Thermodynamics of consciousness: A non-invasive perturbational framework

The quest for reliable and objective measures of consciousness is critical in basic and clinical neuroscience. Across species, the Perturbational Complexity Index (PCI) has emerged as a robust empirical marker by directly perturbing the brain, yet its underlying principles of physics are not fully understood. Here, we bridge this gap by introducing a non-invasive framework based on generative whole-brain models of non-equilibrium brain dynamics. Using these models, we identified violations of the Fluctuation-Dissipation Theorem (FDT) in humans and rodents across wakefulness, anesthesia, and disorders of consciousness. Mirroring the patterns observed with PCI, we found decreased FDT violations in unresponsive disorders of consciousness and anesthesia compared to conscious conditions. This reveals a close link between PCI and non-equilibrium dynamics in spontaneous brain signals, grounding PCI in fundamental principles of physics. Overall, this framework offers new complementary, non-invasive, model-based avenues for understanding the nature of consciousness and for developing objective tools to assess its loss and recovery in health and disease. It also provides a principled foundation for discovering novel strategies to restore consciousness.