Spatial-Temporal Characterization of The Hemodynamic Response to Neural Activity

神经活动血流动力学反应的时空特征

• 批准号: 8746820
• 负责人: Afonso Silva
• 金额: $ 152.63万
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8746820
• 关键词: Acclimatization; Alzheimer' s Disease; Animals; Anisotropy; Architecture; Attention; Blood Vessels; Brain; Brain Diseases; Brain Pathology; Callithrix; Callithrix jacchus jacchus; Cells; Cerebrum; Characteristics; Complement; Complex; Conscious; Core-Binding Factor; Coupling; Data; Dependence; Event; Evolution; Experimental Autoimmune Encephalomyelitis; Experimental Models; Fiber; Functional Imaging; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Growth; Head; Helmet; Human; Human Pathology; Hyperemia; Hypertension; Ischemic Stroke; Light; Manuscripts; Maps; Measurable; Measures; Microcirculation; Modeling; Multiple Sclerosis; Myelin Sheath; National Institute of Drug Abuse; Nature; Neurons; Obsessive-Compulsive Disorder; Optics; Parkinson Disease; Pathway interactions; Peer Review; Phase; Photic Stimulation; Physical Restraint; Physiology; Positioning Attribute; Predisposition; Process; Protocols documentation; Radiation; Regulation; Relative (related person); Relaxation; Research; Resolution; Rest; Role; Specificity; Stimulus; Stroke; Structure; Surface; Techniques; Time; Training; Translations; Vision; Visual Cortex; Work; awake; base; brain tissue; data acquisition; design; hemodynamics; improved; in vivo; interest; neuroimaging; nonhuman primate; novel; relating to nervous system; research study; response; restraint; somatosensory; spatiotemporal; tool; white matter

We have a long-standing interest in investigating the spatiotemporal evolution of the hemodynamic response function (HRF) as an important way to understand the role of functional hyperemia in supporting neuronal activity. The determination of both spatial and temporal characteristics of the HDR to focal brain activity is a topic of great relevance as it dictates the accuracy of functional neuroimaging techniques in mapping activation regions, establishes the ultimately achievable spatial and temporal resolution, and influences the interpretation of the data. We are working on optimizing stimulus parameters and measuring, in space and in time, the ensuing HDR, with the long-term goal of determining the ultimate spatial domain of CBF control and its associated temporal evolution. We believe such work will require extremely brief stimuli, delivered under well-controlled conditions, to elicit minute, yet measurable vascular events, which can presumably serve as the building blocks of the integrative CBF response to more complex stimuli. In the current review cycle, we focused on studying the influence of the stimulus duration on the spatiotemporal characteristics of the HRF in conscious, awake marmosets. For this, we developed a simple yet effective acclimatization protocol to condition and train the marmosets to tolerate physical restraint during the data acquisition, and we designed a helmet-based head restraint that is completely non-invasive and able to hold the head still without sacrificing comfort. After undergoing such training, the marmosets produced robust and reproducible fMRI responses in S1, S2, and caudate. We were able to reliably detect the BOLD and the CBV response to a single 333-μs-long stimulus. We observed that the CBV-HRF onsets and peaks significantly faster than the BOLD-HRF, indicating a significant arterial contribution to the CBV response. By varying the stimulus duration, we observed a quick growth and saturation of both the size of the regions of activation and the peak amplitude of the BOLD-HRFs, which collectively suggest that functional hyperemia is a fast and integrative process that involves the entire cortical region. We have also been working with our collaborators on improving both anatomical and functional imaging of the marmoset brain in a way to impact research in a number of different directions. With Jeff Duyn and Danny Reich groups, we have been investigating the nature of T2* and phase contrast as related to brain tissue structure and composition. We have been able to determine that R₂ relaxation in white matter is highly sensitive to the fiber orientation relative to the main field. We directly demonstrated this orientation dependence by performing in vivo multi-gradient-echo experiments in two orthogonal brain positions, uncovering a nearly 50% change in the R₂ relaxation rate constant of the optic radiations, and attributed this substantial R₂ anisotropy to local subvoxel susceptibility effects arising from the highly ordered and anisotropic structure of the myelin sheath. With David Leopold, weve been developing the experimental tools to perform fMRI of the marmoset visual cortex. More than 25% of the cortical surface of the marmoset brain is dedicated to vision, and there has been no fMRI of the marmoset visual cortex performed to date. Pushing to perform fMRI of visual stimulation in concisous marmosets puts us in the very exciting pathway of studying neurovascular coupling in conditions under which the animal needs to pay active attention to the task, and may bring in novel results that will complement the information we have been currently acquiring from passive somatosensory stimulation. We have also been helping the group of Elliot Stein at NIDA to obtain resting-state and fMRI data from a marmoset model of Obsessive-Compulsive Disorder (OCD). We have been involved with the EAE work performed inour lab by the groups of Steve Jacobson and Danny Reich. All of the above are works in progress, in which a few manuscripts have been submitted but are currently in peer review.

长期以来，我们一直对研究血流动力学反应功能（HRF）的时空演变感兴趣，这是了解功能性充血在支持神经元活动中的作用的重要途径。确定HDR对局灶性大脑活动的空间和时间特征是一个非常相关的主题，因为它决定了功能神经成像技术在绘制激活区域时的准确性，建立了最终可实现的空间和时间分辨率，并影响了数据的解释。我们正致力于优化刺激参数，并在空间和时间上测量随后的HDR，其长期目标是确定CBF控制的最终空间域及其相关的时间演变。我们相信这样的工作将需要极短的刺激，在良好的控制条件下传递，以引起微小的，但可测量的血管事件，这可能是作为对更复杂刺激的综合CBF反应的基石。