If switching between abstract rules, and the reconfiguration it e

If switching between abstract rules, and the reconfiguration it engenders in both

stimulus and response sets, is cortically mediated, PD should only be associated with switching deficits in the presence of cortical dysfunction (HY stage II), but not when it might be assumed to be generally limited to the striatum (HY stage I). Second, we aimed to validate our hypothesis concerning the sensitivity of the rule reconfiguration manipulation to cortical involvement in task switching by including a group of patients A-769662 cost with frontal lesions which spare the basal ganglia. Although neuropsychological and imaging studies have dissociated to some extent frontal contributions to components of cognitive control (e.g., Brass et al., 2005; Braver et al., 2003; Wylie, Javitt, & Foxe, 2004; Yeung et al., 2006), the current neuropsychological investigation is the first,

to our knowledge, to address this issue as a function of whether reconfiguration in the rule that maps stimuli to responses determines cortical involvement. AP24534 Based on previous findings of impaired abstract rule switching in cortically compromised stage II but not hypothetically cortically intact stage I PD patients (Kehagia et al., 2009), frontal patients were predicted to show SC deficits only when response rule reconfiguration is required on a switch of task, that is, only with abstract rules, but not when switching between concrete rules governing attentional selection where MCE公司 the superordinate rule that maps a task-relevant stimulus to a response remains unchanged. Such a finding in

patients with frontal cortical damage and intact basal ganglia would strengthen the claim that switching between abstract rules is a paradigm sensitive to frontal cortical deficits in PD. Third, we addressed whether disease severity also differentiates task switching impairments with concrete naming rules known to be l-dopa responsive. Previous dopaminergic withdrawal studies using naming rules have been inconsistent in that they have shown that dopaminergic medication can either ameliorate PD switching deficits to control levels (Cools et al., 2003) or simply temper them (Cools et al., 2001a), and deficits have also been reported in a large group of medicated patients, that is, despite medication (Cools et al., 2001b). In this case, the efficacy of pharmacotherapy may depend not only on the degree of the neurochemical deficit, but also on the functional integrity of the neural substrate targeted by the pharmacotherapeutic regime, that is, the basal ganglia and their connections to cortex. Thus, we investigated how disease severity at these early HY stages, that represent differential degrees of nigrostriatal and cortical neuronal loss, impacts on the cognitive remediation effects conferred by dopa-therapy.

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