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: 8940087
• 负责人: Afonso Silva
• 金额: $ 135.92万
• 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/8940087
• 关键词: Acclimatization; Alzheimer' s Disease; Animals; Anterior; Architecture; Area; Auditory; Auditory area; Bilateral; Blood Vessels; Brain; Brain Diseases; Brain Pathology; Callithrix; Callithrix jacchus jacchus; Categories; Cells; Cerebrovascular Circulation; Cerebrum; Characteristics; Complex; Conscious; Core-Binding Factor; Cortical Column; Coupling; Custom; Data; Electrocorticogram; Elements; Event; Evolution; Experimental Autoimmune Encephalomyelitis; Experimental Models; Eye; Face; Face Processing; Frequencies; Functional Imaging; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Growth; Haplorhini; Head; Helmet; Human; Human Pathology; Hyperemia; Hypertension; Image; Implant; Ischemic Stroke; Life; Light; Liquid substance; Macaca; Manuscripts; Maps; Measurable; Measures; Microcirculation; Modeling; Monitor; Multiple Sclerosis; Myelin; National Institute of Drug Abuse; Neurons; Noise; Obsessive-Compulsive Disorder; Parkinson Disease; Pathway interactions; Peer Review; Photic Stimulation; Physical Restraint; Physiology; Play; Positive Reinforcements; Primates; Process; Protocols documentation; Pulvinar structure; RF coil; Regulation; Research; Resolution; Rest; Rewards; Role; Scanning; Somatosensory Cortex; Source; Specificity; Stimulus; Stream; Stroke; Structure; System; Techniques; Thalamic structure; Time; Training; Translations; Ursidae Family; Visual Cortex; Work; awake; blood oxygenation level dependent response; data acquisition; design; gaze; hemodynamics; improved; interest; neuroimaging; nonhuman primate; preference; relating to nervous system; response; restraint; somatosensory; sound; spatiotemporal

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 have optimized stimulus parameters and measured, 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 requires 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 expanded the use of our conscious awake marmoset model to obtain multi-sensorial functional data using fMRI. Following a simple yet effective acclimatization protocol to condition and train the marmosets to tolerate physical restraint during the data acquisition, we were able to obtain functional maps while the animal underwent somatosensory, auditory, or visual stimulation. The head was restrained with a custom-built helmet restraint that is completely non-invasive and able to hold the head still without sacrificing comfort. RF coils arrays with either 4 or 8 element coils were placed inside the helmets to obtain cortical responses with optimal sensitivity. After undergoing such training, the marmosets produced robust and reproducible fMRI responses in all senses. From somatosensory cortex, S1, S2, and caudate produced reliable BOLD and CBV responses to a single 333 s-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. In auditory cortex, we were able to detect activation in the main core of the auditory cortex (A1), as well as in the belt and parabelt areas to tones and broadband noise played in the 0.5 22 kHz range. Using a conventional block design paradigm and scanning the marmoset brain with a period of 3.6 s, we were able to elicit robust bilateral responses of silence versus sound. When contrasting low frequency to high-frequency tones, tonotopic maps were obtained, showing that the spatial specificity of the BOLD response is sufficient to resolve fundamental functional cortical columns. In visual cortex, the animals had to be trained to attend to images being presented in a monitor placed outside the magnet. We used a positive reinforcement liquid delivery system to reward the animals whenever they sustained their gaze to the screens. Eye gaze was monitored and recorded sing an eye-tracking system. We trained animals to actively direct their gaze to images of faces, bodies and objects, and measured functional responses in occipitotemporal cortex (OT) and thalamus (LGN and Pulvinar) of awake marmosets using both implanted electrocorticography (ECoG) arrays and fMRI. Robust stimulus-evoked responses were obtained with both techniques. Using ECoG, we found that responses within the high gamma range (50-150 Hz) were selective for stimulus categories, particularly for faces. Strong category-specific fMRI activation was observed in discrete patches throughout OT. Combining ECoG with fMRI mapping, we identified at least six face-selective patches that appear to occupy two parallel pathways within the ventral stream, similar to previous findings in macaques and humans. For both fMRI and ECoG responses, the preference for structured versus scrambled stimuli increased gradually along a posterior to anterior gradient. The results demonstrate that the marmoset OT has a set of face-processing regions that bear similar organization to those previously described in humans and macaques, suggesting that core elements of the face processing network were already present in the common anthropoid primate ancestor living 35 million years ago. We have also continued to work 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 role of myelin as a source of contrast for anatomical fMRI. 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 in our 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，我们一直有兴趣研究血流动力学反应功能(HRF)的时空演变，以此作为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对局灶脑活动的空间和时间特征是一个非常相关的话题，因为它决定了功能神经成像技术在绘制激活区域图方面的准确性，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。我们优化了刺激参数，并在空间和时间上测量了随后的HDR，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。我们认为，这项工作需要极其短暂的刺激，在良好控制的条件下提供，以引发微小的、但可测量的血管事件，这可能是CBF对更复杂刺激的综合反应的基础。 在当前的综述周期中，我们扩展了我们的清醒绒猴模型的使用，以获得使用功能磁共振成像的多感觉功能数据。按照一种简单而有效的驯化方案，在数据采集期间，我们能够在动物经历体感、听觉或视觉刺激的同时，获得功能图，以适应和训练绒猴耐受身体束缚。头部被定制的头盔约束，这是完全非侵入性的，能够在不牺牲舒适性的情况下保持头部不动。在头盔内放置具有4个或8个单元线圈的RF线圈阵列，以获得最佳灵敏度的皮质响应。在经历了这样的训练后，这些绒猴在所有感官上都产生了健壮且可重现的fMRI反应。来自躯体感觉皮层的S_1、S_2和尾状核对单个S长刺激产生可靠的BOLD和CBV反应。我们观察到CBV-HRF的起始和峰值明显快于BOLD-HRF，表明动脉对CBV反应有显著贡献。通过改变刺激持续时间，我们观察到激活区的大小和BOLD-HRF峰值的快速增长和饱和，这共同表明功能性充血是一个涉及整个皮质区域的快速和综合的过程。在听觉皮层，我们能够检测到听觉皮质主要核心(A1)以及腰带和副耳带区域对0.522 kHz范围内播放的音调和宽带噪声的激活。使用传统的区块设计范式，扫描周期为3.6%的S的绒猴大脑，我们能够引发强大的双边无声与声音反应。当对比低频和高频音调时，获得了调性图，表明大胆反应的空间特异性足以分辨基本的功能皮质柱。在视觉皮质中，这些动物必须接受训练，以便注意放置在磁铁外的监视器上呈现的图像。我们使用了一种积极的强化液体输送系统，每当动物持续凝视屏幕时，我们就奖励它们。眼睛的凝视被监控并通过眼球跟踪系统进行记录。我们训练动物主动地将它们的视线引导到面部、身体和物体的图像上，并使用植入的皮层脑电(ECoG)阵列和功能磁共振成像(FMRI)测量觉醒的恒河猴的枕颞叶皮质(OT)和丘脑(LGN和枕枕)的功能反应。这两种技术都获得了强大的刺激诱发反应。使用ECoG，我们发现高伽马范围(50-150赫兹)内的反应对刺激类别是有选择性的，特别是对面孔。在整个OT的离散斑块中观察到强烈的类别特异性fMRI激活。结合ECoG和功能磁共振成像，我们识别了至少六个面部选择性斑块，它们似乎占据了腹侧流中的两条平行路径，类似于之前在猕猴和人类身上的发现。对于fMRI和ECoG反应，结构刺激相对于杂乱刺激的偏好沿着从后到前的梯度逐渐增加。结果表明，绒猴OT有一组面部加工区域，这些区域具有与之前在人类和猕猴中描述的相似的组织，这表明面部加工网络的核心元素已经存在于3500万年前常见的类人灵长类动物祖先中。 我们还继续与我们的合作者合作，改进对绒猴大脑的解剖和功能成像，以此来影响多个不同方向的研究。与Jeff Duyn和Daniel Reich团队一起，我们一直在研究髓鞘作为解剖功能磁共振成像对比度来源的作用。我们还一直在帮助NIDA的Elliot Stein团队从强迫症(OCD)的绒猴模型中获得静息状态和功能磁共振数据。我们参与了史蒂夫·雅各布森和丹尼·赖克团队在我们实验室进行的EAE工作。以上都是正在进行的工作，其中一些手稿已经提交，但目前正在进行同行审查。