Jalewa Jaishree, Todd Juanita, Michie Patricia T, Hodgson Deborah M, Harms Lauren
School of Psychological Sciences, College of Engineering, Science and Environment, University of Newcastle, Callaghan, New South Wales, Australia.
Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
Clin EEG Neurosci. 2025 Jan;56(1):35-45. doi: 10.1177/15500594241300726. Epub 2024 Nov 20.
Mismatch negativity (MMN), an auditory prediction error signal, is an enhanced response to unexpected (deviant) stimuli compared to expected (standard) stimuli. There is strong interest in MMN due to reliable findings of reduced MMN in schizophrenia. To interpret reduced MMN in schizophrenia, an enhanced understanding of the factors that influence MMN amplitude could lead to a better understanding of neural mechanisms underpinning the reduction. While several laboratories have observed mismatch responses (MMRs) in rodents, this study assesses how MMR is altered in more complex auditory sequences in rats. Prediction-errors are elicited in relation to "predictive" internal models of regularities. These internal models are updated dynamically when a regularity changes, but human MMN exhibits order effects when two regularities alternate; while deviants in both regularities elicit MMN (ie, the model updates) there is a slower build-up in MMN amplitude over time in the second encountered regularity type. We investigate whether order effects occur in rat MMRs. MMRs were studied to rare ascending and descending frequency deviations in awake, freely moving Wistar rats using wireless telemetry in both separate sequences (one regularity at a time) and in alternating sequences where regularities changed back and forth. The rat MMR did not show order effects, however, substantial MMRs occurred in response to both ascending and descending deviants in the alternating context but to the ascending deviant only when the same regularities were presented separately. The longer-term sequence structure altered prediction-error signalling in rat auditory system revealing a long term context sensitivity in internal models.
失匹配负波（MMN）是一种听觉预测误差信号，与预期（标准）刺激相比，它对意外（偏差）刺激的反应增强。由于在精神分裂症患者中可靠地发现MMN降低，因此人们对MMN产生了浓厚的兴趣。为了解释精神分裂症患者中MMN降低的原因，深入了解影响MMN幅度的因素可能有助于更好地理解其降低背后的神经机制。虽然几个实验室已经在啮齿动物中观察到了失匹配反应（MMR），但本研究评估了在大鼠更复杂的听觉序列中MMR是如何改变的。预测误差是相对于规律的“预测性”内部模型引发的。当规律发生变化时，这些内部模型会动态更新，但当两种规律交替出现时，人类MMN会表现出顺序效应；虽然两种规律中的偏差都会引发MMN（即模型更新），但在第二次遇到的规律类型中，MMN幅度随时间的增长会更慢。我们研究大鼠MMR中是否会出现顺序效应。在清醒、自由活动的Wistar大鼠中，使用无线遥测技术，在单独的序列（每次一种规律）和规律来回变化的交替序列中，研究了对罕见的频率上升和下降偏差的MMR。大鼠的MMR没有表现出顺序效应，然而，在交替环境中，对频率上升和下降的偏差都会出现显著的MMR，但当相同的规律分别呈现时，仅对频率上升的偏差出现MMR。长期的序列结构改变了大鼠听觉系统中的预测误差信号，揭示了内部模型中的长期情境敏感性。
