Mid-frontal delta/theta rhythms and cognitive control in PD

PD 中额叶 delta/theta 节律和认知控制

• 批准号: 10187663
• 负责人: Nandakumar Narayanan
• 金额: $ 42.91万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-25 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10187663
• 关键词: Acetylcholine; Affect; Age; Alpha Rhythm; Alzheimer' s Disease; Anterior; Area; Attention; Attenuated; Big Data; Biological Markers; Brain; Cell Nucleus; Cognitive; Cognitive Therapy; Complex; Conflict (Psychology); Data; Decision Making; Deep Brain Stimulation; Delusions; Dementia; Dementia with Lewy Bodies; Detection; Diagnosis; Disease; Dopamine; Electrodes; Electroencephalography; Etiology; Failure; Frequencies; Functional disorder; Genetic; Goals; Hallucinations; Human; Impaired cognition; Impairment; Individual; Lead; Machine Learning; Medial; Memory; Modeling; Motor; Neurobehavioral Manifestations; Neurodegenerative Disorders; Neurons; Parkinson Disease; Parkinson' s Dementia; Patients; Performance; Population; Process; Public Health; Reaction Time; Risk; Role; Scalp structure; Short-Term Memory; Signal Transduction; Site; Societies; Structure; Structure of subthalamic nucleus; Techniques; Testing; Theta Rhythm; Time; Visuospatial; Work; alpha synuclein; cognitive control; cognitive function; cognitive impairment in Parkinson' s; cognitive task; cost; disorder risk; effective therapy; experimental study; frontal lobe; implantation; improved; insight; mild cognitive impairment; motor symptom; neuronal patterning; neurophysiology; new therapeutic target; novel; novel diagnostics; patient population; public health relevance; tool

Abstract Up to 80% of patients with Parkinson's disease (PD) will suffer from cognitive symptoms, including impaired attention, planning, reasoning and working memory as well as hallucinations, visuospatial dysfunction, and delusions. These impairments lead to mild cognitive impairment (PD-MCI) and dementia (PDD) in PD. Cognitive symptoms of PD are associated with enormous cost to our society. There are no clear biomarkers and few effective treatments for PD-MCI/PDD. Because risk for PD increases dramatically with age, this problem will surge as our population grows older. The mechanisms contributing to PD-MCI/PDD are unknown. Our group has found that low-frequency (1-8 Hz; or delta/theta bands) brain rhythms might be helpful in diagnosing cognitive dysfunction in PD. This delta/theta activity originates from areas of medial frontal cortex such as the anterior cingulate, and is detectable by mid-frontal scalp EEG electrodes. We have found that mid-frontal delta/theta brain rhythms are engaged when healthy individuals detect novelty, errors, and conflict, or make decisions. These rhythms are attenuated in PD patients. Our working model is that PD patients manifest diverse neuronal and network deficits that impair mid-frontal delta/theta activity, leading to failures in engaging cognitive control. These abnormalities contribute to PD-MCI and PDD. In this proposal we combine `big-data' machine learning tools, intraoperative neurophysiology in humans, and new brain-stimulation paradigms to investigate the role of mid-frontal delta/theta rhythms in PD. We will test the overall hypothesis that mid-frontal delta/theta impairments are a mechanism of cognitive dysfunction in PD. In Aim 1 we will determine if mid-frontal delta/theta activity predicts PD-MCI/PDD. In Aim 2 we will use unique intraoperative recordings to determine how delta/theta activity within medial frontal cortex influences neurons in the subthalamic nucleus, a key site of functional convergence that is targeted by current deep-brain stimulation for PD. Notably, the subthalamic nucleus is a compact structure that receives highly overlapping input from cognitive and motor cortical regions, making it likely that our recordings will capture cognitive processing within this nucleus. Finally, in Aim 3 we will determine if subthalamic nucleus deep-brain stimulation at delta/theta frequencies improves cognitive control in PD patients. Because these experiments involve recordings across several PD patient populations (Aim 1), from single subthalamic neurons (Aim 2), and brain stimulation (Aim 3), each of these aims will provide independent mechanistic insight into cognitive dysfunction in PD. PD is a complex disease, but if cortical EEG abnormalities are a consistent theme it might inspire new diagnostic tools or new brain-stimulation therapies for cognitive dysfunction in PD. Results from this proposal could also be important for other neurodegenerative diseases such as dementia with Lewy bodies and Alzheimer's disease.

抽象的 高达 80% 的帕金森病 (PD) 患者会出现认知症状，包括 注意力、计划、推理和工作记忆受损以及幻觉、视觉空间 功能障碍和妄想。这些损害会导致轻度认知障碍 (PD-MCI) 和 PD 中的痴呆症 (PDD)。帕金森病的认知症状给我们的社会带来巨大的损失。 PD-MCI/PDD 尚无明确的生物标志物，有效的治疗方法也很少。因为PD风险 随着年龄的增长，这个问题将随着人口老龄化而加剧。机制 导致 PD-MCI/PDD 的因素尚不清楚。我们的小组发现低频（1-8 Hz；或 δ/θ 带）大脑节律可能有助于诊断 PD 认知功能障碍。这 δ/θ 活动起源于内侧额叶皮层区域，例如前扣带回，并且是 可通过中额头皮脑电图电极检测到。我们发现中额叶 delta/theta 大脑节律 当健康的人发现新奇、错误和冲突或做出决定时，他们就会参与其中。这些 PD 患者的节律减弱。我们的工作模型是 PD 患者表现出不同的神经元 以及损害中额叶 Delta/Theta 活动的网络缺陷，导致认知能力失败 控制。这些异常导致 PD-MCI 和 PDD。在这个提案中，我们结合了“大数据” 机器学习工具、人类术中神经生理学以及新的大脑刺激范例 研究中额叶δ/θ节律在帕金森病中的作用。我们将检验总体假设 中额叶δ/θ损伤是帕金森病认知功能障碍的一种机制。在目标 1 中，我们将 确定中额叶 delta/theta 活动是否可以预测 PD-MCI/PDD。在目标 2 中，我们将使用独特的 术中记录以确定内侧额叶皮质内的 delta/theta 活动如何影响 丘脑底核中的神经元是当前电流所针对的功能收敛的关键部位 PD 的深部脑刺激。值得注意的是，丘脑底核是一个紧凑的结构，接收 来自认知和运动皮质区域的高度重叠的输入，使得我们的录音很可能 捕捉这个核心内的认知处理。最后，在目标 3 中，我们将确定底丘脑是否 δ/θ 频率的核深部脑刺激可改善 PD 患者的认知控制。 因为这些实验涉及多个 PD 患者群体的记录（目标 1）， 单个底丘脑神经元（目标 2）和大脑刺激（目标 3），每个目标都将提供 对 PD 认知功能障碍的独立机制洞察。 PD 是一种复杂的疾病，但如果皮质 脑电图异常是一个一致的主题，它可能会激发新的诊断工具或新的大脑刺激 PD 认知功能障碍的治疗。该提案的结果对于其他方面也很重要 神经退行性疾病，例如路易体痴呆和阿尔茨海默病。

项目成果

A pilot study of machine learning of resting-state EEG and depression in Parkinson's disease.

帕金森病静息态脑电图和抑郁症机器学习的初步研究。

• 发表时间: 2022
• 作者: Espinoza, Arturo I;May, Patrick;Anjum, Md Fahim;Singh, Arun;Cole, Rachel C;Trapp, Nicholas;Dasgupta, Soura;Narayanan, Nandakumar S
• 通讯作者: Narayanan, Nandakumar S

Neuromodulation of cognition in Parkinson's disease.

帕金森病认知的神经调节。

• 发表时间: 2022
• 作者: Cole, Rachel C;Okine, Derrick N;Yeager, Brooke E;Narayanan, Nandakumar S
• 通讯作者: Narayanan, Nandakumar S

Timing variability and midfrontal ~4 Hz rhythms correlate with cognition in Parkinson's disease.

时间变异性和中额叶〜4Hz节律与帕金森病的认知相关。

• 发表时间: 2021-02-15
• 作者: Singh, Arun;Cole, Rachel C;Espinoza, Arturo I;Evans, Aron;Cao, Scarlett;Cavanagh, James F;Narayanan, Nandakumar S
• 通讯作者: Narayanan, Nandakumar S

A Pilot Study of Ex Vivo Human Prefrontal RNA Transcriptomics in Parkinson's Disease.

帕金森病离体人类前额叶 RNA 转录组学的初步研究。

• 发表时间: 2023-08
• 影响因子: 4
• 作者: Lin, Li;Cole, Rachel C;Greenlee, Jeremy D W;Narayanan, Nandakumar S
• 通讯作者: Narayanan, Nandakumar S

A human prefrontal-subthalamic circuit for cognitive control.

用于认知控制的人类前额叶-底丘脑回路。

• 发表时间: 2018-01-01
• 作者: Kelley, Ryan;Flouty, Oliver;Emmons, Eric B;Kim, Youngcho;Kingyon, Johnathan;Wessel, Jan R;Oya, Hiroyuki;Greenlee, Jeremy D;Narayanan, Nandakumar S
• 通讯作者: Narayanan, Nandakumar S