Effects of ketamine and midazolam on resting state connectivity and comparison with ENIGMA connectivity deficit patterns in schizophrenia
JournalHuman Brain Mapping
PublisherJohn Wiley and Sons Inc.
MetadataShow full item record
AbstractSubanesthetic administration of ketamine is a pharmacological model to elicit positive and negative symptoms of psychosis in healthy volunteers. We used resting‐state pharmacological functional MRI (rsPhfMRI) to identify cerebral networks affected by ketamine and compared them to the functional connectivity (FC) in schizophrenia. Ketamine can produce sedation and we contrasted its effects with the effects of the anxiolytic drug midazolam. Thirty healthy male volunteers (age = 19–37 years) underwent a randomized, three‐way, cross‐over study consisting of three imaging sessions, with 48 hr between sessions. A session consisted of a control period followed by infusion of placebo or ketamine or midazolam. The ENIGMA rsfMRI pipeline was used to derive two long‐distance (seed‐based and dual‐regression) and one local (regional homogeneity, ReHo) FC measures. Ketamine induced significant reductions in the connectivity of the salience network (Cohen's d: 1.13 ± 0.28, p = 4.0 × 10−3), auditory network (d: 0.67 ± 0.26, p = .04) and default mode network (DMN, d: 0.63 ± 0.26, p = .05). Midazolam significantly reduced connectivity in the DMN (d: 0.77 ± 0.27, p = .03). The effect sizes for ketamine for resting networks showed a positive correlation (r = .59, p = .07) with the effect sizes for schizophrenia‐related deficits derived from ENIGMA's study of 261 patients and 327 controls. Effect sizes for midazolam were not correlated with the schizophrenia pattern (r = −.17, p = .65). The subtraction of ketamine and midazolam patterns showed a significant positive correlation with the pattern of schizophrenia deficits (r = .68, p = .03). RsPhfMRI reliably detected the shared and divergent pharmacological actions of ketamine and midazolam on cerebral networks. The pattern of disconnectivity produced by ketamine was positively correlated with the pattern of connectivity deficits observed in schizophrenia, suggesting a brain functional basis for previously poorly understood effects of the drug. Copyright 2019 The Authors.
SponsorsSupport was received from NIH grants U54EB020403, U01MH108148, R01EB015611, R01MH112180, R01DA027680, R01MH085646, and T32MH067533.
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85074322972&doi=10.1002%2fhbm.24838&partnerID=40&md5=a61145b1044e1b8565ac28ad481eabb0; http://hdl.handle.net/10713/11403
- Pharmacological fMRI: Effects of subanesthetic ketamine on resting-state functional connectivity in the default mode network, salience network, dorsal attention network and executive control network.
- Authors: Mueller F, Musso F, London M, de Boer P, Zacharias N, Winterer G
- Issue date: 2018
- Functional network connectivity impairments and core cognitive deficits in schizophrenia.
- Authors: Adhikari BM, Hong LE, Sampath H, Chiappelli J, Jahanshad N, Thompson PM, Rowland LM, Calhoun VD, Du X, Chen S, Kochunov P
- Issue date: 2019 Nov 1
- Resting-state Network-specific Breakdown of Functional Connectivity during Ketamine Alteration of Consciousness in Volunteers.
- Authors: Bonhomme V, Vanhaudenhuyse A, Demertzi A, Bruno MA, Jaquet O, Bahri MA, Plenevaux A, Boly M, Boveroux P, Soddu A, Brichant JF, Maquet P, Laureys S
- Issue date: 2016 Nov
- Decreased regional homogeneity and increased functional connectivity of default network correlated with neurocognitive deficits in subjects with genetic high-risk for schizophrenia: A resting-state fMRI study.
- Authors: Ma X, Zheng W, Li C, Li Z, Tang J, Yuan L, Ouyang L, Jin K, He Y, Chen X
- Issue date: 2019 Nov
- Resting-state functional EEG connectivity in salience and default mode networks and their relationship to dissociative symptoms during NMDA receptor antagonism.
- Authors: de la Salle S, Choueiry J, Shah D, Bowers H, McIntosh J, Ilivitsky V, Carroll B, Knott V
- Issue date: 2021 Feb