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Abstract Impulse Control Disorder (ICD) in Parkinson’s disease is a behavioral addiction induced by dopaminergic therapies, but otherwise unclear etiology. The current study investigates the interaction of reward processing variables, dopaminergic therapy, and risky decision-making and subjective feelings in patients with versus without ICD. Patients with (n = 18) and without (n = 12) ICD performed a risky decision-making task both ‘on’ and ‘off’ standard-of-care dopaminergic therapies (the task was performed on 2 different days with the order of on and off visits randomized for each patient). During each trial of the task, participants choose between two options, a gamble or a certain reward, and reported how they felt about decision outcomes. Subjective feelings of ‘pleasure’ are differentially driven by expectations of possible outcomes in patients with, versus without ICD. While off medication, the influence of expectations about risky-decisions on subjective feelings is reduced in patients with ICD versus without ICD. While on medication, the influence of expected outcomes in patients with ICD versus without ICD becomes similar. Computational modeling of behavior supports the idea that latent decision-making factors drive subjective feelings in patients with Parkinson’s disease and that ICD status is associated with a change in the relationship between factors associated with risky behavior and subjective feelings about the experienced outcomes. Our results also suggest that dopaminergic medications modulate the impact expectations have on the participants' subjective reports. Altogether our results suggest that expectations about risky decisions may be decoupled from subjective feelings in patients with ICD, and that dopaminergic medications may reengage these circuits and increase emotional reactivity in patients with ICD.

Plain Language Summary Management of uncontrollable motor movements in patients with advanced Parkinson’s disease rely on oral levodopa-based treatments. Non-motor symptoms such as depression and anxiety are managed with additional oral medications. Over time, higher and more frequent dosing of oral medications is required, resulting in complex medication regimens that impact quality of life and adherence. A real-world study of 10,752 Parkinson’s disease patients between 2014 and 2018 evaluated the effectiveness of two device-aided therapies to reduce pill burden, carbidopa/levodopa enteral suspension and deep brain stimulation. Carbidopa/levodopa suspension treatment involves continuous delivery of levodopa to the intestines through a surgical port attached to a portable pump. Brain stimulation involves surgery to attach metal wires to the brain to send electrical pulses via an implanted stimulator. As Parkinson’s disease predominately affects the elderly, we compared Medicare patients on carbidopa/levodopa suspension to a matched control group receiving no suspension and to those receiving brain stimulation. Average pill burden/day was measured prior to receiving a device-aided treatment (baseline) and at 0–6 months and 7–12 months post-treatment (follow-up). The top graph shows that by 6-months post-treatment, patients on carbidopa/levodopa suspension required fewer pills than those without suspension (4.7 versus 11.4), with further pill reduction at 12 months (3.5 versus 11.1). The bottom graph shows that by 6 months, patients on carbidopa/levodopa suspension required fewer pills than patients treated with brain stimulation (4.8 versus 7.4), with further reduction at 12 months (3.6 versus 7.0). The reduction in oral pill burden suggests that the carbidopa/levodopa suspension may present an opportunity to simplify treatment regimens.

Introduction: As Parkinson's disease (PD) progresses, the number/frequency of PD medications tend to increase, which is correlated with decreased patient compliance and suboptimal control of PD symptoms. We investigated efficacy and safety of levodopa-carbidopa intestinal gel (LCIG) daytime monotherapy (with or without nighttime oral levodopa-carbidopa) compared with polytherapy (LCIG with ≥1 adjunctive PD therapy) in advanced PD patients. Methods: This post hoc descriptive study compared LCIG stable daytime monotherapy with LCIG stable polytherapy in all six phase 3/3b open-label studies from both US and international sites; because of study design variability, pooling data for comparison was not appropriate. Efficacy assessments included PD diary data (mean change from baseline in “Off” time and “On” time with or without troublesome dyskinesia), mean Unified PD Rating Scale scores (Parts II and III), and 39-item Parkinson's Disease Questionnaire (PDQ-39) summary index. Adverse events were also assessed. Results: Overall, LCIG daytime monotherapy and polytherapy demonstrated similar efficacy/safety profiles in advanced PD patients, regardless of treatment duration or population. LCIG monotherapy vs. polytherapy groups experienced similar mean decreases in “Off” time (4.6 vs. 4.1 h/day) and similar increases in “On” time without troublesome dyskinesia (4.6 vs. 4.1 h/day). In most studies, PDQ-39 summary index scores were reduced from baseline by ≥5 points, regardless of patient population or study duration. Adverse events not related to the procedure/device were similar in both groups. Conclusion: Our data suggest that, for appropriate patients, LCIG monotherapy can provide a more simplified treatment option with similar efficacy and safety.

Introduction Currently, sub-second monitoring of neurotransmitter release in humans can only be performed during standard of care invasive procedures like DBS electrode implantation. The procedure requires acute insertion of a research probe and additional time in surgery, which may increase infection risk. We sought to determine the impact of our research procedure, particularly the extended time in surgery, on infection risk. Methods We screened 602 patients who had one or more procedure codes documented for DBS electrode implantation, generator placement, programming, or revision for any reason performed at Wake Forest Baptist Medical Center between January 2011 through October 2020 using International Classification of Diseases (ICD) codes for infection. During this period, 116 patients included an IRB approved 30-minute research protocol, during the Phase 1 DBS electrode implantation surgery, to monitor sub-second neurotransmitter release. We used Fisher’s Exact test (FET) to determine if there was a significant change in the infection rate following DBS electrode implantation procedures that included, versus those that did not include, the neurotransmitter monitoring research protocol. Results Within 30-days following DBS electrode implantation, infection was observed in 1 (0.21%) out of 486 patients that did not participate in the research procedure and 2 (1.72%) of the 116 patients that did participate in the research procedure. Notably, all types of infection observed were typical of those expected for DBS electrode implantation. Conclusion Infection rates are not statistically different across research and non-research groups within 30-days following the research procedure (1.72% vs. 0.21%; p = 0.0966, FET). Our results demonstrate that the research procedures used for sub-second monitoring of neurotransmitter release in humans can be performed without increasing the rate of infection.