Psychedelics muddy fMRI results: Q&A with Adam Bauer and Jonah Padawer-Curry

Psychedelics muddy fMRI interpretation because they disrupt neurovascular coupling, meaning blood-flow related signals do not reliably track neuronal activity. In a Q&A, Adam Bauer and Jonah Padawer-Curry explain that fMRI reads hemodynamics indirectly (via oxygenation) and assumes a relatively constant relationship between vascular and neuronal activity. Their work using 2,5-dimethoxy-4-iodoamphetamine (DOI) in mice indicates that neuronal and hemodynamic changes can diverge by brain region and across resting state and sensory stimulation. The researchers connect these ideas to human imaging findings, highlighting regions such as the default mode network and prefrontal cortex where both connectivity and neurovascular coupling appear affected. They argue that psychedelics-related fMRI results should be treated with caution and that using a more holistic, neurophysiology-focused interpretation (and potentially multiple modalities) can reduce overconfident, purely neuronal conclusions.