The unique neural signature of your trip: Functional connectome fingerprints of subjective psilocybin experience

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 behavioral 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 owing to greater intersubject 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 characterized 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 behavior, while demonstrating the value of a brain-fingerprinting approach to pharmacological neuroimaging.