Dopaminergic modulation of cognitive function-implications for l-DOPA treatment in Parkinson's disease
Abstract
It is well recognised that patients with Parkinson's disease exhibit cognitive deficits, even in the earliest disease stages. Whereas, L-DOPA therapy in early Parkinson's disease is accepted to improve the motor symptoms, the effects on cognitive performance are more complex: both positive and negative effects have been observed. The purpose of the present article is to review the effects of L-DOPA medication in Parkinson's disease on cognitive functions in the broad domains of cognitive flexibility and working memory. The review places the effects in Parkinson's disease within a framework of evidence from studies with healthy human volunteers, rodents and non-human primates as well as computational modeling work. It is suggested that beneficial or detrimental effects of L-DOPA are observed depending on task demands and basal dopamine levels in distinct parts of the striatum. The study of the beneficial and detrimental cognitive effects of L-DOPA in Parkinson's disease has substantial implications for the understanding and treatment development of cognitive abnormalities in Parkinson's disease as well as normal health.
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Executive control emerges from the interplay between cognitive stability and flexibility, related to the prefrontal cortex and striatum, both modulated by dopamine.
“Interestingly, executive control has been considered to emerge from the interplay between cognitive stability (defined as the maintenance of task-relevant representations) and flexibility (defined as the ability to adapt, update, and shift between informational states) – two major, but partially antagonistic functions of cognitive control, related correspondingly to the prefrontal cortex (PFC) and”
From Working Memory Reloaded: Tyrosine Repletes Updating in the N-Back Task (2013) · cites this paper as Cools, 2006
High dopamine levels in the PFC that benefit stability may reduce flexible alteration of cognitive representations, while low PFC dopamine levels may benefit flexible updating but impair maintenance against distractors.
“According to Cools (2006), the same high DA levels in the PFC that are beneficial for the stability of representations may reduce the ability to flexibly alter cognitive representations. Low DA levels in the PFC may in turn be beneficial for the flexible updating of cognitive representations, but at the same time impair the ability to maintain representations in the face of intervening distractors”
From Working Memory Reloaded: Tyrosine Repletes Updating in the N-Back Task (2013) · cites this paper as Cools (2006)
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- Authors
- Cools, R.
- Affiliations
- University of California, Berkeley (US)
- Corresponding author
- Cools, Roshan
- ORCID
- Cools, Roshan
- Venue
- Neuroscience & Biobehavioral Reviews
- Publisher
- Elsevier BV
- Published
- 2006-01
- Volume
- 30
- Issue
- 1
- Pages
- 1-23
- ISSN
- 0149-7634 (ISSN-L)
- OpenAlex
- W1972010893
- Cited by
- 903
- References
- 25
- Citations by year
- 2026: 21 · 2025: 31 · 2024: 38 · 2023: 30 · 2022: 27 · 2021: 29 · 2020: 34 · 2019: 37 · 2018: 36 · 2017: 56 · 2016: 67 · 2015: 56 · 2014: 54 · 2013: 70 · 2012: 63
- FWCI
- 4.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience & Biobehavioral Reviews (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- Parkinson's disease, L-DOPA, dopaminergic modulation, cognitive impairment, cognitive flexibility, working memory, striatum, computational modeling, rodent models, non-human primates
- MeSH terms
- Animals, Antiparkinson Agents, Cognition, Dopamine, Humans, Levodopa, Neuronal Plasticity, Parkinson Disease
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