Trial reportPLoS computational biology2022
Noradrenergic deficits contribute to apathy in Parkinson's disease through the precision of expected outcomes.
Trial report in PLoS computational biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 48 citations in OpenAlex.
- Uncovering lipid biomarkers linked to methylphenidate efficacy in treating apathy in Alzheimer's disease: insights from the ADMET 2 trial.Alzheimer's research & therapy · 2026Trial
- Pharmacological and pupillary evidence for the noradrenergic contribution to reinforcement learning in Parkinson's disease.Communications biology · 2025Trial
- Efficacy and safety of clonidine for the treatment of impulse control disorder in Parkinson's disease: a multicenter, parallel, randomised, double-blind, Phase 2b Clinical trial.Journal of neurology · 2023Trial
- Apathy in Parkinson's Disease: Distinguishing Overlapping Symptoms Via Network Analysis.Movement disorders clinical practice · 2026Article
- Dopamine Boosts Motivation for Prosocial Effort in Parkinson's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Self-delivered arousal-heightening stimuli to improve mobility in persons with parkinsonism: A case series.Journal of Parkinson's disease · 2026Article
- Apathy and Reduced Voluntary Activity in Older Adults with Parkinson's Disease: Mechanisms, Clinical Assessment, and Rehabilitation Implications.Clinical interventions in aging · 2026Review
- Short-term heart rate variability is preserved in Parkinson's disease under atomoxetine.Brain communications · 2026Article
- Apathy linked to higher amyloid burden and cognitive deterioration in Parkinson's disease.Journal of Parkinson's disease · 2025Observational
- Caudate serotonin signaling during social exchange distinguishes essential tremor and Parkinson's disease patients.Nature communications · 2025Article
- Behavioural changes in frontotemporal dementia and their cognitive and neuroanatomical correlates.Brain : a journal of neurology · 2025Article
- Article
- Central Involvement in Pure Autonomic Failure: Insights from Neuromelanin-Sensitive Magnetic Resonance Imaging andMovement disorders : official journal of the Movement Disorder Society · 2025Article
- Behavioral disorders in Parkinson disease: current view.Journal of neural transmission (Vienna, Austria : 1996) · 2025Review
- Loss of excitatory inputs and decreased tonic and evoked activity of locus coeruleus neurons in aged P301S mice.bioRxiv : the preprint server for biology · 2025Article
- Dopamine alters functional gradients in Parkinson's disease.Imaging neuroscience (Cambridge, Mass.) · 2025Article
- Noradrenergic therapies in neurodegenerative disease: from symptomatic to disease modifying therapy?Brain communications · 2025Review
- Anatomical correlates of apathy and impulsivity co-occurrence in early Parkinson's disease.Journal of neurology · 2024Article
- Impaired value-based decision-making in Parkinson's disease apathy.Brain : a journal of neurology · 2024Article
- Noradrenergic alterations in Parkinson's disease: a combined 11C-yohimbine PET/neuromelanin MRI study.Brain : a journal of neurology · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 7 institutions in 6 countries.
Funding
Abstract
Apathy is a debilitating feature of many neuropsychiatric diseases, that is typically described as a reduction of goal-directed behaviour. Despite its prevalence and prognostic importance, the mechanisms underlying apathy remain controversial. Degeneration of the locus coeruleus-noradrenaline system is known to contribute to motivational deficits, including apathy. In healthy people, noradrenaline has been implicated in signalling the uncertainty of expectations about the environment. We proposed that noradrenergic deficits contribute to apathy by modulating the relative weighting of prior beliefs about action outcomes. We tested this hypothesis in the clinical context of Parkinson's disease, given its associations with apathy and noradrenergic dysfunction. Participants with mild-to-moderate Parkinson's disease (N = 17) completed a randomised double-blind, placebo-controlled, crossover study with 40 mg of the noradrenaline reuptake inhibitor atomoxetine. Prior weighting was inferred from psychophysical analysis of performance in an effort-based visuomotor task, and was confirmed as negatively correlated with apathy. Locus coeruleus integrity was assessed in vivo using magnetisation transfer imaging at ultra-high field 7T. The effect of atomoxetine depended on locus coeruleus integrity: participants with a more degenerate locus coeruleus showed a greater increase in prior weighting on atomoxetine versus placebo. The results indicate a contribution of the noradrenergic system to apathy and potential benefit from noradrenergic treatment of people with Parkinson's disease, subject to stratification according to locus coeruleus integrity. More broadly, these results reconcile emerging predictive processing accounts of the role of noradrenaline in goal-directed behaviour with the clinical symptom of apathy and its potential pharmacological treatment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.