AMYGDALA CONNECTIVITY MAP IN 'IN VIVO' HUMAN BRAINS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在过去的15年里，我们看到人们对了解杏仁核的作用越来越感兴趣，杏仁核是一种复杂的结构，涉及广泛的正常行为功能和精神疾病。杏仁核所在的颞叶受损，会导致原始行为(恐惧、进食和性行为)的深刻变化。几项功能神经成像研究探索了杏仁核在情绪处理和调节中所起的作用，以及更广泛地说，在人类社会行为(奖励、动机和学习)中所起的作用，建立在先前人类和动物死后研究的细胞结构发现的假设基础上。然而，由于缺乏对杏仁核组织及其与其他大脑区域的联系的了解，以及通过行为任务测量的情绪功能的复杂性，限制了我们的理解，需要在活体人类受试者中进行进一步的研究。在我们的初步数据中，我们已经能够重建连接种子区域杏仁核和同侧皮质(额叶、颞叶、顶叶、岛叶和枕叶)的纤维。有趣的是，尽管目标区域范围很广，但我们发现杏仁核连接到这些皮质的高度功能专门化的子域，突出情绪过程和调节。此外，通过重建连接杏仁核和皮质下核(伏隔核、基底节、丘脑)的纤维，我们已经能够在人类受试者中识别杏仁核是否直接或间接通过杏仁核-皮质下-皮质回路连接到同侧皮质，这与动物研究中的组织学标记的发现是平行的，而且远远超出了组织学标记的发现。此外，从单个皮质表面播种为我们提供了值得注意的优势，即考虑到主体间的巨大解剖可变性，最大限度地减少了假阳性连接，例如当使用几何或模板派生的掩膜(MNI、Talairach等)时，在种子/目标位置附近跨越脑回的连接。这个项目的规模远远超过了我们目前管理/处理数据的能力。事实上，我们的硬件无法支持这些分析。然而，通过增加计算能力和并行处理器，我们可以极大地提高完成项目的速度。在过去的一年里，在已经收集的35名健康受试者中，我们只完成了18名健康受试者的分析。此外，探索50名健康对照的杏仁核连接图将只是该项目的第一阶段。事实上，目前正在收集50名抑郁双相患者、50名缓解双相患者和50名抑郁单相患者的神经成像数据(约50人已经收集完毕，正在等待分析)。在我们初步观察的支持下，我们假设，如果有足够的计算能力，我们的多模式神经成像方法将同意绘制健康个体的正常杏仁核连接，更广泛地说，将同意在体内绘制情感性障碍中的异常杏仁核连接。因此，为了检验我们的假设，我们提出了以下具体目标。具体目标1：在50名健康活体受试者中，结合高分辨率MPRAGE成像和68个方向的扩散加权成像序列。在这个目标中，我们建议首次在活体内绘制杏仁核解剖连接图。首先(I)我们将使用基于处理流的大脑皮质和皮质下体积的自动重建，该处理流由在freesurfer中实现的外壳脚本(recon-all)控制。第二，(Ii)这些在单个解剖空间中定义的皮质和皮质下掩膜，然后将作为种子/目标区域来运行概率纤维束成像(在FSL中实现的bedpostx和protrackx)。具体目的2：寻找情感障碍潜在的神经解剖学标志物。在这一目标中，我们建议比较50名健康个体和如此大且具有代表性的广泛情绪障碍样本中杏仁核的连接性。该项目的成功不仅取决于解决上述研究挑战的能力，还取决于实现研究进展和直接用于神经成像研究的高性能计算的能力。这个项目雄心勃勃，需要大量的计算，但它将通过澄清人类大脑的杏仁核连接图，在健康个体和情感障碍的大样本中，成为情感文学中的一个里程碑。这些神经解剖学证据将作为发展杏仁核功能作用的现代和整体理论的基础，以及随后更协调的行为fMRI任务的发展。限速-步骤：首先，为了自动重建大脑的皮质和皮质下区域，recon_all(自由冲浪)大约需要两天/受试者。第二，Bedpostx(FSL)，它代表使用采样技术获得的扩散参数的贝叶斯估计，运行马尔可夫链蒙特卡罗抽样来建立每个体素的扩散参数的分布，并且需要大约3天的处理时间/对象(切片)。该脚本允许并行作业；实际上，每个片都可以单独进行预处理。第三(Iii)，为了重建我们目前正在探索的30条概率轨迹并最终绘制杏仁核的图谱，Protackx(FSL)大约需要24小时。同样，每个概率航迹都可以独立地进行预处理。我们的招聘率约为1门/周。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In the last 15 years, we have seen an increasing interest in understanding the role of the amygdala, a complex structure involved in a wide range of normal behavioral functions and psychiatric conditions. Damage to the temporal lobe, where the amygdala is located, results in profound changes in primordial behaviors (fear, feeding and sexuality). Several functional neuroimaging studies have explored the role that the amygdala plays in emotional processing and regulation and, more broadly, in human social behavior (reward, motivation and learning), building upon hypotheses of previous cytoarchitectural findings of post-mortem human and animal studies. However, the lack of knowledge of amygdala organization and its connections to other brain areas and the complexity of emotional functions measured by behavioral tasks limits our understanding and require further investigation in "in vivo" human subjects. In our preliminary data we have been able to reconstruct fibers connecting the seed region, amygdala, to the ipsilateral cortices (frontal, temporal, parietal, insular, occipital cortices). Interestingly, despite the fact that the targets regions are wide-ranging, we found that the amygdala connects to highly functionally specialized sub-domains of these cortices, salient to the emotional process and regulation. Additionally, reconstructing the fibers connecting the amygdala to subcortical nuclei (nucleus accumbens, basal ganglia, thalamus), we have been able to identify in human subjects whether the amygdala connects to the ipsilateral cortices directly or indirectly via amygdala-subcortical-cortical circuits, paralleling and going far beyond findings of histological markers in animal studies. Moreover, seeding from individual cortical surface provided us with the noteworthy advantage of taking into account the large intersubjective anatomical variability, minimizing false positive connections such as those crossing a gyrus near the seed/target location that occurs when geometrical or template-derived masks (MNI, Talairach, etc ) are employed. The scale of this project far outpaces our current ability to manage/process data. Our hardware, in fact, is unable to support these analyses. However, the speed at which we could complete our projects could be greatly improved with additional computational power and parallel processors. In the past year, we have been able to finalize the analyses of only 18 healthy subjects out of the 35 already collected. Furthermore, exploring the amygdala connectivity map in 50 healthy controls will be just a first stage of this project. In fact, neuroimaging data are currently being collected in 50 depressed bipolar, 50 remitted bipolar, and 50 depressed unipolar individuals (about 50 have already been collected and are waiting to be analyzed). Supported by our initial observation we hypothesize that our multimodal neuroimaging approach, if facilitated by adequate computational power, will consent the mapping of the normative amygdala connectivity in healthy individuals and, more broadly of the abnormal amygdala connectivity in affective disorders, in vivo. Hence, to test our hypothesis we propose the following specific aims. Specific Aim 1: To combine a high-resolution MPRAGE acquisition with a 68-directions diffusion-weighted imaging sequence in 50 living healthy subjects. In this aim we propose to map the amygdala anatomical connectivity for the first time in vivo. First (i) we will employ an automated reconstruction of the brain's cortical and subcortical volumes based on a processing stream, controlled by a shell script (recon-all), implemented in FREESURFER. Second, (ii) these cortical and subcortical masks, defined in individual anatomical space, will then serve as seed/target regions to run probabilistic tractography (bedpostx and probtrackx, implemented in FSL). Specific Aim 2: To identify potential neuroanatomical marker of affective disorders. In this aim we propose to compare the amygdala connectivity in 50 healthy individuals and in such a large and representative sample of the wide spectrum of mood disorders. The success of this project depends on the ability not only to address the research challenges just listed but also to implement research advances and high performance computing of direct utility to the neuroimaging research. This project is ambitious and computationally-demanding, but it will be a milestone in the literature of emotion by clarifying the amygdala connectivity map of the human brain, in a large sample of healthy individuals and affective disorders. Such neuro-anatomical evidence will serve as groundwork to develop modern and holistic theories of the functional role of the amygdala and subsequent development of more tuned behavioral fMRI tasks. Rate-limiting-steps: First (i), to automatically reconstruct brain's cortical and subcortical regions, recon_all (FREESURFER) takes about 2 ¿ days/subject. Second (ii), bedpostx (FSL), which stand for Bayesian Estimation of Diffusion Parameters Obtained using Sampling Techniques, runs Markov Chain Monte Carlo sampling to build up distributions on diffusion parameters at each voxel and requires about 3 days processing time/subject (64 slices). This script allows parallel jobs; indeed, each slice could be preprocessed independently. Third (iii), to reconstruct the 30 probability tracks that we are currently exploring and ultimately map the amygdala, probtackx (FSL) takes about 24 hours/subject. Again, each probability tracks could be preprocessed independently. Our recruitment rate is about 1 subject/week.