NIH research projects on interoception to improve understanding of brain-body function

The National Institutes of Health (NIH) is awarding seven projects a total of $18.15 million over five years for a new effort focused on interoception—the ways in which organisms sense and regulate signals within their bodies. Interoception is not well understood and is a new area of research focus for NIH. This coordinated effort, which involves multiple NIH Institutes and Centers, will address critical knowledge gaps and challenges in understanding interoception that are not tackled by other major NIH research initiatives.

The interoception research effort is part of NIH’s Blueprint for Neuroscience Research, and the seven studies receiving grants are expected to advance researchers’ understanding of nervous system function and disorders and the role of interoception in human health.

“Dysfunctions in interoception may play important roles in many neurological, psychiatric, and behavioral disorders,” said Helene M. Langevin, M.D., director of NIH’s National Center for Complementary and Integrative Health (NCCIH). “Gaining a better understanding of how interoception works may help us develop better ways to treat these conditions.”

The Blueprint for Neuroscience Research is a collaborative framework through which 14 NIH Institutes, Centers, and Offices, including NCCIH, jointly support research on the nervous system. The seven projects funded through this award will study the neural circuits involved in functional communication between organ systems and the brain for processes such as digestion, metabolism, and breathing in experimental model systems. They will also seek to understand the health consequences of disrupting signals between the brain and these organ systems.

“Research is needed to understand how a host of bodily functions interact with our neural circuits to determine ‘how we feel,’ and how neural activity automatically modulates critical body functions on a continuous basis. Understanding the integration of neural systems with our bodies may lead to treatment for a host of illnesses, and help many to ‘feel better’,” said Walter Koroshetz, M.D., director of the National Institute on Neurological Disorders and Stroke (NINDS).

The seven projects funded by the Blueprint for Neuroscience Research are:

• Functional Neural Circuits of Stomach-Brain Interoception; University of Michigan at Ann Arbor, Ann Arbor, Michigan: Zhongming Liu, Ph.D. and Jiande Chen, Ph.D. This project will map the two-way communication pathways between the brain and the stomach. It will also examine how nutrients and other stomach stimuli affect brain activity as well as study the regions of the brain that send signals to control gastric function. (Grant # R01 AT011665-01)
• Dissecting the Interoception Circuit That Controls Airway Constriction; University of California, San Diego, La Jolla, California: Xin Sun, Ph.D. This project will map the neural circuits by which signals travel between the lungs and the brain when an allergen is detected. It also seeks to determine which neurons are activated by signals in the peripheral ganglia and brain regions including the nucleus of the solitary tract, among others. It will use various stimuli to assess gain and loss of lung function relating to key vagal, spinal, and brain connections. (Grant # R01 AT011676-01)
• Metabolic Changes: Connecting Temperature Sensing Neurons to Sympathetic Adipose Tissue Stimulation; Louisiana State University Pennington Biomedical Research Center, Baton Rouge, Louisiana: Heike Muenzberg-Gruening, Ph.D. This project will investigate how the brain and adipose tissues communicate using the sympathetic nervous system to regulate leptin hormone levels. It will use cutting-edge techniques to identify new excitatory and inhibitory neural circuits to brown and white adipose tissue. It will also study how various physiological conditions—high versus low body temperature, fasting versus fed states—influence interactions between adipose tissues and areas of the brain involved in temperature control and taste perception. (Grant # R01 AT011683-01)
• Functional Identification of Vagal Sensory Neurons Innervating the Liver; Albert Einstein College of Medicine, Bronx, New York: Young-Hwan Jo, Ph.D. This project will map the pathway through which the liver and the brain communicate using the sympathetic nervous system to regulate the body’s glucose production, metabolism, and control processes and direct other functions governed by the liver. It will also explore the potential effects of disruptions in this pathway. (Grant # R01 AT011653-01)
• Dissecting Neural Circuits for Breathing Patterns; University of Michigan at Ann Arbor, Ann Arbor, Michigan: Peng Li, Ph.D. This project seeks to understand if distinct brainstem neurons and neural circuits are central in the control of two respiratory reflexes that protect the airways during breathing: sighing and coughing. It will also study brain circuit responses to signals associated with these reflexes. By identifying the cells and molecules involved in this signaling, the project expects to demonstrate how the brain processes interoceptive signals related to sighing and coughing. (Grant # R01 AT011652-01)
• Unravelling Lung Interoception and Its Functional Consequence in the Developing Ovine Lung; Loma Linda University, Loma Linda, California: Arlin B. Blood, Ph.D. and Christopher G. Wilson, Ph.D. This project will investigate the role of intrinsic lung interoceptors and their circuits in the normal development of the lung and central respiratory networks. It will map the pulmonary interoceptor circuitry from the lung to the brain as well as explore the potential effects of disruptions in this pathway on lung structure and function during the fetal and newborn stages of life. (Grant # R01 AT011691-01)
• Spinal Sensory Ganglia and Gut Sensation; Icahn School of Medicine at Mount Sinai, New York, New York: Ivan De Araujo, Ph.D. This project will study how the body uses sensory nerves in the spine to send signals to the lateral reticular nucleus area of the brain about changes in the gut such as distension. It will also investigate how stomach-spine-brain pathways influence brain circuits in the parietal cortex, insular cortex, and orbitofrontal cortex as well as functions such as the reward response in the brain. (Grant # R01 AT011697-01)  

“Interoceptive processes play important roles in a range of different cognitive and emotional behaviors. Basic research studies, such as those supported under the Blueprint Initiative, will provide the foundational anatomical and functional data needed to further our understanding of interoception, and to foster future studies focusing on how dysfunction in interoceptive pathways might contribute to mental illnesses and other brain disorders,” said Joshua A. Gordon, M.D., Ph.D., director of the National Institute of Mental Health.

Read more about the Blueprint for Neuroscience Research in the Trends in Neurosciences Editorial Special Issue: The Neuroscience of Interoception at https://www.cell.com/trends/neurosciences/fulltext/S0166-2236(20)30270-8.