Cortical effects of dopamine replacement account for clinical response variability in Parkinson’s disease
Bibliographic record
Abstract
Individual variability in clinical response to dopaminergic replacement therapy (DRT) is a key barrier to efficacious treatment for patients with Parkinson's disease (PD). A better understanding of the neurobiological sources of such inter-individual differences is necessary to inform future clinical interventions and motivate translational research. One potential source of this variability is an unintended secondary activation of extra-nigrostriatal dopamine systems by DRT, particularly in the neocortex. In this study, we use magnetoencephalography data collected from patients with PD before and after DRT to map their individual cortical neurophysiological responses to dopaminergic pharmacotherapy. By combining these DRT response maps with normative atlases of cortical dopamine receptor and transporter densities, we link the variable enhancement of rhythmic beta activity by DRT to dopamine-rich cortical regions. Importantly, patients who exhibited a larger dopaminergic beta cortical enhancement showed a smaller clinical improvement from DRT, indicating a potential source of individual variability in medication response for patients with PD. We conclude that these findings inform our understanding of the dopaminergic basis of neurophysiological variability often seen in patients with PD, and indicate that our methodological approach may be useful for data-driven contextualization of medication effects on cortical neurophysiology in future research and clinical applications.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.007 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".