PsiConnect: A Large-Scale fMRI and EEG Study of Sensory-Context Modulated Psilocybin-Induced Changes to Brain Connectivity and Behaviour

Background: Serotonergic psychedelic psilocybin induces alterations in consciousness described as profoundly meaningful experiences with significant clinical implications [1-3]. However, their effects on the brain are variable [4] and highly context dependent [5-8]. This study collected the largest psychedelic dataset to date to elucidate hemodynamic response and electrophysiological activity change across diverse conditions during acute psychedelic-altered conscious states.

Methods: In an open-label, placebo-controlled study, at Monash Biomedical Imaging, fMRI and EEG data were collected from sixty healthy adults (18-58 years) during rest, meditation, music, and naturalistic stimuli, before and after 19mg psilocybin. Additional assessments included measurement of mindset, personality, music and mindfulness before, during and longitudinally after imaging. We analysed effective and functional connectivity, focusing on changes in resting-state networks and global functional connectivity (GFC) using a high-resolution cortical surface template. Furthermore, we conducted spatiotemporal analyses of 64-channel EEG data under the same conditions immediately post-MRI sessions.

Results: fMRI analysis revealed increased GFC in associative areas and decreased GFC in sensory areas. Under naturalistic stimuli, this pattern reversed, with a global increase in GFC observed. EEG data demonstrated power reductions across lower frequency bands. Effective and functional connectivity analyses confirmed default-mode network modulation. Behavioural assessments revealed that most participants had transformative subjective experiences, linked to positive mindset changes and interconnectedness.

Conclusions: Our multi-modal approach provides a comprehensive view of psilocybin's acute effects on brain connectivity, electrophysiology, and hierarchical modulation by sensory context. These findings provide crucial insights into the neurobiological mechanisms underlying psychedelic-induced brain changes and their potential clinical significance.

References: [1] Stoliker et al. 2024. Biological Psychiatry; [2] Griffiths et al. 2016. Journal of Psychopharmacology; [3] Stoliker et al. 2022. Pharmacological Reviews;
[4] Siegel et al. 2024. Nature; [5] Griffiths et al. 2018. Journal of Psychopharmacology; [6] Carhart-Harris et al. 2018. Journal of Psychopharmacology; [7] Kaelen et al. 2016. European Neuropsychopharmacology; [8] Kaelen et al. 2015. Psychopharmacology