Late neurologic and functional outcomes in patients with severe anoxic brain injury after cardiopulmonary arrest: a multicenter cohort study.

Stress is a fundamental component of human adaptation, enabling individuals to respond effectively to environmental challenges. Importantly, stress does not uniformly impair performance; its effects depend on its intensity, duration, and context. Moderate acute stress can enhance alertness and cognitive efficiency, consistent with the inverted U-shaped relationship between arousal and performance described by the Yerkes–Dodson law []. In contrast, excessive stress, particularly in socially evaluative contexts such as examinations or competitive situations, can overwhelm cognitive resources and degrade performance, leading to increased error rates and impaired decision-making [,]. Stress can be categorized as either acute or chronic: acute stress refers to the body's immediate response to a specific stressor, typically short-lived and adaptive, while chronic stress arises from prolonged exposure to a persistent stressor or from a failure to return to a homeostatic state, as observed in individuals experiencing long-term traumatic stress []. The accurate assessment of acute stress is therefore crucial in high-stakes environments where optimal performance and rapid decision-making are required. In the medical field, healthcare professionals frequently face acute stress during emergency procedures, which can impair key cognitive functions []. Similarly, in aviation, pilots are exposed to time-critical and high-pressure situations where stress can lead to performance degradation and increased error rates []. Monitoring acute stress responses in these contexts is therefore essential not only to ensure safety and performance, but also to implement timely stress management interventions []. Given its immediate impact on psychophysiological functioning, quantifying acute stress through physiological measures may provide a valuable tool to enhance performance, reduce errors, and protect health in demanding professions [,]. Stressful situations, particularly those involving cognitive demands, trigger two key physiological systems: the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS). The HPA axis regulates the secretion of cortisol, a glucocorticoid essential for managing prolonged stress and restoring homeostasis []. Cortisol remains the gold-standard biomarker of stress responses and systemic regulation [,]. SNS activation triggers rapid autonomic adjustments, including increased heart rate (HR), reduced heart rate variability (HRV) [,], and elevated respiratory rate [,]. It also induces pupillary dilation (mydriasis), a fast-reacting indicator of autonomic arousal and cognitive effort [, , ]. In parallel, levels of salivary α-amylase rise in response to adrenergic stimulation, providing a non-invasive biomarker of sympathetic activation [, , ]. However, cortisol and α-amylase responses appear with a time lag, making them unsuitable for real-time stress monitoring. While cardiorespiratory parameters are more immediate, they may lack the sensitivity to detect subtle differences in stress intensity []. In this context, pupillometry represents a particularly promising approach for capturing rapid and subtle variations in stress responses []. Pupil size is closely linked to activity in the locus coeruleus-norepinephrine (LC-NE) system—a key regulator of attention, arousal, and stress responses []. LC-NE activation enhances norepinephrine release, suppresses parasympathetic control, and results in pupil expansion []. This response reflects both cognitive and emotional load and offers continuous, non-invasive measurement of neurophysiological reactivity []. Consistent with this view, previous studies have shown that pupillary responses are sensitive not only to cognitive demand, but also to emotional and social modulation of stress responses. For example, pupillometry has been shown to reflect variations in emotional stress reactivity during socially supportive or emotionally salient situations [,], further supporting its relevance as a dynamic index of cognitive-emotional arousal. Importantly, the LC-NE system is closely interconnected with the HPA axis and contributes to the coordination of rapid autonomic and endocrine stress responses. While LC-NE activation supports immediate vigilance and arousal adjustments, cortisol release reflects a slower neuroendocrine cascade involved in stress adaptation and homeostatic regulation [,]. Yet, it remains to be determined whether pupillary responses can reliably discriminate slightly different stress conditions, especially when the cognitive task remains constant and only the emotional or motivational context changes by adding social-evaluative pressure. In laboratory settings, acute stress is commonly elicited using cognitively demanding tasks such as the Stroop task [], which engage attentional control and executive functions []. These paradigms offer the advantage of precisely controlling task difficulty while enabling the assessment of physi