Defining the role of the subthalamic nucleus in language production through deep brain stimulation

摘要 丘脑底核脑深部电刺激（STN-DBS）是治疗帕金森病的有效方法。之一 在考虑这种疗法时，主要关注的是认知变化恶化的可能性。赤字 语言表达能力，通常以语言流畅性来衡量，是最常被报道的认知变化 在STN-DBS之后。然而，这一机制仍然知之甚少，主要是因为我们缺乏对 基底神经节（BG）在语言产生中的作用。为了充分理解文字的机制- 生产缺陷和语言中的角色，我们首先需要定义的语言概况， DBS本提案的总体目的是全面评估2005年后的语言变化， DBS并了解单词产生过程的哪一部分受到影响。通过评估患者， 单侧植入，我们的项目将提供一个更精细的了解BG偏侧的作用， 语言变化（目标1）。BG在通过调节额叶运动程序选择中的作用 皮质已经很好地建立。在BG内，通过抑制或抑制细胞增殖， 拖延不合适的选择语言模型提出了一个类似的过程，其中多个词汇选项 激活，有效地抑制不正确的是一个必要的步骤，及时的结果发生。我们 将通过以下方式确定单词产生缺陷的变化是否与抑制障碍有关： 言语和非言语抑制任务的变化（目标2）。最后，我们将评估物联网连接的作用 到语言皮层区域，特别是额下回，以及在多大程度上中断， DBS引起的连通性影响语言表现（目标3）。总的来说，这个项目将建立在一个 全面的语言评估和网络科学，以促进翻译和个性化的研究 帕金森病以及其他形式的失语症。它将促进认知和 STN-DBS中的语言变化，提供有关语言处理的机械信息，并确定 DBS相关认知变化的标志物。

Abstract Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective therapy for Parkinson disease. One of the main concerns when considering this therapy is the possibility of worsening cognitive changes. Deficits in word production ability, often measured as verbal fluency, is the most frequently reported cognitive change after STN-DBS. However, the mechanism remains poorly understood, largely due to our lack of knowledge on the role of the basal ganglia (BG) in language production. To fully understand the mechanisms of word- production deficits and the role of the STN in language we first need to define the language profile of STN- DBS. The overarching purpose of this proposal is to comprehensively evaluate language changes after STN- DBS and understand what part of the process of word production is affected. By evaluating patients with unilateral implants, our project will provide a more refined understanding of the role of the BG laterality in language changes (Aim 1). The role of the BG in motor program selection through modulation of the frontal cortex is well established. Within the BG, the STN plays a significant role in this process by inhibiting or delaying inappropriate options. Language models suggest a similar process where multiple lexical options are activated, and efficient inhibition of the incorrect ones is a necessary step for a timely outcome to occur. We will determine if changes in word production deficits are related to impairments in inhibition by correlating changes with verbal and non-verbal inhibitory tasks (Aim 2). Finally, we will assess the role of STN connectivity to language cortical areas, particularly the inferior frontal gyrus, and to what extent disruptions of that connectivity due to DBS affects language performance (Aim 3). Overall, this project will build on a comprehensive language assessment and network science to advance translational and personalized research in Parkinson disease as well as other forms of aphasia. It will advance knowledge on the cognitive and language changes in STN-DBS, provide mechanistic information about language processing and determine markers for DBS-related cognitive changes.