The 40 Hz auditory steady-state response (ASSR), an oscillatory brain response to periodically modulated auditory stimuli, is a promising, noninvasive physiological biomarker for schizophrenia and related neuropsychiatric disorders. The 40 Hz ASSR might be amplified by synaptic interactions in cortical circuits, which are, in turn, disturbed in neuropsychiatric disorders. Here, we tested whether the 40 Hz ASSR in the 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 (13 males, 7 females). All participants exhibited a robust 40 Hz ASSR in auditory cortices, especially in the right hemisphere, under a placebo. The GABA_A receptor–agonist lorazepam increased the amplitude of the 40 Hz ASSR, while no effect was detectable under the NMDA blocker memantine. Our findings indicate that the 40 Hz ASSR in the 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.

40 Hz 听觉稳态反应 (ASSR) 是一种对周期性调制的听觉刺激的振荡大脑反应，是精神分裂症和相关神经精神疾病的一种有前景的非侵入性生理生物标志物。 40 Hz ASSR 可能会因皮质回路中的突触相互作用而放大，而皮质回路中的突触相互作用反过来又会在神经精神疾病中受到干扰。在这里，我们测试了人类听觉皮层中的 40 Hz ASSR 是否取决于皮层回路内神经元相互作用的两个关键突触成分：通过 N-甲基天冬氨酸谷氨酸 (NMDA) 受体的激发和通过 γ-氨基丁酸 (GABA) 的抑制）受体。我们将脑磁图 (MEG) 记录与安慰剂对照、低剂量药物干预结合起来，对相同的健康人类参与者（13 名男性，7 名女性）进行治疗。在安慰剂作用下，所有参与者的听觉皮层（尤其是右半球）都表现出强劲的 40 Hz ASSR。 GABA _A 受体激动剂劳拉西泮增加了 40 Hz ASSR 的幅度，而在 NMDA 阻滞剂美金刚下未检测到任何影响。我们的研究结果表明，听觉皮层中的 40 Hz ASSR 涉及通过 GABA _A 受体进行的突触（可能还有皮质内）抑制，从而突出了其作为涉及 GABA 能抑制的皮质回路功能障碍的机制特征的实用性。