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Simultaneous EEG/fMRI to disentangle neural and vascular mechanisms of Alzheimer's disease pathology

同步脑电图/功能磁共振成像可解开阿尔茨海默病病理学的神经和血管机制

基本信息

批准号：
10525421
负责人：
Tatiana Sitnikova
金额：
$ 59.26万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-15 至 2027-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10525421
关键词：
Address Affect Aging Alleles Alzheimer&apos s Disease Alzheimer&apos s disease pathology Alzheimer&apos s disease risk Amyloid beta-42 Amyloid beta-Protein Animal Model Apolipoprotein E Area Attention Biological Markers Biological Process Blood Blood Vessels Brain Brain region Cells Cerebrovascular Circulation Clinical Cognition Cognitive Cognitive deficits Complex Coupling Data Dementia Deposition Disease Dorsal Early Intervention Elderly Electroencephalography Enrollment Episodic memory Event Exhibits Functional Magnetic Resonance Imaging Functional disorder Future Hematological Disease High Prevalence Homeostasis Human Image Imaging Techniques Imaging technology Impaired cognition Individual Investigation Link Longitudinal cohort Machine Learning Maintenance Measurement Measures Mediating Memory Metabolic Metabolism Methods Multivariate Analysis Nerve Degeneration Neurodegenerative Disorders Neurofibrillary Tangles Neurons Neurophysiology - biologic function Pathologic Pathology Patients Performance Pharmacology Physiological Population Predisposition Preventive therapy Process Property Proteins Public Health Records Recurrence Regulation Reporting Rest Scanning Senile Plaques Signal Transduction Structure Symptoms System Techniques Technology Testing Time Work base blood oxygen level dependent blood oxygenation level dependent response brain abnormalities brain cell cohort cost effective cost estimate density effective therapy executive function follow-up functional magnetic resonance imaging/electroencephalography genetic risk factor imaging modality in vivo interest invention mild cognitive impairment neural network neural patterning neurophysiology neurovascular neurovascular coupling novel prevent relating to nervous system response source localization tau Proteins

项目摘要

Abstract. Alzheimer’s disease (AD) is presently an untreatable neurodegenerative disorder with a massive public health burden. With invention of biomarker technologies for imaging β-amyloid (Aβ) plaques and neurofibrillary tangles in the living human brain, it became clear that these pathologies that define AD begin decades prior to overt dementia symptoms resulting from this disease. This prolonged pre-dementia period offers opportunities for early interventions. However, much is currently unknown about the complex AD pathophysiology in these early stages. One intriguing observation is that the early Aβ pathology is often localized to highly metabolic regions of the brain. These regions, also known as ‘cortical hubs’ due to their high functional interconnectivity with other brain areas, may display activity related susceptibility. Animal models show that, in functionally active brain regions, disrupted rapid temporal structure of intrinsic neural activity and neurovascular dysregulation can influence Aβ homeostasis. It is possible that these pathophysiological mechanisms hold true in the aging human brain. However, precise measurement of rapid neural activity and neurovascular regulation in the higher-order brain areas most vulnerable to AD has been challenging. Currently available imaging techniques, when used alone, have severe limitations. The signal measured by functional magnetic resonance imaging (fMRI) reflects coupling between metabolic demand of active brain cells and a nutritive increase in cerebral blood flow and cannot differentiate between dysfunctions in neural activity itself and this neurovascular coupling (NVC). Techniques, such as electroencephalography (EEG), cannot unambiguously localize the recorded neurophysiological signal to specific neural networks. To overcome this critical barrier, we developed a cutting-edge scanning and analysis paradigm that [1] simultaneously records EEG and fMRI data, [2] detects and quantifies short timescale structure of transient events of intrinsic neurophysiological activity in cortical networks, and [3] uses these neural network events to anchor assessment of capacity to adjust vascular energy delivery in response to activity demands. Such selective measurements in unique neural networks will be used in the current project to test if disrupted rapid neural function and NVC in the active ‘cortical hubs’ are associated and show temporal precedence to Aβ pathology and the linked deficits in higher-order cognitive domains in a longitudinal cohort of older adults without clinical dementia. We will quantify Aβ pathology by leveraging novel ultra-sensitive blood biomarkers. Successful implementation of this approach would suggest that, in the aging human brain, abnormal fast neural dynamics and NVC in specific cortical regions are disease states predisposing to Aβ pathological changes. If such disease states are an upstream process to Aβ pathology, then in future studies, it may be possible to regulate Aβ homeostasis through pharmacological or brain stimulation approaches that target fast neural dynamics and NVC, and consequently, prevent progressive pathology and cognitive decline.

摘要。阿尔茨海默病（AD）是目前一种无法治疗的神经退行性疾病