Characterization of neurovascular and neurometabolic coupling of the negative BOLD response in human

项目摘要 对于基于任务的功能磁共振成像(FMRI)，阳性的血氧水平依赖 (BOLD)反应被广泛使用，通常认为它是局部神经活动的线性反映。 然而，很大一部分大脑区域在激活时会做出信号减少的反应，这被称为 负面大胆回应(NBR)。尽管负面的大胆回应(NBR)及其来源 广泛探索的NBR的时间特征和空间结构，以及相应的基础 人们对生理动力学仍知之甚少。 我们建议研究由短暂刺激--负血流动力学--诱发的NBR的动力学 使用我们的新技术的反应功能(NHRF)及其潜在的神经血管和神经代谢反应 高时空分辨率BOLD和动脉自旋标记(ASL)功能磁共振成像的实验范式 医疗模式。高空间和时间分辨率的BOLD测量将解决 NHRF是皮质深度和沿皮质距离相邻的阳性大胆反应的函数 浮出水面。我们还通过测量NBR的动态变化来评估平移不变的时间线性度 刺激持续时间。精细时空采样ASL测量与一种新的刺激- 起效时间抖动方案将提供与脑血流相关的准确量化 灰质内的NBR。我们提出了基于即时动脉动力学的新的计算模型 在最近的实验研究中观察到，使估计现实的神经代谢反应相关 与nHRF合作。该模型将对潜在的生理成分提供更详细的解释 与nHRF相关联。 我们提议的研究将提供对神经血管和神经代谢的详细了解。 (去偶联)与nHRF相关，扩大了我们对正常大脑功能的了解。这样的细节与 在以前的研究中，无法精确地了解NBR及其生理学。最终，成功 我们建议的研究将促进建议的脑功能磁共振成像方法和建模方案的使用 涉及神经血管和神经代谢耦合的病理学。

Project Summary For task-based functional magnetic resonance imaging (fMRI), the positive blood-oxygen-level-dependent (BOLD) response has been widely used and often assumed that it linearly reflects local neural activity. However, a significant portion of brain regions responds with signal decreases upon activation, known as the negative BOLD response (NBR). Although the negative BOLD response (NBR) and its origin have been explored extensively, temporal characteristics and spatial structure of the NBR, and corresponding underlying physiological dynamics are still poorly understood. We propose to investigate dynamics of the NBR evoked by a brief stimulus –the negative hemodynamic response function (nHRF) and its underlying neurovascular and neurometabolic responses using our novel experimental paradigms with high spatiotemporal resolution BOLD and arterial spin labelling (ASL) fMRI modalities. High spatial and temporal resolution BOLD measurements will resolve temporal dynamics of the nHRF as a functional of cortical depth and distance from adjacent positive BOLD responses along the cortical surface. We also evaluated shift-invariant temporal linearity by measuring dynamics of the NBR for varying stimulus durations. Fine spatiotemporal sampling ASL measurements in conjunction with a novel stimulus- onset-time dithering scheme will provide accurate quantification of the cerebral blood flow associated with the NBR within gray matter. We advance our novel computational model based on prompt arterial dynamics observed in recent experimental studies, enabling estimation of realistic neurometabolic response associated with the nHRF. The model will offer a better detailed interpretation of the underlying physiological components associated with the nHRF. Our proposed research will provide a detailed understanding of neurovascular and neurometabolic (de-)coupling associated with nHRF, expanding our knowledge of normal brain functions. Such details with precision to understand the NBR and its physiology was not available in previous studies. Ultimately, success of our proposed research will motivate use of the proposed fMRI approaches and modeling schemes for brain pathologies that involve neurovascular and neurometabolic coupling.