Resting GABA and glutamate concentrations do not predict visual gamma frequency or amplitude

Abstract

Gamma band oscillations arise in neuronal networks of interconnected GABAergic interneurons and excitatory pyramidal cells. A previous study found a correlation between visual gamma peak frequency, as measured with magnetoencephalography, and resting GABA levels, as measured with magnetic resonance spectroscopy (MRS), in 12 healthy volunteers. If true, this would allow studies in clinical populations testing modulation of this relationship, but this finding has not been replicated. We addressed this important question by measuring gamma oscillations and GABA, as well as glutamate, in 50 healthy volunteers. Visual gamma activity was evoked using an established gratings paradigm, and we applied a beamformer spatial filtering technique to extract source-reconstructed gamma peak frequency and amplitude from the occipital lobe. We determined gamma peak frequency and amplitude from the location with maximal activation and from the location of the MRS voxel to assess the relationship of GABA with gamma. Gamma peak frequency was estimated from the highest value of the raw spectra and by a Gaussian fit to the spectra. MRS data were acquired from occipital cortex. We did not replicate the previously found correlation between gamma peak frequency and GABA concentration. Calculation of a Bayes factor provided strong evidence in favor of the null hypothesis. We also did not find a correlation between gamma activity and glutamate or between gamma and the ratio of GABA/glutamate. Our results suggest that cortical gamma oscillations do not have a consistent, demonstrable relationship to excitatory/inhibitory network activity as proxied by MRS measurements of GABA and glutamate. G amma band oscillations (30-90 Hz) are found in many cortical areas and are thought to play an important role in cognitive processing (1). Both experimental and modeling studies have shown that the gamma rhythm is inextricably linked to synaptic inhibition (2-4). GABA-mediated inhibition is both necessary and sufficient for the generation of gamma oscillations, and mutually connected inhibitory interneuron networks are major generators of gamma oscillations (4-6). In addition, fast recurrent excitation followed by slower feedback inhibitions can give rise to gamma oscillations (3, 7). Most likely, excitation-inhibition and inhibition-inhibition hybrid gamma networks work together to generate gamma frequency oscillations (2, 8).In vitro and modeling studies have clearly shown the importance of GABA for the generation of gamma oscillations, but the relationship between GABA and gamma is not easily assessed in the human brain. Muthukumaraswamy and colleagues (9) attempted to assess this relationship by correlating resting GABA concentrations as measured by magnetic resonance spectroscopy (MRS) with visual gamma oscillations as measured by magnetoencephalography (MEG). MRS provides a noninvasive method of quantifying metabolite concentrations in discrete regions of the human brain, but it can only detect the total concentration of a neurochemical and cannot...

Glutamatergic metabolites are associated with visual plasticity in humans

“…Yet, two recent studies did not find significant correlations between GABA and BOLD in five brain regions [59] or GABA and magnetoencephalography (MEG) peak gamma levels [60] while two other studies in the insula found a positive correlation between BOLD signal and GABA+ levels [61] and BOLD signal and GABA/NAA levels [62]. In this study, our data revealed a relationship between higher GABA and greater visual plasticity, which may seem counterintuitive.…”

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

“…Cousijn et al, 2014; Muthukumaraswamy et al, 2009]. Invigorating this debate, a very recent flumazenil‐positron emission tomography (PET) study demonstrated a positive correlation between the frequency of visually induced gamma oscillations and the density of GABA A receptors in early visual areas [Kujala et al, 2015].…”

Measuring neural excitation and inhibition in autism: Different approaches, different findings and different interpretations

“…This position is also supported by pharmalogical manipulations of GABA, as administration of propofol (a GABA agonist) leads to an increase in induced gamma band power (Saxena, Muthukumaraswamy, & Diukova, 2013). However, other studies have not found any association between GABA levels (in occipital cortex) and induced gamma band power (Cousijn et al, 2014;Muthukumaraswamy, Edden, Jones, Swettenham, & Singh, 2009). Therefore currently, it seems that little can be learnt about E/I balance by measuring gamma power in ASD.…”

“…Peak gamma frequency has been shown to be stable over time, and also to be highly heritable (van Pelt, Boomsma, & Fries, 2012), therefore peak gamma frequency may represent a more useful way to investigate E/I balance in human participants. Some studies have shown that visuallyinduced peak gamma frequency is correlated with resting GABA levels in occipital cortex Gaetz, Edgar, Wang, & Roberts, 2011;Muthukumaraswamy et al, 2009) although others have failed to replicate this relationship (Cousijn et al, 2014;Saxena et al, 2013). The technical difficulty in measuring GABA concentration in vivo with MRS and the different scan parameters used in these studies may contribute to the lack of convergence in results, Nevertheless, peak gamma frequency elicited by visual stimuli has been found to be higher in ASD (Dickinson et al, 2016), and correlated with autistic traits in the neurotypical population (Dickinson, Bruyns-Haylett, Jones, & Milne, 2015).…”