Interpretable machine learning predicts Parkinson's disease severity using motion-corrected QSM MRI and multiband multiecho fMRI features

Parkinson's disease (PD) is a progressive disorder in which symptom burden and functional impairment evolve over time, making severity staging essential for clinical monitoring and treatment planning. However, many computational studies emphasize binary PD detection and do not fully use repeated follow-up clinical assessments for stage-aware prediction. This study proposes STEP-PD, a severity-aware machine learning framework to classify PD severity using clinically interpretable boundaries. It leverages all available visits from the Parkinson's Progression Markers Initiative (PPMI) and integrates routinely collected subjective questionnaires and objective clinician-assessed measures. Disease severity is defined using Hoehn and Yahr staging and grouped into three clinically meaningful categories: Healthy, Mild PD (stages 1-2), and Moderate-to-Severe PD (stages 3-5). Three binary classification problems and a three-class severity task were evaluated using stratified cross-validation with imbalance-aware training. To enhance interpretability, SHAP was used to provide global explanations and local patient-level waterfall explanations. Across all tasks, XGBoost achieved the strongest and most stable performance, with accuracies of 95.48% (Healthy vs. Mild), 99.44% (Healthy vs. Moderate-to-Severe), and 96.78% (Mild vs. Moderate-to-Severe), and 94.14% accuracy with 0.8775 Macro-F1 for three-class severity classification. Explainability results highlight a shift from early motor features to progression-related axial and balance impairments. These findings show that multimodal clinical assessments within the PPMI cohort can support accurate and interpretable visit-level PD severity stratification.

Real-world digital Parkinson's disease assessment faces challenges such as heterogeneous modalities, cross-device bias, and incomplete labeling. Existing methods often focus on average predictive performance, lacking the reliability mechanisms needed for retrospective reliability-aware assessment - namely, determining when the model is reliable, when to reject an assessment, when to retest, and from which symptom dimensions the predictions are based. This paper proposes SGC-RML, which maps speech, gait, wearable motion, mobility tasks, and clinical variables to a shared 8-dimensional symptom node space (7 clinical symptom nodes and 1 reliability_state auxiliary node), unifying motor and non-motor representations through a symptom atlas. By jointly introducing uncertainty estimation, conformal calibration, and selective decision routing, the model can not only predict symptoms and severity but also reject assessments or suggest retests when evidence is insufficient. We validate this framework on five real-world PD datasets, covering classification, regression, event detection, and longitudinal severity prediction. Experiments show that SGC-RML achieves an MAE of 4.579 / R^2 of 0.772 on PPMI, an AUC of 0.953 on mPower, and an AUC of 0.825 on PADS. Under leak-free temporal anchoring, as few as 5 subject-specific anchors transform UCI from an essentially non-predictive subject-independent setting (motor MAE 8.38, CCC 0.02) into a calibrated longitudinal assessment (motor MAE 3.24, CCC 0.756) with split-conformal coverage held at the 0.80 target. Under the Daphnet LOSO protocol, it achieves an F1 of 0.803 / AUC of 0.872. These results demonstrate that SGC-RML provides a unified paradigm for accurate, calibrated, auditable, and symptom-interpretable retrospective longitudinal assessment of PD under incomplete multimodal conditions.

Keystroke dynamics have been explored extensively as a passive digital biomarker for Parkinson's disease (PD), typically by extracting summary statistics from typing timing and training a classifier to discriminate PD from healthy controls. We instead apply inverse reinforcement learning (IRL) to keystroke data, modeling each keystroke as a discrete choice over typing speed and recovering, per subject, an interpretable reward function that explains their observed timing behavior. To our knowledge this is the first application of IRL to keystroke dynamics. On the public neuroQWERTY MIT-CSXPD dataset (85 subjects, 42 with PD), an initial four-parameter reward decomposition (speed, effort, smoothness, hand-alternation cost) was found to suffer severe feature collinearity between two terms ($r=1.000$ in typical contexts); we diagnose and correct this, yielding an identifiable three-parameter model. The recovered speed-preference weight correlates with UPDRS-III severity at $r=-0.607$ ($p<0.001$, $n=42$), replicates independently across two sub-cohorts, is stable across nine sensitivity configurations, and retains a statistically significant contribution beyond raw typing speed alone (incremental $R^2$ from 0.194 to 0.338, $p=0.006$). Two other recovered weights (consistency, hand-alternation) did not survive confound checks and are reported as negative results. We document two implementation bugs found during adversarial code review (session-boundary contamination, a rolling-window data leakage) and show the headline result is materially unchanged after fixing both. We discuss this result in the context of a literature where reported accuracies vary widely between studies (pooled AUC 0.85, I^2=94% in a 2022 meta-analysis), and argue that the validation process itself, not only the correlation coefficient, is part of the contribution.