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• W2943733170 abstract "Executive dysfunctions occur in a number of neurodegenerative diseases that have traditionally been thought to be restricted to the motor system. For example, patients with Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS) have repeatedly been reported to show deficits in cognitive flexibility (i.e., the ability to shift cognitive sets). A large part of the literature on cognitive inflexibility in neurodegenerative diseases relies on data from the Wisconsin Card Sorting Test (WCST). The WCST is often regarded as the best-established neuropsychological test of cognitive flexibility. However, the WCST is unlikely to be a pure measure of cognitive flexibility as successful performance on the WCST has also been shown to require a wide range of other cognitive processes. The present work aimed at dissociating the cognitive components of WCST performance to elucidate whether impaired WCST performance in neurodegenerative diseases can rather be attributed to cognitive inflexibility or to deficits in other processes. By combining neuropsychological and electrophysiological methods, it was possible to identify distinct indicators of the cognitive and neural processes underlying individuals’ performance on a computerized version of the WCST (cWCST). In a first step, the construct validity of these indicators was assessed in three studies involving healthy individuals. Behavioral data analysis suggested that dissociable processes of set shifting, rule inference, and set maintenance are reflected in different cWCST performance measures. These performance measures were differentially affected by age-related changes and the experimental manipulation of cWCST task parameters. In addition, two event-related potential (ERP) deflections elicited by cues on the cWCST were found to be related to distinct cognitive processes. Whereas the frontocentral P3a deflection might serve as an index of attentional orienting for rule inference on the WCST, the posterior switch positivity (PSP) seems to reflect the neural resources allocated to cognitive set shifting. In a second step, the acquired knowledge about these behavioral and electrophysiological cWCST measures was applied in five clinical studies to examine the origins of WCST performance deficits in three neurological disorders: PD, ALS, and primary dystonia. In contrast to PD and ALS, primary dystonia develops in the absence of gross neurodegenerative changes but has been related to microstructural alterations in the basal ganglia. Throughout the studies and irrespective of the particular disorder, patients showed moderate performance deficits both on the standard and the computerized version of the WCST. Fine-grained analyses of behavioral performance and ERP measures revealed that cWCST deficits are qualitatively different in PD, ALS, and primary dystonia. In ALS, attenuated amplitudes of the PSP seem to indicate dysfunction in the frontoparietal brain networks underlying cognitive set shifting. In contrast, attenuated P3a amplitudes in patients with primary dystonia may reflect disruption in the frontostriatal circuits that give rise to proactive attentional orienting for rule inference. Finally, cWCST performance in patients with PD was observed to be particularly impaired when the amplitudes of both ERP deflections were attenuated. These findings indicate that different neurophysiological changes can result in WCST performance deficits and that these deficits are most pronounced when the neural substrates of multiple cognitive processes are affected. In sum, the present work illustrates how a fine-grained analysis of behavioral performance and its neural correlates can advance the understanding of executive impairment in general and cognitive inflexibility in particular. One implication is that the complexity of the WCST should not preclude its use for the assessment of specific cognitive functions. In fact, the data presented in this thesis suggest that by decomposing the complex cognitive and neural processes required by the WCST into functionally distinct subprocesses, it may be possible to concurrently measure several different aspects of executive functioning. In light of the present results, ERP measures appear to be promising for the dissociation of closely intertwined processes and for the detection of subtle pathological changes in the neural systems underlying executive processes. ERP recordings may thus be a valuable supplement to the diagnosis of executive dysfunctions in PD, ALS, and primary dystonia." @default.
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• W2943733170 date "2016-01-01" @default.
• W2943733170 modified "2023-09-27" @default.
• W2943733170 title "Cognitive flexibility and its alterations in neurodegenerative diseases" @default.
• W2943733170 hasPublicationYear "2016" @default.
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