Background

Mismatch negativity (MMN) and P3a are event-related potential measures of early auditory information processing that are increasingly used as translational biomarkers in the development of treatments for neuropsychiatric disorders. These responses are reduced in schizophrenia patients over the frontocentral scalp electrodes and are associated with important domains of cognitive and psychosocial functioning. While MMN and P3a responses are generated by a dynamic network of cortical sources distributed across the temporal and frontal brain regions, it is not clear how these sources independently contribute to MMN and P3a at the primary frontocentral scalp electrode or to abnormalities observed in schizophrenia. This study aimed to determine the independent source contributions and characterize the magnitude of impairment in source-level MMN and P3a responses in schizophrenia patients.

Methods

A novel method was applied to back-project the contributions of 11 independent cortical source components to Fz, the primary scalp sensor that is used in clinical studies, in n = 589 schizophrenia patients and n = 449 healthy comparison subjects.

Results

The groups showed comparable individual source contributions underlying both MMN and P3a responses at Fz. Source-level responses revealed an increasing magnitude of impairment in schizophrenia patients from the temporal to more frontal sources.

Conclusions

Schizophrenia patients have a normal architecture of source contributions that are accompanied by widespread abnormalities in source resolved mismatch and P3a responses, with more prominent deficits detected from the frontal sources. Quantification of source contributions and source-level responses accelerates clarification of the neural mechanisms underlying the networks underlying MMN reduction at Fz in schizophrenia.

中文翻译：

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精神分裂症患者和健康对照受试者额中枢错配负性和 P3a 反应的来源

背景

错配负性 (MMN) 和 P3a 是与事件相关的早期听觉信息处理的潜在测量方法，它们越来越多地用作神经精神疾病治疗开发中的转化生物标志物。这些反应在精神分裂症患者的额中央头皮电极上减少，并且与认知和心理社会功能的重要领域相关。虽然 MMN 和 P3a 反应是由分布在颞叶和额叶区域的皮层源的动态网络产生的，但尚不清楚这些源如何独立地促成初级额中央头皮电极的 MMN 和 P3a 或精神分裂症中观察到的异常。

方法

一种新的方法被应用在n  = 589 名精神分裂症患者和n  = 449 名健康对照受试者中，对 11 个独立皮质源成分对 Fz（临床研究中使用的主要头皮传感器）的贡献进行反向投影。

结果

这些组在 Fz 处显示了 MMN 和 P3a 响应的可比较的个体源贡献。源级反应显示，精神分裂症患者的损伤程度从时间源到更多额源。

结论

精神分裂症患者具有正常的源贡献结构，伴随着源解析不匹配和 P3a 反应的广泛异常，从额叶源检测到更突出的缺陷。源贡献和源级响应的量化加速了对精神分裂症 Fz 处 MMN 减少的网络背后的神经机制的澄清。