Bibliographic record
Abstract
It has become increasingly apparent that Parkinson's disease involves many transmitter systems other than dopamine. This nondopaminergic involvement impacts on the generation of symptoms, on the neurodegenerative process, but, most tellingly, in the generation of side effects of current treatments, in particular, levodopa-induced dyskinesia (LID). Such mechanisms contribute not only to the expression of LID once it has been established but also to the mechanisms responsible for the development, or priming, of the dyskinetic state and the subsequent maintenance of the brain in that primed state. Within the basal ganglia, abnormalities in different nondopaminergic components of the circuitry have been defined in LID. In particular, a role for enhanced inhibition of basal ganglia outputs by the GABAergic direct pathway has been suggested as a basic mechanism generating LID. We speculate that the external globus pallidus and subthalamic nucleus may play distinct roles in different forms of dyskinesia, e.g., chorea/dystonia; peak/diphasic/off. At the cellular level, an appreciation of abnormal signaling by, among others, glutamatergic (NMDA and AMPA receptors in particular), alpha2 adrenergic, serotonergic (5HT), cannabinoid and opioid mechanisms in both priming and expression of LID has begun to emerge over the last decade. This is being consolidated, though in many cases questions remain regarding the specific sites of such abnormality within the circuitry. Very recently, at the molecular level, mechanisms controlling neurotransmitter release and impacting on the ability of neurons to maintain particular forms of firing patterning and synchronization, e.g., SV2A, have been identified. This increased understanding has already delivered and will continue to define novel approaches to treatment that target both pre- and postsynaptic signaling molecules throughout the basal ganglia circuitry.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".