, Volume 235, Issue 12, pp 3479–3493 | Cite as

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

  • Anna Forsyth
  • Rebecca McMillan
  • Doug Campbell
  • Gemma Malpas
  • Elizabeth Maxwell
  • Jamie Sleigh
  • Juergen Dukart
  • Joerg F Hipp
  • Suresh D MuthukumaraswamyEmail author
Original Investigation


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.


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.


Electroencephalography Functional magnetic resonance imaging Simultaneous EEG/fMRI Ketamine Midazolam Frequency analysis 



This work was funded by F Hoffman La Roche Ltd.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

213_2018_5064_MOESM1_ESM.docx (1.6 mb)
Online Resource 1 The impact of physiological nose on the BOLD signal (DOCX 1.55 mb)
213_2018_5064_MOESM2_ESM.docx (1.1 mb)
Online Resource 2 Contrasting drug and placebo sessions (DOCX 1.06 mb)
213_2018_5064_MOESM3_ESM.docx (27 kb)
Online Resource 3 EEG/BOLD temporal correlations during placebo (DOCX 27 kb)
213_2018_5064_MOESM4_ESM.docx (19 kb)
Online Resource 4 Drug physiologies (DOCX 19 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Anna Forsyth
    • 1
  • Rebecca McMillan
    • 1
  • Doug Campbell
    • 2
  • Gemma Malpas
    • 2
  • Elizabeth Maxwell
    • 2
  • Jamie Sleigh
    • 3
  • Juergen Dukart
    • 4
  • Joerg F Hipp
    • 4
  • Suresh D Muthukumaraswamy
    • 1
    Email author
  1. 1.School of Pharmacy, Faculty of Medical and Health SciencesThe University of AucklandAucklandNew Zealand
  2. 2.Department of AnaesthesiologyAuckland District Health BoardAucklandNew Zealand
  3. 3.Department of Anaesthesiology, Faculty of Medical and Health SciencesThe University of AucklandAucklandNew Zealand
  4. 4.Roche Pharma Research and Early Development, Neuroscience, Ophthalmology and Rare Diseases, Roche Innovation CenterF Hoffman La RocheBaselSwitzerland

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