Levodopa improves response inhibition and enhances striatal activation in early-stage Parkinson's disease

Manza, Peter; Schwartz, Guy; Masson, M; Kann, Sarah J.; Volkow, Nora D.; Li, Chiang‐Shan R.; Leung, Hoi‐Chung

doi:10.1016/j.neurobiolaging.2018.02.003

Cited by 30 publications

(26 citation statements)

References 103 publications

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“…As reported previously, both in the LPD and RPD groups, 7 patients of 17 were under dopaminergic treatment. As it has been suggested that dopaminergic treatment improves inhibitory control in early‐stage PD patients, but not in moderate to advanced patients, we assessed whether those patients of our sample who were under drug therapy had a better reactive inhibition with respect to drug‐naïve patients. As reported in Supplemental Data 6, we did not find any difference between treated and untreated patients.…”

Section: Resultsmentioning

confidence: 99%

Early‐Stage Parkinson's Patients Show Selective Impairment in Reactive But Not Proactive Inhibition

et al. 2019

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Background It is well known that a deficit in inhibitory control is a hallmark of Parkinson's disease (PD). However, inhibition is not a unitary construct, and it is unclear whether patients in the early stage of the disease (Hoehn and Yahr stage 1) exhibit a deficit in outright stopping (reactive inhibition), a deficit in the ability to shape their response strategies according to the context (proactive inhibition), or both. Objective We assessed whether PD patients at Hoehn and Yahr stage 1 show a global or selective impairment in inhibitory control. As it has been suggested that inhibition relies upon a right‐lateralized pathway, we tested whether left‐dominant PD patients suffered from a more severe deficit in this executive function than right‐dominant PD patients. Methods Via a reaching stop‐signal task, we assessed both proactive and reactive inhibition in 17 left‐dominant PD and 17 right‐dominant PD patients and in 24 age‐matched participants. Results We found that reactive inhibition was more impaired in PD patients than in healthy participants. However, proactive inhibition was not affected. Furthermore, we found no differences between left‐dominant PD and right‐dominant PD patients. Conclusions For the first time, we found evidence for a deficit of reactive inhibition in the early‐stage PD patients in the absence of evidence for deficits in proactive inhibition. These findings have clinical relevance as they provide critical insights on the time course of the disease. In addition, we confirmed, on a population of PD patients at Hoehn and Yahr stage 1, previous results showing that the onset of the disease does not affect inhibition. © 2019 International Parkinson and Movement Disorder Society

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Section: Resultsmentioning

confidence: 99%

Early‐Stage Parkinson's Patients Show Selective Impairment in Reactive But Not Proactive Inhibition

et al. 2019

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“…Finally, many treatments of PD target the putamen and/or SNc, including L-DOPA as the first-line medication. L-DOPA restores dopaminergic signaling and improves motor control including response inhibition by enhancing striatal activation in early-stage Parkinson's disease (Manza et al, 2018). High-frequency deep brain stimulation of the putamen (Montgomery et al, 2011), low-frequency deep brain stimulation of the SN pars reticulata (Valldeoriola, 2019;Weiss et al, 2019), and crocin (Haeri et al, 2019) for treatment-refractory patients have also demonstrated efficacy in the treatment of PD.…”

Section: Introductionmentioning

confidence: 99%

KTN1 Variants Underlying Putamen Gray Matter Volumes and Parkinson’s Disease

et al. 2020

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Background: Selective loss of dopaminergic neurons and diminished putamen gray matter volume (GMV) represents a central feature of Parkinson's disease (PD). Recent studies have reported specific effects of kinectin 1 gene (KTN1) variants on the putamen GMV. Objective: To examine the relationship of KTN1 variants, KTN1 mRNA expression in the putamen and substantia nigra pars compacta (SNc), putamen GMV, and PD. Methods: We examined the associations between PD and a total of 1847 imputed KTN1 single nucleotide polymorphisms (SNPs) in one discovery sample [2,000 subjects with PD vs. 1,986 healthy controls (HC)], and confirmed the nominally significant associations (p < 0.05) in two replication samples (900 PD vs. 867 HC, and 940 PD vs. 801 HC, respectively). The regulatory effects of risk variants on the KTN1 mRNA expression in putamen and SNc and the putamen GMV were tested. We also quantified the expression levels of KTN1 mRNA in the putamen and/or SNc for comparison between PD and HC in five independent cohorts. Results: Six replicable and two non-replicable KTN1-PD associations were identified (0.009 ≤ p ≤ 0.049). The major alleles of five SNPs, including rs12880292, rs8017172, rs17253792, rs945270, and rs4144657, significantly increased risk for PD (0.020 ≤ p ≤ 0.049) and putamen GMVs (19.08 ≤ β ≤ 60.38; 2.82 ≤ Z ≤ 15.03;

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“…However, the exact effects of l ‐dopa on decision‐making are still unclear. Indeed, experimental data suggest that l ‐dopa can impair (e.g., by increasing impulsive activation of muscles), improve (e.g., by increasing response inhibition), or not influence cognitive processes involved in decision‐making as well as inhibitory processes. According to computational models of decision‐making, a hyperdopaminergic state could lead to failure of the cognitive processes involved in decision‐making .…”

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confidence: 99%

Effects of subthalamic nucleus stimulation and levodopa on decision‐making in Parkinson's disease

et al. 2019

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A BS TRACT: Background: Parkinson's disease (PD) is frequently associated with behavioral disorders, particularly within the spectrum of motivated behaviors such as apathy or impulsivity. Both pharmacological and neurosurgical treatments have an impact on these impairments. However, there still is controversy as to whether subthalamic nucleus deep brain stimulation (STN-DBS) can cause or reduce impulsive behaviors. Objectives: We aimed to identify the influence of functional surgery on decision-making processes in PD. Methods: We studied 13 PD patients and 13 healthy controls. The experimental task involved squeezing a dynamometer with variable force to obtain rewards of various values under four conditions: without treatment, with L-dopa or subthalamic stimulation alone, and with both L-dopa and subthalamic stimulation. Statistical analyses consisted of generalized linear mixed models including treatment condition, reward value, level of effort, and their interactions. We analyzed acceptance rate (the percentage of accepted trials), decision time, and force applied.Results: Comparatively to controls, patients without treatment exhibited lower acceptance rate and force applied. Patients under L-dopa alone did not exhibit increased acceptance rate. With subthalamic stimulation, either with or without added L-dopa, all measures were improved so that patients' behaviors were undistinguishable from healthy controls'. Conclusions: Our study shows that L-dopa administration does not fully restore cost-benefit decision-making processes, whereas STN-DBS fully normalizes patients' behaviors. These findings suggest that dopamine is partly involved in cost-benefit valuation, and that STN-DBS can have a beneficial effect on motivated behaviors in PD and may improve certain forms of impulsive behaviors.

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Levodopa improves response inhibition and enhances striatal activation in early-stage Parkinson's disease

Cited by 30 publications

References 103 publications

Early‐Stage Parkinson's Patients Show Selective Impairment in Reactive But Not Proactive Inhibition

Early‐Stage Parkinson's Patients Show Selective Impairment in Reactive But Not Proactive Inhibition

KTN1 Variants Underlying Putamen Gray Matter Volumes and Parkinson’s Disease

Effects of subthalamic nucleus stimulation and levodopa on decision‐making in Parkinson's disease

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