JoVE Journal > Neuroscience
Summary
Abstract
Introduction
Protocol
Resultados
Discussion
Declarações
Acknowledgements
Materials
Referências
Tadução automática
Please note that all translations are automatically generated. Click here for the English version.
Neurociência

一种免费呼吸功能磁共振成像方法研究人类嗅觉功能

Published: July 30, 2017
doi:
10.3791/54898
, , , , , , ,
1Center for NMR Research, Department of Radiology,Pennsylvania State University College of Medicine, 2Department of Neurosurgery,Pennsylvania State University College of Medicine

Summary

我们介绍从人类中心嗅觉系统获得可靠的功能磁共振成像（fMRI）数据的技术挑战和解决方案。这包括嗅觉fMRI范式设计中的特殊考虑，使用MRI兼容嗅觉仪的fMRI数据采集描述，气味选择以及用于数据后处理的专用软件工具。

Abstract

人类嗅觉的研究是一个非常复杂和有价值的领域，应用范围从生物医学研究到临床评估。目前，功能磁共振成像（fMRI）的人体中枢嗅觉系统的功能评估仍然是一个挑战，因为有几个技术难点。在考虑使用fMRI映射中心嗅觉系统的功能的有效方法时，需要考虑一些重要的变量，包括适当的气味选择，气味呈现和呼吸之间的相互作用以及对气味剂的潜在预期或习惯。与事件相关的呼吸引发的嗅觉功能磁共振成像技术可以精确地管理气味，以刺激嗅觉系统，同时最大限度地减少潜在的干扰。使用我们的数据后处理方法，可以有效地捕获原始嗅觉皮质中fMRI信号的精确定位。技术前这里提供了一种有效和实用的方法来产生可靠的嗅觉功能磁共振成像。随着我们开始进一步了解人类嗅觉系统的复杂性，这种技术最终可以应用于临床领域，作为与嗅觉退化有关的疾病的诊断工具，包括阿尔茨海默病和帕金森病。

Introduction

人类嗅觉系统被认为远远超过感觉系统，因为嗅觉也在稳态调节和情绪中起重要作用。临床上，人的嗅觉系统已知是易受许多流行的神经疾病和精神疾病，如阿尔茨海默氏病，帕金森氏病，创伤后应激障碍和抑郁症1，2，3，4，5的攻击。目前，具有血氧水平依赖性（BOLD）对比度的功能磁共振成像（fMRI）是映射人脑功能的最有价值的技术。已经获得了关于中心嗅觉结构（ 例如梨状皮层，眶额叶皮质，杏仁核和岛状皮层）的特定功能的大量知识神游6，7，8，9，10。

然而，fMRI在人类中枢嗅觉系统及相关疾病研究中的应用受到两个主要障碍的阻碍：BOLD信号的快速习惯和呼吸可变调制。在日常生活中，当一段时间暴露于气味时，我们很快就习惯了香味。事实上，使用嗅觉功能磁共振成像研究的情况下，气味引起的磁共振成像信号迅速被习惯化，这对上刺激范例设计8，10，11，12，13，14是一个挑战衰减。原始嗅皮层初始显着的BOLD信号仅持续存在在发臭后几秒钟。因此，嗅觉fMRI范例应避免在短时间内长时间或频繁的气味刺激。为了减少习惯效应，一些研究试图在fMRI范式中呈现交替气味。然而，这种方法可能使数据分析复杂化，因为每种气味剂都可以被视为独立的刺激事件。

另一个技术问题出现在受试者呼吸模式的变异性;在固定时间范式下，吸入并不总是与加臭剂给药同步。嗅觉刺激的发作和持续时间由每个人的呼吸调节，这混淆了fMRI数据质量和分析。一些研究尝试通过视觉或听觉线索来缓解这个问题，以使呼吸和气味发作同步，但受试者的依从性是可变的，特别是在临床人群中。大脑激活相关联在某些应用中，这些线索也可能使数据分析复杂化。因此，同步吸入与气味输送对于嗅觉功能磁共振成像研究至关重要15 。

对嗅觉功能磁共振成像，特别是在数据分析过程中至关重要的另外一个考虑因素是气味选择。相对于感知强度找到合适的加味剂浓度对于在各种实验条件或疾病下的大脑中的活化水平的定量和比较是重要的。气味选择还必须考虑到气味价格或愉悦度。这就是所谓的嗅觉学习16，17，以引起不同时间轮廓。为此，选择薰衣草气味进行部分验证。根据具体研究的目的，不同的气味剂可能是更好的选择。此外，三叉神经刺激必须最小化以减少e激活与嗅觉没有直接关系18 。

在本报告中，我们展示了在磁共振环境中使用嗅觉仪设置和运行呼吸触发范式的fMRI技术。我们还提供一个后处理工具，可以减少在数据采集期间可能发生的一些时序错误，以进一步改进数据分析。

Protocol

以下实验方案遵循宾夕法尼亚州立大学医学院机构审查委员会的指导方针，人体受试者在参加研究之前给予书面知情同意书。 注意：为了演示的目的，提出了一种使用市售的MRI兼容嗅觉计的简单气味刺激范例。已经证明这一范例有效降低了习惯效应，并产生了可靠的嗅觉功能磁共振成像数据15 。本协议中概述的某些步骤可能特定于使用的嗅觉仪的类型。然?…

Representative Results

图1显示了考虑MR兼容性的磁体室内外的嗅觉功能磁共振成像的设置。 图2a示出了标准固定时间范例，而图2b展示了一个范例，其中“呼吸触发”允许气味输送和吸入的同步。 具有清晰吸入峰值的常规呼吸模式对于实施准确的呼吸触发范式至关重要。因此，呼?…

Discussion

应仔细考虑实验程序，并妥善执行收集可靠的嗅觉激活数据。协议中的关键步骤包括实施呼吸引发的范例，使气味传递与图像采集同步，制备适当浓度的气味来控制心理物理反应，用可靠稳定的呼吸信号和恒定气流设置嗅觉仪，以及后处理呼吸和使用ONSET的气味施用定时数据追溯调整气味发起向量。在设计范例和分析数据时，需要考虑诸如习惯，心理物理反应和呼吸模式等混淆因素。当受试者暴?…

Declarações

The authors have nothing to disclose.

Acknowledgements

作者没有确认。

Materials

3T MR scanner Siemens Any MR scanner is acceptable. 
Olfactometer Emerging Tech Trans, LLC Any olfactometer with similar capabilities is acceptable.
6-channel odorant carrier Emerging Tech Trans, LLC
Nosepiece/applicator Emerging Tech Trans, LLC
PTFE tubing Emerging Tech Trans, LLC
TTL convertor box Emerging Tech Trans, LLC
Respiratory sensor belt Emerging Tech Trans, LLC
Lavender oil Givaudan Flavors Corporation
1,2 propanediol Sigma P6209
ONSET www.pennstatehershey.org/web/nmrlab/resources/software/onset
SPM8  Wellcome Trust Center for Neuroimaging, University College London, London, UK 
DOWNLOAD MATERIALS LIST

Referências

  1. Doty, R. L., Reyes, P. F., Gregor, T. Presence of both odor identification and detection deficits in Alzheimer’s disease. Brain Res Bull. 18 (5), 597-600 (1987).
  2. Hummel, T., et al. Olfactory FMRI in patients with Parkinson’s disease. Front Integr Neurosci. 4, 125 (2010).
  3. Mesholam, R. I., Moberg, P. J., Mahr, R. N., Doty, R. L. Olfaction in neurodegenerative disease: a meta-analysis of olfactory functioning in Alzheimer’s and Parkinson’s diseases. Arch Neurol. 55 (1), 84-90 (1998).
  4. Pause, B. M., Miranda, A., Göder, R., Aldenhoff, J. B., Ferstl, R. Reduced olfactory performance in patients with major depression. J Psychiatr Res. 35 (5), 271-277 (2001).
  5. Vasterling, J. J., Brailey, K., Sutker, P. B. Olfactory identification in combat-related posttraumatic stress disorder. J Trauma Stress. 13 (2), 241-253 (2000).
  6. Anderson, A. K., et al. Dissociated neural representations of intensity and valence in human olfaction. Nat Neurosci. 6 (2), 196-202 (2003).
  7. Gottfried, J. A., Deichmann, R., Winston, J. S., Dolan, R. J. Functional heterogeneity in human olfactory cortex: an event-related functional magnetic resonance imaging study. J Neurosci. 22 (24), 10819-10828 (2002).
  8. Sobel, N., et al. Sniffing and smelling: separate subsystems in the human olfactory cortex. Nature. 392 (6673), 282-286 (1998).
  9. Sun, X., Wang, J., Weitekamp, C. W., Yang, Q. X. A Novel Data Processing Method for Olfactory fMRI Examinations. Proc Intl Soc Mag Res Med. 18 (2010), 1161 (2010).
  10. Zatorre, R. J., Jones-Gotman, M., Evans, A. C., Meyer, E. Functional localization and lateralization of human olfactory cortex. Nature. 360 (6402), 339-340 (1992).
  11. Boley, J. C., Pontier, J. P., Smith, S., Fulbright, M. Facial changes in extraction and nonextraction patients. Angle Orthod. 68 (6), 539-546 (1998).
  12. Furman, J. M., Koizuka, I. Reorientation of poststimulus nystagmus in tilted humans. J Vestib Res. 4 (6), 421-428 (1994).
  13. Loevner, L. A., Yousem, D. M. Overlooked metastatic lesions of the occipital condyle: a missed case treasure trove. Radiographics. 17 (5), 1111-1121 (1997).
  14. Tabert, M. H., et al. Validation and optimization of statistical approaches for modeling odorant-induced fMRI signal changes in olfactory-related brain areas. Neuroimage. 34 (4), 1375-1390 (2007).
  15. Wang, J., Sun, X., Yang, Q. X. Methods for olfactory fMRI studies: Implication of respiration. Hum Brain Mapp. 35 (8), 3616-3624 (2014).
  16. Gottfried, J. A., O’Doherty, J., Dolan, R. J. Appetitive and aversive olfactory learning in humans studied using event-related functional magnetic resonance imaging. J Neurosci. 22 (24), 10829-10837 (2002).
  17. Popp, R., Sommer, M., Müller, J., Hajak, G. Olfactometry in fMRI studies: odor presentation using nasal continuous positive airway pressure. Acta Neurobiol Exp (Wars). 64 (2), 171-176 (2004).
  18. Wang, J., et al. Olfactory Habituation in the Human Brain. Proc Intl Soc Mag Res Med. 20, 2150 (2012).
  19. Grunfeld, R., et al. The responsiveness of fMRI signal to odor concentration). , A237-A238 (2005).
  20. Jia, H., et al. Functional MRI of the olfactory system in conscious dogs. PLoS One. 9 (1), e86362 (2014).
  21. Karunanayaka, P., et al. Networks involved in olfaction and their dynamics using independent component analysis and unified structural equation modeling. Hum Brain Mapp. 35 (5), 2055-2072 (2014).
  22. Royet, J. P., et al. Functional neuroanatomy of different olfactory judgments. Neuroimage. 13 (3), 506-519 (2001).
  23. Doty, R. L. Influence of age and age-related diseases on olfactory function. Ann N Y Acad Sci. 561, 76-86 (1989).
  24. Wang, J., et al. Olfactory deficit detected by fMRI in early Alzheimer’s disease. Brain Res. 1357, 184-194 (2010).
  25. Moessnang, C., et al. Altered activation patterns within the olfactory network in Parkinson’s disease. Cereb Cortex. 21 (6), 1246-1253 (2011).
  26. Vasavada, M. M., et al. Olfactory cortex degeneration in Alzheimer’s disease and mild cognitive impairment. J Alzheimers Dis. 45 (3), 947-958 (2015).
  27. Jacobs, H. I., Radua, J., Lückmann, H. C., Sack, A. T. Meta-analysis of functional network alterations in Alzheimer’s disease: toward a network biomarker. Neurosci Biobehav Rev. 37 (5), 753-765 (2013).
  28. Murphy, C., Cerf-Ducastel, B., Calhoun-Haney, R., Gilbert, P. E., Ferdon, S. ERP, fMRI and functional connectivity studies of brain response to odor in normal aging and Alzheimer’s disease. Chem Senses. 30 Suppl 1, i170-i171 (2005).
  29. Hummel, T., Kobal, G. Differences in human evoked potentials related to olfactory or trigeminal chemosensory activation. Electroen Clin Neuro. 84 (1), 84-89 (1992).
  30. Cerf-Ducastel, B., Murphy, C. FMRI brain activation in response to odors is reduced in primary olfactory areas of elderly subjects. Brain Res. 986 (1-2), 39-53 (2003).
  31. Cain, W. S. Contribution of the trigeminal nerve to perceived odor magnitude. Ann NY Acad Sci. 237, 28-34 (1974).
  32. Murphy, C., Gilmore, M. M., Seery, C. S., Salmon, D. P., Lasker, B. R. Olfactory thresholds are associated with degree of dementia in Alzheimer’s disease. Neurobiol Aging. 11 (4), 465-469 (1990).
  33. Doty, R. L., Brugger, W. E., Jurs, P. C., Orndoff, M. A., Snyder, P. J., Lowry, L. D. Intranasal trigeminal stimulation from odorous volatiles: Psychometric responses from anosmic and normal humans. Physiol Behav. 20 (2), 175-185 (1978).
  34. Kobal, G., Hummel, T. Olfactory and intranasal trigeminal event-related potentials in anosmic patients. Laryngoscope. 108 (7), 1033-1035 (1998).
  35. Frasnelli, J., Lundström, J. N., Schöpf, V., Negoias, S., Hummel, T., Lepore, F. Dual processing streams in chemosensory perception. Front Hum Neurosci. 6, (2012).
  36. Yousem, D. M., et al. Gender effects on odor-stimulated functional magnetic resonance imaging. Brain Res. 818 (2), 480-487 (1999).
  37. Koulivand, P. H., Ghadiri, M. K., Gorji, A. Lavender and the nervous system. Evid Based Compl Alt Med. 2013, (2013).
  38. Yousem, D. M., et al. Functional MR imaging during odor stimulation: Preliminary data. Neuroradiology. 204 (3), 833-838 (1997).
  39. Hummel, T., Doty, R. L., Yousem, D. M. Functional MRI of intranasal chemosensory trigeminal activation. Chem Senses. 30 (suppl. 1), i205-i206 (2005).

Tags

Keywords: FMRIOlfactory FunctionRespiration-triggered Olfactory StimulationOlfactometerOdorant ChannelsOdor PresentationEvent-related ParadigmHabituationTrigeminal StimulationHuman Olfactory System
check_url/pt/54898?article_type=t

Play Video
PDF
DOI
DOWNLOAD MATERIALS LIST
Citar este artigo
Wang, J., Rupprecht, S., Sun, X., Freiberg, D., Crowell, C., Cartisano, E., Vasavada, M., Yang, Q. X. A Free-breathing fMRI Method to Study Human Olfactory Function. J. Vis. Exp. (125), e54898, doi:10.3791/54898 (2017).
Baixar citação
Reimpressões e Permissões

View Video

✖

To prove you're not a robot, please enter the text in the image below

CAPTCHA Image
Play CAPTCHA Audio
Refresh Image