Abstract
High-frequency oscillations in the gamma-band reflect rhythmic synchronization of spike timing in active neural networks. The modulation of gamma oscillations is a widely established mechanism in a variety of neurobiological processes, yet its neurochemical basis is not fully understood. Modeling, in-vitro and in-vivo animal studies suggest that gamma oscillation properties depend on GABAergic inhibition. In humans, search for evidence linking total GABA concentration to gamma oscillations has led to promising -but also to partly diverging- observations. Here, we provide the first evidence of a direct relationship between the density of GABAA receptors and gamma oscillatory gamma responses in human primary visual cortex (V1). By combining Flumazenil-PET (to measure resting-levels of GABAA receptor density) and MEG (to measure visually-induced gamma oscillations), we found that GABAA receptor densities correlated positively with the frequency and negatively with amplitude of visually-induced gamma oscillations in V1. Our findings demonstrate that gamma-band response profiles of primary visual cortex across healthy individuals are shaped by GABAA-receptor-mediated inhibitory neurotransmission. These results bridge the gap with in-vitro and animal studies and may have future clinical implications given that altered GABAergic function, including dysregulation of GABAA receptors, has been related to psychiatric disorders including schizophrenia and depression.
Highlights
This, gamma-oscillations measured with Magnetoencephalography (MEG) have been shown to depend on GABA concentration levels estimated via magnetic resonance spectroscopy (MRS) in primary visual[17,18], primary motor[19], left dorsolateral prefrontal cortex[20]
We investigated the relationships between the timing, amplitude and frequency of alpha, beta- and gamma-band oscillatory activity and GABAA receptor density in primary visual cortex (V1)
The FMZ-PET data used to determine the GABAA receptor density were collected while the subjects were resting in the scanner, and the characteristics of oscillatory neuromagnetic signals in each individual were estimated from their visual responses in a standard n-back working memory task
Summary
This, gamma-oscillations measured with Magnetoencephalography (MEG) have been shown to depend on GABA concentration levels estimated via magnetic resonance spectroscopy (MRS) in primary visual[17,18], primary motor[19], left dorsolateral prefrontal cortex[20]. Ample evidence from modeling and in-vitro studies point to the key role of GABAA receptor mediated inhibition in the generation of gamma oscillations[8,16,27,28]. Reliable evidence for such a link in humans is still missing. We set out to evaluate the effects of variations in GABAA receptor distribution, estimated during rest, on rhythmic activity recorded during visual perception To this end, we investigated the relationships between the timing, amplitude and frequency of alpha-, beta- and gamma-band oscillatory activity (determined with MEG) and GABAA receptor density (determined with 11C-flumazenil positron emission tomography, FMZ-PET) in primary visual cortex (V1). Our results demonstrate that the density of GABAA receptors correlates positively with gamma peak frequency and negatively with gamma amplitude in human primary visual cortex
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