Abstract
Reliable measures of cognitive brain activity from functional neuroimaging techniques may provide early indications of efficacy in clinical trials. Functional magnetic resonance imaging and electroencephalography provide complementary spatiotemporal information and simultaneous recording of these two modalities can remove inter-session drug response and environment variability. We sought to assess the effects of ketamine and midazolam on simultaneous electrophysiological and hemodynamic recordings during working memory (WM) processes. Thirty participants were included in a placebo-controlled, three-way crossover design with ketamine and midazolam. Compared to placebo, ketamine administration attenuated theta power increases and alpha power decreases and midazolam attenuated low beta band decreases to increasing WM load. Additionally, ketamine caused larger blood-oxygen-dependent (BOLD) signal increases in the supplementary motor area and angular gyrus, and weaker deactivations of the default mode network (DMN), whereas no difference was found between midazolam and placebo. Ketamine administration caused positive temporal correlations between frontal-midline theta (fm-theta) power and the BOLD signal to disappear and attenuated negative correlations. However, the relationship between fm-theta and the BOLD signal from DMN areas was maintained in some participants during ketamine administration, as increasing theta strength was associated with stronger BOLD signal reductions in these areas. The presence of, and ability to manipulate, both positive and negative associations between the BOLD signal and fm-theta suggest the presence of multiple fm-theta components involved in WM processes, with ketamine administration disrupting one or more of these theta-linked WM strategies.
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Data Availability
Data are available from the corresponding author upon reasonable request. Nifti files of main fMRI result images are available to download at https://doi.org/10.17608/k6.auckland.13726486.v1.
Code Availability
Available from the corresponding author upon reasonable request.
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AF: Conceptualisation, methodology development, data collection, formal analysis, writing and revision of manuscript. RM: Data collection, revision and editing of manuscript. JD: Conceptualisation, methodology development, revision and editing of manuscript. JFH Conceptualisation, methodology development, revision and editing of manuscript. SDM: Conceptualisation, methodology development, data collection, revision and editing of manuscript.
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study was approved by a local Ethics Committee (Central Health and Disability Ethics Committee Ref: 15/CEN/254)). The trial registration can be found at https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370230.
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Forsyth, A.E.M., McMillan, R., Dukart, J. et al. Effects of Ketamine and Midazolam on Simultaneous EEG/fMRI Data During Working Memory Processes. Brain Topogr 34, 863–880 (2021). https://doi.org/10.1007/s10548-021-00876-8
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DOI: https://doi.org/10.1007/s10548-021-00876-8