Cerebral Mechanisms Underlying Dyspnea

描述（申请人提供）：呼吸困难（呼吸短促）是心肺疾病的主要症状。当它促使患者改变行为或寻求及时治疗时，呼吸困难可能是有益的，但在其他情况下，只会导致生产力下降、痛苦和残疾。在过去的二十年里，我们的实验室已经了解了很多关于呼吸困难的外周神经通路，但刚刚开始研究中枢神经（前脑）机制。利用正电子发射断层扫描（PET）和功能性磁共振成像（fMRI），我们的实验室发现了几个边缘/副边缘结构的激活：前岛，前扣带和杏仁核。因为有些区域可能碰巧被激活了，或者参与了感知过程下游的行为反应，所以fMRI和PET并没有揭示哪些结构对产生这种感觉是必不可少的。因此，为了补充功能磁共振成像和PET研究，我们现在建议研究神经病变；通过检查功能磁共振成像和PET研究中发现的结构损伤引起的功能破坏，我们可以推断这些结构是否对功能至关重要。对人类来说，这可以通过检查中风损伤后的变化来实现，这是一个多世纪前第一个用于给各种大脑结构分配功能的科学方法。由于用于定位激活和脑卒中损伤的现代成像技术，病变和记录研究的结合现在更加强大和精确。我们将测试那些最近中风损伤了脑岛和其他感兴趣区域的患者的空气饥饿感知。我们将实施产生急性空气饥饿的刺激，并将其感知量化，与适当的对照受试者进行比较。我们将在一年后重新测试感知和诊断成像，以确定是否有可能通过神经可塑性恢复。

DESCRIPTION (provided by applicant): 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.