Oscillatory Underpinnings of Mismatch Negativity and Their Relationship with Cognitive Function in Patients with Schizophrenia

BackgroundImpairments in mismatch negativity (MMN) generation have been consistently reported in patients with schizophrenia. However, underlying oscillatory activity of MMN deficits in schizophrenia and the relationship with cognitive impairments have not been investigated in detail. Time-frequency power and phase analyses can provide more detailed measures of brain dynamics of MMN deficits in schizophrenia. Method21 patients with schizophrenia and 21 healthy controls were tested with a roving frequency paradigm to generate MMN. Time-frequency domain power and phase-locking (PL) analysis was performed on all trials using short-time Fourier transforms with Hanning window tapering. A comprehensive battery (CANTAB) was used to assess neurocognitive functioning. ResultsMean MMN amplitude was significantly lower in patients with schizophrenia (95% CI 0.18 - 0.77). Patients showed significantly lower EEG power (95% CI -1.02 - -0.014) in the ~4-7 Hz frequency range (theta band) between 170 and 210 ms. Patients with schizophrenia showed cognitive impairment in multiple domains of CANTAB. However, MMN impairments in amplitude and power were not correlated with clinical measures, medication dose, social functioning or neurocognitive performance. ConclusionThe findings from this study suggested that while MMN may be a useful marker to probe NMDA receptor mediated mechanisms and associated impairments in gain control and perceptual changes, it may not be a useful marker in association with clinical or cognitive changes. Trial-by-trial EEG power analysis can be used as a measure of brain dynamics underlying MMN deficits which also can have implications for the use of MMN as a biomarker for drug discovery.

研究背景：精神分裂症患者的失匹配负波（mismatch negativity, MMN）生成损伤已被反复报道。然而，精神分裂症患者MMN缺陷的潜在振荡活动，以及其与认知损伤的关联，尚未得到详细研究。时频功率与相位分析能够为精神分裂症患者MMN缺陷的脑动态特征提供更为精细的量化指标。

研究方法：本研究纳入21名精神分裂症患者与21名健康对照受试者，采用流动频率范式诱发MMN。通过采用汉宁窗锥化的短时傅里叶变换，对所有试次进行时频域功率与相位锁定（phase-locking, PL）分析。使用剑桥自动化神经心理测试成套工具（CANTAB）评估受试者的神经认知功能。

研究结果：精神分裂症患者的平均MMN波幅显著降低（95%置信区间：0.18~0.77）。患者在170~210ms时段的4~7Hz频段（θ频段）的脑电功率显著更低（95%置信区间：-1.02~-0.014）。精神分裂症患者在CANTAB测试的多个认知维度中均表现出认知损伤。但MMN的波幅与功率缺陷与临床指标、药物剂量、社会功能或神经认知表现均无显著相关性。

研究结论：本研究结果表明，尽管MMN可作为探究N-甲基-D-天冬氨酸（NMDA）受体介导机制以及增益控制与知觉改变相关损伤的有效标志物，但其或许无法作为与临床或认知改变相关的理想标志物。逐试次脑电功率分析可作为反映MMN缺陷潜在脑动态特征的量化指标，这一发现对MMN作为药物研发生物标志物的应用亦具有参考价值。