Action reprogramming in Parkinson's disease: Response to prediction error is modulated by levels of dopamine
Open accessAbstract
Humans are able to use knowledge of previous events to estimate the probability of future actions. Consequently, an unexpected event will elicit a prediction error as the prepared action has to be replaced by an unprepared option in a process known as "action reprogramming" (AR). Here we show that people with Parkinson's disease (PD) have a dopamine-sensitive deficit in AR that is proportional to the size of the prediction error. Participants performed a probabilistic reaction time (RT) task in the context of either a predictable or unpredictable environment. For an overall predictable sequence, PD patients, on and off dopamine medication, and healthy controls showed similar improvements in RT. However, in the context of a generally predictable sequence, PD patients off medication were impaired in reacting to unexpected events that elicit large prediction errors and require AR. Critically, this deficit in AR was modulated by the prediction error associated with the upcoming event. The prolongation of RT was not observed during an overall unpredictable sequence, in which relatively unexpected events evoke little prediction error and the requirement for AR should be minimal, given the context. The data are compatible with recent theoretical accounts suggesting that levels of dopamine encode the reliability, i.e., precision, of sensory information. In this scheme, PD patients off medication have low dopamine levels and may therefore be less confident about incoming sensory information and more reliant on top-down predictions. Consequently, when these internal predictions are incorrect, PD patients take longer to respond appropriately to unexpected sensory information.
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Precision is thought to be signaled by neuromodulators such as dopamine and acetylcholine, depending on the particular inferential hierarchy.
“Precision is thought to be signaled by neuromodulators such as dopamine and acetylcholine, depending on the particular inferential hierarchy (21–23).”
From The Predictive Coding Account of Psychosis (2018) · cites this paper as [22]
The Discussion (page not provided) proposes that dopamine may encode the precision of sensory prediction errors. It does not address acetylcholine or say that the neuromodulator signaling precision depends on the inferential hierarchy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe dopaminergic system is crucial for predictive abilities.
“which is crucial for predictive abilities (Galea et al., 2012)”
From Predictive coding in neuropsychiatric disorders: a systematic transdiagnostic review. (2025) · cites this paper as Galea et al., 2012
The Discussion (page not supplied) links dopamine to responding to sensory prediction errors, but distinguishes that response from forming predictions: patients off medication could learn predictable information yet reacted more slowly to violations. Thus the paper supports a role for dopamine in responding to prediction errors, not the broader claim that it is crucial for predictive abilities generally. (LLM, conf=0.86)
Experimental — accuracy not yet measured
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“In addition, when it was attempted to restore the dopaminergic system – which is crucial for predictive abilities (Galea et al., 2012) – through the use of dopaminergic medications, it was found that the performance did not improve.”
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- Authors
- Galea, J. M., Bestmann, S., Beigi, M., Jahanshahi, M., & Rothwell, J. C.
- Affiliations
- UCL Queen Square Institute of Neurology (GB)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2012-01-11
- Volume
- 32
- Issue
- 2
- Pages
- 542-550
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6621072
- OpenAlex
- W2112918447
- Cited by
- 52
- References
- 53
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 4 · 2023: 1 · 2022: 3 · 2021: 3 · 2020: 5 · 2019: 3 · 2018: 6 · 2017: 6 · 2016: 3 · 2015: 3 · 2014: 6 · 2013: 6
- FWCI
- 3.13
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion, cc-by-nc)
- Funders
- Medical Research Council (MR/K00414X/1)
- Biotechnology and Biological Sciences Research Council (BB/F02424X/1)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Motor Control and Adaptation
- Keywords
- Parkinson's disease, prediction error, dopamine, unexpected events, top-down prediction, reaction time (psychology)
- MeSH terms
- Aged, Aged, 80 and over, Basal Ganglia, Cues, Dopamine, Female, Humans, Male, Middle Aged, Models, Neurological, Parkinson Disease, Probability Learning, Reaction Time, Dopamine Agents, Anticipation, Psychological
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