The effects of elevated endogenous GABA levels on movement-related network oscillations

Muthukumaraswamy, Suresh; Myers, Jim; Wilson, Sue; Nutt, David; Lingford‐Hughes, Anne; Singh, Krish Devi; Hamandi, Khalid

doi:10.1016/j.neuroimage.2012.10.054

Cited by 152 publications

(190 citation statements)

References 43 publications

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“…In sensorimotor regions, administration of a benzodiazepine GABA A positive allosteric modulator produced an alteration of the beta rhythm consisting of decreased frequency and increased amplitude [Jensen et al, 2005]. In other studies, no differences in gamma frequency were observed over motor regions using alcohol [Campbell et al, 2014], lorazepam [Lozano‐Soldevilla et al, 2014], ketamine [Shaw et al, 2015], or tiagabine [Muthukumaraswamy et al, 2013b]. Overall, therefore, the functional significance of shifts in oscillation frequency remains a subject of significant interest.…”

Section: Discussionmentioning

confidence: 99%

Significant reductions in human visual gamma frequency by the gaba reuptake inhibitor tiagabine revealed by robust peak frequency estimation

Magazzini

Muthukumaraswamy

Campbell

et al. 2016

Human Brain Mapping

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The frequency of visual gamma oscillations is determined by both the neuronal excitation–inhibition balance and the time constants of GABAergic processes. The gamma peak frequency has been linked to sensory processing, cognitive function, cortical structure, and may have a genetic contribution. To disentangle the intricate relationship among these factors, accurate and reliable estimates of peak frequency are required. Here, a bootstrapping approach that provides estimates of peak frequency reliability, thereby increasing the robustness of the inferences made on this parameter was developed. The method using both simulated data and real data from two previous pharmacological MEG studies of visual gamma with alcohol and tiagabine was validated. In particular, the study by Muthukumaraswamy et al. [2013a] (Neuropsychopharmacology 38(6):1105–1112), in which GABAergic enhancement by tiagabine had previously demonstrated a null effect on visual gamma oscillations, contrasting with strong evidence from both animal models and very recent human studies was re‐evaluated. After improved peak frequency estimation and additional exclusion of unreliably measured data, it was found that the GABA reuptake inhibitor tiagabine did produce, as predicted, a marked decrease in visual gamma oscillation frequency. This result demonstrates the potential impact of objective approaches to data quality control, and provides additional translational evidence for the mechanisms of GABAergic transmission generating gamma oscillations in humans. Hum Brain Mapp 37:3882–3896, 2016. © 2016 Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 99%

Significant reductions in human visual gamma frequency by the gaba reuptake inhibitor tiagabine revealed by robust peak frequency estimation

Magazzini

Muthukumaraswamy

Campbell

et al. 2016

Human Brain Mapping

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“…This suggests that beta-ERS is sensitive to global levels of corticomotor excitability post-stroke, and that the integrity of descending motor pathways such as the corticospinal tract, which are known to be important for the presence of MEPs (Stinear et al, 2007), may also influence the presence of a clearly identifiable beta-ERS. Magnetic resonance spectroscopy (Gaetz et al, 2011) and experimental pharmacological modulation of inhibitory neurotransmitter GABA (Hall, et al, 2011;Muthukumaraswamy et al, 2013) have demonstrated a positive association between beta-ERS strength and resting GABA levels. Thus beta-ERS may represent a decrease in cortical excitability and/or active inhibition following task execution (Pfurtscheller et al, 1996;Salmelin et al, 1995) so that a reduced or absent beta-ERS could be interpreted as disinhibition or increased excitability within the cortex.…”

Section: Discussionmentioning

confidence: 99%

“…A rebound event-related synchronisation (ERS) or increase in beta power above baseline is typically observed following movement (Pfurtscheller et al, 1996). Pharmacological (Hall et al, 2011;Muthukumaraswamy et al, 2013) and TMS (Aono et al, 2013;Chen et al, 1998;Takemi et al, 2013) studies suggest that the strength and peak frequency of beta oscillations are related to cortical excitability.…”

Section: Introductionmentioning

confidence: 99%

Cortical beta oscillations and motor thresholds differ across the spectrum of post-stroke motor impairment, a preliminary MEG and TMS study

et al. 2015

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“…Extra-synaptic and pre-synaptic GABA mechanisms such as tonic inhibition and feedback autoinhibition may be activated by reuptake blockade (Axmacher and Draguhn, 2004). The effect of tiagabine on waking EEG in man has not been reported, although there are MEG studies of stimulus-related responses after tiagabine (Muthukumaraswamy et al, 2012(Muthukumaraswamy et al, , 2013b. In the rat in the awake state there was a small increase in beta band power in one study (Cleton et al, 1999) and no significant change in any spectral band in another (Lancel et al, 1998).…”

Section: Introduction and Rationalementioning

confidence: 99%

“…We studied the effect of zolpidem and gaboxadol on resting MEG and compared with previously collected but not reported resting data from a previous study of tiagabine, using a similar protocol (Muthukumaraswamy et al, 2012).…”

Section: Introduction and Rationalementioning

confidence: 99%

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

et al. 2015

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A range of medications target different aspects of the GABA system; understanding their effects is important to inform further drug development. Effects on the waking EEG comparing these mechanisms have not been reported; in this study we compare the effects on resting MEG spectra of the benzodiazepine receptor agonist zolpidem, the delta sub-unit selective agonist gaboxadol (also known as THIP) and the GABA reuptake inhibitor tiagabine. These were two randomised, single-blind, placebo-controlled, crossover studies in healthy volunteers, one using zolpidem 10 mg, gaboxadol 15 mg and placebo, and the other tiagabine 15 mg and placebo. Whole head MEG recordings and individual MEG spectra were divided into frequency bands. Baseline spectra were subtracted from each post-intervention spectra and then differences between intervention and placebo compared. After zolpidem there were significant increases in beta frequencies and reduction in alpha frequency power; after gaboxadol and tiagabine there were significant increases in power at all frequencies up to beta. Enhancement of tonic inhibition via extrasynaptic receptors by gaboxadol gives rise to a very different MEG signature from the synaptic action of zolpidem. Tiagabine theoretically can affect both types of receptor; from these MEG results it is likely that the latter is the more prominent effect here.

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The effects of elevated endogenous GABA levels on movement-related network oscillations

Cited by 152 publications

References 43 publications

Significant reductions in human visual gamma frequency by the gaba reuptake inhibitor tiagabine revealed by robust peak frequency estimation

Significant reductions in human visual gamma frequency by the gaba reuptake inhibitor tiagabine revealed by robust peak frequency estimation

Cortical beta oscillations and motor thresholds differ across the spectrum of post-stroke motor impairment, a preliminary MEG and TMS study

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

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