Stock Ann-Kathrin, Reuner Ulrike, Gohil Krutika, Beste Christian
Cognitive Neurophysiology, Department of Child and Adolescent Psychiatry, Faculty of Medicine of the TU Dresden, Schubertstraße 42, 01309, Dresden, Germany.
Department of Neurology, Faculty of Medicine of the TU Dresden, Dresden, Germany.
Arch Toxicol. 2016 Jul;90(7):1623-30. doi: 10.1007/s00204-015-1609-3. Epub 2015 Oct 5.
Wilson's disease (WD) is a rare genetic disease causing copper deposits in various tissues. Given the specificity of the underlying pathology, it is a good model to investigate the effects of copper toxicity on cognitive functions in humans. If left untreated, WD results in neurodegeneration and organ failure, but irrespective of potential brain damage, the medication might reduce cortical norepinephrine (NE) levels. In line with this, dysexecutive symptoms including increased impulsivity have been reported for WD patients, but the underlying mechanisms have remained elusive. We investigated inhibition and the associated neurophysiological correlates in n = 26 WD patients with mild-to-moderate clinical symptoms and matched healthy controls who completed a Go/Nogo task, while an EEG was recorded. Although the behavioral data do not show increased impulsivity in WD, the neurophysiological data show that evaluative processing of successful inhibition (as reflected by the P3 component) was strongly compromised. This was reflected by a decrease in ACC activity which was positively correlated with the severity of WD symptoms, stressing the importance of copper (toxicity) for neurocognitive functioning and impulsivity. These changes are most likely due to a combination of NE deficiency induced by WD medication as well as WD-induced brain damage. The fact that changes were still evident on a neurophysiological level suggests that neurophysiological correlates of cognitive processes and functions provide a more sensitive index of toxicity and/or treatment efficiency than purely behavioral measures.
威尔逊氏病（WD）是一种罕见的遗传性疾病，会导致铜在各种组织中沉积。鉴于其潜在病理的特殊性，它是研究铜毒性对人类认知功能影响的良好模型。如果不进行治疗，WD会导致神经退行性变和器官衰竭，但无论是否存在潜在的脑损伤，药物治疗都可能降低皮质去甲肾上腺素（NE）水平。与此一致的是，已有报道称WD患者存在包括冲动性增加在内的执行功能障碍症状，但其潜在机制仍不清楚。我们对n = 26名有轻度至中度临床症状的WD患者以及匹配的健康对照者进行了抑制及相关神经生理相关性的研究，他们完成了一项Go/Nogo任务，同时记录脑电图。虽然行为数据未显示WD患者的冲动性增加，但神经生理数据表明，成功抑制的评估性加工（由P3成分反映）受到严重损害。这表现为前扣带回皮质（ACC）活动减少，且与WD症状的严重程度呈正相关，强调了铜（毒性）对神经认知功能和冲动性的重要性。这些变化很可能是由于WD药物引起的NE缺乏以及WD导致的脑损伤共同作用的结果。在神经生理水平上变化仍然明显这一事实表明，认知过程和功能的神经生理相关性比单纯的行为测量提供了更敏感的毒性和/或治疗效果指标。
