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><tbody><tr><td>Cleartrace electrodes</td><td>P.J. Dahlhausen &amp;amp; Co. GmbH, K&amp;ouml;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&amp;uuml;nwalder GmbH, Bad T&amp;ouml;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）。

Watch this Scientific Journal Video about How to Study Placebo Responses in Motion Sickness with a Rotation Chair Paradigm in Healthy Participants at JoVE.com

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, ...

how-to-study-placebo-responses-motion-sickness-with-rotation-chair

Universidad de Cartagena UDEC

Research

JoVE Journal

Behavior

9.2K 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

MPI CyberMotion Simulator: Implementation of a Novel Motion Simulator to Investigate Multisensory Path Integration in Three Dimensions

Path integration is a process in which self-motion is integrated over time to obtain an estimate of one's current position relative to a starting point 1. Humans can do path integration based exclusively on visual 2-3, auditory 4, or inertial cues 5. However, with multiple cues present, inertial cues - particularly kinaesthetic - seem to dominate 6-7. In the absence of vision, humans tend to overestimate short distances (&lt;5 m) and turning angles (&lt;30&deg;), but underestimate longer ones 5. Movement through physical space therefore does not seem to be accurately represented by the brain.
Extensive work has been done on evaluating path integration in the horizontal plane, but little is known about vertical movement (see 3 for virtual movement from vision alone). One reason for this is that traditional motion simulators have a small range of motion restricted mainly to the horizontal plane. Here we take advantage of a motion simulator 8-9 with a large range of motion to assess whether path integration is similar between horizontal and vertical planes. The relative contributions of inertial and visual cues for path navigation were also assessed.
16 observers sat upright in a seat mounted to the flange of a modified KUKA anthropomorphic robot arm. Sensory information was manipulated by providing visual (optic flow, limited lifetime star field), vestibular-kinaesthetic (passive self motion with eyes closed), or visual and vestibular-kinaesthetic motion cues. Movement trajectories in the horizontal, sagittal and frontal planes consisted of two segment lengths (1st: 0.4 m, 2nd: 1 m; &plusmn;0.24 m/s2 peak acceleration). The angle of the two segments was either 45&deg; or 90&deg;. Observers pointed back to their origin by moving an arrow that was superimposed on an avatar presented on the screen.
Observers were more likely to underestimate angle size for movement in the horizontal plane compared to the vertical planes. In the frontal plane observers were more likely to overestimate angle size while there was no such bias in the sagittal plane. Finally, observers responded slower when answering based on vestibular-kinaesthetic information alone. Human path integration based on vestibular-kinaesthetic information alone thus takes longer than when visual information is present. That pointing is consistent with underestimating and overestimating the angle one has moved through in the horizontal and vertical planes respectively, suggests that the neural representation of self-motion through space is non-symmetrical which may relate to the fact that humans experience movement mostly within the horizontal plane.

An efficient way to gain insight into how humans navigate themselves in three dimensions is described. The method takes advantage of a motion simulator capable of moving observers in ways unattainable by traditional simulators. Results confirm that movement in the horizontal plane is underestimated, while vertical movement is overestimated.

MPI Cyber​​Motion模拟器:一种新型的运动模拟器的执行情况调查三个维度的多感官的路径积分

Path integration is a process in which self-motion is integrated over time to obtain an estimate of one's current position relative to a starting point 1. ...

科研

神经科学

Three Dimensional Vestibular Ocular Reflex Testing Using a Six Degrees of Freedom Motion Platform

The vestibular organ is a sensor that measures angular and linear accelerations with six degrees of freedom (6DF). Complete or partial defects in the vestibular organ results in mild to severe equilibrium problems, such as vertigo, dizziness, oscillopsia, gait unsteadiness nausea and/or vomiting. A good and frequently used measure to quantify gaze stabilization is the gain, which is defined as the magnitude of compensatory eye movements with respect to imposed head movements. To test vestibular function more fully one has to realize that 3D VOR ideally generates compensatory ocular rotations not only with a magnitude (gain) equal and opposite to the head rotation but also about an axis that is co-linear with the head rotation axis (alignment). Abnormal vestibular function thus results in changes in gain and changes in alignment of the 3D VOR response.
Here we describe a method to measure 3D VOR using whole body rotation on a 6DF motion platform. Although the method also allows testing translation VOR responses 1, we limit ourselves to a discussion of the method to measure 3D angular VOR. In addition, we restrict ourselves here to description of data collected in healthy subjects in response to angular sinusoidal and impulse stimulation.
Subjects are sitting upright and receive whole-body small amplitude sinusoidal and constant acceleration impulses. Sinusoidal stimuli (f = 1 Hz, A = 4&deg;) were delivered about the vertical axis and about axes in the horizontal plane varying between roll and pitch at increments of 22.5&deg; in azimuth. Impulses were delivered in yaw, roll and pitch and in the vertical canal planes. Eye movements were measured using the scleral search coil technique 2. Search coil signals were sampled at a frequency of 1 kHz.
The input-output ratio (gain) and misalignment (co-linearity) of the 3D VOR were calculated from the eye coil signals 3.
Gain and co-linearity of 3D VOR depended on the orientation of the stimulus axis. Systematic deviations were found in particular during horizontal axis stimulation. In the light the eye rotation axis was properly aligned with the stimulus axis at orientations 0&deg; and 90&deg; azimuth, but gradually deviated more and more towards 45&deg; azimuth.
The systematic deviations in misalignment for intermediate axes can be explained by a low gain for torsion (X-axis or roll-axis rotation) and a high gain for vertical eye movements (Y-axis or pitch-axis rotation (see Figure 2). Because intermediate axis stimulation leads a compensatory response based on vector summation of the individual eye rotation components, the net response axis will deviate because the gain for X- and Y-axis are different.
In darkness the gain of all eye rotation components had lower values. The result was that the misalignment in darkness and for impulses had different peaks and troughs than in the light: its minimum value was reached for pitch axis stimulation and its maximum for roll axis stimulation.
Case Presentation
Nine subjects participated in the experiment. All subjects gave their informed consent. The experimental procedure was approved by the Medical Ethics Committee of Erasmus University Medical Center and adhered to the Declaration of Helsinki for research involving human subjects.
Six subjects served as controls. Three subjects had a unilateral vestibular impairment due to a vestibular schwannoma. The age of control subjects (six males and three females) ranged from 22 to 55 years. None of the controls had visual or vestibular complaints due to neurological, cardio vascular and ophthalmic disorders.
The age of the patients with schwannoma varied between 44 and 64 years (two males and one female). All schwannoma subjects were under medical surveillance and/or had received treatment by a multidisciplinary team consisting of an othorhinolaryngologist and a neurosurgeon of the Erasmus University Medical Center. Tested patients all had a right side vestibular schwannoma and underwent a wait and watch policy (Table 1; subjects N1-N3) after being diagnosed with vestibular schwannoma. Their tumors had been stabile for over 8-10 years on magnetic resonance imaging.

A method is described to measure three-dimensional vestibulo ocular reflexes (3D VOR) in humans using a six degrees of freedom (6DF) motion simulator. The gain and misalignment of the 3D angular VOR provide a direct measure of the quality of vestibular function. Representative data on healthy subjects are provided

三维前庭眼反射测试使用六度自由度运动平台

The vestibular organ is a sensor that measures angular and linear accelerations with six degrees of freedom (6DF). Complete or partial defects in the ...

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 ...

行为学

Using Unidirectional Rotations to Improve Vestibular System Asymmetry in Patients with Vestibular Dysfunction

The vestibular system provides information about head movement and mediates reflexes that contribute to balance control and gaze stabilization during daily activities. Vestibular sensors are located in the inner ear on both sides of the head and project to the vestibular nuclei in the brainstem. Vestibular dysfunction is often due to an asymmetry between input from the two sides. This results in asymmetrical neural inputs from the two ears, which can produce an illusion of rotation, manifested as vertigo. The vestibular system has an impressive capacity for compensation, which serves to rebalance how asymmetrical information from the sensory end organs on both sides is processed at the central level. To promote compensation, various rehabilitation programs are used in the clinic; however, they primarily use exercises that improve multisensory integration. Recently, visual-vestibular training has also been used to improve the vestibulo-ocular reflex (VOR) in animals with compensated unilateral lesions. Here, a new method is introduced for rebalancing the vestibular activity on both sides in human subjects. This method consists of five unidirectional rotations in the dark (peak velocity of 320&#176;/s) toward the weaker side. The efficacy of this method was shown in a sequential, double-blinded clinical trial in 16 patients with VOR asymmetry (measured by the directional preponderance in response to sinusoidal rotations). In most cases, VOR asymmetry decreased after a single session, reached normal values within the first two sessions in one week, and the effects lasted up to 6 weeks. The rebalancing effect is due to both an increase in VOR response from the weaker side and a decrease in response from the stronger side. The findings suggest that unidirectional rotation can be used as a supervised rehabilitation method to reduce VOR asymmetry in patients with longstanding vestibular dysfunction.

A new rehabilitation method is presented for rebalancing the vestibular system in patients with asymmetric responses, which consists of unidirectional rotations toward the weaker side. By directly modifying the vestibular pathway rather than enhancing the multisensory aspects of compensation, asymmetry can be normalized within 1-2 sessions and show lasting effects.

使用单向旋转改善前庭功能障碍患者的前庭系统不对称性

The vestibular system provides information about head movement and mediates reflexes that contribute to balance control and gaze stabilization during ...

Controlled Rotation of Human Observers in a Virtual Reality Environment

The low cost and availability of Virtual Reality (VR) systems have supported a recent acceleration of research into perception and behavior under more naturalistic, multisensory, and immersive conditions. One area of research that has particularly benefited from the use of VR systems is multisensory integration, for example, the integration of visual and vestibular cues to give rise to a sense of self-motion. For this reason, an accessible method for the controlled physical rotation of an observer in a virtual environment represents a useful innovation. This paper presents a method for automating the rotation of an office swivel chair along with a method for integrating that motion into a VR experience. Using an example experiment, it is demonstrated that the physical motion, thus produced, is integrated with the visual experience of an observer in a way consistent with expectations; high integration when the motion is congruent with the visual stimulus and low integration when the motion is incongruent.

The controlled physical rotation of a human observer is desirable for certain experimental, recreational, and educational applications. This paper outlines a method for converting an office swivel chair into a medium for controlled physical rotation in a virtual reality environment.

虚拟现实环境中人类观察者的受控旋转

The low cost and availability of Virtual Reality (VR) systems have supported a recent acceleration of research into perception and behavior under more ...

Estimating Vestibular Perceptual Thresholds Using a Six-Degree-Of-Freedom Motion Platform

Vestibular perceptual thresholds refer to the motion intensity required to enable a participant to detect or discriminate a motion based on vestibular input. Using passive motion profiles provided by six degree-of-motion platforms, vestibular perceptual thresholds can be estimated for any kind of motion and thereby target each of the sub-components of the vestibular end-organ. Assessments of vestibular thresholds are clinically relevant as they complement diagnostic tools such as caloric irrigation, the head impulse test (HIT), or vestibular evoked myogenic potentials (VEMPs), which only provide information on sub-components of the vestibular system, but none of them allow for assessing all components. There are several methods with different advantages and disadvantages for estimating vestibular perceptual thresholds. In this article, we present a protocol using an adaptive staircase algorithm and sinusoidal motion profiles for an efficient estimation procedure. Adaptive staircase algorithms consider the response history to determine the peak velocity of the next stimuli and are the most commonly used algorithms in the vestibular domain. We further discuss the impact of motion frequency on vestibular perceptual thresholds.

In this article, we describe the methods, procedures, and technologies required to estimate vestibular perceptual thresholds using a six-degree-of-freedom motion platform.

使用六自由度运动平台估计前庭知觉阈值

Vestibular perceptual thresholds refer to the motion intensity required to enable a participant to detect or discriminate a motion based on vestibular ...

Long-term Sensory Conflict in Freely Behaving Mice

Long-term sensory conflict protocols are a valuable means of studying motor learning. The presented protocol produces a persistent sensory conflict for experiments aimed at studying long-term learning in mice. By permanently wearing a device fixed on their heads, mice are continuously exposed to a sensory mismatch between visual and vestibular inputs while freely moving in home cages. Therefore, this protocol readily enables the study of the visual system and multisensory interactions over an extended timeframe that would not be accessible otherwise. In addition to lowering the experimental costs of long-term sensory learning in naturally behaving mice, this approach accommodates the combination of in vivo and in vitro experiments. In the reported example, video-oculography is performed to quantify the vestibulo-ocular reflex (VOR) and optokinetic reflex (OKR) before and after learning. Mice exposed to this long-term sensory conflict between visual and vestibular inputs presented a strong VOR gain decrease but exhibited few OKR changes. Detailed steps of device assembly, animal care, and reflex measurements are hereby reported.

The presented protocol produces a persistent sensory conflict for experiments aimed at studying long-term learning. By permanently wearing a fixed device on their heads, mice are continuously exposed to a sensory mismatch between visual and vestibular inputs while freely moving in home cages.

自由生育小鼠的长期感觉冲突

Long-term sensory conflict protocols are a valuable means of studying motor learning. The presented protocol produces a persistent sensory conflict for ...

Assessment of Static Graviceptive Perception in the Roll-Plane using the Subjective Visual Vertical Paradigm

Vestibular disorders are among the most common syndromes in medicine. In recent years, new vestibular diagnostic systems have been introduced that allow the examination of all semicircular canals in the clinical setting. Assessment methods of the otolithic system, which is responsible for the perception of linear acceleration and perception of gravity, are far less in clinical use. There are several experimental approaches for measuring the perception of gravity. The most frequently used method is the determination of the subjective visual vertical. This is usually measured with the head in an upright position. We present here an assessment method for testing otolith function in the roll plane. The subjective visual vertical is measured in the head upright position as well as with head inclination of &#177; 15&#176; and &#177; 30&#176; in the roll plane. This extended functional paradigm is an easy-to-perform clinical test of otolith function and ensures increased information content for the detection of impaired graviceptive perception.

The perception of gravity is commonly determined by the subjective visual vertical in the head upright position. The additional assessment at head tilts of &#177; 15&#176; and &#177; 30&#176; in the roll plane ensures increased information content for the detection of impaired graviceptive perception.

使用主观视觉垂直范式对卷平面中的静态视觉感知的评估

Vestibular disorders are among the most common syndromes in medicine. In recent years, new vestibular diagnostic systems have been introduced that allow ...

医学

Virtual Prism Adaptation Therapy: Protocol for Validation in Healthy Adults

Hemispatial neglect is a common impairment after stroke. It is associated with poor functional and social outcomes. Therefore, an adequate intervention is imperative for the successful management of hemispatial neglect. However, the clinical use of various interventions is limited in real clinical practice. Prism adaptation therapy is one of the most evidence-based rehabilitation modalities to treat hemispatial neglect. To overcome any possible shortcoming that may occur with prism therapy, we developed a new system using immersive virtual reality and depth-sensing camera to create a virtual prism adaptation therapy (VPAT). To validate the VPAT system, we designed an experimental protocol investigating the behavioral errors and changes in cortical activation via the VPAT system. Cortical activation was measured by functional near infrared spectroscopy (fNIRS). The experiment consisted of four phases. All four included clicking, pointing or rest applied to right-handed healthy people. Clicking versus pointing was used for investigating the cortical region related with the gross motor task, and pointing with VPAT versus pointing without VPAT was used for investigating the cortical region associated with visuospatial perception. The preliminary results from four healthy participants showed that pointing errors by the VPAT system was similar to the conventional prism adaptation therapy. Further analysis with more participants and fNIRS data, as well as a study in patients with stroke may be required.

This experimental protocol demonstrates the use of virtual prism adaptation therapy (VPAT) in healthy adults and the association between VPAT and functional near infrared spectroscopy to determine the effect of VPAT on cortical activation. Results suggest that VPAT may be feasible and could induce similar behavioral adaptation as conventional prism adaptation therapy.

虚拟棱镜适应疗法:健康成人验证协议

Hemispatial neglect is a common impairment after stroke. It is associated with poor functional and social outcomes. Therefore, an adequate intervention is ...

Measuring the Influence of Magnetic Vestibular Stimulation on Nystagmus, Self-Motion Perception, and Cognitive Performance in a 7T MRT

Strong magnetic fields induce dizziness, vertigo, and nystagmus due to Lorentz forces acting on the cupula in the semi-circular canals, an effect called magnetic vestibular stimulation (MVS). In this article, we present an experimental setup in a 7T MRT scanner (MRI scanner) that allows the investigation of the influence of strong magnetic fields on nystagmus as well as perceptual and cognitive responses. The strength of MVS is manipulated by altering the head positions of the participants. The orientation of the participants&#39; semicircular canals with respect to the static magnetic field is assessed by combining a 3D magnetometer and 3D constructive interference in steady-state (3D-CISS) images. This approach allows to account for intra- and inter-individual differences in participants&#8217; responses to MVS. In the future, MVS can be useful for clinical research, for example, in the investigation of compensatory processes in vestibular disorders. Furthermore, it could foster insights into the interplay between vestibular information and cognitive processes in terms of spatial cognition and the emergence of self-motion percepts under conflicting sensory information. In fMRI studies, MVS can elicit a possible confounding effect, especially in tasks influenced by vestibular information or in studies comparing vestibular patients with healthy controls.

In this article, we describe the experimental setup, material, and procedures to assess reflexive eye movements, self-motion perception, and cognitive tasks under magnetic vestibular stimulation, as well as the anatomical orientation of the vestibular organs, in a 7 Tesla Magnetic resonance tomography (7T-MRT) scanner.

测量磁前庭刺激对7T MRT眼球震颤、自我运动知觉和认知表现的影响

Strong magnetic fields induce dizziness, vertigo, and nystagmus due to Lorentz forces acting on the cupula in the semi-circular canals, an effect called ...

如何学习安慰剂反应晕车了旋转椅范式健康参与者

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MPI CyberMotion模拟器:一种新型的运动模拟器的执行情况调查三个维度的多感官的路径积分

三维前庭眼反射测试使用六度自由度运动平台

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

使用单向旋转改善前庭功能障碍患者的前庭系统不对称性

虚拟现实环境中人类观察者的受控旋转

使用六自由度运动平台估计前庭知觉阈值

自由生育小鼠的长期感觉冲突

使用主观视觉垂直范式对卷平面中的静态视觉感知的评估

虚拟棱镜适应疗法:健康成人验证协议

测量磁前庭刺激对7T MRT眼球震颤、自我运动知觉和认知表现的影响

如何学习安慰剂反应晕车了旋转椅范式健康参与者

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MPI Cyber​​Motion模拟器:一种新型的运动模拟器的执行情况调查三个维度的多感官的路径积分

三维前庭眼反射测试使用六度自由度运动平台

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

使用单向旋转改善前庭功能障碍患者的前庭系统不对称性

虚拟现实环境中人类观察者的受控旋转

使用六自由度运动平台估计前庭知觉阈值

自由生育小鼠的长期感觉冲突

使用主观视觉垂直范式对卷平面中的静态视觉感知的评估

虚拟棱镜适应疗法:健康成人验证协议

测量磁前庭刺激对7T MRT眼球震颤、自我运动知觉和认知表现的影响

MPI CyberMotion模拟器:一种新型的运动模拟器的执行情况调查三个维度的多感官的路径积分