Cortical-Subcortical Interaction in PD and Normal Speech

描述(申请人提供)：该项目将继续和扩展我们目前关于言语过程中皮质-皮质下相互作用的研究，利用PD和DBS的效应来探索运动性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，我们将增加结构成像、扩散张量成像和使用MRI的纤维束成像。我们将继续通过阅读、背诵、重复和自发演讲等一系列任务来探索演讲。我们将评估清晰度和感知评级，使用这些结果为声学分析提供信息。我们正在将统计建模和核磁共振应用方面的专业知识添加到嗓音病理学研究中。我们的目标是回答基本的临床和语音科学问题。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导致更大言语障碍的频率，以及它发生的时间和特征。我们需要了解DBS相关的言语障碍在多大程度上是由于言语大脑网络的变化、全脑效应和/或刺激邻近丘脑底核的运动束造成的。从语言科学的角度来看，我们需要描述一系列语音任务中皮质-皮质下相互作用的特征，以更好地理解基底节、皮质和小脑区域在语音中的作用。我们正在通过良好控制的实验研究、可能特别有用的特殊病例研究以及临床调查研究的创新方法相结合来接近该项目的目标。我们的发现是，DBS增强了言语的某些成分，而抑制了其他成分，这为理解不一致的文献提供了重要的一步。此外，对我们的正电子发射计算机断层扫描数据的分析表明，DBS改变了语音和皮质-皮质下相互作用之间的基本关系。我们的主要工作假设是：皮质侧向不对称与流利性有关；皮质下区域与发声密切相关，特别是前两个共振峰，这些区域在DBS过程中发生移位；当DBS增强发音时，发音控制增加了负担；大脑和言语的影响都与任务有关，在对话中观察到的难度最大。我们的工作还表明，在有DBS的情况下，以及在没有DBS的PD受试者中，全局血流与讲话时的停顿有关。这可能反映了帕金森病患者中枢神经系统的完整性，并将进一步用扩散张量成像进行检查。除了详细的影像研究，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。综上所述，这些研究应该能更好地了解DBS后言语变化的范围和严重性，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.