这项研究得到了荷兰科学研究组织（NWO）、荷兰（赠款ID 452-17-002）和比利时佛兰德斯研究基金会高级研究金（授予ID:12E3717N）授予安·默德斯的支持。约翰·弗拉延的贡献得到了比利时佛兰芒政府"阿塞内斯"长期结构资金梅图萨勒姆赠款的支持。
作者要感谢马斯特里赫特大学的雅科·朗纳和理查德·本宁为实验任务编程，并为描述的实验设计和创建图形。

这里提出的议定书符合KU Leuven社会和社会伦理委员会（注册号:S-56505）和马斯特里赫特大学心理学和神经科学伦理审查委员会（注册号:185_09_11_2017_S1和185_09_11_2017_S2_A1）的要求。
1. 为测试会议准备实验室
<ol><li>测试会话前:向参与者发送一封电子邮件，告知他/她有关疼痛刺激的传递、实验的总体大纲和排除标准。健康参与者的排除标准包括:未满18岁:慢性疼痛;厌食症或诊断出诵读困难;怀孕;左撇子;心血管疾病、慢性或急性呼吸系统疾病（如哮喘、支气管炎）、神经系统疾病（如癫痫）和/或精神疾病（如临床抑郁症、恐慌/焦虑症）:听力或视力问题未纠正;占统治地位的手、手腕、肘部或肩部疼痛，可能妨碍执行到达任务;植入式电子医疗设备（如心脏起搏器）:和任何其他严重的医疗条件的存在。</li>
	<li>由于 COVID-19 安全防范措施，请参与者在抵达实验室时洗手/消毒，并自行洗手。在整个测试期间佩戴一次性面罩，并在需要与参与者进行身体接触时戴上乳胶手套。</li>
	<li>在实验环境中使用两个独立的房间或部分:一个用于参与者，另一个用于实验者。</li>
	<li>使用一台带有两个独立屏幕的计算机:一台用于实验者的计算机屏幕，另一台用于参与者的大屏幕电视屏幕。</li>
	<li>要打开机械臂（例如触觉大师），按下机器人前面的电源开关（此机器人特定于此机器人）。随后，打开紧急开关，必要时可以使用紧急开关关闭机器人。</li>
	<li>在每个测试日之前重新校准机械臂。这是通过与机械臂的直接应用程序编程接口 （API） 连接完成的，只需要在测试日开始时完成一次。<ol>
<li>要建立 API 连接，在计算机上打开互联网浏览器，并键入机械臂的特定 API 地址。</li>
		<li>在网页上，选择触觉下的状态。随后，按下 Init旁边的"开始"按钮（以进行初始化）。 注:这是这个机器人的标准校准程序。不同的机器人可能需要不同的校准程序。</li>
	</ol>
</li>
	<li>使用连接到计算机的恒定电流刺激器（参见第 1.4 步）。在实验期间，疼痛刺激通过在计算机上运行的实验脚本提供。该实验使用跨平台游戏引擎进行编程（参见 材料表）。<ol>
<li>出于安全原因，通过在刺激器前控制面板右上角切换橙色切换开关来禁用恒定的电流刺激器输出。</li>
		<li>使用前控制面板中间的橙色切换开关将输出范围设置为 x 10 mA。</li>
		<li>使用前控制面板左上角的黑色旋转旋钮将脉冲持续时间设置为 2 毫秒（2000 μs）。</li>
		<li>要打开恒定电流刺激器，只需按下前控制面板左下角的电源按钮。</li>
	</ol>
</li>
</ol>2. 筛选排除标准并获得知情同意
<ol><li>将参与者放置在距离电视屏幕约 2.5 米的地方（见第 1.4 步），距离机械臂的手柄（传感器）有舒适的距离（约 15 厘米），放在带扶手的椅子上（图 1）。</li>
	<li>通过自我报告筛选参与者的排除标准（有关排除标准，请参阅步骤 1.1）。</li>
	<li>告知参与者疼痛刺激的传递和实验的总体轮廓。此外，通知他/她，他/她可以自由地在实验期间的任何时候退出参与，没有任何影响。获得书面知情同意。</li>
	<li>为了尽量减少与参与者的物理接触，请确保实验室的参与者部分包括一张表格，其中包含排除和知情同意表，以及在参与者到达之前放置一个调查问卷平板电脑（见第 6.2 步）。参与者应该能够使用此表独立访问和签署表格。</li>
</ol>3. 附加刺激电极
注:疼痛刺激是通过两个不锈钢筋刺激电极（电极直径8毫米，电极距离30毫米）可爱地传递的2毫秒方波电刺激。
<ol><li>如果参与者穿着长袖，请他/她卷起袖子，他/她的右臂至少10厘米以上的他/她的肘部。</li>
	<li>用导电电解质凝胶填充刺激电极的中心，并将电极电缆插入紧急开关，该开关连接到实验室实验部分的恒定电流刺激器。</li>
	<li>使用表带将刺激电极连接到参与者右臂的三头肌腱上。确保表带既不要太紧，也不能松动。一旦电极被连接，告诉参与者放松他/她的手臂。</li>
</ol>4. 校准疼痛刺激
<ol><li>通过在电视屏幕上显示疼痛校准过程和相应的比例来解释疼痛校准过程（参见第 1.4 步）。<ol>
<li>向参与者澄清，他/她可能会选择在实验期间接受的刺激，但解释说，为了数据完整性，他/她被要求选择一种刺激，他/她将描述为"非常痛苦，需要付出一些努力来容忍"。</li>
		<li>要求参与者根据电视屏幕上显示的数字尺度对每个刺激进行评分，范围从 0+10 到 0，其中 0 被标记为"我什么感觉不到":1作为"我觉得的东西，但这不是令人不快的:它只是一种感觉"（即检测阈值），2作为"刺激尚未痛苦，但开始令人不快":3 作为"刺激开始疼痛"（即疼痛阈值）;和10作为"这是我所能想象的最严重的痛苦"。</li>
	</ol>
</li>
	<li>通过打开橙色切换开关（参见步骤 1.7.1）来实现恒定电流刺激器输出。</li>
	<li>在疼痛校准过程中，使用恒定电流刺激器前控制面板上的旋转旋钮手动增加疼痛刺激的强度。疼痛刺激的强度可以在这个旋钮上方看到。<ol>
<li>从 1 mA 的强度开始，逐步增加强度，增加 1、2、3 和 4 mA 增量。在 mA 中使用以下刺激演示顺序:1、2、4、6、8、11、14、17、20、24、28、32、36、40、44、48、52 等。</li>
	</ol>
</li>
	<li>要一次提供一次刺激一次疼痛刺激，请按下前控制面板上的橙色触发按钮手动触发恒定电流刺激器。<ol>
<li>在触发恒定的当前刺激器之前，先向参与者宣布每个刺激。</li>
	</ol>
</li>
	<li>一旦参与者达到疼痛强度水平，就终止校准程序，他/她将描述为"非常痛苦，需要付出一些努力来容忍"。理想情况下，这应该对应于疼痛校准额定等级尺度上的 7–8。</li>
	<li>以 mA 记录参与者的最终疼痛强度及其疼痛强度等级 （0+10），并在实验的剩余部分保持此强度。</li>
</ol>5. 执行实验任务
<ol><li>口头通知参与者，他/她将收到关于他/她面前电视屏幕上的机械臂触角模式的指示，之后他/她将能够在实验者的监督下执行任务。</li>
	<li>向参与者提供屏幕上任务的标准化书面说明。</li>
	<li>练习:通过电视屏幕上的实验脚本，呈现位于运动平面中途的三个拱门（T1–T3）。最简单的手臂运动 （T1） 配对无偏差或阻力，中间臂运动 （T2） 与中度偏差和阻力配对，最远的手臂运动 （T3） 与最大的偏差和最强阻力配对。<ol>
<li>指示参与者使用他/她占主导地位的手操作以电视屏幕上的绿色球为代表的机械臂传感器，并将球/传感器从运动平面左下角的起点移动到运动平面左上角的目标。</li>
		<li>指示参与者，他/她可以自由选择每个试验中要执行的可用运动轨迹之一。</li>
	</ol></li>
	<li>在练习阶段，不要施用疼痛刺激（见第 3 节:注意和步骤 5.7.6）。但是，确保偏差和阻力之间的关系（见第 5.3 步）到位。</li>
	<li>在参与者执行练习阶段时，向他们提供口头反馈。<ol>
<li>确保参与者在视觉和听觉"启动信号"之前不会开始移动，并且当视觉和听觉"停止信号"出现时，他/她会立即释放机械臂。 注:两个不同的听觉信号（"启动音"和"评分音"）和两个不同的视觉信号（目标和虚拟"红绿灯"分别变绿变红: 图1）已用作启动和停止信号。听觉和视觉启动信号同时呈现，听觉和视觉停止信号也同时呈现。</li>
		<li>指示参与者通过在三脚开关上使用两个分别的脚踏板在秤上向左和向右滚动，在连续额定尺度上提供疼痛预期和对运动相关疼痛的恐惧的自我报告测量。指示他/她用第三脚踏板确认他/她的答案。 注:针对每个运动轨迹分别提出关于固定的、预先确定的试验的自我报告问题。通过实验脚本确保机械臂固定，并在参与者回答问题期间保持固定。</li>
	</ol></li>
	<li>在练习阶段结束时，回答参与者的问题。离开实验区/房间，使灯光变暗。参与者自己按下"确认"脚踏板开始实验（见第5.5.2步）。</li>
	<li>获取:在避免获取期间，类似于练习阶段，让参与者选择在每个试验中执行的运动轨迹 （T1–T3）。<ol>
<li>在避免获取过程中，参与者受制于实验反应-结果（运动轨迹-疼痛）突发事件，以及避免成本，即通过实验脚本在痛苦和努力之间的权衡。</li>
		<li>具体来说，如果参与者执行最简单的运动轨迹 （T1），始终呈现疼痛刺激（100% 疼痛/无偏差或阻力）。</li>
		<li>如果他/她执行中间运动轨迹（T2），呈现疼痛刺激与50%的机会，但确保他/她将不得不付出更多的努力（中度偏差和阻力）。</li>
		<li>如果参与者执行最远、最费力的运动轨迹 （T3），则根本不会显示疼痛刺激，但确保他/她必须尽最大努力达到目标（0% 疼痛/最大偏差、最强抵抗力）。 注:如果适用于该设计，则可以使用Yoked组作为控制。在紧要关头的程序中，每个控制参与者都与实验组的参与者配对，这样两人将获得相同的强化时间表48。因此，在目前的范式中，每个Yoked Group参与者都接受疼痛刺激，无论他/她选择的轨迹如何，他/她的实验组参与者都会接受与实验组对应方相同的试验。鉴于缺乏纵的响应结果（运动轨迹 - 疼痛）意外事件， Yoked 集团预计不会收购回避行为。</li>
		<li>如适用，请在计算机上保存每个实验组参与者的数据（见第 1.4 节），并用作每个 Yoked（控制）组参与者的强化时间表的参考。<ol>
<li>如果使用Yoked程序（即每个对照参与者与实验组的参与者配对，使两者获得相同的强化时间表48），使用随机化时间表将参与者分配给组，并规定第一个参与者必须在实验组中。在此之后，参与者被随机分配到任一组，只要在每个点，实验组参与者的数量超过Yoked组参与者的数量。</li>
		</ol>
</li>
		<li>在具有疼痛刺激的试验中，一旦执行了三分之二的运动，即参与者通过轨迹拱门，就会呈现疼痛刺激。恒定电流刺激器通过实验脚本自动触发。</li>
		<li>视觉和听觉停止信号的呈现表明试验成功完成。随后，通过实验脚本确保机械臂自动返回其保持固定的起始位置。3，000 ms 后，呈现视觉和听觉启动信号，参与者可以开始下一次试用。 注:由于运动速度不同，试验时间因试验和参与者而异。每个实验阶段的试验次数也可以在实验之间变化。我们建议至少进行 2 x 12 次试验，以成功获得回避。包括上述步骤，收购协议持续约 45 分钟。</li>
	</ol></li>
	<li>概括:在通用协议中，在收购阶段后对避免的概括性测试（见第5.7节）。 注:在进行避免一般化测试时，屏幕轨迹拱门在采集过程中分离，为位于采集轨迹拱门之间的通用轨迹拱门留出空间（见图 1）。<ol>
<li>在电视屏幕上，呈现三种新颖的运动轨迹，而不是收购轨迹T1–T3。确保这些"通用轨迹"（G1–G3）位于收购轨迹附近。具体来说，G1 位于 T1 和 T2 之间，G2 位于 T2 和 T3 之间，G3 位于 T3 右侧（见 图 1）。不要将泛化轨迹与疼痛刺激配对。 注:包括上述步骤，一般阶段为3 x 12试验，避免泛化协议持续约1.5小时。测试避免的概括性需要 Yoked 组48（ 参见步骤 5.7.5）。但是，根据特定的研究问题（在主题内设计24中，回避的上下文调制）可以使用不同的控件。</li>
	</ol></li>
	<li>与响应预防 （RPE） 的灭绝:在 RPE 协议中，在收购阶段（见第 5.7 节）之后，向参与者提供标准化的书面说明，说明在即将到来的阶段，他们只能执行 T1。<ol>
<li>在 RPE 阶段，通过实验脚本，在视觉上（例如，用门阻挡轨迹拱门）和/或以手写方式（例如，用触觉墙阻止参与者的手臂运动）块 T2 和 T3，因此仅提供 T1。在此阶段，T1 不与疼痛刺激配对。包括上述步骤，RPE 相位为 4 x 12 试验，此会话持续约 60 分钟。</li>
	</ol></li>
	<li>自发恢复测试:对于测试自发恢复的避免，管理一个为期 2 天的协议与 24 小时± 3 小时在会话之间。在第 1 天，管理 RPE 协议（参见第 5.9 节）。<ol>
<li>在第2天，附加刺激电极（见第3节）。提供任务的屏幕复习说明。不包括任何有关疼痛刺激的信息。</li>
		<li>在没有疼痛刺激的情况下，呈现三个收购轨迹（T1–T3，比较收购阶段，见第5.7节）。包括实验后问卷（见第6.2节）和4×12试验的自发恢复阶段，本会话持续约45分钟。 注意:为了防止恐惧的恢复（即在意外遇到疼痛刺激42后恢复恐惧;见讨论），不要在第2天重新校准疼痛刺激。</li>
	</ol></li>
</ol>6. 结束实验
<ol><li>参与者完成实验后，分离刺激电极。</li>
	<li>为参与者提供位于实验室参与者部分表上的平板电脑（见第 2.4 节），用于响应关于疼痛刺激和避免成本的强度和不愉快性的退出调查问卷，以及对实验反应结果（运动轨迹-疼痛）突发事件的认识。</li>
	<li>当参与者完成心理特征问卷时，从刺激电极中清除电解质凝胶。</li>
	<li>参与者完成心理特征问卷后，提供汇报和报销。</li>
	<li>用适合清洁医疗器械的消毒液彻底清洁刺激电极:去除电极内和周围的所有凝胶。用软纸巾干燥电极。用消毒湿巾或喷雾剂清洁机械臂的传感器。</li>
</ol>

作者没有什么可透露的。

鉴于避免在慢性疼痛残疾1、2、3、4、5方面的关键作用，以及传统避免模式19所面临的局限性，有必要采用方法调查（与疼痛有关的）避免行为。此处介绍的机械臂触手范式解决了其中的一些限制。我们在一系列研究中采用了这种范式，这些研究一直证明我?...

回避是对疼痛的适应性反应，它发出身体威胁的信号。然而，当疼痛成为慢性，疼痛和疼痛相关的避免失去他们的适应性目的。与此一致，慢性疼痛1、2、3、4、5、6、7、8的避险模式认为，将疼痛错误地解释为灾难性疼痛，引发对疼痛的恐惧增加，从而激发避免行为。 过度回避可导致慢性疼痛残疾的发展和维持，由于身体不使用和减少参与日常活动和愿望1，2，3，4，5，9。此外，鉴于没有疼痛可能被错误地归于避免而不是恢复，可以建立一个与疼痛有关的恐惧和避免的自我维持循环。
尽管最近对《焦虑文学11》、《12》中的回避感兴趣，但关于疼痛领域回避的研究仍处于起步阶段。先前的焦虑研究，以有影响力的双重理论13为指导，通常认为恐惧会驱使避险。相应地，传统的回避范式12包括两个实验阶段，每个阶段对应一个因素:第一个建立恐惧（帕夫洛夫调理14阶段），第二个检查回避（仪器15阶段）。在帕夫洛夫的差别化调节过程中，中性刺激（有条件的刺激，CS+;例如，一个圆圈）与内在的逆向刺激（美国无条件刺激，例如电击）配对，自然产生无条件的反应（URs，例如恐惧）。第二个控制刺激从未与美国配对（CS-;例如，一个三角形）。在CS与美国配对后，CS+将在美国缺席的情况下引起恐惧本身（有条件的反应，CRs）。CS-来信号安全，不会触发CR。之后，在仪器调理过程中，参与者了解到，他们自己的行为（响应，R:例如，按下按钮）会导致某些后果（结果:O，例如，没有受到冲击）15，16。如果响应阻止负面结果，则重复响应的机会增加;这被称为负加固15。因此，在传统回避模式的帕夫洛夫阶段，参与者首先学习CS-US协会。随后，在工具阶段，引入了实验者指示的避免响应 （R），如果在 CS 演示期间执行，则取消美国，从而建立 R-O 关联。因此，CS 成为一种歧视性刺激 （SD），表示条件 R15的适当时机并激励其性能。除了一些实验显示疼痛报告17和疼痛相关的面部表情18的工具调节外，对疼痛工具学习机制的调查一般来说是有限的。
虽然上述标准回避范式阐明了许多回避的基本过程，但它也有几个限制5，19。首先，它不允许检查回避本身的学习或获取，因为实验者指示回避反应。让参与者在多个轨迹之间自由选择，因此，了解哪些反应是痛苦的/安全的，哪些轨迹是避免/不避免的，更准确地模型现实生活中，其中避免出现作为对疼痛的自然反应9。其次，在传统的避免模式中，按钮按下避免响应是免费的。然而，在现实生活中，回避对个人来说可能变得极其昂贵。事实上，高成本的避免尤其扰乱了日常运作。例如，避免慢性疼痛会严重限制人们的社会和工作生活。第三，按下/不按按钮等二分法反应也不太能很好地代表现实生活，因为现实生活中会发生不同程度的回避。在下列部分，我们描述了机械臂触手范式20如何解决这些限制，以及如何将基本范式扩展到多个新颖的研究问题。
获取回避 在范式中，参与者使用机械臂执行从起点到目标的触臂动作。运动被用作工具反应，因为它们非常类似于疼痛特异性，发人恐惧的刺激。球实际上代表参与者在屏幕上的动作（图1），使参与者能够实时跟踪自己的动作。在每次试验中，参与者在三个运动轨迹（由三个拱门（T1+T3）代表的三个运动轨迹之间自由选择，在努力程度和与痛苦的触电刺激（即疼痛刺激）配对的可能性方面各不相同。努力纵为偏离尽可能短的轨迹，并增加机械臂的阻力。具体来说，机器人的编程使阻力随着偏差而线性增加，这意味着参与者越偏离，对机器人施加的力就越大。此外，疼痛管理被编程为最短，最简单的轨迹 （T1） 总是与疼痛刺激配对 （100% 疼痛/无偏差或阻力）。中间轨迹 （T2） 与接受疼痛刺激的 50% 机会配对，但需要付出更多努力（中度偏差和阻力）。最长、最费力的轨迹 （T3） 从未与疼痛刺激配对，但需要付出最大努力才能达到目标（0% 疼痛/最大偏差、最强阻力）。避免行为作为每次试验中与最短轨迹（ T1 ）的最大偏差，这是一种更连续的避免措施，例如，按下或不按下按钮。此外，回避对策是以加大努力为代价的。此外，鉴于参与者在运动轨迹之间自由选择，并且没有明确了解实验性R-O（运动轨迹疼痛）突发事件，避免行为是工具性获得的。网上自我报告的恐惧与运动相关的疼痛和疼痛预期已被收集，作为对不同运动轨迹的有条件恐惧的衡量指标。疼痛预期也是应急意识和威胁评估21的指标。这种变量组合允许仔细研究恐惧、威胁评估和避免行为之间的相互作用。利用这个范式，我们不断证明实验性地获得回避20，22，23，24。
避免的概括 我们已经扩展了范式来研究回避23的概括性——一种可能导致过度回避的可能机制。帕夫洛夫恐惧泛化是指将恐惧传播到类似原始CS+的刺激或情况（一般刺激、GSs），恐惧随着与CS+相似性降低而下降（泛化梯度）25、26、27、28。恐惧概括最大限度地减少了重新学习刺激之间的关系，从而能够在不断变化的环境中迅速发现新威胁25、26、27、28。然而，过度的泛化导致对安全刺激的恐惧（GS类似于CS-），从而造成不必要的痛苦28，29。与此相呼应的是，使用巴甫洛夫恐惧泛化的研究表明，慢性疼痛患者过度概括与疼痛相关的恐惧30、31、32、33、34，而健康控制则表现出选择性的恐惧泛化。然而，如果过度的恐惧导致不适，过度回避可能最终导致功能障碍，由于避免安全运动和活动，并增加日常活动脱离1，2，3，4，9。尽管它在慢性疼痛残疾中起着关键作用，但关于避免的概括性研究很少。在适应研究回避概括的范式中，参与者首先获得回避，遵循上述20个程序。在随后的概括阶段，在没有疼痛刺激的情况下引入了三种新的运动轨迹。这些概括轨迹（G1–G3）与收购轨迹位于同一连续体上，分别类似于每个轨迹。具体来说，G1 的通用轨迹位于 T1 和 T2 之间，G2 位于 T2 和 T3 之间，G3 位于 T3 右侧。这样，就可以研究避免向新安全轨迹的概括。在之前的一项研究中，我们展示了自我报告的概括，但不是回避，可能暗示了疼痛相关的恐惧和避免泛化23的不同基础过程。
与响应预防一起避免的灭绝 治疗慢性肌肉骨骼疼痛中高度恐惧运动的主要方法是暴露疗法35-临床对应帕夫洛夫灭绝36，即通过在美国36缺乏CS+的反复经验减少CR。在接触慢性疼痛期间，患者进行可怕的活动或运动，以消除灾难性的信念和伤害预期34，37。由于这些信念不一定涉及疼痛本身，而是潜在的病理学，运动并不总是进行无痛在诊所34。根据抑制性学习理论38，39，灭绝学习不会抹去原来的恐惧记忆（如运动轨迹疼痛）:相反，它创造了一种新的抑制灭绝记忆（如运动轨迹-无痛），它与原始的恐惧记忆竞争检索40，41。新颖的抑制记忆比原来的恐惧记忆40更依赖于上下文，认为被消灭的恐惧记忆容易重新出现（恐惧的回归）40，41，42。患者经常在暴露治疗期间（通过预防反应的灭绝，RPE）执行甚至微妙的避免行为，通过防止将安全误配到避免10，43来建立真正的恐惧灭绝。
回避的回报 即使在恐惧43、44、45、46灭绝之后，在避免回归方面复发在临床人群中仍然很常见。虽然已发现多个机制导致恐惧47的回归，但与回避有关的机制却鲜为人知。在这份手稿中，我们特别描述了自发的恢复，即由于时间的流逝，恐惧和回避的回归。机器人手臂接触模式已在为期两天的协议中实施，以调查回避的回归。在第1天，参与者首先接受收购培训的范式，如上所述20。在随后的 RPE 阶段，参与者无法执行避免响应，即他们只能执行灭绝下与疼痛相关的轨迹 （T1）。在第2天，为了测试自发恢复，所有轨迹都再次可用，但在没有疼痛刺激的情况下。使用这个范式，我们表明，在成功灭绝一天后，回避返回22。

<table>
	<tbody>
		<tr>
			<td>1 computer and computer screen</td>
			<td>Intel Corporation</td>
			<td>64-bit Intel Core</td>
			<td>Running the experimental script</td>
		</tr>
		<tr>
			<td>40 inch LCD screen</td>
			<td>Samsung Group</td>
			<td></td>
			<td>Presenting the experimental script</td>
		</tr>
		<tr>
			<td>Blender 2.79</td>
			<td>Blender Foundation</td>
			<td></td>
			<td>3D graphics software for programming the graphics of the experiment</td>
		</tr>
		<tr>
			<td>C#</td>
			<td></td>
			<td></td>
			<td>Programming language used to program the experimental task</td>
		</tr>
		<tr>
			<td>Conductive gel</td>
			<td>Reckitt Benckiser</td>
			<td>K-Y Gel</td>
			<td>Facilitates conduction from the skin to the stimulation electrodes</td>
		</tr>
		<tr>
			<td>Constant current stimulator</td>
			<td>Digitimer Ltd</td>
			<td>DS7A</td>
			<td>Generates electrical stimulation</td>
		</tr>
		<tr>
			<td>HapticMaster</td>
			<td>Motekforce Link</td>
			<td></td>
			<td>Robotic arm</td>
		</tr>
		<tr>
			<td>Matlab</td>
			<td>MathWorks</td>
			<td></td>
			<td>For writing scripts for participant randomization schedule, and for extracting maximum deviation from shortest trajectory per trial</td>
		</tr>
		<tr>
			<td>Qualtrics</td>
			<td>Qualtrics</td>
			<td></td>
			<td>Web survey tool for psychological questionnaires</td>
		</tr>
		<tr>
			<td>Rstudio</td>
			<td>Rstudio Inc.</td>
			<td></td>
			<td>Statistical analyses</td>
		</tr>
		<tr>
			<td>Sekusept Plus</td>
			<td>Ecolab</td>
			<td></td>
			<td>Disinfectant solution for cleaning medical instruments</td>
		</tr>
		<tr>
			<td>Stimulation electrodes</td>
			<td>Digitimer Ltd</td>
			<td>Bar stimulating electrode</td>
			<td>Two reusable stainless steel disk electrodes; 8mm diameter with 30mm spacing</td>
		</tr>
		<tr>
			<td>Tablet</td>
			<td>AsusTek Computer Inc.</td>
			<td>ASUS ZenPad 8.0</td>
			<td>For providing responses to psychological trait questinnaires</td>
		</tr>
		<tr>
			<td>Triple foot switch</td>
			<td>Scythe</td>
			<td>USB-3FS-2</td>
			<td>For providing self-report measures on VAS scale</td>
		</tr>
		<tr>
			<td>Unity 2017</td>
			<td>Unity Technologies</td>
			<td></td>
			<td>Cross-platform game engine for writing the experimental script including presentations of electrocutaneous stimuli</td>
		</tr>
	</tbody>
</table>

investigating pain-related avoidance behavior using a robotic arm-reaching paradigm

回避行为是从急性疼痛向慢性疼痛残疾过渡的关键原因。然而，缺乏生态上有效的范式来实验性地研究疼痛相关的避免。为了填补这一空白，我们开发了一个范式（机械臂接触范式），以研究疼痛相关避免行为发展背后的机制。现有的回避模式（主要是在焦虑研究的背景下）通常将回避作为实验者指导的低成本反应来运作，叠加在与巴甫洛夫恐惧调理过程中与威胁相关的刺激。相比之下，当前方法在避免工具学习（获取）和增加避免响应成本方面提供了更大的生态有效性。在范式中，参与者使用机械臂执行从起点到目标的触臂动作，并自由选择三种不同的运动轨迹。运动轨迹与痛苦的触电刺激配对的概率不同，在偏差和阻力方面需要努力。具体来说，痛苦的刺激可以（部分）避免，但代价是需要加大努力的动作。回避行为被作为每个试验中最短轨迹的最大偏差来操作。除了解释新范式如何帮助理解避免的获取之外，我们还描述了机械臂触手模式的适应（1）检查避免传播到其他刺激（一般化）、（2） 在实验室中建模临床治疗（使用反应预防避免的消亡），以及（3） 建模复发和灭绝后避免的回归（自发恢复）。鉴于生态有效性的提高，以及扩展和/或适应的多种可能性，机械臂接触模式提供了一个很有前途的工具，以促进对回避行为的调查，并进一步加深我们对其基本过程的理解。

与收购阶段（图2，由A表示）20的开始相比，参与者在收购阶段结束时避免更多（显示与最短轨迹有较大最大偏差），或与Yoked对照组（图3）23，48相比，表现出更多的避免行为。
与T1和T2相比，参与者对T3的恐惧程度较低，预计T3期间与T1和T220相比疼痛?...

Watch this Scientific Journal Video about Investigating Pain-Related Avoidance Behavior using a Robotic Arm-Reaching Paradigm at JoVE.com

Investigating Pain-Related Avoidance Behavior using a Robotic Arm-Reaching Paradigm

回避是慢性疼痛残疾的核心，但缺乏足够的范例来研究与疼痛有关的避免。因此，我们开发了一个范式，允许研究如何学习疼痛相关的避免行为（获取），传播到其他刺激（一般化），可以减轻（灭绝），以及它如何随后可能重新出现（自发恢复）。

使用机械臂接触范式调查疼痛相关避免行为

Avoidance behavior is a key contributor to the transition from acute pain to chronic pain disability. Yet, there has been a lack of ecologically valid ...

investigating-pain-related-avoidance-behavior-using-robotic-arm

Research

JoVE Journal

Behavior

3.8K 次观看.  Maastricht University. 回避是慢性疼痛残疾的核心，但缺乏足够的范例来研究与疼痛有关的避免。因此，我们开发了一个范式，允许研究如何学习疼痛相关的避免行为（获取），传播到其他刺激（一般化），可以减轻（灭绝），以及它如何随后可能重新出现（自发恢复）。

视频: Investigating Pain-Related Avoidance Behavior using a Robotic Arm-Reaching Paradigm

The Resident-intruder Paradigm: A Standardized Test for Aggression, Violence and Social Stress

This video publication explains in detail the experimental protocol of the resident-intruder paradigm in rats. This test is a standardized method to measure offensive aggression and defensive behavior in a semi natural setting. The most important behavioral elements performed by the resident and the intruder are demonstrated in the video and illustrated using artistic drawings. The use of the resident intruder paradigm for acute and chronic social stress experiments is explained as well. Finally, some brief tests and criteria are presented to distinguish aggression from its more violent and pathological forms.

This video shows the resident-intruder paradigm in rats. This test is a standardized method to measure offensive aggression, defensive behavior and violence in a semi-natural setting. The use of the paradigm for social stress experiments is explained as well.

驻地入侵者范式:一种标准化考试的侵略，暴力和社会压力

This video publication explains in detail the experimental protocol of the resident-intruder paradigm in rats. This test is a standardized method to ...

科研

行为学

Examining Recall Memory in Infancy and Early Childhood Using the Elicited Imitation Paradigm

The ability to recall the past allows us to report on details of previous experiences, from the everyday to the significant. Because recall memory is commonly assessed using verbal report paradigms in adults, studying the development of this ability in preverbal infants and children proved challenging. Over the past 30 years, researchers have developed a non-verbal means of assessing recall memory known as the elicited or deferred imitation paradigm. In one variant of the procedure, participants are presented with novel three-dimensional stimuli for a brief baseline period before a researcher demonstrates a series of actions that culminate in an end- or goal-state. The participant is allowed to imitate the demonstrated actions immediately, after a delay, or both. Recall performance is then compared to baseline or to performance on novel control sequences presented at the same session; memory can be assessed for the individual target actions and the order in which they were completed. This procedure is an accepted analogue to the verbal report techniques used with adults, and it has served to establish a solid foundation of the nature of recall memory in infancy and early childhood. In addition, the elicited or deferred imitation procedure has been modified and adapted to answer questions relevant to other aspects of cognitive functioning. The broad utility and application of imitation paradigms is discussed, along with limitations of the approach and directions for future research.

The elicited imitation procedure was established to examine the development of recall memory in infancy and early childhood. This procedure has been widely used to establish a solid foundation of the nature of recall memory in infancy and early childhood.

使用仿引起范式检查召回内存在婴幼儿时期

The ability to recall the past allows us to report on details of previous experiences, from the everyday to the significant. Because recall memory is ...

Investigating Motor Skill Learning Processes with a Robotic Manipulandum

Skilled reaching tasks are commonly used in studies of motor skill learning and motor function under healthy and pathological conditions, but can be time-intensive and ambiguous to quantify beyond simple success rates. Here, we describe the training procedure for reach-and-pull tasks with ETH Pattus, a robotic platform for automated forelimb reaching training that records pulling and hand rotation movements in rats. Kinematic quantification of the performed pulling attempts reveals the presence of distinct temporal profiles of movement parameters such as pulling velocity, spatial variability of the pulling trajectory, deviation from midline, as well as pulling success. We show how minor adjustments in the training paradigm result in alterations in these parameters, revealing their relation to task difficulty, general motor function or skilled task execution. Combined with electrophysiological, pharmacological and optogenetic techniques, this paradigm can be used to explore the mechanisms underlying motor learning and memory formation, as well as loss and recovery of function (e.g. after stroke).

A paradigm is presented for training and analysis of an automated skilled reaching task in rats. Analysis of pulling attempts reveals distinct subprocesses of motor learning.

调查运动技能的学习过程与机器人Manipulandum

Skilled reaching tasks are commonly used in studies of motor skill learning and motor function under healthy and pathological conditions, but can be ...

Psychophysically-anchored, Robust Thresholding in Studying Pain-related Lateralization of Oscillatory Prestimulus Activity

In perceptual studies, it is often important to objectively assess the equality of delivered stimulation across participants or to quantify the intra-individual sensation magnitude that is evoked by stimulation over multiple trials. This requires a robust mapping of stimulus magnitude to perceived intensity and is commonly achieved by psychophysical estimation methods such as the staircase procedure. Newer, more efficient procedures like the QUEST algorithm fit a psychophysical function to the data in real time while at the same time maximizing the efficiency of data collection. A robust estimate of the threshold intensity between painful and nonpainful perceptions can then be used to reduce the influence of variations in sensory input in subsequent analyses of oscillatory brain activity. By stimulating at a constant threshold intensity determined by an adaptive estimation procedure, the variance in the ratings can be directly attributed to perceptual processes. Oscillatory activity can then be contrasted between &#34;pain&#34; and &#34;no-pain&#34; trials directly, yielding activity that closely relates to perceptual classification processes in nociception.

Psychophysical methods such as the QUEST estimation procedure can efficiently yield robust estimates of the stimulation intensity at which nonpainful sensations transition into painful sensations. By stimulating repeatedly at the threshold intensity, the variability in rating responses can directly be attributed to perceptual classifications in subsequent analyses.

在研究疼痛相关振荡Prestimulus活动偏侧Psychophysically锚，乐百氏阈值

In perceptual studies, it is often important to objectively assess the equality of delivered stimulation across participants or to quantify the ...

Reinstatement of Drug-seeking in Mice Using the Conditioned Place Preference Paradigm

The present protocol describes the Conditioned Place Preference (CPP) as a model of relapse in drug addiction. In this model, animals are first trained to acquire a conditioned place preference in a drug-paired compartment, and after the post-conditioning test, they perform several sessions to extinguish the established preference. The CPP permits the evaluation of the conditioned rewarding effects of drugs related to environmental cues. Then, the extinguished CPP can be robustly reinstated by the non-contingent administration of a priming dose of the drug, and by exposure to stressful stimuli. Both methods will be explained here. When the animal reinitiates the behavioral response, a reinstatement of the conditioned reward is considered to have taken place.
The main advantages of this protocol are that it is non-invasive, inexpensive, and simple with good validity criteria. In addition, it allows the study of different environmental manipulations, such as stress or diet, which can modulate relapse into drug seeking behaviors. However, one limitation is that if the researcher aims to explore the motivation and primary reinforcing effects of the drug, it should be complemented with self-administration procedures, as they involve operant responses of animals.

This protocol describes the Conditioned Place Preference (CPP) as a model of relapse. This procedure permits the measurement of relapse in laboratory animals, considering the impact of drug-associated environmental cues as craving and relapse in abstaining addicts is currently the focus of drug-abuse treatment programs.

用条件位置偏好范式恢复小鼠药物寻毒作用

The present protocol describes the Conditioned Place Preference (CPP) as a model of relapse in drug addiction. In this model, animals are first trained to ...

The HoneyComb Paradigm for Research on Collective Human Behavior

Collective human behavior such as group movement frequently shows surprising patterns and regularities, such as the emergence of leadership. Recent literature has revealed that these patterns, often visible at the global level of the group, are based on self-organized, individual behaviors that follow several simple local parameters. Understanding the dynamics of human collective behavior can help to improve coordination and leadership in group and crowd scenarios, such as identifying the ideal placement and number of emergency exits in buildings.
In this article, we present the experimental paradigm HoneyComb, which can be used to systematically investigate conditions and effects of human collective behavior. This paradigm uses a computer-based multi-user platform, providing a setting that can be shaped and adapted to various types of research questions. Situational conditions (e.g., cost-benefit ratios for specific behavior, monetary incentives and resources, various degrees of uncertainty) can be set by experimenters, depending on the research question. Each participant's motions are recorded by the server as hexagonal coordinates with timestamps at an accuracy of 50 ms and with individual IDs. Thus, a metric can be defined on the playfield, and movement parameters (e.g., distances, velocity, clustering, etc.) of participants can be measured over time. Movement data can in turn be combined with non-computerized data from questionnaires garnered within the same experiment setup.
The HoneyComb paradigm is paving the way for new types of human movement experiments. We demonstrate here that these experiments can render results with sufficient internal validity to meaningfully deepen our understanding of human collective behavior.

Here, we present the computer-based, multi-agent game HoneyComb, which enables experimental investigations of collective human movement behavior via black-dot-avatars on a virtual 2D hexagonal playfield. Different experimental conditions, like variable&#160;incentives on goal fields or vision radius, can be set, and their effects on human movement behavior can be investigated.

集体人类行为研究的蜂窝范式

Collective human behavior such as group movement frequently shows surprising patterns and regularities, such as the emergence of leadership. Recent ...

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 ...

A Novel Pavlovian Fear Conditioning Paradigm to Study Freezing and Flight Behavior

Fear- and anxiety-related behaviors significantly contribute to an organism&#8217;s survival. However, exaggerated defensive responses to perceived threat are characteristic of various anxiety disorders, which are the most prevalent form of mental illness in the United States. Discovering the neurobiological mechanisms responsible for defensive behaviors will aid in the development of novel therapeutic interventions. Pavlovian fear conditioning is a widely used laboratory paradigm to study fear-related learning and memory. A major limitation of traditional Pavlovian fear conditioning paradigms is that freezing is the only defensive behavior monitored. We recently developed a modified Pavlovian fear conditioning paradigm that allows us to study both conditioned freezing and flight (also known as escape) behavior within individual subjects. This model employs higher intensity footshocks and a greater number of pairings between the conditioned stimulus and unconditioned stimulus. Additionally, this conditioned flight paradigm utilizes serial presentation of pure tone and white noise auditory stimuli as the conditioned stimulus. Following conditioning in this paradigm, mice exhibit freezing behavior in response to the tone stimulus, and flight responses during the white noise. This conditioning model can be applied to the study of rapid and flexible transitions between behavioral responses necessary for survival.

Defensive behavioral responses are contingent upon threat intensity, proximity, and context of exposure. Based on these factors, we developed a classical conditioning paradigm that elicits clear transitions between conditioned freezing and flight behavior within individual subjects. This model is crucial for the understanding the pathologies involved in anxiety, panic, and post-traumatic stress disorders.

研究冻结和飞行行为的新型帕夫洛夫恐惧调理范式

Fear- and anxiety-related behaviors significantly contribute to an organism&#8217;s survival. However, exaggerated defensive responses to perceived threat ...

Using a Murine Model of Psychosocial Stress in Pregnancy as a Translationally Relevant Paradigm for Psychiatric Disorders in Mothers and Infants

The peripartum period is considered a sensitive period where adverse maternal exposures can result in long-term negative consequences for both mother and offspring, including the development of neuropsychiatric disorders. Risk factors linked to the emergence of affective dysregulation in the maternal-infant dyad have been extensively studied. Exposure to psychosocial stress during pregnancy has consistently emerged as one of the strongest predictors. Several rodent models have been created to explore this association; however, these models rely on the use of physical stressors or a limited number of psychosocial stressors presented in a repetitive fashion, which do not accurately capture the type, intensity, and frequency of stressors experienced by women. To overcome these limitations, a chronic psychosocial stress (CGS) paradigm was generated that employs various psychosocial insults of different intensity presented in an unpredictable fashion. The manuscript describes this novel CGS paradigm where pregnant female mice, from gestational day 6.5 to 17.5, are exposed to various stressors during the day and overnight. Day stressors, two per day separated by a 2 h break, range from exposure to foreign objects or predator odor to frequent changes in bedding, removal of bedding, and cage tilting. Overnight stressors include continuous light exposure, changing cage mates, or wetting bedding. We have previously shown that exposure to CGS results in the development of maternal neuroendocrine and behavioral abnormalities, including increased stress reactivity, the emergence of fragmented maternal care patterns, anhedonia, and anxiety-related behaviors, core features of women suffering from perinatal mood and anxiety disorders. This CGS model, therefore, becomes a unique tool that can be used to elucidate molecular defects underlying maternal affective dysregulation, as well as trans-placental mechanisms that impact fetal neurodevelopment and result in negative long-term behavioral consequences in the offspring.

The chronic psychosocial stress (CGS) paradigm employs clinically relevant stressors during pregnancy in mice to model psychiatric disorders of mothers and infants. Here, we provide a step-by-step procedure of applying the CGS paradigm and downstream assessments to validate this model.

使用妊娠期心理社会压力的Murine模型作为母亲和婴儿精神障碍的翻译相关范式

The peripartum period is considered a sensitive period where adverse maternal exposures can result in long-term negative consequences for both mother and ...

Investigating Migraine-Like Behavior Using Light Aversion in Mice

Migraine is a complex neurological disorder characterized by headache and sensory abnormalities, such as hypersensitivity to light, observed as photophobia. Whilst it is impossible to confirm that a mouse is experiencing migraine, light aversion can be used as a behavioral surrogate for the migraine symptom of photophobia. To test for light aversion, we utilize the light/dark assay to measure the time mice freely choose to spend in either a light or dark environment. The assay has been refined by introducing two critical modifications: pre-exposures to the chamber prior to running the test procedure and adjustable chamber lighting, permitting the use of a range of light intensities from 55 lux to 27,000 lux. Because the choice to spend more time in the dark is also indicative of anxiety, we also utilize a light-independent anxiety test, the open field assay, to distinguish anxiety from light-aversive behavior. Here, we describe a modified test paradigm for the light/dark and open field assays. The application of these assays is described for intraperitoneal injection of calcitonin gene-related peptide (CGRP) in two mouse strains and for optogenetic brain stimulation studies.

Rodents are not able to report migraine symptoms. Here, we describe a manageable test paradigm (light/dark and open field assays) to measure light aversion, one of the most common and bothersome symptoms in patients with migraines.