The motor inhibition system in Parkinson's disease with levodopa‐induced dyskinesias

Cerasa, Antonio; Donzuso, Giulia; Morelli, Maurizio; Mangone, Graziella; Salsone, Maria; Passamonti, Luca; Augimeri, Antonio; Arabia, Gennarina; Quattrone, Aldo

doi:10.1002/mds.26378

Cited by 31 publications

(33 citation statements)

References 27 publications

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“…Accumulating preclinical experiments indicate a role for the cortex, with LIDs correlating with supersensitive excitatory transmission at corticostriatal synapses and high‐frequency cortical oscillations . Additionally, human neuroimaging studies suggest that abnormal dopaminergic modulation of striato‐cortical networks underlies LIDs, and that alterations in activity of frontal cortex areas were linked to LIDs in PD patients . Dyskinetic patients exhibited decreased activity of the right inferior frontal cortex after l ‐dopa, whereas patients without dyskinesias showed a reverse effect.…”

Section: Discussionmentioning

confidence: 99%

α7 nicotinic receptor agonists reduce levodopa‐induced dyskinesias with severe nigrostriatal damage

et al. 2015

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Background ABT-126 is a novel, safe and well-tolerated α7 nicotinic receptor agonist in a Phase 2 Alzheimer's disease study. Here we test the antidyskinetic effect of ABT-126 in MPTP-treated squirrel monkeys with moderate and more severe nigrostriatal damage. Methods Monkeys (n=21, Set 1) were lesioned with MPTP 1-2×. When parkinsonian, they were gavaged with levodopa (10 mg/kg)/carbidopa (2.5 mg/kg) twice daily and dyskinesias rated. They were then given nicotine in drinking water (n=5), or treated with vehicle (n=6) or ABT-126 (n=10) twice daily orally 30 min before levodopa. Set 1 was then re-lesioned 1-2 times for a total of 3-4 MPTP injections. The antidyskinetic effect of ABT-126, nicotine and the β2* nicotinic receptor agonist ABT-894 was re-assessed. Another group of monkeys (n=23, Set 2) was lesioned with MPTP only 1-2×. They were treated with levodopa/carbidopa, administered the α7 agonist ABT-107 (n=6), ABT-894 (n=6), nicotine (n=5) or vehicle (n=6) and dyskinesias evaluated. All monkeys were euthanized and the dopamine transporter measured. Results With moderate nigrostriatal damage (MPTP 1-2×), ABT-126 dose-dependently decreased dyskinesias (~60%), with similar results with ABT-894 (~60%) or nicotine (~60%). With more severe damage (MPTP 3-4×), ABT-126 and nicotine reduced dyskinesias, but ABT-894 did not. The dopamine transporter was 41% and 8.9% of control with moderate and severe nigrostriatal damage, respectively. No drug modified parkinsonism. Conclusion The novel α7 nicotinic receptor drug ABT-126 reduced dyskinesias in monkeys with both moderate and severe nigrostriatal damage. ABT-126 may be useful to reduce dyskinesias in both early and later stage Parkinson's disease.

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Section: Discussionmentioning

confidence: 99%

α7 nicotinic receptor agonists reduce levodopa‐induced dyskinesias with severe nigrostriatal damage

et al. 2015

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“…This task has been employed to explore a range of psychological questions such as the relationship between response initiation and inhibition [26, 27] and the characteristics of inhibitory control [28–31]. The stop signal task has also proved useful for characterizing deficits in behavioral inhibition in Parkinson’s disease [32], schizophrenia [33], ADHD [34], and in individuals with alcohol- and drug-dependencies [35, 36]. …”

Section: Motor Inhibition Associated With Action Stoppingmentioning

confidence: 99%

Physiological Markers of Motor Inhibition during Human Behavior

Duqué

Greenhouse

Labruna

et al. 2017

Trends in Neurosciences

223

228

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Transcranial magnetic stimulation (TMS) studies in humans have shown that many behaviors engage processes that suppress excitability within the corticospinal tract. Inhibition of the motor output pathway has been extensively studied in the context of action stopping, where a planned movement needs to be abruptly aborted. Recent TMS work has also revealed markers of motor inhibition during the preparation of movement. Here, we review the evidence for motor inhibition during action stopping and action preparation, focusing on studies that have used TMS to monitor changes in the excitability of the corticospinal pathway. We discuss how these physiological results have motivated theoretical models of how the brain selects actions, regulates movement initiation and execution, and switches from one state to another.

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“…This excessive striato-cortical connectivity in response to levodopa may play a role in the pathophysiology of LID [54, 55]. Another study showed that the connectivity of inferior frontal cortex was decreased with M1 and increased with the putamen in patients with LID [56]. This finding suggests that the neural network centered on the inferior frontal cortex may also involve in the pathophysiological mechanisms underlying LID.…”

Section: Intervention-related Network Changesmentioning

confidence: 99%

The study of brain functional connectivity in Parkinson’s disease

Gao

2016

Transl Neurodegener

100

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Parkinson’s disease (PD) is a neurodegenerative disorder primarily affecting the aging population. The neurophysiological mechanisms underlying parkinsonian symptoms remain unclear. PD affects extensive neural networks and a more thorough understanding of network disruption will help bridge the gap between known pathological changes and observed clinical presentations in PD. Development of neuroimaging techniques, especially functional magnetic resonance imaging, allows for detection of the functional connectivity of neural networks in patients with PD. This review aims to provide an overview of current research involving functional network disruption in PD relating to motor and non-motor symptoms. Investigations into functional network connectivity will further our understanding of the mechanisms underlying the effectiveness of clinical interventions, such as levodopa and deep brain stimulation treatment. In addition, identification of PD-specific neural network patterns has the potential to aid in the development of a definitive diagnosis of PD.

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The motor inhibition system in Parkinson's disease with levodopa‐induced dyskinesias

Abstract: Our study demonstrated that levodopa intake in dyskinetic patients tends to alter the functioning of some parts of the neural network involved in motor inhibition.

Cited by 31 publications

References 27 publications

α7 nicotinic receptor agonists reduce levodopa‐induced dyskinesias with severe nigrostriatal damage

α7 nicotinic receptor agonists reduce levodopa‐induced dyskinesias with severe nigrostriatal damage

Physiological Markers of Motor Inhibition during Human Behavior

The study of brain functional connectivity in Parkinson’s disease

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