Brima Tufikameni, Freedman Edward G, Prinsloo Kevin D, Augustine Erika F, Adams Heather R, Wang Kuan Hong, Mink Jonathan W, Shaw Luke H, Mantel Emma P, Foxe John J
The Frederick J. and Marion A. Schindler Cognitive Neurophysiology Laboratory, Department of Neuroscience and The Ernest J. Del Monte Institute for Neuroscience, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
University of Rochester Batten Center (URBC), Department of Neurology and The Ernest J. Del Monte Institute for Neuroscience, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
Res Sq. 2023 Aug 17:rs.3.rs-3203894. doi: 10.21203/rs.3.rs-3203894/v1.
We interrogated auditory sensory memory capabilities in individuals with CLN3 disease (juvenile neuronal ceroid lipofuscinosis), specifically for the feature of "duration" processing, a critical cue in speech perception. Given decrements in speech and language skills associated with later-stage CLN3 disease, we hypothesized that the duration-evoked mismatch negativity (MMN) of the event related potential (ERP) would be a marker of progressively atypical cortical processing in this population, with potential applicability as a brain-based biomarker in clinical trials.
We employed three stimulation rates (fast: 450 ms, medium: 900 ms, slow: 1800 ms), allowing for assessment of the sustainability of the auditory sensory memory trace. The robustness of MMN directly relates to the rate at which the regularly occurring stimulus stream is presented. As presentation rate slows, robustness of the sensory memory trace diminishes. By manipulating presentation rate, the strength of the sensory memory trace is parametrically varied, providing greater sensitivity to detect auditory cortical dysfunction. A secondary hypothesis was that duration-evoked MMN abnormalities in CLN3 disease would be more severe at slower presentation rates, resulting from greater demand on the sensory memory system.
Data from individuals with CLN3 disease (N=21; range 6-28 years of age) showed robust MMN responses (i.e., intact auditory sensory memory processes) at the medium stimulation rate. However, at the fastest rate, MMN was significantly reduced, and at the slowest rate, MMN was not detectable in CLN3 disease relative to neurotypical controls (N=41; ages 6-26 years).
Results reveal emerging insufficiencies in this critical auditory perceptual system in individuals with disease.
我们研究了患有CLN3病（青少年神经元蜡样脂褐质沉积症）的个体的听觉感觉记忆能力，特别是针对“持续时间”处理这一语音感知中的关键线索。鉴于晚期CLN3病会导致言语和语言技能下降，我们假设事件相关电位（ERP）的持续时间诱发失匹配负波（MMN）将是该人群中逐渐出现的非典型皮质处理的标志物，有可能作为基于大脑的生物标志物应用于临床试验。
我们采用了三种刺激速率（快：450毫秒，中：900毫秒，慢：1800毫秒），以评估听觉感觉记忆痕迹的可持续性。MMN的稳健性直接与呈现规律出现的刺激流的速率相关。随着呈现速率减慢，感觉记忆痕迹的稳健性会降低。通过操纵呈现速率，感觉记忆痕迹的强度会参数性地变化，从而提供更高的灵敏度来检测听觉皮质功能障碍。第二个假设是，CLN3病中持续时间诱发的MMN异常在较慢的呈现速率下会更严重，这是由于感觉记忆系统的需求增加所致。
来自CLN3病个体（N = 21；年龄范围6 - 28岁）的数据显示，在中等刺激速率下有稳健的MMN反应（即完整的听觉感觉记忆过程）。然而，在最快速率下，MMN显著降低，在最慢速率下，与神经典型对照组（N = 41；年龄6 - 26岁）相比，CLN3病个体中无法检测到MMN。
结果揭示了患有该病的个体在这个关键听觉感知系统中出现了新的功能不足。
