1978). Although none of the participants met the criteria for major learn more depressive episodes and other psychiatric disorders, we further investigated the presence of depressive and anxiety symptoms using the Beck Depression Inventory and the Hamilton Rating Scale Anxiety, respectively (Hamilton 1959; Beck and Steer 1987). In PD patients, these cognitive functions were only evaluated Off-therapy given the short half-life of apomorphine (see next section). Inhibitors,research,lifescience,medical Overall, the neuropsychological session lasted approximately 1 h. Demographic and neuropsychological data were analyzed using independent two-sample t-tests within SPSS (Statistical Package for Social

Sciences, http://www-01.ibm.com/software/analytics/spss/). Apomorphine test in PD patients To prevent vomiting and/or nausea, patients were administered domperidone (60 mg/daily) for 48 h before Inhibitors,research,lifescience,medical the apomorphine test (Bowron 2004). Fourteen hours prior to scanning, all medications except domperidone were withdrawn.

PD patients attended two distinct sessions (i.e., Off- and On-apomorphine). The apomorphine test was executed either at the first or second fMRI session in a counterbalanced order across patients (sessions were separated by at least 1 day). This protocol ensured a complete Inhibitors,research,lifescience,medical drug clearance in case apomorphine was administered at the first session (apomorphine half-life is ~45 min; Bowron 2004; LeWitt 2004). Apomorphine was subcutaneously injected 10 min before Inhibitors,research,lifescience,medical scanning at the dose of 0.04 mg/kg (mean dose ~3 mg). This schedule and dosage allow us to study apomorphine effects on cognitive functions approximately at drug peak dose and under a strong postsynaptic pharmacological action (Bowron 2004; LeWitt 2004). Motor symptoms were assessed via UPDRS before and after apomorphine injection. Inhibitors,research,lifescience,medical To account for nonspecific drug effects on arousal, patients were also asked to report their arousal level via a specific questionnaire (Mackay et al. 1978) before and after apomorphine injection. fMRI task Participants executed a modified version of a verbal working-memory paradigm that

has been previously validated Casein kinase 1 in PD patients and that evokes robust activations within the PFC and striatum (Lewis et al. 2003, 2004). There were three types of trials: (1) high-load working memory: subjects were instructed to remember a string of six uppercase letters presented for 2 sec and followed by a 3-sec delay of blank screen. Next, a lowercase probe letter was displayed for 2 sec and subjects were asked, within this time-window, to press a button when the probe matched any of the letters previously displayed in the string. Alternatively, no response was required. A 1-sec delay of blank screen concluded the trial that lasted 8 sec in total; (2) medium-load working memory: trials were identical to previous ones except for a string that contained three letters intermixed to three abstract symbols (#).