Multimodal analysis of human PFC 4 Hz rhythms in cognition and speech in PD

PD 认知和言语中人类 PFC 4 Hz 节律的多模态分析

• 批准号: 10283245
• 负责人: ERGUN Y UC
• 金额: $ 12.21万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-17 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10283245
• 关键词: Affect; Anatomy; Anterior; Attenuated; Basic Science; Biological Markers; Brain; Characteristics; Cognition; Cognitive; Control Groups; Data; Deep Brain Stimulation; Development; Diffusion Magnetic Resonance Imaging; Dyskinetic syndrome; Electroencephalogram; Executive Dysfunction; Frequencies; Functional Magnetic Resonance Imaging; Functional disorder; Future; Gene Expression; Generations; Goals; Human; Impairment; Levodopa; Link; Magnetic Resonance Imaging; Methods; Motor; National Institute of Neurological Disorders and Stroke; Parkinson Disease; Participant; Pathway interactions; Patient Recruitments; Patients; Physiological; Prefrontal Cortex; Publishing; Quality of life; Research; Rest; Severities; Severity of illness; Specific qualifier value; Speech; Structural defect; Structure; Symptoms; Testing; Thick; Transcranial magnetic stimulation; Work; caudate nucleus; cingulate cortex; cognitive impairment in Parkinson' s; cognitive performance; density; executive function; experimental study; improved; insight; motor disorder; motor symptom; multimodality; neurophysiology; neuroregulation; operation; standard care; synergism; tractography

Abstract In addition to motor dysfunction, cognitive and speech impairments in Parkinson's disease (PD) strongly affect quality of life in PD patients. Executive dysfunction is an early hallmark of cognitive impairment in PD. Because standard treatments for motor symptoms in PD, such as levodopa and high frequency deep brain stimulation (DBS), can potentially worsen cognition and speech, there is a critical need to develop treatments targeting cognitive and speech impairments in PD. Our long-term goal is to understand the physiological basis of cognition and speech impairments in PD. Our prior work suggests that cognitive and speech deficits in PD are associated with altered PFC 4 Hz oscillations. Despite this data, the network mechanisms that underlie prefrontal (PFC) 4 Hz rhythms are unknown. The overall objective of the proposed research is to determine the anatomical basis of PFC 4 Hz changes in PD. Our published work demonstrates that PFC 4 Hz rhythms are attenuated in PD, and our preliminary data indicate that these rhythms are specifically linked with cognitive and speech impairments. We will collect EEG and MRI data to determine key correlates of cognitive and speech symptoms. We will concentrate on dorsolateral PFC (DLPFC), ventrolateral PFC (VLPFC), and anterior cingulate cortex (ACC) as key PFC regions involved in executive functions and speech generation, and their subcortical connections with STN (hyperdirect pathway) and the caudate nucleus which are critical cognitive nodes. These methods will generate fundamental insights about how PFC 4 Hz rhythms affect cognition and speech in human PD patients. We will test the hypothesis that PFC 4 Hz oscillations coordinate brain-wide activity during cognitive and speech tasks. Our first aim is to determine the structural origin of the deficits in PFC 4 Hz oscillations in PD by using a combination of structural MRI to assess the cortical thickness of key PFC regions, structural connectivity using diffusion-tensor imaging (DTI) tractography between key PFC regions and subcortical structures (STN and caudate), and high-density electroencephalogram (EEG) at rest and during performance of cognitive and speech tasks in participants with PD across different levels of severity (mild, moderate, and advanced). Our second aim is to determine how PFC functional network mechanisms are linked with deficits in PFC 4 Hz oscillations by using simultaneous EEG-fMRI to examine BOLD changes during cognitive and speech tasks used in Aim 1 and in Project 2. We will examine resting-state connectivity of key PFC regions and subcortical structures. As in Aim 1, we will also use a control group and work with moderate PD participants identified from Project 2. Understanding the anatomical and functional basis of 4Hz PFC rhythms might be eventually useful for neuromodulation to treat cognitive and speech impairments in PD.

摘要 帕金森病（PD）除了运动功能障碍外， 影响PD患者的生活质量。执行功能障碍是认知障碍的早期标志， 警局因为帕金森病运动症状的标准治疗，如左旋多巴和高频深 脑刺激（DBS）可能会使认知和语言恶化，因此迫切需要开发 针对PD中认知和言语障碍的治疗。我们的长期目标是了解 认知和言语障碍的生理基础。我们之前的研究表明， PD患者的言语缺陷与PFC 4 Hz振荡的改变有关。尽管有这些数据， 作为前额叶（PFC）4 Hz节律基础的网络机制是未知的。的总体目标 本研究拟探讨帕金森病PFC 4 Hz变化的解剖学基础。我们的出版 研究表明，PFC 4 Hz节律在PD中衰减，我们的初步数据表明， 这些节奏与认知和语言障碍有着特定的联系。我们会收集脑电图， MRI数据，以确定认知和语言症状的关键相关性。我们将集中于 背外侧PFC（DLPFC）、腹外侧PFC（VLPFC）和前扣带皮层（ACC）作为关键PFC 参与执行功能和言语生成的区域，以及它们与 超直接通路（hyperdirect pathway）和尾状核是关键的认知节点。这些方法 将产生关于PFC 4 Hz节律如何影响人类认知和言语的基本见解 PD患者。我们将测试PFC 4 Hz振荡协调全脑活动的假设， 认知和言语任务。 我们的第一个目标是通过使用一个 结合结构MRI评估关键PFC区域的皮质厚度、结构连接性 在关键PFC区域和皮质下结构之间使用扩散张量成像（DTI）纤维束成像 (STN和尾状核），和高密度脑电图（EEG）在休息和执行期间， 不同严重程度（轻度、中度和重度）PD参与者的认知和言语任务 先进）。我们的第二个目标是确定PFC功能网络机制如何与 PFC 4 Hz振荡的缺陷，同时使用EEG-fMRI检查BOLD的变化， 目标1和项目2中使用的认知和言语任务。我们将研究 关键PFC区域和皮质下结构。与目标1一样，我们也将使用控制组， 从项目2中识别出中度PD受试者。了解的解剖和功能基础， 4 Hz PFC节律可能最终用于神经调节以治疗认知和言语 PD的损伤。