作者是为美国国立卫生研究院授予支持表示感谢： 美国国立卫生研究院/ NIBIB 5R01EB006204 - 03多元影像学分析方法 NIH / NIA的5R01AG026114 - 02早期AD与ASL MRI及协方差分析检测 ADNI：阿尔茨海默氏病影像学倡议（ADNI）研究院（NIH U01AG024904）提供影像数据。这个项目的数据收集和共享的阿尔茨海默病的神经影像学倡议（ADNI）（美国国立卫生格兰特U01 AG024904研究院）资助。 ADNI是由国家老龄问题研究所，国家生物医学成像和生物工程研究所，并通过从以下几个：雅培，阿斯利康AB，拜耳先灵医药公司，施贵宝，卫材全球临床开发，Elan公司的慷慨捐助， Genentech公司，GE医疗集团，葛兰素史克，Innogenetics，强生公司，礼来公司，Medpace公司，默克公司和有限责任公司，诺华公司，辉瑞公司，F.霍夫曼罗氏，先灵葆雅，Synarc公司和惠氏公司，以及非营利性的合作伙伴阿尔茨海默氏症协会和老年痴呆症的药物发现基金会，与来自美国食品和药物管理局的参与。促进私营部门的贡献ADNI为国家健康（研究院基金会<a href="http://www.fnih.org">http://www.fnih.org</a> ）。承批人的组织是北加州理工学院的研究和教育，这项研究是由阿尔茨海默氏病，圣地亚哥加州大学的合作研究协调。在加州大学洛杉矶分校神经影像实验室ADNI数据传播。也支持这项研究是由美国国立卫生研究院拨款P30 AG010129，K01 AG030514，和达纳基金会。

<ol><li>为了让一个多元分析的概念概述，我们可以想像一个非常简单的情况：50人的参与者，只有三个地区，在大脑中体素（图1 = 3维像素）表示一个假设的数据进行测量。 （此处插入图1，请阅读标题为语音结束。） </li><li>多元分析的总体目标是，以确定数据的方差的主要来源，然后在利益产生重大影响的方差这些来源的数据描述。图2显示了一个简单的例子。 （此处插入图2，阅读标题为语音“结束了。） </li><li>现在，我们应用单因素和多因素分析临床资料一套。我们下载了95早期阿尔茨海默氏症患者和阿尔茨海默氏病影像学倡议（http://www.loni.ucla.edu/ADNI/）网站102的年龄匹配的对照FDG - PET的休息扫描。我们随机挑选20个病人和控制的扫描，并指定他们作为我们的推导样本。余下的75％和82扫描，分别构成复制样本。现在将得到单因素和多因素阿尔茨海默氏病（AD）的标记在推导样本，并在复制样本测试其诊断疗效。 </li><li>对于元标记，我们对比20与20控制广告扫描扫描推导样本，并挑选大脑的位置，显示最大的PET信号在AD患者的减少，t检验所示。为了本地区的测试诊断疗效，我们在这个位置检查复制样本中的数据，并绘制其作为疾病状态的功能PET信号。 </li><li>多元的标记，我们首先执行上，结合40推导样本扫描PCA，然后构建一个从第5主成分，其主题缩放系数显示了最大的AD患者和健康对照组之间的平均差异的协方差模式。 （详情可在这2个有代表性的论文。）诊断协模式，取得形式的推导样本然后前瞻性应用到复制样本。由此产生的主体缩放因素绘制作为疾病状态的功能。 </li><li>为了提供一个更普遍的单因素和多步骤4和5的方法比较，我们执行“分裂样品”模拟并重复这两个步骤，重采样数据的1000倍，每次形成20/20推导样品和75/82 AD患者和健康对照组重新复制。从推导样本计算单因素和多因素的疾病标志物和决定的阈值设置，错误归类为AD（=特异性为95％）1健康对照。其具体的决策阈值的疾病标志物，然后前瞻性应用复制样本。所有重采样迭代复制样本的分类错误率记录。 </li></ol>代表性的成果 单因素表现的结果可以看出，图3中详细。在超级颞上回，布罗德曼38区，面积最大的广告相关的葡萄糖赤字。取得的ROC曲线下面积AUC = 0.90。这种反差的复制样本的泛化是相当不错的，根据ROC曲线下面积AUC = 0.84。 多元的表现 ，结果可以看出，在图4的细节。积极负荷相对保存在面对疾病的信号提示，地区被发现在小脑，而相关的信号损失被发现parietotemporal和正面的地区，后扣带回。根据中华民国曲线推导和复制样本地区比0.96和0.88的单变量标记稍微好一点。 分割样本模拟的结果可以看出，图5中详细。数字显示，多元标记提供了更好的诊断性能比单变量标记复制。多元标记的平均总误差率是0.203，而为单变量的标记，它是0.307。 <img src="/files/ftp_upload/1988/1988fig1.jpg" alt="图1" /> 图1：这个简单的数字描述了单因素和多因素分析战略之间的差别：一个假设的三维数据集，在此图中显示。在左侧，有3绘制变量之间没有相关性。相反的右侧，可以看到一个表明所有三个体素之间的正相关性变异的主要来源。一个单因素分析，仅仅考虑对一个体素的体素的基础上平均值，不能告诉任何这两种情况之间的差异。多因素分析，对比，确定的主要来源瓦里安CE中的数据（红色箭头），然后再继续兴建神经激活模式，形成这些来源。 <img src="/files/ftp_upload/1988/1988fig2.jpg" alt="图2" /> 图2：这张幻灯片显示了一个简化的形式，任何神经影像数据的多变量分析的基本素养。数据数组Y（S，X），这取决于一个主题索引S，和一个体素指数X，表明大脑中的体素的位置，被分解成几个术语的总和。首先，一个纯粹的受依赖的因子得分，SSF（S），和一个纯粹的体素依赖的协方差模式的产品，V（X）。二，激活，不能占协模式是在主题和体素依赖，噪声项E（S，X）抓获。下面的方程的两个图形的主题缩放系数和协方差模式的一个例子。每一个参与者，体现了协模式，只是在不同程度上的主题因子得分所示。而不是保持跟踪每个体素的行为分开，协方差模式，其主体表达提供一个吝啬的方差的主要来源总结。作为主体的缩放因子增加的幅度，以蓝色表示在协模式的地区降低其相关的激活，而在红色区域，同时表示，增加其相关的激活。主题因子得分可以与外部变量的利益，如受年龄或行为表现在认知任务，并没有被应用到这种关联的多重比较校正。 这种分解的几个技术存在，但最常见的一种主要成分分析（PCA）。这是我们的首选技术。注意：主题缩放因子可以通过平等维度设置任何数据投影到协模式，不只是生产摆在首位的协方差模式的数据集。这使得协模式适合用于测试是否可以在不同的数据集复制大脑的行为，在一个数据集的关系。 <img src="/files/ftp_upload/1988/1988fig3.jpg" alt="图3" /> 图3，此图显示的单因素分析的结果。在左下方的面板，FDG的信号值绘制的区域显示的最大的广告相关的推导样本中的赤字。它的MNI的坐标是X = 2毫米，Y = -48毫米，Z = 30毫米（楔前叶/盈科，布罗德曼31区）。右下面板显示FDG的信号在此复制样本的位置。人们可以欣赏复制样本中的AD患者和控制之间的FDG的差异，但总体仍然显着，减少与组之间的重叠。 <img src="/files/ftp_upload/1988/1988fig4.jpg" alt="图4" /> 图4这个数字显示的多因素分析的结果。在顶部面板中，我们显示显着积极和消极加权领域中的红色和蓝色的协方差模式（P &lt;0.001），分别显示多个轴位片。请注意，我们按比例缩减其全球平均值每次扫描，让红色和蓝色表示相对而不是绝对增加，并降低与疾病严重程度的PET信号。因此，红色区域相对保存在面对疾病的暗示，而蓝色表示的信号损失，为疾病的后果。红色区域主要分布在小脑，而蓝色区域出现在后扣带回，parietotemporal和额叶区域。左下面板：AD相关的协方差模式的主题因子得分显示在推导样本。高等教育的学科分数发现AD患者。右下面板：这里绘制主体因素导致AD相关的协方差模式复制样本应用前景的分数。一个可以理解的复制样本中增加了重叠的诊断对比略有恶化，但泛化诊断疗效明显比在单因素的情况下更好。 <img src="/files/ftp_upload/1988/1988fig5.jpg" alt="图5" /> 图5：此图显示了1000分割样本模拟结果。上市是手段和复制样本的单因素和多因素诊断错误率的标准偏差。人们可以欣赏多元标记的泛化性能相当好，虽然有点超过一元标记的变量。

<ol>
	<li>Moeller, J. R., Strother, S. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+regional+covariance+approach+to+the+analysis+of+functional+patterns+in+positron+emission+tomographic+data.">A regional covariance approach to the analysis of functional patterns in positron emission tomographic data.</a> J Cereb Blood Flow Metab. 11 (2), A121-A121 (1991).</li><li>Scarmeas, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Covariance+PET+patterns+in+early+Alzheimer's+disease+and+subjects+with+cognitive+impairment+but+no+dementia:+utility+in+group+discrimination+and+correlations+with+functional+performance.">Covariance PET patterns in early Alzheimer's disease and subjects with cognitive impairment but no dementia: utility in group discrimination and correlations with functional performance.</a> Neuroimage. 23 (1), 35-35 (2004).</li><li>Siedlecki, K. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Examining+the+multifactorial+nature+of+cognitive+aging+with+covariance+analysis+of+positron+emission+tomography+data.">Examining the multifactorial nature of cognitive aging with covariance analysis of positron emission tomography data.</a> J Int Neuropsychol Soc. 15 (6), 973-973 (2009).</li><li>Burnham, K. P., Anderson, D. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Model selection and multimodel inference a practical information-theoretic approach. , (2002).</li><li>Moeller, J. R., Strother, S. C., Sidtis, J. J., Rottenberg, D. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Scaled+subprofile+model:+a+statistical+approach+to+the+analysis+of+functional+patterns+in+positron+emission+tomographic+data.">Scaled subprofile model: a statistical approach to the analysis of functional patterns in positron emission tomographic data.</a> J Cereb Blood Flow Metab. 7 (5), 649-649 (1987).</li><li>Habeck, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Multivariate+and+univariate+neuroimaging+biomarkers+of+Alzheimer's+disease.">Multivariate and univariate neuroimaging biomarkers of Alzheimer's disease.</a> Neuroimage. 40 (4), 1503-1503 (2008).</li><li>Habeck, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+new+approach+to+spatial+covariance+modeling+of+functional+brain+imaging+data:+ordinal+trend+analysis.">A new approach to spatial covariance modeling of functional brain imaging data: ordinal trend analysis.</a> Neural Comput. 17 (7), 1602-1602 (2005).</li><li>McIntosh, A. R., Bookstein, F. L., Haxby, J. V., Grady, C. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Spatial+pattern+analysis+of+functional+brain+images+using+partial+least+squares.">Spatial pattern analysis of functional brain images using partial least squares.</a> Neuroimage. 3 Pt 1, 143-143 (1996).</li><li>McIntosh, A. R., Lobaugh, N. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Partial+least+squares+analysis+of+neuroimaging+data:+applications+and+advances.">Partial least squares analysis of neuroimaging data: applications and advances.</a> Neuroimage. 23, S250-S250 (2004).</li></ol>

我们希望给观众的多元分析的基础气息;鼓励有兴趣的观众是来检查我们的网​​站。多变量分析中的参数作了一些选择，可相当多的争论议题的辩论。我们不遗余力地在这篇文章中讨论这些问题，以避免重大问题分心。首先，我们选择了第6个主成分来构造我们的广告相关的协方差模式。这种选择有理论方面的原因，我们没有讨论4。特别是6个主成分的选择，虽然不是对于我们的观点是至关重要的：一个可以选择的范围从2到20个，仍取得优异的泛化性能的多元分割样本模拟标记。结果推导和复制样本科目数量的选择方面也同样强劲。我们选择了20个科目复制样本两组，但是这是纯粹数学的方便，以加快计算。同样，如果在推导样本科目的数量增加，这两种技术的相对优势，我们的研究结果将举行。 其次，我们只介绍最基本的一种多因素分析。从机器学习文学，线性和非线性PCA的转换之前，和其他各种皱纹借来的技术相当复杂化是可行的，可以提高泛化性能更。为了简单起见，我们没有在这篇文章中谈到这些可能性。

basics of multivariate analysis in neuroimaging data

神经影像数据的多变量分析技术最近日益受到重视，因为他们有许多吸引人的特点，比较常用的一元，体素的智慧，技术，不能轻易实现的<sup&gt; 1,5,6,7,8,9</sup&gt;。多元方法评估整个大脑区域激活的相关性/协方差，而不是由一个体素体素的基础上进行。因此，他们的结果可以更容易地解释作为神经网络的签名。另一方面，单因素的方法，不能直接解决在大脑区域间的相关性。多元方法也可能导致更大的统计力量，与单变量技术相比，这是被迫体素明智的多重比较采用非常严格的校正。此外，多元的技术也借给自己好得多从一个数据集的分析结果的应用前景，以全新的数据集。多元技术，从而很好地提供与行为的平均差异和相关性，同样以单变量的方法与统计力量和潜在的更大更好的可重复性检查，信息。在这些优势是高进入障碍多元方法的使用，防止在社会上的更广泛应用。神经学家成为熟悉多元分析技术，该领域的初步调查可能目前的一个，虽然算法类似，不同的侧重点，通常是由有数学背景的人的方法五花八门。我们相信，多元分析技术有足够的潜力，以保证更好地传播。研究人员应该可以聘请他们在知情和通俗易懂的方式。目前的文章是在说教对于新手的多元技术引进的尝试。其次是一个非常简单的应用程序，以诊断阿尔茨海默病的神经影像学倡议（ADNI）清楚地表明多元方法的性能优越，设置数据的一个概念引入。

Watch this Scientific Journal Video about Basics of Multivariate Analysis in Neuroimaging Data at JoVE.com

Basics of Multivariate Analysis in Neuroimaging Data

本文介绍的多因素分析的基础知识和对比比较常用的体素明智的单因素分析。分析这两种类型的应用到临床神经科学数据集。补充分半的模拟显示出更好的复制在独立的数据集的多元结果。

多元分析的基础，在影像学资料

Multivariate analysis techniques for neuroimaging data have recently received increasing attention as they have many attractive features that cannot be ...

basics-of-multivariate-analysis-in-neuroimaging-data

Research

JoVE Journal

Neuroscience

16.7K 次观看.  Columbia University. 本文介绍的多因素分析的基础知识和对比比较常用的体素明智的单因素分析。分析这两种类型的应用到临床神经科学数据集。补充分半的模拟显示出更好的复制在独立的数据集的多元结果。

视频: Basics of Multivariate Analysis in Neuroimaging Data

Cross-Modal Multivariate Pattern Analysis

Multivariate pattern analysis (MVPA) is an increasingly popular method of analyzing functional magnetic resonance imaging (fMRI) data1-4. Typically, the method is used to identify a subject's perceptual experience from neural activity in certain regions of the brain. For instance, it has been employed to predict the orientation of visual gratings a subject perceives from activity in early visual cortices5 or, analogously, the content of speech from activity in early auditory cortices6.
Here, we present an extension of the classical MVPA paradigm, according to which perceptual stimuli are not predicted within, but across sensory systems. Specifically, the method we describe addresses the question of whether stimuli that evoke memory associations in modalities other than the one through which they are presented induce content-specific activity patterns in the sensory cortices of those other modalities. For instance, seeing a muted video clip of a glass vase shattering on the ground automatically triggers in most observers an auditory image of the associated sound; is the experience of this image in the "mind's ear" correlated with a specific neural activity pattern in early auditory cortices? Furthermore, is this activity pattern distinct from the pattern that could be observed if the subject were, instead, watching a video clip of a howling dog?
In two previous studies7,8, we were able to predict sound- and touch-implying video clips based on neural activity in early auditory and somatosensory cortices, respectively. Our results are in line with a neuroarchitectural framework proposed by Damasio9,10, according to which the experience of mental images that are based on memories - such as hearing the shattering sound of a vase in the "mind's ear" upon seeing the corresponding video clip - is supported by the re-construction of content-specific neural activity patterns in early sensory cortices.

Classical multivariate pattern analysis predicts sensory stimuli a subject perceives from neural activity in the corresponding cortices (e.g. visual stimuli from activity in visual cortex). Here, we apply pattern analysis cross-modally and show that sound- and touch-implying visual stimuli can be predicted from activity in auditory and somatosensory cortices, respectively.

跨模态的多元格局分析

Multivariate pattern analysis (MVPA) is an increasingly popular method of analyzing functional magnetic resonance imaging (fMRI) data1-4. Typically, the ...

科研

神经科学

Functional Neuroimaging Using Ultrasonic Blood-brain Barrier Disruption and Manganese-enhanced MRI

Although mice are the dominant model system for studying the genetic and molecular underpinnings of neuroscience, functional neuroimaging in mice remains technically challenging. One approach, Activation-Induced Manganese-enhanced MRI (AIM MRI), has been used successfully to map neuronal activity in rodents 1-5. In AIM MRI, Mn2+ acts a calcium analog and accumulates in depolarized neurons 6,7. Because Mn2+ shortens the T1 tissue property, regions of elevated neuronal activity will enhance in MRI. Furthermore, Mn2+ clears slowly from the activated regions; therefore, stimulation can be performed outside the magnet prior to imaging, enabling greater experimental flexibility. However, because Mn2+ does not readily cross the blood-brain barrier (BBB), the need to open the BBB has limited the use of AIM MRI, especially in mice.
One tool for opening the BBB is ultrasound. Though potentially damaging, if ultrasound is administered in combination with gas-filled microbubbles (i.e., ultrasound contrast agents), the acoustic pressure required for BBB opening is considerably lower. This combination of ultrasound and microbubbles can be used to reliably open the BBB without causing tissue damage 8-11.
Here, a method is presented for performing AIM MRI by using microbubbles and ultrasound to open the BBB. After an intravenous injection of perflutren microbubbles, an unfocused pulsed ultrasound beam is applied to the shaved mouse head for 3 minutes. For simplicity, we refer to this technique of BBB Opening with Microbubbles and UltraSound as BOMUS 12. Using BOMUS to open the BBB throughout both cerebral hemispheres, manganese is administered to the whole mouse brain. After experimental stimulation of the lightly sedated mice, AIM MRI is used to map the neuronal response.
To demonstrate this approach, herein BOMUS and AIM MRI are used to map unilateral mechanical stimulation of the vibrissae in lightly sedated mice 13. Because BOMUS can open the BBB throughout both hemispheres, the unstimulated side of the brain is used to control for nonspecific background stimulation. The resultant 3D activation map agrees well with published representations of the vibrissae regions of the barrel field cortex 14. The ultrasonic opening of the BBB is fast, noninvasive, and reversible; and thus this approach is suitable for high-throughput and/or longitudinal studies in awake mice.

A technique is described for broadly opening the blood-brain barrier in the mouse using microbubbles and ultrasound. Using this technique, manganese can be administered to the mouse brain. Because manganese is an MRI contrast agent that accumulates in depolarized neurons, this approach enables imaging of neuronal activity.

使用超声波血脑屏障破坏和锰增强MRI的脑功能成像

Although mice are the dominant model system for studying the genetic and molecular underpinnings of neuroscience, functional neuroimaging in mice remains ...

Applications of EEG Neuroimaging Data: Event-related Potentials, Spectral Power, and Multiscale Entropy

When considering human neuroimaging data, an appreciation of signal variability represents a fundamental innovation in the way we think about brain signal. Typically, researchers represent the brain's response as the mean across repeated experimental trials and disregard signal fluctuations over time as "noise". However, it is becoming clear that brain signal variability conveys meaningful functional information about neural network dynamics. This article describes the novel method of multiscale entropy (MSE) for quantifying brain signal variability. MSE may be particularly informative of neural network dynamics because it shows timescale dependence and sensitivity to linear and nonlinear dynamics in the data.

Neuroimaging researchers typically consider the brain's response as the mean activity across repeated experimental trials and disregard signal variability over time as "noise". However, it is becoming clear that there is signal in that noise. This article describes the novel method of multiscale entropy for quantifying brain signal variability in the time domain.

脑电图神经影像数据：事件相关电位，光谱功率，和多尺度熵的应用

When considering human neuroimaging data, an appreciation of signal variability represents a fundamental innovation in the way we think about brain ...

TIRFM and pH-sensitive GFP-probes to Evaluate Neurotransmitter Vesicle Dynamics in SH-SY5Y Neuroblastoma Cells: Cell Imaging and Data Analysis

Synaptic vesicles release neurotransmitters at chemical synapses through a dynamic cycle of fusion and retrieval. Monitoring synaptic activity in real time and dissecting the different steps of exo-endocytosis at the single-vesicle level are crucial for understanding synaptic functions in health and disease.
Genetically-encoded pH-sensitive probes directly targeted to synaptic vesicles and Total Internal Reflection Fluorescence Microscopy (TIRFM) provide the spatio-temporal resolution necessary to follow vesicle dynamics. The evanescent field generated by total internal reflection can only excite fluorophores placed in a thin layer (&#60;150 nm) above the glass cover on which cells adhere, exactly where the processes of exo-endocytosis take place. The resulting high-contrast images are ideally suited for vesicles tracking and quantitative analysis of fusion events.
In this protocol, SH-SY5Y human neuroblastoma cells are proposed as a valuable model for studying neurotransmitter release at the single-vesicle level by TIRFM, because of their flat surface and the presence of dispersed vesicles. The methods for growing SH-SY5Y as adherent cells and for transfecting them with synapto-pHluorin are provided, as well as the technique&#160;to perform TIRFM and imaging. Finally, a strategy aiming to select, count, and analyze fusion events at whole-cell and single-vesicle levels is presented.
To validate the imaging procedure and data analysis approach, the dynamics of pHluorin-tagged vesicles are&#160;analyzed under resting and stimulated (depolarizing potassium concentrations) conditions. Membrane depolarization increases the frequency of fusion events and causes a parallel raise of the net fluorescence signal recorded in whole cell. Single-vesicle analysis reveals modifications of fusion-event behavior (increased peak height and width). These data suggest that potassium depolarization not only induces a massive neurotransmitter release but also modifies the mechanism of vesicle fusion and recycling.
With the appropriate fluorescent probe, this technique can be employed in different cellular systems to dissect the mechanisms of constitutive and stimulated secretion.

This paper provides a method for investigating neurotransmitter vesicle dynamics in neuroblastoma cells, using a synaptobrevin2-pHluorin construct and Total Internal Reflection Fluorescence Microscopy. The strategy developed for image processing and data analysis is also reported.

TIRFM和pH敏感的GFP-探针来评估神经递质囊泡动力学SH-SY5Y神经母细胞瘤：细胞成像和数据分析

Synaptic vesicles release neurotransmitters at chemical synapses through a dynamic cycle of fusion and retrieval. Monitoring synaptic activity in real ...

Analyzing Synaptic Modulation of Drosophila melanogaster Photoreceptors after Exposure to Prolonged Light

The nervous system has the remarkable ability to adapt and respond to various stimuli. This neural adjustment is largely achieved through plasticity at the synaptic level. The Active Zone (AZ) is the region at the presynaptic membrane that mediates neurotransmitter release and is composed of a dense collection of scaffold proteins. AZs of Drosophila melanogaster (Drosophila) photoreceptors undergo molecular remodeling after prolonged exposure to natural ambient light. Thus the level of neuronal activity can rearrange the molecular composition of the AZ and contribute to the regulation of the functional output.
Starting from the light exposure set-up preparation to the immunohistochemistry, this protocol details how to quantify the number, the spatial distribution, and the delocalization level of synaptic molecules at AZs in Drosophila photoreceptors. Using image analysis software, clusters of the GFP-fused AZ component Bruchpilot were identified for each R8 photoreceptor (R8) axon terminal. Detected Bruchpilot spots were automatically assigned to individual R8 axons. To calculate the distribution of spot frequency along the axon, we implemented a customized software plugin. Each axon&#39;s start-point and end-point were manually defined and the position of each Bruchpilot spot was projected onto the connecting line between start and end-point. Besides the number of Bruchpilot clusters, we also quantified the delocalization level of Bruchpilot-GFP within the clusters. These measurements reflect in detail the spatially resolved synaptic dynamics in a single neuron under different environmental conditions to stimuli.

Analyzing Synaptic Modulation of Drosophila melanogaster Photoreceptors after Exposure to Prolonged Light

Here we show how to quantify the number and spatial distribution of synaptic active zones in Drosophila melanogaster&#160;photoreceptors, highlighted with a genetically encoded molecular marker, and their modulation after prolonged exposure to light.

分析突触调制<em&gt;果蝇</em&gt;曝光时间延长后，光光感受器

The nervous system has the remarkable ability to adapt and respond to various stimuli. This neural adjustment is largely achieved through plasticity at ...

Neuroimaging Field Methods Using Functional Near Infrared Spectroscopy (NIRS) Neuroimaging to Study Global Child Development: Rural Sub-Saharan Africa

Portable neuroimaging approaches provide new advances to the study of brain function and brain development with previously inaccessible populations and in remote locations. This paper shows the development of field functional Near Infrared Spectroscopy (fNIRS) imaging to the study of child language, reading, and cognitive development in a rural village setting of C&#244;te d&#39;Ivoire. Innovation in methods and the development of culturally appropriate neuroimaging protocols allow&#160;a first-time look into the brain&#39;s development and children&#39;s learning outcomes in understudied environments. This paper demonstrates protocols for transporting and setting up a mobile laboratory, discusses considerations for field versus laboratory neuroimaging, and presents a guide for developing neuroimaging consent procedures and building meaningful long-term collaborations with local government and science partners. Portable neuroimaging methods can be used to study complex child development contexts, including the impact of significant poverty and adversity on brain development. The protocol presented here has been developed for use in C&#244;te d&#39;Ivoire, the world&#39;s primary source of cocoa, and where reports of child labor in the cocoa sector are common. Yet, little is known about the impact of child labor on brain development and learning. Field neuroimaging methods have the potential to yield new insights into such urgent issues, and the development of children globally.

Neuroimaging Field Methods Using Functional Near Infrared Spectroscopy NIRS Neuroimaging to Study Global Child Development: Rural Sub-Saharan Africa

Portable neuroimaging approaches (functional Near Infrared Spectroscopy) provide advances to the study of the brain in previously inaccessible regions; here, rural C&#244;te d&#39;Ivoire. Innovation in methods and development of culturally-appropriate neuroimaging protocols permits novel study of the brain&#39;s development and children&#39;s learning outcomes in environments with significant poverty and adversity.

利用功能近红外光谱成像技术研究全球儿童发展: 农村撒哈拉以南非洲地区的神经影像场方法

Portable neuroimaging approaches provide new advances to the study of brain function and brain development with previously inaccessible populations and in ...

Data Acquisition and Analysis In Brainstem Evoked Response Audiometry In Mice

Brainstem evoked response audiometry (BERA) is of central relevance in the clinical neurophysiology. As other evoked potential (EP) techniques, such as visually evoked potentials (VEPs) or somatosensory evoked potentials (SEPs), the auditory evoked potentials (AEPs) are triggered by the repetitive presentation of identical stimuli, the electroencephalographic (EEG) response of which is subsequently averaged resulting in distinct positive (p) and negative (n) deflections. In humans, both the amplitude and the latency of individual peaks can be used to characterize alterations in synchronization and conduction velocity in the underlying neuronal circuitries. Importantly, AEPs are also applied in basic and preclinical science to identify and characterize the auditory function in pharmacological and genetic animal models. Even more, animal models in combination with pharmacological testing are utilized to investigate for potential benefits in the treatment of sensorineural hearing loss (e.g., age- or noise-induced hearing deficits). Here we provide a detailed and integrative description of how to record auditory brainstem-evoked responses (ABRs) in mice using click and tone-burst application. A specific focus of this protocol is on pre-experimental animal housing, anesthesia, ABR recording, ABR filtering processes, automated wavelet-based amplitude growth function analysis, and latency detection.

Brainstem evoked response audiometry is an important tool in clinical neurophysiology. Nowadays, brainstem evoked response audiometry is also applied in the basic science and preclinical studies involving both pharmacological and genetic animal models. Here we provide a detailed description of how auditory brainstem responses can be successfully recorded and analyzed in mice.

脑干中的数据采集与分析 在小鼠中引发响应音频测量

Brainstem evoked response audiometry (BERA) is of central relevance in the clinical neurophysiology. As other evoked potential (EP) techniques, such as ...

Meta-analysis of Voxel-Based Neuroimaging Studies using Seed-based d Mapping with Permutation of Subject Images (SDM-PSI)

Most methods for conducting meta-analysis of voxel-based neuroimaging studies do not assess whether effects are not null, but whether there is a convergence of peaks of statistical significance, and reduce the assessment of the evidence to a binary classification exclusively based on p-values (i.e., voxels can only be &ldquo;statistically significant&rdquo; or &ldquo;non-statistically significant&rdquo;). Here, we detail how to conduct a meta-analysis using Seed-based d Mapping with Permutation of Subject Images (SDM-PSI), a novel method that uses a standard permutation test to assess whether effects are not null. We also show how to grade the strength of the evidence according to a set of criteria that considers a range of statistical significance levels (from more liberal to more conservative), the amount of data or the detection of potential biases (e.g., small-study effect and excess of significance). To exemplify the procedure, we detail the conduction of a meta-analysis of voxel-based morphometry studies in obsessive-compulsive disorder, and we provide all the data already extracted from the manuscripts to allow the reader to replicate the meta-analysis easily. SDM-PSI can also be used for meta-analyses of functional magnetic resonance imaging, diffusion tensor imaging, position emission tomography and surface-based morphometry studies.

Meta-analysis of Voxel-Based Neuroimaging Studies using Seed-based d Mapping with Permutation of Subject Images SDM-PSI

We detail how to conduct a meta-analysis of voxel-based neuroimaging studies using Seed-based d Mapping with Permutation of Subject Images (SDM-PSI).

使用基于种子的 d 映射对基于体素的神经成像研究进行元分析，并结合主题图像的排列 （SDM-PSI）

Most methods for conducting meta-analysis of voxel-based neuroimaging studies do not assess whether effects are not null, but whether there is a ...

Measuring Statistical Learning Across Modalities and Domains in School-Aged Children Via an Online Platform and Neuroimaging Techniques

Statistical learning, a fundamental skill to extract regularities in the environment, is often considered a core supporting mechanism of the first language development. While many studies of statistical learning are conducted within a single domain or modality, recent evidence suggests that this skill may differ based on the context in which the stimuli are presented. In addition, few studies investigate learning as it unfolds in real-time, rather focusing on the outcome of learning. In this protocol, we describe an approach for identifying the cognitive and neural basis of statistical learning, within an individual, across domains (linguistic vs. non-linguistic) and sensory modalities (visual and auditory). The tasks are designed to cast as little cognitive demand as possible on participants, making it ideal for young school-aged children and special populations. The web-based nature of the behavioral tasks offers a unique opportunity for us to reach more representative populations nationwide, to estimate effect sizes with greater precision, and to contribute to open and reproducible research. The neural measures provided by the functional magnetic resonance imaging (fMRI) task can inform researchers about the neural mechanisms engaged during statistical learning, and how these may differ across individuals on the basis of domain or modality. Finally, both tasks allow for the measurement of real-time learning, as changes in reaction time to a target stimulus is tracked across the exposure period. The main limitation of using this protocol relates to the hour-long duration of the experiment. Children might need to complete all four statistical learning tasks in multiple sittings. Therefore, the web-based platform is designed with this limitation in mind so that tasks may be disseminated individually. This methodology will allow users to investigate how the process of statistical learning unfolds across and within domains and modalities in children from different developmental backgrounds.

Presented here is a protocol introducing a set of child-friendly statistical learning tasks geared towards examining children&#8217;s learning of temporal statistical patterns across domains and sensory modalities. The developed tasks collect behavioral data using the web-based platform and task-based functional magnetic resonance imaging (fMRI) data for examining neural engagement during statistical learning.

通过在线平台和神经成像技术测量学龄儿童跨模式和领域的统计学习

Statistical learning, a fundamental skill to extract regularities in the environment, is often considered a core supporting mechanism of the first ...

Head Implants for the Neuroimaging of Awake, Head-Fixed Rats

Anesthetics, commonly used in preclinical and fundamental scientific research, have a depressive influence on the metabolic, neuronal, and vascular functions of the brain and can adversely influence neurophysiological results. The use of awake animals for research studies is advantageous but poses the major challenge of keeping the animals calm and stationary to minimize motion artifacts throughout data acquisition. Awake imaging in smaller-sized rodents (e.g., mice) is very common but remains scant in rats as rats are bigger, stronger, and have a greater tendency to oppose movement restraints and head fixation over the long durations required for imaging. A new model of neuroimaging of awake, head-fixed rats using customized hand-sewn slings, 3D-printed head implants, head caps, and a headframe is described. The results acquired following a single trial of single-whisker stimulation suggest an increase in the intensity of the evoked functional response. The acquisition of the evoked functional response from awake, head-fixed rats is faster than that from anesthetized rats, reliable, reproducible, and can be used for repeated longitudinal studies.

A detailed new procedure for functional imaging of awake, head-fixed rats is described.

用于清醒、头部固定大鼠神经成像的头部植入物

Anesthetics, commonly used in preclinical and fundamental scientific research, have a depressive influence on the metabolic, neuronal, and vascular ...