PreSight: Preoperative Outcome Prediction for Parkinson's Disease via Region-Prior Morphometry and Patient-Specific Weighting

Parkinson's disease (PD) affects over ten million people worldwide. Although temporal interference (TI) and deep brain stimulation (DBS) are promising therapies, inter-individual variability limits empirical treatment selection, increasing non-negligible surgical risk and cost. Previous explorations either resort to limited statistical biomarkers that are insufficient to characterize variability, or employ AI-driven methods which is prone to overfitting and opacity. We bridge this gap with a pretraining-finetuning framework to predict outcomes directly from resting-state fMRI. Critically, a generative virtual brain foundation model, pretrained on a collective dataset (2707 subjects, 5621 sessions) to capture universal disorder patterns, was finetuned on PD cohorts receiving TI (n=51) or DBS (n=55) to yield individualized virtual brains with high fidelity to empirical functional connectivity (r=0.935). By constructing counterfactual estimations between pathological and healthy neural states within these personalized models, we predicted clinical responses (TI: AUPR=0.853; DBS: AUPR=0.915), substantially outperforming baselines. External and prospective validations (n=14, n=11) highlight the feasibility of clinical translation. Moreover, our framework provides state-dependent regional patterns linked to response, offering hypothesis-generating mechanistic insights.

Introduction: Objective neuroimaging biomarkers may improve Parkinson's disease motor assessment by capturing brain variation not directly observable from clinical examination. We used interpretable machine learning to predict current motor severity, measured by MDS-UPDRS Part III, from QSM and multiband multi-echo resting-state fMRI-derived ReHo features. Methods: Regional QSM and ReHo features were extracted from 28 participants, including 24 individuals with Parkinson's disease and 4 controls. Thirteen feature-set experiments evaluated imaging-only, clinical-only, imaging-plus-clinical, full, reduced, and multimodal inputs. Support vector regression, Elastic Net, Random Forest, and XGBoost models were trained using nested cross-validation. Performance was assessed using pooled held-out R^2, RMSE, MAE, Pearson correlation, permutation testing, and the proportion of participants predicted within +/-5 MDS-UPDRS Part III points. Results: Imaging-only models carried meaningful predictive signal, whereas the clinical-only model performed weakly. Full fMRI, full QSM, and clinical variables provided the strongest global fit, explaining 45.4% of variance in motor severity. Selected QSM plus clinical variables produced the most clinically close predictions, with 75.0% of participants predicted within +/-5 points and the lowest MAE among top-performing models. SHAP highlighted cerebellar, thalamic, striatal, insular, and motor cortical features. Conclusion: QSM and multiband multi-echo fMRI-derived ReHo capture distinct, interpretable dimensions of Parkinson's disease motor severity. These findings show that structural and functional imaging contribute differently depending on the clinical prediction goal.

Parkinson's disease (PD) manifests early neuromotor impairments that become observable in controlled hand-drawn patterns such as spirals and meanders, where tremor-induced oscillations, stroke irregularity, and curvature instability reflect underlying motor degradation. In this work, we present an explainable framework for PD screening from offline hand-drawn patterns that integrates discriminative visual modeling with clinically grounded reasoning. The predictive model captures distributed structural distortions and fine-grained texture variations. It is evaluated under subject-disjoint protocols to ensure reliable generalization. To move beyond black-box classification, we introduce a multi-stage explainability pipeline that combines visual attribution with structured symptom abstraction. Salient regions are identified using attention- and gradient-based localization, followed by extraction of clinically meaningful motor descriptors quantifying contour roughness, curvature irregularity, stroke variability, and tremor-frequency energy. These descriptors are subsequently translated into coherent clinical rationales through a language-based reasoning module, linking model evidence to established PD symptomatology. By bridging visual attribution and clinical interpretation, the proposed framework advances interpretable document intelligence for neurological screening using hand-drawn patterns. Experimental results on publicly available Parkinson's disease handwriting datasets demonstrate competitive predictive performance and clinically consistent explanations.