Differences between magnetoencephalographic (MEG) spectral profiles of drugs acting on GABA at synaptic and extrasynaptic sites: A study in healthy volunteers

Nutt, David; Wilson, Sue; Lingford‐Hughes, Anne; Myers, Jim; Papadopoulos, A.; Muthukumaraswamy, Suresh

doi:10.1016/j.neuropharm.2014.08.017

Cited by 36 publications

(41 citation statements)

References 49 publications

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“…However, this can be largely excluded as one previous study found significant effects on TMS‐EMG measures with the same dose (15 mg; Werhahn et al, ). Furthermore, we found that TGB strongly increased preTMS EEG power in all frequency bands (Figure and Supporting Information Figure S3), confirming findings of two resting‐state magnetoencephalographic studies (Muthukumaraswamy & Liley, ; Nutt et al, ) and, therefore, indicating a significant effect of TGB on brain activity in the present experiments.…”

Section: Discussionsupporting

confidence: 91%

Effects of antiepileptic drugs on cortical excitability in humans: A TMS‐EMG and TMS‐EEG study

Darmani

Bergmann

Zipser

et al. 2018

Human Brain Mapping

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Brain responses to transcranial magnetic stimulation (TMS) recorded by electroencephalography (EEG) are emergent noninvasive markers of neuronal excitability and effective connectivity in humans. However, the underlying physiology of these TMS‐evoked EEG potentials (TEPs) is still heavily underexplored, impeding a broad application of TEPs to study pathology in neuropsychiatric disorders. Here we tested the effects of a single oral dose of three antiepileptic drugs with specific modes of action (carbamazepine, a voltage‐gated sodium channel (VGSC) blocker; brivaracetam, a ligand to the presynaptic vesicle protein VSA2; tiagabine, a gamma‐aminobutyric acid (GABA) reuptake inhibitor) on TEP amplitudes in 15 healthy adults in a double‐blinded randomized placebo‐controlled crossover design. We found that carbamazepine decreased the P25 and P180 TEP components, and brivaracetam the N100 amplitude in the nonstimulated hemisphere, while tiagabine had no effect. Findings corroborate the view that the P25 represents axonal excitability of the corticospinal system, the N100 in the nonstimulated hemisphere propagated activity suppressed by inhibition of presynaptic neurotransmitter release, and the P180 late activity particularly sensitive to VGSC blockade. Pharmaco‐physiological characterization of TEPs will facilitate utilization of TMS‐EEG in neuropsychiatric disorders with altered excitability and/or network connectivity.

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Section: Discussionsupporting

confidence: 91%

Effects of antiepileptic drugs on cortical excitability in humans: A TMS‐EMG and TMS‐EEG study

Darmani

Bergmann

Zipser

et al. 2018

Human Brain Mapping

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“…For an overview of the respective MEG acquisition and preprocessing procedures for the psychedelic compounds, see Schartner et al (2017). Full details are given in Carhart-Harris et al (2016) [LSD], Muthukumaraswamy et al (2013) [PSI], Muthukumaraswamy et al (2015b) [KET], and Nutt et al (2015) [TGB]. The MEG data were source-localised to 90 cortical regions according to the standard Automated Anatomical Labelling (AAL) brain atlas (Tzourio-Mazoyer et al, 2002).…”

Section: Experimental Procedure Data Acquisition and Preprocessingmentioning

confidence: 99%

Decreased Directed Functional Connectivity in the Psychedelic State

Barnett

Muthukumaraswamy

Carhart‐Harris

et al. 2019

Preprint

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Neuroimaging studies of the psychedelic state offer a unique window onto the neural basis of conscious perception and selfhood. Despite well understood pharmacological mechanisms of action, the largescale changes in neural dynamics induced by psychedelic compounds remain poorly understood. Using source-localised, steady-state MEG recordings, we describe changes in functional connectivity following the controlled administration of LSD, psilocybin and low-dose ketamine, as well as, for comparison, the (non-psychedelic) anticonvulsant drug tiagabine. We compare both undirected and directed measures of functional connectivity between placebo and drug conditions. We observe a general decrease in directed functional connectivity for all three psychedelics, as measured by Granger causality, throughout the brain. These data support the view that the psychedelic state involves a breakdown in patterns of functional organisation or information flow in the brain. In the case of LSD, the decrease in directed functional connectivity is coupled with an increase in undirected functional connectivity, which we measure using correlation and coherence. This surprising opposite movement of directed and undirected measures is of more general interest for functional connectivity analyses, which we interpret using analytical modelling. Overall, our results uncover the neural dynamics of information flow in the psychedelic state, and highlight the importance of comparing multiple measures of functional connectivity when analysing time-resolved neuroimaging data.

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“…us, looking at large-scale MEG resting state networks may give us an insight into the functional organisation of the injured brain and the effects of various drugs on it. It has been shown that MEG can pick up changes in GABA function in the brain and that zolpidem has an influence on changes in GABA action [17]. is makes the analysis of resting state brain oscillations using MEG particularly relevant to understanding the effects of zolpidem.…”

Section: Introductionmentioning

confidence: 99%

Effect of Zolpidem in the Aftermath of Traumatic Brain Injury: An MEG Study

Sripad

Rosenberg

Boers

et al. 2020

Case Reports in Neurological Medicine

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In the past two decades, many studies have shown the paradoxical efficacy of zolpidem, a hypnotic used to induce sleep, in transiently alleviating various disorders of consciousness such as traumatic brain injury (TBI), dystonia, and Parkinson’s disease. The mechanism of action of this effect of zolpidem is of great research interest. In this case study, we use magnetoencephalography (MEG) to investigate a fully conscious, ex-coma patient who suffered from neurological difficulties for a few years due to traumatic brain injury. For a few years after injury, the patient was under medication with zolpidem that drastically improved his symptoms. MEG recordings taken before and after zolpidem showed a reduction in power in the theta-alpha (4–12 Hz) and lower beta (15–20 Hz) frequency bands. An increase in power after zolpidem intake was found in the higher beta/lower gamma (20–43 Hz) frequency band. Source level functional connectivity measured using weighted-phase lag index showed changes after zolpidem intake. Stronger connectivity between left frontal and temporal brain regions was observed. We report that zolpidem induces a change in MEG resting power and functional connectivity in the patient. MEG is an informative and sensitive tool to detect changes in brain activity for TBI.

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Differences between magnetoencephalographic (MEG) spectral profiles of drugs acting on GABA at synaptic and extrasynaptic sites: A study in healthy volunteers

Cited by 36 publications

References 49 publications

Effects of antiepileptic drugs on cortical excitability in humans: A TMS‐EMG and TMS‐EEG study

Effects of antiepileptic drugs on cortical excitability in humans: A TMS‐EMG and TMS‐EEG study

Decreased Directed Functional Connectivity in the Psychedelic State

Effect of Zolpidem in the Aftermath of Traumatic Brain Injury: An MEG Study

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