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Comparison of local spectral modulation, and temporal correlation, of simultaneously recorded EEG/fMRI signals during ketamine and midazolam sedation

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Abstract

Rationale and objectives

The identification of biomarkers of drug action can be supported by non-invasive brain imaging techniques, such as electroencephalography (EEG) and functional magnetic resonance imaging (fMRI), with simultaneous collection plausibly overcoming the limitations of either modality alone. Despite this, few studies have assessed the feasibility and utility of recording simultaneous EEG/fMRI in a drug study.

Methods

We used simultaneous EEG/fMRI to assess the modulation of neural activity by ketamine and midazolam, in a placebo-controlled, single-blind, three-way cross-over design. Specifically, we analysed the sensitivity and direction of the spectral effects of each modality and the temporal correlations between the modulations of power of the common EEG bands and the blood-oxygen-level-dependent (BOLD) signal.

Results and conclusions

Demonstrating feasibility, local spectral effects were similar to those found in previous non-simultaneous EEG and fMRI studies. Ketamine administration resulted in a widespread reduction of BOLD fractional amplitude of low frequency fluctuations (fALFF) and a diverse pattern of effects in the different EEG bands. Midazolam increased fALFF in occipital, parietal, and temporal areas, and frontal delta and beta EEG power. While EEG spectra were more sensitive to pharmacological modulations than the fALFF bands, there was no clear spatial relationship between the two modalities. Additionally, ketamine modulated the temporal correlation strengths between the theta EEG band and the BOLD signal, whereas midazolam altered temporal correlations with the alpha and beta bands. Taken together, these results demonstrate the utility of simultaneous recording: each modality provides unique insights, and combinatorial analyses elicit more information than separate recordings.

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Funding

This work was funded by F Hoffman La Roche Ltd.

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Authors and Affiliations

  1. School of Pharmacy, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag, Auckland, 92019, New Zealand

    Anna Forsyth, Rebecca McMillan & Suresh D Muthukumaraswamy

  2. Department of Anaesthesiology, Auckland District Health Board, Auckland, New Zealand

    Doug Campbell, Gemma Malpas & Elizabeth Maxwell

  3. Department of Anaesthesiology, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand

    Jamie Sleigh

  4. Roche Pharma Research and Early Development, Neuroscience, Ophthalmology and Rare Diseases, Roche Innovation Center, F Hoffman La Roche, Basel, Switzerland

    Juergen Dukart & Joerg F Hipp

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  1. Anna Forsyth
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Correspondence to Suresh D Muthukumaraswamy.

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The impact of physiological nose on the BOLD signal (DOCX 1.55 mb)

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Contrasting drug and placebo sessions (DOCX 1.06 mb)

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EEG/BOLD temporal correlations during placebo (DOCX 27 kb)

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Drug physiologies (DOCX 19 kb)

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Forsyth, A., McMillan, R., Campbell, D. et al. Comparison of local spectral modulation, and temporal correlation, of simultaneously recorded EEG/fMRI signals during ketamine and midazolam sedation. Psychopharmacology 235, 3479–3493 (2018). https://doi.org/10.1007/s00213-018-5064-8

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