New research from the Salk Institute identifies brain circuits that control voluntary breathing and emotional regulation, potentially helping develop treatments for anxiety and stress disorders.

While breathing is mostly automatic, we also have an incredible ability to self-soothe by slowing down. Throughout history, people have used slow breathing to manage emotions, and practices such as mindfulness and yoga have popularized formal techniques such as box breathing. But there is little scientific understanding of how the brain consciously regulates our breathing and whether this directly affects our anxiety and emotional state.

Groundbreaking discovery in neuroscience at Salk Institute

Neuroscientists at the Salk Institute have identified for the first time a specific brain circuit that regulates voluntary breathing. Using mice, the researchers identified a group of neurons in the frontal cortex that connect to the brainstem and control basic functions such as breathing. The findings suggest that this connection between more complex parts of the brain and the respiratory center in the lower brainstem allows us to coordinate our breathing with our current behavior and emotional state.

A recently published study Nature NeuroscienceIt identifies a new set of brain cells and molecules that can be targeted therapeutically to prevent hyperventilation and regulate anxiety, panic, or PTSD.

Potential for therapeutic use

“The body naturally regulates itself with deep breaths, so it seems almost intuitive for us to match our breathing with our emotions, but we didn’t really know how this worked in the brain,” says senior author Sun Han, associate professor and Pioneer Fund Developmental. The chair at Salk. “By identifying a specific brain mechanism responsible for slowing breathing, our discovery may provide a scientific explanation for the beneficial effects of practices such as yoga and mindfulness in alleviating negative emotions and place them on a scientific basis.”

Switching on brain circuits for breathing control

Breathing patterns and emotional state are difficult to decipher; If anxiety increases or decreases, breathing rate also increases. Despite this apparent link between emotional regulation and breathing, previous studies have only carefully investigated the subconscious mechanisms of breathing in the brainstem. Although new research began to identify top-down mechanisms of consciousness, no specific brain circuits were identified until Salk’s team solved the case.

The researchers hypothesized that the frontal cortex, which controls complex thoughts and behavior, somehow communicates with an area of ​​the brainstem called the medulla, which controls automatic breathing. To test this, they first consulted a database of neural connections and then conducted experiments to trace the connections between these different brain regions.

These early experiments revealed a potential new respiratory circuit: Neurons in a frontal region called the anterior cingulate cortex connected to an intermediate region of the brainstem in the pons, which then connected to the medulla immediately below.

Experimental Evidence for Breath Control

It was important to consider the physical connections between these brain regions, as well as the types of messages they might send to each other. For example, when the medulla oblongata is active, it initiates breathing. However, messages from the pons actually slow down the respiratory rate by inhibiting activity in the medulla. Khan’s team hypothesized that certain emotions or behaviors might cause cortical neurons to activate the pontine, which would reduce activity in the medulla, leading to slower breathing.

To test this, researchers recorded brain activity in mice during breathing-altering behaviors such as sniffing, swimming, and drinking, as well as conditions that induce fear and anxiety. They also used a technique called optogenetics to turn parts of this brain circuit on and off in different emotional and behavioral contexts by measuring the animals’ breathing and behavior.

Their findings confirmed that when the connection between the cerebral cortex and pons was activated, mice were calmer and breathed slower, but when the mice were in anxiety-provoking situations, this connection decreased and breathing rate increased. What’s more, when the researchers artificially activated this cortex-pons-brain layer circuit, the animals’ breathing slowed and they showed fewer signs of anxiety. On the other hand, when the researchers turned off this circuit, they found that breathing rates increased and the mice became more anxious.

Overall, this anterior cingulate cortex-pontine-brain layer supported voluntary coordination of respiratory rate with behavioral and emotional states.

Implications and future research directions

“Our findings made me wonder: Could we develop drugs that would activate these neurons and manually slow our breathing or prevent hyperventilation in panic disorder?” says the study’s first author, Gino Zhang, a senior scientist in Khan’s lab. “My sister, who is 3 years younger than me, has suffered from panic disorder for many years. She continues to inspire my research questions and my determination to answer them.”

Researchers will continue to analyze the circuit to determine whether drugs can activate it to slow breathing on command. The team is also trying to find circuit-to-circuit feedback fast They believe breathing is also likely related to emotions. They hope their findings will lead to long-term solutions that inspire people with anxiety, stress and panic disorders to explore and give back.

“I want to use these findings to develop a yoga pill,” says Khan. “It may seem silly, and it will take years to translate our work into a commercial drug, but we now have a brain circuit that is potentially targetable for therapeutics that can instantly slow breathing and induce a calm, meditative state.”