这项研究是由赠款BCS-0963581从美国国家科学基金会（以EAK和JDP）的支持。作者感谢恭考克斯的数据，以及哈雷祖克，约翰·莫里斯，克里斯托弗凝视，桑德拉寇根，和迈特巴尔达为他们的数据收集方面的援助对她有益的讨论。请针对对应凯利A.本尼恩（kelly.bennion @ bc.edu; 140联邦大道，波士顿学院心理学，MCGUINN 300，栗山，马02467）。

1，参与者的筛选和准备实验<ol><li>招募参与者谁是英语为母语正常或矫正视力正常。他们应该是免费的神经，精神，睡眠障碍，且不得参加影响中枢神经系统或睡眠结构的任何药物。一定要招收的利益所需的年龄范围（ 例如 ，18至35岁）中男性和女性参加了类似的平衡，同时要注意改变睡眠结构会发生，早在30年代中期16。 </li><li>为了最准确地评估睡眠对认知的影响，与会者都保持有规律的睡眠时间表，并限制他们的饮酒量导致了这项研究。要求学员睡觉至少7小时的夜间在床上由早上2:00作为五个晚上研究前。此外，还要确保他们限制他们的饮酒量最大为在5天前研究2饮品，完全没有饮酒的前一天或研究的一天。 </li><li>在调度，确保参与者将遵守相关的唾液皮质醇样的指导方针（参见第4节）:他们必须避免体力活动，进食，饮水（水之外的任何东西），吸烟，刷牙为2小时在编码之前。他们还必须从饮用水至少15分钟之前编码的事。 </li><li>调度参与者。如果全随机分配是不可能的，确保参与者不会在年龄的不同，分数在清晨型- Eveningness问卷17（MEQ），贝克忧郁量表18（BDI），贝克焦虑量 ​​表19（BAI）及睡眠量获得在检索前一天晚上。 </li></ol> 2，条件及实验设计<ol><li>附表睡眠参与者，使得日Ë编码会话发生在晚上（晚上7:00-10:00）和检索会话发生12小时后，下面睡在实验室一整夜。附表唤醒参加这样的编码会话发生在早上（7:00-10:00 AM）和发生的检索会话清醒一整天12小时后下;确保它们不会在会话之间打盹。 </li><li>在实验设计包括早上和傍晚短延迟条件（即那些仅有20分钟的延迟编码和提取之间，相比于12小时延迟睡眠和唤醒组），以尽量减少关切之间存在的任何分歧睡眠和唤醒群体是由于测试的时间（早晨与傍晚），而不是由于整合延迟期间发生的睡眠。这些短延迟条件下，也可看作是"生物钟控制"的条件。 <ol><li>安排参加者在早上短延迟条件刺激B编码etween上午7:00-10:00，并为参与者晚报短延迟条件7:00-10:00时之间的刺激进行编码。编码后进行测试的参与者20分钟。 </li></ol></li></ol> 3，施工刺激<ol><li>刺激建筑进行编码。选择的基础上，具体的实验问题的刺激。这个协议着重于睡眠和皮质醇对情绪记忆的作用，正因为如此，在编码过程中的视觉刺激或者是负的对象或放置在一个中性背景的中性对象组成的场景。 <ol><li>确保所有的情绪刺激已经不是以前额定愉悦度和唤醒20,21，或者说，他们正在使用的是李克特量表从1到7在完成额定的研究参与者。否定的对象，应评定为高度激发和低的价（ 例如 ，觉醒:5-7;价&lt;上采用7点量表3高值，表示高的觉醒和积极性高，respe沉着应对）和中性的物体应被评为为非徒增和中性的化合价（ 例如 ，觉醒&lt;4;价:3-5）。 </li><li>随机化和设计。随机混杂块（如适用）之间的负和中性的场面。本研究采用2块每次持续约10分钟，让参与者有一个短暂的休息，从眼动仪之间休息他们的眼睛。休息时间可能会有所帮助每10-15分钟为最年轻的成年参与者，但如果测试不同人群（ 如儿童），更频繁的暂停可能需要。 </li></ol></li><li>刺激建筑进行检索。选择的基础上，具体的实验问题的刺激。这里，存储器中的对象是焦点，因此，与会者都带有分别在检索过程中（其中有一半的编码过程中被提出，并且半新）对象和背景。 </li></ol> 4，皮质醇程序<ol><li>确保参与者都遵守了所有的要求在1.3:无体力活动，进食，饮水（水之外的任何东西），吸烟，刷牙的2小时前编码，以及没有水至少15分钟前编码。 </li><li>紧接在编码之前，指导学员进行冲洗自己的嘴巴约1盎司水。提醒他们不要吞水，以避免样品稀释。 </li><li>有与会者就垂涎三尺的口腔棉签（见材料）2分钟​​。 </li><li>当有与会者将口腔棉签拭子中存储管，存储拭子在0ºF的近似温度，直到分析。 </li></ol> 5，眼睛跟踪/编码过程<ol><li>眼动追踪程序。这里使用的眼动仪跟踪参与者的左眼注视模式在500赫兹（见材料）。替代跟踪器可以使用;为了在编码，福卢最准确地评估关注w一起使用特定的眼动仪的指示。 <ol><li>首先，要求学员坐在与他们的腮托和额头顶在酒吧下巴。做出调整椅子的高度，并根据需要腮托，确保屏幕中心对齐参与者的目光。 </li><li>确保眼动仪是通过让每个参与者完成校准任务准确跟踪精度范围内以1°与会者的目光。理想的是，9 - 或17 - 点校准将被使用，这取决于系统，但是一个3 - 或5 - 点校准也可能是足够的。 </li><li>首先，要求学员跟着一个黑点用自己的眼睛，因为它移动到不同的点在屏幕上，并注视它时，它会停止。 </li><li>一旦眼动仪的精确校准，要求学员，如果他们准备开始工作，然后按下"记录"按钮。 </li></ol></li><li>编码过程。要求学员执行任务T帽子很可能会导致深编码，如让他们通过鼠标单击指示他们是否会接近或退离现场（ 例如 ，左=方法;右=往回走），如果他们在现实生活中10遇到它。参见图2的编码过程的可视化描述。 <ol><li>让参与者有一个简短的自我决定中断（ 例如 ，〜10-60秒）块之间，使他们可以坐下来从眼动仪，并继续之前的休息眼睛。请他们指出，当他们准备继续。 </li></ol></li><li>分析眼睛凝视数据。为了测量与会者注意现场的某些部分，用软件绘制周围的部分利息22（兴趣区）的区域。 <ol><li>绘制兴趣区后，计算时间参加看看AOI相对于场景的其余部分的比例。另外，算上扫视数量参与者作出了AO我在一定的时间范围内。 </li></ol></li></ol> 6，研究，测试延迟<ol><li>确保用于睡眠和唤醒条件编码与提取之间的延迟长度等于（ 例如 ，12小时），以及延迟长度为2的控制条件（ 例如 ，20分钟）。 <ol><li>对于睡眠的参与者，确保12小时延迟包括约8小时的睡眠。反之，确保唤醒参与者在此期间不睡觉或午睡。 </li><li>问早上和晚上短延时参与者在其20分钟的延迟停留在实验室。告诉他们，他们可以为所欲为，请在这段时间内，只要他们不午睡。 </li></ol></li></ol> 7，承认程序<ol><li>随着延迟时间，让参加者记忆测试。 <ol><li>要求学员以指示显示的刺激是否是"老"（INC在先前研究的场景luded），或"新"（以前没有研究）通过按键盘（ 例如 ，"1"=旧上相应的键，"2"=新）。 </li></ol></li></ol>

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J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cortisol+variation+in+humans+affects+memory+for+emotionally+laden+and+neutral+information.">Cortisol variation in humans affects memory for emotionally laden and neutral information.</a> Behav. Neurosci. 117 (3), 505-516 (2003).</li></ol>

作者宣称，他们有没有竞争的财务权益。

这个实验的设计提供了第一手的证据，对内存预编码皮质醇的有益效果是显著只有在睡眠过程中的盘整期发生。只有两个测量皮质醇水平和操作合并间隔是否包括睡眠是可以确定的睡眠和皮质醇对内存的互动效果。这样的设计是在确定关键的，在以前的研究已经绑预先学习皮质醇来促进记忆为负性刺激1,5，皮质醇这些效果可能表现，因为固结的时间间隔期间发生的睡眠。 考虑到睡眠与唤醒的设计必要在两组试验参与者在一天的不同时间这一发现是由更有趣。以下皮质醇昼夜节律26，最高的皮质醇水平在清晨，最低在电子逆Vening。因此，睡眠的参与者都在一个狭窄的范围内相对较低的皮质醇水平，在晚上有编码的，而唤醒参与者有更高，更多变的皮质醇水平，早上有编码。通过采用这样的设计，似乎在相对低的皮质醇水平甚至微小的差别，足以影响记忆巩固一段睡眠。与此同时，然而，皮质醇的昼夜变化也复杂的设计。今后的工作中可以考虑如何控制皮质醇的昼夜变化以不同的方式影响。其中一个方法是使用午睡模式复制目前的研究结果。因为午睡和唤醒状态之间的皮质醇水平，将统计学等同，皮质醇的昼夜波动，这样的模式会不会成为问题。 虽然许多问题依然是关于皮质醇睡眠如何互动，提高情绪记忆CONSOlidation，目前的工作提供了证据，对情绪记忆预编码皮质醇以下的至少24小时的延迟包括睡眠1,5,27的促进作用可能是由于皮质醇和睡眠相关的固结过程之间的相互作用。如果没有设计，其中一个条件的延迟包括睡眠和其他不，这是不可能孤立睡眠是否有必要对这种影响待观察。此外，通过评估在编码过程中参与者的视线，它被确定皮质醇的情感记忆的这种促进作用可能是由于皮质醇在调节睡眠时编码和随后的整合这些信息关注情感信息之间的关系:随着升高皮质醇，之间存在什么编码，以及他们后来还记得在参与者看一个更强的关系。这是可能的，这是因为皮质醇升高在编码&#39;标签"这种情感信息，重要的是要记住，这导致睡眠选择性地加强巩固间隔期间的重要资料。 这种独特的方法组合 - 睡眠与唤醒的设计，静息唾液皮质醇值的测量，眼睛凝视的编码过程中的评估，以及一个行为认记忆测验的管理 - 不仅导致皮质醇揭露和睡眠的互动效应于综合账目，而且要确定这背后影响的潜在注意力机制。总体而言，本研究可作为如何结合这通常是独立使用，以达到更好的理解，影响认知变量之间复杂的相互作用的方法的例子。

整合信息的能力依赖于无数的因素，睡眠和应激激素皮质醇作为两个最有影响力的变量。此前的研究表明，皮质醇水平升高，通过外源性皮质醇管理或心理压力，无论是诱导往往 ​​有选择性增强记忆的情感相对于中性刺激1-7关联。睡眠已经显示出对情绪记忆8,9类似的选择性作用:当参与者都带有放置在中性背景负或中性物体组成的场景，睡眠解除绑定的场景，保存存储器用于负极的对象，同时允许内存对于不太突出场景组件（中性对象和中性的背景）衰减10-12。 虽然这两个文献集中于皮质醇和睡眠对情绪记忆的独立作用，它可能是共rtisol和睡眠有一个互动的效果。有趣的是，因为研究调查皮质醇对记忆的影响，包括至少24小时，其中必然包括一夜的睡眠中保留延迟，这是不可能的，以确定是否睡眠是必要的皮质醇对巩固一个促进作用。同样地，尽管有研究表明，睡眠优先受益存储器为情感信息，这是可能的，这些作用可能在较高的皮质醇水平的个体进行编码时加剧。 由于这些原因，它不仅要了解如何睡眠和皮质醇独立支持记忆的形成，同时也探讨睡眠和皮质醇是否进行交互，支持记忆的形成是非常重要的。毕竟，在正常老化13精神病理学是与记忆障碍14,15相关形式的睡眠和皮质醇之间的重要联系，并。仅通过使用一个组合方法是可以理解的睡眠和皮质醇之间复杂的相互作用，以及它们对记忆的巩固作用。具体地，通过唾液皮质醇集合的方法与睡眠与唤醒的设计相结合，这是可能的，以确定是否存在于合并这两个变量的交互效果。还可贵的是，通过使用眼动追踪编码过程中测量眼睛的注视下，它可以阐明这个基本作用的潜力注意力机制。

<table border="0" cellpadding="0" cellspacing="0" width="634">
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:243px;">Salimetrics oral swabs (SOS)</td>
			<td style="width:105px;">Salimetrics</td>
			<td style="width:119px;">5001.02</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:243px;">Swab storage tubes (SST)</td>
			<td style="width:105px;">Salimetrics</td>
			<td style="width:119px;">5001.05</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="84">
			<td height="84" style="height:84px;width:243px;">Eye-tracker</td>
			<td style="width:105px;">SensoMotoric Instruments (SMI)</td>
			<td style="width:119px;">iView X Hi-Speed</td>
			<td style="width:167px;"></td>
		</tr>
	</tbody>
</table>

eye tracking, cortisol, and a sleep vs. wake consolidation delay: combining methods to uncover an interactive effect of sleep and cortisol on memory

虽然上涨的皮质醇可以受益记忆的巩固，因为可以编码后很快入睡，但目前文献的缺乏，如何这两个因素可能会相互作用，影响整合。在这里，我们提出了一个协议来检查皮质醇和睡眠对记忆的巩固的交互影响，结合三种方法:眼跟踪，唾液皮质醇的分析，并在睡眠和唤醒延迟行为记忆测试。为了评估静息皮质醇水平，参与者的场景中观看阴性和中性的对象之前，给了唾液样本。为了测量显性的关注，参与者的眼睛凝视被编码过程中进行跟踪。要操作是否合并窗口过程中出现的睡眠，参加者无论是编码的场景在晚上，睡了一夜，并采取了识别测试，第二天早上，或编码在早上的场景和一个同等长的停留时间间隔内保持清醒。其他对照组分别为德一个20分钟的延迟在早晨或傍晚，以控制时间 - 日期后遗症STED。总之，结果表明，存在于编码和后续的存储器休息皮质醇之间有直接的关系，仅经过一段时间的睡眠。通过眼动追踪，它被进一步确定，对于负性刺激，皮质醇在随后的记忆这种有益的作用可能是由于皮质醇加强地方之间在编码过程中的参与者看，它们是什么以后能够记住的关系。总体来说，通过这些方法的组合得到的结果发现睡眠和皮质醇对记忆巩固的互动效果。

关于内存的情绪和中性刺激作用睡眠和皮质醇处理的第一个假设是，在编码期间皮质醇升高会促进记忆比中性刺激情绪更多，而且这种效果是依赖于编码和检索之间睡眠发生。 图4A绘制皮质醇对存储器为负的物体的效果。皮质醇（x-轴）和存储器的标准化水平为负的对象（y-轴）直接相关的睡眠组（红色）中，但不唤醒组（灰色）。本集团（休眠与唤醒）由皮质醇交互作用显著[T（41）= 2.23，β= 2.92，P = 0.031]:较高的皮质醇在编码预测内存负的对象，如果参加者编码和提取[吨 （24间睡）= 2.31，β= 0.43，P = 0.031]，但如果他们保持清醒[T（16）= 0.40，β </EM&gt; = 0.10，P = 0.70; 见图4A]。这些显著作用并不因性别，月经周期，或批判，一天的时间，这是通过运行另外的分析与早晨和傍晚短延时群体决定的。对于中性存储器（ 见图4B），类似的，但较弱的模式进行了观察。有前编码（x轴）和内存的中性物体（y轴）的睡眠组[蓝色的皮质醇水平之间的轻微显著关系; 吨（24）= 1.76，β= 0.34，P = .092 ]，但没有叫醒组[灰色; 吨 （16）= 0.98，β= 0.25，P = 0.34]。皮质醇和集团之间的相互作用是轻微显著[T（41）= 1.95，β= 2.55，P = 0.059]。 在编码和整合过程中注意之间的互作效应睡眠和皮质醇这是低thesized皮质醇的情感记忆的这种有益作用可能部分是由于皮质醇的能力，"标签"信息同样重要要记住，在编码时，睡眠时导致该信息的后续优先。这种"情绪标记"的概念表明编码引起的刺激激活的神经机制，导致在标记标签23-25 ​​突触长期的可塑性。这可能是在编码期间升高的皮质醇协助来设置这些标记，在固结过程中，导致该信息的选择性保护。为了研究这种可能性，眼动跟踪数据进行分析，以确定较高的皮质醇是否增加的可能性，睡眠为基础的整合进程优先加强记忆的编码过程中获得最多关注的信息。首先，时间每个参与者的比例花在寻找在每个对象中的每个场景内（&lt;EM&gt;即AOI）相对于总的场景的观看时间计算。这些场景，然后整理在事后基础上，用每个参与者的识别数据的场景分类到那些为其参与者后来回忆的对象，那些为其参与者后来忘了对象。最后，一个得分被计算，以反映后来想起，随后遗忘物体之间在美观的时间之差（参见图5）。例如，如果学员看着他们随后想起，平均时的场景是在屏幕上75％的对象，又看了看对象，他们后来忘了平均为65％时的场面在屏幕上，他们在寻找时间的得 ​​分差别是10％。 类似于对睡眠和皮质醇的存储器（ 图4）的效果进行了分析，线性回归被用来测试该睡眠和皮质醇在看时间编码为以后记忆功能这种差异的影响。对于负的对象（参见图6A），休息皮质醇（x轴）轻微预测看着时间编码为以后的内存（y轴）的睡眠组[红色在函数的区别，T（23）= 1.869 ，β= 0.37，P = 0.075]，但不能唤醒组[灰色T（16）= 0.168，β= 0.043，P = 0.87]。皮质醇和集团之间的相互作用是显著[T（40）= -2.04，β= -2.99，P = 0.049]，而关键的是，这显著作用不是由于性别，月经周期，或一天的时间。对于中性的对象（参见图6B），有皮质醇没有影响睡眠组（蓝色），也不是唤醒组（灰色）中，和皮质醇和集团之间的交互作用不显著。 <imgALT ="图1"FO:内容宽度="5英寸"SRC ="/ files/ftp_upload/51500/51500fig1highres.jpg"宽度="500"/&gt; 图1:在这个视频报告，由集团分开描述的过程的可视化描述。此图显示了四组参与者（休眠，唤醒，早晨短延时，和晚报短延时），以及时机的预编码皮质醇样品，编码和检索对每个组。 <img alt="图2" fo:content-width="5in" src="/files/ftp_upload/51500/51500fig2highres.jpg" width="500" /> 图2的编码过程中使用的刺激的视觉描绘。该图显示每一场景的组成为任一负的或放置在一个中性的背景前面的中性对象。它还表明，与会者认为，这些场景对于每个三秒钟，其中T时IME他们表示，他们是否会接近或退离现场，如果他们在现实生活中遇到它。 <img alt="图3" fo:content-width="5in" src="/files/ftp_upload/51500/51500fig3highres.jpg" width="500" /> 图3。检索过程中使用的刺激的视觉描述。这一数字表明，与会者提交与再认记忆测验中的对象和背景（另发）。这些对象和背景的编码（"旧"）期间无论是以前提出的或以前从未见过的实验（"新"）的背景下。 <img alt="图4" fo:content-width="5in" src="/files/ftp_upload/51500/51500fig4highres.jpg" width="500" /> 图皮质醇4。对内存的负面和中性的对象。一 </strong&gt;的绘制对记忆的负面对象标准化皮质醇水平的影响:B地块标准化皮质醇水平对记忆中性物体的效果。图例:睡眠[红色钻石（NEG），蓝钻（NEU）]，唤醒[灰色方块]，睡眠线性拟合[红线（负），蓝线（神经）]，唤醒线性拟合[灰线]。 <img alt="图5" fo:content-width="5in" src="/files/ftp_upload/51500/51500fig5highres.jpg" width="500" /> 图5。视觉编码（左）和检索（右）的步骤，与在眼睛跟踪分析评估因变量（在编码作为后存储的函数中寻找时间差）的描述，该图显示了依赖在眼球追踪分析（以编码为以后记忆功能在看时间的差异）的变量计算。特别是，这个分数反映出的比例编码参与者看着他们后来回忆（"点击"）减去时间编码，与会者看了看对象，他们后来忘了（"未命中"）中的比重对象中的时间。 <img alt="图6" fo:content-width="5in" src="/files/ftp_upload/51500/51500fig6highres.jpg" width="500" /> 图6。皮质醇对寻找时间在编码作为后存储器，用于阴性和中性对象的函数的差的影响。寻找时间被计算为总场景的观看时间的参与者使用了注视对象在场景中的比例。一个分数，然后计算，以反映在随后寻找记忆，随后忘了对象，线性回归是用来测试皮质醇和睡眠对这个分数的影响之间的时间差， 一个地块为负的影响</em&gt;对象， 而 B地块为中性物体的效果。图例:睡眠[红色钻石（NEG），蓝钻（NEU）]，唤醒[灰色方块]，睡眠线性拟合[红线（负），蓝线（神经）]，唤醒线性拟合[灰线]。

Watch this Scientific Journal Video about Eye Tracking, Cortisol, and a Sleep vs. Wake Consolidation Delay: Combining Methods to Uncover an Interactive Effect of Sleep and Cortisol on Memory at JoVE.c

Eye Tracking, Cortisol, and a Sleep vs. Wake Consolidation Delay: Combining Methods to Uncover an Interactive Effect of Sleep and Cortisol on Memory

我们目前用于发现在记忆巩固睡眠和皮质醇之间的互动作用，特别是对负唤起图像的协议。具体而言，实验设计采用眼睛跟踪，唾液皮质醇分析，和行为的存储器测试 - 的方法，可以与健康的和临床的参与者使用。

眼睛跟踪，皮质醇和睡眠与唤醒延迟合并:合并方法来揭开睡眠和皮质醇的交互式影响记忆

Although rises in cortisol can benefit memory consolidation, as can sleep soon after encoding, there is currently a paucity of literature as to how these ...

eye-tracking-cortisol-sleep-vs-wake-consolidation-delay-combining

Universidad de Cartagena UDEC

Research

JoVE Journal

Behavior

26.9K 次观看.  Boston College. 我们目前用于发现在记忆巩固睡眠和皮质醇之间的互动作用，特别是对负唤起图像的协议。具体而言，实验设计采用眼睛跟踪，唾液皮质醇分析，和行为的存储器测试 - 的方法，可以与健康的和临床的参与者使用。 

视频: Eye Tracking, Cortisol, and a Sleep vs. Wake Consolidation Delay: Combining Methods to Uncover an Interactive Effect of Sleep and Cortisol on Memory

A Method to Quantify Visual Information Processing in Children Using Eye Tracking

Visual problems that occur early in life can have major impact on a child's development. Without verbal communication and only based on observational methods, it is difficult to make a quantitative assessment of a child's visual problems. This limits accurate diagnostics in children under the age of 4 years and in children with intellectual disabilities. Here we describe a quantitative method that overcomes these problems. The method uses a remote eye tracker and a four choice preferential looking paradigm to measure eye movement responses to different visual stimuli. The child sits without head support in front of a monitor with integrated infrared cameras. In one of four monitor quadrants a visual stimulus is presented. Each stimulus has a specific visual modality with respect to the background, e.g., form, motion, contrast or color. From the reflexive eye movement responses to these specific visual modalities, output parameters such as reaction times, fixation accuracy and fixation duration are calculated to quantify a child's viewing behavior. With this approach, the quality of visual information processing can be assessed without the use of communication. By comparing results with reference values obtained in typically developing children from 0-12 years, the method provides a characterization of visual information processing in visually impaired children. The quantitative information provided by this method can be advantageous for the field of clinical visual assessment and rehabilitation in multiple ways. The parameter values provide a good basis to: (i) characterize early visual capacities and consequently to enable early interventions; (ii) compare risk groups and follow visual development over time; and (iii), construct an individual visual profile for each child.

A method is described to quantify the quality of visual information processing based on reflexive eye movements in response to specific visual modalities. Reaction times and fixation output parameters are used to characterize visual performance in children with and without visual impairments from 6 months of age.

一种方法来量化视觉信息加工儿童使用眼动追踪

Visual problems that occur early in life can have major impact on a child's development. Without verbal communication and only based on observational ...

科研

行为学

Eye-Tracking Control to Assess Cognitive Functions in Patients with Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with pathological involvement of upper and lower motoneurons, subsequently leading to progressive loss of motor and speech abilities. In addition, cognitive functions are impaired in a subset of patients. To evaluate these potential deficits in severely physically impaired ALS patients, eye-tracking is a promising means to conduct cognitive tests. The present article focuses on how eye movements, an indirect means of communication for physically disabled patients, can be utilized to allow for detailed neuropsychological assessment. The requirements, in terms of oculomotor parameters that have to be met for sufficient eye-tracking in ALS patients are presented. The properties of stimuli, including type of neuropsychological tests and style of presentation, best suited to successfully assess cognitive functioning, are also described. Furthermore, recommendations regarding procedural requirements are provided. Overall, this methodology provides a reliable, easy to administer and fast approach for assessing cognitive deficits in patients who are unable to speak or write such as patients with severe ALS. The only confounding factor might be deficits in voluntary eye movement control in a subset of ALS patients.

Cognitive deficits are common in about one third of patients with amyotrophic lateral sclerosis, a neurological condition leading to progressive impairments in speech and movement abilities. To conduct cognitive tests in patients unable to speak or write a reliable and easy to administer eye-tracking paradigm was developed.

眼跟踪控制，以评估患者的认知功能与肌萎缩性脊髓侧索硬化症

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with pathological involvement of upper and lower motoneurons, subsequently leading to ...

Manipulation of Epileptiform Electrocorticograms (ECoGs) and Sleep in Rats and Mice by Acupuncture

Ancient Chinese literature has documented that acupuncture possesses efficient therapeutic effects on epilepsy and insomnia. There is, however, little research to reveal the possible mechanisms behind these effects. To investigate the effect of acupuncture on epilepsy and sleep, several issues need to be addressed. The first is to identify the acupoints, which correspond between humans, rats, and mice. Furthermore, the depth of insertion of the acupuncture needle, the degree of needle twist in manual needle acupuncture, and the stimulation parameters for electroacupuncture (EA) need to be determined. To evaluate the effects of acupuncture on epilepsy and sleep, a feasible model of epilepsy in rodents is required. We administer pilocarpine into the left central nucleus of the amygdala (CeA) to simulate focal temporal lobe epilepsy (TLE) in rats. Intraperitoneal (IP) injection of pilocarpine induces generalized epilepsy and status epilepticus (SE) in rats. Five IP injections of pentylenetetrazol (PTZ) with a one-day interval between each injection successfully induces spontaneous generalized epilepsy in mice. Recordings of electrocorticograms (ECoGs), electromyograms (EMGs), brain temperature, and locomotor activity are used for sleep analysis in rats, while ECoGs, EMGs, and locomotor activity are employed for sleep analysis in mice. ECoG electrodes are implanted into the frontal, parietal, and contralateral occipital cortices, and a thermistor is implanted above the cerebral cortex by stereotactic surgery. EMG electrodes are implanted into the neck muscles, and an infrared detector determines locomotor activity. The criteria for categorizing vigilance stages, including wakefulness, rapid eye movement (REM) sleep, and non-REM (NREM) sleep are based on information from ECoGs, EMGs, brain temperature, and locomotor activity. Detailed classification criteria are stated in the text.

Manipulation of Epileptiform Electrocorticograms ECoGs and Sleep in Rats and Mice by Acupuncture

This paper demonstrates the performance of acupuncture, epilepsy models, and the analysis of sleep in rodents. The acupuncture procedure and the identification of acupoints are described. Pilocarpine or pentylenetetrazol (PTZ) is used to induce epilepsy. Electrocorticogram (ECoG), electromyogram (EMG), brain temperature, and locomotor activity recordings are employed for sleep analysis.

癫痫Electrocorticograms（ECoGs）的操作，并睡在针刺大鼠和小鼠

Ancient Chinese literature has documented that acupuncture possesses efficient therapeutic effects on epilepsy and insomnia. There is, however, little ...

Reducing State Anxiety Using Working Memory Maintenance

The purpose of this protocol is to explain how to examine the relationship between working memory processes and anxiety by combining the Sternberg Working Memory (WM) and the threat of shock paradigms. In the Sternberg WM paradigm, subjects are required to maintain a series of letters in the WM for a brief interval and respond by identifying whether the position of a given letter in the series matches a numerical prompt. In the threat of shock paradigm, subjects are exposed to alternating blocks where they are either at risk of receiving unpredictable presentations of a mild electric shock or are safe from the shock. Anxiety is probed throughout the safe and threat blocks using the acoustic startle reflex, which is potentiated under threat (Anxiety-Potentiated Startle (APS)). By conducting the Sternberg WM paradigm during the threat of shock and probing the startle response during either the WM maintenance interval or the intertrial interval, it is possible to determine the effect of WM maintenance on APS.

This protocol demonstrates how to measure anxiety-potentiated startle during the Sternberg Working Memory paradigm.

使用工作记忆维护降低状态焦虑

The purpose of this protocol is to explain how to examine the relationship between working memory processes and anxiety by combining the Sternberg Working ...

Noninvasive, High-throughput Determination of Sleep Duration in Rodents

Traditionally, sleep is monitored by an electroencephalogram (EEG). EEG studies in rodents require surgical implantation of the electrodes followed by a long recovery period. To perform an EEG recording, the animal is connected to a receiver, creating an unnatural tether to the head-mount. EEG monitoring is time consuming, carries risk to the animal, and is not a completely natural setting for the measurement of sleep. Alternative methods to detect sleep, particularly in a high-throughput fashion, would greatly advance the field of sleep research. Here, we describe a validated method for detecting sleep via activity-based home-cage monitoring. Previous studies have shown that sleep assessed via this method has a high degree of agreement with sleep defined by traditional EEG-based measures. Whereas this method is validated for total sleep time, it is important to note that sleep bout duration should be assessed by an EEG which has better temporal resolution. The EEG can also differentiate rapid eye movement (REM) and non-REM sleep, giving more detail about the exact nature of sleep. Nevertheless, activity-based sleep determination can be used to analyze multiple days of undisturbed sleep and to assess sleep as a response to an acute event (like stress). Here, we show the power of this system to detect the response of mice to daily intraperitoneal injections.

We describe a high-throughput method of measuring sleep by means of activity-based home-cage monitoring. This method offers advantages over traditional EEG-based methods. It is well validated for the determination of total sleep duration and can be a powerful tool to monitor sleep in rodent models of human disease.

无创高通量测定啮齿类动物睡眠时间

Traditionally, sleep is monitored by an electroencephalogram (EEG). EEG studies in rodents require surgical implantation of the electrodes followed by a ...

A High-performance Liquid Chromatography Measurement of Kynurenine and Kynurenic Acid: Relating Biochemistry to Cognition and Sleep in Rats

The kynurenine pathway (KP) of tryptophan degradation has been implicated in psychiatric disorders. Specifically, the astrocyte-derived metabolite kynurenic acid (KYNA), an antagonist at both N-methyl-d-aspartate (NMDA) and &#945;7 nicotinic acetylcholine (&#945;7nACh) receptors, has been implicated in cognitive processes in health and disease. As KYNA levels are elevated in the brains of patients with schizophrenia, a malfunction at the glutamatergic and cholinergic receptors is believed to be causally related to cognitive dysfunction, a core domain of the psychopathology of the illness. KYNA may play a pathophysiologically significant role in individuals with schizophrenia. It is possible to elevate endogenous KYNA in the rodent brain by treating animals with the direct bioprecursor kynurenine, and preclinical studies in rats have demonstrated that acute elevations in KYNA may impact their learning and memory processes. The current protocol describes this experimental approach in detail and combines a) a biochemical analysis of blood kynurenine levels and brain KYNA formation (using high-performance liquid chromatography), b) behavioral testing to probe the hippocampal-dependent contextual memory (passive avoidance paradigm), and c) an assessment of sleep-wake behavior [telemetric recordings combining electroencephalogram (EEG) and electromyogram (EMG) signals] in rats. Taken together, a relationship between elevated KYNA, sleep, and cognition is studied, and this protocol describes in detail an experimental approach to understanding function outcomes of kynurenine elevation and KYNA formation in vivo in rats. Results obtained through variations of this protocol will test the hypothesis that the KP and KYNA serve pivotal roles in modulating sleep and cognition in health and disease states.

Alterations in the kynurenine pathway (KP) neuroactive metabolites are implicated in psychiatric illnesses. Investigating the functional outcomes of an altered kynurenine pathway metabolism in vivo in rodents may help elucidate novel therapeutic approaches. The current protocol combines biochemical and behavioral approaches to investigate the impact of an acute kynurenine challenge in rats.

高效液相色谱法测定犬尿氨和 Kynurenic 酸: 对大鼠认知和睡眠的相关生物化学研究

The kynurenine pathway (KP) of tryptophan degradation has been implicated in psychiatric disorders. Specifically, the astrocyte-derived metabolite ...

Chronic Sleep Deprivation in Mouse Pups by Means of Gentle Handling

Sleep is critical for proper development and neural plasticity. Moreover, abnormal sleep patterns are characteristic of many neurodevelopmental disorders. Studying how chronic sleep restriction during development can affect adult behavior may add to our understanding of the emergence of behavioral symptoms of neurodevelopmental disorders. While there are many methods that can be used to restrict sleep in rodents including forced locomotion, constant disruption, presentation of an aversive stimulus, or electric shock, many of these methods are very stressful and cannot be used in neonatal mice. Here, we describe gentle handling, a sleep deprivation technique that can be used chronically throughout development and into adulthood to achieve sleep restriction. Gentle handling involves close observation of the mice throughout the sleep deprivation period and requires the researcher to gently prod the animals whenever they are inactive or display behaviors associated with sleep. Coupled with EEG recordings, gentle handling could be used to selectively disrupt a specific phase of sleep such as rapid eye movement (REM) sleep. The technique of gentle handling is a powerful tool for the study of the effects of chronic sleep restriction even in neonatal mice that circumvents many of the more stressful procedures used for sleep deprivation.

We describe a sleep deprivation technique known as gentle handling where investigators gently prod mice any time sleep behavior is observed. This method is a powerful tool that allows researchers to study the effects that chronic sleep restriction throughout development can have on future brain physiology and behavior.

小鼠幼犬慢性睡眠剥夺的温和处理方法

Sleep is critical for proper development and neural plasticity. Moreover, abnormal sleep patterns are characteristic of many neurodevelopmental disorders. ...

Eye-tracking to Distinguish Comprehension-based and Oculomotor-based Regressive Eye Movements During Reading

Regressive eye movements are eye movements that move backwards through the text and comprise approximately 10-25% of eye movements during reading. As such, understanding the causes and mechanisms of regressions plays an important role in understanding eye movement behavior. Inhibition of return (IOR) is an oculomotor effect that results in increased latency to return attention to a previously attended target versus a target that was not previously attended. Thus, IOR may affect regressions. This paper describes how to design materials to distinguish between regressions caused by comprehension-related and oculomotor processes; the latter is subject to IOR. The method allows researchers to identify IOR and control the causes of regressions. While the method requires tightly controlled materials and large numbers of participants and materials, it allows researchers to distinguish and control the types of regressions that occur in their reading studies.

The method was designed to investigate the role of inhibition of return (IOR) in regressive eye movements during reading. The focus is on differentiating between regressions triggered as a result of comprehension difficulty versus those triggered from oculomotor error, including the role of IOR in the two types of regressions.

眼动追踪在阅读中区分基于理解的和基于眼球的退行性眼球运动

Regressive eye movements are eye movements that move backwards through the text and comprise approximately 10-25% of eye movements during reading. As ...

Automated Measurements of Sleep and Locomotor Activity in Mexican Cavefish

Across phyla, sleep is characterized by highly conserved behavioral characteristics that include elevated arousal threshold, rebound following sleep deprivation, and consolidated periods of behavioral immobility. The Mexican cavefish, Astyanax mexicanus (A. mexicanus), is a model for studying trait evolution in response to environmental perturbation. A. mexicanus exist as in eyed surface-dwelling forms and multiple blind cave-dwelling populations that have robust morphological and behavioral differences. Sleep loss has occurred in multiple, independently-evolved cavefish populations. This protocol describes a methodology for quantifying sleep and locomotor activity in A. mexicanus cave and surface fish. A cost-effective video monitoring system allows for behavioral imaging of individually-housed larval or adult fish for periods of a week or longer. The system can be applied to fish aged 4 days post fertilization through adulthood. The approach can also be adapted for measuring the effects of social interactions on sleep by recording multiple fish in a single arena. Following behavioral recordings, data is analyzed using automated tracking software and sleep analysis is processed using customized scripts that quantify multiple sleep variables including duration, bout length, and bout number. This system can be applied to measure sleep, circadian behavior, and locomotor activity in almost any fish species including zebrafish and sticklebacks.

This protocol details the methodology for quantifying locomotor behavior and sleep in the Mexican cavefish. Previous analyses are extended to measure these behaviors in socially-housed fish. This system can be widely applied to study sleep and activity in other fish species.

墨西哥河鱼睡眠和睡眠活动的自动测量

Across phyla, sleep is characterized by highly conserved behavioral characteristics that include elevated arousal threshold, rebound following sleep ...

Exploring Infant Sensitivity to Visual Language using Eye Tracking and the Preferential Looking Paradigm

We discuss the use of the preferential looking paradigm in eye tracking studies in order to study how infants develop, understand, and attend to the world around them. Eye tracking is a safe and non-invasive way to collect gaze data from infants, and the preferential looking paradigm is simple to design and only requires the infant to be attending to the screen. By simultaneously showing two visual stimuli that differ in one dimension, we can assess whether infants show different looking behavior for either stimulus, thus demonstrating sensitivity to that difference. The challenges in such experimental approaches are that experiments must be kept brief (no more than 10 min) and be carefully controlled such that the two stimuli differ in only one way. The interpretation of null results must also be carefully considered. In this paper, we illustrate a successful example of an infant eye tracking study with a preferential looking paradigm to discover that 6-month-olds are sensitive to linguistic cues in a signed language despite having no prior exposure to signed language, suggesting that infants possess intrinsic or innate sensitivities to these cues.

Eye tracking studies using a preferential looking paradigm can be used to study infants&#39;&#160;emerging understanding of, and attention to, their external visual world.

利用眼动追踪和偏好外观范式探索婴儿对视觉语言的敏感度

We discuss the use of the preferential looking paradigm in eye tracking studies in order to study how infants develop, understand, and attend to the world ...