Study Identifies Nose-to-Brain Circuit That May Explain How Nasal Breathing Influences Anxiety

Anxiety, breathing and brain regulation

Anxiety disorders are the most widespread mental disorders in humanity, affecting around 359 million people worldwide.

Research indicates that controlled breathing can help many people manage anxiety, although precisely why it works is still not fully understood.

A new study in mice, published in PNAS, has identified a previously unknown "nose-to-brain circuit" that could explain one route through which nasal breathing affects anxiety.

People have recognised breathing's emotional influence for centuries, reflected in enduring traditions including pranayama, Taoist breathing techniques and several types of meditation.

Modern research is likewise strengthening the connection between breathing patterns and brain regulation. Emerging evidence indicates that neural activity can respond to even slight breath-by-breath changes.

As the new study's authors note, slow and steady breathing can produce "profound modulatory effects on emotional states" and has clinical effectiveness in treating anxiety disorders.

Our involuntary breathing rhythm is known to originate in the brainstem. Intentionally adjusting that rhythm uses a frontal cortico-brainstem ‘top-down’ pathway, named because it enables us to consciously override an autonomic function such as breathing.

Yet little is known about the precise neural processes through which either form of breathing can alter anxiety. The new study aims to address that gap and help reveal the full potential of breathing exercises as a straightforward, non-invasive anxiety treatment.

Nasal breathing and the olfactory system

Earlier studies had already provided some indications. Breathing can alter emotional states in mice regardless of its origin, including through manipulation of the top-down circuit, which imitates conscious breathing, or of the brainstem.

"This implies the existence of a nonconscious body-brain interaction for breathing-emotion regulation, in addition to volitional control," the authors write.

Slow breathing through the nose appears to reduce anxiety more effectively than slow mouth breathing, suggesting the nose has a distinct role in emotional regulation. The rhythm of nasal breathing has also been found to synchronise brain oscillations in humans and rodents alike.

Specialised cells within the nasal cavity, known as olfactory sensory neurons (OSNs), may be central to this process. OSNs detect odour molecules and relay the resulting signals to the brain, but studies show that they are also mechanically sensitive to airflow in the nose.

OSN activity creates corresponding activity in the olfactory bulb, a forebrain structure linked to smell that also connects to the limbic system – a network of brain structures involved in regulating emotions and stress responses.

Together with other research, these findings point to a possible "nasal-limbic mechanism", the researchers write. Such a mechanism may enable the frequency of nasal breathing to influence OSN activity through sensory signals, which then helps regulate anxiety in the brain.

Mapping the nose-to-brain circuit

To investigate this possibility, the researchers altered the frequency of nasal sensory signals in male mice through optogenetic stimulation of OSNs. They also controlled airflow into the mice's nasal cavities using implanted cannulas.

"We leveraged optogenetics, chemogenetics, electrophysiology, fiber photometry, behavioral tests, and viral tracing to uncover the cellular and circuit mechanisms underlying this nose-emotion modulation," they write.

The identified pathway begins with OSNs, which detect nasal inhalations and transmit signals to mitral cells in the olfactory bulb. The information then reaches long-projecting interneurons in the perirhinal cortex before finally arriving at glutamatergic neurons in the posterior basolateral amygdala.

The study found that nasal airflow affects anxiety-like behaviour through this pathway in a frequency-dependent way, meaning the outcome may be influenced by how frequently air is inhaled through the nose.

The effect also works in both directions. This implies that faster breathing may intensify anxiety, just as slower breathing appears to ease it.

When the researchers chemogenetically silenced the section of the pathway running from the olfactory bulb to the perirhinal cortex, the association between nasal sensory-signal frequency and anxiety regulation disappeared.

Stimulating or suppressing the circuit produced anti-anxiety or pro-anxiety effects, respectively. Low- and high-frequency OSN stimulation produced the same respective effects.

Some mice also underwent a two-week programme of controlled, slow nasal airflow. This restored neural activity and lessened anxiety-like behaviours.

What the mouse study means for anxiety treatment

The research involved only male mice, experimentally induced stress and tightly controlled airflow and stimulation. Considerably more research will therefore be required to establish whether these effects apply to humans.

Nevertheless, the researchers suggest that slow nasal respiration – at roughly half the usual rate – may one day provide a simple, non-invasive method of treating anxiety.

The study was published in the Proceedings of the National Academy of Sciences.

This article was fact-checked by Rebecca Dyer and edited by Rebecca Dyer. Although we take pride in our process, we are only human. If you notice an error, please let us know.