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

Abstract

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.

Peak visual gamma frequency is modified across the healthy menstrual cycle

“…In our case, this may have been due to EEG signal to noise ratio being generally lower than that of MEG (Muthukumaraswamy & Singh, ). However, this is unlikely as the reliability of the peak frequency estimation was as good as, or at least comparable to, the findings of Magazzini et al (), indicating high signal‐to‐noise ratio. It has also been proposed that the neural mechanisms behind amplitude and frequency of gamma can be differentially modulated, with frequency more linked to the time‐constant of inhibitory processes (Magazzini et al, ).…”

“…It has also been proposed that the neural mechanisms behind amplitude and frequency of gamma can be differentially modulated, with frequency more linked to the time‐constant of inhibitory processes (Magazzini et al, ). To support this, when the data for the tiagabine data as presented by Magazzini et al () was subjected to DCM‐SSR by Shaw et al (), it was found that individual variability in the time constant of inhibitory interneurons was found to be significantly modulated by gamma frequency but not amplitude. Furthermore, a contribution analysis was completed in Shaw et al () to determine the key parameters contributing to gamma frequency.…”

“…The pharmaco‐MEG literature provides a number of examples showing that increasing GABAergic inhibition via GABA enhancing drugs leads to a decrease in gamma frequency (Campbell et al, ; Lozano‐Soldevilla et al, ; Magazzini et al, ). From this, it could be speculated that our finding of relatively higher frequency in the luteal compared to the follicular phase found in this study is interpretable as reflecting greater GABAergic inhibition in the follicular phase relative to the luteal phase.…”

“…Drugs that increase GABAergic inhibition via positive allosteric modulation including alcohol, and the benzodiazepine lorazepam have been shown to lead to decreases in gamma frequency and increases in gamma power (Campbell, Sumner, Singh, & Muthukumaraswamy, ; Lozano‐Soldevilla et al, ). Similarly, tiagabine, a GABA reuptake inhibitor used in the treatment of epilepsy has been shown to decrease the frequency but not modify the amplitude of gamma oscillations (Magazzini et al, ). Furthermore, recent research has linked gamma oscillations in the human primary visual cortex (V1) to changes in GABA A receptor density (Kujala et al, ).…”

Searching for Cross-Diagnostic Convergence: Neural Mechanisms Governing Excitation and Inhibition Balance in Schizophrenia and Autism Spectrum Disorders

“…Neural disinhibition yields higher baseline activity across frequency bands and failure of event-related activity to modulate, adapt, or be suppressed over repeated events(44). Pharmacological models altering GABAergic and glutamatergic neurotransmission confirm excitatory and inhibitory signaling contribute significantly to high-frequency oscillations(45,46). Thus, higher baseline excitation and altered stimulus-related evoked response can result from increased excitation, decreased inhibition, or a combination.…”