Tree-of-Evidence: Efficient "System 2" Search for Faithful Multimodal Grounding

Electronic health record (EHR) data are inherently multimodal, and leveraging multiple modalities can improve predictive performance. However, most existing approaches rely on deep fusion, which obscures how individual modalities contribute to predictions and limits the interpretability of multimodal reasoning. We propose an explicit multimodal routing framework for clinical prediction that enables interpretable, robust, and auditable reasoning across three EHR modalities: structured longitudinal variables (L), clinical notes (N), and chest X-rays (I). Our model constructs discrete unimodal, directional bimodal, and trimodal routes to capture both individual modality signals and asymmetric cross-modal interactions. To audit multimodal reasoning and assess robustness, we introduce inference-time route masking, which simulates missing modalities and reweights the remaining routes without retraining. We analyze changes in performance and routing weights under these scenarios to understand model decision-making. We evaluate our framework on multi-label phenotype prediction (K = 25) and binary ICU mortality prediction using trimodal patient stays from MIMIC-IV, revealing systematic differences in modality reliance across clinical condition groups. Overall, our framework offers a transparent, auditable, and practical approach to multimodal clinical prediction, providing interpretability, robustness, and insights into how different data sources drive model decisions.

Multimodal clinical decision-making requires reliable reasoning over heterogeneous evidence from electronic health records, medical images, and physiological signals. Existing models typically map these inputs directly to diagnoses without explicitly assessing evidence sufficiency, tool-use requirements, or diagnostic uncertainty. This paper presents MedTRACE, a tool-augmented multimodal clinical reasoning agent for evidence-grounded decision-making. MedTRACE uses modality-specific encoders to construct a unified patient-state representation and performs an iterative loop of hypothesis formation, toolaware deliberation, and evidence verification. It dynamically invokes visual grounding, evidence retrieval, and structured parsing tools to locate diagnosis-relevant regions, retrieve clinical knowledge and similar cases, and extract structured findings. The acquired evidence enters an evidence memory, where a consistency verifier confirms or revises the current hypothesis. MedTRACE outputs a diagnosis together with supporting evidence, an auditable reasoning trace, and calibrated confidence. Experiments on multiple multimodal clinical diagnosis benchmarks show that MedTRACE improves diagnostic accuracy by 5.4% and AUROC by 4.7 percentage points over the strongest baseline. It also improves evidenceselection F1 by 8.2 percentage points and visual-grounding IoU by 6.5 percentage points, reduces expected calibration error by 31.6%, and decreases unsupported diagnostic errors by 27.8%. These results demonstrate that active evidence acquisition and verification improve the accuracy, interpretability, and reliability of multimodal clinical decisionmaking.

Neurobiological and neurodegenerative diseases are inherently multifactorial, arising from coupled influences spanning genetic susceptibility, brain alterations, and environmental and behavioral factors. Multimodal modeling has therefore been increasingly adopted for disease diagnosis by integrating complementary evidence across data sources. However, in both large-scale cohorts and real-world clinical workflows, modality coverage is often incomplete, making many multimodal models brittle when one or more modalities are unavailable. Existing approaches to incomplete multimodal diagnosis typically rely on group-wise or static priors, which may fail to capture subject-specific cross-modal dependencies; moreover, many models provide limited interpretability into which evidence sources drive the final decision. To address these limitations, we propose Conditional Evidence Reconstruction and Decomposition (CERD), a framework for interpretable multimodal diagnosis with incomplete modalities. CERD first reconstructs missing modality representations conditioned on each subject's observed inputs, then decomposes diagnostic evidence into shared cross-modal corroboration and modality-specific cues via logit-level attribution. Experiments on the Alzheimer's Disease Neuroimaging Initiative (ADNI) demonstrate that CERD outperforms competitive baselines under incomplete-modality settings while producing structured and clinically aligned evidence attributions for trustworthy decision support.