Dataset Information

A Placebo-Controlled Study to Assess the Sensitivity of Finger Tapping to Medication Effects in Parkinson's Disease.

ABSTRACT:

Background

Movement Disorder Society-Unified Parkinson's Rating Scale Part III (MDS-UPDRS III) is the gold standard for assessing medication effects in patients with Parkinson's disease (PD). However, short and rater-independent measurements would be ideal for future trials.

Objectives

To assess the ability of 3 different finger tapping tasks to detect levodopa/carbidopa-induced changes over time and to determine their correlation and compare their discriminatory power with MDS-UPDRS III.

Methods

This was a randomized, double-blind, crossover study in 20 patients with PD receiving levodopa/carbidopa and placebo capsules after overnight medication withdrawal. Pre- and up to 3.5 hours postdose, MDS-UPDRS III and tapping tasks were performed. Tasks included 2 touchscreen-based alternate finger tapping tasks (index finger versus index-middle finger tapping) and a thumb-index finger task using a goniometer.

Results

In the alternate index finger tapping task, levodopa/carbidopa compared with placebo resulted in significantly faster (total taps: 12.5 [95% confidence interval, CI, 6.7-18.2]) and less accurate tapping (total spatial error: 240 mm [95% CI, 123-357 mm]) with improved rhythm (intertap interval standard deviation [SD], -16.3% [95% CI, -29.9% to 0.0%]). In the thumb-index finger task, tapping was significantly faster (mean opening velocity, 151 degree/s [64-237 degree/s]), with a higher mean amplitude (8.4 degrees [3.7-13.0 degrees]) and improved rhythm (intertap interval SD, -46.4% [95% CI, -63.7% to -20.9%]). The speed-related endpoints showed a moderate-to-strong correlation with the MDS-UPDRS III (r = 0.45-0.70). The effect sizes of total taps and spatial error in the alternate index finger tapping task and opening velocity in the thumb-index finger task were comparable with the MDS-UPDRS III. In contrast, the MDS-UPDRS III performed better than the alternate index-middle finger task.

Conclusion

The alternate index finger and the thumb-index finger tapping tasks provide short, rater-independent measurements that are sensitive to levodopa/carbidopa effects with a similar effect size as the MDS-UPDRS III.

SUBMITTER: Thijssen E

PROVIDER: S-EPMC9631850 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Publications

A Placebo-Controlled Study to Assess the Sensitivity of Finger Tapping to Medication Effects in Parkinson's Disease.

Thijssen Eva E Makai-Bölöni Soma S van Brummelen Emilie E den Heijer Jonas J Yavuz Yalcin Y Doll Robert-Jan RJ Groeneveld Geert Jan GJ

Movement disorders clinical practice 20220927 8

<h4>Background</h4>Movement Disorder Society-Unified Parkinson's Rating Scale Part III (MDS-UPDRS III) is the gold standard for assessing medication effects in patients with Parkinson's disease (PD). However, short and rater-independent measurements would be ideal for future trials.<h4>Objectives</h4>To assess the ability of 3 different finger tapping tasks to detect levodopa/carbidopa-induced changes over time and to determine their correlation and compare their discriminatory power with MDS-UP ...[more]

PMID: 36339295

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Project description:Malfunctions in the neural circuitry of the basal ganglia (BG), induced by alterations in the dopaminergic system, are responsible for an array of motor disorders and milder cognitive issues in Parkinson's disease (PD). Recently Baston and Ursino (2015a) presented a new neuroscience mathematical model aimed at exploring the role of basal ganglia in action selection. The model is biologically inspired and reproduces the main BG structures and pathways, modeling explicitly both the dopaminergic and the cholinergic system. The present work aims at interfacing this neurocomputational model with a compartmental model of levodopa, to propose a general model of medicated Parkinson's disease. Levodopa effect on the striatum was simulated with a two-compartment model of pharmacokinetics in plasma joined with a motor effect compartment. The latter is characterized by the levodopa removal rate and by a sigmoidal relationship (Hill law) between concentration and effect. The main parameters of this relationship are saturation, steepness, and the half-maximum concentration. The effect of levodopa is then summed to a term representing the endogenous dopamine effect, and is used as an external input for the neurocomputation model; this allows both the temporal aspects of medication and the individual patient characteristics to be simulated. The frequency of alternate tapping is then used as the outcome of the whole model, to simulate effective clinical scores. Pharmacokinetic-pharmacodynamic modeling was preliminary performed on data of six patients with Parkinson's disease (both "stable" and "wearing-off" responders) after levodopa standardized oral dosing over 4 h. Results show that the model is able to reproduce the temporal profiles of levodopa in plasma and the finger tapping frequency in all patients, discriminating between different patterns of levodopa motor response. The more influential parameters are the Hill coefficient, related with the slope of the effect sigmoidal relationship, the drug concentration at half-maximum effect, and the drug removal rate from the effect compartment. The model can be of value to gain a deeper understanding on the pharmacokinetics and pharmacodynamics of the medication, and on the way dopamine is exploited in the neural circuitry of the basal ganglia in patients at different stages of the disease progression.

Project description:BackgroundMusic therapy improves neuronal activity and connectivity of healthy persons and patients with clinical symptoms of neurological diseases like Parkinson's disease, Alzheimer's disease, and major depression. Despite the plethora of publications that have reported the positive effects of music interventions, little is known about how music improves neuronal activity and connectivity in afflicted patients.MethodsFor patients suffering from Parkinson's disease (PD), we propose a daily 25-min music-based synchronous finger tapping (SFT) intervention for 8 weeks. Eligible participants with PD are split into two groups: an intervention group and a control arm. In addition, a third cohort of healthy controls will be recruited. Assessment of finger tapping performances, the Unified Parkinson's Disease Rating Scale (UPDRS), an n-back test, the Montreal Cognitive Assessment (MoCA), as well as oxygenated hemoglobin (HbO2), deoxygenated hemoglobin (HbR), and total hemoglobin activation collected by functional near-infrared spectroscopy (fNIRS) are measured at baseline, week 4 (during), week 8 (post), and week 12 (retention) of the study. Data collected from the two PD groups are compared to baseline performances from healthy controls.DiscussionThis exploratory prospective trial study investigates the cortical neuronal activity and therapeutic effects associated with an auditory external cue used to induce automatic and implicit synchronous finger tapping in patients diagnosed with PD. The extent to which the intervention is effective may be dependent on the severity of the disease. The study's findings are used to inform larger clinical studies for optimization and further exploration of the therapeutic effects of movement-based music therapy on neural activity in neurological diseases.Trial registrationClinicalTrials.gov NCT04212897 . Registered on December 30, 2019. The participant recruitment and study protocol have received ethical approval from the First Affiliated Hospital of Dalian Medical University. The hospital Protocol Record number is PJ-KY-2019-123. The protocol was named "fNIRS Studies of Music Intervention of Parkinson's Disease." The current protocol is version 1.1, revised on September 1, 2020.

Dataset Information

A Placebo-Controlled Study to Assess the Sensitivity of Finger Tapping to Medication Effects in Parkinson's Disease.

Background

Objectives

Methods

Results

Conclusion

Publications

A Placebo-Controlled Study to Assess the Sensitivity of Finger Tapping to Medication Effects in Parkinson's Disease.

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