这项研究是由来自弗吉尼亚州的联邦卫生研究委员会补助经费支持。

为便于说明的协议已被划分成两部分:1）实验步骤和2）的自动分析。所有的动物都根据指南实验动物15的护理和使用治疗，所有手续由机构动物护理和使用委员会批准。 1.实验步骤<ol><li>设置保持架，这是一个黑色的无反射有机玻璃矩形箱（52×25×23 毫升 ）分成三个室:社会，非社会，和中性中间隔间（ 图1）。放置在会议期间在各端隔室的倒置丝杯I和II（下文讨论）和会话第二期间容纳所述刺激小鼠。 </li><li>设置摄像机，所述笼填充的视场的方式。由于照明可以用鼠标行为干预，维持在笼子里面不超过3.5勒克斯的照度，从间接光从未来白炽灯泡和在向上方向上的笼底测量。也使用红外光源，小鼠无法感知但相机可检测。记录所有电影720×480标清。 </li><li>录制后图像处理的空笼（称为"参照系"）的一帧，并保存为灰度图像。 </li><li>第一节:介绍测试鼠标放到笼子里和波拱手笼，表明会话的开始（比较自动分析）。影片记录了10分钟。在10分钟结束时，把鼠标放回原来的笼子里。 </li><li>议题二:把鼠标刺激倒杯之一的（平衡）。 </li><li>使用"社会左"或"社会权利"按钮，选择刺激的鼠标是否是在左侧还是在右侧的倒杯的倒杯。 注:与刺激鼠标倒杯被称为"社会的杯具"，而其他杯"非社会茶杯"。其中社会杯位于被称为社会隔室的隔室，与非社会杯隔室是非社会隔室，中间室是"中性隔室"。 </li><li>引进试验老鼠入笼。波拱手笼指示会话的开始。影片记录了10分钟。重要的是，保持社交性设备移除老鼠倒杯开始第三场之前。 </li><li>议题三:删除倒杯，松开小鼠和允许测试和刺激老鼠相互自由交互。波拱手笼指示会话的开始。影片记录了10分钟。在10分钟结束时，把老鼠都回到各自的笼子里。 </li></ol> 2.自动分析注:在第2的命令经由图形用户界面发出（参见图2），该CONtrols我们的软件。在这里我们讲解一步一步的处理，我们的软件允许;该软件还能够在无用户输入执行批处理模式的分析。 <ol><li>对于每部电影，请执行以下处理步骤: <ol><li>负载电影（点击Load按钮）。 </li><li>选择笼构成，它告诉分析程序笼边界，隔室的边界，和杯位置的位置。选择四个保存的配置中的一种或手动调整所有坐标。 注:配置通常不改变从一个实验到下一个，因此可以重复使用。 </li><li>为电影的每一帧，执行以下的处理步骤（2.1.3.1-2.1.3.6）。 <ol><li>转换帧通过点击"灰度"按钮灰度。 </li><li>通过点击"减去"按钮，数字减去灰度参考框架（见步骤1.3）。注意:该步骤的目的是使像素VA框架非常接近的梅毒到处为零，除了鼠标的位置。 </li><li>通过设置低于某个阈值电平为黑色的所有像素二值化的帧，高于该水平的白色所有像素（点击"二值化"按钮）。 注意:我们的想法是，由于鼠标象素通常具有较高的值比剩余像素，鼠标像素将变成白色，所有其他像素黑色。最佳阈值电平取决于照明条件，并且可以通过在整个电影评估鼠标形状来确定。如果选择阈值太低，则鼠标出现过大，以及不属于鼠标像素可被着色为白色。如果阈值太高，鼠标变小，并且可以分裂成断开件。在记录的电影，最佳阈值总是20和35之间（从0到255的范围）。 </li><li>侵蚀13二进制图像e时代，那么13扩张2E次，然后ERO德再次e时代，按下按钮"EROD /语"。 注意:目的此过程是删除尾部。对于已使用的分辨率（720×480），E = 3在所有情况下工作。 注:该软件的手在画面中存在自动检查（动画的录制过程中，手都通过图片摆手示意会话的开始）。如果手存在，就会有在二值化的帧异常许多白色像素，因为手是比鼠标大得多。一只手的存在的条件是，有在二值化的帧超过10000白色像素。该软件I，II和III，通过检测其手部动作发生的帧的范围确定会议的开端。 </li></ol></li></ol></li><li>在会话I和II，继续如下: <ol><li>检测组白色像素的最大连接组件（点击"LCOMP"）。注:目的ØF该步骤是为了消除该不属于鼠标， 例如 ，引起刺激小鼠的会话第二运动白色像素。最大的连接组件是在几乎所有帧的鼠标。 </li><li>通过点击"查找完"确定了两个最遥远的白色像素（称为鼠标的"目的"）。 注意:软件建立的两端， 即的连续性，对于每个在第一帧的端部到在它们所属的后续帧的端部。总的想法是，由于帧以高速率记录中，端部可以不远处一帧行进到下一个，使得用于从一帧到下一的端部的正确延续是该距离的总和最小化两端移动。见讨论更多细节。 </li><li>确定哪些鼠标到底是鼻子。 <ol><li>确定的方向，其中通过观察一个移动鼠标如何重心（COG）从帧变为帧（焦炉煤气的动议是所有小鼠像素的总和的运动）。 注意:一组象素P 1的COG，...，坐标P N×1，...，×n个被定义为: <img alt="式（1）" src="/files/ftp_upload/52508/52508eq1.jpg" /> 鼠标通常向前（ 即往自己的鼻子）。在几百帧的部分，总是有很高可信度的头部/尾部的检测。 注意:软件自动确定作为所检测到结束鼠标移动;为此被识别为鼻和标有在电影的红色圆圈。当检测到的鼻子被标记在每一个帧中的红色圆圈，用户可以检查该检测的质量。 </li></ol></li></ol></li><li>在会议第三，继续如下: <ol><li>检测两个最大的白色像素组件。 <ol><li>如果两者都为上午可接受大小的乌斯和其重心（COGS）是与前一帧的鼠标COGS，考虑这两个部件的两只小鼠兼容。 </li><li>考虑鼠标尺寸上可接受的，如果他们不超过20％，因为前一帧改变，并且考虑连续两帧为兼容的嵌齿，如果它们的差值不大于鼠标可以在帧之间的时间移动的距离越大（在此距离如下从最大鼠标速度，这可以通过分析多个单独的小鼠的运动被确定为一个实验系列的制剂的一部分（如在会话I和II）。 注意:如果最大的两个组成部分是一个鼠标不能接受尺寸或嵌齿是从那些在先前帧过于不同，直到最大的两个组成部分是可接受的大小的软件自动增加二值化阈值，并且它们的齿轮与兼容那些先前帧。 </li></ol></li><li>点击测试鼠标第一帧。在使用2.3.1分析会议III的每一帧识别测试和刺激鼠标。 </li><li>确定会议III，其中一个鼠标社会接近其他的帧。注意:软件实现此步骤通过自动检查的小鼠之间的距离小于小鼠的典型相互作用距离（我们使用2个厘米）。 </li><li>当软件播放影片与所检测的方式向用户的一个短段，点击一个按钮，以指示该方法是否符合由测​​试小鼠，社交回避由测试鼠标，或既不是社会的方法。 注意:步骤2.3.4能，如果它是已知的鼠标是测试鼠标自动化。由于当小鼠太靠近彼此此信息丢失（或爬在彼此的顶部），而不是因为我们还没有发现一种方法来标记的小鼠中，可以可靠地通过我们的软件进行检测并执行的方式不会影响他们的行为，我们已经恢复了人工分类现在。 </li></ol></li><li>要使用Load按钮评估处理电影，电影负荷。 <ol><li>点击开始会话1显示会话1的第一帧（或开始第二节，显示会话2的第一帧）。 </li><li>点击播放/停止播放和停止影片。 注:处理影片将显示鼠标的头部和尾部标有不同颜色的圆圈。显示在屏幕上的所有社交措施和更新的影片播放。 </li><li>通过点击"导出"导出社交性Excel格式的数据。 </li><li>点击"编译数据"编译文件夹中的所有影片中所有的数据到一个单一的Excel文件。 </li></ol></li></ol>

<ol>
	<li>Brodkin, E. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=BALB/c+mice:+Low+sociability+and+other+phenotypes+that+may+be+relevant+to+autism.">BALB/c mice: Low sociability and other phenotypes that may be relevant to autism.</a> Behavioural Brain Research. 176, 53-65 (2007).</li><li>Deutsch, S. I., Burket, J. A., Urbano, M. R., Herndon, A. L., Winebarger, E. E., Mohammadi, M. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Impaired+sociability+of+the+BALB/c+mouse,+an+animal+model+of+autism+spectrum+disorders,+is+attenuated+by+NMDA+receptor+agonist+interventions:+clinical+implications.">Impaired sociability of the BALB/c mouse, an animal model of autism spectrum disorders, is attenuated by NMDA receptor agonist interventions: clinical implications.</a> Comprehensive Book on Autism Spectrum Disorders. , 323-342 (2011).</li><li>Dunn, M. E., Burbine, T., Bowers, C. A., Tantleff-Dunn, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Moderators+of+stress+in+parents+of+children+with+autism.">Moderators of stress in parents of children with autism.</a> Community Mental Health Journal. 37, 39-52 (2001).</li><li>Babineau, B. A., Yang, M., Berman, R. F., Crawley, J. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Low+home+cage+social+behaviors+in+BTBR+T+tf/J+mice+during+juvenile+development.">Low home cage social behaviors in BTBR T+tf/J mice during juvenile development.</a> Physiology &amp; Behavior. 114-115, 49-54 (2013).</li><li>Benson, A. D., Burket, J. A., Deutsch, S. I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=BALB/c+mice+treated+with+d-cycloserine+arouse+increased+social+interest+in+conspecifics.">BALB/c mice treated with d-cycloserine arouse increased social interest in conspecifics.</a> Brain Research Bulletin. 99, 95-99 (2013).</li><li>Burket, J. A., Benson, A. D., Tang, A. H., Deutsch, S. I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rapamycin+improves+sociability+in+the+BTBR+T(+)Itpr3(tf)/J+mouse+model+of+autism+spectrum+disorders.">Rapamycin improves sociability in the BTBR T(+)Itpr3(tf)/J mouse model of autism spectrum disorders.</a> Brain Research Bulletin. 100, 70-75 (2014).</li><li>Burket, J. A., Benson, A. D., Tang, A. H., Deutsch, S. I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=D-Cycloserine+improves+sociability+in+the+BTBR+T++Itpr3tf/J+mouse+model+of+autism+spectrum+disorders+with+altered+Ras/Raf/ERK1/2+signaling.">D-Cycloserine improves sociability in the BTBR T+ Itpr3tf/J mouse model of autism spectrum disorders with altered Ras/Raf/ERK1/2 signaling.</a> Brain Research Bulletin. 96, 62-70 (2013).</li><li>Burket, J. A., Herndon, A. L., Deutsch, S. I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Locomotor+activity+of+the+genetically+inbred+BALB/c+mouse+strain+is+suppressed+by+a+socially+salient+stimulus.">Locomotor activity of the genetically inbred BALB/c mouse strain is suppressed by a socially salient stimulus.</a> Brain Research Bulletin. 83, 255-256 (2010).</li><li>Deutsch, S. I., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=D-cycloserine+improves+sociability+and+spontaneous+typic+behaviors+in+4-week+old+mice.">D-cycloserine improves sociability and spontaneous typic behaviors in 4-week old mice.</a> Brain Research. 1439, 96-107 (2012).</li><li>Jacome, L. F., Burket, J. A., Herndon, A. L., Deutsch, S. I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Genetically+inbred+BALB/c+mice+differ+from+outbred+Swiss+Webster+mice+on+discrete+measures+of+sociability:+relevance+to+a+genetic+mouse+model+of+autism+spectrum+disorders.">Genetically inbred BALB/c mice differ from outbred Swiss Webster mice on discrete measures of sociability: relevance to a genetic mouse model of autism spectrum disorders.</a> Autism Research. 4, 393-400 (2011).</li><li>Jacome, L. F., Burket, J. A., Herndon, A. L., Cannon, W. R., Deutsch, S. I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=D-serine+improves+dimensions+of+the+sociability+deficit+of+the+genetically-inbred+BALB/c+mouse+strain.">D-serine improves dimensions of the sociability deficit of the genetically-inbred BALB/c mouse strain.</a> Brain Research Bulletin. 84, 12-16 (2011).</li><li>Deutsch, S. I., Burket, J. A., Jacome, L. F., Cannon, W. R., Herndon, A. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=D-Cycloserine+improves+the+impaired+sociability+of+the+BALB/c+mouse.">D-Cycloserine improves the impaired sociability of the BALB/c mouse.</a> Brain Research Bulletin. 84, 8-11 (2011).</li><li>Shih, F. Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Image Processing and Mathematical Morphology: Fundamentals and Applications. , (2009).</li><li>Nixon, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Feature Extraction &amp; Image Processing. , (2008).</li><li>National Research Council. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Guide for the Care and Use of Laboratory Animals. , (2011).</li></ol>

作者什么都没有透露。

通过结合偷拍小鼠和自动电影的分析，我们已经创建了一个经济实惠，可靠的高通量筛选技术。 自动分析的准确度为100多部电影手工分析的结果进行比较。在帧的绝大多数帧（&gt; 99％），鼠标的鼻部被识别以良好的精度。大部分的（少数）误检测的对社交性措施没有效果，因此，电影的80％左右，不需要任何校正。 在那些确实包含错误检测，是迄今为止...

受损社交性是在一系列神经发育障碍，包括孤独症谱系障碍（自闭症）1,2的主要症状域之一。这严重限制了患者的发展关系的能力，并极大地影响了病人，家属和护理人员2,3。 在为了更好地理解受损社交性背后的机理和开发治疗，几种小鼠模型进行了研究1,4-9。一个这样的菌株是BALB / c小鼠，表现出显着低社交性，类似于患者ASD5 8-12可见特征的近交系。例如，BALB / c小鼠显示社会的方法和通过刺激老鼠（ 例如，社交回避）超过瑞士韦伯斯特比较10株对社会的办法通常是一个否定的答复较低的频率。 为了测试提出的治疗是否有效实现了在增加社交E，需要客观的措施。一种广泛接受的框架是分析在具有三个隔室的标准化装置社交性（ 见图1）。 左，右室都包含一个倒线杯里面有一个突出的社会刺激鼠标。测试小鼠被释放到装置的10分钟三个区间（会话Ⅰ-Ⅲ）;会话我评估测试小鼠的运动活性，而会话II和III评估测试小鼠的社交性的不同方面。 在会话我，测试鼠标使其适应该装置。在此会话，测量该测试鼠标使得不同区室之间的转变的数目。重要的是，在标准的三隔室装置得到社交性措施取决于运动活性，并降低了运动活性可混淆的SOCI解释能力数据。 第二场会议，测试鼠标自由移动，并刺激鼠标倒置一只杯子之下（平衡）。刺激小鼠4周龄远系繁殖雄性ICR小鼠，年龄和性别相匹配的测试小鼠。刺激小鼠被封闭在指定为社会隔室侧的倒置的杯，和一个空的倒置的杯被放置在指定为非社会隔室的一侧。第二场会议，测试鼠标的社交性是通过比较其花费附近的"社会"倒杯（小于2厘米的距离） 与它花费附近的"非社会"倒杯时的时间量化，并通过时间它花费在社交车厢与它在非社会隔间花费的时间。瑞士韦伯斯特比较小鼠花费显著更多的时间在社会隔室和邻近相比BALB / c小鼠，显示没有显著偏爱社会社会倒杯倒杯或社会舱12。 在会话III，测试和刺激小鼠被允许自由互动（倒杯被删除）。车厢之间的社交性措施，刻板行为和过渡的测试和刺激小鼠和分析之间的自由互动的第三10分钟会话中获得可靠。在这份报告中，测试鼠标的社交性通过两个措施量化:1）它使向着刺激鼠标，在一个社会的方式被定义为向着刺激鼠标前进（鼻第一）的社交方式号码，这样的鼻子是从刺激小鼠小于2厘米的距离; 2）由刺激小鼠社会方法忌的数量。测试鼠标被认为是避免方法，如果事实证明或刺激鼠标移开，或者如果它的刺激后鼠标会暂时停止移动（"冻结行为"），已接近测试鼠标。 BALB /c小鼠显示在朝向刺激小鼠和增加的由刺激小鼠社会办法否定答复的号码进行社会的方法数量的减少，相比于瑞士韦伯斯特比较应变10。 行为电影的评价历来手工完成， 即通过（可能以较低的速度），仔细观看电影和激活秒表的鼠标在某车厢或接近倒杯10的一个花费的时间。这种方法需要重复的电影的观看，因此是非常耗时。另外，精度由评价者的反应时间为秒表测量和能力的限制来感知鼠标是否为2cm倒杯内。在最近的工作中，两种化合物（D-丝氨酸和D-环丝氨酸）已被证明有效，在BALB / c小鼠9,10,12恢复社交性。已知的是两种成分MODU迟NMDA受体，这是众所周知的社会行为2,12发挥中心作用。化合物的大阵列已知调节在各种良好定义的方式NMDA受体活性，而对于在ASD治疗的突破的潜力，使这些化合物优先将评价高度期望快速自动方法的加速评估。 下面描述的是用于小鼠社交性的评估开发了一种自动分析过程。它使用鼠标电影的所有帧的图像处理方法来确定鼠标或小鼠的位置。在会话I和II，它进一步检测鼻子的位置，并使用它来计算社交性的措施。在会议第三，它会自动检测所有的方法，但需要人工分类（社会的方式，社交回避，或其他）。

<table>
	<tbody>
		<tr>
			<td>Plexiglas cage</td>
			<td>Norva Plastics, Norfolk, VA</td>
			<td>custom made</td>
			<td>Dimensions and layout described in manuscript, 
			can be adjusted according to needs. 
			Use non-reflective plexiglas for to facilitate image processing</td>
		</tr>
		<tr>
			<td>Wire cups</td>
			<td>Kitchen plus</td>
			<td>315</td>
			<td>Use one to house stimulus mouse, one empty</td>
		</tr>
		<tr>
			<td>Video camera</td>
			<td>SONY</td>
			<td>HDR-PJ790</td>
			<td>Can be replaced by any camera with 
			Comparable specifications</td>
		</tr>
		<tr>
			<td>OpenCV (Image processing library)</td>
			<td>Willow Garage</td>
			<td>N/A</td>
			<td>Any modern image processing library 
			can be used.</td>
		</tr>
	</tbody>
</table>

experimental assessment of mouse sociability using an automated image processing approach

鼠标是检验药物设计，增加社交性的首选模式生物。我们提出量化小鼠社交性其中试验小鼠被放置在一个标准化的装置和相关的行为在三个不同的会话评估（称为会话I，II和III）的方法。 该装置具有三个隔室（参见图1），左和右室含有一个倒置的杯，可容纳一个鼠标（称为"刺激小鼠"）。 在会话我，测试小鼠被放置在笼和其移动性的特征在于舱室之间进行转换的数量。第二场会议，刺激老鼠置于倒杯之一的，测试鼠标的社交性是由一次花费近包含封闭刺激鼠标与空倒杯杯的数额量化。在会话III，倒杯卸下了<html> ð两个小鼠自由互动。在会议III测试鼠标的社交性是由它使向着刺激老鼠的社会方式的数量和次数它避免受了刺激鼠标一个社会的办法量化。 影片的自动评估检测测试鼠标，它允许会话I和II的所有描述社交性措施的决心鼻子（会话III，方法被自动识别，但手动分类）。找到鼻，一个空的保持器的图像被数字从影片的每一帧中减去，所得的图像进行二值化，以识别鼠标像素。小鼠尾部被自动删除，剩余的小鼠的两个最远点被确定;这些都是接近机头和机尾的基地。通过分析鼠标的移动和使用的连续性参数，鼻子识别。 <img alt="&lt;/ HTML">"图1"的src ="/文件/ ftp_upload / 52508 / 52508fig1.jpg"/&gt; 图1.社交性的评估期间3届 会议我 （上）:测试鼠标的驯化笼子第二节 （中）:当鼠标刺激被封闭在一个倒杯测试鼠标在笼子里自由移动的第三场 （下图）:两种测试鼠标和鼠标刺激允许自由移动和互动与对方。

图3示出一个行为电影的与空笼一个彩色帧。鼠标还没有被引入笼子里呢。的杯子，（社会和非社会）以及隔室边界的位置重叠。 如图4和用作基准帧的空笼的彩色帧被转换为8位灰度。基准帧被从捕获的电影的每隔一帧中减去。 图5显示从电影会话我在帧中的一个，再次叠加隔间边界和杯子的位置。参照帧是从样本帧，其结果，所谓的差?...

Watch this Scientific Journal Video about Experimental Assessment of Mouse Sociability Using an Automated Image Processing Approach at JoVE.com

Experimental Assessment of Mouse Sociability Using an Automated Image Processing Approach

本协议描述的量化鼠标社交性的方法。因为它们移动和在一个特殊的笼相互作用小鼠录像。电影处理允许社交性具有优良的准确性和可靠性的自动化定量。

使用自动图像处理方法鼠标社交性的实验评估

Mouse is the preferred model organism for testing drugs designed to increase sociability. We present a method to quantify mouse sociability in which the ...

experimental-assessment-mouse-sociability-using-an-automated-image

Universidad de Cartagena UDEC

Research

JoVE Journal

Behavior

8.4K 次观看.  Old Dominion University. 本协议描述的量化鼠标社交性的方法。因为它们移动和在一个特殊的笼相互作用小鼠录像。电影处理允许社交性具有优良的准确性和可靠性的自动化定量。 

视频: Experimental Assessment of Mouse Sociability Using an Automated Image Processing Approach

Assessment of Age-related Changes in Cognitive Functions Using EmoCogMeter, a Novel Tablet-computer Based Approach

The main goal of this study was to assess the usability of a tablet-computer-based application (EmoCogMeter) in investigating the effects of age on cognitive functions across the lifespan in a sample of 378 healthy subjects (age range 18-89 years). Consistent with previous findings we found an age-related cognitive decline across a wide range of neuropsychological domains (memory, attention, executive functions), thereby proving the usability of our tablet-based application. Regardless of prior computer experience, subjects of all age groups were able to perform the tasks without instruction or feedback from an experimenter. Increased motivation and compliance proved to be beneficial for task performance, thereby potentially increasing the validity of the results. Our promising findings underline the great clinical and practical potential of a tablet-based application for detection and monitoring of cognitive dysfunction.

We tested the usability of a tablet-computer-based application (EmoCogMeter) in investigating the effects of age on cognition. Results show an age-related cognitive decline, thereby proving the usability of our application. Findings underline the great clinical and practical potential of a tablet-based application for detection and monitoring of cognitive dysfunction.

与年龄相关的变化认知功能使用EmoCogMeter，新型平板计算机基础法评估

The main goal of this study was to assess the usability of a tablet-computer-based application (EmoCogMeter) in investigating the effects of age on ...

科研

行为学

Quantitative Assessment of Cortical Auditory-tactile Processing in Children with Disabilities

Objective and easy measurement of sensory processing is extremely difficult in nonverbal or vulnerable pediatric patients. We developed a new methodology to quantitatively assess children&#39;s cortical processing of light touch, speech sounds and the multisensory processing of the 2 stimuli, without requiring active subject participation or causing children discomfort. To accomplish this we developed a dual channel, time and strength calibrated air puff stimulator that allows both tactile stimulation and sham control. We combined this with the use of event-related potential methodology to allow for high temporal resolution of signals from the primary and secondary somatosensory cortices as well as higher order processing. This methodology also allowed us to measure a multisensory response to auditory-tactile stimulation.

Objective and easy measurement of sensory processing is extremely difficult in nonverbal or vulnerable pediatric patients. We developed a new methodology to quantitatively assess infants and children&#39;s cortical processing of light touch, speech sounds, and the multisensory processing of the 2 stimuli, without requiring active subject participation or causing discomfort in vulnerable patients.

皮质听觉，触觉加工的残疾儿童定量评价

Objective and easy measurement of sensory processing is extremely difficult in nonverbal or vulnerable pediatric patients. We developed a new methodology ...

Behavioral Assessment of the Aging Mouse Vestibular System

Age related decline in balance performance is associated with deteriorating muscle strength, motor coordination and vestibular function. While a number of studies show changes in balance phenotype with age in rodents, very few isolate the vestibular contribution to balance under either normal conditions or during senescence. We use two standard behavioral tests to characterize the balance performance of mice at defined age points over the lifespan: the rotarod test and the inclined balance beam test. Importantly though, a custom built rotator is also used to stimulate the vestibular system of mice (without inducing overt signs of motion sickness). These two tests have been used to show that changes in vestibular mediated-balance performance are present over the murine lifespan. Preliminary results show that both the rotarod test and the modified balance beam test can be used to identify changes in balance performance during aging as an alternative to more difficult and invasive techniques such as vestibulo-ocular (VOR) measurements.

Motor control and balance performance are known to deteriorate with age. This paper presents a number of standard noninvasive behavioral tests with the addition of a simple rotary stimulus to challenge the vestibular system and show changes in balance performance in a murine model of aging.

衰老小鼠前庭系统的行为评估

Age related decline in balance performance is associated with deteriorating muscle strength, motor coordination and vestibular function. While a number of ...

Assessment of Social Cognition in Non-human Primates Using a Network of Computerized Automated Learning Device (ALDM) Test Systems

Fagot &#38; Paleressompoulle1 and Fagot &#38; Bonte2 have published an automated learning device (ALDM) for the study of cognitive abilities of monkeys maintained in semi-free ranging conditions. Data accumulated during the last five years have consistently demonstrated the efficiency of this protocol to investigate individual/physical cognition in monkeys, and have further shown that this procedure reduces stress level during animal testing3. This paper demonstrates that networks of ALDM can also be used to investigate different facets of social cognition and in-group expressed behaviors in monkeys, and describes three illustrative protocols developed for that purpose. The first study demonstrates how ethological assessments of social behavior and computerized assessments of cognitive performance could be integrated to investigate the effects of socially exhibited moods on the cognitive performance of individuals. The second study shows that batteries of ALDM running in parallel can provide unique information on the influence of the presence of others on task performance. Finally, the last study shows that networks of ALDM test units can also be used to study issues related to social transmission and cultural evolution. Combined together, these three studies demonstrate clearly that ALDM testing is a highly promising experimental tool for bridging the gap in the animal literature between research on individual cognition and research on social cognition.

Assessment of Social Cognition in Non-human Primates Using a Network of Computerized Automated Learning Device ALDM Test Systems

Fagot &#38; Paleressompoulle1 have published an automated learning device (ALDM) aimed at testing individual cognitive abilities in semi-free ranging monkeys. The main goal of our protocol is to use a network of ALDM test units to study social cognition in non-human primates.

社会认知的非人类灵长类动物评估使用电脑自动学习设备（ALDM）测试系统的网络

Fagot &#38; Paleressompoulle1 and Fagot &#38; Bonte2 have published an automated learning device (ALDM) for the study of cognitive abilities of monkeys ...

An Objective and Child-friendly Assessment of Arm Function by Using a 3-D Sensor

Progressive and irreversible muscle atrophy characterizes Spinal Muscular Atrophy (SMA) and other similar muscle disorder diseases. Objective assessment of muscle functions is an essential and important, although challenging, prerequisite for successful clinical trials. Current clinical rating scales restrain the movement abnormalities to certain predefined coarse-grained individual items. The Kinect 3-D sensor has emerged as a low-cost and portable motion sensing technology used to capture and track people&#39;s movement in many medical and research fields. A novel approach using this 3-D sensor was developed and a game-like test was designed to objectively measure the upper limb function of patients with SMA. The prototype test targeted joint movement capability. While sitting in a virtual scene, the patient was instructed to extend, flex, and lift the whole arm in order to reach and place some objects. Both kinematic and spatiotemporal characteristics of upper limb movement were extracted and analyzed, e.g., elbow extension and flexion angles, hand velocity, and acceleration. The first study included a small cohort of 18 ambulant SMA patients and 19 age- and gender-matched healthy controls. A comprehensive analysis of arm movement was achieved; however, no significant difference between the groups were found due to the mismatch of patient&#39;s capability and the test difficulty. Based on this experience, a second version of the test consisting of a modified version of the first game with increased difficulties and a second game targeting muscle endurance were designed and implemented. The new test has not been conducted in any patient groups yet. Our work has demonstrated the potential capability of the 3-D sensor in assessing such muscle function and suggested an objective approach to complement the clinical rating scales.

An objective measure of muscle functions is challenging especially in children. Based on a commercially available digital 3-D sensor, a child-friendly gaming test was developed to assess upper limb function for clinical trials.

基于3维传感器的 Arm 功能的客观和儿童友好评估

Progressive and irreversible muscle atrophy characterizes Spinal Muscular Atrophy (SMA) and other similar muscle disorder diseases. Objective assessment ...

Systematic Assessment of Well-Being in Mice for Procedures Using General Anesthesia

In keeping with the 3R Principle (Replacement, Reduction, Refinement) developed by Russel and Burch, scientific research should use alternatives to animal experimentation whenever possible. When there is no alternative to animal experimentation, the total number of laboratory animals used should be the minimum needed to obtain valuable data. Moreover, appropriate refinement measures should be applied to minimize pain, suffering, and distress accompanying the experimental procedure. The categories used to classify the degree of pain, suffering, and distress are non-recovery, mild, moderate, or severe (EU Directive 2010/63). To determine which categories apply in individual cases, it is crucial to use scientifically sound tools.
The well-being-assessment protocol presented here is designed for procedures during which general anesthesia is used. The protocol focuses on home cage activity, the Mouse Grimace Scale, and luxury behaviors such as burrowing and nest building behavior as indicators of well-being. It also uses the free exploratory paradigm for trait anxiety-related behavior. Fecal corticosterone metabolites as indicators of acute stress are measured over the 24-h post-anesthetic period.
The protocol provides scientifically solid information on the well-being of mice following general anesthesia. Due to its simplicity, the protocol can easily be adapted and integrated in a planned study. Although it does not provide a scale to classify distress in categories according to the EU Directive 2010/63, it can help researchers estimate the degree of severity of a procedure using scientifically sound data. It provides a way to improve the assessment of well-being in a scientific, animal-centered manner.

We developed a protocol to assess well-being in mice during procedures using general anesthesia. A series of behavioral parameters indicating levels of well-being as well as glucocorticoid metabolites were analyzed. The protocol can serve as a general aid to estimate the degree of severity in a scientific, animal-centered manner.

全身麻醉下小鼠幸福度的系统评价

In keeping with the 3R Principle (Replacement, Reduction, Refinement) developed by Russel and Burch, scientific research should use alternatives to animal ...

An Electrophysiology Protocol to Measure Reward Anticipation and Processing in Children

We present a protocol designed to measure the neural correlates of reward in children. The protocol allows researchers to measure both reward anticipation and processing. Its purpose is to create a reward task that is appropriate for young children with and without autism while controlling reward properties between two conditions: social and nonsocial. The current protocol allows for comparisons of brain activity between social and nonsocial reward conditions while keeping the reward itself identical between conditions. Using this protocol, we found evidence that neurotypical children demonstrate enhanced anticipatory brain activity during the social condition. Furthermore, we found that neurotypical children anticipate social reward more robustly than children with autism diagnoses. As the task uses snacks as a reward, it is most appropriate for young children. However, the protocol may be adapted for use with adolescent or adult populations if snacks are replaced by monetary incentives. The protocol is designed to measure electrophysiological events (event-related potentials), but it may be customized for use with eye-tracking or fMRI.

This protocol is designed to measure reward anticipation and processing in young children with and without autism. Specifically, the protocol is designed to study the neural correlates of reward during social and nonsocial conditions while controlling for reward between conditions.

儿童奖励预期与处理的电生理学协议

We present a protocol designed to measure the neural correlates of reward in children. The protocol allows researchers to measure both reward anticipation ...

An Experimental Paradigm for Measuring the Effects of Ageing on Sentence Processing

Previous studies have found that older adults have greater difficulties in processing syntactically complex sentences than younger adults. However, the exact regions where the difficulties arise have not been fully identified. In this study, a maze task was implemented to investigate how older adults and younger adults differentially processed two types of sentences with different levels of syntactic complexity, namely subject relative clauses and object relative clauses. Participants were asked to choose between two alternatives at each segment of the sentences. The task required participants to engage in a strictly incremental mode of processing. The reading times for each segment were recorded, allowing the quantification of the difficulty of sentence reading. The task allowed us to identify the exact locations of the processing difficulty and thus facilitate a more accurate assessment of the age-related decline in sentence processing. The results indicate that the effect of ageing was found mainly at the head nouns, but not at other regions of the sentences, a finding which suggests that the maze task is an effective method to identify the exact location of the ageing effect on sentence processing. The implications of this experimental paradigm for investigating the effect of ageing on sentence processing are discussed.

Here, we present a protocol to examine the age-related decline in sentence processing using a maze task that allowed us to localize the processing difficulty at each word of the sentences during reading.

测量衰老对句子处理影响的实验范式

Previous studies have found that older adults have greater difficulties in processing syntactically complex sentences than younger adults. However, the ...

Assessment of Stress Effects on Cognitive Flexibility using an Operant Strategy Shifting Paradigm

Stress affects cognitive function. Whether stress enhances or impairs cognitive function depends on several factors, including the 1) type, intensity, and duration of the stressor; 2) type of cognitive function under study; and 3) timing of the stressor in relation to learning or executing the cognitive task. Furthermore, sex differences among the effects of stress on cognitive function have been widely documented. Described here is an adaptation of an automated operant strategy shifting paradigm to assess how variations in stress affect cognitive flexibility in male and female Sprague Dawley rats. Specifically, restraint stress is used before or after training in this operant-based task to examine how stress affects cognitive performance in both sexes. Particular brain areas associated with each task in this automated paradigm have been well-established (i.e., the medial prefrontal cortex and orbitofrontal cortex). This allows for targeted manipulations during the experiment or the assessment of particular genes and proteins in these regions upon completion of the paradigm. This paradigm also allows for the detection of different types of performance errors that occur after stress, each of which has defined neural substrates. Also identified are distinct sex differences in perseverative errors after a repeated restraint stress paradigm. The use of these techniques in a preclinical model may reveal how stress affects the brain and impairs cognition in psychiatric disorders, such as post-traumatic stress disorder (PTSD) and major depressive disorder (MDD), which display marked sex differences in prevalence.

Stressful life events impair cognitive function, increasing the risk of psychiatric disorders. This protocol illustrates how stress affects cognitive flexibility using an automated operant strategy shifting paradigm in male and female Sprague Dawley rats. Specific brain areas underlying particular behaviors are discussed, and translational relevance of results are explored.

使用操作策略转移范式评估压力对认知灵活性的影响

Stress affects cognitive function. Whether stress enhances or impairs cognitive function depends on several factors, including the 1) type, intensity, and ...

Concept Development and Use of an Automated Food Intake and Eating Behavior Assessment Method

The vast majority of dietary and eating behavior assessment methods are based on self-reports. They are burdensome and also prone to measurement errors. Recent technological innovations allow for the development of more accurate and precise dietary and eating behavior assessment tools that require less effort for both the user and the researcher. Therefore, a new sensor-based device to assess food intake and eating behavior was developed. The device is a regular dining tray equipped with a video camera and three separate built-in weighing stations. The weighing stations measure the weight of the bowl, plate, and drinking cup continuously over the course of a meal. The video camera positioned to the face records eating behavior characteristics (chews, bites), which are analyzed using artificial intelligence (AI)-based automatic facial expression software. The tray weight and the video data are transported at real-time to a personal computer (PC) using a wireless receiver. The outcomes of interest, such as the amount eaten, eating rate and bite size, can be calculated by subtracting the data of these measures at the timepoints of interest. The information obtained by the current version of the tray can be used for research purposes, an upgraded version of the device would also facilitate the provision of more personalized advice on dietary intake and eating behavior. Contrary to the conventional dietary assessment methods, this dietary assessment device measures food intake directly within a meal and is not dependent on memory or the portion size estimation. Ultimately, this device is therefore suited for daily main meal food intake and eating behavior measures. In the future, this technology based dietary assessment method can be linked to health applications or smart watches to obtain a complete overview of exercise, energy intake, and eating behavior.

This protocol shows and explains a new technology-based dietary assessment method. The method consists of a dining tray with multiple built-in weighing scales and a video camera. The device is unique in the sense that it incorporates automated measures of food and drink intake and eating behavior over the course of a meal.

自动食物摄入和饮食行为评估方法的概念开发和使用

The vast majority of dietary and eating behavior assessment methods are based on self-reports. They are burdensome and also prone to measurement errors. ...