Pharmacological Reviews
September 9, 2022
Devon Stoliker, Adeel Razi, Gary F. Egan et al.
83 citations
Classic psychedelics work primarily by binding to serotonergic 5-HT2A receptors, and their agonist activity at these receptors changes synaptic efficacy, profoundly affecting hierarchical message-passing in the brain. This review synthesizes cognitive and neuroimaging evidence showing that psychedelics influence selfhood and subject-object boundaries—a phenomenon called ego dissolution—which may underlie their subjective and therapeutic effects. Because 5-HT2A receptors sit at the apex of the cortical hierarchy, their agonism may powerfully affect sentience and consciousness. Effects can last beyond the pharmacological half-life, suggesting psychedelics promote neural plasticity. Psychologically, they may disarm ego resistance, expanding the repertoire of perceptual hypotheses and enabling alternate pathways for thought and behavior. The authors interpret these effects through hierarchical predictive coding, offering testable predictions about effective connectivity in cortical hierarchies.
Biological psychiatry
February 1, 2023
Devon Stoliker, Leonardo Novelli, Franz X Vollenweider et al.
49 citations
Under the peak effect of LSD, the inhibitory influence from the salience network to the default mode network becomes excitatory, and inhibition from the default mode network to the dorsal attention network weakens. These changes in effective connectivity between resting-state networks may reduce their normal anticorrelation, offering a neural mechanism for ego dissolution—the blurring of the boundary between self and world. The findings suggest that alterations in the sense of self across different conscious states depend on the organized balance of effective connectivity among these networks.
Biological Psychiatry
January 5, 2024
Devon Stoliker, Leonardo Novelli, Adeel Razi et al.
42 citations
Temporary reduction in amygdala signaling is linked to changes in how brain networks connect at rest. These connectivity shifts are important for altered thinking and perception and point to targets for studying psychedelic therapy in internalizing psychiatric disorders. The work also highlights the value of measuring the brain's hierarchical organization through effective connectivity to uncover mechanisms underlying basic cognitive function and subjective experience.
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.
Frontiers in Neuroscience
March 17, 2022
Devon Stoliker, Gary F Egan, Adeel Razi
19 citations
Classic psychedelics are thought to reduce the precision of belief updating, allowing access to a wider range of hypotheses for making sense of the world. This process in higher cortices may explain their therapeutic effects on internalizing disorders. The authors argue that reduced precision also underlies changes in consciousness known as ego dissolution, and that alterations in consciousness and attention under psychedelics share a common mechanism of reduced precision in Bayesian belief updating. Evidence linking serotonergic receptors to large-scale connectivity changes in the cortex suggests that the precision of Bayesian belief updating may be a mechanism for modifying and investigating consciousness and attention.
Biological psychiatry. Cognitive neuroscience and neuroimaging
May 1, 2024
Mihai Avram, Felix Müller, Katrin H Preller et al.
13 citations
In a double-blind, placebo-controlled, crossover study with 25 healthy participants, LSD, MDMA, and d-amphetamine all increased effective connectivity from the thalamus to specific unimodal cortices while reducing the influence of those cortices back onto the thalamus, indicating stronger bottom-up and weaker top-down information flow. For transmodal cortices, including parts of the salience network, amphetamines showed opposite effects. LSD uniquely increased effective connectivity from the thalamus to both unimodal and transmodal cortices, suggesting a breakdown in the hierarchical organization of brain activity. These findings refine models of how psychedelics alter brain connectivity.
bioRxiv (Cold Spring Harbor Laboratory)
March 11, 2025
Devon Stoliker, Leonardo Novelli, Moein Khajehnejad et al.
8 citations
preprint
Psychedelics like psilocybin alter consciousness by reorganizing brain connectivity in a context-sensitive way. In the largest psychedelic neuroimaging dataset to date, 62 adults underwent functional MRI and EEG before and after ingesting 19 mg of psilocybin, during rest and naturalistic stimuli. Under psilocybin, brain signals during eyes-closed conditions became similar to those during eyes-open conditions, with increased global functional connectivity in associative regions and decreased connectivity in sensory areas. Machine learning linked subjective effects to structured neural activity patterns. Stronger self-dissolving effects were associated with more distinct neural representations and next-day mindset changes, revealing a state of 'embeddedness' where networks that usually segregate internal and external processing integrate coherently, aligning neural dynamics with context.
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.
medRxiv
September 9, 2022
Devon Stoliker, Leonardo Novelli, Franz X. Vollenweider et al.
4 citations
preprint
Psilocybin reduces the brain's top-down control from resting state networks to the amygdala, which is involved in emotion appraisal and regulation. In a randomized, double-blind, placebo-controlled trial of 24 healthy adults given 0.215 mg/kg psilocybin, effective connectivity decreased from the default mode network and salience network to the amygdala, and within the DMN and SN, while connectivity within the central executive network increased. These changes were linked to altered emotion and meaning under the drug, suggesting that attenuation of the amygdala signal may serve as a biomarker for psilocybin's therapeutic effects in conditions like addiction and depression.
bioRxiv (Cold Spring Harbor Laboratory)
April 14, 2025
Leonardo Novelli, Devon Stoliker, Tamrin Barta et al.
3 citations
preprint
PsiConnect is a large-scale neuroimaging study that examined brain activity in 62 participants before and after a 19 mg dose of psilocybin using functional, structural, and diffusion-weighted MRI combined with EEG. The design included resting-state scans and three naturalistic conditions: guided meditation, music listening, and movie watching. Half of the participants completed an 8-week meditation training program, allowing exploration of interactions among meditation, psilocybin, and brain function. Multi-echo fMRI improved signal-to-noise ratio and reduced artifacts. Behavioral and self-report measures captured acute and longitudinal effects, with follow-ups extending to one year. The data is curated according to open science principles.
medRxiv
June 25, 2025
Devon Stoliker, Fosco Bernasconi, Olaf Blanke et al.
1 citation
preprint
Psilocybin reduces effective connectivity between the right and left anterior insula and between the right anterior insula and right temporoparietal junction in people who report intense out-of-body experiences. These changes parallel disruptions in TPJ–insula circuits observed in clinical and experimental OBEs, particularly in the right hemisphere. The findings highlight how psilocybin-induced disembodiment corresponds to altered causal neural dynamics underlying bodily self-consciousness.
Scientific data
May 21, 2026
Leonardo Novelli, Devon Stoliker, Tamrin Barta et al.
PsiConnect is a large-scale neuroimaging study that investigates how psilocybin affects brain activity and subjective experience depending on context. Sixty-two participants received a 19 mg dose of psilocybin and underwent functional, structural, and diffusion-weighted MRI, as well as EEG, before and after administration. Scans included resting-state and three naturalistic conditions: guided meditation, music listening, and movie watching. Half of the participants completed an 8-week meditation training program, allowing examination of interactions between meditation, psilocybin, and brain function. Multi-echo fMRI improved signal quality. Behavioral and self-report measures captured acute and long-term effects, with follow-ups up to one year. Data is openly shared to support future research.
bioRxiv (Cold Spring Harbor Laboratory)
September 12, 2025
Navid Shams Masjedi, Adeel Razi
preprint
The claustrum, a brain region with extensive connections to both cortical and subcortical areas, may help synchronize brain networks. Psychedelics like psilocybin appear to disrupt this synchrony by altering claustral signaling. Using brain scans from the Human Connectome Project and PsiConnect datasets, this work provides the first in vivo description of how the claustrum communicates with key brain networks in humans, both at rest and under psilocybin. The claustrum showed widespread bidirectional connections and a strong inhibitory influence on target regions. Psilocybin increased this inhibition on cortical networks while reducing it on subcortical areas, partly linked to subjective psychedelic effects, supporting a role for claustro-cortical inhibition in regulating network synchrony.
bioRxiv (Cold Spring Harbor Laboratory)
August 22, 2025
Matthew D. Greaves, Tamrin Barta, Leonardo Novelli et al.
preprint
Psilocybin reorganizes directed influences between brain regions while preserving the underlying structural connectivity, according to fMRI data analyzed with a dynamic causal model. Across four contexts—rest, guided meditation, music listening, and movie viewing—effects converged on outgoing influences from the left hippocampus, a hub linking memory and association systems with the default-mode network and thalamus. The left-hippocampus-to-thalamus pathway showed a sign-reversed association with mystical-experience scores: downregulation during guided meditation and upregulation during music listening. Left-hippocampal efferents predicted individual differences in mystical-experience intensity in cross-validation, and a simpler measure of hippocampal signal variability showed modest associations.
October 10, 2022
Devon Stoliker, Adeel Razi
In a study with 60 healthy volunteers who took psilocybin (magic mushrooms) in a laboratory, researchers used brain scans to record neural activity during the psychedelic experience. The work is part of a broader effort to find new treatments for mental health disorders, which affect about half of Australians over their lifetime. The text reports that scientists at Monash University are scanning the brains of healthy participants to understand how psilocybin alters brain function, potentially informing future therapeutic applications.
arXiv Preprint Archive
June 23, 2025
Moein Khajehnejad, Forough Habibollahi, Devon Stoliker et al.
A lightweight foundation model called BrainSymphony integrates fMRI time series and diffusion-derived structural connectivity, enabling unimodal or multimodal training without architectural changes and requiring less data than larger models. It processes fMRI data through parallel spatial and temporal transformer streams, distills embeddings via a Perceiver module, and encodes anatomical connectivity with a signed graph transformer. The model outperforms larger counterparts on benchmarks for prediction, classification, and network discovery. Attention maps from an independent psilocybin dataset reveal drug-induced reorganization of cortical hierarchies, demonstrating interpretability and generalizability. The work shows that architecturally informed multimodal models can surpass much larger models, advancing AI applications in neuroscience.