Sign-specific stimulation "hot" and "cold" spots in Parkinson's disease validated with machine learning
Bibliographic record
Abstract
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become a standard therapy for Parkinson’s disease (PD). Despite extensive experience, however, the precise target of optimal stimulation and the relationship between site of stimulation and alleviation of individual signs remains unclear. We examined whether machine learning could predict the benefits in specific parkinsonian signs when informed by precise locations of stimulation. We studied 275 PD patients who underwent STN-DBS between 2003 and 2018. We selected pre-DBS and best available post-DBS scores from motor items of the Unified Parkinson's Disease Rating Scale (UPDRS-III) to discern sign-specific changes attributable to DBS. Volumes of tissue activated (VTAs) were computed and weighted by i) tremor, ii) rigidity, iii) bradykinesia, and iv) axial signs changes. Then, sign-specific sites of optimal (“hot spots”) and suboptimal efficacy (“cold spots”) were defined. These areas were subsequently validated using machine learning prediction of sign-specific outcomes with in-sample and out-of-sample data (n=51 STN-DBS patients from another institution). Tremor and rigidity hot spots were largely located outside and dorsolateral to STN whereas hot spots for bradykinesia and axial signs had larger overlap with STN. Using VTA overlap with sign-specific hot and cold spots, support vector machine (SVM) classified patients into quartiles of efficacy with ≥92% accuracy. The accuracy remained high (68-98%) when only considering VTA overlap with hot spots but was markedly lower (41-72%) when only using cold spots. The model also performed poorly (44-48%) when using only stimulation voltage, irrespective of stimulation location. Out-of-sample validation accuracy was ≥96% when using VTA overlap with the sign-specific hot and cold spots. In two independent datasets, distinct brain areas could predict sign-specific clinical changes in PD patients with STN-DBS. With future prospective validation, these findings could individualize stimulation delivery to optimize quality of life improvement. Hot and cold spots for each sign are publicly available as binary labels in NIfTI format.
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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 | 0.003 |
| 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 | 0.000 | 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".