Parkinson's Disease

Parkinson's disease is a progressive neurodegenerative disorder characterised by gradual deterioration of movement control. Automated freezing-of-gait (FOG) detection supports the objective assessment of gait-related motor impairment. Two common approaches are used for FOG prediction: (i) analysing video recordings of the patient's movements and (ii) analysing data collected using inertial measurement unit (IMU) wearable sensors attached to the patient's lower limbs. Video-based approaches may suffer detection errors during continuous turning-in-place tasks because the lower limbs undergo substantial geometric self-occlusion, degrading pose-estimation accuracy. IMU-based approaches are generally less affected by visual occlusion; however, they are difficult to deploy outside clinical or laboratory settings, as the sensors must be attached securely and remain in place throughout the assessment. Motivated by this, we propose a cross-modal subspace distillation framework to mitigate the limitations of unimodal FOG detection by combining IMU accuracy with video-based practicality. We extract invariant latent topologies from a pre-trained kinematic oracle to structurally supervise a non-encoded visual architecture during training. To resolve periods of severe spatial occlusion, a dual-stream visual model probabilistically fuses skeletal graph nodes and continuous spatial pixels, dynamically shifting reliance to uninterrupted pixel boundaries as joint tracking confidence drops. Evaluated against a public, multi-modal sequence dataset of Parkinson's individuals executing continuous $360^\circ$ turns, empirical results demonstrate that applying sensory boundary topologies strictly mitigates tracking evaluation entropy. Our constrained optimisation confirms that highly precise FOG prediction bounds can be achieved over zero-wearable inference environments.

Self-supervised learning (SSL) speech representations achieve strong performance for Parkinson's disease (PD) detection within individual corpora. However, it remains unclear whether these models capture disease-related characteristics or exploit dataset-specific confounds, particularly since most SSL backbones are pretrained exclusively on healthy speech. To investigate this question, we perform a layer-wise analysis of nine SSL speech backbones using a low-capacity logistic regression probe across three languages. We structure the evaluation as multiple scenarios that progressively introduce distribution shifts in participant identity, recording conditions, language, and pathology. Our results reveal two key findings. First, layer selection is highly corpus-dependent: the optimal representation layer is determined primarily by the source dataset rather than by the SSL architecture itself. Second, the transferred discriminative signal lacks pathological specificity: classifiers trained to detect PD assign similarly high probabilities to both PD and dementia speech in the target corpus. These results highlight critical limitations that must be addressed before speech-based pathology recognition models can be reliably deployed in clinical settings.

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.

Parkinson's disease (PD) affects millions worldwide and causes severe motor symptoms. Adaptive deep brain stimulation (aDBS) delivers physiologically informed stimulation that can track fluctuations in PD motor symptoms, enabling more intelligent DBS control. However, most existing aDBS approaches are primarily algorithm- and software-driven, with limited efforts toward circuit realization, particularly low-power and implantable integrated circuits. This paper presents the Silicon Leaky Integrate-and-Fire Deep Brain Stimulation (SiLIF-DBS) controller, a neuromorphic silicon neuron stimulator implemented with metal-oxide-semiconductor (CMOS) technology. For system-level evaluation, a simplified computational model of the SiLIF-DBS controller is derived and embedded within a Parkinsonian cortico-basal ganglia framework for closed-loop validation. The system is driven by beta-band subthalamic nucleus local field potentials (STN-LFPs), with their average rectified value (Beta ARV) used as the control biomarker. Our SiLIF-DBS controller for aDBS suppresses pathological beta activity while consuming only 25% of the power required by open-loop stimulation and achieving a suppression efficiency of $5.85\%$/$μ$W. Overall, our SiLIF-DBS controller achieves strong beta suppression at substantially reduced power, delivering high suppression efficiency that demonstrates it is a viable foundation for low-power implantable aDBS.

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).

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.

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.

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.

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.

Large audio and language models have recently demonstrated zero-shot reasoning capabilities across various domains. However, it remains unclear how the form of audio input, whether handcrafted acoustic features extracted from speech or the raw audio waveform itself, affects performance for Parkinson's disease (PD) detection across different languages. In this study, we systematically compare two input modalities for zero-shot PD detection: (i) handcrafted acoustic features extracted from speech recordings analyzed by a general-purpose LLM, and (ii) direct waveform input analyzed by audio-capable models. Experiments on PD speech datasets in four languages show that performance varies across input modalities, speech tasks, and languages. Handcrafted acoustic features provide more stable performance in a low-resource language (e.g., Bengali), whereas audio input yields dataset-dependent gains. These findings highlight the impact of input modality on zero-shot PD detection from speech.

Effective medication management in Parkinson's Disease (PD) is challenging due to heterogeneous disease progression, variable patient response, and medication side effects. While AI models can forecast levodopa equivalent daily dose (LEDD) as a measure of medication needs, standard uncertainty quantification often fails to communicate the reliability of these predictions, treating high and low confidence clinical decisions identically. We introduce CASCADE (Calibrated Adaptive Scaling via Conformal And Distributional Estimation), a novel conformal prediction framework that propagates epistemic uncertainty from a screening classifier to adapt downstream predictions. Unlike standard conformal methods that rely on auxiliary residual regression, we leverage epistemic uncertainty from a primary classification task (identifying whether a medication change is needed) to dynamically scale the prediction intervals of a secondary regression task (predicting how much change). By mapping Venn-Abers multi-probabilistic uncertainty directly to non-conformity scores, our framework achieves continuous risk adaptation. We demonstrate that this cascade effect produces highly efficient intervals for confident patients (38.9% narrower than standard conformal baselines) while automatically expanding intervals to ensure robust coverage for uncertain cases, bridging the gap between discrete clinical decision-making and continuous dose forecasting in PD.

Understanding adaptive biomechanical systems requires distinguishing observable performance, static multivariate representation, longitudinal displacement, and internal approximation of observed change. This study introduces Level 5, which examines whether the M1-M2 transformation observed in a single-subject gait dataset can be approximated within a selected PCA representation. Gait was recorded with instrumented insoles in a participant with Parkinson's disease under six occlusal observational probes during two sessions eleven weeks apart. A simplified feed-forward neural network was trained to approximate M2 PC1-PC2 coordinates from M1 coordinates, occlusal-probe descriptors, and the longitudinal-transition indicator. In the core analysis aligned with Level 4, the model preserved the Euclidean centroid-displacement hierarchy dOC3 < dONL < dOC2.5. In the extended six-probe analysis, it preserved the broad structure of the exploratory ordering. Held-out M2 and leave-condition-out analyses provided internal tests beyond the full-dataset fit, while a within-session analysis described probe positions relative to ONL. The term predictive is used only in a restricted methodological sense. The model does not provide prospective clinical prediction, patient-level forecasting, or generalization to unseen individuals. Occlusal conditions are treated as observational probes applied during measurement, not as continuous causal drivers of longitudinal evolution. The findings are exploratory, retrospective, representation dependent, and non causal. They do not establish causal occlusal effects, validated viability thresholds, therapeutic superiority, distinct physiological states, or generalizable predictive validity.

Early-stage Parkinson's disease (EarlyPD) detection from speech is clinically meaningful yet underexplored, and published results are hard to compare because studies differ in datasets, languages, tasks, evaluation protocols, and EarlyPD definitions. To address this issue, we propose the first benchmark for speech-based EarlyPD detection, with a speaker-independent split designed for fair and replicable cross-method evaluation on researcher-accessible datasets. The benchmark covers three common speech tasks and evaluates methods under different training-resource settings. We also present multi-dimensional evaluation breakdowns by dataset, aggregation level, gender, and disease stage to support fine-grained comparisons and clinical adoption. Our results provide a replicable reference and actionable insights, encouraging the adoption of this publicly available benchmark to advance robust and clinically meaningful EarlyPD detection from speech.

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.

In biomechanical systems, observable performance is often used as a proxy for underlying organization, although similar outputs may arise from different adaptive configurations. This study considers the vertical dimension of occlusion (VDO) as a constraint applied to an adaptive neuromechanical system. A single-case design in a patient with Parkinson's disease enabled repeated intra-individual gait observations under six occlusal probes. Three complementary analytical levels were examined: (i) an aggregated scalar score of observable performance, (ii) a conceptual dynamical systems framework, and (iii) an exploratory UMAP representation of 55 standardized biomechanical variables from 270 M1 observations. The revised Level 1 analysis showed that the relative ranking of OC2.5 and OC3 depended on score construction, while their scalar distributions remained close. The Level 3 embedding showed substantial overlap among all six probes and did not identify independently separated condition-specific clusters. OC2.5 and OC3 displayed limited centroid displacement but broad observation-level overlap. The principal result is therefore representational non-identifiability: neither the aggregated score nor the selected low-dimensional embedding uniquely identifies an occlusal-condition-specific system state. VDO is interpreted as a constraint parameter rather than a causal determinant. The findings are exploratory, model dependent, and non causal. They do not establish distinct physiological states, an optimal VDO, clinical thresholds, or diagnostic, predictive, mechanistic, or prescriptive validity.

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.

Parkinson's disease (PD) is a chronic neurodegenerative disease. It shows multiple motor symptoms such as tremor, bradykinesia, postural instability, freezing of gait (FoG). PD is currently diagnosed clinically through physical exam by health-care professionals, which can be time consuming and highly subjective. Wearable IMU sensors has become a promising gateway for passive monitoring of PD patients. We propose a self-supervised cross-attention encoder that processes bilateral wrist-worn IMU signals from a public dataset called PADS, consisting of three groups, PD (Parkinson Disease), HC (Healthy Control) and DD (Differential Diagnosis) of a total of 469 subjects. We have achieved a mean accuracy of 93.12% for HC vs. PD classification and 87.04% for PD vs. DD classification. The results emphasize the clinical challenge of distinguishing Parkinson's from other neurodegenerative diseases. Self-supervised representation learning using contrastive infoNCE loss gained an accuracy of 93.56% for HC vs. PD and 92.50% for PD vs. DD using only 20% of labelled data. This demonstrates the effectiveness of our method in transfer learning for clinical use with minimal labels. The real-time applicability was tested by deploying the optimized model with a mean inference time of 48.32 ms per window on a Raspberry Pi CPU.

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.

The limited availability of dysarthric speech data makes cross-lingual detection an important but challenging problem. A key difficulty is that speech representations often encode language-dependent structure that can confound dysarthria detection. We propose a representation-level language shift (LS) that aligns source-language self-supervised speech representations with the target-language distribution using centroid-based vector adaptation estimated from healthy-control speech. We evaluate the approach on oral DDK recordings from Parkinson's disease speech datasets in Czech, German, and Spanish under both cross-lingual and multilingual settings. LS substantially improves sensitivity and F1 in cross-lingual settings, while yielding smaller but consistent gains in multilingual settings. Representation analysis further shows that LS reduces language identity in the embedding space, supporting the interpretation that LS removes language-dependent structure.

Drug recommendation requires a deep understanding of individual patient context, especially for complex conditions like Parkinson's disease. While LLMs possess broad medical knowledge, they fail to capture the subtle nuances of actual prescribing patterns. Existing RAG methods also struggle with these complexities because guideline-based retrieval remains too generic and similar-patient retrieval often replicates majority patterns without accounting for the unique clinical nuances of individual patients. To bridge this gap, we propose PACE-RAG (Patient-Aware Contextual and Evidence-Constrained RAG). Rather than directly copying frequent medications from retrieved patients, PACE-RAG personalizes recommendations by first extracting patient-specific clinical features, retrieving cases around these features, and then refining the final prescription using the patient's current symptoms, active medication history, and focus-specific prescribing tendencies. By analyzing treatment patterns tailored to specific clinical features, PACE-RAG generates patient-specific medication recommendations along with an explainable clinical summary. PACE-RAG achieved the strongest performance among the evaluated inference-only LLM-based methods, reaching F1 scores of 80.84% and 47.22% on the Parkinson's disease and MIMIC-IV cohorts, respectively. Our code is available at: https://github.com/ChaeYoungHuh/PACE-RAG.

Discrepancies between clinical diagnoses and omics profiles within a characterized cohort may reflect misdiagnosis, hidden subgroups or prodromal disease states. We propose MLASDO, a tool to detect and characterize such discrepancies before downstream analyses. MLASDO (1) detects outliers using two unsupervised methods, thereby flagging potential poor-quality samples; and (2) identifies and characterizes anomalous samples (ASs), i.e., individuals whose molecular profile resembles the opposite clinical class. We applied MLASDO to the Parkinson's Progression Markers Initiative (PPMI) and Parkinson's Disease Biomarkers Program (PDBP) Parkinson's disease (PD) cohorts. In PPMI, it detected 26 outliers and 12 ASs: 5 anomalous healthy controls (AHCs) and 7 anomalous PD cases (APDs). AHCs exhibited higher cerebrospinal fluid (CSF) A\b{eta}1-42 levels than controls (P < 0.0396), suggesting resistance to cognitive decline. AHC-specific genes were enriched for the MAPK pathway (P<0.0145), implicated in PD pathogenesis. One AHC later received a different neurological disorder, three months after enrollment. In PDBP, it identified 10 outliers and 8 ASs: 2 AHCs and 6 APDs. One AHC exhibited 24 clinical features consistent with a PD-like phenotype, including severe motor impairment. Results are compiled in an interactive report for inspection and querying, highlighting clinically meaningful individuals otherwise overlooked in conventional analyses.

In this work, we introduce language-aligned motion representations for domain-generalizable UPDRS-Gait severity estimation, aiming to learn semantically structured motion features that generalize across heterogeneous clinical domains. We first learn motion representations using a Bi-GRU backbone that captures the temporal dynamics of SMPL sequences. Prior to model training, motion captions are generated offline using Qwen2.5-7B-Instruct. The backbone is then trained with both classification and text-alignment objectives to learn discriminative and semantically structured motion representations while accounting for the class imbalance present in the training data. We subsequently adapt the learned backbone independently to each source domain so that the model can capture domain-specific motion characteristics. The resulting source-specific models are then merged at the parameter level to consolidate complementary knowledge across source domains into a single domain-generalized model. To further mitigate class imbalance, we perform GPT-5.5-based pseudo labeling, and our final merged models for each site do not use any class-prior correction during inference. The resulting model is evaluated under the unseen-site setting of the MoCha Challenge, using Macro F1 as the primary evaluation metric. Our method achieves a macro-F1 of 0.57 on the hidden test set with only 637K active parameters at inference, ranking 3rd among 58 leaderboard entries in the MoCha 2026 Challenge. The challenge attracted 1,669 submissions from 112 participants and offered monetary prizes sponsored by Machine Medicine Technologies.