Horsthuis Douwe J, Molholm Sophie, Foxe John J, Francisco Ana A
The Cognitive Neurophysiology Laboratory, Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York, USA.
Department of Neuroscience, Rose F. Kennedy Center, Albert Einstein College of Medicine, Bronx, New York, USA.
bioRxiv. 2023 Apr 2:2023.03.31.535154. doi: 10.1101/2023.03.31.535154.
Cystinosis, a rare lysosomal storage disease, is characterized by cystine crystallization and accumulation within tissues and organs, including the kidneys and brain. Its impact on neural function appears mild relative to its effects on other organs, but therapeutic advances have led to substantially increased life expectancy, necessitating deeper understanding of its impact on neurocognitive function. Behavioral difficulties have been reported in cystinosis in the visual and visual-processing domain. Very little is known, however, about how the brains of people living with cystinosis process visual information, although cysteamine accumulation in the retina is a prominent feature of cystinosis. Here, electrophysiology was recorded during a Go/No-Go task to investigate early visual processing in cystinosis, compared to an age-matched control group. Analyses focused on early stages of cortical visual processing. The groups differed in their initial cortical response, with individuals with cystinosis exhibiting a significantly larger visual evoked potential (VEP) in the 130 to 150 ms time window. The timing and topography of this response suggested an enhanced P1 in cystinosis that could be the result of cortical hyperexcitability and/or differences in attentional engagement and explain, at least partially, the visual and visual-spatial difficulties described in this population. The groups also differed in the associations between neural responses and verbal abilities: While controls with higher IQ scores presented larger neural responses, that relationship was not observed in cystinosis.
胱氨酸贮积症是一种罕见的溶酶体贮积病，其特征是胱氨酸在包括肾脏和大脑在内的组织和器官中结晶并蓄积。相对于它对其他器官的影响，其对神经功能的影响似乎较为轻微，但治疗方面的进展已使预期寿命大幅延长，因此有必要更深入地了解其对神经认知功能的影响。已有报道称胱氨酸贮积症患者在视觉和视觉处理领域存在行为困难。然而，尽管半胱胺在视网膜中的蓄积是胱氨酸贮积症的一个显著特征，但对于患有胱氨酸贮积症的人的大脑如何处理视觉信息却知之甚少。在此，与年龄匹配的对照组相比，在一项“是/否”任务中记录了电生理数据，以研究胱氨酸贮积症患者的早期视觉处理情况。分析集中在皮质视觉处理的早期阶段。两组在初始皮质反应上存在差异，患有胱氨酸贮积症的个体在130至150毫秒的时间窗口内表现出明显更大的视觉诱发电位（VEP）。这种反应的时间和地形图表明胱氨酸贮积症患者的P1增强，这可能是皮质兴奋性过高和/或注意力参与差异的结果，并且至少可以部分解释该人群中描述的视觉和视觉空间困难。两组在神经反应与语言能力之间的关联方面也存在差异：虽然智商得分较高的对照组表现出更大的神经反应，但在胱氨酸贮积症患者中未观察到这种关系。
