Cortical-Subcortical Interaction in PD and Normal Speech

描述（由申请人提供）：拟议项目将继续并扩展我们目前对言语过程中皮质-皮质下相互作用的研究，利用 PD 和 DBS 的影响来探讨运动言语控制的神经学基础，以及 PD 和 DBS 对言语的影响。继续我们的 PET 功能成像，我们将添加结构成像、扩散张量成像和使用 MRI 的纤维束成像。我们将继续通过一系列任务探索言语，包括阅读、背诵、重复和自发言语。我们将评估清晰度和感知等级，并利用这些结果为声学分析提供信息。我们正在将统计建模和 MRI 应用方面的专业知识添加到声音病理学研究中。我们的目标是回答基本的临床和言语科学问题。该领域需要解决几个基本问​​题。在临床上，我们需要更好地估计 DBS 导致严重言语障碍的频率，以及何时发生，如何表征。我们需要了解与 DBS 相关的言语障碍在多大程度上是由言语大脑网络的变化、整体大脑效应和/或丘脑底核附近运动束的刺激引起的。从言语科学的角度来看，我们需要表征一系列言语任务的皮质-皮质下相互作用，以更好地理解基底神经节、皮质和小脑区域在言语中的作用。我们正在通过结合良好控制的实验研究、可能特别丰富的特殊案例研究以及临床调查研究的创新方法来实现该项目的目标。我们发现 DBS 增强了言语的某些成分，同时阻碍了其他成分，这为理解不一致的文献提供了重要的一步。此外，对我们的 PET 数据的分析表明，DBS 改变了言语和皮质-皮质下相互作用之间的基本关系。我们的主要工作假设是： 皮质横向不对称与流畅性相关；皮质下区域与发声密切相关，特别是前两个共振峰，并且这些区域在 DBS 期间发生了变化；当 DBS 加强发声时，发音控制就会承受额外的负担；大脑和言语效果都依赖于任务，在对话过程中观察到的难度最大。我们的工作还表明，在开启和关闭 DBS 的情况下，以及在没有 DBS 的 PD 受试者中，整体血流与言语停顿有关。这可能反映了帕金森病中枢神经系统的完整性，并将通过弥散张量成像进一步检查。除了详细的影像学研究之外，我们还将对 DBS 手术前后的对话和重复言语进行更广泛的、基于临床的研究。总而言之，这些研究应该可以更好地了解 DBS 后言语变化的范围和严重程度，以及与这些变化相关的大脑变化。 公共卫生相关性：帕金森病 (PD) 是一种进行性运动障碍，会损害清晰说话的能力。深部脑刺激（DBS）可以改善帕金森病的许多运动症状，但对说话能力没有帮助，有时甚至会损害。该项目旨在了解 PD 和 DBS 对言语的影响，长期目标是 (1) 修改 DBS 以保留或改善 PD 中的言语，以及 (2) 提高我们对言语过程中皮质-皮质下相互作用的理解。

DESCRIPTION (provided by applicant): The proposed project will continue and extend our present studies on cortical-subcortical interactions during speech using the effects of PD and DBS to probe the neurological basis of motor speech control, and the effects of PD and DBS on speech. Continuing our functional imaging with PET, we will add structural imaging, diffusion tensor imaging, and tractography using MRI. We will continue probing speech with a range of tasks incorporating reading, recitation, repetition, and spontaneous speech. We will evaluate intelligibility and perceptual ratings, using these results to inform acoustic analyses. We are adding expertise in statistical modeling and the application of MRI to the study of voice pathology. Our goal is to answer basic clinical and speech science questions. Several fundamental questions need to be addressed in this field. Clinically, we need a better estimate of how often DBS results in greater speech impairment, and when it occurs, how it can be characterized. We need to understand the extent to which DBS-related speech impairments result from changes in brain networks for speech, global brain effects, and/or stimulation of motor tracts adjacent to the subthalamic nucleus. From the speech science perspective, we need to characterize cortical-subcortical interactions for a range of speech tasks to better understand the role of the basal ganglia, cortical, and cerebellar regions in speech. We are approaching the goals of this project with a combination of well-controlled experimental studies, studies of special cases that may be especially informative, and an innovative approach to clinical survey studies. Our finding that DBS enhances some components of speech while retarding others provides an important step in understanding an inconsistent literature. Further, analysis of our PET data suggests that DBS changes the basic relationship between speech and cortical-subcortical interactions. Our major working hypotheses are that: cortical lateral asymmetry is associated with fluency; subcortical regions are strongly associated with phonation, particularly the first two formants, and these are shifted during DBS; when DBS strengthens phonation, an additional burden is placed on articulatory control; both brain and speech effects are task dependent, with the greatest difficulty observed during conversation. Our work also suggests that global blood flow is related to pausing during speech, with DBS on and off, and in PD subjects without DBS. This may reflect the integrity of the central nervous system in PD, and will be further examined with diffusion tensor imaging. In addition to the detailed imaging studies, we will conduct a broader, clinic-based study of conversational and repeated speech before and after DBS surgery. Taken together, these studies should provide a better understanding of the range and severity of speech changes following DBS, and the brain changes associated with these changes. PUBLIC HEALTH RELEVANCE: Parkinson's disease (PD) is a progressive movement disorder that impairs the ability to speak clearly. Deep brain stimulation (DBS) improves many of the motor symptoms of PD, but does not help and sometimes harms the ability to speak. This project seeks to understand the effects of PD and DBS on speech with the long-term goals of (1) modifying DBS to preserve or improve speech in PD and (2) improving our understanding of cortical-subcortical interactions during speech.