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