How does the human brain detect and respond to disruptions in breathing? While animal studies have advanced our understanding of respiratory control, breathing distress in humans remains difficult to treat. It often arises not only from pulmonary lesions or brainstem dysfunction, but also from how higher brain regions interpret breathing signals shaped by emotion and experience. We recorded intracranial cortical activity in neurosurgical patients during an interoceptive task involving transient breathing challenges. Conscious detection of these disruptions was predicted by early responses in the anterior insula, which routed signals to orbitofrontal and premotor cortices for appraisal and compensation. These cortical regions preferentially encoded inspiratory effort or airflow, revealing signal-specific processing that echoes functional segregation in brainstem centers. These findings identify a dynamic insular– frontal circuit for sensing and adapting to respiratory challenges, offering insight into the neural basis of breathing awareness and its disruption in disease.

The authors have declared no competing interest.

This work was supported by the National Institutes of Health, National Heart, Lung, and Blood Institute (R01 HL163578) and the National Institute of Mental Health (P50 MH109429). No payment or services were received from any third party for any aspect of the submitted work, including study design, data collection, data analysis, manuscript preparation, or publication.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

[1]Feinstein Institutes for Medical Research, Northwell Health, Manhasset, New York, USA; [2] Zucker School of Medicine at Hofstra-Northwell, Hempstead, New York, USA; [3] Nathan Kline Institute, Orangeburg, New York, USA; [4] Northwell Health Sleep Disorders Center, Manhasset, New York, USA; [5] Sorbonne Universite, Paris F-75005, France. [6] Hopital Pitie-Salpetriere, Paris F-75013, France. Ethical approval was granted by the Institutional Review Board of the Feinstein Institutes for Medical Research, Northwell Health (IRB: 07-125). All patients provided written informed consent in accordance with the Declaration of Helsinki.

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All data produced in the present study are available upon reasonable request to the authors