Parkinson

Training multi-agent drone-swarm policies directly in high-fidelity (HF) rigid-body physics is accurate but computationally expensive. This cost scales poorly with team size, as each additional agent multiplies contact-resolution complexity and sharply raises the in-simulation crash rate. To address this, we propose a mixed-fidelity training scheme that eliminates HF reinforcement learning entirely. A single shared, decentralized policy is optimized inside a fully-differentiable, JAX-native low-fidelity (LF) point-mass simulator. The simulator is corrected by a small, per-agent bagged residual ensemble fit once, offline, using short calibration flights in the HF simulator. Because calibration requires only one isolated drone, the data collection budget does not compound with team size. Reference trajectories are generated by rolling out an existing LF-only policy and tracked in the HF simulator by a zero-training PD controller. Evaluated across four cooperative drone tasks and team sizes from 3 to 18, the residual-corrected policy outperforms an uncorrected LF baseline in all combinations, and a from-scratch HF policy in 22 of 24 combinations tested. It trails an HF-finetuned policy by a margin that narrows steadily with team size. Ultimately, the proposed method achieves near-equivalent performance at the largest team sizes at a fraction of the computational cost, completely avoiding the high crash rates typical of HF training.

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.

Objective assessment of Freezing of Gait (FoG) in Parkinson's disease (PD) relies predominantly on wearable Inertial Measurement Units (IMUs). While IMUs provide optimal kinematic precision, mandatory sensor attachment restricts continuous clinical deployment. Conversely, unobtrusive vision-based alternatives suffer substantial classification errors during turning-in-place tasks, where geometric self-occlusion degrades deterministic skeletal coordinates and obscures the high-frequency precursors required for FoG detection. To resolve these physical observation limits, we propose a supervised cross-modal subspace distillation framework. During optimisation, pre-trained kinematic data from IMU sensors and contextual clinical metadata act as oracles to guide a deployable visual architecture. By incorporating joint velocity and acceleration derivatives, utilising a confidence-based gating mechanism, the visual model mitigates some of the tracking errors during occlusion events. Empirical evaluations confirm this latent alignment transfers the predictive fidelity of hardware sensors directly into the visual representation, yielding $85.5\%$ accuracy, and $82.4\%$ balanced accuracy. All the while maintaining a vision only model at inference.

This study investigates the classification of individuals as healthy or at risk of Parkinson's disease using machine learning (ML) models, focusing on the impact of dataset size and preprocessing techniques on model performance. Four datasets are created from an original dataset: DS_0, (normal dataset), DS_1 (DS_O subjected to Canny edge detection and Hessian filtering), DS_2 (augmented DS_0), and DS_3 (augmented DS_1). We evaluate a range of ML models-Logistic Regression (LR), Decision Tree (DT), Random Forest (RF), Gradient Boosting (GB), XGBoost (XBG), Naive Bayes (NB), Support Vector Machine (SVM), and AdaBoost (AdB)-on these datasets, analyzing prediction accuracy, model size, and prediction latency. The results show that while larger datasets lead to increased model memory footprints and prediction latencies, the Canny edge detection preprocessing supplemented by Hessian filtering (used in DS_1 and DS_3) degrades the performance of most models. In our experiment, we observe that Random Forest (RF) maintains a stable memory footprint of 61 KB across all datasets, while models like KNN and SVM show significant increases in memory usage, from 5.7-7 KB on DS_0 to 102-220 KB on DS_2, and similar increases in prediction time. Logistic Regression, Decision Tree, and Naive Bayes show stable memory footprints and fast prediction times across all datasets. XGBoost's prediction time increases from 180-200 ms on DS_0 to 700-3000 ms on DS_2 (truncated)

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.

Reduced-order models based on Cosserat-rod theory are now well established, and modeling theory is no longer the primary bottleneck in soft-robot control. Their implementations, however, do not support the differentiable, GPU-parallel, and control-oriented workflows that underpin advanced rigid-robotics applications. Here, we fill this gap with SoRoMoX (Soft Robot Models in JAX), a fully numerical, JIT-compilable Python/JAX framework. SoRoMoX implements articulated, Piecewise Constant Strain, and Variable Strain models through a unified, control-ready interface that provides inertia matrices, gravitational and elastic forces, Jacobians, and their derivatives. To our knowledge, it is the first rod/strain-based soft-robot modeling framework that runs directly on GPUs and is end-to-end differentiable with respect to states, inputs, and parameters. Sequential CPU rollouts are up to 18.1x faster than state-of-the-art alternatives, while GPU-parallel rollouts increase throughput by up to 234.6x. This performance enables workflows that were previously impractical or impossible: static-equilibrium system identification with 66% lower marker RMSE; residual-force learning with a further 64% reduction; computed-torque tracking with RMSE reduced by a factor of approximately 500 relative to model-free PD; control-gain optimization with up to 62% lower loss than untuned gains; safety-constrained control using high-order control barrier functions to keep the peak contact force within a prescribed 5 N bound, compared with 33.5 N without the safety constraint; and reinforcement-learning policy training up to 7x faster than a CPU PyElastica discrete-rod baseline through massively parallel rollouts.

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.

Hand spasticity and resulting pain affect 12 million people worldwide, including stroke survivors, arthritis patients, and those with other muscle and nerve deficiencies. Soft robotic exogloves are being introduced to help patients enhance mobility or manage pain; however, there are no current solutions that address both pain and mobility. We present preliminary development of a soft robotic exoglove that both aids in mobility and administers massage-like compression to relax spastic muscles. The glove consists of soft pneumatic actuators that are personalized to an individual's hand topology and kinematics, allowing for optimal conformability and targeted mobility. Novel soft actuators were designed, analyzed, fabricated, assembled into an exoglove, and experimentally tested. Actuators were 3D modeled and analyzed with finite element modeling under pressures of 100 and 200 kPa. Geometries were optimized to minimize stress before fabrication and testing. A dorsal finger actuator was successfully customized to a participant's hand topology, providing full conformal contact and maximal force distribution. A ventral finger actuator was successfully fabricated that can be drastically compressed in size to fit into the tight space of a hyperflexed spastic finger. A palmar actuator was successfully printed with stereolithography, showing potential for 3D-printed soft actuators with more complex geometries. The glove was assembled and successfully worn by a pilot user to validate initial findings in comfort and effectiveness.

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.

Medical image segmentation plays a critical role in clinical diagnostics, treatment planning, disease monitoring, and neurological disorder identification. This article presents a comprehensive review of its systematic development, covering widely used public datasets, representative methods built on the U-Net, Transformer, and SAM architectures, and key evaluation metrics with their differences, followed by an analysis of major challenges from multiple perspectives. Unlike surveys that focus on a single model family or a specific clinical application, this review organizes U-Net-, Transformer-, and SAM-based methods within a unified analytical framework, with a particular focus on their effectiveness in improving segmentation accuracy and efficiency. This work aims to guide future research and support clinical translation of medical image segmentation, with all related resources publicly available in our GitHub repository: https://github.com/andrew-pengyu/Awsome_MedSeg/tree/main.

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

Human-Robot Collaboration (HRC) requires strict adherence to safety standards, such as ISO 10218, to prevent harmful interactions. Standard Speed and Separation Monitoring (SSM) filters calculate safe robotic speeds based on conservative assumptions, such as constant human velocity, which prevents accurate predictions of minimum separation distances and causes unnecessary operational halts. This paper proposes a Control Barrier Function (CBF) that explicitly incorporates human acceleration data to analytically forward-predict the minimum human-robot separation distance during a worst-case robotic stopping trajectory. To guarantee safety at the control level, this predictive CBF is integrated as an inequality constraint within a Sequential Quadratic Programming (SQP) framework. Specifically, two methods are proposed: Method I, a CBF-constrained PD safety filter; and Method II, a task-scaling SQP controller that enforces a spatial tube constraint. Simulated and real-world experiments on a UR10e robot evaluate the two proposed methods against a standard industrial SSM module baseline. Results demonstrate that Method II dynamically modulates execution speed and confines spatial deviations. Compared to Method I, Method II achieves a 63% reduction in mean trajectory error and avoids excessive evasive manoeuvres, ensuring high task throughput while complying with ISO 10218 SSM guidelines.

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.

Parkinson's disease (PD) is a progressive neurodegenerative disorder that frequently causes speech impairments associated with hypokinetic dysarthria. As speech production relies on the precise coordination of complex neuromuscular mechanisms, speech analysis has emerged as a promising non-invasive and cost-effective biomarker for early PD detection. Recent deep learning approaches have shown encouraging results; however, most existing methods rely on a single speech representation, potentially overlooking complementary pathological information encoded across different feature spaces. In this work, we propose a multi-branch deep learning framework for automatic PD detection from speech. Each recording is segmented into 5-second chunks and represented using three complementary modalities: Log-Mel spectrograms, MFCCs, and HuBERT embeddings extracted from raw waveforms. The spectrograms are processed using a pre-trained ResNet-18 encoder, MFCC sequences are modeled through a BiLSTM network, and raw speech is encoded using a pre-trained HuBERT model. To effectively integrate these heterogeneous representations, we introduce a context-guided cross-modal attention mechanism that dynamically weights temporal HuBERT embeddings according to the global acoustic context derived from the spectrogram and MFCC branches. Experiments conducted on the publicly available Spanish PC-GITA corpus under strict speaker-independent 5-fold cross-validation demonstrate the effectiveness of the proposed approach. The proposed architecture achieves an accuracy of 91.51%, an F1-score of 91.24%, and an AUC of 95.97%. Furthermore, ablation studies confirm the contribution of both the proposed context-guided cross-modal attention mechanism and the integration of complementary speech representations. These findings highlight the potential of heterogeneous speech modeling for robust and clinically reliable PD detection.

Objective: To develop and externally test a video-based framework for simultaneous detection of hyperkinetic MDs phenomenologies: dystonia, tremor, myoclonus, chorea, athetosis, ballismus, stereotypies, and tics using routine clinical recordings, with explicit testing of external, cross-cohort transfer from adult to pediatric populations. Methods: In this proof-of-concept study, the framework combines markerless pose estimation, kinematic descriptors, and a pretrained fondation model. A shared predictive backbone was developed on 21 adults with confirmed hyperkinetic MDs and 4 healthy controls assessed under a standardized protocol. External validation was performed on an independent external cohort: a real-world pediatric sample (n=12, monogenic combined MDs). For the external dataset, the backbone was deployed without retraining; lightweight calibration adjusted only the final subject-level decision step using a small labeled subset of patients selected by clinicians as representative of the cohort's phenotypic range. Results: After local calibration of the decision layer on the clinician-selected subset, performance improved consistently on the held-out pediatric patients (n=7): Hamming accuracy rose from 0.804 to 0.839 and the Jaccard index from 0.548 to 0.633. This calibrated performance was preserved, and the Jaccard index further improved, when the evaluation was restricted to the phenomenologies with more definite clinician agreement (Hamming accuracy 0.9, Jaccard index 0.786), indicating that the gains did not rest on the least-reliable labels.

We investigate whether large language models produce different medical triage recommendations for identical symptoms based solely on the language of the patient prompt. Using Gemini 3.5 Flash, we evaluate a neurological symptom profile (persistent headache, blurred vision, nausea) across six languages (English, Spanish, Chinese, Hindi, Japanese, Arabic) with 30 runs per condition (n=450 total API calls). We find that the model recommends emergency room visits at rates ranging from 0% (Japanese, Hindi) to 30% (English, Arabic), despite assigning nearly identical severity scores (7.7-8.0/10) across all languages. Adding a single sentence specifying the patient's US location increases ER recommendations by up to 76.7 percentage points for non-English prompts, while the reverse anchor (English prompt with a Tokyo location) reduces the ER rate from 30% to 6.7%. A back-translation control (Japanese to English) produces ER rates comparable to the English baseline, confirming that the disparity is not caused by translation quality but by implicit geographic inference from the input language. We release the complete dataset, experiment code, and results.

Tremor is a common movement disorder associated with conditions like Parkinson's disease and Essential tremor, traditionally diagnosed through expert clinician assessment. Current automated detection methods rely on frequency-domain features informed by clinical expertise. In this work, we present an explainable, two-stage hierarchical framework for tremor detection in the time domain that learns tremor patterns directly from 3D kinematic marker time-series data across entire tremor-provoking trials. Our framework combined a deep convolutional and long short-term memory network to learn tremor representations from short, discrete, non-overlapping time segments of kinematic time series data from trials, which are then processed by a vision transformer that models their long-term temporal dynamics of time segment features for trial (session) level classification. Evaluated across nine body parts, the framework achieved F1-scores of 0.594 - 0.947 depending on body parts (average: 0.765), falling short of the frequency-domain state-of-the-art performance (0.909) while requiring minimal preprocessing. Attention weights and gradient-based class activation maps (Grad-CAM) identified time-domain features of tremor across body parts. This proof of concept demonstrated the feasibility of data-driven time-domain modeling for tremor detection across anatomically diverse body parts, while reducing reliance on expert-engineered spectral features and providing posthoc interpretability of temporal and anatomical patterns of tremor.

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.

Cerebral Palsy (CP) is a neurological disorder of movement and the most common cause of lifelong physical disability in childhood. Approximately 75% of children with CP are ambulatory, and accurate gait assessment is central to preserving walking function, which deteriorates by mid-adulthood in a quarter to half of adults with CP. The Rodda and Graham classification system quantifies sagittal-plane gait deviations using ankle and knee z-scores derived from 3D Instrumented Gait Analysis (3D-IGA), but 3D-IGA is expensive and limited to specialized centers, while observational assessment shows only moderate inter-rater agreement. We developed a markerless gait analysis pipeline that quantifies Rodda and Graham knee and ankle z-scores directly from single-view clinical gait videos. Across 1,058 bilateral limb samples from 529 trials of 152 children (88 male, 63 female; age 12.1 $\pm$ 4.0 years; 60 distinct primary diagnoses, cerebral palsy the most common at $n=54$), the sagittal-view model achieved $R^2 = 0.80 \pm 0.02$ and CCC $= 0.89 \pm 0.02$ for knee z-scores and $R^2 = 0.57 \pm 0.02$ and CCC $= 0.72 \pm 0.02$ for ankle z-scores against 3D-IGA. Binary screening for excess knee flexion achieves AUROC $= 0.88$, correctly identifying 83% of affected children, and applying Rodda and Graham rules yields $43 \pm 1$% 7-class accuracy with macro-AUROC $= 0.78 \pm 0.01$, ankle prediction error remaining the primary bottleneck. Beyond cross-sectional screening, continuous z-scores support longitudinal trajectory tracking across visits, providing a quantitative substrate for monitoring disease progression and treatment response unavailable from observational scales. These results demonstrate the feasibility of video-based z-score estimation, excess-flexion screening, and longitudinal trajectory tracking as a path toward scalable, objective gait assessment in low-resource clinical settings.

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.

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.

Frontier large language models generate clinically accurate outputs, but their citations are often fabricated. We term this the Provenance Gap. We tested five frontier LLMs across 36 clinician-validated scenarios for three rare neuromuscular disease pairs. No model produced a clinically relevant PubMed identifier without prompting. When explicitly asked to cite, the best model achieved 15.3% relevant PMIDs; the majority resolved to real publications in unrelated fields. We present HEG-TKG (Hierarchical Evidence-Grounded Temporal Knowledge Graphs), a system that grounds clinical claims in temporal knowledge graphs built from 4,512 PubMed records and curated sources with quality-tier stratification and 1,280 disease-trajectory milestones. In a controlled three-arm comparison using the same synthesis model, HEG-TKG matches baseline clinical feature coverage while achieving 100% evidence verifiability with 203 inline citations. Guideline-RAG, given overlapping source documents as raw text, produces zero verifiable citations. LLM judges cannot distinguish fabricated from verified citations without PubMed audit data. Independent clinician evaluation confirms the verifiability advantage (Cohen's d = 1.81, p < 0.001) with no degradation on safety or completeness. A counterfactual experiment shows 80% resistance to injected clinical errors with 100% detectability via citation trace. The system deploys on-premise via open-source models so patient data never leaves institutional infrastructure.

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.

Early detection of PD remains particularly challenging in resource-constrained settings, where voice-based analysis has emerged as a promising non-invasive and cost-effective alternative. However, existing studies predominantly focus on English or other major languages; notably, no voice dataset for PD exists for Bengali -- a language spoken by over 230 million people worldwide -- posing a significant barrier to culturally inclusive and accessible healthcare solutions. We present BenSparX, the first Bengali conversational speech dataset for PD detection, along with a robust and explainable ML framework tailored for early diagnosis. The proposed framework incorporates diverse acoustic feature categories, systematic feature selection methods, and state-of-the-art ML classifiers with extensive hyperparameter optimization. Furthermore, to enhance interpretability and trust in model predictions, the framework incorporates SHAP (SHapley Additive exPlanations) analysis to quantify the contribution of individual acoustic features toward PD detection. Our framework achieves state-of-the-art performance, yielding an accuracy of 95.67%, F1 score of 95.62%, and AUC of 0.990. We further validated our approach by applying the framework to existing PD datasets in other languages, where it consistently outperforms state-of-the-art approaches. This study lays the foundation for identifying subtle yet clinically meaningful vocal biomarkers, particularly in low-resource settings such as Bengali-speaking populations, and represents a significant step toward equitable, explainable, and robust digital health diagnostics for neurodegenerative disorders. The labelled acoustic-feature dataset derived from the audio recordings in this study is available at https://github.com/riadEDU/BenSParX.

Quantitative assessment of muscle MRI is crucial for monitoring neuromuscular disorders (NMD). This study introduces an automated radiomic phenotyping framework based on original features engineered across five main architectural domains: quantitative morphometry, spatial distribution, geometric shape, interactions between progressive fat replacement stages, and graph-based topology. Utilizing 1184 MRI scans from the CoMPaSS-NMD project, we map the complex 3D architecture of heterogeneous intramuscular lipodegeneration into objective, morphologically interpretable biomarkers. We introduce a graph-based skeletonization of fat infiltrates to quantify muscle architectural changes, establishing a multi-dimensional extension of traditional, spatially-agnostic volume metrics by mapping topological networks across the entire 3D muscle volume. Statistical screening via non-parametric Kruskal-Wallis analysis confirmed the discriminative power of these novel descriptors across the genetic hierarchy. Notably, topological network metrics (e.g., SF1_Skel_Nodes, $\epsilon^2$ = 0.2656) and interface dynamics metrics (e.g., SF2_To_SF1_Dist_Min, $\epsilon^2$ = 0.2092) demonstrated substantial effect sizes, providing deeper structural insights than classical volumetric assessments. Post-hoc pairwise evaluations and UMAP projections further indicated the capability of these topological and 3D geometric invariants to capture disease-specific macroscopic infiltration patterns. These results demonstrate that global architectural features represent a highly promising class of biomarkers for differential diagnosis, offering new avenues for tracking longitudinal disease dynamics in neuromuscular diagnostics. The developed automated feature extraction pipeline is integrated and available within the MUSCAT (MUSCle fAt Topology) library.