Selective Effects of Substantia Nigra and Locus Coeruleus Degeneration on Cognition in Parkinson's Disease
Bibliographic record
Abstract
BACKGROUND: The substantia nigra (SN) and locus coeruleus (LC) are among the first brain regions to degenerate in Parkinson's disease (PD). This has important implications for early cognitive deficits because these nuclei are sources of ascending neuromodulators (i.e., dopamine and noradrenaline) that support various cognitive functions such as learning, memory, and executive function. OBJECTIVE: Our aim was to investigate the selective and independent contributions of SN and LC degeneration to cognitive deficits in PD. METHODS: We ran a cross-sectional study testing patients with PD and older adults on tasks of positive reinforcement learning, attention/working memory, executive function, and memory to measure cognitive performance in domains thought to be related to dopaminergic and noradrenergic function. Participants also underwent neuromelanin-sensitive magnetic resonance imaging as a measure of degeneration. RESULTS: Reduced SN neuromelanin signal in PD was independently associated with impaired positive reinforcement learning (β = 0.41, 95% confidence interval [CI]: 0.08, 0.74) controlling for changes in the LC. In contrast, reduced LC neuromelanin signal was independently associated with impairments in attention/working memory (β = 0.20, 95% CI [-0.47, -0.10]) and executive function (β = 0.22, 95% CI: -0.57, -0.24), controlling for changes in the SN. CONCLUSIONS: These results suggest that SN and LC degeneration may contribute to different cognitive deficits, potentially explaining the heterogeneity that exists in the cognitive manifestations of PD. These results also highlight the potential value of leveraging brain-behavior relationships to develop performance-based measures of cognition that could be used to characterize the phenotypic differences associated with underlying patterns of neurodegeneration. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".