Eye-tracking phenotypes reveal clinically meaningful heterogeneity of attention and executive control dysfunction after stroke.

Abstract

Background: Post-stroke impairments in attention and executive control are common and clinically relevant, whereas conventional neuropsychological tests mainly capture task outcomes and provide limited information about process-level task behavior. Eye tracking can quantify fixation behavior, saccadic activity, and visual sampling, but whether integrated eye-tracking features can reveal clinically interpretable heterogeneity after stroke remains insufficiently defined.

Objective: This study examined whether integrated multi-paradigm eye-tracking features could identify exploratory eye-movement phenotypes in individuals with stroke and whether these phenotypes were associated with behavioral, clinical, lesion-related, and functional characteristics.

Methods: In this single-center exploratory case-control study, 72 subacute stroke participants (14-90 days post-onset) and 36 matched healthy controls completed five tasks of attention and executive control and six eye-tracking paradigms. Group differences in behavioral and eye-tracking measures were examined with false discovery rate correction. Within the stroke group, K-means clustering was performed using four nonredundant integrated eye-tracking features: total fixation duration, first-fixation duration, number of fixations, and total saccade distance. Cluster stability and sensitivity analyses were conducted using bootstrap resampling, alternative feature sets, and combined clustering with healthy controls. Post-clustering comparisons and exploratory regression analyses were used to evaluate the clinical relevance of the identified phenotypes.

Results: Compared with healthy controls, participants with stroke showed lower performance across attention/executive-control tasks and altered eye-tracking metrics across paradigms. The most consistent eye-movement pattern was shorter total fixation duration and a higher number of fixations across the six paradigms, whereas total saccade distance differed most clearly during the antisaccade task. K-means clustering identified two exploratory eye-movement phenotypes: a High-Fixation/Low-Saccade phenotype and a Low-Fixation/High-Saccade phenotype. The two-cluster solution remained stable across bootstrap and sensitivity analyses. The Low-Fixation/High-Saccade phenotype showed poorer cognitive performance, greater neurological and functional impairment, higher emotional symptom burden, and more frequent frontal involvement and bilateral or multifocal involvement. In exploratory hierarchical regression, eye-movement phenotype explained additional variance in Barthel Index scores beyond demographic variables, post-stroke timing, neurological severity, and conventional attention/executive-control performance.

Conclusions: Integrated multi-paradigm eye-tracking features identified two exploratory eye-movement phenotypes in individuals with subacute stroke. The Low-Fixation/High-Saccade phenotype was associated with broader clinical burden. These findings suggest that eye tracking may provide process-level information complementary to conventional assessment of post-stroke attention and executive-control dysfunction. Given the single-center and cross-sectional design, these preliminary phenotypes require validation in longitudinal and multicenter studies.