Parkinson's Disease Classification

Smooth pursuit eye movements are frequently altered in Parkinson's disease, but previous studies have relied mainly on conventional parameters that describe the relationship between gaze and target. This study investigates whether complexity and nonlinear dynamics measures of the gaze position sequences can support the automatic screening of Parkinson's disease. Gaze position sequences were recorded with a video eye tracker in 41 participants with early Parkinson's disease and 47 healthy controls during 12 smooth pursuit tasks. Four experimental frameworks and four embedding delay strategies were compared. The selected experimental setting combined baseline wander removal with a fixed embedding delay. After feature selection, a support vector machine was trained for each task and axis and their outputs were combined in a mixture of experts. The pipeline was developed in 70 participants and evaluated on an external test set of 18 participants. On the external test set, the pipeline obtained an area under the receiver operating characteristic curve of 0.86. The most informative features described less persistent and more irregular gaze position sequences in Parkinson's disease, mainly along the horizontal axis. These results support complexity and nonlinear dynamics measures of smooth pursuit as candidate markers for Parkinson's disease screening, pending validation in larger independent cohorts.

As two most prevalent neurodegenerative diseases (NDDs), Alzheimer's disease (AD) and Parkinson's disease (PD) shared commonalities both in symptomology and pathophysiology. However, to what extent and in what way these two distinct disorders overlap remain underexplored. In this study, we propose an explicit, interpretable and spatially adaptive transfer learning framework to elucidate the morphometric biomarkers linked to AD and PD. We applied such high-dimensional machine learning model to two most popular open-source neuroimaging datasets, i.e., Alzheimer's Disease Neuroimaging Initiative (ADNI) and Parkinson's Progression Markers Initiative (PPMI). On the one hand, our cross-disorder classifier revealed neuro-anatomical alteration patterns well aligning with previous neuroimaging research findings and underscoring patients' clinical presentations. On the other hand, the spatially adaptive trained classifier using shared prior achieved statistically superior diagnostic performance compared to respective individual models, which further highlights the cross-disorder framework's efficacy on modeling limited-size datasets across disease domains.

Separating Alzheimer's Disease (AD), Parkinson's Disease (PD), and Healthy Controls (HC) using structural MRI remains challenging because disease signatures overlap and model performance can be strongly affected by data partitioning. We present HybridDualPathNet, a hybrid architecture combining EfficientNetV2-S for local features and Swin-Tiny for global context through a Cross-Fusion Attention (CFA) module. We evaluate the model in two experiments. First, on the Kaggle APD-3-Class dataset using an image-level split, the model achieves 98.25% accuracy. Second, on a combined Kaggle and Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset containing 17,859 slices, we use a per-source split with patient-wise separation for ADNI subjects. In this setting, the model achieves 73.37% standard accuracy and a macro AUC of 0.880. Source-stratified evaluation reveals a substantial domain gap, with 91.2% accuracy on Kaggle test images and 59.2% on ADNI test images. Temperature scaling reduces expected calibration error from 0.130 to 0.015, while split-conformal prediction achieves 89.5% coverage. Saliency analyses using Grad-CAM++, Integrated Gradients, and occlusion indicate that model activations concentrate on brain tissue. These results highlight the importance of patient-level separation, cross-dataset evaluation, and uncertainty estimation when assessing MRI classification systems. The findings also show that strong performance on a single dataset does not necessarily translate to reliable generalization across imaging cohorts.

Participant-disjoint cross-validation prevents direct participant overlap, but it may still produce optimistic estimates when acquisition site and diagnosis are structurally dependent. We examined Parkinson's disease classification using 159 pressure-walkway summary features from 133 WearGait-PD participants, including 65 participants with Parkinson's disease and 68 controls. The cohort was non-factorial: two sites contained only one diagnostic group, whereas VA-Seattle was the only site containing both groups. In repeated participant-level nested cross-validation, site alone achieved an area under the receiver operating characteristic curve (AUC) of 0.955 plus or minus 0.003, exceeding the gait-feature model (0.882 plus or minus 0.014). Under the evaluated logistic-regression pipelines, adding gait features to site, age, and sex produced no measurable improvement in pooled discrimination. More site-controlled evaluations produced lower and imprecise estimates: VA-Seattle same-site AUC was 0.668 (95% bootstrap confidence interval 0.477 to 0.836), and the JHOC + Bayview-to-VA-Seattle transport stress test achieved 0.576 (0.375 to 0.770). Supporting within-diagnosis site-prediction and site-conditioned permutation analyses showed that the gait representation retained substantial acquisition-site structure. These findings indicate that participant-disjoint pooled validation did not isolate disease-related discrimination from site-associated variation. They encourage careful examination of site-label dependence and, where possible, support for pooled results through within-site or independent validation before broader claims are made about generalization across institutions.

Parkinson's disease alters gait and bilateral coordination, but machine-learning performance also depends on how continuous gait signals are represented. This study investigates whether preserving anterior-posterior center-of-pressure (AP-COP) information at fixed locations across normalized stance provides a compact and informative representation of plantar-force gait signals. Bilateral vertical ground reaction force recordings from 165 participants in the Gait in Parkinson's Disease Database were evaluated using repeated fully nested participant-level cross-validation. We propose AP-COP10, comprising AP-COP position and bilateral asymmetry across five stance windows. AP-COP10 achieved an AUC of 0.894 and outperformed three harmonized literature-derived COP representations under the same evaluation pipeline. The complementary 25 non-AP-COP descriptors alone achieved an AUC of 0.856, while the complete 35-feature representation achieved 0.908. Removing AP-COP10 from the complete representation produced a statistically supported loss in discrimination, whereas adding the complementary descriptors to AP-COP10 yielded only a small, unsupported improvement. Feature competition indicated that the most informative stance-indexed descriptors were concentrated in early and early-mid stance, while source-study holdout and sensor-perturbation analyses supported the robustness of the representation. These findings indicate that stance-indexed AP-COP retains discriminative information that is not readily recovered by broader engineered gait descriptors, supporting compact and interpretable representations for machine-learning analysis of pathological gait.

Parkinson's disease (PD) manifests early neuromotor impairments that become observable in controlled hand-drawn patterns such as spirals and meanders, where tremor-induced oscillations, stroke irregularity, and curvature instability reflect underlying motor degradation. In this work, we present an explainable framework for PD screening from offline hand-drawn patterns that integrates discriminative visual modeling with clinically grounded reasoning. The predictive model captures distributed structural distortions and fine-grained texture variations. It is evaluated under subject-disjoint protocols to ensure reliable generalization. To move beyond black-box classification, we introduce a multi-stage explainability pipeline that combines visual attribution with structured symptom abstraction. Salient regions are identified using attention- and gradient-based localization, followed by extraction of clinically meaningful motor descriptors quantifying contour roughness, curvature irregularity, stroke variability, and tremor-frequency energy. These descriptors are subsequently translated into coherent clinical rationales through a language-based reasoning module, linking model evidence to established PD symptomatology. By bridging visual attribution and clinical interpretation, the proposed framework advances interpretable document intelligence for neurological screening using hand-drawn patterns. Experimental results on publicly available Parkinson's disease handwriting datasets demonstrate competitive predictive performance and clinically consistent explanations.

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)

We grade MDS-UPDRS gait severity from SMPL motion using three frozen MotionAGFormer encoders as featurizers, reaching macro-F1 0.58 on a hidden, multi-site test set. Because the system's members differ only in their lifting corpus, evaluating encoders singly on that test set isolates what that corpus contributes. Six pools drawn from one inertial dataset, varying only in which walking tasks they include, score between 0.32 and 0.53, and just one of them beats the 0.51 of an encoder given no outside motion at all. What separates them is not how much data they hold but whether they carry a contrast in walking speed, the variation this representation appears to depend : a further pool adding a third collection site at fixed task composition does worse still. The same rule explains why exact synthetic motion and monocularly reconstructed web video both fail to help. Modifying the learned representation itself, rather than the corpus behind it, cost every variant that attempted it.

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.

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.

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.

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.

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.

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.

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 identification of reliable molecular biomarkers for Parkinson's disease remains challenging due to its multifactorial nature. Although protein sequences constitute a fundamental and widely available source of biological information, their standalone discriminative capacity for complex disease classification remains unclear. In this work, we present a controlled and leakage-free evaluation of multiple representations derived exclusively from protein primary sequences, including amino acid composition, k-mers, physicochemical descriptors, hybrid representations, and embeddings from protein language models, all assessed under a nested stratified cross-validation framework to ensure unbiased performance estimation. The best-performing configuration (ProtBERT + MLP) achieves an F1-score of 0.704 +/- 0.028 and ROC-AUC of 0.748 +/- 0.047, indicating only moderate discriminative performance. Classical representations such as k-mers reach comparable F1 values (up to approximately 0.667), but exhibit highly imbalanced behavior, with recall close to 0.98 and precision around 0.50, reflecting a strong bias toward positive predictions. Across representations, performance differences remain within a narrow range (F1 between 0.60 and 0.70), while unsupervised analyses reveal no intrinsic structure aligned with class labels, and statistical testing (Friedman test, p = 0.1749) does not indicate significant differences across models. These results demonstrate substantial overlap between classes and indicate that primary sequence information alone provides limited discriminative power for Parkinson's disease classification. This work establishes a reproducible baseline and provides empirical evidence that more informative biological features, such as structural, functional, or interaction-based descriptors, are required for robust disease modeling.

Differential diagnosis among parkinsonian syndromes remains a clinical challenge due to overlapping motor symptoms and subtle gait abnormalities. Accurate differentiation is crucial for treatment planning and prognosis. While gait analysis is a well established approach for assessing motor impairments, conventional methods often overlook hidden nonlinear and structural features embedded in foot clearance patterns. We evaluated Topological Data Analysis (TDA) as a complementary tool for Parkinsonism classification using foot clearance time series. Persistent homology produced Betti curves, persistence landscapes, and silhouettes, which were used as features for a Random Forest classifier. The dataset comprised 15 controls (CO), 15 idiopathic Parkinson's disease (IPD), and 14 vascular Parkinsonism (VaP). Models were assessed with leave-one-out cross-validation (LOOCV). Betti-curve descriptors consistently yielded the strongest results. For IPD vs VaP, foot clearance variables minimum toe clearance, maximum toe late swing, and maximum heel clearance achieved 83% accuracy and AUC=0.89 under LOOCV in the medicated (On) state. Performance improved in the On state and further when both Off and On states were considered, indicating sensitivity of the topological features to levodopa related gait changes. These findings support integrating TDA with machine learning to improve clinical gait analysis and aid differential diagnosis across parkinsonian disorders.

We propose a novel swap-adversarial framework that mitigates high inter-subject variability and the high-dimensional low-sample-size problem in electrocorticography (ECoG) data. It achieves robust domain generalization across ECoG and electroencephalography (EEG)-based brain-computer interface datasets. Our framework integrates (1) robust preprocessing, (2) inter-subject balanced channel swap (ISBCS) for cross-subject augmentation, and (3) domain-adversarial learning (DAL) to suppress subject-specific bias. The ISBCS method is a bio-inspired channel swapping strategy that exchanges only functionally corresponding channels across subjects, guided by a brain map, to mitigate inter-subject distribution differences. The DAL strategy encourages the model to learn task-relevant shared features. In addition, we introduce a new ECoG dataset, the first reproducible benchmark, which is constructed from long-term ECoG recordings of 6-hydroxydopamine-induced rat models and annotated with neural responses measured before and after electrical stimulation. We validate the effectiveness of this framework through extensive experiments under cross-subject, cross-session, and cross-dataset settings. Our results show that the proposed framework exhibits the best and robust generalization performance both for our newly constructed ECoG and public EEG datasets.

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.