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Psilocybin Prolongs the Neurovascular Coupling Response in Mouse Visual Cortex.

Rick T Zirkel¹, Matthew Isaacson¹, Clara Liao^1,2

¹Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA.

Biorxiv : the Preprint Server for Biology

|August 6, 2025

Summary

This summary is machine-generated.

Psilocybin prolongs brain blood flow responses to stimuli, independent of neural activity changes. This finding is crucial for accurately interpreting neuroimaging data in psychedelic research.

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Area of Science:

Neuroscience
Pharmacology
Medical Imaging

Background:

Psilocybin shows therapeutic promise for mental health disorders, but its precise mechanisms remain unclear.
Current neuroimaging techniques like fMRI rely on neurovascular coupling, assuming it's unaffected by psychedelics.
This assumption may lead to misinterpretations of brain activity and connectivity changes.

Purpose of the Study:

To investigate the effects of psilocybin on neurovascular coupling.
To determine if psilocybin alters blood flow responses to neural activity.
To assess the implications for interpreting functional magnetic resonance imaging (fMRI) data.

Main Methods:

Simultaneous two-photon imaging of neural activity and capillary blood flow in awake mouse visual cortex.
Multimodal widefield imaging of surface vessel responses.
Computational modeling of neurovascular coupling and BOLD signal.

Main Results:

Psilocybin administration prolonged stimulus-evoked capillary blood flow increases.
This effect was attenuated by a 5-HT2A receptor antagonist.
No significant changes were observed in stimulus-evoked neural responses.
Psilocybin extended stimulus-evoked vascular responses in surface vessels.
Computational simulations indicated that prolonged neurovascular coupling can inflate BOLD-based functional connectivity measures.

Conclusions:

Psilocybin broadly enhances neurovascular responses in the brain.
It is essential to consider altered neurovascular coupling when interpreting fMRI studies of psilocybin.
This research clarifies psilocybin's impact on brain imaging signals, improving data interpretation accuracy.