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

Lorenzo Magazzini,Krish D Singh,David J Nutt,Petroc Sumner,Khalid Hamandi,Anne Lingford‐Hughes,Jim F M Myers,Sue J Wilson,Suresh D Muthukumaraswamy,Anne E Campbell

doi:10.1002/hbm.23283

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.

Highlights

Synchronization of rhythmic neuronal firing in the gamma range (30–90 Hz) is a potential mechanism for information coding in the brain [Buzsaki and Wang, 2012; Fries, 2009]
Contrary to the null result previously reported, we found that pharmacological enhancement of GABAergic neurotransmission by tiagabine produced a marked decrease in the peak frequency of visual gamma oscillations
A partially unresolved question is whether the changes in frequency associated with GABAergic neurotransmission are unique to gamma oscillations, or extend to other frequency ranges

Summary

Introduction

Synchronization of rhythmic neuronal firing in the gamma range (30–90 Hz) is a potential mechanism for information coding in the brain [Buzsaki and Wang, 2012; Fries, 2009]. In the magnetoencephalographic (MEG) signal, sustained narrow-band gamma oscillations are generated in visual cortex in response to simple contrast pattern stimuli [Adjamian et al, 2004; Hoogenboom et al, 2006]. These responses arise from the interaction between local excitatory and inhibitory networks, which are believed to shape the amplitude, as well as the peak frequency of gamma oscillations [Bartos et al, 2007; Gonzalez-Burgos and Lewis, 2012]. Peak gamma frequency is highly reproducible over shorter time scales, and represents a suitable measure for within-subject designs [Muthukumaraswamy et al, 2010; Swettenham et al, 2009]

Methods

Results

Discussion

Conclusion