Electrophysiologic and Anatomic Basis of BOLD fMRI

描述(申请人提供)：血氧水平依赖(BOLD)功能磁共振成像(FMRI)在健康和疾病中普遍用于绘制人脑的图谱。BOLD fMRI不是直接测量神经元的活动，而是检测与神经元活动相耦合的依赖于灌流的信号。由于对电生理活动、功能解剖和功能灌流之间的精确关系的不完全理解，影响了对BOLD功能磁共振信号的准确解释。该研究计划的总体目标是检查电生理学、连接性和跨任务、大脑皮层和疾病状态的大胆功能磁共振信号之间的精确关系。候选人：凭借扎实的神经科学训练、全面的全科和次专科(功能)神经外科训练，以及高质量的研究经验，Nader Pouratian博士已经在人脑图谱领域发表了大量的著作。这份职业发展和研究计划代表了他之前工作的自然延伸，他之前的工作使用多模式成像来表征人类脑血流依赖标测信号的病因、局限性和能力，使用功能磁共振成像、光学成像和电皮质刺激标测(ESM)。在一个拥有丰富成像专业知识的环境中，眼前的目标是发展和确保广度和深度，以便在拨款提案中发挥成像专家的作用。这项提议的具体职业发展目标是(1)获得更多脑成像方法(皮质脑电图术和扩散束成像)的专业知识，以成为更全面和全面的脑成像专家(2)熟练掌握复杂的统计以及信号和图像分析(3)增加候选人在高级系统神经科学方面的知识储备(4)获得科学方法方面的高级培训，以及(5)确保继续进行研究伦理方面的培训。这些目标将通过加州大学洛杉矶分校内外的实验室实践经验、世界知名领导者(Arthur Toga、Susan Bookheimer、Itzhak Fry、Robert Knight和Jeffrey Ojemann博士)的指导和指导以及专门的课程和研讨会来实现。候选人的长期研究重点是精确和准确地绘制和解释人类大脑功能，这既可用于推进运动和语言系统的系统级表征，也可用于开发恢复性神经外科干预措施。环境：研究和职业发展活动将主要在加州大学洛杉矶分校进行，该大学是美国十大研究型大学之一，拥有卓越的记录，这要归功于强大的资源、研究、教育和合作机会网络。包括加州大学洛杉矶分校神经成像实验室(LONI)和Ahmanson-Lovelace脑成像中心在内的最先进的图像采集和分析设施为职业发展提供了无与伦比的丰富环境，尤其适合神经成像和临床神经科学领域的职业提升。LONI内部的研究重点是通过使用计算方法来全面绘制大脑结构和功能图，以提高对健康和疾病中大脑的理解。加州大学洛杉矶分校的制度环境承诺将候选人提升到一个新的学术卓越水平。研究：压倒一切的假设是，BOLD fMRI信号特征是由集成电生理活动(即多个场电势带)的复杂组合决定的，这些电生理活动在不同的皮质和任务中不同，并受系统容量、限制和缓冲器的调制。我们假设，基于独特的反应曲线和解剖连接的模式，功能上重要的信号可以从非特异性激活中区分出来。在具体目标1中，我们将通过使用微调的运动和语言任务以及多变量分析比较受试者中的BOLD和ECoG信号，来具体研究BOLD fMRI信号跨大脑皮层、任务和任务复杂性的空间范围的电生理学基础。我们假设BOLD的空间范围是由电生理决定的，但依赖于低频场电位活动的程度，而不是高频活动的程度，并且存在神经血管缓冲，因此并不是所有的电生理变化都会引起灌注量的变化。在具体目标2中，我们批判性地分析了BOLD信号强度的电生理决定因素，通过详细的BOLD-ECoG比较，旨在确定这些关系在大脑皮层、任务和疾病状态之间的变异性，电生理学和BOLD信号是否遵守类似的相加和适应规则，以及BOLD上限反应如何与电生理学相关。在特定的目标3中，我们解决了这样的假设，即功能相关的大脑映射信号可以基于基于生物标记物的独特连接性来区分。使用多模式比较，我们将严格审查BOLD信号、ESM、DTI波束成像以及BOLD和ECoG信号一致性之间的关系，以阐明连接性在描绘显著的BOLD fMRI激活中的作用。摘要：这项职业发展资助结合了候选人背景的关键因素和独特而杰出的机构资源，以及为实现成为加州大学洛杉矶分校当地独特的神经外科脑图和修复实验室的独立研究员的目标所需的技能发展。

DESCRIPTION (provided by applicant): Blood Oxygen Level Dependent (BOLD) functional magnetic resonance imaging (fMRI) is used ubiquitously to map the human brain, both in health and disease. Instead of directly measuring neuronal activity, BOLD fMRI detects perfusion-dependent signals that are coupled to neuronal activity. The accurate interpretation of BOLD fMRI signals is compromised by an incomplete understanding of the precise relationship between electrophysiological activity, functional anatomy, and function perfusion. The overall goal of this research program is to examine the precise relationship between electrophysiology, connectivity, and BOLD fMRI signals across tasks, cortices, and disease states. Candidate: Given his solid neuroscience training, thorough general and sub-specialty (functional) neurosurgical training, and quality research experiences, Dr. Nader Pouratian has already published extensively in the field of human brain mapping. This career development and research proposal represents a natural extension of his previous work which employed multimodality imaging to characterize the etiology, limitations, and capacities of perfusion-dependent brain mapping signals in humans using fMRI, optical imaging, and electrocortical stimulation mapping (ESM). In an environment rich in imaging expertise, the immediate goals are to develop and ensure the breadth and the depth to function as THE imaging expert on a grant proposal. Specific career development goals of this proposal are (1) to gain expertise in additional brain mapping methodologies (electrocorticography and diffusion tractography) in order to become a more comprehensive and well-rounded brain mapping expert (2) to gain facility with and proficiency in complex statistics and signal and image analyses (3) to augment the candidate's fund of knowledge in advanced systems neuroscience (4) to obtain advanced training in the scientific method and (5) to ensure continued training in the ethical conduct of research. These goals will be accomplished by means of hands-on laboratory experience, mentorship and guidance of world-renowned leaders (Drs. Arthur Toga, Susan Bookheimer, Itzhak Fried, Robert Knight, and Jeffrey Ojemann) both within and outside of UCLA and dedicated coursework and seminars. The candidate's long-term research focus is devoted to the precise and accurate mapping and interpretation of human brain function that can be used both to advance systems-level characterization of motor and language systems and to develop restorative neurosurgical interventions. Environment: Research and career development activity will primarily be conducted at UCLA, which ranks among the nations top ten research universities and has a record of excellence which is attributable to a strong network of resources, research, education and collaborative opportunities. The state-of-the-art image acquisition and analysis facilities including the UCLA Laboratory of Neuro Imaging (LONI) and the Ahmanson-Lovelace Brain Mapping Center provide an unparalleled and enriched environment for career development that is particularly suited for career enhancement in the field of neuroimaging and clinical neuroscience. Research within LONI is focused on improving the understanding of the brain in health and disease by using computational approaches for the comprehensive mapping of brain structure and function. UCLA's institutional environment promises to promote the candidate to a new level of academic excellence. Research: The overriding hypothesis is that BOLD fMRI signal characteristics are determined by a complex combination of integrated electrophysiological activity (i.e., multiple field potential bands) that vary across cortices and tasks and are modulated by system capacities, limitations, and buffers. We hypothesize that functionally significant signals can be differentiated from non-specific activations based on unique response profiles and patterns of anatomic connectivity. In Specific Aim 1, we will specifically investigate the electrophysiologic basis of the spatial extent of BOLD fMRI signals across cortices, tasks, and task complexity by comparing BOLD and ECoG signals within subjects using finely-tuned motor and language tasks and multivariate analyses. We hypothesize that BOLD spatial extent is electrophysiologically-determined but dependent upon the extent of low-frequency field potential activity rather than high-frequency activity and that a neurovascular buffer exists such that not all electrophysiological changes instigate changes in perfusion. In Specific Aim 2, we critically analyze the electrophysiologic determinants of BOLD signal intensities, with detailed BOLD-ECoG comparisons designed to determine the variability of these relationships across cortices, tasks, and disease states, whether electrophysiologic and BOLD signals respect similar rules of additivity and adaptation, and how BOLD ceiling responses relate to electrophysiology. In Specific Aim 3, we address the hypothesis that functionally relevant brain mapping signals can be differentiated based on distinctive connectivity based biomarkers. Using multimodality comparisons, we will critically scrutinize the relationship between BOLD signals, ESM, DTI tractography, and BOLD and ECoG signal coherence to elucidate the role of connectivity in delineating significant BOLD fMRI activations. Summary: This career development grant combines key elements from the candidate's background and unique and outstanding institutional resources with the development of the skills required to achieve the goal of becoming an independent investigator with a locally unique Neurosurgical Brain Mapping and Restoration Lab at UCLA.