Human forebrain neural synchronization and entrainment to breathing during wakefulness, sleep, and external mechanical ventilation.

The ability of the forebrain to track and integrate respiratory signals, a process known as breathing interoception, is critical for detecting respiratory threats and ensuring survival, yet its neural mechanisms remain largely unknown. Using human intracranial recordings, we identified widespread synchronization between forebrain neural oscillations and breathing rhythms across wakefulness, sleep, and external mechanical ventilation. During wakefulness, localized sites within known interoceptive regions such as insula, somatosensory cortex, anterior cingulate cortex, and amygdala robustly synchronized with breathing, highlighting their critical roles in breathing interoception. During sleep, forebrain synchronization with breathing decreased, while persisting in the amygdala and hippocampus, which may support vigilance and memory consolidation. In contrast to rodents, nasal airflow was not required for this synchronization, implicating multiple afferent pathways in respiratory interoception and possible unique evolutionary changes in humans. When breathing was driven by an external mechanical ventilator, the imposed breathing rhythm directly entrained forebrain activity, indicating a causal link. Notably, ventilator-driven slow, deep breathing entrained more forebrain sites, suggesting a potential mechanism through which breath-based practices might influence emotion and cognition. Together, these findings redefine breathing interoception as a pervasive influence within the forebrain, with implications for understanding disorders of respiratory awareness, emotional regulation, and cognitive health.