Neuromodulation of BOLD fMRI Signal during Cognitive Tasks

认知任务期间 BOLD fMRI 信号的神经调节

• 批准号: 7031423
• 负责人: GIEDRIUS T BURACAS
• 金额: $ 20.82万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-01 至 2008-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7031423
• 关键词: acetylcholine; attention; behavioral /social science research tag; brain circulation; clinical research; functional magnetic resonance imaging; human subject; neural information processing; neuropharmacology; neuropsychology; neuroregulation; neurotransmitter transport; nicotine; psychological tests; short term memory; substantia innominata; visual cortex; visual stimulus

DESCRIPTION (provided by applicant): Blood oxygenation level dependent (BOLD) functional MRI (fMRI) has become a workhorse method for noninvasively measuring brain activity during sensorimotor and cognitive tasks and an indispensable diagnostic tool for neurological disorders. BOLD signal is a function of regional cerebral blood flow (rCBF), blood volume (rCBV), and the regional cerebral metabolic rate of oxygen (rCMRO2), and the understanding of the coupling of these factors to the neuronal activity is far from complete. Among those three factors contributing to BOLD, rCBF is probably most susceptible to nonlocal factors, such vasoactive metabolites (such as CO2), hormones, and non-localy released neuromodulators that control brain states such as vigilance, alertness, attention, etc. Indeed, neuromodulators controlling brain states (e.g. acetylcholine, norepinephrine, serotonin, dopamine, etc) exhibit vasoactive properties and cerebral vasculature is known to be innervated by neuronal terminals expressing these neuromodulators. Among these, cholinergic neuromodulatory system is of special interest, since it plays essential role during cognitive tasks engaging selective attention, working memory and learning mechanisms. Imaging of brain activation during tasks engaging this neuromodulatory system is problematic, since cholinergic neuromodulatory system is also involved in global control of cerebral perfusion. We propose to address the role of acetylcholine (Ach), in shaping the relationship between local neuronal activation and BOLD responses during cognitive tasks by testing the following working hypothesis: Regional CBF is regulated not only by local neuronal activity but also by factors controlling allocation of attention and working memory resources, mediated by cholinergic systems. This systemic regulation of rCBF may change the relationship between neuronal activity (as indexed by rCMRO2) and rCBF. We hypothesize that acetylcholine release is essential for mediation of coupling between neuronal responses and CBF during attention and working memory tasks (probably via activation of basal forebrain). We propose to test these hypotheses by measuring CBF and BOLD responses using arterial spin labeling (ASL) method. We will test whether allocation of attentional resources affects BOLD and CBF signal in the same manner as stimulation by visual stumuli alone. In order to investigate the role of cholinergic mechanisms in coupling between CBF and BOLD during cognitive tasks, we will use pharmacological manipulations to affect efficacy of cholinergic modulation. We expect that pharmacological manipulations of the cholinergic modulation will affect CBF/BOLD relationship in the same direction as allocation of attention resources. Proposed experiments will set the ground for systematic inquiry into effects of neuromodulators on coupling between BOLD signal and underlying local neuronal activity, and will develop tools for addressing neuromodulatory mechanisms of cognitive processes by means of fMRI.

描述（由申请人提供）：血液氧合水平依赖性（BOLD）功能性MRI（fMRI）已成为一种在感觉运动和认知任务期间非侵入性测量脑活动的主力方法，并且是神经系统疾病的必不可少的诊断工具。 BOLD信号是区域脑血流（RCBF），血容量（RCBV）和氧气区域代谢速率（RCMRO2）的函数，并且对这些因素与神经元活性的偶联的理解远非完整。 Among those three factors contributing to BOLD, rCBF is probably most susceptible to nonlocal factors, such vasoactive metabolites (such as CO2), hormones, and non-localy released neuromodulators that control brain states such as vigilance, alertness, attention, etc. Indeed, neuromodulators controlling brain states (e.g. acetylcholine, norepinephrine, serotonin, dopamine,等）已知表现出血管活性特性和脑脉管系统，这是由表达这些神经调节剂的神经元末端神经支配的。其中，胆碱能神经调节系统具有特殊的兴趣，因为它在吸引选择性关注，工作记忆和学习机制的认知任务中起着至关重要的作用。在参与此神经调节系统任务过程中大脑激活的成像是有问题的，因为胆碱能神经调节系统也参与了全球脑灌注的控制。我们建议通过测试以下工作假设来解决乙酰胆碱（ACH）在认知任务期间局部神经元激活与大胆反应之间的关系：区域CBF不仅通过局部神经元活动来调节区域CBF。 RCBF的这种系统调节可能会改变神经元活性（由RCMRO2索引）和RCBF之间的关系。我们假设乙酰胆碱释放对于在注意力和工作记忆任务期间神经元反应和CBF之间的耦合至关重要（可能是通过激活基础前脑的激活）。我们建议通过使用动脉自旋标记（ASL）方法测量CBF和粗体反应来检验这些假设。我们将测试注意力资源的分配是否以与单独的视觉抑制相同的方式影响BOLD和CBF信号。为了研究胆碱能机制在认知任务中CBF和BOLD之间的耦合中的作用，我们将使用药理学操纵来影响胆碱能调节的功效。我们预计胆碱能调节的药理操作将影响CBF/BOLD的关系在与注意力资源的分配相同方向上。拟议的实验将为系统的调查为神经调节剂对大胆信号和基础局部神经元活性之间的耦合的影响树立奠定基础，并将开发通过fMRI来解决认知过程的神经调节机制的工具。