LERD: Latent Event-Relational Dynamics for Neurodegenerative Classification

Biological heterogeneity in Alzheimer's Disease (AD) poses a critical diagnostic challenge, particularly for traditional linear methods that fail to capture non-linear neural dynamics. To address this, we propose a diagnostic framework utilizing the Large Brain Model (LaBraM), pretrained on over 2,500 hours of EEG data. By integrating these high-dimensional latent embeddings with a non-linear Random Forest classifier, our approach effectively isolates robust disease markers. Under a rigorous subject-independent 5-fold cross-validation protocol, the method achieves an ROC-AUC of 89.36% +/- 3.49%, PR AUC of 81.45% +/- 4.43%, and Balanced Accuracy of 82.44% +/- 4.34% in distinguishing dementia patients from healthy controls. Notably, this performance uses only 8-second EEG segments, surpassing traditional spectral baselines, including band-power and parameterized oscillatory features (FOOOF). Post-hoc occlusion analysis confirms the model captures clinically validated biomarkers, specifically occipital-frontal Alpha and Theta rhythm degradation. Additional neurophysiological alignment analysis demonstrated that higher LaBraM-predicted dementia probability significantly correlated with worse cognitive performance, greater clinical severity, increased theta and alpha relative power, and higher aperiodic exponent. These findings demonstrate that deep latent representations extract clinically relevant signatures from noisy signals, enabling precise, rapid, and data-efficient diagnosis.

Clinical scalp electroencephalography (EEG) offers a noninvasive window into neural dynamics of neuropsychiatric disorders. However, discriminative deep models often lack anatomically indexed physiological interpretability. We propose NeuroDyn-EEG, a pretraining framework integrating generative priors from neural dynamics. It couples an extended Jansen-Rit neural mass model, leadfield-based source projection, and simulation-based parameter inversion. Trained on synthetic parameter-EEG pairs within physiological ranges, NeuroDyn-EEG estimates 11 regional parameter families across 90 AAL regions plus one global parameter from standard 19-channel EEG, using only ~2.43M trainable parameters. We evaluate the framework across three levels. First, controlled simulations demonstrate robust parameter recovery under diverse noise conditions, while real resting-state EEG evaluations confirm spectral and phase consistency in an inverse-forward closed loop. Second, on four clinical benchmarks (AD65, PD31, Figshare MDD, and TUAB), NeuroDyn-EEG achieves competitive classification performance, securing the highest BACC, AUROC, and AUCPR on PD31 and MDD, and highest BACC on AD65. Third, post hoc regional analyses reveal disease-specific alterations: local synaptic connectivity C_1 involves the most altered regions in AD65, whereas the firing threshold theta ranks first in MDD, offering testable mechanistic hypotheses. Overall, NeuroDyn-EEG maps scalp EEG to anatomically indexed dynamical parameters, bridging representation learning and mechanistic neurophysiology. Code: https://github.com/Gnosis-Neurodynamics/NeuroDyn-EEG.

Modeling neural population dynamics is crucial for foundational neuroscientific research and various clinical applications. Conventional latent variable methods typically model continuous brain dynamics through discretizing time with recurrent architecture, which necessarily results in compounded cumulative prediction errors and failure of capturing instantaneous, nonlinear characteristics of EEGs. We propose ODEBRAIN, a Neural ODE latent dynamic forecasting framework to overcome these challenges by integrating spatio-temporal-frequency features into spectral graph nodes, followed by a Neural ODE modeling the continuous latent dynamics. Our design ensures that latent representations can capture stochastic variations of complex brain states at any given time point. Extensive experiments verify that ODEBRAIN can improve significantly over existing methods in forecasting EEG dynamics with enhanced robustness and generalization capabilities.