Cortical-Subcortical Interaction in PD and Normal Speech

项目描述（由申请人提供）：本项目将继续和扩展我们目前的研究，利用PD和DBS的作用来探索运动语言控制的神经学基础，以及PD和DBS对语言的影响。在PET功能成像的基础上，我们将增加结构成像、弥散张量成像和MRI示踪成像。我们将通过一系列包括阅读、背诵、重复和自发演讲的任务来继续探索语言。我们将评估可理解性和感知评级，使用这些结果来通知声学分析。我们正在增加统计建模方面的专业知识，并将核磁共振成像应用于语音病理学研究。我们的目标是回答基本的临床和语言科学问题。在这一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导致更严重语言障碍的频率，以及何时发生，如何表征。我们需要了解dbs相关的语言障碍在多大程度上是由大脑语言网络的变化、整体大脑效应和/或丘脑下核附近运动束的刺激引起的。从语言科学的角度来看，我们需要描述一系列语言任务中皮层-皮层下相互作用的特征，以更好地理解基底神经节、皮层和小脑区域在语言中的作用。我们正在通过结合控制良好的实验研究、可能提供特别信息的特殊病例研究和临床调查研究的创新方法来接近这个项目的目标。我们发现DBS增强了语言的某些组成部分，而阻碍了其他部分，这为理解不一致的文献提供了重要的一步。此外，对PET数据的分析表明，DBS改变了言语和皮层-皮层下相互作用之间的基本关系。我们的主要假设是：皮层外侧不对称与流畅性有关；皮层下区域与发声密切相关，尤其是前两个共振峰，并且在DBS期间发生移位；当DBS加强发音时，对发音控制施加了额外的负担；大脑和语言的影响都是任务依赖的，在谈话中观察到最大的困难。我们的研究还表明，在启动和关闭DBS时，以及在没有DBS的PD受试者中，全球血流量与说话时的停顿有关。这可能反映了PD中中枢神经系统的完整性，并将通过扩散张量成像进一步检查。除了详细的影像学研究外，我们还将对DBS手术前后的会话和重复言语进行更广泛的临床研究。综上所述，这些研究应该能更好地理解脑起搏术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。

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.