Journal Article

FZJ-2019-05119

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Effects of Ketamine and Midazolam on resting state connectivity and comparison with ENIGMA connectivity deficit patterns in schizophrenia

Adhikari, B. M. ; Dukart, J. ; Hipp, J. F. ; Forsyth, A. ; McMillan, R. ; Muthukumaraswamy, S. D. ; Ryan, M. C. ; Elliot Hong, L. ; Eickhoff, S.FZJ* ; Jahanshad, N. ; Thompson, P. M. ; Rowland, L. M. ; Kochunov, P. (Corresponding author)

2020
Wiley-Liss New York, NY

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Please use a persistent id in citations: http://hdl.handle.net/2128/23996  doi:10.1002/hbm.24838

Abstract: Subanesthetic administration of ketamine is a pharmacological model to elicit positiveand negative symptoms of psychosis in healthy volunteers. We used resting statepharmacological functional MRI (rsPhfMRI) to identify cerebral networks affected by ketamineand compared them to the functional connectivity (FC) in schizophrenia. Ketamine can producesedation 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 hours between sessions. A sessionconsisted of a control period followed by infusion of placebo or ketamine or midazolam. TheENIGMA rsfMRI pipeline was used to derive two long distance (seed-based and dualregression)and one local (regional homogeneity, ReHo) FC measures. Ketamine inducedsignificant 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=0.04) and default mode network (DMN,d:0.63±0.26, p=0.05). Midazolam significantly reduced connectivity in the DMN (d:0.77±0.27,p=0.03). The effect sizes for ketamine for resting networks showed a positive correlation(r=0.59, p=0.07) with the effect sizes for schizophrenia related deficits derived from ENIGMA’sstudy of 261 patients and 327 controls. Effect sizes for midazolam were not correlated with theschizophrenia pattern (r=-0.17, p=0.65). The subtraction of ketamine and midazolam patternsshowed a significant positive correlation with the pattern of schizophrenia deficits (r=0.68,p=0.03).RsPhfMRI reliably detected the shared and divergent pharmacological actions ofketamine and midazolam on cerebral networks. The pattern of disconnectivity produced byketamine was positively correlated with the pattern of connectivity deficits observed inschizophrenia, suggesting a brain functional basis for previously poorly understood effects of thedrug.

Note: NIH. Grant Numbers: T32MH067533, R01MH085646, R01DA027680, R01MH112180, R01EB015611, U01MH108148, U54EB020403

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Contributing Institute(s):

1. Gehirn & Verhalten (INM-7)

Research Program(s):

1. 573 - Neuroimaging (POF3-573) (POF3-573)
2. 571 - Connectivity and Activity (POF3-571) (POF3-571)

Appears in the scientific report 2020

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