The Unique Neural Signature of Your Trip: Functional Connectome Fingerprints of Subjective Psilocybin Experience

Abstract

The emerging neuroscientific frontier of brain fingerprinting has recently established that human functional connectomes (FCs) exhibit fingerprint like idiosyncratic features, which map onto heterogeneously distributed behavioural traits. Here we harness brain fingerprinting tools to extract FC features that predict subjective drug experience induced by the psychedelic psilocybin. Specifically, in neuroimaging data of healthy volunteers under the acute influence of psilocybin or a placebo, we show that, post-psilocybin administration, FCs become more idiosyncratic due to greater inter-subject dissimilarity. Moreover, whereas in placebo subjects idiosyncratic features are primarily found in the frontoparietal network, in psilocybin subjects they concentrate in the default-mode network (DMN). Crucially, isolating the latter revealed an FC pattern that predicts subjective psilocybin experience and is characterised by reduced within-DMN and DMN-limbic connectivity, as well as increased connectivity between the DMN and attentional systems. Overall, these results contribute to bridging the gap between psilocybin-mediated effects on brain and behaviour, while demonstrating the value of a brain-fingerprinting approach to pharmacological neuroimaging.

Resetting the Hippocampal Buffer: A Neurocognitive Account of Psychedelic Therapy for Anxiety-Related Psychopathology

“…However, similar to research on anxiety-related psychopathology, this work has produced several inconsistencies regarding which particular networks are impacted (Müller et al, 2018). Several studies have found that psychedelics acutely decrease connectivity within the DMN (Carhart-Harris et al, 2012Madsen et al, 2021;Mason et al, 2020;Müller et al, 2018;Palhano-Fontes et al, 2015;Timmermann et al, 2023) and decrease connectivity between the DMN and hippocampus (Carhart-Harris et al, 2014;Lebedev et al, 2015;Siegel et al, 2023;Tolle et al, 2023). In contrast, psychedelics may acutely increase connectivity between the DMN and SN (Carhart-Harris et al, 2013Madsen et al, 2021;Stoliker et al, 2023;Timmermann et al, 2023).…”