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In everyday life, we encounter situations that require tradeoffs between potential rewards and associated costs, such as time and (physical) effort. The literature indicates a prominent role for dopamine in discounting of both delay and effort, with mixed findings for delay discounting in humans. Moreover, the reciprocal antagonistic interaction between dopaminergic and cholinergic transmission in the striatum suggests a potential opponent role of acetylcholine in these processes. We found opposing effects of dopamine D2 (haloperidol) and acetylcholine M1 receptor (biperiden) antagonism on specific components of effort-based decision-making in healthy humans: haloperidol decreased, whereas biperiden increased the willingness to exert physical effort. In contrast, delay discounting was reduced under haloperidol, but not affected by biperiden. Together, our data suggest that dopamine, acting at D2 receptors, modulates both effort and delay discounting, while acetylcholine, acting at M1 receptors, appears to exert a more specific influence on effort discounting only. Tradeoffs between potential rewards and associated costs involves the dopaminergic system, which antagonistically interacts with the cholinergic system. This study describes that dopamine and acetylcholine have opposing effects on the modulation of specific components of cost-benefit decision making in humans. [ABSTRACT FROM AUTHOR]

Background: Previous research suggested that quadripulse (QPS)-induced synaptic plasticity is associated with both cognitive and motor function in patients with multiple sclerosis (MS) and does not appear to be reduced compared to healthy controls (HCs). Objective: This study aimed to explore the relationship between the degree of QPS-induced plasticity and clinically significant decline in motor and cognitive functions over time. We hypothesized that MS patients experiencing functional decline would exhibit lower levels of baseline plasticity compared to those without decline. Methods: QPS-induced plasticity was evaluated in 80 MS patients (56 with relapsing-remitting MS and 24 with progressive MS), and 69 age-, sex-, and education-matched HCs. Cognitive and motor functions, as well as overall disability status were evaluated annually over a median follow-up period of 2 years. Clinically meaningful change thresholds were predefined for each outcome measure. Linear mixed-effects models, Cox proportional hazard models, logistic regression, and receiver-operating characteristic analysis were applied to analyse the relationship between baseline plasticity and clinical progression in the symbol digit modalities test, brief visuospatial memory test revised (BVMT-R), nine-hole peg test (NHPT), timed 25-foot walk test, and expanded disability status scale. Results: Overall, the patient cohort showed no clinically relevant change in any functional outcome over time. Variability in performance was observed across time points in both patients and HCs. MS patients who experienced clinically relevant decline in manual dexterity and/or visuospatial learning and memory had significantly lower levels of synaptic plasticity at baseline compared to those without such decline (NHPT: β = -0.25, p = 0.02; BVMT-R: β = -0.50, p = 0.005). Receiver-operating characteristic analysis underscored the predictive utility of baseline synaptic plasticity in discerning between patients experiencing functional decline and those maintaining stability only for visuospatial learning and memory (area under the curve = 0.85). Conclusion: Our study suggests that QPS-induced plasticity could be linked to clinically relevant functional decline in patients with MS. However, to solidify these findings, longer follow-up periods are warranted, especially in cohorts with higher prevalences of functional decline. Additionally, the variability in cognitive performance in both patients with MS and HCs underscores the importance of conducting further research on reliable change based on neuropsychological tests. [ABSTRACT FROM AUTHOR]

Bradykinesia is a cardinal hallmark of Parkinson's disease (PD). Improvement in bradykinesia is an important signature of effective treatment. Finger tapping is commonly used to index bradykinesia, albeit these approaches largely rely on subjective clinical evaluations. Moreover, recently developed automated bradykinesia scoring tools are proprietary and are not suitable for capturing intraday symptom fluctuation. We assessed finger tapping (i.e., Unified Parkinson's Disease Rating Scale (UPDRS) item 3.4) in 37 people with Parkinson's disease (PwP) during routine treatment follow ups and analyzed their 350 sessions of 10-s tapping using index finger accelerometry. Herein, we developed and validated ReTap, an open-source tool for the automated prediction of finger tapping scores. ReTap successfully detected tapping blocks in over 94% of cases and extracted clinically relevant kinematic features per tap. Importantly, based on the kinematic features, ReTap predicted expert-rated UPDRS scores significantly better than chance in a hold out validation sample (n = 102). Moreover, ReTap-predicted UPDRS scores correlated positively with expert ratings in over 70% of the individual subjects in the holdout dataset. ReTap has the potential to provide accessible and reliable finger tapping scores, either in the clinic or at home, and may contribute to open-source and detailed analyses of bradykinesia. [ABSTRACT FROM AUTHOR]