As to the effects of a unilateral brainstem lesion on ventilation, numerous cases of hypoventilation or total loss of automatic ventilation (“Ondine’s curse”—see further on) have been recorded (Bogousslavsky and colleagues). We have observed several such remarkable cases as well, in most instances caused by a large lateral medullary infarction. If the neural oscillators on each side were totally independent, such a syndrome should not be possible. The likely explanation is that a unilateral lesion interrupts the connections between each of the paired groups of nuclei, which normally synchronize the two sides in the generation of rhythmic bursts of excitatory impulses to spinal motor neurons. It is of interest that in a case of a delimited metastasis to the NTS there was no apparent impact on the breathing pattern until a terminal respiratory arrest (Rhodes and Wightman).
Voluntary Control of Breathing
During speech, swallowing, breathholding, or voluntary hyperventilation, the automaticity of the brainstem mechanisms of respiration is arrested in favor of reflexive or of conscious control of diaphragmatic contraction. The observations of Colebatch and coworkers, using PET scanning, indicate that voluntary control of breathing is associated with activity in the motor and premotor cortex. The experiments of Maskill and associates demonstrated that magnetic cortical stimulation of a region near the cranial vertex activates the diaphragm. Although automatic and voluntary breathing utilize the same pools of cervical motor neurons that give rise to the phrenic nerves, the descending cortical pathways for voluntary breathing are distinct from those utilized by automatic brainstem mechanisms as noted earlier. It is not known whether the voluntary signal bypasses the brainstem mechanisms or is possibly integrated there. When both dorsal descending tracts subserving voluntary control are interrupted, as in the “locked-in syndrome,” the independent, automatic respiratory system in the medulla is capable of maintaining an almost perfectly regular breathing rate of 16 per minute with uniform tidal volumes.
These essential facts do not fully depict the rich interactions between the neuronal groups governing respiration and those for laryngeal and glottic activity that come into play during such coordinated acts as swallowing, sneezing, coughing, and speaking. The brainstem regions that hold breathing in abeyance while swallowing occurs are pertinent to aspiration, a common feature of many neurologic diseases, as discussed further on. The drive applied to these systems is damped in processes such as Parkinson disease, causing discoordination between breathing and swallowing, and may contribute to the problem of aspiration, as also discussed further on.
A number of signals that modulate respiratory drive originate in chemoreceptors located in the carotid artery. These receptors are influenced both by changes in pH and by hypoxia. Chemoreceptor afferents pass along the carotid sinus nerves, which join the glossopharyngeal nerves and terminate in the NTS. Aortic body receptors, which are less important as detectors of hypoxia, send afferent volleys to the medulla through the aortic nerves, which join the vagus nerves. There are also chemoreceptors in the brainstem, but their precise location is uncertain. Their main locus is thought to be in the ventral medulla, but other areas that are responsive to changes in pH have been demonstrated in animals. What is clear is that these regions are sensitive not to the pH of CSF, as had been thought, but to the pH of the extracellular fluid of the medulla.