Distinguishing agency and subjectivity in anesthesia: a review and synthesis of neural and theoretical perspectives across scales

Anesthesia research has identified cellular and systems-level changes underlying loss of consciousness, yet these findings remain largely disconnected. Variations in conscious states, such as anesthesia awareness, highlight the distinction between observable responsiveness (agency) and unobservable subjective experience (subjectivity). This review examines and integrates empirical work across scales, from large-scale network dynamics to fine-grained neuronal mechanisms underlying anesthetic-induced unconsciousness. We synthesize findings from existing frameworks, including the Entropic Brain Hypothesis and Dendritic Integration Theory, which explain changes in brain connectivity, dynamics, and neuronal integration under anesthesia. However, neither framework fully addresses how agency and subjectivity may become dissociated. To bridge this gap, we present a neuroscientific interpretation of Irruption Theory as an emerging methodological and conceptual lens. We propose a dual-process synthesis: layer 5 pyramidal cell dendritic coupling provides the structured integration necessary for subjectivity, while neural variability—moment-to-moment fluctuations in neural activity—separately tracks the capacity for agency. This review synthesizes cellular physiology, network neuroscience, and cognitive science, reinterprets existing anesthesia data, and generates testable hypotheses for distinguishing the neural substrates of agency versus subjectivity.