title: Functional connectivity measures after psilocybin inform a novel hypothesis of early psychosis.
abstract: Psilocybin is a classic psychedelic and a candidate drug model of psychosis. This study measured the effects of psilocybin on resting-state network and thalamocortical functional connectivity (FC) using functional magnetic resonance imaging (fMRI). Fifteen healthy volunteers received intravenous infusions of psilocybin and placebo in 2 task-free resting-state scans. Primary analyses focused on changes in FC between the default-mode- (DMN) and task-positive network (TPN). Spontaneous activity in the DMN is orthogonal to spontaneous activity in the TPN, and it is well known that these networks support very different functions (ie, the DMN supports introspection, whereas the TPN supports externally focused attention). Here, independent components and seed-based FC analyses revealed increased DMN-TPN FC and so decreased DMN-TPN orthogonality after psilocybin. Increased DMN-TPN FC has been found in psychosis and meditatory states, which share some phenomenological similarities with the psychedelic state. Increased DMN-TPN FC has also been observed in sedation, as has decreased thalamocortical FC, but here we found preserved thalamocortical FC after psilocybin. Thus, we propose that thalamocortical FC may be related to arousal, whereas DMN-TPN FC is related to the separateness of internally and externally focused states. We suggest that this orthogonality is compromised in early psychosis, explaining similarities between its phenomenology and that of the psychedelic state and supporting the utility of psilocybin as a model of early psychosis.
authors.affiliation: To whom correspondence should be addressed; Imperial College London, Centre for Neuropsychopharmacology, Burlington Danes Building, 160 Du Cane Rd, London, UK. r.carhart-harris@imperial.ac.uk.
authors.forename: Robin L
authors.initials: RL
authors.lastname: Carhart-Harris
authors.forename: Robert
authors.initials: R
authors.lastname: Leech
authors.forename: David
authors.initials: D
authors.lastname: Erritzoe
authors.forename: Tim M
authors.initials: TM
authors.lastname: Williams
authors.forename: James M
authors.initials: JM
authors.lastname: Stone
authors.forename: John
authors.initials: J
authors.lastname: Evans
authors.forename: David J
authors.initials: DJ
authors.lastname: Sharp
authors.forename: Amanda
authors.initials: A
authors.lastname: Feilding
authors.forename: Richard G
authors.initials: RG
authors.lastname: Wise
authors.forename: David J
authors.initials: DJ
authors.lastname: Nutt
mesh_terms: D000328:Adult; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology; D054022:Cerebrum / Q000187:drug effects / Q000503:physiopathology*; D063132:Connectome / Q000295:instrumentation / Q000379:methods*; D005260:Female; D006213:Hallucinogens / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D008297:Male; D009415:Nerve Net / Q000187:drug effects* / Q000503:physiopathology; D011562:Psilocybin / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D011605:Psychoses, Substance-Induced / Q000503:physiopathology; D011618:Psychotic Disorders / Q000503:physiopathology*; D015203:Reproducibility of Results; D013788:Thalamus / Q000187:drug effects / Q000503:physiopathology; D055815:Young Adult
chemical_list: D006213:Hallucinogens; D011562:Psilocybin