Due to severe motor impairments and the lack of expressive language abilities seen in most patients with Rett Syndrome (RTT), it has proven extremely difficult to obtain accurate measures of auditory processing capabilities in this population. Here, we examined early auditory cortical processing of pure tones and more complex phonemes in females with Rett Syndrome (RTT), by recording high-density auditory evoked potentials (AEP), which allow for objective evaluation of the timing and severity of processing deficits along the auditory processing hierarchy. We compared AEPs of 12 females with RTT to those of 21 typically developing (TD) peers aged 4–21 years, interrogating the first four major components of the AEP (P1: 60–90 ms; N1: 100–130 ms; P2: 135–165 ms; and N2: 245–275 ms). Atypicalities were evident in RTT at the initial stage of processing. Whereas the P1 showed increased amplitude to phonemic inputs relative to tones in TD participants, this modulation by stimulus complexity was absent in RTT. Interestingly, the subsequent N1 did not differ between groups, whereas the following P2 was hugely diminished in RTT, regardless of stimulus complexity. The N2 was similarly smaller in RTT and did not differ as a function of stimulus type. The P2 effect was remarkably robust in differentiating between groups with near perfect separation between the two groups despite the wide age range of our samples. Given this robustness, along with the observation that P2 amplitude was significantly associated with RTT symptom severity, the P2 has the potential to serve as a monitoring, treatment response, or even surrogate endpoint biomarker. Compellingly, the reduction of P2 in patients with RTT mimics findings in animal models of RTT, providing a translational bridge between pre-clinical and human research.

由于大多数雷特综合征 (RTT) 患者存在严重的运动障碍和缺乏表达语言能力，因此在该人群中获得准确的听觉处理能力测量已被证明是极其困难的。在这里，我们通过记录高密度听觉诱发电位 (AEP) 来检查患有 Rett 综合征 (RTT) 的女性对纯音和更复杂音素的早期听觉皮层处理，从而可以客观评估处理缺陷的时间和严重程度。听觉处理层次。我们将 12 名 RTT 女性的 AEP 与 21 名 4-21 岁的典型发育 (TD) 同龄人的 AEP 进行比较，询问 AEP 的前四个主要组成部分（P1：60-90 ms；N1：100-130 ms；P2： 135–165 毫秒；和 N2：245–275 毫秒）。在处理的初始阶段，RTT 的非典型性很明显。虽然 P1 相对于 TD 参与者的音调显示出增加的音素输入幅度，但在 RTT 中不存在这种由刺激复杂性引起的调制。有趣的是，随后的 N1 在各组之间没有差异，而随后的 P2 在 RTT 中大大减少，无论刺激复杂性如何。N2 在 RTT 中同样较小，并且作为刺激类型的函数没有差异。尽管我们样本的年龄范围很广，但 P2 效应在区分两组之间几乎完美分离的组之间非常稳健。鉴于这种稳健性，以及观察到 P2 幅度与 RTT 症状严重程度显着相关，P2 有可能用作监测、治疗反应甚至替代终点生物标志物。令人信服的是，