DEVELOPMENT AND APPLICATION OF CLINICAL OLFACTORY DIAGNOSTIC TESTS

这个项目提供了最先进的心理物理方法 对于其他中心项目，专注于嗅觉测试的开发 在临床上的实际应用及其在各种疾病中的应用 疾病状态。在实验1中，我们将继续开发和完善 临床嗅觉测试(例如，测试或气味检测、记忆和 阈值以上的强度和愉悦感)，目标是 找到一组可选的测试以包括在临床有用的 嗅觉测试电池。重测信度、易用性等因素 试验给药，双侧与单侧试验给药，以及 将探索测试之间的相互关联程度。在实验中 2、我们将对患有以下疾病的个人进行各种嗅觉测试 与神经和内分泌疾病相关的特征良好的疾病 理论或经验依据，有嗅觉障碍，以便 (I)确定这些测试在检测嗅觉方面的相对有效性 功能障碍，(Ii)确定各种测试的相关程度 在特定的患者群体中相互影响，以及(Iii)更好 了解此类疾病中嗅觉功能障碍的本质。 要研究的疾病包括家族性帕金森氏病(FPD)， 肌萎缩侧索硬化症(ALS)，多发性硬化症(MS)，多发性 梗死性痴呆(MD)、精神分裂症(SZ)、视网膜色素变性(RP)、 Usher综合征(美国)、假性甲状旁腺功能减退症(PHP)和癫痫。平板显示器 以确定遗传性帕金森病是否伴有 嗅觉障碍的程度与特发性(即散发性)帕金森病相同。 肌萎缩侧索硬化症引起人们的兴趣，因为有证据表明， ALS/PD/痴呆复合体中以ALS症状为主的患者 关岛。RP和US的选择在很大程度上是基于(I)轶事 关于这些疾病中嗅觉丧失的报道以及(Ii)它们之间的联系 眼睛和内耳有纤毛相关的病理--病理 也可能存在于嗅觉感受器细胞中。之所以选择PHP，是因为 与Gα缺陷形式相关的嗅觉问题的报告 而选择SZ和MID是因为较早 关于这些疾病中嗅觉丧失的报道以及改善的必要性 了解这一损失的性质和规模。接受治疗的患者 神经外科手术治疗顽固性癫痫样发作 我们特别感兴趣，因为这样的手术会影响大脑 与中央嗅觉处理相关的区域。在这种情况下，我们 计划比较我们的嗅觉测试在表征 手术切除前后感觉功能障碍。 重要的是，我们将确定(I)嗅觉的性质和程度 手术前鼻部两侧都存在功能障碍， (Ii)该手术对同侧和 对侧功能，(Iii)癫痫发作的第一风险年龄是否 与术前、术后嗅觉程度有关 嗅觉功能障碍，以及(Iv)是否具有嗅觉功能以及嗅觉功能达到何种程度 术后五年的变化。总的来说，这些实验 该项目的实施将进一步推动临床医学的发展 嗅觉测试，并将提供对性质和流行率的洞察 在广泛的医学疾病中的化学感觉功能障碍。

This project, which provides state-of-the-art psychophysical methodology for other Center projects, focuses on the development of olfactory tests of practical use in the clinic and their application to a variety of disease states. In Experiment 1, we will continue to develop and refine clinical olfactory tests (e.g., tests or odor detection, memory, and suprathreshold intensity and pleasantness perception), with the goal of finding an optional set of test for inclusion in a clinically-useful olfactory test battery. Such factors as test-retest reliability, ease of test administration, bilateral vs. unilateral test administration, and the degree of interrelation among tests will be explored. In experiments 2, we will administer a variety of olfactory tests to individuals with well-characterized neurological and endocrine disorders associated, on theoretical or empirical grounds, with olfactory dysfunction in order to (i) establish the relative efficacy of these tests in detecting olfactory dysfunction, (ii) determine the degree to which various tests correlate with one another in specific patient populations, and (iii) better understand the nature of the olfactory dysfunction in such disorders. Among the diseases to be studied are familial Parkinson's disease (fPD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), multi- infarct dementia (MD), schizophrenia (SZ), retinitis pigmentosa (RP), Usher's syndrome (US), pseudohypoparathyroidism (PHP) and epilepsy. fPD was chosen to determine if an inherited form of PD is accompanied by the same degree of olfactory dysfunction as idiopathic (i.e., sporadic) PD. ALS is of interest because of evidence of some olfactory dysfunction in patients with predominantly ALS symptoms in the ALS/PD/dementia complex of Guam. RP and US were selected largely on the basic of (i) anecdotal reports of olfactory loss in these disorders and (ii) their association with cilia-related pathology in the eye and inner ear--pathology which may also be present in olfactory receptor cells. PHP was chosen because of reports of olfactory problems associated with G alpha-deficient forms of this disease, whereas SZ and MID were chosen because of earlier reports of olfactory loss in these disorders and the need to better understand the nature and magnitude of this loss. Patients who undergo neurosurgery for intractable epileptiform seizure activity are of particular interest to us, since such operations impinge upon brain regions associated with central olfactory processing. In such cases, we plan to compare the efficacy of our olfactory tests in characterizing the sensory dysfunction before and after the surgical resection. Importantly, we will determine (i) the nature and degree of olfactory dysfunction that is present on each side of the nose prior to surgery, (ii) the extent to which such surgery influences ipsilateral and contralateral function, (iii) whether age at first risk for seizures is related to the degree of preoperative and postoperative olfactory dysfunction, and (iv) whether and to what degree olfactory function changes over a five-year postoperative period. Overall, the experiments of this program will further advance the development of clinical olfactory tests and will provide insights into the nature and prevalence of chemosensory dysfunction in a wide range of medical disorders.