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

Forsyth, Anna; McMillan, Rebecca; Campbell, Doug; Malpas, Gemma; Maxwell, Elizabeth; Sleigh, Jamie; Dukart, Juergen; Hipp, Joerg F.; Muthukumaraswamy, Suresh

doi:10.1007/s00213-018-5064-8

Cited by 32 publications

(52 citation statements)

References 81 publications

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“…Written informed consent was obtained from all participants and the local Ethics Committee approved the study. The data analyzed here have been previously reported in (Forsyth et al, ; McMillan et al, ).…”

Section: Methodsmentioning

confidence: 96%

Effects of ketamine and midazolam on resting state connectivity and comparison with ENIGMA connectivity deficit patterns in schizophrenia

Adhikari

Dukart

Hipp

et al. 2019

Human Brain Mapping

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Subanesthetic 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 Bhim M. Adhikari and Juergen Dukart contributed equally to this study.

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Section: Methodsmentioning

confidence: 96%

Effects of ketamine and midazolam on resting state connectivity and comparison with ENIGMA connectivity deficit patterns in schizophrenia

Adhikari

Dukart

Hipp

et al. 2019

Human Brain Mapping

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“…The recruitment was limited to males due to the changes in GABA levels (Epperson et al, ) and EEG metrics (Sumner et al, ) across the menstrual cycle, which could confound a repeated measures design. Data from this study have previously been used to assess the sensitivity and direction of the spectral effects of each modality, and the temporal correlations between the BOLD signal and modulations of band‐limited EEG power (Forsyth et al, ), as well as the temporal dynamics of the pharmacological MRI response (McMillan et al, ). Participants were scanned on three separate occasions in a placebo‐controlled, three‐way cross‐over design using ketamine, midazolam, and placebo, where the participants were blinded to which drug they were receiving.…”

Section: Methodsmentioning

confidence: 99%

“…To our knowledge, this is the first attempt to assess the pharmacological modulations of the relationship between fMRI and EEG whole‐brain connectomes and builds on our previous work assessing the drug changes to power associations between these two modalities (Forsyth et al, ). To assess the relationship, whole‐brain all‐to‐all connectivity of the BOLD signal nodes was conducted and compared to electrophysiological connectivity estimates from the same nodes.…”

Section: Introductionmentioning

confidence: 99%

Modulation of simultaneously collected hemodynamic and electrophysiological functional connectivity by ketamine and midazolam

Forsyth

McMillan

Campbell

et al. 2019

Human Brain Mapping

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The pharmacological modulation of functional connectivity in the brain may underlie therapeutic efficacy for several neurological and psychiatric disorders. Functional magnetic resonance imaging (fMRI) provides a noninvasive method of assessing this modulation, however, the indirect nature of the blood‐oxygen level dependent signal restricts the discrimination of neural from physiological contributions. Here we followed two approaches to assess the validity of fMRI functional connectivity in developing drug biomarkers, using simultaneous electroencephalography (EEG)/fMRI in a placebo‐controlled, three‐way crossover design with ketamine and midazolam. First, we compared seven different preprocessing pipelines to determine their impact on the connectivity of common resting‐state networks. Independent components analysis (ICA)‐denoising resulted in stronger reductions in connectivity after ketamine, and weaker increases after midazolam, than pipelines employing physiological noise modelling or averaged signals from cerebrospinal fluid or white matter. This suggests that pipeline decisions should reflect a drug's unique noise structure, and if this is unknown then accepting possible signal loss when choosing extensive ICA denoising pipelines could engender more confidence in the remaining results. We then compared the temporal correlation structure of fMRI to that derived from two connectivity metrics of EEG, which provides a direct measure of neural activity. While electrophysiological estimates based on the power envelope were more closely aligned to BOLD signal connectivity than those based on phase consistency, no significant relationship between the change in electrophysiological and hemodynamic correlation structures was found, implying caution should be used when making cross‐modal comparisons of pharmacologically‐modulated functional connectivity.

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“…2.1. EEG experiment -participants and procedure Thirty healthy males aged between 19 and 37 years old participated in the experiment as described in Forsyth et al (2018). Participants were scanned on three separate occasions in a placebo-controlled, single-blind, three-way cross-over design using ketamine, midazolam, and placebo.…”

Section: Methodsmentioning

confidence: 99%

“…EEG data was recorded continuously using Brain Products (Brain Products GmbH) equipment; two BrainAmp MR plus amplifiers with 64-channel Braincaps. Electrode caps used the manufacturer standard layout as described in Forsyth et al (2018). Data were recorded with a sampling rate of 5 KHz with filters of 0.1-250 Hz with electrode impedances below 10 kΩ and referenced to a common average.…”

Section: Eeg Experiments -Data Acquisition and Preprocessingmentioning

confidence: 99%

Evidence that alpha blocking is due to increases in system-level oscillatory damping not neuronal population desynchronisation

Liley

Muthukumaraswamy²

2019

Preprint

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The attenuation of the alpha rhythm following eyes-opening (alpha blocking) is among the most robust features of the human electroencephalogram with the prevailing view being that it is caused by changes in neuronal population synchrony. To further study the basis for this phenomenon we use theoretically motivated fixed-order Auto-Regressive Moving-Average (ARMA) time series modelling to study the oscillatory dynamics of spontaneous alpha-band electroencephalographic activity in eyes-open and eyes-closed conditions and its modulation by the NMDA antagonist ketamine. We find that the reduction in alpha-band power between eyes-closed and eyes-open states is explicable in terms of an increase in the damping of stochastically perturbed alphaband relaxation oscillatory activity. These changes in damping are putatively modified by the antagonism of NMDA-mediated glutamatergic neurotransmission but are not directly driven by changes in input to cortex nor by reductions in the phase synchronisation of populations of near identical oscillators. These results not only provide a direct challenge to the dominant view of the role that thalamus and neuronal population de-/synchronisation have in the genesis and modulation of alpha electro-/magnetoencephalographic activity but also suggest potentially important physiological determinants underlying its dynamical control and regulation.

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

Cited by 32 publications

References 81 publications

Effects of ketamine and midazolam on resting state connectivity and comparison with ENIGMA connectivity deficit patterns in schizophrenia

Effects of ketamine and midazolam on resting state connectivity and comparison with ENIGMA connectivity deficit patterns in schizophrenia

Modulation of simultaneously collected hemodynamic and electrophysiological functional connectivity by ketamine and midazolam

Evidence that alpha blocking is due to increases in system-level oscillatory damping not neuronal population desynchronisation

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