title: Striatal disorders dissociate mechanisms of enhanced and impaired response selection - Evidence from cognitive neurophysiology and computational modelling.
abstract: Paradoxically enhanced cognitive processes in neurological disorders provide vital clues to understanding neural function. However, what determines whether the neurological damage is impairing or enhancing is unclear. Here we use the performance of patients with two disorders of the striatum to dissociate mechanisms underlying cognitive enhancement and impairment resulting from damage to the same system. In a two-choice decision task, Huntington's disease patients were faster and less error prone than controls, yet a patient with the rare condition of benign hereditary chorea (BHC) was both slower and more error prone. EEG recordings confirmed significant differences in neural processing between the groups. Analysis of a computational model revealed that the common loss of connectivity between striatal neurons in BHC and Huntington's disease impairs response selection, but the increased sensitivity of NMDA receptors in Huntington's disease potentially enhances response selection. Crucially the model shows that there is a critical threshold for increased sensitivity: below that threshold, impaired response selection results. Our data and model thus predict that specific striatal malfunctions can contribute to either impaired or enhanced selection, and provide clues to solving the paradox of how Huntington's disease can lead to both impaired and enhanced cognitive processes.
authors.affiliation: Cognitive Neurophysiology, Department of Child and Adolescent Psychiatry and Psychotherapy, Faculty of Medicine of the TU Dresden, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Beste
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Humphries
authors.affiliation: Department of Neurology, St. Josef Hospital, Ruhr-University, Bochum, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Saft
mesh_terms: D000161:Acoustic Stimulation; D000328:Adult; D000704:Analysis of Variance; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology*; D003198:Computer Simulation; D003265:Contingent Negative Variation; D003342:Corpus Striatum / Q000473:pathology* / Q000503:physiopathology*; D003657:Decision Making / Q000502:physiology*; D004192:Discrimination, Psychological; D004569:Electroencephalography; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000150:complications / Q000235:genetics; D008297:Male; D008959:Models, Neurological; D016202:N-Methylaspartate / Q000494:pharmacology; D009415:Nerve Net / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D009483:Neuropsychological Tests; D055815:Young Adult
chemical_list: D018690:Excitatory Amino Acid Agonists; D016202:N-Methylaspartate
keywords: AMPA, a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; BHC, benign hereditary chorea; Basal ganglia; Benign hereditary chorea; Computational modelling; EEG; EEG, electroencephalography; ERP, event related potential; Executive control; FSIs, fast spiking interneurons; GABA, ?-aminobutyric acid; Huntington's disease; MMN, mismatch negativity; MMSE, Mini Mental Status Examination; MSN, medium spiny neuron; NMDA, N-methyl-d-aspartate; RON, reorientation of attention