Roach Brian J, Ford Judith M, Nicholas Spero, Ferri Jamie M, Gunduz-Bruce Handan, Krystal John H, Jaeger Judith, Mathalon Daniel H
Northern California Institute for Research and Education, San Francisco, California; San Francisco Veterans Affairs Medical Center, San Francisco, California.
San Francisco Veterans Affairs Medical Center, San Francisco, California; University of California, San Francisco, San Francisco, California.
Biol Psychiatry Cogn Neurosci Neuroimaging. 2025 Jan 18. doi: 10.1016/j.bpsc.2025.01.008.
Auditory steady-state response (ASSR) abnormalities in the 40-Hz (gamma band) frequency have been observed in schizophrenia and in rodent studies of NMDA receptor (NMDAR) hypofunction. However, the extent to which 40-Hz ASSR abnormalities in schizophrenia resemble deficits in 40-Hz ASSR induced by acute administration of ketamine, an NMDAR antagonist, is not yet known.
To address this knowledge gap, we conducted parallel electroencephalography studies: a crossover, placebo-controlled ketamine drug challenge study with healthy participants (study 1) and a comparison of patients with schizophrenia and healthy control participants (study 2). Time-frequency analysis of the ASSR was used to calculate baseline, broadband gamma power, evoked power, total power, phase-locking factor, and phase-locking angle.
Relative to healthy control participants, patients with schizophrenia exhibited increases in prestimulus broadband gamma power and reductions in 40-Hz ASSR evoked power, total power, and phase-locking factor, replicating previous studies. However, we failed to replicate previous findings of 40-Hz ASSR phase delay in schizophrenia. Relative to placebo, ketamine increased prestimulus broadband gamma power; reduced 40-Hz ASSR evoked power, total power, and phase-locking factor; and advanced the phase of the 40-Hz ASSR.
Normalized by their respective control groups/conditions, direct comparison of these measures between schizophrenia and ketamine data only revealed significant differences in phase, supporting the role of NMDAR hypofunction in mediating gamma oscillation abnormalities in schizophrenia.
在精神分裂症患者以及NMDA受体（NMDAR）功能低下的啮齿动物研究中，均观察到40赫兹（γ频段）频率下的听觉稳态反应（ASSR）异常。然而，精神分裂症中40赫兹ASSR异常与NMDAR拮抗剂氯胺酮急性给药诱导的40赫兹ASSR缺陷的相似程度尚不清楚。
为填补这一知识空白，我们进行了平行脑电图研究：一项针对健康参与者的交叉、安慰剂对照氯胺酮药物激发研究（研究1）以及一项精神分裂症患者与健康对照参与者的比较研究（研究2）。使用ASSR的时频分析来计算基线、宽带γ功率、诱发功率、总功率、锁相因子和锁相角。
相对于健康对照参与者，精神分裂症患者在刺激前宽带γ功率增加，40赫兹ASSR诱发功率、总功率和锁相因子降低，这与先前的研究结果一致。然而，我们未能重复先前关于精神分裂症中40赫兹ASSR相位延迟的研究结果。相对于安慰剂，氯胺酮增加了刺激前宽带γ功率；降低了40赫兹ASSR诱发功率、总功率和锁相因子；并使40赫兹ASSR的相位提前。
通过各自的对照组/条件进行标准化后，精神分裂症与氯胺酮数据之间这些测量值的直接比较仅显示出相位上的显著差异，支持NMDAR功能低下在介导精神分裂症γ振荡异常中的作用。
