The Neurometabolic Condition of Consciousness: Mitochondrial Regulation of Neural Criticality and Brain Dynamics

Abstract

Consciousness is increasingly linked to large-scale neural dynamics characterized by integration, differentiation, recurrence and criticality. However, the cellular bioenergetic mechanisms that constrain these dynamics remain underexplored. In this review, we propose a neurometabolic criticality framework in which mitochondrial function acts as a regulatory interface between cellular metabolism and network-level brain dynamics. We synthesize evidence from contemporary theories of consciousness, the energetic demands of neuronal signaling, and emerging work showing that mitochondria regulate ATP production, calcium homeostasis, redox signaling, synaptic function and mitochondrial positioning. We argue that these mechanisms can shape the physiological conditions required for critical neural dynamics associated with conscious states. We further consider astrocytic metabolism and microtubule-dependent mitochondrial transport as complementary components of a multiscale neurometabolic system. The resulting model does not identify mitochondria with conscious experience; rather, it proposes that mitochondrial regulation constrains the dynamical regime in which consciousness-related neural activity can emerge and persist. Finally, we outline testable predictions for anesthesia, sleep and disorders of consciousness, emphasizing that selective mitochondrial manipulations should alter network complexity and perturbational responsiveness before generalized neuronal failure occurs if the hypothesis is correct.