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.
Biological Psychiatry
January 13, 2020
Katrin H. Preller, Patricia Duerler, Joshua B. Burt et al.
199 citations
Psilocybin, a hallucinogen derived from mushrooms, significantly enhances serotonin receptor activity, leading to notable changes in brain connectivity. In a study with 30 participants, functional magnetic resonance imaging revealed a 60% increase in functional connectivity in areas linked to sensory processing and emotional regulation after psilocybin administration. This shift suggests profound implications for psychology and medicine, particularly in treating mental health disorders. The findings underscore the potential of psychedelics in pharmacology, highlighting their ability to influence behavior through neurotransmitter pathways and chemical synthesis of alkaloids.
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.
Frontiers in neuroscience
January 1, 2023
Alan Anticevic, Michael M. Halassa
41 citations
Psychosis spectrum disorder affects 1% of the world population and leads to chronic disability. Developing treatments for its cognitive deficits is hindered by a weak link between neurobiological understanding and clinical symptoms. This perspective highlights an opportunity combining non-invasive human neuroimaging with insights into thalamic regulation of cortical connectivity. The thalamus forms forebrain-wide functional loops critical for processing external inputs and updating internal models. Evidence shows PSD symptomatology may stem from faulty network organization with the thalamus as a central coordinator. Animal work clarifies thalamic circuits regulating cortical dynamics and cognition.
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.
Molecular psychiatry
April 1, 2025
Devon Stoliker, Katrin H Preller, Leonardo Novelli et al.
19 citations
Psilocybin, the active compound in magic mushrooms, alters visual perception by changing how brain regions communicate. Under psilocybin, early visual areas and higher visual-association regions showed increased self-inhibition, reducing sensitivity to incoming neural signals. At the same time, top-down feedback from visual-association areas to earlier visual regions was enhanced. This shift in balance—less bottom-up sensitivity and stronger top-down influence—may explain the vivid eyes-closed imagery characteristic of psychedelic experiences. The findings come from a double-blind, placebo-controlled study of 24 healthy adults using functional MRI and dynamic causal modeling, and they advance understanding of both basic visual perception and potential clinical applications.
Biological Psychiatry Cognitive Neuroscience and Neuroimaging
July 17, 2023
Flora Moujaes, Nathalie M. Rieser, Christophe Phillips et al.
19 citations
Four methods of inducing altered states of consciousness—psilocybin, LSD, hypnosis, and meditation—produce distinct patterns of brain connectivity, not a single shared neural signature. Pharmacological and nonpharmacological interventions showed connectivity patterns that could predict which method a person had used. Hypnosis and meditation differed from each other and from the drugs. Psilocybin and LSD did not differ in brain connectivity but showed different relationships between brain activity and behavior. The findings clarify how each method works in the brain and suggest they may offer different therapeutic avenues for psychiatric disorders.
medRxiv
September 9, 2022
Devon Stoliker, Katrin H. Preller, Leonardo Novelli et al.
5 citations
preprint
A double-blind, placebo-controlled study of 24 healthy adults found that psilocybin, the active compound in magic mushrooms, alters visual brain connectivity in ways consistent with preclinical models. Under psilocybin, early visual and higher visual-association regions showed increased self-inhibition, while top-down feedback from association areas to earlier visual regions was enhanced. These connectivity changes were linked to decreased sensitivity to neural inputs and the perception of eyes-closed visual imagery. The findings suggest that psilocybin-induced visual imagery arises from reduced bottom-up gain and strengthened top-down influences, informing basic and clinical understanding of visual perception.
bioRxiv Preprint Server
November 1, 2022
Flora Moujaes, Jie Lisa Ji, Masih Rahmati et al.
4 citations
preprint
Ketamine is a promising therapy for treatment-resistant depression, but why some people respond better than others remains unclear. The molecular mechanisms of ketamine are not yet connected to its effects on brain activity and behavior.
bioRxiv Preprint Server
February 10, 2025
Masih Rahmati, Flora Moujaes, Nina Purg Suljič et al.
1 citation
preprint
Working memory deficits in disorders like schizophrenia may stem from disrupted brain cell tuning. Using fMRI, researchers found that ketamine, which blocks NMDA receptors, broadens neural spatial tuning in healthy people, reducing the precision of brain responses across visual, parietal, and frontal areas and worsening spatial working memory accuracy. These tuning changes were more consistent across individuals and brain regions than overall activation changes and correlated with memory performance. The results link NMDA receptor disruption to altered brain circuit dynamics and memory impairment, offering a target for developing treatments.