Nasal Airflow Activates Broad Regions of the Olfactory Bulb

Key Points

• Nasal breathing information is “encoded” by olfactory sensory neurons in the olfactory bulb

• Breathing activates broad regions of the olfactory bulb, with the intensity changing as total breathing volume changes

• The neural activity stimulated by nasal breathing helps explain how breathing can have immediate physiological effects throughout the body

The Breathing Diabetic Summary

The olfactory bulb (OB) and its neurons (olfactory sensory neurons, OSNs) can sense both odors and airflow.  However, previous studies have rarely examined how airflow is actually encoded by the OB and OSNs.  This study used fMRI and local field potential to figure out how airflow activity is mapped in the OB. 

They studied mice under different airflow stimulation (these can be thought of as different breathing patterns because the mechanical stimulation was occurring through their noses).  The different breathing paradigms included changing respiratory rate, changing tidal volume, or changing both rate and tidal volume while keeping the total airflow the same (that is, keeping Rate X Volume = Constant). 

The results showed that airflow stimulation activated broad regions of the OB.  Odor stimulation, on the other hand, had more localized activity maps.  Furthermore, the overall structure of the activity maps was similar regardless of which breathing paradigm was being studied.  Only the intensity of the signal changed with total airflow.  Greater total volume led to more intense activity in the OB. 

Another interesting result was that nasal airflow affected the physiological state of the mice.  Their resting heart and breathing rates slowed, and EEG power declined in specific ranges. 

These results are important because they show for the first time that nasal breathing information is encoded in the olfactory bulb.  We know that breathing can directly influence emotional state, for example, providing a calming effect.  And, there have been several studies showing a direct correlation between breathing, brain activity, memory, and behavior.  Here, we see why.   

Nasal breathing information is imprinted in the OB.  The OB then projects onto the limbic system, which regulates emotions, olfaction, and the autonomic nervous system.  This helps explain the wide-ranging benefits of slow breathing and how breathing can have such immediate effects on our physiological state.

To summarize, this is the first study to show that nasal airflow elicits broad activity maps in the olfactory bulb.  The patterns are robust and change only in intensity when total airflow is altered.  The effects of nasal respiration on the olfactory bulb are then projected on the limbic system, helping explain how breathing can quickly impact physiological state.

Abstract

Olfactory sensory neurons (OSNs) can sense both odorants and airflows. In the olfactory bulb (OB), the coding of odor information has been well studied, but the coding of mechanical stimulation is rarely investigated. Unlike odor-sensing functions of OSNs, the airflow-sensing functions of OSNs are also largely unknown. Here, the activity patterns elicited by mechanical airflow in male rat OBs were mapped using fMRI and correlated with local field potential recordings. In an attempt to reveal possible functions of airflow sensing, the relationship between airflow patterns and physiological parameters was also examined. We found the following: (1) the activity pattern in the OB evoked by airflow in the nasal cavity was more broadly distributed than patterns evoked by odors; (2) the pattern intensity increases with total airflow, while the pattern topography with total airflow remains almost unchanged; and (3) the heart rate, spontaneous respiratory rate, and electroencephalograph power in the β band decreased with regular mechanical airflow in the nasal cavity. The mapping results provide evidence that the signals elicited by mechanical airflow in OSNs are transmitted to the OB, and that the OB has the potential to code and process mechanical information. Our functional data indicate that airflow rhythm in the olfactory system can regulate the physiological and brain states, providing an explanation for the effects of breath control in meditation, yoga, and Taoism practices.

SIGNIFICANCE STATEMENT Presentation of odor information in the olfactory bulb has been well studied, but studies about breathing features are rare. Here, using blood oxygen level-dependent functional MRI for the first time in such an investigation, we explored the global activity patterns in the rat olfactory bulb elicited by airflow in the nasal cavity. We found that the activity pattern elicited by airflow is broadly distributed, with increasing pattern intensity and similar topography under increasing total airflow. Further, heart rate, spontaneous respiratory rate in the lung, and electroencephalograph power in the β band decreased with regular airflow in the nasal cavity. Our study provides further understanding of the airflow map in the olfactory bulb in vivo, and evidence for the possible mechanosensitivity functions of olfactory sensory neurons.

Journal Reference:

Wu R, Liu Y, Wang L, Li B, Xu F.  Activity patterns elicited by airflow in the olfactory bulb and their possible functions.  J Neurosci. 2017;37(44):10700-10711. doi: 10.1523/JNEUROSCI.2210-17.2017.

Nasal Nitric Oxide: Nature’s Answer to Gravity?

Key Points

• Nitric oxide redistributes blood flow in the lungs to be more uniform

• Nitric oxide increases gas exchange in the lungs

• Nasal nitric oxide might be an evolutionary adaptation to counter gravity

The Breathing Diabetic Summary

Blood flow in the lungs is essential for gas exchange and defense against infections. However, lung blood flow is not as uniform as we might think. And, although several factors account for this, gravity plays a significant role.  Gravity acts to focus blood flow toward the bottom of the lungs.  

Interestingly, in humans and higher primates, a large amount of nitric oxide (NO) is released in the nasal passages. As we learned, NO is critical for blood flow and whole-body oxygenation. The authors of this study wondered if nasal NO might also redistribute blood flow in the lungs, thus countering the effects of gravity and increasing gas exchange in the lungs. This adaptation would have allowed us to evolve into the bipedal mammals we are today.

To test this, they examined how different breathing protocols affected lung blood flow. Participants were injected with a radionuclide that acted as a passive tracer of blood flow, which could then be imaged to show relative “heat maps” of blood flow in the lungs.

Fourteen participants were broken into three groups. The first group served as a control to ensure the radiotracer imaging technique worked as intended. The second group was used to see how nasally produced NO affected lung blood flow. These participants sat in an upright position and breathed through their mouths for 20 min. The tracer was injected, and their lung blood flow was imaged. Then, they switched to nasal breathing for 10 min. Tracer was again injected imagery was taken.

The final group was used to see if NO was, in fact, the driver of lung blood flow redistribution. These participants breathed through their mouths but were given supplemental NO. If NO was the driver, mouth breathing with additional NO should result in similar blood flow redistribution as nasal breathing.

They found that nasal breathing redistributed blood flow both vertically and horizontally in the lungs, making it more uniform. The same occurred when mouth breathing with supplemental NO. Thus, NO, whether produced naturally in the nasal passages or supplemented, acts to redistribute blood flow and increase gas exchange in the lungs.

The authors hypothesize that the NO produced in the nasal passages is an evolutionary adaptation to walking upright.  The NO acts to make blood flow and gas exchange more uniform, thus countering the effects of gravity.

In summary, nasal nitric oxide counteracts the effects of gravity and makes lung blood flow more uniform in the upright position. Interestingly, this only occurs in humans and higher primates. Thus, NO production in the upper airways might have been a critical evolutionary adaptation that allowed us to walk upright.

Abstract

There are a number of evidences suggesting that lung perfusion distribution is under active regulation and determined by several factors in addition to gravity. In this work, we hypothesised that autoinhalation of nitric oxide (NO), produced in the human nasal airways, may be one important factor regulating human lung perfusion distribution in the upright position. In 15 healthy volunteers, we used single-photon emission computed tomography technique and two tracers (99mTc and 113mIn) labeled with human macroaggregated albumin to assess pulmonary blood flow distribution. In the sitting upright position, subjects first breathed NO free air through the mouth followed by the administration of the first tracer. Subjects then switched to either nasal breathing or oral breathing with the addition of exogenous NO-enriched air followed by the administration of the second tracer. Compared with oral breathing, nasal breathing induced a blood flow redistribution of approximately 4% of the total perfusion in the caudal to cranial and dorsal to ventral directions. For low perfused lung regions like the apical region, this represents a net increase of 24% in blood flow. Similar effects were obtained with the addition of exogenous NO during oral breathing, indicating that NO and not the breathing condition was responsible for the blood flow redistribution. In conclusion, these results provide evidence that autoinhalation of endogenous NO from the nasal airways may ameliorate the influence of gravity on pulmonary blood flow distribution in the upright position. The presence of nasal NO only in humans and higher primates suggest that it may be an important part of the adaptation to bipedalism.

Journal Reference:

Sánchez Crespo A, Hallberg J, Lundberg JO, Lindahl SG, Jacobsson H, Weitzberg E, Nyrén S.  Nasal nitric oxide and regulation of human pulmonary blood flow in the upright position.  J Appl Physiol.  2010;108:181–188.

Nasal breathing synchronizes brain wave activity and improves cognitive function

Key Points

• Nasal breathing synchronizes brain wave oscillations in the piriform cortex, amygdala, and hippocampus

• Nasal breathing improves cognitive function when compared to mouth breathing

• Breathing affects emotional and mental state, shifting the paradigm for why we breathe

The Breathing Diabetic Summary

It is established that emotions and mental state affect breathing.  When you’re anxious, you breathe faster and shallower.  When you’re relaxed, you breathe quiet and light.  Intuitively, I think we all know that the opposite is true too: Your breathing can affect your emotions and mental state.  However, the brain mechanisms behind this shift have remained elusive.

This study sheds light on the issue.  Intracranial EEG (iEEG) was used to assess how breathing impacts electrical oscillations in different regions of the brain.  Then, emotional recognition and memory tests were used to see how breathing impacts cognitive function.

The results showed that oscillations in the piriform cortex are directly related to nasal breathing. The piriform cortex is associated with the nose through smell, so it makes sense that nasal breathing would cause oscillations in this region (although the participants were breathing odorless air).

Interestingly, two other regions of the brain also showed these oscillations: the amygdala and hippocampus.  When breathing was switched to the mouth, however, this brainwave activity became disorganized.  Thus, nasal breathing is critical to synchronizing electrical brainwave oscillations.

If nasal breathing affects these regions of the brain, it follows that it would potentially impact cognition.  And that’s exactly what they found.

They showed participants faces expressing either fear or surprise and had them quickly decide which one it was.  When breathing through the nose, the response times were faster than when breathing through the mouth.  Additionally, the participants identified fearful faces faster during inhalation than exhalation.  This effect wasn’t present when mouth breathing. 

Next, they had the participants perform a memory task involving picture recognition.  They found that their memory retrieval was more accurate during nasal inhalation, which was not observed for mouth breathing.  However, there was not a statistically significant difference in the overall accuracy between nose and mouth breathing.

Taken together, the iEEG measurements and cognitive tasks suggest that nasal breathing promotes coherent brainwave oscillations in the piriform cortex, amygdala, and hippocampus.  This coherence leads to improved cognitive function, especially during nasal inhalation.

“We also found that the route of breathing was critical to these effects, such that cognitive performance significantly declined during oral breathing.”

We’ve already established that breathing can no longer be thought of as a 2-gas system.  Now, we might have to extend beyond gases altogether.  Breathing acts to synchronize brain activity and enhance cognitive function…but only when performed through the nose.

I think that bears repeating.  Nasal breathing synchronizes brainwave activity and enhances cognitive function.  Pretty remarkable.

Abstract

The need to breathe links the mammalian olfactory system inextricably to the respiratory rhythms that draw air through the nose. In rodents and other small animals, slow oscillations of local field potential activity are driven at the rate of breathing (∼2-12 Hz) in olfactory bulb and cortex, and faster oscillatory bursts are coupled to specific phases of the respiratory cycle. These dynamic rhythms are thought to regulate cortical excitability and coordinate network interactions, helping to shape olfactory coding, memory, and behavior. However, while respiratory oscillations are a ubiquitous hallmark of olfactory system function in animals, direct evidence for such patterns is lacking in humans. In this study, we acquired intracranial EEG data from rare patients (Ps) with medically refractory epilepsy, enabling us to test the hypothesis that cortical oscillatory activity would be entrained to the human respiratory cycle, albeit at the much slower rhythm of ∼0.16-0.33 Hz. Our results reveal that natural breathing synchronizes electrical activity in human piriform (olfactory) cortex, as well as in limbic-related brain areas, including amygdala and hippocampus. Notably, oscillatory power peaked during inspiration and dissipated when breathing was diverted from nose to mouth. Parallel behavioral experiments showed that breathing phase enhances fear discrimination and memory retrieval. Our findings provide a unique framework for understanding the pivotal role of nasal breathing in coordinating neuronal oscillations to support stimulus processing and behavior.

 SIGNIFICANCE STATEMENT:

Animal studies have long shown that olfactory oscillatory activity emerges in line with the natural rhythm of breathing, even in the absence of an odor stimulus. Whether the breathing cycle induces cortical oscillations in the human brain is poorly understood. In this study, we collected intracranial EEG data from rare patients with medically intractable epilepsy, and found evidence for respiratory entrainment of local field potential activity in human piriform cortex, amygdala, and hippocampus. These effects diminished when breathing was diverted to the mouth, highlighting the importance of nasal airflow for generating respiratory oscillations. Finally, behavioral data in healthy subjects suggest that breathing phase systematically influences cognitive tasks related to amygdala and hippocampal functions.

Journal Reference:

Zelano C, Jiang H, Zhou G, Arora N, Schuele S, Rosenow J, Gottfried JA.  Nasal Respiration Entrains Human Limbic Oscillations and Modulates Cognitive Function.  J Neurosci. 2016;36(49):12448-12467.