Predicting Neuromodulation Outcome for Parkinson's Disease with Generative Virtual Brain Model

Forecasting the progression of neurodegenerative diseases, such as Parkinson's disease, is essential for effective long-term planning and personalized therapeutic intervention. Existing systems typically produce scalar clinical scores that ignore the rich structure of longitudinal neuroimaging, while traditional generative approaches suffer from a loss of anatomical details and blurring subtle progression patterns. To address this, we introduce a novel treatment-conditioned diffusion framework that predicts high-fidelity future brain states by conditioning the generative process on patients' screening DaTscan images and levodopa equivalent daily dose over one year. The pipeline uses a Transformer-based encoder to represent non-linear, time-dependent pharmacological dynamics and optimizes generation through a multi-weight region-of-interest mask that focuses on biologically critical areas. Experimental evaluation shows that our framework maintains sharp anatomical boundaries and significantly improves clinical fidelity relative to the baseline, achieving 14.0% lower MSE, 7.2% lower MAE, and 4.9% higher SSIM.

Preoperative improvement rate prediction for Parkinson's disease surgery is clinically important yet difficult because imaging signals are subtle and patients are heterogeneous. We address this setting, where only information available before surgery is used, and the goal is to predict patient-specific postoperative motor benefit. We present PreSight, a presurgical outcome model that fuses clinical priors with preoperative MRI and deformation-based morphometry (DBM) and adapts regional importance through a patient-specific weighting module. The model produces end-to-end, calibrated, decision-ready predictions with patient-level explanations. We evaluate PreSight on a real-world two-center cohort of 400 subjects with multimodal presurgical inputs and postoperative improvement labels. PreSight outperforms strong clinical, imaging-only, and multimodal baselines. It attains 88.89% accuracy on internal validation and 85.29% on an external-center test for responder classification and shows better probability calibration and higher decision-curve net benefit. Ablations and analyses confirm the contribution of DBM and the patient-specific weighting module and indicate that the model emphasizes disease-relevant regions in a patient-specific manner. These results demonstrate that integrating clinical prior knowledge with region-adaptive morphometry enables reliable presurgical decision support in routine practice.

Current fMRI foundation models primarily rely on a limited range of brain states and mismatched pretraining tasks, restricting their ability to learn generalized representations across diverse brain states. We present Brain-DiT, a universal multi-state fMRI foundation model pretrained on 349,898 sessions from 24 datasets spanning resting, task, naturalistic, disease, and sleep states. Unlike prior fMRI foundation models that rely on masked reconstruction in the raw-signal space or a latent space, Brain-DiT adopts metadata-conditioned diffusion pretraining with a Diffusion Transformer (DiT), enabling the model to learn multi-scale representations that capture both fine-grained functional structure and global semantics. Across extensive evaluations and ablations on 7 downstream tasks, we find consistent evidence that diffusion-based generative pretraining is a stronger proxy than reconstruction or alignment, with metadata-conditioned pretraining further improving downstream performance by disentangling intrinsic neural dynamics from population-level variability. We also observe that downstream tasks exhibit distinct preferences for representational scale: ADNI classification benefits more from global semantic representations, whereas age/sex prediction comparatively relies more on fine-grained local structure.