative, predictive, discriminative, and external validity. For example, increased brain entropy under psilocybin predicts improved wellbeing one month later. Changes in brain entropy selectively index the breadth of subjective experience rather than arousal. An entropy-related function is also applied in generative artificial intelligence. The entropic brain is a useful model of conscious states.
Brain
October 19, 2025
Rebecca C. Coray, Vincent Beliveau, Josua Zimmermann et al.
1 citation
Regular recreational use of MDMA (Ecstasy) is linked to verbal memory problems, and this study examined the brain changes underlying these deficits. Comparing 61 MDMA users with 61 matched non-users, the researchers found reduced grey matter volume in hippocampal regions and impaired verbal learning, short-term recall after interference, long-term recall, and recognition in users. Self-reported MDMA use over the past six months correlated with several memory scores. Hippocampal volume, especially in the CA1 subregion, was inversely related to verbal long-term memory and to MDMA use intensity measured by hair concentrations. Differences in grey matter between groups correlated with brain serotonin receptor densities, suggesting a serotonergic basis for the structural and memory changes.
Brain
May 15, 2026
The authors argue that the consequences of MDMA use cannot be easily separated from the effects of other drug use or lifestyle factors, highlighting the difficulty in attributing specific outcomes solely to MDMA.
Brain
April 30, 2026
The effects of MDMA use are difficult to separate from the influence of other drugs and lifestyle factors.