Specifically, ventrolateral regions are involved in the general retrieval and maintenance of rules (Donohue, Wendelken, Crone, & Bunge, 2005), and dorsolateral regions in rule-based response selection (Bunge, 2004; Bunge, Hazeltine, Scanlon, Rosen, & Gabrieli, 2002), which is especially relevant to the current formulations. Furthermore, regions such as the supplementary motor area (SMA and pre-SMA), insula and lateral

PFC, as well as parietal areas, are consistently implicated in switching between categorization rules (e.g., Badre & Wagner, 2006; Brass, Ullsperger, Knoesche, von Cramon, & Phillips, 2005; Brass & von Cramon, 2004; Braver, Reynolds, & Donaldson, 2003; Ruge et al., 2005; Rushworth, Hadland, Paus, & Sipila, 2002a; GSK2118436 clinical trial Rushworth, Passingham, & Nobre, 2002b; Slagter et al., 2006; Yeung, Nystrom, Aronson, & Cohen, 2006). Thus, the consideration

that the neural underpinnings of cognitive flexibility differ depending on the types of rules that are switched is a salient one with respect to deciphering whether and what kind of task switching deficits are present at different stages of PD. In addition to rule differences in task switching designs, the dynamic nature of PD in terms of its evolving pathology creates a further challenge in interpreting patterns of switching performance. Studies have grouped together patients at HY stages I–III, despite conceivably diverse neuropathological profiles. On one hand, the mild unilateral signs at HY stage I probably reflect an asymmetrical, but relatively circumscribed RG7420 cost Selleck Fer-1 DA deficit which is most pronounced unilaterally in the dorsal striatum (Nahmias, Garnett, Firnau, & Lang, 1985). However, stages II and III, characterized by bilateral motor signs, postural and gait disturbance, arguably reflect not only greater DA dysfunction in the caudate, nucleus accumbens and PFC but also significantly increased deposition

of cortical Lewy bodies in posterior and temporal cortical regions (Brooks & Piccini, 2006; Kehagia, Barker, & Robbins, 2010; Wolters & Braak, 2006). Given this additional pathology that emerges as the disease progresses, consideration of clinical differences even early on in the disease is particularly relevant to investigations of cognitive control, and specifically in understanding the role of the PFC and basal ganglia in task switching. Disease severity, addressed categorically (HY staging) or continuously (UPDRS score), is an essential factor that determines the switching profile of the parkinsonian patient (Kehagia et al., 2009). We test our hypotheses concerning rule reconfiguration and disease severity in PD by directly contrasting for the first time switching between concrete naming rules and abstract categorization rules in medicated stage I and stage II PD patients, drawing also on the performance of a group of patients with frontal lesions but intact basal ganglia.