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The parasympathetic nervous system is phylogenetically ancient. In humans, the vagus nerve is the brain’s only pathway for bidirectional parasympathetic signaling with the thorax, abdomen, and upper pelvis. Unsurprisingly, the vagus nerve has played a significant role in scientific discovery and therapeutic applications, attracting the attention of Galen, Darwin, and Pavlov, among others. For example, Otto Loewi used the vagus nerve to gather data that confirmed Santiago Ramón y Cajal’s Neuron Doctrine. This intensive focus has led to a number of clinical advances related to vagus nerve function, including theories about mind–body connections. Interestingly, reducing vagus nerve activity has been a successful strategy for some clinical conditions, such as peptic ulcer disease and obesity. In other conditions, increasing vagus nerve activity has been successful at improving patient outcomes, for example, in refractory seizures, drug-resistant depression, and stroke recovery; in each of these three conditions, the FDA has approved vagus nerve stimulation as a therapeutic intervention. Potential future developments in the therapeutic modulation of vagus nerve activity are discussed, including its role in perinatal brain development; manipulation of the vagus nerve as a portal for CNS access, as suggested in Parkinson’s disease; and closed-loop systems that modulate vagus nerve activity in response to measurement of various forms of signaling, an approach that would be aided by the capacity to directly measure activity in individual vagus nerves.
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Steven C. Cramer (2026) studied this question.
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