Frontal–Subcortical Dysfunction in Toxic Oil Syndrome: A Proof-of-Concept Eye-Tracking and Cognitive Study Four Decades After Exposure

Julián Benito León^1*José Lapela¹Mariano Ruiz-Ortiz¹Glen Michael Doniger²Sonia Álvarez-Sesmero¹Verónica Giménez de Bejar¹María Antonia Nogales¹Montserrat Morales¹Ritwick Mondal³SHRAMANA DEB³Fernando Bartolome¹Carolina Alquezar¹Cecilia García-Cena⁴

• ¹Hospital Universitario 12 de Octubre, Madrid, Spain
• ²NeuroTrax Corporation, Medina, United States
• ³Manipal Hospitals, Kolkata, India
• ⁴Universidad Politecnica de Madrid, Madrid, Spain

Toxic Oil Syndrome (TOS) emerged in Spain in 1981 following ingestion of rapeseed oil adulterated with aniline derivatives. More than four decades later, survivors continue to report cognitive complaints, yet objective evidence of long-term dysfunction remains limited. We investigated saccadic eye movements and cognitive function in TOS survivors using validated eye-tracking paradigms and a standardized neuropsychological battery. In this case-control study, 47 TOS survivors and 44 matched healthy controls completed visually guided, memory-guided, and antisaccade tasks, as well as cognitive testing. The groups did not differ significantly in age, sex, or education. TOS participants showed preserved performance on visually guided and memory-guided saccades, with no significant group differences in latency, gain, peak velocity, or spatial error (all p > 0.05). By contrast, they exhibited significantly fewer correct antisaccades (mean 3.6 vs. 5.0; p = 0.029), more reflexive saccades (mean 7.0 vs. 5.7; p = 0.033), and increased backward reflexive saccades (mean 6.3 vs. 5.1; p = 0.040). Cognitive testing revealed selective impairments in executive function, attention, and processing speed, with preserved memory. Structural equation modeling confirmed that antisaccade impairment remained significant after adjustment for potential confounders and demonstrated an independent contribution of attention to performance. These findings indicate persistent frontal–subcortical circuit dysfunction in TOS survivors, resembling profiles observed in other toxic-immune encephalopathies. Eye-tracking provides a noninvasive, objective biomarker of latent executive dysfunction and may be valuable for long-term monitoring of populations exposed to environmental factors.