To what extent do we learn from the positive versus negative outcomes of our decisions? The neuromodulator dopamine plays a key role in these reinforcement learning processes. Patients with Parkinson's disease, who have depleted dopamine in the basal ganglia, are impaired in tasks that require learning from trial and error. Here we show, using two cognitive procedural learning tasks, that Parkinson's patients off medication are better at learning to avoid choices that lead to negative outcomes than they are at learning from positive outcomes. Dopamine medication reverses this bias, making patients more sensitive to positive than negative outcomes. This pattern was predicted by our biologically-based computational model of basal ganglia/dopamine interactions in cognition, which has separate pathways for "Go" and "NoGo" responses that are differentially modulated by positive and negative reinforcement.

In clinical trials for patients with Parkinson's disease (PD) with motor fluctuations, efficacy is generally ascribed to an intervention if motor function is significantly improved or if "off" time is significantly reduced. However, we have argued that patients might not be improved if off time is reduced only to the extent that unwanted dyskinesia is increased. Therefore, a home diary should include an assessment of dyskinesia to provide an accurate reflection of clinical status over a period of time. We undertook two studies to develop a home diary to assess functional status in patients with PD with motor fluctuations and dyskinesia. In both studies, patients concurrently completed a test and a reference diary. In Study I, we evaluated the impact of different severities of dyskinesia on patient-defined functional status. There were 1,149 evaluable half-hour time periods from 24 patients; 94.3% of off time was considered "bad" time and 90.2% of "on" time without dyskinesia, 72.6% of on time with mild dyskinesia, 43.0% of on time with moderate dyskinesia, and 15.2% of on time with severe dyskinesia was considered "good" time. In Study II, we evaluated a new home diary designed to separate dyskinesia that had a negative impact on patient-defined functional status from dyskinesia that did not. There were 816 evaluable time periods from 17 patients; 84.9% of off time and 89.9% of on time with troublesome dyskinesia was considered bad time while 85.5% of on time without dyskinesia and 93.8% of on time with nontroublesome dyskinesia was considered good time. With this diary (Diary II), the effect of an intervention can be expressed as the change in off time and the change in on time with troublesome dyskinesia (bad time). The sum can be used as an outcome variable and compared to baseline or across groups. In evaluating the efficacy of an intervention, assessment of change in off time and change in on time with troublesome dyskinesia provides a more accurate reflection of clinical response than change in off time alone.

Botulinum toxin type A (Dysport) has been shown in European studies to be a safe and effective treatment for cervical dystonia. This multicenter, double-blind, randomized, controlled trial assessed the safety and efficacy of Dysport in cervical dystonia patients in the United States. Eighty patients were randomly assigned to receive one treatment with Dysport (500 units) or placebo. Participants were followed up for 4 to 20 weeks, until they needed further treatment. They were assessed at baseline and weeks 2, 4, 8, 12, 16, and 20 after treatment. Dysport was significantly more efficacious than placebo at weeks 4, 8, and 12 as assessed by the Toronto Western Spasmodic Torticollis Rating Scale (10-point vs. 3.8-point reduction in total score, respectively, at week 4; P < or = 0.013). Of participants in the Dysport group, 38% showed positive treatment response, compared to 16% in the placebo group (95% confidence interval, 0.02-0.41). The median duration of response to Dysport was 18.5 weeks. Side effects were generally similar in the two treatment groups; only blurred vision and weakness occurred significantly more often with Dysport. No participants in the Dysport group converted from negative to positive antibodies after treatment. These results confirm previous reports that Dysport (500 units) is safe, effective, and well-tolerated in patients with cervical dystonia.

Mutations in the parkin gene occur among individuals with PD with an older age at onset (> or =60 years) who have a positive family history of the disease. In addition, the clinical findings of parkin-positive individuals are remarkably similar to those without mutations.