ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: Proc Natl Acad Sci U S A. 2019; 116(52): 26321-8. PMID: 31871146.

The ‘mind–body connection’ is essential for normal organ function and is viewed as the basis for psychosomatic disorders. There is abundant evidence that shows how the mind or mental processes influence our health and well-being, as well as the negative impact of emotional stress on the gastrointestinal, cardiovascular, metabolic and immune systems. The connection between the central nervous system and internal organs is mediated by sympathetic and parasympathetic subdivisions of the autonomic nervous system. Although ample information is available about the neural connections that link autonomic output from centers in the brainstem and spinal cord to specific organs (1), the neural circuits that link higher brain function and central sites (e.g., the cerebral cortex) to autonomic output and organ function have not been clearly defined (2). Specific questions that have not been answered include the following: How does the mind (conceptually associated with the cerebral cortex) influence autonomic and endocrine systems that control internal organs? Also, which regions of the cerebral cortex represent the origin of descending commands to direct organ function?

To address these questions, Dum et al. used transneuronal transport of rabies virus (RV) in monkeys and rats to identify regions of cerebral cortex that have multisynaptic connections with a major sympathetic effector, the adrenal medulla. In rats, the authors also examined multisynaptic connections with the kidney. RV is transported transneuronally in the retrograde direction in a time-dependent fashion. By varying of the survival time, the extent of transport can be limited to 1st-order (sympathetic preganglionic 1 neurons), 2nd-order (spinal interneurons, brainstem, hypothalamus), 3rd-order (cerebral cortex) or 4th-order neurons (neurons at multiple sites, including cortical layers II–IV and VI) (3). The power of transneuronal tracing with RV 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.

The authors found that in monkeys, the cortical influence over the adrenal medulla originates from 3 distinct networks that are involved in movement, cognition and affect. Each of these networks has a human equivalent. One clear implication of this organization is that the sympathetic responses that occur during activities such as exercise, the performance of demanding cognitive tasks, and the experience of emotions are generated by neural activity from the same cortical areas that are responsible for these behaviors. The largest influence originates from a motor network that includes all 7 motor areas in the frontal lobe. These motor areas are involved in all aspects of skeleto-motor control, from response selection to motor preparation and movement execution. The motor areas provide a link between body movement and the modulation of stress. The cognitive and affective networks are located in regions of the cingulate cortex. They provide a link between how we think and feel and the function of the adrenal medulla. Together, the 3 networks can mediate the effects of stress and depression on organ function and provide a concrete neural substrate for some psychosomatic illnesses. In rats, cortical influences over the adrenal medulla and the kidney originate mainly from 2 motor areas and adjacent somatosensory cortex. The cognitive and affective networks present in monkeys are largely absent in rats. Thus, nonhuman primate research is essential to understand the neural substrate that links cognition and affect to the function of internal organs. These observations provide a network perspective on the neuroanatomical organization of the cortical influences over the sympathetic nervous system.

References:

1. Ulrich-Lai YM, Herman JP. Neural regulation of endocrine and autonomic stress responses. Nat Rev Neurosci. 2009; 10(6): 397–409.

2. Williamson JW, Fadel PJ, Mitchell JH. New insights into central cardiovascular control during exercise in humans: a central command update. Exp Physiol. 2006; 91(1): 51–8.

3. Kelly RM, Strick PL. Rabies as a transneuronal tracer of circuits in the central nervous system. J Neurosci Methods. 2000; 103(1): 63–71.