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）：血氧水平依赖性（BOLD）功能性磁共振成像（fMRI）已成为在感觉运动和认知任务期间无创测量大脑活动的主力方法，也是神经系统疾病不可或缺的诊断工具。 BOLD信号是区域脑血流量（rCBF）、血容量（rCBV）和区域脑氧代谢率（rCMRO2）的函数，并且对这些因素与神经元活动的耦合的理解还远未完成。在导致 BOLD 的这三个因素中，rCBF 可能最容易受到非局部因素的影响，例如血管活性代谢物（例如 CO2）、激素和非局部释放的控制大脑状态（例如警惕性、警觉性、注意力等）的神经调节剂。事实上，控制大脑状态的神经调节剂（例如乙酰胆碱、去甲肾上腺素、血清素、多巴胺等）表现出血管活性特性，并且脑血管系统是已知的受到表达这些神经调节剂的神经元末梢的支配。其中，胆碱能神经调节系统特别令人感兴趣，因为它在涉及选择性注意、工作记忆和学习机制的认知任务中发挥着重要作用。在涉及这种神经调节系统的任务期间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脑灌注的整体控制。我们建议通过测试以下工作假设来解决乙酰胆碱 (Ach) 在塑造认知任务期间局部神经元激活和 BOLD 反应之间关系中的作用：区域 CBF 不仅受到局部神经元活动的调节，还受到控制神经元分配的因素的调节。由胆碱能系统介导的注意力和工作记忆资源。 rCBF 的这种系统性调节可能会改变神经元活动（以 rCMRO2 为索引）和 rCBF 之间的关系。我们假设乙酰胆碱的释放对于注意力和工作记忆任务期间神经元反应和 CBF 之间耦合的介导至关重要（可能通过基底前脑的激活）。我们建议通过使用动脉自旋标记 (ASL) 方法测量 CBF 和 BOLD 反应来检验这些假设。我们将测试注意力资源分配是否以与单独视觉刺激刺激相同的方式影响 BOLD 和 CBF 信号。为了研究认知任务期间胆碱能机制在 CBF 和 BOLD 耦合中的作用，我们将使用药理学操作来影响胆碱能调节的功效。我们预计胆碱能调节的药理学操作将以与注意力资源分配相同的方向影响 CBF/BOLD 关系。拟议的实验将为系统探究神经调节剂对 BOLD 信号与潜在局部神经元活动之间耦合的影响奠定基础，并将开发通过功能磁共振成像解决认知过程神经调节机制的工具。