Levodopa Improves Procedural Motor Learning in Chronic Stroke Patients

Department of Neurology, University of Münster, Münster, Germany.
Archives of physical medicine and rehabilitation (Impact Factor: 2.57). 10/2008; 89(9):1633-41. DOI: 10.1016/j.apmr.2008.02.030
Source: PubMed


To test the hypothesis that administration of dopamine precursor levodopa improves procedural motor learning (defined as the ability to acquire novel movement patterns gradually through practice) in patients with residual motor deficits in the chronic phase after stroke (> or =1 y after stroke).
A double-blind, placebo-controlled, randomized crossover design.
Neurology department in a German university.
Eighteen patients with chronic motor dysfunction because of stroke (13 men, 5 women; age range, 53-78 y; mean time poststroke +/- SD, 3.3+/-2.1 y).
Patients received 3 doses of levodopa (100mg of levodopa plus 25mg of carbidopa) or placebo before 1 session of procedural motor learning.
Procedural motor learning performed by using the paretic hand assessed by using a modified version of the serial reaction time task with a probabilistic sequence. The primary outcome measure was the difference in reaction times between random and sequential elements.
Levodopa significantly improved our primary outcome measure, procedural motor learning, compared with placebo (P<.05). Reaction times to random elements, analysis of error rates, psychophysical assessments, and performance in a simple motor task were comparable between conditions, indicating that better learning under levodopa was not caused by differences in response styles, arousal, mood, or motor reaction times but that levodopa modulated learning.
Our results show that levodopa may improve procedural motor learning in patients with chronic stroke, in line with our hypothesis. These findings suggest that this interventional strategy in combination with customary rehabilitative treatments could significantly improve the outcome of neurorehabilitation in the chronic stage after stroke. ( identifier NCT00126087.)

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    • "A first randomized, double-blind study vs. placebo in ischemic stroke patients (n = 53), showed that a treatment with 100 mg per day for three weeks was associated with a decrease in motor impairments and the result lingered for three weeks after the end of the treatment. However, other studies did not corroborate these results [13] [14] [15] [16] [17]. "
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    ABSTRACT: La thrombolyse IV par le rTPA en urgence, est actuellement la seule thérapeutique médicamenteuse validée (bénéficiant d’une autorisation de mise sur le marché) capable d’améliorer la récupération fonctionnelle après un accident vasculaire cérébral ischémique. Toutefois, la dernière décennie nous a appris que la récupération fonctionnelle spontanée s’accompagnait d’une réorganisation intracérébrale constante et complexe du cerveau lésé. La modulation de cette plasticité cérébrale base rationnelle de la récupération fonctionnelle, par des facteurs externes tels que des médicaments, est maintenant largement d’actualité avec pour objectif d’améliorer la récupération et de réduire le handicap final. Cet article rassemble les arguments précliniques et cliniques qui soutiennent le rôle des inhibiteurs de la recapture de la sérotonine dans la récupération de la fonction motrice après accident vasculaire cérébral ischémique.
    Annals of Physical and Rehabilitation Medicine 11/2014; 57(8). DOI:10.1016/
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    • "Instead, the dopamine dysfunction in PD that impairs reinforcement and use-dependent plasticity mechanisms was used to explore the role of these mechanisms in savings and interference. Our interpretation was built upon current knowledge of the role of reinforcement in adaptation learning (Diedrichsen et al., 2010; Huang et al., 2011; Izawa and Shadmehr, 2011; Pekny et al., 2011; Shmuelof et al., 2012), the role of dopamine in reinforcement (Frank, 2005) and use-dependent plasticity (Floel, 2005; Floel et al., 2008; Rösser et al., 2008). However, we cannot rule out the possibility that other mechanisms might additionally contribute to savings and interference. "
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    ABSTRACT: Reinforcement and use-dependent plasticity mechanisms have been proposed to be involved in both savings and anterograde interference in adaptation to a visuomotor rotation (cf. Huang et al., 2011). In Parkinson's disease (PD), dopamine dysfunction is known to impair reinforcement mechanisms, and could also affect use-dependent plasticity. Here, we assessed savings and anterograde interference in PD with an A1-B-A2 paradigm in which movement repetition was (1) favored by the use of a single-target, and (2) manipulated through the amount of initial training. PD patients and controls completed either limited or extended training in A1 where they adapted movement to a 30 • counter-clockwise rotation of visual feedback of the movement trajectory, and then adapted to a 30 • clockwise rotation in B. After subsequent washout, participants readapted to the first 30 • counter-clockwise rotation in A2. Controls showed significant anterograde interference from A1 to B only after extended training, and significant A1-B-A2 savings after both limited and extended training. However, despite similar A1 adaptation to controls, PD patients showed neither anterograde interference nor savings. That extended training was necessary in controls to elicit anterograde interference but not savings suggests that savings and anterograde interference do not result from equal contributions of the same underlying mechanism(s). It is suggested that use-dependent plasticity mechanisms contributes to anterograde interference but not to savings, while reinforcement mechanisms contribute to both. As both savings and anterograde interference were impaired in PD, dopamine dysfunction in PD might impair both reinforcement and use-dependent plasticity mechanisms during adaptation to a visuomotor rotation.
    Frontiers in Human Neuroscience 02/2013; 7. DOI:10.3389/fnhum.2013.00055 · 3.63 Impact Factor
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    • "This is why improving motor skill learning is a major target for neurorehabilitation. It is therefore not surprising that several neurorehabilitation methods have recently been developed on the premise of enhancing motor skill learning (Boyd and Winstein, 2001; Bhatt et al., 2007; Rosser et al., 2008; Abe et al., 2011). Given their capacity to modulate cortical excitability and enhance behavioral performances, non-invasive brain stimulations such as repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) are particularly attractive as add-on interventions for enhancing post-stroke recovery (Reis et al., 2008). "
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    ABSTRACT: Background: Since motor learning is a key component for stroke recovery, enhancing motor skill learning is a crucial challenge for neurorehabilitation. Transcranial direct current stimulation (tDCS) is a promising approach for improving motor learning. The aim of this trial was to test the hypothesis that dual-tDCS applied bilaterally over the primary motor cortices (M1) improves online motor skill learning with the paretic hand and its long-term retention. Methods: Eighteen chronic stroke patients participated in a randomized, cross-over, placebo-controlled, double bind trial. During separate sessions, dual-tDCS or sham dual-tDCS was applied over 30 min while stroke patients learned a complex visuomotor skill with the paretic hand: using a computer mouse to move a pointer along a complex circuit as quickly and accurately as possible. A learning index involving the evolution of the speed/accuracy trade-off was calculated. Performance of the motor skill was measured at baseline, after intervention and 1 week later. Results: After sham dual-tDCS, eight patients showed performance worsening. In contrast, dual-tDCS enhanced the amount and speed of online motor skill learning compared to sham (p < 0.001) in all patients; this superiority was maintained throughout the hour following. The speed/accuracy trade-off was shifted more consistently after dual-tDCS (n = 10) than after sham (n = 3). More importantly, 1 week later, online enhancement under dual-tDCS had translated into superior long-term retention (+44%) compared to sham (+4%). The improvement generalized to a new untrained circuit and to digital dexterity. Conclusion: A single-session of dual-tDCS, applied while stroke patients trained with the paretic hand significantly enhanced online motor skill learning both quantitatively and qualitatively, leading to successful long-term retention and generalization. The combination of motor skill learning and dual-tDCS is promising for improving post-stroke neurorehabilitation.
    Frontiers in Human Neuroscience 01/2013; DOI:10.3389/fnhum.2012.00343 · 3.63 Impact Factor
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