Respiratory regulation comprises respiratory rhythmogenesis, formation of the respiratory motor pattern, control of blood oxygen and carbon dioxide, increase of minute ventilation during physical activity, adaptation of respiration to the sleep-wake cycle, coordination of breathing with swallowing, cough, sneezing, choking and voluntary activity such as speech or singing. Other factors such as growth and maturation, emotion, pregnancy, injury, disease, body temperature, pain and aging lead to changes in respiration. The presence of a respiratory rhythm generator in the brainstem is now known to be a common feature of all vertebrates. Knowledge about respiratory regulation is mainly derived from animal models, but respiratory regulation in humans is subject to an increasing number of physiological, electrophysiological, neuroradiographic, histopathological and genetic studies. This chapter provides an overview of respiratory regulation, focused on neuroanatomical, neurophysiological and clinical apsects.

In times past, an inquisitive physician-scientist must have pondered these questions: How do we unknowingly breathe? What brain structures control our breathing? Why is breathing so perfectly rhythmic? Is there a lung-brain communication, and if so, how? But an even more fundamental question must have been: how much brain injury can one sustain before breathing stops?

It took two centuries (more or less) to answer the above-mentioned questions and gradually add small pieces to a large (still incomplete) puzzle. The respiratory center in the brainstem was identified and characterized in the late 1800s and early 1900s. Similarly, the function of the respiratory muscles and its neural connection with cranial nerves (CN) became better known.

This chapter recounts the history of the neurology of breathing and, thus, the discovery of the respiratory center and the respiratory mechanics. Sections of the chapter review experimental and clinical discoveries of those parts of the central and the peripheral nervous system involved with breathing while acknowledging their interplay.