Sleep-wake transitions provide a powerful model for studying how conscious states emerge, evolve, and dissipate. The transitions reorganize electrical activity, metabolic demand, and information flow across the human brain; however, the driving mechanisms cannot be directly examined in humans and differ in animals. Thus, we lack a human-based system for testing competing theories of consciousness or for identifying the biological principles that govern transitions between states.
This project introduces a novel experimental model that combines human brain organoids with integrated electrical and metabolic recording, and theory-guided analysis. First, we will establish robust sleep-like and wake-like states in cortical organoids and identify the neural and metabolic signatures that distinguish them. Next, we will study how the states evolve in patterned MorphoCortex organoids that contain different forebrain regions relevant to arousal and state regulation. By inducing controlled transitions, we will determine how activity propagates across these regions and whether the resulting dynamics align with the abrupt ignition posited by Global Neuronal Workspace theory, the more graded integration proposed by Integrated Information Theory, or a combination of both, while also exploring new mechanisms emerging from electrical–metabolic interactions not captured by current frameworks. Finally, we will use spatially targeted perturbations to test if causal influence and learning-related plasticity depend on sleep-wake cycles.
The significance of this work lies in providing the first human-derived system capable of evaluating mechanistic predictions about conscious-state transitions. By uncovering how electrical activity, metabolic constraints, and circuit architecture jointly shape these transitions, the project aims to advance foundational understanding of consciousness while informing related areas such as anesthesia, sleep regulation, and disorders of consciousness.
