March 2, 2001
Volume XXXIV, No. 9



Newly Granted


PET images reveal brain's response to hunger for air

CO2 Stimulation and Breathlessness PET scans 1. CO2 inhalation strongly activates the amygdala (left).
2. Breathlessness strongly activates the anterior cingulate cortex (right).

Texan and Australian researchers have identified, for the first time, key brain circuits that activate when a person feels short of breath. The research ultimately may help explain the severity and frequency of breathlessness in conditions such as asthma, congestive heart failure, emphysema and panic disorder.

Collaborators from the Health Science Center, the Southwest Foundation for Biomedical Research and the University of Melbourne's Howard Florey Institute reported their findings in the Feb. 13 issue of the Proceedings of the National Academy of Sciences. "Of keen interest is the identification of distinct neural circuits mediating automatic respiration and conscious perception of breathlessness," said Dr. Stephen Brannan, assistant professor of psychiatry at the Health Science Center.

The journal included three papers by the group. "Each paper introduces a new concept," said Dr. Mario Liotti, assistant professor of radiology at UTHSC. "In the first paper, the novel finding is the demonstration of a major role for the amygdala in the automatic regulation of breathing. The second paper reveals for the first time the prominent involvement of the anterior cingulate cortex in breathlessness. The third paper unveils a major contribution of the cerebellum to respiratory regulation."

The scientists used an advanced neuroimaging technique called positron emission tomography (PET) to study changes in brain activity during perceived air hunger. They induced breathlessness in healthy volunteers by adding a small amount of carbon dioxide (CO2) to the subjects' inspired air. The resulting PET images revealed consistent blood flow changes (a measure of brain activity) in the amygdala, anterior cingulate cortex, cerebellum and other brain areas. These changes then were correlated with measures of the participants' physiological and subjective responses to better characterize the brain circuitry involved in unconscious and conscious detection of air hunger.

The amygdala, a brain structure that is present in all animals and regulates the subconscious ability to perceive threat, was strongly activated by CO2 inhalation. However, when subjects felt breathless, blood flow to the anterior cingulate cortex increased dramatically. "We believe this reflects a key role for the anterior cingulate in mediating conscious awareness of breathlessness," stated Dr. Liotti.

"Our physiological drives run on autopilot to a certain point," continued Dr. Brannan. "We breathe without thinking; we eat when it seems time; we drink when we feel thirsty. What we have identified here is part of an adaptive brain circuit involved in automatic respiratory control and conscious perception of air hunger. The amygdala continuously senses our internal states and detects potential threats to our survival. The anterior cingulate sounds the alarm when there is conscious perception of immediate danger."

The current studies build upon previous work by Dr. Derek Denton, a renowned physiologist, founding director of Melbourne's Howard Florey Institute of Experimental Physiology and Medicine, and a member of the National Academy of Sciences. Dr. Denton espouses a new theory of consciousness. "Consciousness evolved as primal emotions generated by sensors of the basic vegetative systems of the body," he said. "These include hunger for air, thirst, hunger and pain, and are inexorably melded with compelling specific intentions such as fighting to breathe."

Breathlessness is a dominant and distressing symptom in a number of common and important illnesses, including asthma, congestive heart failure, emphysema and panic disorder. It can complicate the course and management of these disorders, resulting in unnecessary suffering and emergency room visits. However, patients can be taught to control their emotional responses when shortness of breath occurs, suggesting a possible "learned" modification of the brain's instinctive response. A better understanding of the emotional and conscious response to breathlessness might lead to improved management of these conditions and better outcomes for patients.

"Our studies to date identify these neural mechanisms operating in normal subjects," stated Dr. Brannan. "We suspect that abnormalities occur in these circuits in subjects with panic disorder. This suggests a direction for future studies."

The international team of neuroscientists, physiologists and psychiatrists conducted this series of experiments at the Research Imaging Center in San Antonio. "Such a complex study would have been impossible without the combined efforts of experts from all these disciplines," said Dr. Peter T. Fox, director of the center. The Research Imaging Center is one of the world's leading neuroimaging facilities and is home to numerous research collaborations aimed at mapping the brain and its function in health and disease. The Health Science Center, the South Texas Veterans Health Care System and the U.S. Air Force jointly own the PET system.

Glossary of Terms

Amygdala - an almond-shaped mass of gray matter in the temporal lobe; part of the limbic system; implicated in the detection of threat and the processes involved in emotional learning; commonly associated with "flight or fight" responses.

Anterior cingulate cortex - a crescent-shaped mass of gray matter found in the midline of the brain; part of the limbic system; involved in the integration of emotion and cognition.

Cerebellum - part of the brain situated just above the brain stem; previously found to be involved in the coordination of muscles and maintenance of bodily equilibrium; recently shown to play a part in attention, cognition, sensory processing and breathing.

PET - short for Positron Emission Tomography; imaging system that detects changes in the glucose utilization, oxygen use and blood flow in tissues; allows production of images showing the changing activity levels of structures in the brain and other parts of the body.