title: Subjective Effects of Ethanol, Morphine, Δ(9)-Tetrahydrocannabinol, and Ketamine Following a Pharmacological Challenge Are Related to Functional Brain Connectivity.
abstract: This analysis examines the neuronal foundation of drug-induced psychomimetic symptoms by relating the severity of these symptoms to changes in functional connectivity for a range of different psychoactive compounds with varying degrees of psychomimetic effects. The repeated measures design included 323 resting-state functional magnetic resonance imaging time series and measures of subjective effects in 36 healthy male volunteers. Four different pharmacological challenges with ethanol, morphine, Δ(9)-tetrahydrocannabinol, and ketamine (12 subjects per drug) were applied. A set of 10 "template" resting-state networks was used to determine individual connectivity maps. Linear regression was used for each individual subject to relate these connectivity maps to three clusters of drug-induced subjective psychomimetic effects ("perception," "relaxation," and "dysphoria") as measured with visual analogue scales. Group analysis showed that the subjective effects of perception correlated significantly across drugs with the connectivity of the posterior cingulate cortex and precentral gyrus with the sensorimotor network (p < 0.005, corrected). No significant correlations were found for relaxation or dysphoria. The posterior cingulate cortex has a role in visuospatial evaluation and the precentral gyrus has been associated with auditory hallucinations. Both the posterior cingulate cortex and the precentral gyrus show changes in activation in patients with schizophrenia, which can be related to the severity of positive symptoms (i.e., hallucinations and delusions), and have previously been related to changes induced by psychoactive drugs. The similarity of functional connectivity changes for drug-induced psychomimetic effects and symptoms of psychosis provides further support for the use of pharmacological challenges with psychomimetic drugs as models for psychosis.
authors.affiliation: 1 Centre for Human Drug Research , Leiden, The Netherlands .|2 Leiden Institute for Brain and Cognition , Leiden, The Netherlands .|3 Leiden University Medical Centre , Leiden, The Netherlands .
authors.forename: Daniël
authors.initials: D
authors.lastname: Kleinloog
authors.affiliation: 2 Leiden Institute for Brain and Cognition , Leiden, The Netherlands .|3 Leiden University Medical Centre , Leiden, The Netherlands .|4 Institute of Psychology, Leiden University , Leiden, The Netherlands .
authors.forename: Serge
authors.initials: S
authors.lastname: Rombouts
authors.affiliation: 1 Centre for Human Drug Research , Leiden, The Netherlands .
authors.forename: Remco
authors.initials: R
authors.lastname: Zoethout
authors.affiliation: 1 Centre for Human Drug Research , Leiden, The Netherlands .
authors.forename: Linda
authors.initials: L
authors.lastname: Klumpers
authors.affiliation: 3 Leiden University Medical Centre , Leiden, The Netherlands .
authors.forename: Marieke
authors.initials: M
authors.lastname: Niesters
authors.affiliation: 2 Leiden Institute for Brain and Cognition , Leiden, The Netherlands .|3 Leiden University Medical Centre , Leiden, The Netherlands .
authors.forename: Najmeh
authors.initials: N
authors.lastname: Khalili-Mahani
authors.affiliation: 3 Leiden University Medical Centre , Leiden, The Netherlands .
authors.forename: Albert
authors.initials: A
authors.lastname: Dahan
authors.affiliation: 1 Centre for Human Drug Research , Leiden, The Netherlands .|3 Leiden University Medical Centre , Leiden, The Netherlands .
authors.forename: Joop
authors.initials: J
authors.lastname: van Gerven
mesh_terms: D000328:Adult; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D001931:Brain Mapping / Q000379:methods; D013759:Dronabinol / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D005625:Frontal Lobe / Q000187:drug effects / Q000502:physiology; D006179:Gyrus Cinguli / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D007649:Ketamine / Q000494:pharmacology*; D016014:Linear Models; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000494:pharmacology*; D009434:Neural Pathways / Q000502:physiology; D012146:Rest / Q000502:physiology
chemical_list: D000431:Ethanol; D007649:Ketamine; D009020:Morphine; D013759:Dronabinol
keywords: connectivity; fMRI; pharmacologic; resting state; subjective effects