40 Hz Steady-State Responses in Human Auditory Cortex Depend on GABAergic Neuronal Inhibition

Abstract

AbstractThe 40 Hz auditory steady-state response (ASSR), an oscillatory brain response to periodically modulated auditory stimuli, is a promising, non-invasive physiological biomarker for schizophrenia and related disorders. Because the 40Hz oscillation is injected into the brain by means of the sensory input, ASSR responses measured in the cortex may, in principle, just result from the passive propagation of stimulus oscillations across the auditory pathways, without any intracortical generation or amplification. Alternatively, the ASSR responses may involve cortical circuit interactions that amplify the stimulus-evoked oscillation, which would imply it as mechanistic signature of cortical circuit dysfunctions. Here, we tested whether the 40 Hz ASSR in human auditory cortex depends on two key synaptic components of neuronal interactions within cortical circuits: excitation via N-methyl-aspartate glutamate (NMDA) receptors and inhibition via gamma-amino-butyric acid (GABA) receptors. We combined magnetoencephalography MEG recordings with placebo-controlled, low-dose pharmacological interventions in the same healthy human participants. All participants exhibited a robust 40 Hz ASSR in auditory cortices (stronger on the right) under placebo. The GABAAreceptor-agonist lorazepam increased the amplitude of this ASSR, while no effect was detectable under the NMDA-blocker memantine. Our findings indicate that the 40 Hz ASSR in auditory cortex involves synaptic (and likely intracortical) inhibition via the GABA-A receptor, thus highlighting its utility as a mechanistic signature of cortical circuit dysfunctions involving GABAergic inhibition.