Decision letter: Neural underpinning of a respiration-associated resting-state fMRI network

Abstract

What does the brain do when we breathe? Humans and other animals with lungs depend on breathing to supply their cells with oxygen for energy production. Neurons in the brain are supplied oxygen through an intricate system of blood vessels. When active, neurons consume a lot of energy and require a steady supply of oxygen-rich blood. In fact, this relationship between blood vessels and activity of neurons in the brain is so tightly linked that to study neuron activity researchers and clinicians often use an approach called functional magnetic resonance imaging (fMRI) to analyze the flow of oxygenated blood in the brain. This imaging technique allows scientists to map how active different parts of the brain are at any given time without the need for an invasive medical procedure. Unfortunately, fMRI results are affected by the cycles of inhalation and exhalation that take place while breathing, even when an individual is at rest. This is because the rate and depth of respiration can vary, resulting in the body moving unpredictably and in CO2 levels fluctuating in the brain, which can lead to changes in fMRI signals that do not correlate with neuron activity. Such misleading measurements are called ‘artifacts’. The assumption that these fMRI results do not represent real brain activity has meant that the effects of breathing on neuron activity in different parts of the brain is poorly understood. To solve this issue, Tu and Zhang performed fMRI on rats and combined the results with measurements of the depth and rate of respiration, and with electrophysiology, an approach that allowed them to directly record the electrical properties of neurons. This allowed them to map out the network of neurons that become active in response to breathing. The results show that breathing leads to a specific fMRI signal that can be distinguished from the artifacts introduced by fluctuating CO2 levels and body movements. The signal correlates with the activity of neurons measured using electrophysiology and with breathing patterns, and it disappears when the electrical activity of neurons in the brain is suppressed, even if the rats are still breathing. This suggests that breathing affects brain activity that is independent of the previously described artifacts. Future studies may focus on how the brain responds to breathing or how respiration itself is controlled by the brain, with the methods developed allowing researchers to explore regions of the brain that increase their activity while breathing. This clears the path towards investigating the neural mechanisms underlying therapies and exercises that focus on breathing.