作者要感谢Hannah Zamore，Emily Saks和Josh Searle在Grafe实验室中建立这种操作性策略转变范式的帮助。他们还要感谢 Kevin Snyder 对 MATLAB 代码的分析帮助。

本研究中的所有程序均由Bryn Mawr学院的机构动物护理和使用委员会（IACUC）批准。在订购实验动物和开始实验之前，获得IACUC或其他适用的监管批准。
1. 动物准备
<ol><li>获得雄性和雌性成年斯普拉格道利大鼠。 注意:大鼠可以在65日之前分娩，但在此之前不要开始手术，以确保雄性和雌性都完全成熟。</li>
	<li>配对同性大鼠尽可能长的时间，长期隔离是一种压力源24。对于食物限制，在操作策略转移协议之前单独饲养老鼠。</li>
	<li>适应1周后，每天轻轻开始处理大鼠3-5分钟。收集每只大鼠的体重。此外，如果有兴趣评估性腺激素如何影响结果，请收集雌性大鼠的阴道灌洗（在第2节中描述）。</li>
	<li>在训练开始前至少3天限制（从食物中）将在操作策略中运行的动物转变范式，以便它们成功学习任务。确保水始终是免费提供的。应为每只动物保留书面记录，以记录日常食物和液体的消耗，水合作用状况以及用作暂时或永久将动物从方案中移除的标准的任何行为和临床变化（Morton 2000;NRC 2003b）。<ol>
<li>如果在训练前采用压力程序超过3天，请调整食物限制以匹配压力的天数（例如，5天的约束加食物限制25）。</li>
		<li>每天，提供正常每日食物摄入量的80%（即每100克体重4克食物）26.使用大鼠的每日体重收集来计算每天给多少食物。</li>
		<li>在培训和测试日继续限制食物。但是，在老鼠完成当天的训练或测试之前，不要将食物放在家庭笼子里，否则它们将没有动力执行食物颗粒奖励的任务。确保在完成任务后向老鼠提供食物的时间是相当不可预测的，因为这有助于避免降低在操作室中执行的动机（有利于简单地在家庭笼子中等待食物）。 注意:经历约束压力范式的动物不会表现出比对照，无压力受试者显着更大的体重减轻。然而，各种压力程序本身可能会诱发体重减轻，导致在基于体重的食物限制期间，大鼠接受的食物少于未受压力的对应物。这可能会带来额外的、令人困惑的压力源。如果出现这种情况，或者使用固定量的食物给予每个受试者，无论重量如何27。</li>
	</ol>
</li>
</ol>2. 阴道灌洗
注意:已知性腺激素（即雌激素和孕激素）会影响应激反应和认知28，29，30。这些激素在雌性大鼠的发情周期中波动31。如果有兴趣跟踪自由循环的雌性啮齿动物的发情周期，以与压力或认知灵活性数据相关联，请按如下所述收集阴道灌洗。未提供考虑发情周期阶段的代表性数据。
<ol><li>为了从女性那里获得阴道灌洗样品，请将温水收集在干净的烧杯，玻璃滴管，"灌洗"载玻片（带有丙烯酸涂料圆圈的显微镜载玻片以容纳灌洗样品）和一个空烧杯中。</li>
	<li>用少量温水（约0.5毫升）填充滴管，然后将尖端插入雌性大鼠的阴道（通过尾巴抬起）。将无菌水排出2x-3x，并将收集的液体排出到显微载玻片上。不要溢出灌洗滑梯圈。</li>
	<li>将多余的液体排出到空的烧杯中。用大鼠编号标记灌洗载玻片，并按该顺序放置来自每只大鼠的样品，以便清楚哪个样品属于每只大鼠。</li>
	<li>在填充滴管以对下一只大鼠进行采样之前，通过移液干净的温水并将其分配到"多余的"烧杯中几次，彻底冲洗滴管。</li>
	<li>小心地将灌洗载玻片带到明场显微镜中，对灌洗样品进行成像，并对发情周期内的一天进行分类，如Becker等人31中所述。 注意:理想情况下，洗烟应持续数周，以正确跟踪女性的周期，并应在每天非常相似的时间进行，以控制昼夜节律。优选地，该程序应在应力和操作性策略转移程序之前进行。使用棉签和无菌盐水也可以用作这种滴管技术的替代品。雌性大鼠的数据可以根据发情周期日进行事后分析（考虑进行压力的周期天数和/或测试发生时的周期日）。</li>
</ol>3. 设备和软件
<ol><li>使用操作室进行行为训练和测试。<ol>
<li>确保腔室包含至少两个可伸缩的杠杆，上面有两个刺激灯，一个室内灯和一个用于加固这些任务的分配器。</li>
		<li>检查杠杆是否位于中央钢筋输送区域的任一侧，每个杠杆上方有一个刺激灯。</li>
		<li>使用房屋灯照亮房间，而不会干扰光刺激的检测（最好是房屋灯位于房间的后壁上，与杠杆和刺激灯相对）。</li>
	</ol>
</li>
	<li>使用无尘食品颗粒（这里使用45毫克颗粒:18.7%蛋白质，5.6%脂肪和4.7%纤维）在食物限制的大鼠中加强。不要使用蔗糖或脂肪含量高的颗粒（除非对压力如何影响可口的食物摄入量感兴趣）。</li>
	<li>使用能够操作腔室的软件（材料表）从计算机控制刺激，杠杆操作和数据收集的呈现。 注:有关使用此软件对程序进行编码的信息，请与作者联系。MED-PC 脚本作为补充文件包含在内。该软件收集有关动物对每次试验的反应的信息（按下哪个杠杆，是否正确/不正确/没有反应，以及做出选择的延迟）。根据此信息，用户可以计算行为范式中的各种度量，如行为分析部分所述。</li>
	<li>每天在同一时间进行训练/测试，以控制压力荷尔蒙32（ 和其他相关措施）的昼夜节律。</li>
	<li>在每个操作箱的底部托盘中装满新鲜的床上用品，以收集粪便/废物。每次疗程后，用酒精湿巾或IACUC批准的消毒剂倾倒每个托盘，清洁托盘和腔室内部，并在将新动物放入腔室之前更换新鲜的床上用品。</li>
</ol>4. 压力程序
<ol><li>决定压力程序是否应在操作性策略转换范式训练之前、期间和/或之后进行（例如，在 3 天的操作性训练之前进行 5 天的约束应激， 而不是 在 3 天的操作性训练之后进行单次约束和测试）。</li>
	<li>每天在同一时间执行有关操作性训练的压力程序。（例如，从 9 A.M. 开始 30 分钟的约束应力，然后置于操作室中）。</li>
	<li>在与蚁群室和策略转换范式室分开的房间中执行应力程序（以确保没有与证人压力相关的混杂因素）33。简而言之，将老鼠放在布鲁姆式透明约束管中并密封开口，注意不要捏住四肢或尾巴。在每个受试者之间，使用IACUC批准的消毒剂清洁布鲁姆式管。不正确的消毒会留下信息素，从而对测试方案产生不利影响。 注意:估计第一组大鼠将在操作室中度过多长时间。这将根据培训 与 考试日而有所不同;但是，在运行多个队列后，可以计算完成每个任务以估计未来任务的平均时间。</li>
	<li>根据可用的操作室数量，错开受试者的压力程序。例如，四只大鼠经历约束应激，并被放置在四个操作室中。一小时后，又有四只动物接受应激手术，然后进行手术室。</li>
</ol>5. 培训
注意:该范例是从Floresco等人开发的操作性集合转换程序修改而来的，因此可以在3天内完成19。 大鼠的训练程序需要3天（1天学习每个任务，如下所述）。老鼠很少不学习这些任务。如果一只老鼠未能学习每项任务，则应将其排除在最终研究之外。有关下面描述的训练范式的可视化描述，请参见图 1A。
<ol><li>在将大鼠放入腔室之前，请确保分配器中有足够的食物颗粒，并且操作盒功能正常。为此，请在空腔室中加载并启动训练或测试日计划，手动测试正确的杠杆是否每次按下杠杆都能适当地提供一次奖励。</li>
	<li>训练老鼠按压每个杠杆<ol>
<li>在将大鼠放入盒子进行第一天的训练之前，在每个腔体内加载训练程序时，在正确的杠杆上手动设置一个食物颗粒奖励。</li>
		<li>使用固定比率（FR-1）时间表训练大鼠，使得每次正确的杠杆按压都会得到一次加固的奖励。每天在受试者和/或实验条件下平衡正确的杠杆（一次只塑造一个杠杆），方法是在操作腔室的计算机上加载训练程序时指定正确的杠杆。</li>
		<li>让大鼠按下杠杆，直到它达到标准，方法是按压正确的杠杆50次，通常在30-45分钟之间完成任务。</li>
		<li>第二天，强制老鼠使用与训练第一天相同的程序在相反的杠杆上执行此任务，但将相反的杠杆指定为正确的杠杆。在训练的这一天，没有必要用食物颗粒"塑造"杠杆。通常，在大鼠学会按下第一个杠杆后，该标准会很快获得。</li>
	</ol>
</li>
	<li>训练老鼠对光提示做出反应<ol>
<li>在训练的第三天，点亮两个杠杆上方的灯进行15秒的试验，在此期间，老鼠可以按下其中一个杠杆，以可能获得食物颗粒奖励。在光辨别任务期间，该程序将逐个试验地随机选择哪个杠杆是正确的。</li>
		<li>如果老鼠按下正确的杠杆，请确保灯保持亮起3秒并给予奖励，然后是5秒的时间段，在此期间，灯在下一次试验之前关闭。如果老鼠按下了不正确的杠杆，请确保没有提供任何奖励，并且在下一次试验之前关闭灯10秒。</li>
		<li>在训练的最后一天之后，计算"侧偏置"，通过将一个杠杆的按压次数除以杠杆压力的总数，确定大鼠是否偏左或右杠杆。在测试当天，老鼠将从它最不喜欢的一侧开始，以确保它正在学习特定的响应 - 奖励偶然性，而不是响应首选杠杆。</li>
	</ol>
</li>
</ol>6. 测试
注:有关下面描述的测试范例的直观描述，请参见图1B。
<ol><li>在第4天（测试日），按照压力程序将大鼠置于操作室中，并连续测试侧面辨别，侧面反转和光辨别任务。确保分光任务仅照亮"正确"杆上方的光。在每项任务中，大鼠必须连续完成八次正确的试验，以完成每一次歧视，而不会按下无回报的，不正确的杠杆。按下不正确的杠杆将重置此试验链。<ol>
<li>使用侧面辨别任务测试大鼠。使用侧面辨别程序，奖励老鼠将杠杆按在训练的第三天确定的最不喜欢的一侧，而不管光线提示如何。连续按压正确拉杆 8 次后，任务结束（不包括遗漏）。</li>
		<li>通过再次使用侧面识别程序运行大鼠来执行侧面反转测试，但这次将侧面识别任务中与正确操纵杆相反的杠杆指定为正确。确保老鼠按下此杠杆会得到奖励，而不管光线提示如何。连续按压正确拉杆 8 次后，任务结束（不包括遗漏）。</li>
		<li>执行光辨别任务，奖励老鼠在上面照亮的光下按下杠杆。每次操作测试在连续按压正确拉杆8次后完成（不包括遗漏）。 注意:根据以前的研究，这些任务编码至少30次试验，无论连续按压，以确保大鼠有足够的时间来学习每个任务的规则18。因此，如果大鼠在30次试验发生之前连续达到八次正确试验，则任务将继续进行，直到30次试验完成。</li>
	</ol>
</li>
</ol>7. 行为分析
注意:只要启动并允许完成每个任务的MED-PC脚本，就可以自动记录和保存在测试当天为每只动物获取的数据（请参阅MED-PC脚本的补充材料）。
<ol><li>使用计算机程序打开每个测试日任务（侧面辨别、侧面反转和光辨别）的数据。该计划记录的主要措施是试验到标准，标准错误和时间到标准。这些措施详述如下。 注意:作者生成了一个 MATLAB 脚本，该脚本允许分析过程的自动化以及固有性错误与回归错误的分析（联系作者以获取代码信息以简化数据分析）。<ol>
<li>以试验为标准（指大鼠连续完成八项正确试验（包括那八项试验）所需的试验总数[不包括遗漏]）作为准确性的主要指标。此数据位于 MED-PC 脚本为测试当天的任何任务生成的数据文件中数组 B 的第一列中。</li>
		<li>检查每个任务期间发生的错误总数。此数据位于 MED-PC 脚本为测试日的任何任务生成的数据文件中数组 B 的第三列中。这些错误也分为坚持不懈或倒退错误。当老鼠继续遵循上一个任务中的先前规则时，就会发生持久性错误。回归错误是在它脱离前一个规则但继续尝试获取新规则后发生的（有关如何计算这些类型的错误的更多详细信息，请参阅已发布的方法18）。</li>
		<li>如果大鼠在15秒内对轻微的提示没有反应，则该试验被归类为遗漏，并且不计入标准的试验总数。首先将正确响应数（位于数据文件中数组 B 的第二列中）和错误数（位于数据文件中数组 B 的第三列中）相加来计算此值。接下来，从标准试验总数中减去此数字（这是数据文件中数组 B 第一列中的最后一个数字，与试验到标准不同）。</li>
		<li>使用程序记录的开始和结束时间（位于测试日由 MED-PC 脚本为任何任务生成的数据文件的顶部）来计算标准时间。第一次按下杠杆的延迟也可以从数据文件中计算出来，方法是从时间到标准减去变量K（从第一次按下杠杆开始的经过时间，以秒为单位）。</li>
		<li>对同一治疗组中大鼠的每种行为测量的数据进行平均。执行适当的统计分析（取决于要检查的变量数）。</li>
	</ol>
</li>
</ol>8. 脑基质
<ol><li>确定感兴趣的大脑区域和/或认知灵活性方面。例如，如果压力增加了侧面反转任务中的毅力误差，则眼眶额叶皮层（OFC）可能特别令人感兴趣，因为先前的病变研究表明，该大脑区域在许多形式的逆转学习中发挥作用（即，在侧面反转任务中测试的空间反转）34，35，36。在该示例中，牺牲大鼠在策略转换范式完成后，并使用描述的免疫组织化学方法25检查OFC中的c-fos（神经激活37的测量）并在此处简要描述。<ol>
<li>首先，从动物身上提取大脑并切成40μm的切片。</li>
		<li>在磷酸盐缓冲盐水（PBS）中洗涤组织4x，每次5分钟，然后在0.3%过氧化氢中孵育10分钟以淬灭内源性过氧化物酶。</li>
		<li>在PBS 2x中洗涤组织5分钟，然后孵育在小鼠抗c-fos一抗（1:500），3%正常驴血清（NDS）和0.3%Triton X中过夜。</li>
		<li>第二天，在PBS 3x中洗涤组织各5分钟，然后在生物素-SP偶联的驴抗小鼠抗体（1:500）中孵育2小时。</li>
		<li>在PBS 3x中洗涤组织5分钟，然后在avidin-streptavidin AB复合物中孵育1小时。</li>
		<li>在PBS 3x中洗涤组织5分钟，然后在DAB溶液中孵育长达10分钟，因为组织经历氧化显色反应。</li>
		<li>在PBS 3x中洗涤组织5分钟，然后将脑切片安装在玻璃显微镜载玻片上。</li>
		<li>使用基于甲苯的安装介质覆盖组织，并使用明场显微镜进行成像。 注意:这里，正如代表性结果所反映的那样，在策略转换范式结束后30分钟，大约在逆转任务完成后的60-90分钟（取决于每只老鼠在轻度任务中的表现），大鼠被处死。这应该代表c-fos表达式38的最佳时机，反映反转任务中的表现。</li>
	</ol>
</li>
	<li>或者，在执行压力或操作策略转变范式之前，将特定的脑区域用于药物注射或病毒注射。 注意:研究人员可能想研究操纵神经基质如何改变压力对认知灵活性的影响。例如，研究人员可以在测试之前阻断前额叶皮层中的特定神经递质受体。</li>
</ol>

作者没有什么可透露的。

该协议展示了如何测量压力对认知功能的影响。具体而言，在啮齿动物中使用了修改后的操作策略转移范式，该范式测量认知灵活性（类似于人类的威斯康星州卡片分类任务）1。认知灵活性表示适应认知处理策略以面对环境中的新条件的能力，并且对于正常的日常功能至关重要2。由于人类对认知灵活性的研究主要局限于大脑成像11，在动物中...

在人类中，压力性生活事件会损害认知功能（即认知灵活性1），这表示适应认知处理策略以面对环境中的新条件的能力2。认知障碍会诱发和加剧许多精神疾病，如创伤后应激障碍（PTSD）和重度抑郁症（MDD）3，4。这些疾病在女性5、6、7、8中的患病率是女性的两倍，但这种差异的生物学基础仍然未知。人类执行功能的各个方面可以使用威斯康星州卡片分类任务进行评估，这是认知灵活性的证明2。在PTSD9和MDD10患者中，这项任务的表现受损，但这种变化的神经基础只能通过脑成像11来检查。
通过使用动物模型，特别是啮齿动物，在理解压力如何影响大脑方面取得了进展。由于认知灵活性在应激相关疾病中受到影响，因此它是啮齿动物中检查的特别相关的表型。迄今为止，大多数压力神经生物学文献都使用了另一种认知灵活性范式（有时称为挖掘任务）12，13，14，15。虽然这项任务已经过广泛审查，但实验者需要更多的时间和精力来训练啮齿动物。这里改编和描述的是一种完善的自动集合转换方案16，以使用各种应激模型17，18评估雄性和雌性Sprague Dawley大鼠的认知灵活性。该过程需要实验者的最小监督，并允许同时测试多只大鼠。此外，与这个自动化任务19的其他版本不同，这种范式的适应只需要3天的训练，并且包括一个有效的编程数据分析。
压力是否增强或损害认知功能取决于压力源的类型，强度和持续时间，以及压力源与学习或执行认知任务相关的时间20，21。因此，该协议在操作训练之前和之后都包含了应激程序。它还检查了压力研究的代表性结果。此外，集合转换的特定方面的潜在大脑区域已经得到很好的建立2，16，22;因此，该报告还描述了如何在压力和策略转换程序期间或之后定位和评估特定的大脑区域。
关于直接检查认知灵活性的性别差异的研究有限18，23。 该协议描述了如何1）将雄性和雌性大鼠纳入实验范式，然后2）在自由循环的雌性大鼠的手术前和手术期间跟踪发情周期。先前的研究表明，操作性训练前的压力可导致大鼠17的认知灵活性的性别特异性缺陷。特别是，雌性大鼠在压力后表现出认知灵活性的破坏，而雄性大鼠在压力后表现出认知灵活性的改善17。有趣的是，与压力相关的精神疾病的一个主要标志是认知不灵活性，这种疾病在人类中具有性别偏见。这些结果表明，女性可能比男性更容易受到这种类型的认知障碍的影响。在动物模型中使用这些技术将揭示压力对大脑的影响以及它如何损害人类精神疾病的认知。

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assessment of stress effects on cognitive flexibility using an operant strategy shifting paradigm

压力会影响认知功能。压力是否增强或损害认知功能取决于几个因素，包括1）压力源的类型，强度和持续时间;2）所研究的认知功能类型;3）与学习或执行认知任务相关的压力源的时间。此外，压力对认知功能的影响之间的性别差异已被广泛记录。这里描述的是一种自动操作策略转移范式的改编，以评估压力的变化如何影响雄性和雌性Sprague Dawley大鼠的认知灵活性。具体来说，在这种基于操作性的任务中，约束压力在训练之前或之后使用，以检查压力如何影响两性的认知表现。与这种自动化范式中的每个任务相关的特定大脑区域已经得到很好的建立（即，内侧前额叶皮层和眶额叶皮层）。这允许在实验期间进行靶向操作，或者在完成范式后评估这些区域中的特定基因和蛋白质。这种范式还允许检测压力后发生的不同类型的性能错误，每种错误都定义了神经基质。还确定了在反复的约束压力范式之后，毅力错误中明显的性别差异。在临床前模型中使用这些技术可以揭示压力如何影响大脑并损害精神疾病的认知，例如创伤后应激障碍（PTSD）和重度抑郁症（MDD），它们在患病率上显示出显着的性别差异。

上面概述的自适应自动操作策略转移范式用于确定重复的约束压力是否影响雄性和雌性Sprague Dawley大鼠的认知。代表性行为数据在下面 的图 2 中进行了描述。简而言之，对照和反复约束的大鼠进行了这种操作性策略转移测试，该测试由一系列任务组成:侧面辨别，侧反转和轻度辨别。
每个任务的标准试验如图 2A所示。通常，每项任?...

Watch this Scientific Journal Video about Assessment of Stress Effects on Cognitive Flexibility using an Operant Strategy Shifting Paradigm at JoVE.com

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

压力性生活事件会损害认知功能，增加患精神疾病的风险。该协议说明了压力如何影响男性和女性Sprague Dawley大鼠的自动操作策略转移范式来影响认知灵活性。讨论了特定行为背后的特定大脑区域，并探讨了结果的转化相关性。

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 ...

assessment-stress-effects-on-cognitive-flexibility-using-an-operant

Research

JoVE Journal

Behavior

3.2K 次观看.  Bryn Mawr College. 压力性生活事件会损害认知功能，增加患精神疾病的风险。该协议说明了压力如何影响男性和女性Sprague Dawley大鼠的自动操作策略转移范式来影响认知灵活性。讨论了特定行为背后的特定大脑区域，并探讨了结果的转化相关性。

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

The Crossmodal Congruency Task as a Means to Obtain an Objective Behavioral Measure in the Rubber Hand Illusion Paradigm

The rubber hand illusion (RHI) is a popular experimental paradigm. Participants view touch on an artificial rubber hand while the participants' own hidden hand is touched. If the viewed and felt touches are given at the same time then this is sufficient to induce the compelling experience that the rubber hand is one's own hand. The RHI can be used to investigate exactly how the brain constructs distinct body representations for one's own body. Such representations are crucial for successful interactions with the external world. To obtain a subjective measure of the RHI, researchers typically ask participants to rate statements such as "I felt as if the rubber hand were my hand". Here we demonstrate how the crossmodal congruency task can be used to obtain an objective behavioral measure within this paradigm.
The variant of the crossmodal congruency task we employ involves the presentation of tactile targets and visual distractors. Targets and distractors are spatially congruent (i.e. same finger) on some trials and incongruent (i.e. different finger) on others. The difference in performance between incongruent and congruent trials - the crossmodal congruency effect (CCE) - indexes multisensory interactions. Importantly, the CCE is modulated both by viewing a hand as well as the synchrony of viewed and felt touch which are both crucial factors for the RHI.
The use of the crossmodal congruency task within the RHI paradigm has several advantages. It is a simple behavioral measure which can be repeated many times and which can be obtained during the illusion while participants view the artificial hand. Furthermore, this measure is not susceptible to observer and experimenter biases. The combination of the RHI paradigm with the crossmodal congruency task allows in particular for the investigation of multisensory processes which are critical for modulations of body representations as in the RHI.

We demonstrate how an objective measure can be employed in the widely employed rubber hand illusion paradigm. This measure is obtained by modifying the well-established crossmodal congruency task. This task allows the investigation of multisensory processes which are critical for modulations of body representations as in the rubber hand illusion.

一致性的任务作为一种手段来获取目标行为的措施中的橡胶手错觉范式Crossmodal

The rubber hand illusion (RHI) is a popular experimental paradigm. Participants view touch on an artificial rubber hand while the participants' own hidden ...

科研

行为学

Irrelevant Stimuli and Action Control: Analyzing the Influence of Ignored Stimuli via the Distractor-Response Binding Paradigm

Selection tasks in which simple stimuli (e.g. letters) are presented and a target stimulus has to be selected against one or more distractor stimuli are frequently used in the research on human action control. One important question in these settings is how distractor stimuli, competing with the target stimulus for a response, influence actions. The distractor-response binding paradigm can be used to investigate this influence. It is particular useful to separately analyze response retrieval and distractor inhibition effects. Computer-based experiments are used to collect the data (reaction times and error rates). In a number of sequentially presented pairs of stimulus arrays (prime-probe design), participants respond to targets while ignoring distractor stimuli. Importantly, the factors response relation in the arrays of each pair (repetition vs. change) and distractor relation (repetition vs. change) are varied orthogonally. The repetition of the same distractor then has a different effect depending on response relation (repetition vs. change) between arrays. This result pattern can be explained by response retrieval due to distractor repetition. In addition, distractor inhibition effects are indicated by a general advantage due to distractor repetition. The described paradigm has proven useful to determine relevant parameters for response retrieval effects on human action.

The distractor-response binding paradigm is described. It can be used to shed light on the influence irrelevant stimuli, competing with targets for a response, can have on human action. Both response retrieval effects and distractor inhibition effects can be analyzed within the paradigm.

不相干的刺激和动作控制:通过分心 - 响应绑定范式忽略刺激的影响分析

Selection tasks in which simple stimuli (e.g. letters) are presented and a target stimulus has to be selected against one or more distractor stimuli are ...

The Attentional Set Shifting Task: A Measure of Cognitive Flexibility in Mice

Cognitive impairment, particularly involving dysfunction of circuitry within the prefrontal cortex (PFC), represents a core feature of many neuropsychiatric and neurodevelopmental disorders, including depression, post-traumatic stress disorder, schizophrenia and autism spectrum disorder. Deficits in cognitive function also represent the most difficult symptom domain&#160;to successfully treat, as serotonin reuptake inhibitors and tricyclic antidepressants have only modest effects. Functional neuroimaging studies and postmortem analysis of human brain tissue implicate the PFC as being a primary region of dysregulation in patients with these disorders. However, preclinical behavioral assays used to assess these deficits in mouse models which can be readily manipulated genetically and could provide the basis for studies of new treatment avenues have been underutilized. Here we describe the adaptation of a behavioral assay, the attentional set shifting task (AST), to be performed in mice to assess prefrontal cortex mediated cognitive deficits. The neural circuits underlying behavior during the AST are highly conserved across humans, nonhuman primates and rodents, providing excellent face, construct and predictive validity.

The goal of this protocol is to perform a behavioral assay such as the attentional set shifting task (AST) to assess prefrontal cortex-mediated cognitive flexibility in mice.

在注意定势转移任务:测量小鼠认知的灵活性

Cognitive impairment, particularly involving dysfunction of circuitry within the prefrontal cortex (PFC), represents a core feature of many ...

Investigating the Effects of Antipsychotics and Schizotypy on the N400 Using Event-Related Potentials and Semantic Categorization

Within the field of cognitive neuroscience, functional magnetic resonance imaging (fMRI) is a popular method of visualizing brain function. This is in part because of its excellent spatial resolution, which allows researchers to identify brain areas associated with specific cognitive processes. However, in the quest to localize brain functions, it is relevant to note that many cognitive, sensory, and motor processes have temporal distinctions that are imperative to capture, an aspect that is left unfulfilled by fMRI&#8217;s suboptimal temporal resolution. To better understand cognitive processes, it is thus advantageous to utilize event-related potential (ERP) recording as a method of gathering information about the brain. Some of its advantages include its fantastic temporal resolution, which gives researchers the ability to follow the activity of the brain down to the millisecond. It also directly indexes both excitatory and inhibitory post-synaptic potentials by which most brain computations are performed. This sits in contrast to fMRI, which captures an index of metabolic activity. Further, the non-invasive ERP method does not require a contrast condition: raw ERPs can be examined for just one experimental condition, a distinction from fMRI where control conditions must be subtracted from the experimental condition, leading to uncertainty in associating observations with experimental or contrast conditions. While it is limited by its poor spatial and subcortical activity resolution, ERP recordings&#8217; utility, relative cost-effectiveness, and associated advantages offer strong rationale for its use in cognitive neuroscience to track rapid temporal changes in neural activity. In an effort to foster increase in its use as a research imaging method, and to ensure proper and accurate data collection, the present article will outline &#8211; in the framework of a paradigm using semantic categorization to examine the effects of antipsychotics and schizotypy on the N400 &#8211; the procedure and key aspects associated with ERP data acquisition.

Using event-related EEG potentials (ERPs), we investigate the effects of antipsychotic medications on abnormal semantic brain activations in healthy individuals with schizotypal traits. We use ERPs to track distinct changes in brain activity, shedding insight into the cognitive processes associated with semantic categorization.

使用事件相关电位和语义分类调查抗精神病药和Schizotypy在N400的影响

Within the field of cognitive neuroscience, functional magnetic resonance imaging (fMRI) is a popular method of visualizing brain function. This is in ...

A Cognitive Paradigm to Investigate Interference in Working Memory by Distractions and Interruptions

Goal-directed behavior is often impaired by interference from the external environment, either in the form of distraction by irrelevant information that one attempts to ignore, or by interrupting information that demands attention as part of another (secondary) task goal. Both forms of external interference have been shown to detrimentally impact the ability to maintain information in working memory (WM). Emerging evidence suggests that these different types of external interference exert different effects on behavior and may be mediated by distinct neural mechanisms. Better characterizing the distinct neuro-behavioral impact of irrelevant distractions versus attended interruptions is essential for advancing an understanding of top-down attention, resolution of external interference, and how these abilities become degraded in healthy aging and in neuropsychiatric conditions. This manuscript describes a novel cognitive paradigm developed the Gazzaley lab that has now been modified into several distinct versions used to elucidate behavioral and neural correlates of interference, by to-be-ignored distractors versus to-be-attended interruptors. Details are provided on variants of this paradigm for investigating interference in visual and auditory modalities, at multiple levels of stimulus complexity, and with experimental timing optimized for electroencephalography (EEG) or functional magnetic resonance imaging (fMRI) studies. In addition, data from younger and older adult participants obtained using this paradigm is reviewed and discussed in the context of its relationship with the broader literatures on external interference and age-related neuro-behavioral changes in resolving interference in working memory.

A novel cognitive paradigm is developed to elucidate behavioral and neural correlates of interference by to-be-ignored distractors versus interference by to-be-attended interruptors during a working memory task. In this manuscript, several variants of this paradigm are detailed, and data obtained with this paradigm in younger/older adult participants is reviewed.

认知范式调查干扰工作记忆的干扰和中断

Goal-directed behavior is often impaired by interference from the external environment, either in the form of distraction by irrelevant information that ...

Operant Procedures for Assessing Behavioral Flexibility in Rats

Executive functions consist of multiple high-level cognitive processes that drive rule generation and behavioral selection. An emergent property of these processes is the ability to adjust behavior in response to changes in one&#8217;s environment (i.e., behavioral flexibility). These processes are essential to normal human behavior, and may be disrupted in diverse neuropsychiatric conditions, including schizophrenia, alcoholism, depression, stroke, and Alzheimer&#8217;s disease. Understanding of the neurobiology of executive functions has been greatly advanced by the availability of animal tasks for assessing discrete components of behavioral flexibility, particularly strategy shifting and reversal learning. While several types of tasks have been developed, most are non-automated, labor intensive, and allow testing of only one animal at a time. The recent development of automated, operant-based tasks for assessing behavioral flexibility streamlines testing, standardizes stimulus presentation and data recording, and dramatically improves throughput. Here, we describe automated strategy shifting and reversal tasks, using operant chambers controlled by custom written software programs. Using these tasks, we have shown that the medial prefrontal cortex governs strategy shifting but not reversal learning in the rat, similar to the dissociation observed in humans. Moreover, animals with a neonatal hippocampal lesion, a neurodevelopmental model of schizophrenia, are selectively impaired on the strategy shifting task but not the reversal task. The strategy shifting task also allows the identification of separate types of performance errors, each of which is attributable to distinct neural substrates. The availability of these automated tasks, and the evidence supporting the dissociable contributions of separate prefrontal areas, makes them particularly well-suited assays for the investigation of basic neurobiological processes as well as drug discovery and screening in disease models.

The ability to assess executive functions such as behavioral flexibility in rats is useful for investigating the neurobiology of cognition in both intact animals and disease models. Here we describe automated tasks for assessing strategy shifting and reversal learning, which are particularly sensitive to disruptions in prefrontal cortical networks.

操作性程序，以评估大鼠的行为灵活性

Executive functions consist of multiple high-level cognitive processes that drive rule generation and behavioral selection. An emergent property of these ...

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 ...

Assessing the Effects of Music Listening on Psychobiological Stress in Daily Life

Music listening is associated with stress-reducing effects. However, most of the results on music listening and stress were gathered in experimental settings. As music listening is a popular activity of daily life, it is of utmost importance to study the effects of music listening on psychobiological stress in an everyday, daily-life setting. Here, a study protocol is presented that allows the assessment of associations between music listening and psychobiological stress in daily life by noninvasively measuring salivary cortisol (as a marker of the Hypothalamic-Pituitary-Adrenal (HPA) axis) and salivary alpha-amylase (as a marker of the Autonomic Nervous System (ANS)). The protocol includes advice on the study design (e.g., sampling protocol), the materials and methods (e.g., the assessment of psychobiological stress in daily life, the assessment of music listening, and the manual), the selection of participants (e.g., the approval of the institutional review board and inclusion criteria), and the statistical analyses (e.g., the multilevel approach). The representative results provide evidence for a stress-reducing effect of music listening in daily life. Particularly, specific reasons for listening to music (especially relaxation), as well as the presence of others while doing so, increase this stress-reducing effect. At the same time, music listening in daily life differentially affects the HPA axis and ANS functioning, thus emphasizing the need for a multi-dimensional assessment of stress in daily life.

A study protocol is presented on how to assess associations between music listening and psychobiological stress (as measured by subjective stress levels, salivary cortisol, and salivary alpha-amylase) in daily life. Advice on study design, materials, methods, selection of participants, and statistical handling is provided. Representative results are presented and discussed.

评估音乐的影响听力在日常生活Psychobiological压力

Music listening is associated with stress-reducing effects. However, most of the results on music listening and stress were gathered in experimental ...

New Variations for Strategy Set-shifting in the Rat

Behavioral flexibility is crucial for survival in changing environments. Broadly defined, behavioral flexibility requires a shift of behavioral strategy based on a change in governing rules. We describe a strategy set-shifting task that requires an attentional shift from one stimulus dimension to another. The paradigm is often used for testing cognitive flexibility in primates. However, the rodent version has not been as extensively developed. We have recently extended an established set-shifting task in the rat1 by requiring attention to different stimuli according to context. All the experimental conditions required animals to choose either a left or right lever. Initially, all animals had to choose on the basis of the location of the lever. Subsequently, a change in the rule occurred, which required a shift in set from location-based rule to a rule in which the correct lever was indicated by a light cue. We compared performance on three different versions of the task, in which the light stimulus was either novel, previously relevant, or previously irrelevant. We found that specific neurochemical lesions selectively impaired the ability to make particular types of set shift as measured by the performance on the different versions of the task.

Set-shifting, a form of behavioral flexibility, requires an attentional shift from one stimulus dimension to another. We extended an established rodent set-shifting task1 by requiring attention to different stimuli according to context. The task was combined with specific lesions to identify neuron subtypes underlying a successful shift.

对于战略的新变化集移在大鼠

Behavioral flexibility is crucial for survival in changing environments. Broadly defined, behavioral flexibility requires a shift of behavioral strategy ...

Eye Tracking During Visually Situated Language Comprehension: Flexibility and Limitations in Uncovering Visual Context Effects

The present work is a description and an assessment of a methodology designed to quantify different aspects of the interaction between language processing and the perception of the visual world. The recording of eye-gaze patterns has provided good evidence for the contribution of both the visual context and linguistic/world knowledge to language comprehension. Initial research assessed object-context effects to test&#160;theories of modularity in language processing. In the introduction, we describe how subsequent investigations have taken the role of the wider visual context in language processing as a research topic in its own right, asking questions such as how our visual perception of events and of speakers contributes to&#160;comprehension informed by&#160;comprehenders&#39; experience. Among the examined aspects of the visual context are actions, events, a speaker&#39;s gaze, and emotional facial expressions, as well as spatial object configurations. Following an overview of the eye-tracking method and its different applications, we list the key steps of the methodology in the protocol, illustrating how to successfully use it to study visually-situated language comprehension. A final section presents three sets of representative results and illustrates the benefits and limitations of eye tracking for investigating the interplay between the perception of the visual world and language comprehension.

The present article reviews an eye-tracking methodology for studies on language comprehension. To obtain reliable data, key steps of the protocol must be followed. Among these are the correct set-up of the eye tracker (e.g., ensuring good quality of the eye and head images) and accurate calibration.

视觉语言理解中的眼动追踪: 发现视觉语境效果的灵活性和局限性

The present work is a description and an assessment of a methodology designed to quantify different aspects of the interaction between language processing ...