Swerdlow Neal R, Gonzalez Christopher E, Raza Muhammad Ummear, Gautam Deepshila, Miyakoshi Makoto, Clayson Peter E, Joshi Yash B, Molina Juan L, Talledo Jo, Thomas Michael L, Light Gregory A, Sivarao Digavalli V
Department of Psychiatry, University of California San Diego School of Medicine, La Jolla, California; VISN 22 Mental Illness Research, Education, and Clinical Center, San Diego Veterans Administration Health System, La Jolla, California.
Department of Psychiatry, University of California San Diego School of Medicine, La Jolla, California; VISN 22 Mental Illness Research, Education, and Clinical Center, San Diego Veterans Administration Health System, La Jolla, California.
Biol Psychiatry Cogn Neurosci Neuroimaging. 2024 Mar;9(3):346-355. doi: 10.1016/j.bpsc.2023.08.009. Epub 2023 Sep 6.
Click trains elicit an auditory steady-state response (ASSR) at the driving frequency (1F) and its integer multiple frequencies (2F, 3F, etc.) called harmonics; we call this harmonic response the steady-state harmonic response (SSHR). We describe the 40 Hz ASSR (1F) and 80 Hz SSHR (2F) in humans and rats and their sensitivity to the uncompetitive NMDA antagonist memantine.
In humans (healthy control participants, n = 25; patients with schizophrenia, n = 28), electroencephalography was recorded after placebo or 20 mg memantine in a within-participant crossover design. ASSR used 1 ms, 85-dB clicks presented in 250 40/s 500-ms trains. In freely moving rats (n = 9), electroencephalography was acquired after memantine (0, 0.3, 1, 3 mg/kg) in a within-participant crossover design; 65-dB click trains used 5-mV monophasic, 1-ms square waves (40/s).
Across species, ASSR at 1F generated greater evoked power (EP) than the 2F SSHR. 1F > 2F intertrial coherence (ITC) was also detected in humans, but the opposite relationship (ITC: 2F > 1F) was seen in rats. EP and ITC at 1F were deficient in patients and were enhanced by memantine across species. EP and ITC at 2F were deficient in patients. Measures at 2F were generally insensitive to memantine across species, although in humans the ITC harmonic ratio (1F:2F) was modestly enhanced by memantine, and in rats, both the EP and ITC harmonic ratios were significantly enhanced by memantine.
ASSR and SSHR are robust, nonredundant electroencephalography signals that are suitable for cross-species analyses that reveal potentially meaningful differences across species, diagnoses, and drugs.
短声序列在驱动频率（1F）及其整数倍频率（2F、3F等，即谐波）处引发听觉稳态反应（ASSR）；我们将这种谐波反应称为稳态谐波反应（SSHR）。我们描述了人类和大鼠中的40 Hz ASSR（1F）和80 Hz SSHR（2F）及其对非竞争性N-甲基-D-天冬氨酸（NMDA）拮抗剂美金刚的敏感性。
在人类（健康对照参与者，n = 25；精神分裂症患者，n = 28）中，采用参与者内交叉设计，在给予安慰剂或20 mg美金刚后记录脑电图。ASSR使用1毫秒、85分贝的短声，以250次/秒的频率、每次500毫秒的序列呈现。在自由活动的大鼠（n = 9）中，采用参与者内交叉设计，在给予美金刚（0、0.3、1、3 mg/kg）后记录脑电图；65分贝的短声序列使用5毫伏的单相、1毫秒方波（40次/秒）。
在所有物种中，1F处的ASSR产生的诱发功率（EP）高于2F处的SSHR。在人类中也检测到1F > 2F的试次间相干性（ITC），但在大鼠中观察到相反的关系（ITC：2F > 1F）。患者中1F处的EP和ITC不足，且在所有物种中美金刚均使其增强。患者中2F处的EP和ITC不足。尽管在人类中美金刚适度增强了ITC谐波比（1F：2F），在大鼠中美金刚显著增强了EP和ITC谐波比，但在所有物种中2F处的测量指标通常对美金刚不敏感。
ASSR和SSHR是强大的、非冗余的脑电图信号，适用于跨物种分析，揭示物种、诊断和药物之间潜在的有意义差异。
