利用错配负性(MMN)复杂模式偏差,开发对早期精神病具有潜在敏感性的生物标志物。

D. Salisbury, Fran López Caballero, B. Coffman
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摘要

重复序列中不常见的刺激偏差甚至会被动地引起错配负性(MMN),这使得 MMN 在临床应用中非常实用。听觉 MMN 通常是由一个(或多个)物理刺激参数(如音调、持续时间)的变化引起的。在长期精神分裂症患者中,这种低阶简单听觉神经网络(sMMN)会受到损害。然而,sMMN 包含刺激适应释放产生的活动,这使其纯粹与偏差相关的表面有效性变得模糊不清。更重要的是,它在首发精神病样本中的降低并不可靠,从而限制了其作为生物标记物的效用。复杂模式偏差MMN(cMMN)任务会引起早期和晚期反应,基于高阶抽象,能更好地分离偏差检测。它们的抽象性可能会提高对早期精神病处理缺陷的敏感度。然而,早期和晚期 cMMN 都很小,限制了健康样本和精神病样本之间的分离。我们在 29 名健康人中测试了一种新的双规则 cMMN 范式,以评估偏差的附加性。声音在左侧和右侧、低音和高音之间交替出现,形成左低右高的交替模式。偏差是一种重复的左低、违反侧化和音调模式。双规则任务的早期和晚期 cMMN 明显大于单规则额外音 cMMN 任务(P 分别为 0.48 和 0.28)。这些结果表明,违反规则的 cMMN 模式具有可加性。cMMN 振幅的增大应能增加组间差异效应的大小,从而使其成为首次精神病发作时,甚至可能在精神病出现之前,作为疾病存在的生物标志物的主要候选者。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Development of Biomarkers Potentially Sensitive to Early Psychosis Using Mismatch Negativity (MMN) to Complex Pattern Deviations.
Infrequent stimulus deviations from repetitive sequences elicit mismatch negativity (MMN) even passively, making MMN practical for clinical applications. Auditory MMN is typically elicited by a change in one (or more) physical stimulus parameters (eg, pitch, duration). This lower-order simple MMN (sMMN) is impaired in long-term schizophrenia. However, sMMN contains activity from release from stimulus adaptation, clouding its face validity as purely deviance-related. More importantly, it is unreliably reduced in samples of first-episode psychosis, limiting its utility as a biomarker. Complex pattern-deviant MMN (cMMN) tasks, which elicit early and late responses, are based on higher-order abstractions and better isolate deviance detection. Their abstract nature may increase the sensitivity to processing deficits in early psychosis. However, both the early and late cMMNs are small, limiting separation between healthy and psychotic samples. In 29 healthy individuals, we tested a new dual-rule cMMN paradigm to assess additivity of deviance. Sounds alternated lateralization between left and right, and low and high pitches, creating a left-low, right-high alternating pattern. Deviants were a repeated left-low, violating lateralization and pitch patterns. Early and late cMMNs on the dual-rule task were significantly larger than those on the one-rule extra tone cMMN task (P < .05). Further, the dual-rule early cMMN was not significantly smaller than pitch or duration sMMNs (P > .48, .28, respectively). These results demonstrate additivity for cMMN pattern-violating rules. This increase in cMMN amplitude should increase group difference effect size, making it a prime candidate for a biomarker of disease presence at first psychotic episode, and perhaps even prior to the emergence of psychosis.
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