Placebo effects, exercise highs, getting sick when you’re stressed out—the popular press and the scientific literature alike are replete with examples of how the mind or mental processes influence our health and well-being. This “mind-body connection” is essential for normal organ function and also is viewed as the basis for psychosomatic disorders. Yet the concept that our thoughts can influence the function of a variety of organ systems is often viewed with some skepticism, in part because it has lacked a firm biological basis.
That’s changing. We are now starting to provide the scientific evidence to reveal the important dynamic between our brains and our bodies. And in the process, we are learning how the brains of primates are different from those of other animals—a reality that has important implications for research into the causes and treatment of neurologic disorders.
The connection between the central nervous system and internal organs is mediated by sympathetic (fight or flight) and parasympathetic (rest and digest) subdivisions of the autonomic nervous system. We know a great deal about the neural connections that link autonomic output from centers in the brainstem and spinal cord to specific organs.
However, the neural circuits that link higher brain function and central sites, such as the cerebral cortex, to autonomic output and organ function have not been clearly defined. That’s because most conventional tracers are capable of defining only the direct inputs to and outputs from an organ and not the background web of connections that provide indirect, but meaningful, neural signals.
Our research team has overcome this challenge by using neurotropic viruses, which specifically target neurons, as transneuronal tracers. In the Proceedings of the National Academy of Sciences we recently described using a rabies virus tracer to reveal the areas of the cerebral cortex that influence the adrenal medulla of the monkey and rat, as well as rabies transport from the kidney in the rat.
In our nonhuman primate studies, we injected the rabies tracer into the adrenal medulla, a gland at the top of the kidney, and tracked its path back to brain regions involved in movement, cognition and mood. These cortical areas represent key nodes in a "stress and depression connectome." In the rat, descending influences over the adrenal medulla, as well as the kidney, originate largely from cortical motor areas. In fact, the cortical areas that are the major source of cognitive control in the monkey appear to be absent in the rat. Thus, the mind-body connection in primates is more widespread and complex than in rats.
These observations provide a new perspective on the neuroanatomical organization of the cortical influences over the sympathetic nervous system. The power of transneuronal tracing with rabies virus is that it reveals the entire extent of the cortical influence over this system. In this way, it identifies the potential origins of the elusive “central commands” from the cerebral cortex.
This general experimental paradigm is one that can be applied to reveal multisynaptic circuits in a wide variety of networks. For example, rabies tracer injections into limb muscles can reveal the networks involved in the voluntary control of movement; tracer injections into laryngeal muscles can reveal the central circuits responsible for vocalization; tracer injections into the heart and stomach can reveal circuits responsible for the central control over the cardiovascular and gastrointestinal systems; and tracer injections into the spleen can reveal the central neural circuits that influence immune function.
The adrenal medulla can be considered as our “first responder” in situations requiring fight or flight. Thus, one might expect the input to it to be highly conserved across species. Indeed, the cortical motor areas are a major source of input to the adrenal medulla in both the rat and the monkey. But here the similarities end. The primary motor cortex, primary somatosensory cortex and a single secondary motor area account for about 93 percent of the cortical input to the adrenal medulla in the rat. In contrast, the monkey adrenal medulla receives input not only from cortical motor areas (about 53 percent) but also from cortical areas involved in cognition and affect (about 35 percent).
Furthermore, the monkey adrenal medulla receives substantial input from motor areas on the medial wall of the hemisphere that don’t exist in the rat. Thus, the monkey adrenal medulla is the target of output from a broader set of cortical areas and is influenced by a more diverse set of behaviors. Each network found in the monkey has a human equivalent. Taken together, these observations suggest that nonhuman primate models are essential for examining the influences of higher-order aspects of movement, cognition and mood on sympathetic function.
Modern medicine has generally viewed the concept of psychosomatic disease with suspicion. This is partly because of a lack of information about the neural networks that connect the "mind," conceptually associated with the cerebral cortex, with autonomic and endocrine systems that regulate internal organs. As a consequence, some definitions of psychosomatic disorders include dismissive descriptions such as, “all in the mind,” “irrational" or “subconscious.”
Our findings should correct this perspective because they provide a concrete neural substrate for cortical areas involved in movement, cognition and affect to influence a major sympathetic effector, the adrenal medulla. We suggest the adoption of the view reflected in the dialogue at the end of Harry Potter and the Deathly Hallows where Harry says, “Tell me one last thing, is this real? Or has this been happening inside my head?” Professor Dumbledore replies, “Of course it is happening inside your head, Harry, but why on earth should that mean that it is not real?”