Breathing is automatic mainly but can be influenced by behavior and emotions. This indicates that the brain’s cortex sends signals to the brainstem’s respiratory networks, a poorly studied process.
Researchers at the Salk Institute have identified a specific brain circuit that controls voluntary breathing. They found a group of brain cells in the frontal cortex in mice that connect to the brainstem’s breathing center. This connection helps coordinate breathing with behaviors and emotions.
The study explains a new set of brain cells and molecules that could be targeted with therapeutics to prevent hyperventilation and regulate anxiety, panic, or post-traumatic stress disorders.
Senior author Sung Han, associate professor and Pioneer Fund Developmental Chair at Salk, said, “The body naturally regulates itself with deep breaths, so aligning our breathing with our emotions seems almost intuitive to us—but we didn’t know how this worked in the brain.”
“By uncovering a specific brain mechanism responsible for slowing breathing, our discovery may offer a scientific explanation for the beneficial effects of yoga and mindfulness on alleviating negative emotions, grounding them further in science.”
Breathing patterns and emotional states are closely linked, but previous studies have mostly focused on subconscious breathing mechanisms in the brainstem. While newer research explored conscious control, the Salk team identified specific brain circuits when investigating.
Credit: Salk Institute
They hypothesized that the frontal cortex, which manages complex behaviors, communicates with the medulla, the brainstem area controlling automatic breathing. Through experiments and a neural connectivity database, they identified a potential new circuit: neurons in the anterior cingulate cortex connect to the pons, which connect to the medulla.
The researchers explored the physical connections between brain areas and the messages they send. They hypothesized that emotions or behaviors could trigger cortical neurons to activate the pons, which inhibits the medulla and slows breathing.
To test this, they recorded brain activity in mice during activities that affect breathing, like sniffing, swimming, and drinking, as well as during fear and anxiety. Using optogenetics, they manipulated parts of the brain circuit to observe how these changes influenced breathing and behavior.
The researchers found that activating the cortex-pons connection calmed mice and slowed their breathing, while anxiety reduced this communication, increasing breathing rates. When they artificially activated the circuit, the mice’s breathing slowed, and anxiety decreased; conversely, shutting it off led to faster breathing and more anxiety.
These results confirm that the anterior cingulate cortex-pons-medulla circuit is key in voluntarily coordinating breathing with emotional and behavioral states.
The study’s first author, Jinho Jhang, a senior research associate in Han’s lab, said, “Our findings got me thinking: Could we develop drugs to activate these neurons and manually slow our breathing or prevent hyperventilation in panic disorder?”
“My sister, three years younger than me, has suffered from panic disorder for many years. She continues inspiring my research questions and dedication to answering them.”
The researchers plan to investigate the circuit further to see if drugs could be used to activate it and control breathing. They also explore the possibility of a “fast breathing” circuit, likely linked to emotion. Their ultimate goal is to develop long-term solutions for people with anxiety, stress, and panic disorders, which motivated their research.
Han said, “I want to use these findings to design a yoga pill. It may sound silly, and translating our work into a marketable drug will take years. Still, we now have a potentially targetable brain circuit for creating therapeutics that could instantly slow breathing and initiate a peaceful, meditative state.”
Journal Reference:
- Jhang, J., Park, S., Liu, S. et al. A top-down slow breathing circuit that alleviates negative affect in mice. Nat Neurosci (2024). DOI: 10.1038/s41593-024-01799-w