Functional Imaging of the Brainstem and Cortical Sites of Autonomic Control in Human Subjects


  • Vaughan G. Macefield

    Corresponding author
    1. School of Medicine, University of Western Sydney, Sydney, Australia
    2. Neuroscience Research Australia, Sydney, Australia
    • Professor of Integrative Physiology, School of Medicine, University of Western Sydney, Locked Bag 1797, Penrith, NSW 2751, Australia
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The autonomic nervous system—comprising the sympathetic, parasympathetic, and enteric branches—is classically considered to be a self-regulating system that subserves the homeostatic principles essential for life. However, it is being increasingly recognized that the components of the autonomic nervous system, while typically operating within a narrow range governed by negative feedback loops, are modules that can be “mixed and matched” to bring about a particular change in the body's physiological state. The autonomic nervous system does not operate in a blunt fashion; rather, there is differential control of each of its output arms that can further be controlled in a regional manner. Some components are fairly well understood, such as the sensorimotor loops within the enteric nervous system that coordinate the unidirectional waves of intestinal contraction underlying peristalsis, or the negative feedback loop that maintains blood pressure essentially constant via the baroreceptors acting on vasoconstrictor and cardiomotor drives. Disturbances to any of these homeostatic elements underpin many disease states, such as the selective increases in sympathetic outflow to the sweat glands in “hyperhidrosis,” or the selective loss of sudomotor drive that results in “anhidrosis.” In the first case, an increase in sweat release, typically of the hands and feet, can lead to social embarrassment, but in the second case, an inability to sweat greatly compromises thermoregulation that can precipitate dangerous fevers and death.

Of course, the operation of the autonomic nervous system is not restricted to maintaining a constant internal environment—for example, we do not know why we cry or why we sweat when we are anxious, but these changes are clearly mediated by specific components of the autonomic nervous system. Indeed, our brains appear to have commandeered all of these components as a means of emotional expression; whereas the sympathetic innervation of the skin primarily subserves thermoregulation through its actions on the blood vessels, sweat glands and hairs, vasoconstriction, sudomotor, and pilomotor drives all increase when we are scared. Conversely, when we are cold, vasoconstrictor and pilomotor drives increases while sudomotor drive decreases; when we are hot cutaneous vasoconstrictor and pilomotor drive decreases and sudomotor activity increases. How are these components brought into play and controlled?

Much has been learnt about how the autonomic nervous system is organized and controlled from studies in anaesthetized experimental animals, but studies in awake animals are few and far between. Moreover, studies in awake human subjects have mostly been limited to noninvasive studies on the effector organs of the autonomic nervous system—heart rate, blood pressure, pupillary diameter, sweat release, skin blood flow, and so forth—or invasive studies of sympathetic nerve outflow via intraneural microelectrodes or by measurement of regional noradrenaline spillover. However, little is known about the central nervous control of the autonomic nervous system in human subjects, particularly with regard to the involvement of “higher centers” in the “awake state.“

The following three contributions, based on presentations in a symposium I organized for the 2011 meeting of the International Society for Autonomic Neuroscience—held in Buzios, Brazil—each cover different aspects of higher order control of the autonomic nervous system in human subjects. The aim of the symposium was to discuss recent developments in the use of functional magnetic resonance imaging (fMRI) of the brain to identify cortical and subcortical sites of autonomic control. Although fMRI has been used widely to investigate sites of cortical and subcortical activation during various sensory, motor, or cognitive tasks, relatively little work has been done on the autonomic nervous system. This is particularly so for the brainstem—considered “tiger country” by many performing fMRI. The medulla is the oldest structure of the brain, containing nuclei that coordinate many homeostatically critical functions, such as respiration, heart rate, and blood pressure. Much of what we know of the functions of the medulla we have learnt from experiments in anaesthetized or decerebrate animals. Although its small size makes it difficult to study its function in awake humans, recent work has revealed the operation of some of its fundamental circuitry. Importantly, as we will see in the following papers, areas above the brainstem have also been shown to play key roles in control of the autonomic nervous system. It is the involvement of cortical areas especially that has allowed us to be able to exert voluntary control over the autonomic nervous system—a system that can no longer be considered simply as a primitive, automatic—some would say “robotic”—collection of neurons whose only role is to support homeostasis.