Section Computational Cognitive Neuroscience, Department of Neurophysiology and Pathophysiology, University Medical Center Hamburg- Eppendorf, Hamburg 20251, Germany
Section Computational Cognitive Neuroscience, Department of Neurophysiology and Pathophysiology, University Medical Center Hamburg- Eppendorf, Hamburg 20251, Germany.
J Neurosci. 2024 Jun 12;44(24):e2029232024. doi: 10.1523/JNEUROSCI.2029-23.2024.
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 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 receptor, thus highlighting its utility as a mechanistic signature of cortical circuit dysfunctions involving GABAergic inhibition.
40Hz 听觉稳态反应（ASSR）是一种对周期性调制听觉刺激产生的振荡脑反应，是精神分裂症和相关神经精神疾病有前途的非侵入性生理生物标志物。40Hz ASSR 可能是皮质回路中突触相互作用放大的结果，而这些相互作用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 40Hz ASSR 是否依赖于皮质回路中神经元相互作用的两个关键突触成分：通过 N-甲基-D-天冬氨酸谷氨酸（NMDA）受体的兴奋和通过γ-氨基丁酸（GABA）受体的抑制。我们结合了脑磁图（MEG）记录和在同一批健康人类参与者（13 名男性，7 名女性）中进行的安慰剂对照、低剂量药物干预。在安慰剂下，所有参与者在听觉皮层中都表现出强烈的 40Hz ASSR，尤其是在右半球。GABA 受体激动剂劳拉西泮增加了 40Hz ASSR 的振幅，而 NMDA 阻断剂美金刚则没有可检测到的作用。我们的发现表明，听觉皮层中的 40Hz ASSR 涉及通过 GABA 受体的突触（可能是皮质内）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效用。
