Search bioRxiv⌕ Search

bioRxiv · 10.64898/2026.02.02.703144

ExSEnt for explainable dementia detection: disentangling temporal and amplitude-driven complexity boosts EEG-based classification

Abstract

Early detection of dementia enables timely intervention and better care planning. Electroencephalography, being accessible and noninvasive, offers a practical avenue for monitoring pathological alterations in neural activity. Classical biomarkers like the theta-to-alpha power ratio (TAR) along with complexity measures are common methods that are usually evaluated and used for dementia detection. In this study, we aimed to assess the discriminative ability of a novel entropy-based family of measures, Extrema-Segmented Entropy (ExSEnt), summarized by multiple robust statistics per subject for dementia, along with classical measures, and evaluate the incremental value of these metrics. We analyzed an EEG dataset comprising healthy controls, individuals with Alzheimers disease, or frontotemporal dementia. Following preprocessing and group-level analyses of independent components, we focused on source-space activity from the prefrontal cortex and visual association cortices--regions implicated in early disease. From these sources, we computed complexity metrics: Sample Entropy, Katz Fractal Dimension, Higuchi Fractal Dimension, and Hurst exponent and ExSEnt metrics along with TAR and band-limited power at delta, beta, low and high gamma bands. Using stability-based selection with elastic net logistic models, we identified a reliable set of discriminative features and quantified their cross-subject robustness. This framework isolates interpretable and trustworthy source-local biomarkers from single-region time series. We observed that the alpha/theta temporal entropy measures (ExSEnt) are selected as the most reliably informative metrics in the left prefrontal cortex, yielding a classification performance comparable to what was recently reported with high-dimensional deep learning methods for this dataset, with a simple logistic regression model on a single brain source.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Kamali, S., Baroni, F., Varona, P.. 2026-02-04. ExSEnt for explainable dementia detection: disentangling temporal and amplitude-driven complexity boosts EEG-based classification. https://doi.org/10.64898/2026.02.02.703144

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

The Unreasonable Effectiveness of Cell Types in Describing Neuronal Physiological Features

Single-cell RNA sequencing (scRNA-seq) captures detailed gene expression profiles at scale, while patch-clamp recordings measure intrinsic neuronal electrophysiological properties. Modeling the relations between these two modalities remains a challenge. Here, we compare how well electrophysiological features can be predicted by traditional transcriptomic cell type classification, representations derived from a foundational model (scGPT) pretrained on large-scale scRNA-seq datasets, ion channel-coding genes, and highly variable genes. Using paired transcriptomic and electrophysiological patch-sequencing data from 495 human neurons from neurosurgical tissue, we find that cluster-level cell type representations consistently outperform highly variable gene selection, ion channel gene selection, and context-enriched scGPT embeddings. Notably, performance varies across model architectures and initializations, and the best results are obtained by combining the outputs of separate cell type and scGPT-based models. Together, these findings suggest that traditional discrete cellular classification is highly effective in predicting physiological features. For maximum performance it can be complemented by pretrained transformer models.

neuroscience↗

A nonlinear inhibition pathway underlying cortical responses to tuned holographic optogenetic perturbations

Optogenetics enables causal manipulation of cortical activity. Perturbation responses can be counterintuitive due to network interactions, making theory essential for predicting them. Existing approaches often rely on linear approximations, which fail for many biologically relevant perturbations. Here we develop a nonlinear theory of responses to holographic perturbations in cell-type-specific recurrent networks with structured connectivity. We fit a nonlinear model to mouse V1 data, which shows cotuned-ensemble suppression: perturbing spatially clustered neurons with similar preferred orientations yields markedly stronger short-range suppression than perturbing untuned ensembles. We show that cotuned-ensemble suppression arises from a feature-tuned, nonlinear inhibition pathway implicating somatostatin-positive (SST) interneurons. The theory predicts that cotuned ensembles suppress parvalbumin-positive (PV) neurons but facilitate SST neurons, and links the degree of cotuned-ensemble suppression or facilitation to the variance of the SST response. This framework identifies mechanisms by which nonlinear inhibition sculpts cortical dynamics and establishes a predictive basis for targeted optogenetic interventions.

neuroscience↗

Proteomic signatures of APOE ε4 across human tissues and cell types in Alzheimers disease

The apolipoprotein E {varepsilon}4 (APOE {varepsilon}4) allele is the strongest genetic risk factor for late-onset Alzheimers disease (AD). However, the underlying molecular mechanisms remain unclear. This study included 1691 participants from the Religious Orders Study and Rush Memory and Aging Project (ROSMAP), 1226 participants from the Accelerating Medicines Partnership - Alzheimers Disease (AMP-AD) Diverse Cohorts Study, and 735 participants from the Alzheimers Disease Neuroimaging Initiative (ADNI). To characterise APOE {varepsilon}4 molecular effects, we analysed proteomic data from plasma, cerebrospinal fluid (CSF), and induced pluripotent stem cell (iPSC)-derived astrocytes and neurons, as well as transcriptomic and proteomic data from multiple brain regions. The association of APOE {varepsilon}4 with AD neuropathology was also examined. APOE {varepsilon}4 carriers shared a plasma proteomic signature enriched for immune processes, irrespective of AD diagnosis. A machine learning classifier trained on this signature discriminated APOE {varepsilon}4 carriers from non-carriers in an independent cohort using CSF proteomics. APOE {varepsilon}4 carriage was associated with higher Braak stages and Consortium to Establish a Registry for Alzheimers Disease (CERAD) score. However, only limited APOE {varepsilon}4-associated transcriptomic and proteomic changes were observed in bulk brain tissue, with poor cross-layer concordance. Proteomic analyses of iPSC-derived astrocytes and neurons further revealed cell-type-specific APOE {varepsilon}4-associated changes. APOE {varepsilon}4 is associated with a consistent proteomic signature across plasma and CSF. Its molecular effects in the brain differ across cell types, brain regions and molecular layers. These findings support the need for cell-type-resolved multi-omic studies to elucidate how APOE {varepsilon}4 confers AD risk.

neuroscience↗