Nasal Respiration Entrains Human Limbic Oscillations and Modulates Cognitive Function

Author: Christina Zelano1, Heidi Jiang2, Guangyu Zhou2, Nikita Arora2, Stephan Schuele2, Joshua Rosenow3, Jay A Gottfried2,4
1 Departments of Neurology and
2 Departments of Neurology and.
3 Neurosurgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, and.
4 Department of Psychology, Weinberg College of Arts and Sciences, Northwestern University, Evanston, Illinois 60208.
Conference/Journal: J Neurosci
Date published: 2016 Dec 7
Other: Volume ID: 36 , Issue ID: 49 , Pages: 12448-12467 , Special Notes: doi: 10.1523/JNEUROSCI.2586-16.2016. , Word Count: 357

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.

Keywords: amygdala; hippocampus; local field potential; piriform cortex; respiration; respiratory oscillations.

PMID: 27927961 PMCID: PMC5148230 DOI: 10.1523/JNEUROSCI.2586-16.2016