评估由三角刺激引起的由Locus Coeruleus介导的觉醒中与学生相关的变化
1Department of Translational Research and of New Surgical and Medical Technologies,University of Pisa, 2The BioRobotics Institute,Scuola Superiore Sant’Anna, 3Department of Excellence in Robotics & AI,Scuola Superiore Sant’Anna, 4Institut des Maladie Neurodegeneratives,University of Bordeaux, 5Department of Physics,University of Pisa, 6Department of Surgical, Medical, Molecular Pathology and Critical Care Medicine,University of Pisa, 7Department of Developmental Neuroscience,IRCCS Foundation Stella Maris
Summary
为了验证三元对认知表现的影响是否涉及位点性球菌活动，提出了两个协议，旨在评估咀嚼引起的性能和与任务相关的学生大小变化之间的可能相关性。这些协议可应用于怀疑原点贡献的条件。
Abstract
目前的科学文献提供了证据，证明与咀嚼相关的三叉体感觉运动活动可能会影响觉醒、注意力和认知表现。这些影响可能是由于三叉星系统与上升性视网膜激活系统 （ARAS） 的广泛连接，而基拉图（LC）的角质神经元属于这个系统。LC神经元包含对整个大脑的投影，并且已知它们的放电随学生大小共同变化。LC 激活对于引发与任务相关的突起体炎是必要的。如果咀嚼对认知性能的影响由LC调节，那么有理由期望认知性能的变化与任务相关突起系统的变化相关。这里提出了两种新颖的协议来验证这一假设，并证明咀嚼效果不能归因于特定的运动激活。在这两种协议中，在特定任务期间观察到的性能和学生大小变化都会在 2 分钟之后记录在 2 分钟之后和半小时内记录：a） 无活动、b） 有节奏、双边握把、c） 双边咀嚼软颗粒和 d）双边咀嚼硬颗粒。第一个协议测量在数字矩阵中显示的目标数字的识别性能级别。由于学生大小记录由适当的学生表记录，该测速仪会妨碍视力以确保恒定的照明水平，因此在触觉任务期间会评估与任务相关的霉菌病。该协议的结果表明，1） 咀嚼引起的性能和任务相关的突起病的变化是相关的，2） 性能和突动都不能通过手柄增强。在第二个协议中，使用可穿戴的孔径计可以测量同一任务期间的学生大小变化和性能，从而获得关于LC参与认知活动三元效应的更有力的证据。这两种协议都运行在比萨大学ARAS的发现者朱塞佩·莫鲁齐教授的历史办公室。
Introduction
在人类中，众所周知，咀嚼会加速认知处理1，2，并改善觉醒3，4，注意5，学习和记忆6，7。这些影响与缩短皮质事件相关电位8的延迟和增加几个皮质和皮下结构2，9的灌注增加有关。
在颅神经内，最相关的信息维持皮质去同步和唤醒是由三叉纤维10携带，可能是由于强烈的三叉线连接到上升的视网膜激活系统（ARAS）11 。在ARAS结构中，球位（LC）接收三元位输入11，调制唤醒12，13，其活动与学生大小14，15，16，17，18。虽然LC休息活动与认知表现之间的关系是复杂的，但与任务相关的LC活动的增强导致觉醒相关的19名学生心肌炎20和增强认知性能21。LC活动与学生大小之间存在可靠的共性差异，后者目前被认为是22、23、24、25、26的中央诺瑞纳活性的代理。
传感器运动三叉叶分支的不对称激活诱导学生不对称（双子座）27，28，确认三角-科鲁里亚连接的强度。如果LC参与咀嚼对认知表现的刺激作用，它可能会影响平行的任务相关的突起症，这是在任务期间LC相发生数激活的指标。它还可能影响性能，因此，咀嚼引起的性能变化与支数症之间存在相关性。此外，如果三叉体效应是特定的，咀嚼效果应该大于那些由另一个有节奏的运动任务引起的。为了检验这些假设，特此提出了两个实验方案。它们基于认知表现和学生大小的综合测量，在短暂的咀嚼活动前后进行。这些协议利用一个测试，包括查找数字关注矩阵29中显示的目标数，以及非目标数字。此测试验证专注和认知性能。
这些协议的总体目标是说明三元刺激会引起认知性能的具体变化，这不能具体归因于电机命令的生成，并且与LC介导的与学生相关的变化有关觉醒。该协议的应用扩展到所有行为条件，其中可以测量性能，并怀疑 LC 的参与。
Protocol
所有步骤都遵循比萨大学道德委员会的指导方针。 1. 参与者招聘 根据研究的具体目标（即正常受试者和/或患者、男性和/或女性、年轻人和/或老年人）招募受试者群体。 2. 材料准备 准备软颗粒;使用市售口香糖（材料表;初始硬度=20肖氏OO）。 准备硬颗粒;使用硅橡胶颗粒（材料表;恒定硬度= 60肖氏OO）<s…
Representative Results
图 4显示了将协议 1 应用于单个主体（46 岁，女性）时获得的结果的代表性示例。PI 在咀嚼 （T7） 后很快增加（从 1.73 麻木/s 到 2.27 麻木/s） 和软颗粒 （从 1.67 麻木/s 到 1.87 麻木/s） （图 4A）。然而，30分钟后（T37），增加的性能只坚持硬颗粒。另一方面，缺乏活动和握把运动对性能有负面影响，从1.73麻木/秒下降到1.67麻木/秒，从1.6麻木/…
Discussion
本研究提出的方案涉及感觉运动三叉体活动对认知性能的急性影响以及LC在这一过程中的作用。这个话题有一定的相关性，考虑到1）在老化期间，咀嚼活性的恶化与认知衰减32，33，34;维护口腔健康的人不太容易出现神经退行性现象;2） 闭塞和牙齿提取诱导神经退行性作用在动物在海马和皮质水平35，<…
Declarações
The authors have nothing to disclose.
Acknowledgements
这项研究得到了比萨大学的资助。我们感谢保罗·奥尔西尼先生、弗朗切斯科·蒙塔纳里先生和克里斯蒂娜·普奇夫人的宝贵技术援助，并感谢国际投资公司S.R.R.L.公司为玛丽亚·保拉·特拉蒙蒂·范托齐博士提供奖学金。最后，我们感谢 OCM 项目公司准备硬颗粒并执行硬度和弹簧恒定测量。
Materials
| Anti-stress ball | Artengo, Decathlon, France | TB600 | |
| Chewing gum | Vigorsol, Perfetti, Italy | Commercially available product | |
| Infrared Camera-Wearable pupillometer | Pupil Labs, Berlin, Germany | Pupil Labs headset | |
| Pupillographer | CSO, Florence, Italy | MOD i02, with chin support | |
| Silicon rubber | Prochima, Italy | gls50 | |
| Software for pupil detection – wearable pupillometer | Pupil Labs, Berlin, Germany | Pupil Labs headset | |
| Tangram Puzzle | Città del Sole srl, Milano, Italy | Tangram Puzzle | |
| Wearable pupillometer | Pupil Labs, Berlin, Germany | Pupil labs model | Dimension of the frame: 13.5 x 15.5cm |
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Citar este artigo
Fantozzi, M. P. T., Banfi, T., De Cicco, V., Barresi, M., Cataldo, E., De Cicco, D., Bruschini, L., d’Ascanio, P., Ciuti, G., Faraguna, U., Manzoni, D. Assessing Pupil-linked Changes in Locus Coeruleus-mediated Arousal Elicited by Trigeminal Stimulation. J. Vis. Exp. (153), e59970, doi:10.3791/59970 (2019).