这项工作是由安东尼奥和Hanna达马西奥马瑟斯基金会和国立卫生研究院（授权号5P50NS019632 - 27）的赠款支持。

1。简介多元模式分析（MVPA）1-4功能磁共振成像（fMRI）数据分析的方法越来越流行。通常情况下，该方法是用来确定一个主题的感性经验在大脑的某些区域的神经活动。例如，它已被用来预测一个主题从早期视觉皮层5的活动或类似的是，从年初的听觉皮层6活动的讲话内容感知的视觉光栅方向。在这个视频文章中，我们描述了一个MVPA新颖的应用程序，它增加了一个额外的扭曲这一基本的，内部模式的范式。在这种方法中，感性的刺激，预计内没有，但整个感觉系统。 2。多元格局分析虽然现在MVPA方法以及建立的神经影像学领域内，我们将开始由pointi吴出MVPA和传统，单因素的fMRI分析之间的主要区别。为此，可以考虑以下两种方法如何去研究在视觉皮层的神经活动在一个简单的视觉<a href="http://www.jove.com/files/ftp_upload/3307/3307_Meyer-Kaplan_Video_1.mov">任务（例如</a>视频剪辑1）: <ol><li>一个主题是两个不同的视觉刺激，例如，一个橘子和苹果的形象的形象。 </li><li>这两种刺激诱发初级视觉皮层的神经活动的具体模式，标志着由6个假想的体素激活水平。 （当然，活动模式由单一的橙色或在现实中的苹果图像演示诱导，将是非常嘈杂;考虑从大量的试验造成的平均图文并茂的模式。） </li><li>在传统的功能磁共振成像分析，可以分析这些模式基本上有两种方式。首先，我们可以专注于平均LEVEL的跨整个地区的利益的活动。 </li><li>在给定的例子中，平均活动水平的差异不显著，使对应的两个刺激的模式，不能从这个角度来看区分。 </li><li>分析这两种模式的另一种方法是在它们之间建立的加减对比:每个体素，激活水平在"苹果"的条件是从激活水平减去在"橙色"的条件。由此产生的差额，然后可以为每个体素在全脑造影图像的可视化。 </li><li>然而，这些差异可能小，可达到所需的统计标准，只对极少数体素。 </li><li>这是决定性的优势，MVPA发挥其优越的权力派生的事实，单因素分析方法不同，它认为所有体素的同时激活水平，从而能够检测模式。同时，作为mentioneD，只有少数可激活差异显著，当孤立地考虑，这两种模式，在他们的整体考虑，可能确实统计学差异。 </li></ol>之间的第二个主要区别传统的功能磁共振成像分析和MVPA（ <a href="http://www.jove.com/files/ftp_upload/3307/3307_Meyer-Kaplan_Video_2.mov">片段二</a> ）。前一种方法通常试图证明之间有一定的感官刺激和某些大脑活动模式，在一个"转发方式"的统计依赖，换句话说，它要求的类型的问题:"将两种不同的视觉刺激，如面临的图片和一所房子的图片，感兴趣的特定区域的不同活动水平，如梭形面面积？"相比之下，MVPA的成功通常是表示"反向推论"或"解码";类型的典型问题是:"基于神经活动在一个特定的章的模式<html>利益（如初级视觉皮层）的离子，可以预测是否受感知刺激，如橙色，或刺激乙，如一个苹果吗？"注意，但是，在哪个方向和感性的刺激之间的相关性大脑活动的映射并不重要，从统计的角度看:它相当于说，两个刺激导致不同的活动模式，在一个特定的大脑区域，并说，在大脑区域的活动模式允许预测的诱导刺激11换句话说，MVPA灵敏度优于单因素分析，因为它认为体素同时，并没有因为它是一个反方向的收益。 以下的步骤说明如何MVPA一个典型的范式解决问题，是否看到一个苹果诱导比看到一个橙色的初级视觉皮层的神经活动的不同模式（_upload/3307/3307_Meyer-Kaplan_Video_3.mov"&gt;视频短片3）: <ol><li> fMRI数据采集而受看到大量的苹果和橙刺激。 </li><li>采集到的数据被分成一个训练数据集和测试数据集。在目前的例子不同，训练数据集往往是选择大于测试数据集，作为分类的性能可与培训试验的数量预计将增加。 </li><li>从训练集的数据输入到一个模式分类。使用几种可能的数学算法，分类尝试检测在神经模式的特点，区分不同的两个类型的刺激。一个常用（也是我们在自己以前的研究）类型的分类，所谓支持向量机;进一步的细节，读者可以参考在介绍中提到的审查。 </li><li>分类后的培训，已培训试验是provid版与测试数据。从测试数据集的单个试验未标记;换言之，分类并不"知道"是否从"苹果"或"橙色"审判模式。 </li><li>分类属性的一致性，它能够探测到在训练数据集的基础上，最有可能的标签每个测试试验。 </li><li>对于每个模式，"猜"的分类，可以比较正确的刺激标签。 </li><li>如果分类是无法检测到由两种刺激引起的任何模式之间一致的差异，其性能应在机会水平;在例子中给出的双向歧视，这将对应于50％正确的标签。一个显著高于此值的预测性能表明，确实有两类刺激之间的差异。 </li></ol>请注意，它是至关重要的anoth从一个独立的训练和测试数据集呃。只有在这种情况下，可以得出任何结论作为训练集所得的模式的普遍性。 MVPA研究通常使用交叉验证的范式<a href="http://www.jove.com/files/ftp_upload/3307/3307_Meyer-Kaplan_Video_4.mov">（视频剪辑4</a> ）评估分类器的性能。假设MVPA实验包括八个功能运行。在第一个交叉验证一步，从运行1到7和8从运行的数据测试数据分类培训。在第二个步骤，分类，然后训练贯穿6以及运行8 1，随后7上运行测试。这个模式之后，8个交叉验证的步骤进行，每运行一次试运行服务。总体分类器的性能是作为对个体的交叉验证步骤的表演平均计算。虽然此过程中保证独立的培训和测试数据集上的每一步，同时也最大限度地提高总体数量测试试验，它可以是优势时，评估的统计分类的表现意义。 有执行MVPA在互联网上自由可用的软件包;两个例子PyMVPA 12（基于Python <a href="http://www.pymvpa.org">;</a> http://www.pymvpa.org）和普林斯顿大学神经科学研究所（基于Matlab提供的<a href="http://code.google.com/p/princeton-mvpa-toolbox/">工具箱</a> ;呻<a href="http://code.google.com/p/princeton-mvpa-toolbox/">/ code.google.com / P /普林斯顿MVPA工具箱/</a> ）。 3。跨通道MVPA和收敛 - 发散区的框架在介绍中提到，像刚才所描述的实验范式已成功地用于预测相应的感觉皮层的神经活动的感性刺激，换句话说，在视觉皮层和听觉刺激的活动为基础的视觉刺激的基础上在听觉皮层的活动。在这里，我们目前这一基本概念的延伸。具体来说，我们推测，它应该是可以预测的感性刺激，不仅在，但跨越的方式。感官知觉是错综复杂地联系在一起召回的回忆;例如，一个视觉刺激有一个强烈的听觉的含义，如看到一个玻璃在地上打碎花瓶，，将自动触发我们的"心灵的耳朵"图像共享相似之处与听觉形象，我们经历了以前遇到玻璃破碎。据达马西奥两个以上十年前9,10引入一个框架中，看到的花瓶和相应的声音图像之间的内存协会是存储在所谓的收敛发散区（ <a href="http://www.jove.com/files/ftp_upload/3307/3307_Meyer-Kaplan_Video_5.mov">CDZs;视频</a>剪辑5 ）。 CDZs在收到趋同自下而上从各种早期皮层一个预测协会皮层的神经元合奏reas（通过几个层次）和，反过来，发回分歧的自上而下的预测相同皮质网站。由于收敛自下而上的预测，CDZs可以被激活感性陈述，以多种方式的视线和一个惊天动地的花瓶声音 - 例如，由于分歧的自上而下的预测，他们就可以促进重建相关的其他方式的早期皮层信号的图像。达马西奥强调后者点:协会皮层激活CDZs将不会有足够的图像从内存中的自觉召回，只有一次CDZs年初感觉皮层重建明确的神经表征的形象自觉经历。因此，框架预测（纯粹）的视觉刺激，这意味着声音的神经处理的具体<a href="http://www.jove.com/files/ftp_upload/3307/3307_Meyer-Kaplan_Video_6.mov">顺序（</a>视频剪辑6）: <ol><li>首先刺激诱导早期视皮层的神经活动在特定的模式（红色矩形）。 </li><li>通过收敛自下而上的预测，在早期的视觉皮层的神经元，项目推进到一个CDZs（CDZ 1）第一级。收敛的连接模式，允许CDZ 1秒检测一定的活动方式，在早期视皮层。根据确切的模式，CDZ可能或可能不会成为激活。 CDZs从而作为功能榨汁。在这个例子中，两个CDZ 1秒被激活（如红色表示），而第三个是没有在早期视皮层的相应部门的特定活动模式触发。 </li><li> CDZ 1秒发送收敛自下而上的预测CDZ 2秒 ;因此，正如CDZ 1秒检测到一定的活动模式，在早期的视觉皮层，CDZ 2 S能够探测到的活动模式之间CDZ 1 </suB&gt;第几个CDZ 2 S可能成为激活激活CDZ 1秒的具体配置;简单的原因，只有一个 CDZ 2描绘这里。在这个例子中，CDZ 1秒之间的活动模式是足够的，以激活此 CDZ 2。 </li><li>值得注意的是，CDZ 1秒不唯一项目CDZ 2 S也回的早期皮层（蓝色箭头）。这些自上而下的信号就可以完成（可能是噪音）最初由诱导刺激（蓝色矩形）的活动模式。一般来说，红色表示自下而上的激活，而蓝色代表自上而下的激活。 </li><li>通过几个额外的CDZs水平，CDZ 2 S项目提出高阶协会皮层CDZ N S（虚线箭头）。 CDZ N S的一种或几种可能应对具体问题的视觉刺激（只有一个单一的一个描述） 。 </li><li>再次，应该指出的是，CDZ 2 S ALS<html> O信号落后CDZ 1小号，这反过来，可能会进一步修改原本在早期视皮层诱发模式。 </li><li> CDZ N S信号CDZ 2所有方式的小号。在视觉皮层，这可能导致在较低水平CDZs完成的活动模式。在听觉皮层，神经模式将构建- CDZ 2 S和CDZ 1秒的水平，最终在早期的听觉皮层-允许听觉形象与视觉刺激相关的意识经验。请注意，也有自上而下信号，以体感方式虽然比听觉方式，以较小的程度，。这反映了一个事实，几乎任何视觉刺激有一定的触觉协会。然而，由于视觉刺激在当前的例子是假设意味着声音，自上而下的信号听觉皮层更加广泛。 </li></ol>ove_content"&gt;基于神经处理的建议序列，该框架使得一个具体的预测。包含的对象和事件，强烈暗示声音的视觉刺激唤起早期听觉皮层的神经活动，此外，听觉的活动模式应该是刺激特定的;换句话说，一个惊天动地的花瓶的视频剪辑应该是诱发，一个比一个嚎叫的狗剪辑不同的模式，如果这一预测是正确的，那么我们的确应该能够执行MVPA跨模态:举例来说，我们应该能够预测的基础上在早期听觉皮层的神经活动的指纹，一个人是否看到一个打碎的花瓶或一个<a href="http://www.jove.com/files/ftp_upload/3307/3307_Meyer-Kaplan_Video_7.mov">嚎叫狗（</a>视频剪辑7），当然，类似的范例，调用其他感官方式之间的信息传输也应该成功。例如，如果视频剪辑显示主题的隐含联系，而不是健全的，我们应引起早期体感皮层的活动模式，他们能够预测这些剪辑。 4。刺激 MVPA研究的一般范式是在第2节中描述。我们的做法是不同于以往的研究，它试图执行跨感觉系统的MVPA，因此使用，是专门在感觉比它们出现的其他方式的影响刺激。例如，在以前的研究中，我们记录从初级躯体感觉皮层的神经活动，而科目看着每天被人的手8（操纵的对象<a href="http://www.jove.com/files/ftp_upload/3307/3307_Meyer-Kaplan_Video_8.mov">5秒</a>的<a href="http://www.jove.com/files/ftp_upload/3307/3307_Meyer-Kaplan_Video_9.mov">视频短片，</a>视频剪辑和视频剪辑9）。在另一项研究中，我们研究在早期听觉皮层WHI的神经活动乐科目观看视频片段，描绘的对象和事件，强烈暗示声音 7 <a href="http://www.jove.com/files/ftp_upload/3307/3307_Meyer-Kaplan_Video_10.mov">（10视频</a>剪辑<a href="http://www.jove.com/files/ftp_upload/3307/3307_Meyer-Kaplan_Video_11.mov">和视频剪辑</a> 11） 。然而，根据CDZ框架，所有方式的感官刺激可能受聘于这个一般范式，只要他们的其他方式的影响。 5。地区景点一般来说，一个神经影像学研究感兴趣的地区可确定功能或解剖学。我们相信，我们在这里描述的实验范式，解剖本地化更适合的原因有两个。首先，这是不平凡的功能定义一个给定的感官模式（初级视觉皮层的可能是个例外）的小学或早期皮层的，作为PE的加工提交在该模式的主体rceptual的刺激，通常不会被限制到这些领域。举例来说，这将是难以界定申请主体的双手触摸到，此过程诱导活动，在所有的可能性，会蔓延到躯体协会皮层以及初级躯体感觉皮层。其次，一个功能航向未必所有的体素，可能有潜在贡献的分类的性能标签:它已被证明的地方，做不显示在传统意义上的感官刺激（即，地区，做到不出现上净激活对比度图像刺激与休息]）可以包含有关刺激尽管如此13,14的信息。对于这两个原因，我们主张在解剖学上定义的地区利益，宏观地标时，这允许使用;例如，中央后回的大体解剖代表一个合理的初级躯体感觉皮层近似，我们用这种方法来定义感兴趣的区域，在我们的体感研究 8（图1） 。 6。主题 MVPA研究课题的样品往往比在传统的fMRI研究小，可以在单一学科的水平进行分析。当然，这并不能阻止随后在组级别的个别科目的分析结果以及实验者。在两项研究中提到，例如，以前，我们进行了个别科目的结果t检验，以评估其重要意义，在组级别。每项研究涉及8个科目;虽然这必须考虑的一个非常小的主题样本参数测试，我们发现许多歧视，我们被评定为显著（见下文）。 7。代表性的成果: 如上所述，两个以前的研究中，我们的目的是预测的声音，这意味着视频剪辑在早期听觉皮层的神经活动 7的基础上（见图2，在这项研究中使用的面具）和触摸暗示8初级体感皮层的活动为基础的视频剪辑。这种尝试是成功的:在这两项研究，MVPA分类执行之间的双向刺激对所有可能的歧视，上述的50％的机会水平（N = 36听觉研究中，给定的有9种不同的刺激; N = 10体感的研究，给予有不同的刺激5）。在听觉研究，26 36歧视达到统计学意义;在体感的研究，这是8时10歧视（双尾t -检验，N = 8在这两项研究;图3）。 <img src="/files/ftp_upload/3307/3307fig1.jpg" alt="图1" /> 图1。解剖学上定义的初级躯体感觉皮层的面具的范围，如Meyer等人，2011使用。分类器算法能够预测触摸暗示划定的区域限制，以大脑活动模式的视频剪辑。复制与牛津大学出版社的许可。 <img src="/files/ftp_upload/3307/3307fig2.jpg" alt="图2" /> 图2。解剖学上定义的早期听觉皮层面具的程度，如Meyer 等人使用 。2010年。一个分类算法能够预测（沉默）的声音暗示划定的区域限制，以大脑活动模式的视频剪辑。转载自然出版集团的许可。 <img src="/files/ftp_upload/3307/3307fig3.jpg" alt="图3" /> 图3:我们以前的跨模态MVPA研究的结果摘要。分类器是用来预测，暗示无论是声音或在早期听觉或初级躯体感觉皮层的活动触摸，分别的视觉刺激。前面板:在两个螺栓IES，预测性能高于0.5机会水平之间的双向刺激对所有歧视。底部面板:在听觉研究中，分类器的性能达到了26 36的歧视统计学意义;在体感的研究，这是8 10歧视的情况下。再现自然出版集团与牛津大学出版社的许可。

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Neurosci. 4, 101-109 (2009).</li><li>Kamitani, Y., Tong, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Decoding+the+visual+and+subjective+contents+of+the+human+brain.">Decoding the visual and subjective contents of the human brain.</a> Nat. Neurosci. 8, 679-685 (2005).</li><li>Formisano, E., De Martino, F., Bonte, M., Goebel, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term="Who"+is+saying+"what"?+Brain-based+decoding+of+human+voice+and+speech?.">"Who" is saying "what"? Brain-based decoding of human voice and speech?.</a> Science. 322, 970-973 (2008).</li><li>Meyer, K., Kaplan, J. T., Essex, R., Webber, C., Damasio, H., Damasio, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Predicting+visual+stimuli+on+the+basis+of+activity+in+auditory+cortices.">Predicting visual stimuli on the basis of activity in auditory cortices.</a> Nat. Neurosci. 13, 667-668 (2010).</li><li>Meyer, K., Kaplan, J. T., Essex, R., Damasio, H., Damasio, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Seeing+touch+is+correlated+with+content-specific+activity+in+primary+somatosensory+cortex.">Seeing touch is correlated with content-specific activity in primary somatosensory cortex.</a> Cereb. Cortex. 21, 2113-2121 (2011).</li><li>Damasio, A. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Time-locked+multiregional+retroactivation:+a+systems-level+proposal+for+the+neural+substrates+of+recall+and+recognition.">Time-locked multiregional retroactivation: a systems-level proposal for the neural substrates of recall and recognition.</a> Cognition. 33, 25-62 (1989).</li><li>Meyer, K., Damasio, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Convergence+and+divergence+in+a+neural+architecture+for+recognition+and+memory.">Convergence and divergence in a neural architecture for recognition and memory.</a> Trends. Neurosci. 32, 376-382 (2009).</li><li>Friston, K. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Modalities,+modes,+and+models+in+functional+neuroimaging.">Modalities, modes, and models in functional neuroimaging.</a> Science. 326, 399-403 (2009).</li><li>Hanke, M., Halchenko, Y. O., Sederberg, P. B., Hanson, S. J., Haxby, J. V., Pollmann, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=PyMVPA:+a+Python+toolbox+for+multivariate+pattern+analysis+of+fMRI+data.">PyMVPA: a Python toolbox for multivariate pattern analysis of fMRI data.</a> Neuroinformatics. 7, 37-53 (2009).</li><li>Harrison, S. A., Tong, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Decoding+reveals+the+contents+of+visual+working+memory+in+early+visual+areas.">Decoding reveals the contents of visual working memory in early visual areas.</a> Nature. 458, 632-635 (2009).</li><li>Serences, J. T., Ester, E. F., Vogel, E. K., Awh, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Stimulus-specific+delay+activity+in+human+primary+visual+cortex.">Stimulus-specific delay activity in human primary visual cortex.</a> Psych Sci. 20, 207-214 (2009).</li></ol>

没有利益冲突的声明。

我们以前的研究结果表明，跨模态MVPA是一个有用的工具，研究在"心灵的耳朵"，"心灵的亲密接触"经验丰富的心理图像的神经关联。具体来说，结果显示这些图像的内容与在早期听觉和体感皮层的神经活动，分别达马西奥的收敛发散区的框架提供了直接的实证支持。 在许多方面，我们描述了可扩展的基本范式。最明显的是，类似的研究可以进行感官的方式使用不同的组合。在这方面，它是可能的，建立一定的交叉模式协会在实验之前，可能会增加成功的机会。例如，要研究在嗅皮层的跨模态的陈述，人们可以同时使他们的视线和食物种类数目的气味的主要科目。小号hortly后，里面的功能磁共振成像扫描仪，气味的嗅觉记忆会引发视觉线索，并MVPA可以尝试分配的试验，以正确的食物单靠嗅觉皮层活动的项目。 感兴趣的另一个问题是，是否活动的跨模态诱导的模式，在早期的感官皮质承担与诱导模式时，声音或触摸实际上是经历相似，换句话说，没有看到玻璃花瓶打破调用了类似的模式在早期的听觉皮层的神经活动，实际上听证相同的事件吗？再次，这个问题可以解决通过MVPA:是一个已经训练而听到某些声音能够正确歧视记录受试者观看相应的视频剪辑的数据记录的数据的分类？在我们的听觉研究中，我们没有尝试这样的分类，但结果是边际（见图3文献。）。然而，在这项研究中，参与者的听觉协会没有以任何方式控制;换句话说，我们不知道类似的听觉形象如何与影片相关的每个主题被用来训练分类的音频轨道。再次，它可能是有趣的解决同样的问题，以上所述为visuo嗅觉协会已催芽的科目后，具体的跨模态协会。这将允许控制更可靠的视频试验的受试者在心理体验，从而可能增加分类的预测性能。 总括而言，我们引入了一个扩展MVPA古典范式表明可预测不仅在刺激，而且还跨感官的方式。因此，我们表明，MVPA使用不仅限于调查直接相关的外部感官刺激诱导的感性陈述。相反，MVPA也可以评估的，是引发国内的心理图像的神经基板:按照达马西奥的收敛，发散区的框架，我们的研究结果建议说的，是重建的基础上记忆的心理图像意识的经验是与特定内容的神经交涉相关的初感觉皮层。

cross-modal multivariate pattern analysis

多元模式分析（MVPA）1-4功能磁共振成像（fMRI）数据分析的方法越来越流行。通常情况下，该方法是用来确定一个主题的感性经验在大脑的某些区域的神经活动。例如，它已被用来预测一个主题从早期视觉皮层5的活动或类似的是，从年初的听觉皮层6活动的讲话内容感知的视觉光栅方向。 在这里，我们目前MVPA古典范式的延伸，根据感性刺激不预测范围内，但是在感官系统。具体来说，我们所描述的方法，地址是否唤起其他方式比通过它们出现的的内存协会的刺激诱导的感觉皮层的其他方式的具体内容的活动模式的问题。例如，看到一个一个玻璃在地上打碎花瓶的静音视频剪辑自动触发一个相关联的声音的听觉形象;在大多数观察家这个图片的"心灵的耳朵"的经验与一个特定的早期神经活动模式相关性听觉皮层？此外，这一活动模式，可观察到的模式不同，如果这个问题，而是一个嚎叫的狗观看视频剪辑？ 在两个7,8以前的研究中，我们能够预测的声音和触摸这意味着在早期听觉和体感皮层的神经活动的基础上，分 ​​别视频剪辑。我们的结果是达马西奥9,10提出一个neuroarchitectural框架，根据这一精神图像的经验基础上的记忆-比如听证会的花瓶在"心灵的耳朵"惊天动地的声音，后看到相应的视频片段 - 支持的内容重新建设具体年初感觉皮层的神经活动模式。

Watch this Scientific Journal Video about Cross-Modal Multivariate Pattern Analysis at JoVE.com

Cross-Modal Multivariate Pattern Analysis

古典的多元格局分析预测，认为在相应的皮层（如视觉刺激在视觉皮层的活动）神经活动主题的感官刺激。在这里，我们应用模式分析跨模态显示，声音和触摸，这意味着视觉刺激，可以预见，从听觉和体感皮层的活动，分别。

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 ...

cross-modal-multivariate-pattern-analysis

Research

JoVE Journal

Neuroscience

19.8K 次观看.  University of Southern California. 古典的多元格局分析预测，认为在相应的皮层（如视觉刺激在视觉皮层的活动）神经活动主题的感官刺激。在这里，我们应用模式分析跨模态显示，声音和触摸，这意味着视觉刺激，可以预见，从听觉和体感皮层的活动，分别。

视频: Cross-Modal Multivariate Pattern Analysis

Basics of Multivariate Analysis in Neuroimaging Data

Multivariate analysis techniques for neuroimaging data have recently received increasing attention as they have many attractive features that cannot be easily realized by the more commonly used univariate, voxel-wise, techniques1,5,6,7,8,9. Multivariate approaches evaluate correlation/covariance of activation across brain regions, rather than proceeding on a voxel-by-voxel basis. Thus, their results can be more easily interpreted as a signature of neural networks. Univariate approaches, on the other hand, cannot directly address interregional correlation in the brain. Multivariate approaches can also result in greater statistical power when compared with univariate techniques, which are forced to employ very stringent corrections for voxel-wise multiple comparisons. Further, multivariate techniques also lend themselves much better to prospective application of results from the analysis of one dataset to entirely new datasets. Multivariate techniques are thus well placed to provide information about mean differences and correlations with behavior, similarly to univariate approaches, with potentially greater statistical power and better reproducibility checks. In contrast to these advantages is the high barrier of entry to the use of multivariate approaches, preventing more widespread application in the community. To the neuroscientist becoming familiar with multivariate analysis techniques, an initial survey of the field might present a bewildering variety of approaches that, although algorithmically similar, are presented with different emphases, typically by people with mathematics backgrounds. We believe that multivariate analysis techniques have sufficient potential to warrant better dissemination. Researchers should be able to employ them in an informed and accessible manner. The current article is an attempt at a didactic introduction of multivariate techniques for the novice. A conceptual introduction is followed with a very simple application to a diagnostic data set from the Alzheimer s Disease Neuroimaging Initiative (ADNI), clearly demonstrating the superior performance of the multivariate approach.

The current article describes the basics of multivariate analysis and contrasts it to the more commonly used voxel-wise univariate analysis. Both types of analysis are applied to a clinical-neuroscience data set. Supplementary split-half simulations show better replication of the multivariate results in independent data sets.

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 ...

科研

神经科学

Transcriptome Analysis of Single Cells

Many gene expression analysis techniques rely on material isolated from heterogeneous populations of cells from tissue homogenates or cells in culture.1,2,3 In the case of the brain, regions such as the hippocampus contain a complex arrangement of different cell types, each with distinct mRNA profiles. The ability to harvest single cells allows for a more in depth investigation into the molecular differences between and within cell populations. We describe a simple and rapid method for harvesting cells for further processing. Pipettes often used in electrophysiology are utilized to isolate (using aspiration) a cell of interest and conveniently deposit it into an Eppendorf tube for further processing with any number of molecular biology techniques. Our protocol can be modified for the harvest of dendrites from cell culture or even individual cells from acute slices.
We also describe the aRNA amplification method as a major downstream application of single cell isolations. This method was developed previously by our lab as an alternative to other gene expression analysis techniques such as reverse-transcription or real-time polymerase chain reaction (PCR).4,5,6,7,8 This technique provides for linear amplification of the polyadenylated RNA beginning with only femtograms of material and resulting in microgram amounts of antisense RNA. The linearly amplified material provides a more accurate estimation than PCR exponential amplification of the relative abundance of components of the transcriptome of the isolated cell. The basic procedure consists of two rounds of amplification. Briefly, a T7 RNA polymerase promoter site is incorporated into double stranded cDNA created from the mRNA transcripts. An overnight in vitro transcription (IVT) reaction is then performed in which T7 RNA polymerase produces many antisense transcripts from the double stranded cDNA. The second round repeats this process but with some technical differences since the starting material is antisense RNA. It is standard to repeat the second round, resulting in three rounds of amplification. Often, the third round in vitro transcription reaction is performed using biotinylated nucleoside triphosphates so that the antisense RNA produced can be hybridized and detected on a microarray.7,8

In this article we describe a simple method for the harvesting of single cells from rat primary neuronal cultures and subsequent transcriptome analysis using aRNA amplification. This approach is generalizable to any cell type.

单细胞的转录组学分析

Many gene expression analysis techniques rely on material isolated from heterogeneous populations of cells from tissue homogenates or cells in ...

T-maze Forced Alternation and Left-right Discrimination Tasks for Assessing Working and Reference Memory in Mice

Forced alternation and left-right discrimination tasks using the T-maze have been widely used to assess working and reference memory, respectively, in rodents. In our laboratory, we evaluated the two types of memory in more than 30 strains of genetically engineered mice using the automated version of this apparatus. Here, we present the modified T-maze apparatus operated by a computer with a video-tracking system and our protocols in a movie format. The T-maze apparatus consists of runways partitioned off by sliding doors that can automatically open downward, each with a start box, a T-shaped alley, two boxes with automatic pellet dispensers at one side of the box, and two L-shaped alleys. Each L-shaped alley is connected to the start box so that mice can return to the start box, which excludes the effects of experimenter handling on mouse behavior. This apparatus also has an advantage that in vivo microdialysis, in vivo electrophysiology, and optogenetics techniques can be performed during T-maze performance because the doors are designed to go down into the floor. In this movie article, we describe T-maze tasks using the automated apparatus and the T-maze performance of &alpha;-CaMKII+/- mice, which are reported to show working memory deficits in the eight-arm radial maze task. Our data indicated that &alpha;-CaMKII+/- mice showed a working memory deficit, but no impairment of reference memory, and are consistent with previous findings using the eight-arm radial maze task, which supports the validity of our protocol. In addition, our data indicate that mutants tended to exhibit reversal learning deficits, suggesting that &alpha;-CaMKII deficiency causes reduced behavioral flexibility. Thus, the T-maze test using the modified automatic apparatus is useful for assessing working and reference memory and behavioral flexibility in mice.

This article presents the protocol of T-maze tests using a modified automated apparatus for assessing the learning and memory functions in mice.

T-迷宫强迫交替和评估工作，并参考在小鼠记忆的左，右的歧视任务

Forced alternation and left-right discrimination tasks using the T-maze have been widely used to assess working and reference memory, respectively, in ...

Creating Objects and Object Categories for Studying Perception and Perceptual Learning

In order to quantitatively study object perception, be it perception by biological systems or by machines, one needs to create objects and object categories with precisely definable, preferably naturalistic, properties1. Furthermore, for studies on perceptual learning, it is useful to create novel objects and object categories (or object classes) with such properties2.
Many innovative and useful methods currently exist for creating novel objects and object categories3-6 (also see refs. 7,8). However, generally speaking, the existing methods have three broad types of shortcomings.
First, shape variations are generally imposed by the experimenter5,9,10, and may therefore be different from the variability in natural categories, and optimized for a particular recognition algorithm. It would be desirable to have the variations arise independently of the externally imposed constraints.
Second, the existing methods have difficulty capturing the shape complexity of natural objects11-13. If the goal is to study natural object perception, it is desirable for objects and object categories to be naturalistic, so as to avoid possible confounds and special cases.
Third, it is generally hard to quantitatively measure the available information in the stimuli created by conventional methods. It would be desirable to create objects and object categories where the available information can be precisely measured and, where necessary, systematically manipulated (or 'tuned'). This allows one to formulate the underlying object recognition tasks in quantitative terms.
Here we describe a set of algorithms, or methods, that meet all three of the above criteria. Virtual morphogenesis (VM) creates novel, naturalistic virtual 3-D objects called 'digital embryos' by simulating the biological process of embryogenesis14. Virtual phylogenesis (VP) creates novel, naturalistic object categories by simulating the evolutionary process of natural selection9,12,13. Objects and object categories created by these simulations can be further manipulated by various morphing methods to generate systematic variations of shape characteristics15,16. The VP and morphing methods can also be applied, in principle, to novel virtual objects other than digital embryos, or to virtual versions of real-world objects9,13. Virtual objects created in this fashion can be rendered as visual images using a conventional graphical toolkit, with desired manipulations of surface texture, illumination, size, viewpoint and background. The virtual objects can also be 'printed' as haptic objects using a conventional 3-D prototyper.
We also describe some implementations of these computational algorithms to help illustrate the potential utility of the algorithms. It is important to distinguish the algorithms from their implementations. The implementations are demonstrations offered solely as a 'proof of principle' of the underlying algorithms. It is important to note that, in general, an implementation of a computational algorithm often has limitations that the algorithm itself does not have.
Together, these methods represent a set of powerful and flexible tools for studying object recognition and perceptual learning by biological and computational systems alike. With appropriate extensions, these methods may also prove useful in the study of morphogenesis and phylogenesis.

We describe a novel methodology for creating naturalistic 3-D objects and object categories with precisely defined feature variations. We use simulations of the biological processes of morphogenesis and phylogenesis to create novel, naturalistic virtual 3-D objects and object categories that can then be rendered as visual images or haptic objects.

创建对象和对象类别学习的认知与知觉学习

In order to quantitatively study object perception, be it perception by biological systems or by machines, one needs to create objects and object ...

Visualization and Genetic Manipulation of Dendrites and Spines in the Mouse Cerebral Cortex and Hippocampus using In utero Electroporation

In utero electroporation (IUE) has become a powerful technique to study the development of different regions of the embryonic nervous system 1-5. To date this tool has been widely used to study the regulation of cellular proliferation, differentiation and neuronal migration especially in the developing cerebral cortex 6-8. Here we detail our protocol to electroporate in utero the cerebral cortex and the hippocampus and provide evidence that this approach can be used to study dendrites and spines in these two cerebral regions.
Visualization and manipulation of neurons in primary cultures have contributed to a better understanding of the processes involved in dendrite, spine and synapse development. However neurons growing in vitro are not exposed to all the physiological cues that can affect dendrite and/or spine formation and maintenance during normal development. Our knowledge of dendrite and spine structures in vivo in wild-type or mutant mice comes mostly from observations using the Golgi-Cox method 9. However, Golgi staining is considered to be unpredictable. Indeed, groups of nerve cells and fiber tracts are labeled randomly, with particular areas often appearing completely stained while adjacent areas are devoid of staining. Recent studies have shown that IUE of fluorescent constructs represents an attractive alternative method to study dendrites, spines as well as synapses in mutant / wild-type mice 10-11 (Figure 1A). Moreover in comparison to the generation of mouse knockouts, IUE represents a rapid approach to perform gain and loss of function studies in specific population of cells during a specific time window. In addition, IUE has been successfully used with inducible gene expression or inducible RNAi approaches to refine the temporal control over the expression of a gene or shRNA 12. These advantages of IUE have thus opened new dimensions to study the effect of gene expression/suppression on dendrites and spines not only in specific cerebral structures (Figure 1B) but also at a specific time point of development (Figure 1C).
Finally, IUE provides a useful tool to identify functional interactions between genes involved in dendrite, spine and/or synapse development. Indeed, in contrast to other gene transfer methods such as virus, it is straightforward to combine multiple RNAi or transgenes in the same population of cells. 
In summary, IUE is a powerful method that has already contributed to the characterization of molecular mechanisms underlying brain function and disease and it should also be useful in the study of dendrites and spines.

Visualization and Genetic Manipulation of Dendrites and Spines in the Mouse Cerebral Cortex and Hippocampus using In utero Electroporation

This article describes in detail a protocol to electroporate in utero the cerebral cortex and the hippocampus at E14.5 in mice. We also show that this is a valuable method to study dendrites and spines in these two cerebral regions.

可视化和遗传操作在小鼠大脑皮层和使用海马树突和棘<em&gt;在子宫内</em&gt;电穿孔

In utero electroporation (IUE) has become a powerful technique to study the development of different regions of the embryonic nervous system 1-5. To date ...

The Swimmeret System of Crayfish: A Practical Guide for the Dissection of the Nerve Cord and Extracellular Recordings of the Motor Pattern

Here we demonstrate the dissection of the crayfish abdominal nerve cord. The preparation comprises the last two thoracic ganglia (T4, T5) and the chain of abdominal ganglia (A1 to A6). This chain of ganglia includes the part of the central nervous system (CNS) that drives coordinated locomotion of the pleopods (swimmerets): the swimmeret system. It is known for over five decades that in crayfish each swimmeret is driven by its own independent pattern generating kernel that generates rhythmic alternating activity 1-3. The motor neurons innervating the musculature of each swimmeret comprise two anatomically and functionally distinct populations 4. One is responsible for the retraction (power stroke, PS) of the swimmeret. The other drives the protraction (return stroke, RS) of the swimmeret. Motor neurons of the swimmeret system are able to produce spontaneously a fictive motor pattern, which is identical to the pattern recorded in vivo 1.
The aim of this report is to introduce an interesting and convenient model system for studying rhythm generating networks and coordination of independent microcircuits for students&#8217; practical laboratory courses. The protocol provided includes step-by-step instructions for the dissection of the crayfish&#8217;s abdominal nerve cord, pinning of the isolated chain of ganglia, desheathing the ganglia and recording the swimmerets fictive motor pattern extracellularly from the isolated nervous system.
Additionally, we can monitor the activity of swimmeret neurons recorded intracellularly from dendrites. Here we also describe briefly these techniques and provide some examples. Furthermore, the morphology of swimmeret neurons can be assessed using various staining techniques. Here we provide examples of intracellular (by iontophoresis) dye filled neurons and backfills of pools of swimmeret motor neurons. In our lab we use this preparation to study basic functions of fictive locomotion, the effect of sensory feedback on the activity of the CNS, and coordination between microcircuits on a cellular level.

Here we describe the dissection of the crayfish abdominal nerve cord. We also demonstrate an electrophysiological technique to record fictive locomotion from swimmeret motor neurons.

小龙虾的游泳足系统:实用指南为神经线及电机模式外记录的解剖

Here we demonstrate the dissection of the crayfish abdominal nerve cord. The preparation comprises the last two thoracic ganglia (T4, T5) and the chain of ...

Peering at Brain Polysomes with Atomic Force Microscopy

The translational machinery, i.e., the polysome or polyribosome, is one of the biggest and most complex cytoplasmic machineries in cells. Polysomes, formed by ribosomes, mRNAs, several proteins and non-coding RNAs, represent integrated platforms where translational controls take place. However, while the ribosome has been widely studied, the organization of polysomes is still lacking comprehensive understanding. Thus much effort is required in order to elucidate polysome organization and any novel mechanism of translational control that may be embedded. Atomic force microscopy (AFM) is a type of scanning probe microscopy that allows the acquisition of 3D images at nanoscale resolution. Compared to electron microscopy (EM) techniques, one of the main advantages of AFM is that it can acquire thousands of images both in air and in solution, enabling the sample to be maintained under near physiological conditions without any need for staining and fixing procedures. Here, a detailed protocol for the accurate purification of polysomes from mouse brain and their deposition on mica substrates is described. This protocol enables polysome imaging in air and liquid with AFM and their reconstruction as three-dimensional objects. Complementary to cryo-electron microscopy (cryo-EM), the proposed method can be conveniently used for systematically analyzing polysomes and studying their organization.

While ribosome structure has been extensively characterized, the organization of polysomes is still understudied. To overcome this lack of knowledge, we present here a detailed preparation protocol for accurate imaging of mammalian polysomes by atomic force microscopy (AFM) in air and liquid.

在脑核糖凝视与原子力显微镜

The translational machinery, i.e., the polysome or polyribosome, is one of the biggest and most complex cytoplasmic machineries in cells. Polysomes, ...

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 ...

Visualization of the Axonal Projection Pattern of Embryonic Motor Neurons in Drosophila

The establishment of functional neuromuscular circuits relies on precise connections between developing motor axons and target muscles. Motor neurons extend growth cones to navigate along specific pathways by responding to a large number of axon guidance cues that emanate from the surrounding extracellular environment. Growth cone target recognition also plays a critical role in neuromuscular specificity. This work presents a standard immunohistochemistry protocol to visualize motor neuron projections of late stage-16 Drosophila melanogaster embryos. This protocol includes a few key steps, including a genotyping procedure, to sort the desired mutant embryos; an immunostaining procedure, to tag embryos with fasciclin II (FasII) antibody; and a dissection procedure, to generate filleted preparations from fixed embryos. Motor axon projections and muscle patterns in the periphery are much better visualized in flat preparations of filleted embryos than in whole-mount embryos. Therefore, the filleted preparation of fixed embryos stained with FasII antibody provides a powerful tool to characterize the genes required for motor axon pathfinding and target recognition, and it can also be applied to both loss-of-function and gain-of-function genetic screens.

Visualization of the Axonal Projection Pattern of Embryonic Motor Neurons in Drosophila

This work details a standard immunohistochemistry method to visualize motor neuron projections of late stage-16 Drosophila melanogaster embryos. The filleted preparation of fixed embryos stained with FasII antibody provides a powerful tool to characterize the genes required for motor axon pathfinding and target recognition during neural development.

胚胎运动神经元轴突投影模式的可视化<em&gt;果蝇</em

The establishment of functional neuromuscular circuits relies on precise connections between developing motor axons and target muscles. Motor neurons ...

Isolation of Adult Spinal Cord Nuclei for Massively Parallel Single-nucleus RNA Sequencing

Probing an individual cell&#39;s gene expression enables the identification of cell type and cell state. Single-cell RNA sequencing has emerged as a powerful tool for studying transcriptional profiles of cells, particularly in heterogeneous tissues such as the central nervous system. However, dissociation methods required for single cell sequencing can lead to experimental changes in the gene expression and cell death. Furthermore, these methods are generally restricted to fresh tissue, thus limiting studies on archival and bio-bank material. Single nucleus RNA sequencing (snRNA-Seq) is an appealing alternative for transcriptional studies, given that it accurately identifies cell types, permits the study of tissue that is frozen or difficult to dissociate, and reduces dissociation-induced transcription. Here, we present a high-throughput protocol for rapid isolation of nuclei for downstream snRNA-Seq. This method enables isolation of nuclei from fresh or frozen spinal cord samples and can be combined with two massively parallel droplet encapsulation platforms.

Here, we present a protocol to rapidly isolate high-quality nuclei from the fresh or frozen tissue for downstream massively parallel RNA sequencing. We include detergent-mechanical and hypotonic-mechanical tissue disruption and cell lysis options, both of which can be used for isolation of nuclei.

成人脊髓细胞核在大规模平行单核 RNA 测序中的分离

Probing an individual cell&#39;s gene expression enables the identification of cell type and cell state. Single-cell RNA sequencing has emerged as a ...