Interoception and Neural Control of Homeostasis

Balance

The University of Iowa has a rich history of accomplishments in sensory signaling; autonomic, cardiovascular and respiratory regulation; control of body homeostasis; and effects of interoception on higher brain functions.

There are long-running collaborations between basic, clinical and translational researchers working in these areas. While most of the programs have been in the area of cardiovascular/autonomic regulation, other prominent laboratories are studying visceral sensation (interoception), neural control of metabolism and respiration, effects of interoception on higher brain centers/functions, and forebrain influences on body homeostasis. Major areas of investigation are summarized below.

Sensory Signaling, including ion channels and neuromodulators mediating sensory transduction and changes in excitability of sensory neurons that influence autonomic outflow and organ system function. These include baroreceptor and chemoreceptor afferents, central respiratory chemoreceptors, and vagal and spinal afferents innervating heart, viscera and skeletal muscle.

Control of Cardiovascular Function, Breathing and Metabolism is explored at molecular, cellular and physiological levels with emphasis on sensory, brainstem, hypothalamic and forebrain neural circuits. Mechanisms of dysregulation in aging, prematurity/development, and diseases including hypertension, heart failure, obesity, diabetes, neuromuscular disorders, and chronic pain are under investigation. For many of these, activation of the renin-angiotensin-aldosterone system, adipokines, oxidative stress and inflammation are a major focus. Distinctive features of cardiovascular neurophysiology at Iowa are the use of sophisticated techniques such as microneurography for direct measurement of sympathetic nerve activity in humans and interactive studies in animals and humans.

Neural Mechanisms of Cardio-Respiratory Failure and Sudden Death: Neural mechanisms leading to impaired arousal, hypoventilation, autonomic imbalance and subsequent sudden death are investigated in experimental models and patients including sudden unexplained death in epilepsy (SUDEP), sudden infant death syndrome, and sleep disorders. These mechanisms may contribute to cardiac arrhythmias, inadequate ventilation/oxygenation and sudden death in other cardiorespiratory diseases including sleep apnea.

Interoception and Higher Brain Functions: Several UI laboratories are investigating central mechanisms by which visceral sensation and other neural or humoral inputs to the brain influence higher brain functions, including decision making, memory, psychological traits, personality and mood. Experimental approaches include study of human and animal subjects with defined brain lesions, neuro-imaging and behavioral assays. The association of sympathovagal balance with particular psychological traits in different human populations is also under investigation.

​Therapies Targeting Brain and Autonomic Nervous System: Investigators working in each of the four areas summarized above are developing novel pharmacological, gene-based, and device-based therapies for a variety of diseases and disorders. The latter includes use of deep brain, spinal cord, and vagus nerve stimulation in animal models and patients. Clinical and pre-clinical trials using these devices are ongoing.

The autonomic nervous system (ANS) has been neglected in medical education, reflecting in part its lack of a 'home' among the medical specialties. The major specialties (e.g., cardiology, neurology, gastroenterology, nephrology) focus on specific organ systems. Notably, the ANS is critically important in the regulation of essentially all organ systems, and consequently its dysregulation adversely and broadly affects homeostasis. Autonomic dysregulation is a major cause of morbidity and mortality in diverse disorders and diseases.

The importance of the ANS in human health and disease is increasingly being recognized by the larger scientific community. Recent advances have ignited interest in developing new therapies that target the ANS. The depth and breadth of expertise of the interoception/neural control of homeostasis’ research groups at the University of Iowa uniquely positions us to lead the field, in terms of both basic science discovery and translation of new knowledge to clinical therapies. Development of a clinical ANS fellowship program will increase clinician involvement. Interactions between the research groups are sure to generate new PPGs and other program and training grants.

The expertise of investigators crosses over into the other neuroscience thematic groups, most notably pain, aging mind and brain and neurodegenerative diseases, neuroimaging, behavioral and cognitive neuroscience and molecular psychiatry: mechanisms of behavior and disease. The Iowa Neuroscience Institute will facilitate interactions between basic scientists and clinicians and between disciplines, underscoring the importance of the integrated whole in program development and in advancing the science and clinical care.

Participating Research Centers, Projects and Programs