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Cerebral Mechanisms Underlying Dyspnea


Dyspnea (shortness of breath) is the primary symptom of cardiopulmonary disease. When it motivates the patient to modify behavior or seek timely treatment, dyspnea can be beneficial, but in other cases causes only lost productivity, suffering, and disability. In the past two decades our laboratory has learned much about the peripheral neural pathways underlying dyspnea, but has just begun to investigate the central neural (forebrain) mechanisms. Using both positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), our lab found activation of several limbic/para-limbic structures: anterior insula, anterior cingulate, and amygdala. Because some areas are probably coincidentally activated, or are involved in behavioral response downstream of the perceptual process, fMRI and PET do not reveal which structures are actually essential to produce the sensation. To compliment the fMRI and PET studies, therefore, we now propose to study neural lesions; by examining the disruption of function caused by damage to the structures identified in fMRI and PET studies, we can infer whether the structures are essential to function. In humans, this is possible by examining changes following damage by stroke, the first scientific method used to assign function to various brain structures more than a century ago. The combination of lesion and recording studies is now more powerful and precise due to modern imaging techniques for localizing activation and localizing stroke damage. We will test air hunger perception in patients who have had recent stroke damage to the insula and other regions of interest. We will administer stimuli that produce acute air hunger, and quantify their perceptions in comparison to appropriate control subjects. We will re-test perception and diagnostic imaging after one year to determine whether recovery through neural plasticity is possible.


Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541.