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Subjective Effects of Ethanol, Morphine, Δ(9)-Tetrahydrocannabinol, and Ketamine Following a Pharmacological Challenge Are Related to Functional Brain Connectivity.
Brain Connect 2015; 5(10):641-8BC

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+Show Affiliations

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 .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 .1 Centre for Human Drug Research , Leiden, The Netherlands .1 Centre for Human Drug Research , Leiden, The Netherlands .3 Leiden University Medical Centre , Leiden, The Netherlands .2 Leiden Institute for Brain and Cognition , Leiden, The Netherlands . 3 Leiden University Medical Centre , Leiden, The Netherlands .3 Leiden University Medical Centre , Leiden, The Netherlands .1 Centre for Human Drug Research , Leiden, The Netherlands . 3 Leiden University Medical Centre , Leiden, The Netherlands .

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26390148

Citation

Kleinloog, Daniël, et al. "Subjective Effects of Ethanol, Morphine, Δ(9)-Tetrahydrocannabinol, and Ketamine Following a Pharmacological Challenge Are Related to Functional Brain Connectivity." Brain Connectivity, vol. 5, no. 10, 2015, pp. 641-8.
Kleinloog D, Rombouts S, Zoethout R, et al. Subjective Effects of Ethanol, Morphine, Δ(9)-Tetrahydrocannabinol, and Ketamine Following a Pharmacological Challenge Are Related to Functional Brain Connectivity. Brain Connect. 2015;5(10):641-8.
Kleinloog, D., Rombouts, S., Zoethout, R., Klumpers, L., Niesters, M., Khalili-Mahani, N., ... van Gerven, J. (2015). Subjective Effects of Ethanol, Morphine, Δ(9)-Tetrahydrocannabinol, and Ketamine Following a Pharmacological Challenge Are Related to Functional Brain Connectivity. Brain Connectivity, 5(10), pp. 641-8. doi:10.1089/brain.2014.0314.
Kleinloog D, et al. Subjective Effects of Ethanol, Morphine, Δ(9)-Tetrahydrocannabinol, and Ketamine Following a Pharmacological Challenge Are Related to Functional Brain Connectivity. Brain Connect. 2015;5(10):641-8. PubMed PMID: 26390148.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Subjective Effects of Ethanol, Morphine, Δ(9)-Tetrahydrocannabinol, and Ketamine Following a Pharmacological Challenge Are Related to Functional Brain Connectivity. AU - Kleinloog,Daniël, AU - Rombouts,Serge, AU - Zoethout,Remco, AU - Klumpers,Linda, AU - Niesters,Marieke, AU - Khalili-Mahani,Najmeh, AU - Dahan,Albert, AU - van Gerven,Joop, Y1 - 2015/09/21/ PY - 2015/9/22/entrez PY - 2015/9/22/pubmed PY - 2016/10/1/medline KW - connectivity KW - fMRI KW - pharmacologic KW - resting state KW - subjective effects SP - 641 EP - 8 JF - Brain connectivity JO - Brain Connect VL - 5 IS - 10 N2 - 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. SN - 2158-0022 UR - https://www.unboundmedicine.com/medline/citation/26390148/Subjective_Effects_of_Ethanol_Morphine_Δ_9__Tetrahydrocannabinol_and_Ketamine_Following_a_Pharmacological_Challenge_Are_Related_to_Functional_Brain_Connectivity_ L2 - https://www.liebertpub.com/doi/full/10.1089/brain.2014.0314?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -