Jonah Padawer-Curry, PhD

Yet another phenomenal paper! @audreycluo.bsky.social is an absolutely star!

Anatomical White Matter Tracts Span the Cortical Hierarchy to Support Cognitive Diversity Long-range white matter (WM) tracts support cognition by enabling communication between distant cortical regions, which are organized along a hierarchy defined by the sensorimotor-to-association (S-A)...

Ever wondered how white matter tracts actually map onto the cortical hierarchy and cognition—beyond the usual “projection vs association” labels?
Our new preprint tackles exactly that! 🧠✨ doi.org/10.64898/202...
Thread below 🧵

Earlier versions did! There are word limitations that make mentioning everything quite hard.

Psychedelics muddy fMRI results: Q&A with Adam Bauer and Jonah Padawer-Curry The drugs disrupt the link between vascular and neuronal activity, which complicates interpretations of fMRI data. Adopting a more holistic view of what constitutes brain activity may help…

Psychedelics disrupt the link between vascular and neuronal activity, which complicates interpretations of fMRI data. Adopting a more holistic view of what constitutes brain activity may help.

By @callimcflurry.bsky.social

#neuroskyence

www.thetransmitter.org/psychedelics...

🧠I am excited to announce that our manuscript introducing a new data resource – PennLEAD (Penn Longitudinal Executive functioning in Adolescent Development) – is now available on bioRxiv. Below are some details highlighting our data resource🧵funded by NIMH R01MH113550
www.biorxiv.org/content/10.1...

Psychedelic 5-HT2A receptor agonism alters neurovascular coupling and differentially affects neuronal and hemodynamic measures of brain function - Nature Neuroscience Padawer-Curry et al. show that the hallucinogenic 5-HT2A receptor agonist DOI alters neurovascular coupling in mice, with implications for the interpretation of human fMRI studies of psychedelics.

Psychedelic 5-HT2A receptor agonism alters neurovascular coupling and differentially affects neuronal and hemodynamic measures of mouse and human brain function

@adamqbauer.bsky.social
@jordacular.bsky.social
@realjoshsiegel.bsky.social
@oliverk28.bsky.social

www.nature.com/articles/s41...

This image is figure 5 from the paper showing how hallucinogenic 5HT2AR agonism alters neurovascular coupling at local and global scales.

A study in Nature Neuroscience finds psychedelics disrupt the relationship between neuronal activity and blood flow in humans and mice. This suggests fMRI results under psychedelics may reflect vascular effects as much as neural ones and should be interpreted with caution. go.nature.com/47hqVPH 🧪

And the story continues to grow!!!

New preprint from collaboration with @sn-lab.bsky.social - 2p imaging of psilocybin's effects on neurovascular coupling 🧠🔬

We found that psilocybin prolongs the neurovascular response, independent of neural activity.

This would affect how we should interpret fMRI BOLD studies of psychedelics ‼️

And I want to thank the wonderful reviewers (among them was @theborislab.bsky.social )who made the paper all that much stronger

All of this work was made possible by the wonderful team. @AdamBauer @jordacular.bsky.social @realjoshsiegel.bsky.social @oliverk28.bsky.social @washumedicine.bsky.social @washumedmir.bsky.social

8/ So now what!?

Next steps:
• Validate in humans 🧍‍♂️
• Build “vascular correction” models
• Revisit classic fMRI psychedelic studies

7/ Serotonin is vasoactive—it affects blood vessels, not just neurons (it’s right there in the etymology!). 🩸
Yet most imaging studies barely account for that.

6/ Take-home: neuronal and hemodynamic measures of brain function can dissociate under psychedelics, which has huge implications for interpreting human imaging data when under the influence of psychedelics.

5/ And here's a little mechanistic clue: blocking 5-HT₂A receptors (with MDL100907) predominantly reversed the dissociated reports of brain function → receptor-specific!?

4/ fMRI (BOLD) signals depend on blood flow.
So, some “functional” effects in psychedelic imaging may reflect vascular—not neuronal—changes. We observe divergent patterns across multiple functional measures, including FC, modularity, power, and stimulus response (
@every
figure)

3/ Even tripper: we saw similar shifts in human psilocybin fMRI data.

2/ After DOI (blue trace, right), neurovascular coupling (the link between brain ⚡️and blood 🩸signals) went off script.
The hemodynamic response got tighter—and even sprouted an acausal feature (suggesting an emergent vasculo-neuronal relation!). Wild stuff. 🤯

1/ We concurrently tracked pan-cortical neural ⚡️and hemodynamic 🩸signals before and after psychedelic intoxication in mice. SURPRISE: these signals reported different effects!

Psychedelic 5-HT2A receptor agonism alters neurovascular coupling and differentially affects neuronal and hemodynamic measures of brain function Nature Neuroscience - Padawer-Curry et al. show that the hallucinogenic 5-HT2A receptor agonist DOI alters neurovascular coupling in mice, with implications for the interpretation of human fMRI...

🚨 New science alert! Our cross-species study, now in Nature Neuroscience, demonstrates psychedelics distort how we should interpret functional brain imaging.
👇🧵

nature.com/articles/s41...
#Neuroscience #Psychedelics #BrainImaging