title: Effects of copper toxicity on response inhibition processes: a study in Wilson's disease.
abstract: 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.
authors.affiliation: Cognitive Neurophysiology, Department of Child and Adolescent Psychiatry, Faculty of Medicine of the TU Dresden, Schubertstraße 42, 01309, Dresden, Germany.
authors.forename: Ann-Kathrin
authors.initials: AK
authors.lastname: Stock
authors.affiliation: Department of Neurology, Faculty of Medicine of the TU Dresden, Dresden, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Reuner
authors.affiliation: Cognitive Neurophysiology, Department of Child and Adolescent Psychiatry, Faculty of Medicine of the TU Dresden, Schubertstraße 42, 01309, Dresden, Germany.
authors.forename: Krutika
authors.initials: K
authors.lastname: Gohil
authors.affiliation: Cognitive Neurophysiology, Department of Child and Adolescent Psychiatry, Faculty of Medicine of the TU Dresden, Schubertstraße 42, 01309, Dresden, Germany. christian.beste@uniklinikum-dresden.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Beste
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D015913:Chelation Therapy; D003071:Cognition / Q000187:drug effects*; D003300:Copper / Q000378:metabolism* / Q000633:toxicity*; D004569:Electroencephalography; D005260:Female; D006527:Hepatolenticular Degeneration / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000523:psychology*; D006801:Humans; D007266:Inhibition, Psychological; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D009638:Norepinephrine / Q000378:metabolism*
chemical_list: D003300:Copper; D009638:Norepinephrine
keywords: Cognition; Copper; DBH; EEG; Impulsivity; Response inhibition; Toxicity; Wilson’s disease