bioRxiv Science⌕ Search

bioRxiv · 10.64898/2026.02.02.703416

Predicting Post-Stroke Aphasia Speech Performance from Multimodal Data with Explainable Machine Learning

Abstract

Aphasia, an acquired language deficit, is the most common post-stroke focal cognitive impairment, and roughly 60% cases become chronic (duration >6 months). Aphasia therapies could be optimized if clinicians could make personalized predictions of how individual persons with aphasia (PWA) would be likely to perform on particular language tasks. However, current approaches relying on imaging, lesion volume, patient demographics, and clinical scores achieve less than 50% accuracy in predicting performance in PWA. Research algorithms using complex imaging and fMRI can make binary predictions about the presence or absence of aphasia but do not give more clinically relevant information. We aim to predict word-by-word speech accuracy in PWA to better enable personalized speech therapies. To be clinically informative, machine learning models developed for this purpose should use clinically available inputs, explain key features behind a prediction, and generalize to new PWA and previously unseen words. This study combines multimodal input features from clinical testing scores and structural MRI neuroimaging with a novel data source: word-by-word linguistic difficulty. We computed metrics of cognitive burden, such as semantic selection and recall demands, and articulatory burden, such as word length in phonemes and syllables, using naturalistic corpora containing over a billion words of English text. Retrospective training, ten-fold cross validation and 500-run bootstrapping of different machine learning models with various combinations of input features was conducted using 4620 trials. A simplified version of the best model using widely available inputs was deployed clinically through a web app, and prospective generalization was tested on 570 trials with unseen words and different naming tasks in new PWA. We found the best performances with random forest classifiers using linguistic difficulty combined with either clinical information (AUROC {+/-} SEM = 0.87 {+/-} 0.07), or all together with structural imaging connectivity (0.90 {+/-} 0.04). Classifiers using multimodal inputs significantly outperformed others employing single inputs (range 0.66-0.85, p<0.05). Extracting feature importances from the best model showed that Western Aphasia Battery scores, semantic demands, number of phonemes, and syllables were predictive of PWA speech accuracy. Structural integrity in peri-lesional brain regions predicted better language performance whereas higher connectivity of select contralateral homotopes contributed to prediction of worse speech. Without the inclusion of MRI data, lesion volume was a key predictor of PWA speech as well. A simplified, clinically ready, explainable model (publicly available as AphasiaLENS web application) predicted PWA accuracy for any user-entered word, not restricted to a standardized battery. Its prospective generalization performance was not significantly different from the best model using full inputs (AUROC ranges 0.81-0.89, p>0.05). Thus, our research can help inform individualized treatment planning for PWA, while also suggesting research targets through better understanding of brain-behavior relationships.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Parchure, S., Gupta, A., Kelkar, A., Vnenchak, L., Faseyitan, O., Medaglia, J. D., Harvey, D. Y., Coslett, H. B., Hamilton, R. H.. 2026-02-05. Predicting Post-Stroke Aphasia Speech Performance from Multimodal Data with Explainable Machine Learning. https://doi.org/10.64898/2026.02.02.703416

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

KEEP EXPLORING

Related preprints

Surfactant-Assisted Colorimetric Signal Enhancement in Paper-Based Glucose Sensing

Paper-based colorimetric sensors offer a low-cost and accessible platform for point-of-care (POC) analysis, but enzyme activity loss during coating and drying can weaken analytical signals and require high enzyme loadings or complex immobilization procedures. Although surfactants are widely used to improve wettability in paper-based assays, their potential contribution to colorimetric performance beyond these effects remains unclear. Here, we investigated surfactant-assisted colorimetric signal enhancement in a glucose assay implemented on a 96-puddle paper plate (96-PPP) and identified Tween 20 as the most effective surfactant. Its effect on detection performance became more pronounced as glucose oxidase (GOx) loading decreased; at 0.1 mg/mL GOx, Tween 20 lowered the limit of detection (LoD) from 0.113 to 0.034 mg/mL (approximately 3.3-fold) over a working range of 0-5 mg/mL, despite no statistically significant change in the measured contact angle at this loading. Tween 20 had no appreciable effect on the reaction in solution but preserved 95% of the apparent reaction rate constant after drying, compared with 11% without it, and atomic force microscopy (AFM) revealed a more dispersed dried enzyme morphology on mica. Tween 20-containing sensors also showed slower signal decay during repeated wetting-drying cycles and thermal stress, retained 77% (vs 26%) of the response at 400 mM NaCl, and exhibited within-PPP and between-batch coefficients of variation (CVs) below 10% (vs 12.3-19.5%), while maintaining glucose selectivity over potentially interfering molecules. These results indicate that Tween 20 enhances paper-based glucose sensing beyond wettability, in part by retaining enzyme cascade activity during drying, although the contributions of the individual enzymes and the underlying mechanism remain to be established.

bioengineering↗

Engineering CAR-T cells to remodel the mucin-rich cancer cell glycocalyx

The dense glycocalyx of cancer cells can restrict immune-cell access to surface antigens and limit CAR-T cell activity. Here, we show that mucin density and epitope position determine how glycocalyx remodeling affects CAR-T cell recognition and killing. We identify KLK5 as a human protease that cleaves tumor-associated mucins, increases access to membrane-proximal antigens, and enhances CAR-T cell function. We then engineer CAR-T cells to display or secrete KLK5, enabling remodeling of the tumor glycocalyx during antigen recognition. KLK5-engineered CAR-T cells improved tumor control across multiple xenograft models, and KLK5-secreting MUC17 CAR-T cells produced the strongest in vivo benefit, prolonging survival compared with conventional MUC17 CAR-T cells. These findings show that CAR-T cells can be engineered to breach the mucin-rich glycocalyx while preserving accessible target epitopes.

bioengineering↗

Wall stiffening is a primary contributor to motility loss in Crohn's disease: an electromechanical modeling study

Fibrotic strictures are among the most disabling complications of Crohn's disease, permanently narrowing the bowel and impairing motility, yet no approved therapy reverses them. Chronic inflammation alters pacemaker-network coupling, smooth-muscle excitability, and calcium-dependent contractility, while fibrosis thickens the bowel wall, narrows the lumen, and changes tissue mechanics. The relative contributions of these coupled electrical, contractile, and structural alterations to motility loss remain unclear. To address this gap, we develop an integrated electromechanical finite-element framework for fibrostenosing Crohn's disease that couples a fibrosis-driven growth model with a FitzHugh-Nagumo electromechanical model. A full-factorial 25 design of experiments is used to quantify the relative effects of electrical diffusivity, excitation threshold, peak active stress, wall stiffness, and hypertrophic remodeling on cyclic lumen-volume deformation. Motility is quantified by the standard deviation of lumen volume over one contraction cycle. Within the parameter ranges examined, increased wall stiffness emerged as the dominant contributor to motility loss, followed by impaired smooth-muscle contractility. Changes in excitation threshold, hypertrophic remodeling, and electrical diffusivity produced substantially smaller effects. Pairwise interactions were small relative to the dominant main effects, indicating that the mechanisms contributed largely through their individual effects. Our findings suggest that limiting wall stiffening while preserving smooth-muscle contractile function may provide a therapeutic strategy for maintaining intestinal motility in fibrostenosing Crohn's disease.

bioengineering↗