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Digital Twin Model of Treatment Outcomes in Post-Stroke Aphasia

N. Busby,Nicholas Riccardi,Janina Wilmskoetter,Eleanor N. Jeakle,R. Newman-Norlund,Sigfus Kristinsson,Chris Rorden,Julius Fridriksson,Leo Bonilha

Published 2026 in medRxiv

ABSTRACT

Background: Recovery from chronic post-stroke aphasia is highly heterogeneous and shaped by lesion characteristics, brain integrity, and systemic health. Traditional group-level models struggle to capture this multidimensional, dynamic variability. Digital twin approaches - patient-specific, continually updating models - may enable individualized prediction and counterfactual evaluation of modifiable risk factors. Therefore, the aim was to develop and validate a proof-of-concept digital twin that predicts individual naming outcomes during language treatment and quantifies the estimated impact of modifiable health factors on naming. This study represents the first application of digital twin modeling to aphasia recovery, and we hypothesize that this could constitute a critical first step toward dynamically adaptive, personalized models for aphasia rehabilitation. Methods: We analyzed longitudinal data from 106 chronic stroke survivors with aphasia enrolled in the POLAR randomized clinical trial. For each participant we combined baseline demographic/health variables (age, sex, education, days post-stroke, hypertension, diabetes, BMI), lesion load in left-hemisphere language ROIs (JHU atlas), ROI-level white-matter microstructure (FA), and resting-state functional connectivity restricted to language regions. A continual-learning linear model (River framework; Adam optimizer) was pretrained on baseline data and updated across timepoints. Model performance was assessed by R2 at the final timepoint. Counterfactual simulations systematically altered hypertension, diabetes, and BMI to estimate isolated and combined effects on predicted Philadelphia Naming Test (PNT) scores. Results: The digital twin predicted final PNT scores with R2 = 0.5848 (explaining approximately 58% of variance). The largest contributors were prior naming performance, age, lesion load in language regions, and white-matter integrity in temporal regions (notably right MTG and STG pole). Counterfactual results estimated modest but consistent effects of health factors, with them collectively accounting for approximately 25% of the variance in treatment gains. The average change in PNT score with counterfactual changes was 7.92 (SD = 16.11). Therefore, diabetic status explained 2% of the variance in treatment gains, hypertensive status explained 4.75%, and increasing BMI explained 18.5%. Conclusions: This study demonstrate the feasibility and clinical potential of applying a digital twin framework to chronic post-stroke aphasia, with the model successfully predicting more than half the variance in naming performance during language treatment. Through counterfactual simulation, we demonstrated that modifiable health factors exert measurable, bidirectional influences on predicted treatment outcomes, underscoring the role of systemic health in shaping language recovery. Although the individual effects of these factors were modest in magnitude, their cumulative influence on treatment gains illustrates how multiple small biological contributors can add up to shape meaningful differences in language outcomes. More broadly, these findings illustrate the potential value of digital twin models for aphasia treatment, particularly as a tool to integrate diverse biological factors and generate individualized, dynamically updated predictions.

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