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Summary
Abstract
Introduction
Protocol
Results
Discussion
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神经科学

将呼吸同步嗅觉计与大脑模拟相结合，研究气味对皮质脊髓兴奋性和有效连接性的影响

Published: January 19, 2024
doi:
10.3791/65714
, , , , , ,
1PSYR2, Centre de Recherche en Neurosciences de Lyon, Institut National de la Santé et de la Recherche Médicale U1028, Centre National de la Recherche Scientifique UMR5292,Université Claude Bernard Lyon 1, 2Centre Hospitalier Le Vinatier, 3NEUROPOP, Centre de Recherche en Neurosciences de Lyon, Institut National de la Santé et de la Recherche Médicale U1028, Centre National de la Recherche Scientifique UMR5292,Université Claude Bernard Lyon 1

Summary

本文描述了在与人类鼻呼吸同步的气味呈现过程中，使用呼吸同步嗅觉计触发单线圈和双线圈经颅磁刺激 （TMS）。这种组合使我们能够客观地研究令人愉快和不愉快的气味如何影响特定个体的皮质脊髓兴奋性和大脑有效连接。

Abstract

人们普遍认为，嗅觉刺激会引发动物和人类的运动行为，例如接近令人愉悦的气味并避免令人不快的气味。最近，使用脑电图和经颅磁刺激 （TMS） 的研究表明，嗅觉系统的处理与人类运动皮层的活动之间存在密切联系。为了更好地理解嗅觉和运动系统之间的相互作用，并克服以前的一些方法学局限性，我们开发了一种新方法，将嗅觉计与嗅觉计同步具有不同享乐值的气味剂的随机顺序呈现，以及TMS（单线圈和双线圈）触发与鼻呼吸阶段。这种方法可以探测皮质脊髓兴奋性的调节以及背外侧前额叶皮层和初级运动皮层之间的有效同侧连接，这些连接可能在愉快和不愉快的气味感知期间发生。该方法的应用将允许客观地区分给定参与者中气味剂的愉悦值，表明气味剂对大脑有效连接性和兴奋性的生物学影响。此外，这可能为神经或神经精神疾病患者的临床研究铺平道路，这些患者可能表现出气味享乐改变和适应不良的回避行为。

Introduction

人们普遍认为，嗅觉刺激会引起自动反应和运动行为。例如，在人类中，最近已经证明在负气味发作后 500 毫秒内存在回避运动反应（远离气味源）1。Chalençon 等人（2022 年）通过记录自由移动的人类参与者探索烧瓶散发出的气味，表明运动行为（即接近鼻子的速度和取出含有气味剂的烧瓶）与气味享乐密切相关2.此外，最近通过使用脑电图1，在人类中证明了嗅觉系统的处理与运动皮层活动之间的密切联系。具体来说，在负气味开始后大约 350 毫秒，在初级运动皮层 （M1） 上方和内部观察到特定的 mu 节律不同步，已知反映了动作准备过程，随后不久是行为向后运动1。最近的另一项研究表明，与无气味条件相比，暴露于令人愉悦的气味剂会增加皮质脊髓兴奋性3。在这项研究中，对 M1 施加单脉冲经颅磁刺激 （spTMS） 以唤起目标手肌中的运动诱发电位 （MEP），在气味感知期间用肌电图 （EMG） 在外周记录。暴露于令人愉悦的气味剂是通过浸有纯佛手柑精油的纸条被动提供的，并放置在鼻子下方的金属支架上 3.在这种情况下，尚不清楚皮质脊髓兴奋性的促进是由于令人愉悦的气味刺激还是由于非特异性行为影响，例如嗅探和咬牙4,5。此外，目前尚不清楚令人不快的气味如何调节 TMS 探测的 M1 兴奋性。

总之，这突出了开发一种方法的必要性，该方法与先前研究中使用的现有技术相比具有以下优势3,6：（1）在同一实验阶段随机呈现不同的气味条件（令人愉悦/令人不快/无气味），（2）在研究运动系统时，根据人类鼻呼吸阶段（吸气和呼气）精确同步气味呈现和TMS时间。

TMS 还可以用作研究多个皮质区域和 M1 之间皮质-皮质相互作用的工具，也称为有效连接，具有高时间分辨率7、8、9、10、11、12。在这里，我们使用双位点 TMS （dsTMS） 范式，其中第一次调节刺激 （CS） 激活目标皮质区域，第二次测试刺激 （TS） 使用另一个线圈在 M1 上施加以唤起 MEP。通过将条件 MEP（dsTMS 条件）的振幅归一化为非条件 MEP（spTMS 条件）的振幅来评估 CS 的影响13。然后，负比率值表示抑制性皮质-皮质相互作用，而正比率值表示两个刺激区域之间的促进皮质-皮质相互作用。因此，dsTMS 范式提供了一个独特的机会来识别预激活区域和 M1 之间有效连接的性质（即促进或抑制）、强度和调节。重要的是，皮质-皮层相互作用反映了促进和抑制的复杂平衡，这种平衡可能在不同的时间和精神状态或任务中受到调节7,14。

据我们所知，相对较新的dsTMS范式从未用于研究具有不同享乐值的气味感知过程中的皮质-皮质相互作用。然而，神经影像学研究表明，暴露于令人愉悦和令人不快的气味会诱导情绪、决策和行动控制区域的连接性变化，包括辅助运动区、前扣带回皮层和背外侧前额叶皮层 （DLPFC）15,16。事实上，DLPFC是介导情绪控制、感觉处理和运动控制的更高层次方面的关键节点，例如准备过程17,18,19。此外，人类和动物研究都提供了证据表明，DLPFC 对 M117、18、20、21、22 具有不同的神经元投射。根据上下文，这些 DLPFC 投影可以促进或抑制 M1 活性 7,19,20。因此，DLPFC 和 M1 之间的有效连接似乎有可能在气味呈现过程中受到调节，并且令人愉快和令人不快的气味会招募分离的皮层网络，从而导致对 DLPFC-M1 连接的不同影响。

在这里，我们提出了一种新方法，适用于方法学上的严格研究，即在感知令人愉快和不愉快的气味时可能发生的皮质脊髓兴奋性和有效连接的调节，所有这些都与人类鼻呼吸同步传递。

Protocol

以下各节中描述的所有实验程序均已获得伦理委员会（CPP Ile de France VII，法国巴黎，协议编号 2022-A01967-36）根据赫尔辛基宣言的批准。所有受试者在入组前都提供了书面知情同意书。 1. 参与者招募 纳入/排除标准。包括成人（> 18 岁）参与者。根据国际专家指南筛查所有参与者是否有任何 TMS 禁忌症23. 排除植入医疗设备（例…

Representative Results

这里提供的代表性数据反映了参与者在完成上述分步协议后的录音，以初步了解我们可能期望的内容。 图 2 显示了使用嗅觉计软件记录的代表性参与者的呼吸信号示例。当超过阈值时，呼气期和吸气期可以很好地检测到。气味剂在过期阈值后立即触发并扩散 5 秒。在吸气相位阈值之后，以延迟（600 ms）触发 TMS 脉冲。 该结果表明，?…

Discussion

上述方案描述了一种新方法，将呼吸同步嗅觉计与单线圈和双线圈 TMS 的使用相结合，以根据气味剂的享乐值研究皮质脊髓兴奋性和有效连接的变化。这种设置将允许客观地区分给定参与者中气味剂的愉悦值，表明气味剂对大脑有效连接和反应性的生物学影响。该协议中的关键步骤涉及 TMS 参数（位置、强度）和嗅觉计参数（气味选择、相对于呼吸相的时间）。

spTMS 和 dsTMS 与…

Disclosures

The authors have nothing to disclose.

Acknowledgements

这项工作得到了法兰西基金会的支持，资助号：00123049/WB-2021-35902（J.B.和N.M.获得的资助）。作者要感谢皮埃尔·丹尼克基金会（Pierre Deniker）的支持（C.N.获得的资助）和Neuro-Immersion平台的工作人员在设计设置方面的宝贵帮助。

Materials

Acquisition board (8 channels)  National Instrument NI USB-6009 
Air compressor Jun-Air  Model6-15
Alcohol prep pads Any
Butyric acid Sigma-Aldrich B103500 Negative odorant
Desktop computer Dell Latitude 3520
EMG system Biopac System MP150
Isoamyl acetate Sigma-Aldrich W205508 Positive odorant
Nasal cannula SEBAC France O1320
Programmable pulse generator A.M.P.I  Master-8
Surface electrodes Kendall Medi-trace FS327
TMS coil (X2) MagStim D40 Alpha B.I. coil 
TMS machine MagStim Bistim2
Tube 6 mm x 20 m Radiospare 686-2671 Pneumatic connection
USB-RS232 Radiospare 687-7806
U-shaped tubes VS technologies VS110115
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Tags

Keywords: OlfactometerBrain SimulationCorticospinal ExcitabilityEffective ConnectivityOlfactory-motor InteractionsPleasant And Unpleasant OdorsTranscranial Magnetic Stimulation (TMS)Nasal BreathingPsychiatric DisordersAutonomic PerceptionApproach-avoidance Behaviors
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Neige, C., Imbert, L., Dumas, M., Athanassi, A., Thévenet, M., Mandairon, N., Brunelin, J. Combining a Breath-Synchronized Olfactometer with Brain Simulation to Study the Impact of Odors on Corticospinal Excitability and Effective Connectivity. J. Vis. Exp. (203), e65714, doi:10.3791/65714 (2024).
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