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 reduces connectivity in associative brain regions while increasing connectivity in sensory regions, a pattern that emerges over time from administration to peak effects. Baseline connectivity predicts the extent of these changes. The shifts correlate with spatial gene expression patterns of the serotonin 2A and 1A receptors, pinpointing their critical role in the psychedelic state. These findings suggest that sensory integration and associative disintegration may underlie the psychedelic experience, and baseline connectivity could serve as a predictive marker for personalized psychedelic treatment.
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.
Biological Psychiatry
December 7, 2022
Flora Moujaes, Katrin H. Preller, Jie Lisa Ji et al.
44 citations
Precision psychiatry seeks markers of individual differences to predict the best treatment for each patient, but linking molecular changes to brain-system alterations remains a challenge. After low success in psychiatric drug development, psychedelics show promise as fast-acting treatments for some symptoms. Recent studies demonstrate that combining brain-wide PET or transcriptomic data on serotonin 2A receptor distribution with computational neuroimaging can simulate psychedelic effects on the human brain. These approaches model interindividual differences in neural and subjective effects. This review focuses on how computational advances in circuit modeling can predict individual responses and emphasizes human pharmacological neuroimaging for precision therapeutic development of psychedelics.
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.
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.