Biological Psychiatry
October 15, 2009
Yvette I. Sheline, Marcus E. Raichle, Abraham Z. Snyder et al.
608 citations
Functional connections within the default mode network are disrupted in Alzheimer's disease, likely due to amyloid-beta plaque toxicity. In cognitively normal participants with preclinical amyloid deposition, resting-state fMRI revealed differences in functional connectivity between the precuneus and several brain regions—including the hippocampus, parahippocampus, and cingulate cortex—that matched the pattern seen in Alzheimer's disease patients. These findings suggest that early amyloid-beta toxicity can be detected with resting-state fMRI before any cognitive or behavioral changes appear.
medRxiv
August 24, 2023
Subha Subramanian, Demetrius Perry, Caterina Gratton et al.
14 citations
preprint
Psilocybin disrupts connectivity across cortical networks and subcortical structures, producing more than three-fold greater acute changes in functional networks than methylphenidate. These changes are driven by desynchronization of brain activity across spatial scales, strongest in the default mode network (DMN), which is connected to the anterior hippocampus and thought to create our sense of self. Performing a perceptual task reduces psilocybin-induced network changes, suggesting a neurobiological basis for grounding during psychedelic therapy. Psilocybin induces a persistent decrease in functional connectivity between the anterior hippocampus and cortex (and DMN in particular), lasting for weeks but normalizing after six months. This persistent suppression of hippocampal-DMN connectivity represents a candidate neuroanatomical and mechanistic correlate for psilocybin's pro-plasticity and anti-depressant effects.
Nature Neuroscience
October 13, 2025
Jonah A. Padawer-Curry, Oliver J. Krentzman, Chao‐cheng Kuo et al.
9 citations
Psychedelics like psilocybin and DOI alter the brain's hemodynamic response, potentially disrupting the normal coupling between neuronal activity and blood flow. In human fMRI scans, psilocybin induced changes in hemodynamic response functions. In awake mice, DOI differentially affected the relationship between cortical excitatory neuronal activity and hemodynamic signals, both during whisker stimulation and at rest, leading to discordant changes in functional connectivity measures depending on whether they were based on neuronal or hemodynamic data. A selective serotonin-2A receptor antagonist reversed many of these effects. The findings indicate that the vasoactive effects of psychedelics must be considered when interpreting blood-based measures of brain function.
bioRxiv (Cold Spring Harbor Laboratory)
September 24, 2023
Xiaodan Wang, Jonah A. Padawer-Curry, Oliver J. Krentzman et al.
9 citations
preprint
Psychedelics show promise for treating mood disorders, but their effects on brain blood vessels have been overlooked. Psilocybin altered hemodynamic response functions in humans, suggesting changes in neurovascular coupling (NVC). Using wide-field optical imaging in awake mice, the psychedelic DOI (a serotonin-2A receptor agonist) partially altered task-based NVC but caused more pronounced NVC changes during rest, especially in association brain regions. Calcium and hemodynamic signals gave different accounts of resting-state functional connectivity under DOI. Co-administration with a 5-HT2A antagonist reversed many effects. The dissociation between neuronal and hemodynamic signals highlights the need to consider neurovascular effects when interpreting fMRI measures in psychedelic studies.
Scientific Data
June 5, 2025
Subha Subramanian, Travis Rick Renau, Demetrius Perry et al.
4 citations
A psychedelic drug, psilocybin, and a comparison drug, methylphenidate, produce distinct acute and persistent changes in brain networks measurable with precision functional mapping, a technique that improves signal detection by repeatedly scanning individuals. Seven healthy adults underwent extensive baseline brain imaging, imaging shortly after drug intake, and follow-up scans for up to two weeks. Four participants repeated the psilocybin protocol months later. The dataset includes resting-state and task-based functional MRI, structural scans, and subjective experience reports. The authors release this resource to help researchers study how psilocybin and methylphenidate alter brain network organization over time.