Effects of psilocybin on functional connectivity measured with fNIRS: Insights from a single-subject pilot study

: The serotonergic hallucinogen psilocybin has characteristic effects on human brain activity and subjective experience. Previous functional magnetic resonance imaging (fMRI) studies showed alternations of functional connectivity (FC) under the influence of psilocybin in humans. No study, as yet, investigated psilocybin-induced changes in brain hemodynamics and oxygenation with functional near-infrared spectroscopy (fNIRS) optical neuroimaging. Our aim was to perform the first fNIRS single-subject pilot study in order to investigate the ability of fNIRS to detect changes induced by psychedelic substances. To this end, psilocybin (17 mg) was administered orally to a 31-year old man while resting-state changes in cerebral tissue hemodynamic and oxygenation were measured with fNIRS bilaterally over the frontal and occipital cortex. Measurements were performed before the intake of the substance as well as during its effective period (30 min and 60 min after intake). We observed psilocybin-induced changes in the bilateral frontal FC, bilateral occipital FC as well as right and left frontooccipital FC. In addition, the pulse rate of the subject showed non-random variations during the experiment, possibly related to psilocybin administration. This study demonstrates that fNIRS is able to detect psilocybin-induced changes in resting-state FC. The results of this initial single-subject pilot study are promising and warrants repetition with a larger number of subjects and an improved/extended fNIRS setup. We anticipate that fNIRS neuroimaging will play an important role in future studies investigating the neuronal/physiological effects of psychedelic substances in humans. Abstract The serotonergic hallucinogen psilocybin has characteristic eﬀects on human brain activity and subjective experience. Previous functional magnetic resonance imaging (fMRI) studies showed alternations of functional connectivity (FC) under the inﬂuence of psilocybin in humans. No study, as yet, investigated psilocybin-induced changes in brain hemodynamics and oxygenation with functional near-infrared spectroscopy (fNIRS) optical neuroimaging. Our aim was to perform the ﬁrst fNIRS single-subject pilot study in order to investigate the ability of fNIRS to detect changes induced by psychedelic substances. To this end, psilocybin (17 mg) was administered orally to a 31-year old man while resting-state changes in cerebral tissue hemodynamic and oxygenation were measured with fNIRS bilaterally over the frontal and occipital cortex. Measurements were performed before the intake of the substance as well as during its eﬀective period (30 min and 60 min after intake). We observed psilocybin-induced changes in the bilateral frontal FC, bilateral occipital FC as well as right and left frontooccipital FC. In addition, the pulse rate of the subject showed non-random variations during the experiment, possibly related to psilocybin administration. This study demonstrates that fNIRS is able to detect psilocybin-induced changes in resting-state FC. The results of this initial single-subject pilot study are promising and warrants repetition with a larger number of subjects and an improved/extended fNIRS setup. We anticipate that fNIRS neuroimaging will play an important role in future studies investigating the neuronal/physiological eﬀects of psychedelic substances in humans. ministration with respect to BF-FC, R-FO-FC and L-FO-FC and associated changes in PR. Our results indicate that fNIRS is able to detect psilocybin-induced changes in RSFC thereby oﬀering a new brain imaging modality to investigate neural and physiological eﬀects induced by psilocybin. Our single-subject study requires repetition within a larger number of subjects and an optimized fNIRS setup (including measurement channels with short source-detector distances, and broader coverage of cortical regions). Measurements with fNIRS have great potential to capture fast dynamical changes of RSFC during psilocybin intake (due to its high time resolution) and are able to capture physiological changes with only minimal disturbance of the subjects as compared to fMRI. We expect that fNIRS will play an important role in future human studies investigating the eﬀects of psychedelics in general.