The publication of this study was supported by the Initial Training Network NEUROGUT funded by the European Commission under the Seventh Framework Programme (PITN-GA-2013-607652). We thank J&#246;rg Schulte, Annamaria Maichle and Damaris Schrade for their help conducting the described studies, Jenna L. Scisco for her training in analyzing EGG data, and Sibylle Klosterhalfen for sharing her expertise in motion sickness research.

道德守则该研究方案经大学医学院德国图宾根的伦理审查委员会。参加了书面之前列入知情同意，并完成披露的研究目的，是提供给所有参与者在研究17完成后。 1.学习准备<ol><li>准备用“药”：填写类似的寻找，品尝和闻胶囊用）生姜粉​​，和b）“安慰剂粉”，如淀粉。胶囊应准备并存储在编号信封由第三人以保持实验者盲的条件。 </li><li>随机指定的参与者的四个研究组的上述（ 表1）所描述的均衡安慰剂设计中的一个。 </li><li>准备评估结果的措施。 <ol><li>准备一份调查问卷填写相提并论症状评级ticipant。七症状（眩晕，头痛，恶心，督促呕吐，疲劳，出汗，肚子意识）在实验过程中会在额定0（无症状）到5（最大症状）的六倍。 </li><li>准备一个表，以填补在旋转时间和头部运动的过程中的旋转过程五次运行的数目，并且使用秒表来评估循环时间。 </li><li>准备设备记录EGG：3皮肤电极，与Fetrode技术（主动电极）煮蛋器。 </li></ol></li></ol> 2.准备参加<ol><li>准备EGG记录。 <ol><li>放置在参与者的胃上方的皮肤3皮肤电极如由Miller和穆斯（2004）24。放置在第一电极上的肚脐和胸骨之间的中线的下三分之一。放置在45°角的第二电极向上从所述第一电极而在最低裂口的左侧。从第一电极到右侧放置第三电极（参考电极）在一个45°角向下。 </li><li>将电极连接到煮蛋器，并开始录音软件。 </li></ol></li><li>座椅旋转椅的参与者，并在袋煮蛋器存储在椅子的背面。 </li></ol> 3.基线评估和药物摄入量<ol><li>服药前，先基线评估。 <ol><li> EGG记录至少15分钟以前的任何干预。指导参与者不要动，说话或在这段时间深呼吸。 </li></ol></li><li>给药。 <ol><li>据组分配，参与者需要丸（药物或安慰剂），而不会收到关于其内容的任何信息。 </li></ol></li><li>服药后，第二个基线评估。 <ol><li>服药后至少获得15分钟的胃。指导参与者不要动，SPE在这段时间AK或深呼吸。 </li><li>随后，要求参与者七个症状晕车（见上文）的规模从0（未症状）到5（严重症状）。 </li></ol></li><li>可选：根据不同的假设时间直到发病被测药物的作用，如上所述进行进一步的基线评估。 </li></ol> 4.通知参加有关组分配<ol><li>紧接在旋转过程之前，通知参与者关于他/她的组分配根据均衡安慰剂设计， 即如果他/她接收到的实际的药物或安慰剂。 注：参加者接收到这个信息在一个封闭的信封，以保持实验者盲目的状态。 </li></ol> 5.旋转过程<ol><li>发出指令的参与者。 <ol><li>旋转过程包括运行5次，每旋转2分钟，在120日的恒定速度grees /秒（20转每分钟）和1分钟的休息之间的运行。 </li><li>参加者将戴上眼罩和耳机，听到蜂鸣声，每10秒。在旋转中，参与者被指示将他/她的头向上和向下，当他/她听到来自耳机的蜂鸣声。 </li><li>参与者不应该在手术过程中呕吐，可以跳过头部运动，或告诉实验者及时停止转动，如果他们强烈地感到一种冲动，呕吐。我们鼓励他们继续进行下一次运行，直到所有5运行都至少已经启动。然而，运行能立即中断，或整个过程可以在必要时被停止。 </li><li>在休息期间在两者之间的运行，最后运行后，学员将被要求对晕车七症状的范围从0（无症状）到5（最大的症状）。 </li></ol></li><li>开始旋转的过程。 </li><li>在旋转过程中，注意实际做头MOVEM需求测试和每次运行的旋转时间。 </li><li>在休息和最后运行后，要求参与者率症状，并注意对问卷的评价。 </li></ol> 6.邮政评估<ol><li>经过上次运行已完成，主观症状被评为，记录EGG期间，参与者不宜动，说话，或采取深呼吸的另一个15分钟。 </li></ol> 7.计算结果的变量<ol><li>通过分别加入每种症状为六个时间点的分数（每次运行在基线和后）计算主观症状的评分。乘坐旋转过程中的最高等级的症状和减去基准症状自评，以获得旋转的过程（SR）在最后的最大症状自评。 注：选择最高症状评分为结局指标规定，也可用于参与者的优势谁也无法忍受在整个过程- 在对比的总和或由运行容忍的数目影响的平均值的计算。 </li><li>加入了旋转时间，以秒为总旋转公差（RT）。 </li><li>对于头部运动的总数（HM）的旋转过程中添加头部运动的数目。 </li></ol> 8.分析EGG数据<ol><li>视觉画面的生鸡蛋数据的文物，并在录制期间选择至少5分钟无瑕疵的记录。作为一个经验法则，神器被定义为快速和突然发作信号，信号强于+/- 1000μV，因为这样的信号是不可能的胃肌电活动。 </li><li>使用快速傅立叶变换软件来分析所述EGG信号的频域。作为定义，2.5至3.75的cpm信号被视为正常胃活性（normogastria）和4.0和9.75之间的cpm被视为胃动过速。 </li><li>计算percenta从0.75的总范围的normogastria和胃动过速频带到15.0的cpm 23 GE频谱功率，并计算normogastria的百分比和胃动过速带（EGG比）之间的比率。对胃动过速的转变（ 即比下降）曾多次被恶心诱导旋转的椅子或对流鼓19,23,24晕车相关。 </li></ol>

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The authors declare that they have no competing financial interests.

描述的方法提供了评估一个多元的方式和药物摄入和信息管理的适当时机在晕车安慰剂反应的可能性。然而，这是难以检测安慰剂的响应在开展研究17。这可能是由于各种事实，关键步骤和限制。 首先，妇女可能更容易受到刺激引发晕车15。此外，妇女和男子可能是差异容易诱发安慰剂的方法。例如，女性更容易受到巴甫洛夫条件反射过程恶化症状，男性更容易受到暗示的症状增加16。此外，有可能是与参与者和实验者的性别27,28互动效果。这必须考虑和研究必须被供电以检测这种相互作用。 第二，我们假定的5次操作，2分钟的持续时间的刺激以120度/秒（20转每分钟）的速度过于强烈而不能受弱草药像只生姜或信息。所有的64参与者报告中度到强烈的症状，虽然不是所有的人都报有去过的议案生病之前， 如在乘坐汽车，船，或游艺游乐项目，作为评估与运动病敏感性问卷（MSSQ）29。此外，评估晕车的敏感性不影响任何在这个结果的措施或随后的研究17,18。对于随后的实验调查的增强安慰剂的指令，我们使用的试点研究，以评估适当的速度：随着10下的速度和15轮每分钟，我们发现18组之间的差异显著。 第三，最关键的步骤是生理结果我的评价ASURE在这项研究中一个鸡蛋。这种方法是将工件非常敏感;因此数据丢失是由于辍学频繁。因此，设备的研究设计和精心参与者指令的准备是至关重要的，以减少文物由于运动，说话，或者深呼吸。这不仅适用于EGG记录还要心电图（ECG）或其他生理方式的记录。 对于安慰剂应答的多元评估未来的应用中，这些临界点必须调查不仅当晕车而且对其他症状，如疼痛或凹陷加以考虑。参与者可以是差异容易受到各种刺激和症状， 如因性别差异30个不同的症状，病史和治疗经验31，或因。此外，诱导的症状的严重程度起着实验安慰剂resear作用通道上晕车强的地方可能症状会导致意想不到的结果17,18,25,26。我们最近表明，症状的下基线严重度可能是在临床试验的安慰剂组为抑郁症和其它精神障碍，神经障碍和疼痛（韦默，K。，Colloca，L的治疗更高安慰剂响应的预测器＆恩克，P。，出版中）。与此相反，在实验研究中安慰剂镇痛效果大小均较高长效刺激相比短持续时间32的疼痛刺激。因此，刺激的种类和强度必须彻底规划的实验研究，以方便安慰剂效应时考虑。 最后，对于多元结果测量评估它的发现，将调查作为一个目标的标记，例如在运动生病的胃肌电活动安慰剂响应的适当生理CORRELATE是重要岬，可以与电图来评估。在某些条件下调查伴随药物为高血压6，但也可以是在象疼痛和抑郁状况更加复杂安慰剂应答时靶器官和根据生理测量是容易发现和评估， 例如心脏功能与心电图和血压测量。例如，Eippert及其同事发现，安慰剂镇痛可以在脊髓疼痛处理的中枢神经系统33可以与高分辨率功能磁共振成像（fMRI）仅可检测的最早阶段的水平起作用。未来的研究应该调查哪些条件激活和调节这种机制。客观的评价也是条件主要由病人监测的重要报告的结果，如问卷抑郁症，可以大大的专家评分结果34偏离，并可能受到偏见。德皮特这个事实，客观的结果，如奖励相关的神经活动的评估只是很少使用35。总之，通过多元的成果评估安慰剂反应将提高我们的预测和安慰剂效应及其潜在的心理和生理机制调解的认识。

所描述的方法的总体目标是安慰剂反应主观，行为和客观的措施，晕车，在健康的参与者旋转椅子范式的多元评价。 安慰剂效应和响应发挥每个医疗干预作用当患者或参与者期望得到有效的治疗，以减轻在日常医疗实践或临床试验1症状。在后者中，包括控制对于安慰剂效应，并可能发生在研究过程中，所有的非特异性效果，例如疾病（自发缓解，症状波动，回归平均值，习惯化），观测器和患者的自然病程安慰剂组偏见（缩放偏见，社会赞许，空调答案），或“真正的”安慰剂应答2。安慰剂反应是个体发生的病人仅仅是因为症状的改善“;或参与者的预期或学习响应特定的治疗。虽然学习是多方面的，假设的学习结果在预期各方面有关处理-无论是通过有意识的期望或无意识的条件反应1,3。 研究，主要目的，调查安慰剂应答必须包括额外的组来控制供相比于纯安慰剂响应上述非特异性的效果。例如，一组与关于所述治疗阳性预期与一组与关于所述处理而两组接收相同的惰性物质没有预期相比。一种可能的研究设计是所谓的平衡安慰剂设计（ 表1），其中一半的参与者接收的实际的药物，而另一半接受安慰剂，而半各药物组的参加者收到正确的信息和其他ħALF接收有关接受药物的错误信息。参与者将被随机分配到四个组，以评估接收到的毒品，并在组间的设计所提供的信息的不同影响之一。因此，四组是真正的药物/药物的信息，真正的药物/安慰剂信息，安慰剂/药物信息，安慰剂/安慰剂信息4。 安慰剂的研究进一步的问题是，是否患者或参与者“只有”感觉好多了主观或是否有生理5,6的客观衡量的变化。影像学检查，尤其是在实验性疼痛的研究，都一再表明，安慰剂组应答与改变神经活动， 例如，在躯体感觉皮层7或延髓前扣带皮层（RACC），它也参与了阿片类镇痛8,9有关。因此，很显然，安慰剂应答不仅スBJECTIVE响应偏见的参与者。然而，有剩余的问题安慰剂反应是否也发生在靶器官如胃晕车。为了研究这个问题，这是必要的，不仅要问的主观症状报告还评估目标器官的具体措施。 诱发晕动病的健康受试者的旋转椅模式是一个有用的和易于建立的方法，调查多变量的方式安慰剂反应。根据神经失配理论10,11，运动病的发生是因为从不同的感官系统的实际和预期的看法，例如前庭和视觉系统之间的不匹配的。这种不匹配导致了一系列的植物神经症状如恶心，眩晕，出汗，或疲劳也改变胃肌电活动12,13，并且可以在根据日实力最健康的参与者被诱发Ë刺激14。我们已经多次采用这种旋转椅范式诱使晕车调查调解员15和安慰剂组和反安慰剂应答16-18。在这个范例中，健康参与者就座于一旋转椅，有穿眼罩和耳机，以减少旋转过程中确定自己的方位的能力，并把他们的头慢慢上升和下降。具体地，头部运动诱发所谓的科里奥利效应，从而导致恶心11症状的虚幻翻滚运动的经验。参与者可以要求对的期间晕车通常发生主观症状的列表，行为的措施，例如头部运动的数量和容忍的总旋转时间可以评估，和胃肌电活动可以客观记录有电图（EGG） 。 要记录EGG的数据，三皮电极ARË放置在胃上方的皮肤，并连接到一记录装置19,20。作为胃肌电信号比从心脏较弱，则建议将它们发送到记录装置之前，直接在电极&#39;侧使用一个有源电极的技术，放大的信号。虽然鸡蛋是通过说话或深呼吸运动伪影敏感的，它的优点在于它是一种非侵入性技术，不影响胃的研究生理反应。相比之下，诸如植入电极浆膜21或22 fluoroscopies技术是更具侵入性和可能影响的不可预见的方式影响行为。分析EGG数据，该数据在视觉筛选工件和用时间序列分析进行分析，如快速傅立叶变换（FFT）。约为每分钟3个循环（CPM）的频率范围内的一个优势被认为是正常胃ACTIV性（normogastria）的范围和从4至10的cpm作为胃动过速。从normogastria的转变在基线评估，以胃动过速曾多次被恶心诱发旋转的椅子或对流鼓19,23,24相关联。 目前只有少数研究已经只有操纵预期晕车调查安慰剂反应，但这些都缺乏成功的诱导，在任何成果的措施25,26安慰剂应答。当参加者被给予安慰剂药片随着信息后暴露于晕车诱发的刺激，它要么：减少症状（安慰剂信息）;加大症状（反安慰剂信息）;或没有效果;谁收到了反安慰剂信息参与者报告较少症状和表现出较少胃动过速相比其他组26。由作者一个可能的解释是，谁给予了积极的信息参与者迪sappointed他们有强烈的症状，尽管他们接受的药物，但谁被赋予负面信息的参与者感到惊讶的是过程并不如他们预期的那样强劲。在一项由我们自己的小组中，只有男性参与者谁被告知，口头发表的药物会增加相比，谁没有收到任何信息表现出降低旋转宽容而对症状分级16的效果参与者症状（反安慰剂效应）。 总之，通过与安慰剂治疗给予正面信息安慰剂反应没有表现出对晕车有旋转座椅模式，除了我们自己组18（魏玛，K.，如虹，B.，Klosterhalfen，S的后期研究，和恩克，P.，2012）。此外，安慰剂组应答很少被研究了多个结局指标在一项研究中。本文的重点，因此，描述方法来评估PL在一个多元的方式acebo反应通过在实验范式来研究晕车主观，行为和客观结果的措施。

<table border="0" cellpadding="0" cellspacing="0">
	<tbody>
		<tr>
			<td>Cleartrace electrodes</td>
			<td>P.J. Dahlhausen &#38; Co. GmbH, K&#246;ln, Germany</td>
			<td>2801700030</td>
			<td>Cutaneous electrodes for the EGG recording</td>
		</tr>
		<tr>
			<td>Eye mask</td>
			<td>(any eye mask)</td>
			<td></td>
			<td>To blindfold participants to reduce orientation</td>
		</tr>
		<tr>
			<td>Fast Fourier Transformation software</td>
			<td>Custom software using Prime Factor FFT for Windows, version 3.03, Alligator Technologies, Costa Mesa, CA, USA</td>
			<td></td>
			<td>Software that analyzes EGG data in the frequency domain using an Fast Fourier Transfomation.</td>
		</tr>
		<tr>
			<td>Fetrode amplifier</td>
			<td>UFI, Morrow Bay, CA, USA</td>
			<td>Model 2283FT</td>
			<td>Cables with integrated active electrodes (Fetrode technology) (http://www.ufiservingscience.com/fetrode.html)</td>
		</tr>
		<tr>
			<td>Ginger capsules</td>
			<td>Gr&#252;nwalder GmbH, Bad T&#246;lz, Germany</td>
			<td>Zintona PZN 3041933</td>
			<td>Capsules filled with ginger powder (http://www.gruenwalder.de/English/Products/Zintona/)</td>
		</tr>
		<tr>
			<td>MP3-Player with earphones</td>
			<td>(any MP3-Player with earphones)</td>
			<td></td>
			<td>To reduce the ability to orientate because of sound in the surrounding, and to provide a beep tone every 10 sec that instruct participants to move their head up and down (http://www.ufiservingscience.com/dat_logs.html)</td>
		</tr>
		<tr>
			<td>Placebo capsules</td>
			<td></td>
			<td></td>
			<td>Capsules filled with starch</td>
		</tr>
		<tr>
			<td>Protocol</td>
			<td>Own protocol</td>
			<td></td>
			<td>Protocol to note head movements and rotation durations</td>
		</tr>
		<tr>
			<td>Rotation chair for medical use</td>
			<td>Standart Instruments GmbH, Karlsruhe, Germany</td>
			<td>Tornado</td>
			<td>Custom made medical rotation chair with variable rotation speed and variable ramp acceleration/deceleration</td>
		</tr>
		<tr>
			<td>Stopwatch</td>
			<td>(any stopwatch)</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Symptom ratings</td>
			<td>Own symptom list (modified Graybiel scale)</td>
			<td></td>
			<td>7-item symptom list to note symptoms on a scale from 0 = none to 5 = maximal</td>
		</tr>
		<tr>
			<td>UFI BioLogs</td>
			<td>UFI, Morrow Bay, CA, USA</td>
			<td>Model 3991</td>
			<td>Ambulatory data logger to record EGGs</td>
		</tr>
	</tbody>
</table>

how to study placebo responses in motion sickness with a rotation chair paradigm in healthy participants

安慰剂反应发生在每一个医疗干预，当患者或参与者期望得到有效的治疗，以缓解症状。然而，底层安慰剂应答的机制尚未完全清楚。它已经多次被证明，安慰剂应答与变化神经活动相关联，但是对于许多情况，目前还不清楚他们是否也影响靶器官，如胃晕车。因此，我们提出了一个方法，安慰剂组应答的主观，行为和客观的措施，转动椅子范式的多元评估晕车。晕车的生理CORRELATE是胃肌电活动一转向，可以记录电图胃动过速。所呈现的研究应用了所谓的平衡安慰剂设计（BPD）调查生姜与安慰剂相比并通过口头信息的期望的效果的影响。然而，研究发现生姜对结果的措施没有显著主要还是互动效应（如药物）或信息，但显示的相互作用时，参与者和实验者性都考虑考虑。我们讨论了在随后的研究表明安慰剂反应时转速降低中使用的介绍和研究报告的修改限制。在一般情况下，未来的研究的安慰剂必须识别适当的靶器官的研究的安慰剂反应和应用的具体方法，以评估生理相关性。

本研究协议已被用于研究生姜对晕车有旋转椅范例症状在健康参与者17的影响和期望。该协议的变体也被用在我们工作组的其他研究调查了期望和调节程序16,18安慰剂效应。 分析结果来看，四组的平衡安慰剂的设计应涉及主观的（SR），行为（RT，HM）进行比较，并用2×2的分析方差（ANOVA）（药物X的目标（EGG比）成果的措施信息）。包括在多变量方差分析的所有变量一次减少字母误差积累。但是，我们决定不包括在此分析是因为由于运动伪影的数据辍学的蛋比，因为这会降低参与者的数字为全分析。此外，蛋比率应当包括在一个重复测量一个OVA，以评估是否有在实验过程中对胃动过速一显著转变。 的进行的研究显示，17生姜对胃肌电活动的效果，即衰减的减小的量正常到心动过速蛋比的旋转过程之前，但没有阻止所述旋转步骤（ 图1）中的比例的减小。给出的信息没有显著影响蛋比，但结果提供该信息可以有一个效果安慰剂/安慰剂组具有最低的蛋比和生姜/姜组具有最高的蛋比率（ 表2）的提示。这一结果的非意义可能是由于施加如下面所讨论的强烈的刺激。 为SR，RT和HM组之间的差异也没有显著。然而，研究显示参与者和实验者性的附加效果互动：解放军检测CEBO反应，当男性参与者分别给予安慰剂药片与女性实验者生姜信息。此外，主观的（SR）和行为（RT，HM）措施相关的女性（SR-RT：R = -0.524，P &lt;0.001，而SR-HM：R = -0.465，P = 0.002），但不在男子17。参与者和实验者的性别的互动效果不是的方法的一部分，并且因此，不作详细此时讨论（对于这一结果的进一步讨论，请参见韦默等人 ，2012 17）。 本研究的设计提供，以评估药物和信息，和安慰剂响应的多元评估的主要和互动影响的可能性：给予药丸之间的显著差异表明，该药物对的结果的措施1的效果，而显著给出的信息之间的差异表明，信息影响结果的措施。一药物与信息之间的互动显著的效果表明，差异提供的信息会影响药效。据有关平衡的安慰剂设计4文献中，最大的不同，预计被赋予了真正的药物以及正确的信息（药加很高的期望），并且给予安慰剂沿着正确的信息群（群之间安慰剂加不期望）。在SR组之间的差异显著只意味着参与者感觉更好，但这不是他们的行为（RT更长，更HM）或客观的衡量标准（高蛋比）镜像。在RT组之间的差异显著只意味着参与者可能试图表明社会需要的行为，但并不觉得自己真的好（SR，蛋比）。在蛋比阿显著差异意味着信息给予和/或药物对胃肌电活动的效果。 图1：电图（EGG）在接受生姜或安慰剂图例文本参与者：胃被评价为在胃动过速带（4.0至9.75的cpm）正常活动（每分钟2.5到3.75个循环，CPM）和活性之间的比率。随着恶心，这比减小。数据段被记录在基线，后两次用药，并旋转后。从基线到张贴旋转比的恒定秋被中断的生姜组中，但姜无法防止恶心发生与旋转（从韦默等人 2012改性权限）。 <table border="0" cellpadding="0" cellspacing="0"><colgroup><col span="2" /><col /><col /></colgroup><tbody><tr><td></td><td></td><td colspan="2">信息</td></tr><tr><td></td><td></td><tD&gt;药品</td><td>安慰剂</td></tr><tr><td rowspan="2">应用</td><td>药</td><td>真阳性</td><td>假阴性</td></tr><tr><td>安慰剂</td><td>假阳性</td><td>真阴性</td></tr></tbody></table> 表1：平衡安慰剂设计。 <table border="0" cellpadding="0" cellspacing="0"><colgroup><col /><col span="5" /></colgroup><tbody><tr><td>应用（药物） </td><td>安慰剂</td><td>安慰剂</td><td>姜</td><td>姜</td><td></td></tr><tr><td>信息</td><td>安慰剂</td><td>姜</td><td>安慰剂</td><td>姜</td><td>统计</td></tr><tr><td> HM </td><td> 46.​​1±17.2 </td><td> 48.1±13.9 </td><td> 38.3±19.0 </td><td> 45.1±13.9 </td><td> NS </td></tr><tr><td> RT（秒） </td><td> 497±163 </td><td> 482±142 </td><td> 436±182 </td><td> 466±152 </td><td> NS </td></tr><tr><td> SR </td><td> 20.2±5.8 </td><td> 20.5±6.3 </td><td> 18.9±6.8 </td><td> 20.8±6.1 </td><td> NS </td></tr><tr><td> EGG（N） </td><td> 12 </td><td> 14 </td><td> 13 </td><td> 13 </td><td> NS </td></tr><tr><td> EGG量正常（％） </td><td> 16.8±5.5 </td><td> 18.2±8.3 </td><td> 21.7±7.2 </td><td> 20.8±9.3 </td><td> NS </td></tr><tr><td> EGG心动过速（％） </td><td> 25.8±9.2 </td><td> 23.6±7.7 </td><td> 27.9±7.9 </td><td> 24.0±6.9 </td><td> NS </td></tr><tr><td>蛋比</td><td> 0.78±0.45 </td><td> 0.92±0.63 </td><td> 0.90±0.59 </td><td> 0.96±0.64 </td><td> NS </td></tr></tbody></table> 表2：在和旋转后组之间的数据。 图例文本：HM=头部运动，RT =旋转宽容，在旋转SR =最大症状自评，EGG（N）=参与者与所有可用的4项措施，EGG量正常（％）=活动在normogastric带百分比数字，EGG心动过速（％） =活动的胃动过速带，蛋比= normogastria和胃动过速带之间的比例比例（从魏玛等，2012改编许可）。

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How to Study Placebo Responses in Motion Sickness with a Rotation Chair Paradigm in Healthy Participants

An experimental rotation chair paradigm is used to investigate whether a placebo intervention on motion sickness affects subjective outcome measures only or also affects behavioral and objective measures in a balanced placebo design.

如何学习安慰剂反应晕车了旋转椅范式健康参与者

Placebo responses occur in every medical intervention when patients or participants expect to receive an effective treatment to relieve symptoms. However, ...

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Research

JoVE Journal

Behavior

9.1K 次观看.  University Hospital Tübingen. An experimental rotation chair paradigm is used to investigate whether a placebo intervention on motion sickness affects subjective outcome measures only or also affects behavioral and objective measures in a balanced placebo design.

视频: How to Study Placebo Responses in Motion Sickness with a Rotation Chair Paradigm in Healthy Participants

How to Detect Amygdala Activity with Magnetoencephalography using Source Imaging

In trace fear conditioning a conditional stimulus (CS) predicts the occurrence of the unconditional stimulus (UCS), which is presented after a brief stimulus free period (trace interval)1. Because the CS and UCS do not co-occur temporally, the subject must maintain a representation of that CS during the trace interval. In humans, this type of learning requires awareness of the stimulus contingencies in order to bridge the trace interval2-4. However when a face is used as a CS, subjects can implicitly learn to fear the face even in the absence of explicit awareness*. This suggests that there may be additional neural mechanisms capable of maintaining certain types of "biologically-relevant" stimuli during a brief trace interval. Given that the amygdala is involved in trace conditioning, and is sensitive to faces, it is possible that this structure can maintain a representation of a face CS during a brief trace interval.
It is challenging to understand how the brain can associate an unperceived face with an aversive outcome, even though the two stimuli are separated in time. Furthermore investigations of this phenomenon are made difficult by two specific challenges. First, it is difficult to manipulate the subject's awareness of the visual stimuli. One common way to manipulate visual awareness is to use backward masking. In backward masking, a target stimulus is briefly presented (&lt; 30 msec) and immediately followed by a presentation of an overlapping masking stimulus5. The presentation of the mask renders the target invisible6-8. Second, masking requires very rapid and precise timing making it difficult to investigate neural responses evoked by masked stimuli using many common approaches. Blood-oxygenation level dependent (BOLD) responses resolve at a timescale too slow for this type of methodology, and real time recording techniques like electroencephalography (EEG) and magnetoencephalography (MEG) have difficulties recovering signal from deep sources.
However, there have been recent advances in the methods used to localize the neural sources of the MEG signal9-11. By collecting high-resolution MRI images of the subject's brain, it is possible to create a source model based on individual neural anatomy. Using this model to "image" the sources of the MEG signal, it is possible to recover signal from deep subcortical structures, like the amygdala and the hippocampus*.

This article describes how to record amygdala activity with magnetoencephalography (MEG). In addition this article will describe how to conduct trace fear conditioning without awareness, a task that activates the amygdala. It will cover 3 topics: 1) Designing a trace conditioning paradigm using backward masking to manipulate awareness. 2) Recording brain activity during the task using magnetoencephalography. 3) Using source imaging to recover signal from subcortical structures.

如何检测杏仁核活动脑磁图源成像

In trace fear conditioning a conditional  stimulus (CS) predicts the occurrence of the unconditional stimulus (UCS),  which is presented after a brief ...

科研

行为学

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 ...

A Procedure to Study the Effect of Prolonged Food Restriction on Heroin Seeking in Abstinent Rats

In human drug addicts, exposure to drug-associated cues or environments that were previously associated with drug taking can trigger relapse during abstinence. Moreover, various environmental challenges can exacerbate this effect, as well as increase ongoing drug intake.
The procedure we describe here highlights the impact of a common environmental challenge, food restriction, on drug craving that is expressed as an augmentation of drug seeking in abstinent rats.
Rats are implanted with chronic intravenous i.v. catheters, and then trained to press a lever for i.v. heroin over a period of 10-12 days. Following the heroin self-administration phase the rats are removed from the operant conditioning chambers and housed in the animal care facility for a period of at least 14 days. While one group is maintained under unrestricted access to food (sated group), a second group (FDR group) is exposed to a mild food restriction regimen that results in their body weights maintained at 90% of their nonrestricted body weight. On day 14 of food restriction the rats are transferred back to the drug-training environment, and a drug-seeking test is run under extinction conditions (i.e.&#160;lever presses do not result in heroin delivery).
The procedure presented here results in a highly robust augmentation of heroin seeking on test day in the food restricted rats. In addition, compared to the acute food deprivation manipulations we have used before, the current procedure is a more clinically relevant model for the impact of caloric restriction on drug seeking. Moreover, it might be closer to the human condition as the rats are not required to go through an extinction-training phase before the drug-seeking test, which is an integral component of the popular reinstatement procedure.

A procedure that allows a demonstration of robust augmentation of drug seeking in food-restricted rats is described. Following heroin self-administration training, rats go through an abstinence period, in a drug-free environment, during which they are mildly food restricted. Drug seeking is then tested in the drug-associated environment.

一个过程来研究延长食品的限制对海洛因寻求戒断大鼠的影响

In human drug addicts, exposure to drug-associated cues or environments that were previously associated with drug taking can trigger relapse during ...

Uncovering Beat Deafness: Detecting Rhythm Disorders with Synchronized Finger Tapping and Perceptual Timing Tasks

A set of behavioral tasks for assessing perceptual and sensorimotor timing abilities in the general population (i.e., non-musicians) is presented here with the goal of uncovering rhythm disorders, such as beat deafness. Beat deafness is characterized by poor performance in perceiving durations in auditory rhythmic patterns or poor synchronization of movement with auditory rhythms (e.g., with musical beats). These tasks include the synchronization of finger tapping to the beat of simple and complex auditory stimuli and the detection of rhythmic irregularities (anisochrony detection task) embedded in the same stimuli. These tests, which are easy to administer, include an assessment of both perceptual and sensorimotor timing abilities under different conditions (e.g., beat rates and types of auditory material) and are based on the same auditory stimuli, ranging from a simple metronome to a complex musical excerpt. The analysis of synchronized tapping data is performed with circular statistics, which provide reliable measures of synchronization accuracy (e.g., the difference between the timing of the taps and the timing of the pacing stimuli) and consistency. Circular statistics on tapping data are particularly well-suited for detecting individual differences in the general population. Synchronized tapping and anisochrony detection are sensitive measures for identifying profiles of rhythm disorders and have been used with success to uncover cases of poor synchronization with spared perceptual timing. This systematic assessment of perceptual and sensorimotor timing can be extended to populations of patients with brain damage, neurodegenerative diseases (e.g., Parkinson&#8217;s disease), and developmental disorders (e.g., Attention Deficit Hyperactivity Disorder).

Behavioral tasks that allow for the assessment of perceptual and sensorimotor timing abilities in the general population (i.e., non-musicians) are presented. Synchronization of finger tapping to the beat of an auditory stimuli and detecting rhythmic irregularities provides a means of uncovering rhythm disorders.

揭开节拍耳聋：检测节律紊乱与同步手指敲击和感知定时任务

A set of behavioral tasks for assessing perceptual and sensorimotor timing abilities in the general population (i.e., non-musicians) is presented here ...

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 ...

Visualizing Motion Patterns in Acupuncture Manipulation

Acupuncture manipulation varies widely among practitioners in clinical settings, and it is difficult to teach novice students how to perform acupuncture manipulation techniques skillfully. The Acupuncture Manipulation Education System (AMES) is an open source software system designed to enhance acupuncture manipulation skills using visual feedback. Using a phantom acupoint and motion sensor, our method for acupuncture manipulation training provides visual feedback regarding the actual movement of the student's acupuncture manipulation in addition to the optimal or intended movement, regardless of whether the manipulation skill is lifting, thrusting, or rotating. Our results show that students could enhance their manipulation skills by training using this method. This video shows the process of manufacturing phantom acupoints and discusses several issues that may require the attention of individuals interested in creating phantom acupoints or operating this system.

Here, we present a protocol for using the Acupuncture Manipulation Education System (AMES) in the training of acupuncture manipulation skills using phantom acupoints.

可视化的运动模式在针刺手法

Acupuncture manipulation varies widely among practitioners in clinical settings, and it is difficult to teach novice students how to perform acupuncture ...

Reversible Cooling-induced Deactivations to Study Cortical Contributions to Obstacle Memory in the Walking Cat

On complex, naturalistic terrain, sensory information about an environmental obstacle can be used to rapidly adjust locomotor movements for avoidance. For example, in the cat, visual information about an impending obstacle can modulate stepping for avoidance. Locomotor adaptation can also occur independent of vision, as sudden tactile inputs to the leg by an expected obstacle can modify the stepping of all four legs for avoidance. Such complex locomotor coordination involves supraspinal structures, such as the parietal cortex. This protocol describes the use of reversible, cooling-induced cortical deactivation to assess parietal cortex contributions to memory-guided obstacle locomotion in the cat. Small cooling loops, known as cryoloops, are specially shaped to deactivate discrete regions of interest to assess their contributions to an overt behavior. Such methods have been used to elucidate the role of parietal area 5 in memory-guided obstacle avoidance in the cat.

Complex locomotion in naturalistic environments requiring careful coordination of the limbs involves regions of the parietal cortex. The following protocol describes the use of reversible cooling-induced deactivation to demonstrate the role of parietal area 5 in memory-guided obstacle avoidance in the walking cat.

可逆冷却诱导 Deactivations 对行走猫的障碍记忆的皮层贡献研究

On complex, naturalistic terrain, sensory information about an environmental obstacle can be used to rapidly adjust locomotor movements for avoidance. For ...

A Networked Desktop Virtual Reality Setup for Decision Science and Navigation Experiments with Multiple Participants

Investigating the interactions among multiple participants is a challenge for researchers from various disciplines, including the decision sciences and spatial cognition. With a local area network and dedicated software platform, experimenters can efficiently monitor the behavior of the participants that are simultaneously immersed in a desktop virtual environment and digitalize the collected data. These capabilities allow for experimental designs in spatial cognition and navigation research that would be difficult (if not impossible) to conduct in the real world. Possible experimental variations include stress during an evacuation, cooperative and competitive search tasks, and other contextual factors that may influence emergent crowd behavior. However, such a laboratory requires maintenance and strict protocols for data collection in a controlled setting. While the external validity of laboratory studies with human participants is sometimes questioned, a number of recent papers suggest that the correspondence between real and virtual environments may be sufficient for studying social behavior in terms of trajectories, hesitations, and spatial decisions. In this article, we describe a method for conducting experiments on decision-making and navigation with up to 36 participants in a networked desktop virtual reality setup (i.e., the Decision Science Laboratory or DeSciL). This experiment protocol can be adapted and applied by other researchers in order to set up a networked desktop virtual reality laboratory.

This paper describes a method for conducting multi-user experiments on decision-making and navigation using a networked computer laboratory.

面向多参与者的决策科学与导航实验的网络化桌面虚拟现实设置

Investigating the interactions among multiple participants is a challenge for researchers from various disciplines, including the decision sciences and ...

Using the Visual World Paradigm to Study Sentence Comprehension in Mandarin-Speaking Children with Autism

Sentence comprehension relies on the ability to rapidly integrate different types of linguistic and non-linguistic information. However, there is currently a paucity of research exploring how preschool children with autism understand sentences using different types of cues. The mechanisms underlying sentence comprehension remains largely unclear. The present study presents a protocol to examine the sentence comprehension abilities of preschool children with autism. More specifically, a visual world paradigm of eye-tracking is used to explore the moment-to-moment sentence comprehension in the children. The paradigm has multiple advantages. First, it is sensitive to the time course of sentence comprehension and thus can provide rich information about how sentence comprehension unfolds over time. Second, it requires minimal task and communication demands, so it is ideal for testing children with autism. To further minimize the computational burden of children, the present study measures eye movements that arise as automatic responses to linguistic input rather than measuring eye movements that accompany conscious responses to spoken instructions.

We present a protocol to examine the use of morphological cues during real-time sentence comprehension by children with autism.

用视觉世界范式研究自闭症普通话儿童的句子理解

Sentence comprehension relies on the ability to rapidly integrate different types of linguistic and non-linguistic information. However, there is ...

Assessing the Autonomic and Behavioral Effects of Passive Motion in Rats using Elevator Vertical Motion and Ferris-Wheel Rotation

The overall goal of this study is to assess the autonomic and behavioral effects of passive motion in rodents using the elevator vertical motion and Ferris-wheel rotation devices. These assays can help confirm the integrity and normal functioning of the autonomic nervous system. They are coupled to quantitative measures based on defecation counting, open-field examination, and balance beam crossing. The advantages of these assays are their simplicity, reproducibility, and quantitative behavioral measures. The limitations of these assays are that the autonomic reactions could be epiphenomena of non-vestibular disorders and that a functioning vestibular system is required. Examination of disorders such as motion sickness will be greatly aided by the detailed procedures of these assays.

Protocols are presented to assess the autonomic and behavioral effects of passive motion in rodents using elevator vertical motion and Ferris-wheel rotation.

使用电梯垂直运动和摩天轮旋转评估大鼠被动运动的自主性和行为效应

The overall goal of this study is to assess the autonomic and behavioral effects of passive motion in rodents using the elevator vertical motion and ...