ArticleJournal of neurology2021
Dopaminergic therapy and prefrontal activation during walking in individuals with Parkinson's disease: does the levodopa overdose hypothesis extend to gait?
Article in Journal of neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Neural correlates of dual-task walking in people with central neurological disorders: a systematic review.Journal of neurology · 2022Pooled it
- Is levodopa induced freezing of gait a paradox or an expected phenomenon?: a clinico-pathophysiological hypothesis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Review
- Technology for measuring freezing of gait: Current state of the art and recommendations.Journal of Parkinson's disease · 2025Review
- Article
- Circadian Intervention Improves Parkinson's Disease and May Slow Disease Progression: A Ten Year Retrospective Study.Brain sciences · 2024Article
- Impact of Acute Dopamine Replacement on Cognitive Function in Parkinson's Disease.Movement disorders clinical practice · 2024Article
- The effect of dopamine replacement therapy on cortical structure in Parkinson's disease.CNS neuroscience & therapeutics · 2024Article
- Role of exercise in modulating prefrontal cortical activation for improved gait and cognition in Parkinson's disease patients.Physical activity and nutrition · 2024Article
- Freezing of gait in Parkinson's disease is related to imbalanced stopping-related cortical activity.Brain communications · 2024Article
- Cortical activation and functional connectivity during locomotion tasks in Parkinson's disease with freezing of gait.Frontiers in aging neuroscience · 2023Article
- Daily-Living Freezing of Gait as Quantified Using Wearables in People With Parkinson Disease: Comparison With Self-Report and Provocation Tests.Physical therapy · 2022Article
- Whole-Head Functional Near-Infrared Spectroscopy as an Ecological Monitoring Tool for Assessing Cortical Activity in Parkinson's Disease Patients at Different Stages.International journal of molecular sciences · 2022Article
- Imaging the neural underpinnings of freezing of gait in Parkinson's disease.NeuroImage. Clinical · 2022Review
- Classification of Parkinson's disease with freezing of gait based on 360° turning analysis using 36 kinematic features.Journal of neuroengineering and rehabilitation · 2021Article
- Executive function and dopamine response in Parkinson's disease freezing of gait.Parkinsonism & related disorders · 2021Article
- Arm swing responsiveness to dopaminergic medication in Parkinson's disease depends on task complexity.NPJ Parkinson's disease · 2021Article
- Study on the effects and mechanisms of rhythmic auditory stimulation on freezing of gait in Parkinson's disease: investigation based on functional near-infrared spectroscopy (fNIRS) technology.Frontiers in neurologyArticle
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
The "levodopa-overdose hypothesis" posits that dopaminergic replacement therapy (1) increases performance on tasks that depend on the nigrostriatal-pathway (e.g., motor-control circuits), yet (2) decreases performance on tasks that depend upon the mesocorticolimbic-pathway (e.g., prefrontal cortex, PFC). Previous work in Parkinson's disease (PD) investigated this model while focusing on cognitive function. Here, we evaluated whether this model applies to gait in patients with PD and freezing of gait (FOG). Forty participants were examined in both the OFF anti-Parkinsonian medication state (hypo-dopaminergic) and ON state (hyper-dopaminergic) while walking with and without the concurrent performance of a serial subtraction task. Wireless functional near-infrared spectroscopy measured PFC activation during walking. Consistent with the "overdose-hypothesis", performance on the subtraction task decreased (p = 0.027) after dopamine intake. Moreover, the effect of walking condition on PFC activation depended on the dopaminergic state (i.e., interaction effect p = 0.001). Gait significantly improved after levodopa administration (p < 0.001). Nonetheless, PFC activation was higher (p = 0.013) in this state than in the OFF state during usual-walking. This increase in PFC activation in the ON state suggests that dopamine treatment interfered with PFC functioning. Otherwise, PFC activation, putatively a reflection of cognitive compensation, should have decreased. Moreover, in contrast to the OFF state, in the ON state, PFC activation failed to increase (p = 0.313) during dual-tasking, perhaps due to a "ceiling effect". These findings extend the "levodopa-overdose hypothesis" and suggest that it also applies to gait in PD patients. While dopaminergic therapy improves certain aspects of motor performance, optimal treatment should consider the "double-edged sword" of levodopa.
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