We grade MDS-UPDRS gait severity from SMPL motion using three frozen MotionAGFormer encoders as featurizers, reaching macro-F1 0.58 on a hidden, multi-site test set. Because the system's members differ only in their lifting corpus, evaluating encoders singly on that test set isolates what that corpus contributes. Six pools drawn from one inertial dataset, varying only in which walking tasks they include, score between 0.32 and 0.53, and just one of them beats the 0.51 of an encoder given no outside motion at all. What separates them is not how much data they hold but whether they carry a contrast in walking speed, the variation this representation appears to depend : a further pool adding a third collection site at fixed task composition does worse still. The same rule explains why exact synthetic motion and monocularly reconstructed web video both fail to help. Modifying the learned representation itself, rather than the corpus behind it, cost every variant that attempted it.
Vishal Subedi, Shashipraba N. K. Rajakaruna, Pratyusha Sarkar +10q-bio.NC cs.AI cs.LG stat.AP stat.ML
Neurodegenexrative diseases such as Alzheimer's disease and Parkinson's disease are diagnosed most reliably only after substantial, often irreversible, neuronal loss has already occurred, creating an urgent need for quantitative tools that can detect subtle, early, and individual-specific brain changes from neuroimaging data. This review surveys a broad and rapidly evolving toolkit of data-driven techniques for translational neuroscience and personalized neuro-health, organized around four complementary methodological pillars. Throughout, we emphasize how these methodologically diverse approaches converge on a common translational goal: personalized, mechanistically grounded, and clinically actionable models of individual brain health, and we close by discussing the principal open statistical, computational, and clinical challenges that remain.
Understanding motion in daily living requires context beyond kinematics, because similar inertial patterns during activities of daily living (ADLs) can reflect intentional stopping, object interaction, or pathological movement impairment. Egocentric vision provides task-related context that may help disambiguate these cases. We investigate this challenge through freezing of gait (FOG) detection in Parkinson's disease (PD), a symptom strongly influenced by contextual factors during ADLs. Using synchronized egocentric video, wearable IMUs, and expert-annotated FOG labels collected from 13 PD participants in their homes, we evaluate frozen representations from pretrained ego-video and time-series foundation models, alongside an IMU-based TCN trained from scratch, under leave-one-subject-out evaluation. The IMU-based TCN achieved the strongest event-detection performance, reaching 42.3 F1 and 83.0 AUROC, compared with 32.6 F1 and 77.2 AUROC for V-JEPA2 ego-video features. Although ego-video alone did not outperform IMU-based sensing, it showed above-chance discrimination, and qualitative analyses suggest that egocentric vision may capture FOG-relevant information independent of IMUs. Together, these results support the use of pretrained ego-video representations to add contextual information to wearable-sensor-based clinical motion understanding in daily living.
Parkinson's disease (PD) is the second most common neurodegenerative disorder. Typical machine learning screening methods require PD labels, but the available data is limited by privacy concerns and the need for expert annotation. We propose a label-free face-plus-voice PD screen built entirely on frozen pretrained encoders--a face-expression Vision Transformer and HuBERT--in which no PD label touches any fit; the reference is training controls only. The voice modality uses a synthetic-dysarthria contrastive activation addition (CAA) direction built from time-stretch and breathy degradation of healthy speech; the face modality uses a k-nearest-neighbor anomaly score to the control embedding cluster. We introduce the alignment principle, a post-hoc analysis showing that a synthetic-degradation CAA detector works when the cosine similarity between the synthetic and real disease directions exceeds zero. Measured on the YouTubePD benchmark, this cosine is +0.37 for voice (CAA works, AUROC 0.765) and -0.48 for face (CAA fails; anomaly succeeds, AUROC 0.751). Equal-weight late fusion reaches AUROC 0.802 (95% CI [0.70,0.89]) with NPV 0.95, supporting a rule-out triage interpretation. An overfitting audit shows the voice detector transfers cleanly, while the face-side--and thus fused--AUROC is potentially optimistic pending external validation.
Accurate gait analysis in Parkinson's disease (PD) typically relies on laboratory-based systems to capture biomechanical data, such as ground reaction forces (GRFs). Estimating GRFs using inertial measurement units (IMUs) provides a feasible alternative. However, this approach remains challenging in pathological gait like PD due to its high variability and complexity. Moreover, existing monitoring approaches often require multiple body-mounted sensors, which limit practicality and reduce patient compliance. To date, no study has investigated the application of deep learning approaches to address this challenge. This study proposes, for the first time, a deep learning framework to estimate bilateral vertical GRFs (vGRFs) in PD using an optimized set of wearable IMUs. A hybrid CNN-BiLSTM model was trained separately on data from 61 PD patients and 65 healthy controls (HC) using 13 IMUs. The model achieved high intra-subject accuracy ($R^2$ = 0.98) and strong inter-subject generalization ($R^2$ = 0.93 for HC, $R^2$ = 0.91 for PD). Sensor configuration was found to significantly influence estimation accuracy, with optimal sensor placement varying between PD patients and HC. For PD patients, estimation accuracy dropped markedly when reducing to a single IMU. The optimal configuration for PD used four IMUs. We identified a minimal setup with only two IMUs still enabled robust estimation. This compact setup offers a practical and scalable solution. Overall, the proposed approach supports the development of wearable vGRF-based gait analysis systems for Parkinsonian gait and potentially other pathological conditions, enabling accessible clinical assessments, remote monitoring, and personalized rehabilitation.
Sana Alamgeera, Denise Goberta, Muhammad Irshad +1cs.CL cs.AI
Accurate interpretation of single-visit and longitudinal clinical assessments for Parkinson's disease is time-consuming and often depends on specialist expertise. Although large language models (LLMs) can generate natural language summaries, they frequently lack domain-specific clinical grounding and struggle to produce factually correct and temporally consistent responses for structured longitudinal assessment data. To address these limitations, we propose MA-RAG, a query-driven multi-agent retrieval-augmented generation framework that decomposes clinical reasoning into domain-specialized agents, combines structured fact extraction, and synthesizes clinically grounded summaries through a final verification stage. The framework supports four clinical analysis tasks: single-session, trajectory, comparison, and cohort summarization. We evaluate MA-RAG using objective metrics, namely Fact Precision, Hallucination Rate, Temporal Fidelity, and Semantic Similarity, together with subjective evaluations conducted by clinical experts. Compared to Traditional, RAG-only, and Single-agent RAG baselines, MA-RAG substantially improves factual correctness, achieving up to a 122% relative increase in Fact Precision (from 0.436 to 0.990) and reducing the Hallucination Rate by up to 98% (from 0.564 to 0.010), while consistently receiving top ratings from clinical experts for organization and clinical usefulness. These results demonstrate that domain-specialized multi-agent reasoning enables reliable query-driven summarization of structured longitudinal clinical assessment data.
Parkinson's disease (PD) selectively impairs distinct stages of motor control. Using backspace events as natural error-correction episodes in the public neuroQWERTY MIT-CSXPD dataset (n=57 subjects, 27 PD with UPDRS-III scores), we test whether passively-collected keystroke timing dissociates a variability-based pre-error monitoring signal from a speed-based post-error recovery signal. Pre-error typing instability does not track PD severity (r=-0.072, p=0.721), while post-error pause duration does (r=+0.656, p=0.0002; subject-level OLS p=1.2x10^-4, n=27, primary analysis given within-subject event clustering). A mixed-effects log-normal model with a random subject intercept confirms this while retaining full event-level power (coef=0.0250, p=1.2x10^-4, n=1,563 events), closely matching the subject-level OLS despite an unrelated estimation strategy. Error-detection latency also correlates with UPDRS-III (r=+0.660), confirming the dissociation is between variability and speed, not detection and correction per se. A log-normal accelerated failure time model yields a coefficient of 0.0255 (bootstrap 95% CI [0.0146, 0.0357]), a 2.6% increase per UPDRS-III point. After controlling the immediately thecoefficient attenuates to 0.0133 (p=3.1x10^-21),consistent w timingincrement above general bradykinesia. Results reacross both S2:r=+0.645), survive jackknife exclusion of every subject, andnatingfinger-tapping and mPower smartphone tapping (group AUC=0.836). cellent(ICC(2,1)=0.945, n=20).
Jisung Park, Seohyeon Kang, Daeun Yoo +8cs.LG cs.AI cs.CV q-bio.QM
Artificial intelligence is transforming our capability to solve biological challenges. In dimensionality bottleneck regimes exacerbated by high-dimensional biological data, Neural networks force distinct concepts into the lower dimensions known as superposition. Although this superposition is widely known to hinder interpretability, its impact on corrupting the geometry of latent spaces remains critically overlooked. Here, we utilized sparse autoencoders (SAEs) trained on over 100,000 multiplexed images of patient-derived Parkinson's disease and healthy neurons to resolve superposition. This approach bypasses the mathematical non-uniqueness of feature attribution by shifting to interpretable latent representation analysis. We theoretically and empirically demonstrate that superposition contaminates representational metric spaces, and thereby SAEs successfully recover geometric fidelity. By treating these geometrically purified representations as single-cell state vectors, we adapted single-cell RNA sequencing (scRNA-seq) data analysis methodologies directly to the image domain. Finally, we introduce GW-map, utilizing Gromov-Wasserstein optimal transport to align these image representations with authentic scRNA-seq data \emph{de novo}. This coupling reconstructs hierarchical neuronal pathology pathways such as Calcium-AIS scaffold, without reference spatial transcriptomics, establishing a scalable foundation for spatial biology. Code is available at https://github.com/jijihihi/Bio_superposition
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.
Qiushuo Cheng, Jingjing Liu, Catherine Morgan +2cs.CV cs.AI
As a prominent symptom of Parkinson's disease (PD), turning impairment is evaluated through parameters such as turning angle, duration, and particularly, the number of steps required to complete a turn, which directly reflects motor dysfunction. Accurate step counting is challenging due to variability in real-world turning movements and atypical shuffling patterns in parkinsonian gait. Existing methods are predominantly wearable-based, requiring users to wear and manage dedicated devices, which can be inconvenient for continuous daily use. To address this, we propose a passive, video-based framework that estimates step count in a coarse-to-fine manner using diverse motion representations. Specifically, an initial step count is estimated from foot movement signals derived from 3D human mesh recovery, providing high-level motion structures. To incorporate fine-grained motion details, a motion encoder learns complementary gait dynamics from mesh and optical flow to refine the initial estimate. In this process, coarse foot movement signals query the pixel-level motion cues via cross attention to capture subtle parkinsonian gait dynamics. To handle varying video lengths, we partition each video into clips and integrate clip-wise motion embeddings via multiple instance learning (MIL) for step count residual prediction. Extensive experiments show our method consistently outperforms existing step counting methods on real-world PD turning datasets.
Existing facial expression quality assessment (FEQA) methods typically produce only a severity score, without explicitly communicating the observable facial motion evidence that supports the prediction. This limits interpretability and makes it difficult to inspect the basis of model outputs in Parkinson's disease assessment. To address this gap, we propose TraMP-LLaMA, a unified multimodal framework that jointly predicts severity scores and generates structured textual reports from facial motion cues. The framework integrates RGB appearance and landmark trajectory cues, and adopts a decoupled instruction-tuning strategy to reduce task interference between severity prediction and language generation. To support this task, we further extend the PFED5 dataset with expert-guided textual motion descriptions and construct PFED5-plus. Experiments on PFED5-plus show that TraMP-LLaMA outperforms competitive video-language baselines in report generation and achieves the best severity prediction performance among the compared methods under joint multi-expression training, improving Spearman's rank correlation by at least 4.39 percent over all competing methods. The text annotations and code are available at https://github.com/shuchaoduan/TraMP-LLaMA.
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.
Gait-based Parkinson's disease assessment increasingly relies on heterogeneous sensors, but clinical systems rarely collect all modalities simultaneously. New sensors may arrive through device upgrades, protocol changes, or multi-center deployment, while historical patient data are often unavailable because of privacy and storage constraints. This modality-incremental setting faces three challenges: unreliable cross-modal distillation, modality-specific statistical shifts, and reduced plasticity after preservation. We propose MOSAIC, a compact continual learning framework. First, we identify the Toxic Teacher phenomenon and introduce Modality-Specific Warm-Up to stabilize newly learned modality representations before distillation. Second, we propose a statistics-decoupled MSBN architecture that isolates sensor statistics while maintaining a shared semantic backbone. Third, we design a curriculum-guided repulsive objective for Plasticity Recovery, preserving legacy knowledge while recovering modality-specific capacity. Experiments on three multimodal Parkinson's gait datasets show that MOSAIC improves final performance and mitigates forgetting. Project code is available at: https://github.com/minlinzeng/MOSAIC_Modality-Specific-Adaptation-for-Incremental-Continual-Learning-in-PD-Gait-Assessment.git
Reduced facial expressivity is a common motor manifestation of Parkinson's disease (PD), often described as hypomimia or facial bradykinesia. This paper examines whether temporal motion descriptors extracted from facial-region keypoints can support in-the-wild PD-related video classification on the YouTubePD benchmark. Each video is represented using geometric descriptors from 14 predefined facial regions. Static geometry, normalized geometry, velocity-based descriptors, relative-velocity descriptors, and a GRU sequence baseline are compared under the same binary classification protocol. To assess stability and interpretability, the study includes seed-robustness analysis, region-level ablation, and permutation importance. The best result is obtained with normalized velocity descriptors and a Random Forest classifier, reaching a balanced accuracy of 0.826 and an AUROC of 0.855 on the held-out test split. Across 10 random seeds, this representation remains stable, with balanced accuracy of 0.810 +/- 0.018 and AUROC of 0.855 +/- 0.005. Overall, the results suggest that normalized facial-region motion is a lightweight and interpretable representation for YouTubePD video classification. The study is framed as a benchmark-level analysis and does not claim clinical severity assessment or MDS-UPDRS facial-expression scoring.
Nicholas R. Rasmussen, Longwei Wang, Rodrigue Rizk +5cs.LG eess.SP q-bio.NC
Developing robust and clinically reliable EEG biomarkers requires evaluation frameworks that explicitly address cross population generalization in multi site settings such as Parkinsons disease (PD) detection. Models trained under i.i.d. assumptions often capture population specific artifacts rather than disease relevant neural structure, leading to poor generalization across clinical cohorts. EEG further amplifies this challenge due to low signal to noise ratio and heterogeneous acquisition conditions. We propose a population aware evaluation framework to assess the robustness and clinical reliability of EEG biomarkers under distribution shift. Using an n gram expansion strategy, we enumerate all cross population train test configurations across five independent cohorts, resulting in 75 directional evaluations. A nested cross validation design with integrated channel selection ensures prospective biomarker identification without population leakage. Results show that cross population transfer is asymmetric and that both accuracy and biomarker stability improve with increasing training population diversity, achieving up to 94.1% accuracy on held out cohorts. A theoretical analysis based on mixture risk optimization and hypothesis space contraction explains these trends, showing that multi population training promotes population robust representations. This work establishes a principled framework for learning robust, generalizable, and clinically reliable EEG biomarkers for multi site biomedical applications.