We investigated the role of dopamine in distinct forms of reversal shifting by comparing two groups of patients with mild Parkinson's disease (PD), one ON and one OFF their normal dopaminergic medication. In accordance with our previous work, patients ON medication exhibited impaired reversal shifting relative to patients OFF medication. The present results extend previous studies by showing that the medication-induced deficit on reversal shifting was restricted to conditions where reversals were signaled by unexpected punishment. By contrast, patients ON medication performed as well as patients OFF medication and controls when the reversal was signaled by unexpected reward. The medication-induced deficit was particularly pronounced in patients on the dopamine D3 receptor agonist pramipexole. These data indicate that dopaminergic medication in PD impairs reversal shifting depending on the motivational valence of unexpected outcomes.
The mesocortical and nigrostriatal dopamine (DA) systems are well known to play a role in cognitive and reward-related processing (Brozoski, Brown, Rosvold, & Goldman, 1979; Castner, Williams, & Goldman-Rakic, 2000; Goldman-Rakic, 1992; Hollerman & Schultz, 1998). Human disorders that implicate the DA system, such as Parkinson's disease (PD), attention-deficit/hyperactivity disorder (ADHD) and schizophrenia, are associated with a variety of cognitive deficits, ranging from impulsivity to inflexibility. Treatment with dopaminergic medication may alleviate some of these deficits. However, the relationship between DA and cognitive performance is complex (Arnsten, 1998; Williams & Goldman-Rakic, 1995; Zahrt, Taylor, Mathew, & Arnsten, 1997): Dopaminergic medication may improve or impair cognitive function depending on a number of factors, such as task demands and baseline DA levels in underlying neural circuitry (Arnsten, 1998; Cools, Barker, Sahakian, & Robbins, 2001; Kimberg, D’Esposito, & Farah, 1997; Mattay et al., 2003).
