Horsthuis Douwe John, Molholm Sophie, Foxe John J, Francisco Ana A
Albert Einstein College of Medicine.
University of Rochester School of Medicine and Dentistry.
Res Sq. 2023 Jul 25:rs.3.rs-3176642. doi: 10.21203/rs.3.rs-3176642/v1.
Cystinosis, a rare lysosomal storage disease caused by mutations in the CTNS gene, is characterized by cystine crystallization and accumulation within multiple tissues, including kidney and brain. Its impact on neural function appears mild relative to its effects on other organs during early disease, but since therapeutic advances have led to substantially increased life expectancy, neurological implications are of increasing interest, necessitating deeper understanding of the impact of cystinosis on neurocognitive function. Behavioral difficulties have been reported in cystinosis in the visual domain. Very little is known, however, about how the brains of people living with cystinosis process visual information. This is especially interesting given that cystine accumulation in the cornea and posterior ocular structures is a hallmark of cystinosis.
Here, high-density scalp electrophysiology was recorded to visual stimuli (during a Go/No-Go task) to investigate early visual processing in individuals with cystinosis, compared to age-matched controls. 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 130-150 ms time window. 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.
The enlarged VEP in cystinosis 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.
胱氨酸贮积症是一种由CTNS基因突变引起的罕见溶酶体贮积病，其特征是胱氨酸在包括肾脏和大脑在内的多个组织中结晶和蓄积。在疾病早期，它对神经功能的影响相对于对其他器官的影响似乎较为轻微，但由于治疗进展使预期寿命大幅延长，神经学方面的影响越来越受到关注，因此有必要更深入地了解胱氨酸贮积症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领域存在行为困难。然而，对于患有胱氨酸贮积症的人的大脑如何处理视觉信息，人们知之甚少。鉴于角膜和眼后结构中胱氨酸蓄积是胱氨酸贮积症的一个标志，这一点尤其有趣。
在此，记录了对视觉刺激（在Go/No-Go任务期间）的高密度头皮电生理，以研究胱氨酸贮积症患者与年龄匹配的对照组相比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，胱氨酸贮积症患者在130 - 150毫秒时间窗口内表现出明显更大的视觉诱发电位（VEP）。两组在神经反应与语言能力之间的关联也存在差异：虽然智商得分较高的对照组呈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。
胱氨酸贮积症中VEP增大可能是皮质兴奋性过高和/或注意力参与差异的结果，并且至少部分地解释了该人群中描述的视觉和视觉空间困难。
