Name: a free-breathing fmri method to study human olfactory function
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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?...

<ol>
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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?...

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。

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>3T MR scanner</td>
			<td>Siemens</td>
			<td></td>
			<td>Any MR scanner is acceptable.&#160;</td>
		</tr>
		<tr>
			<td>Olfactometer</td>
			<td>Emerging Tech Trans, LLC</td>
			<td></td>
			<td>Any olfactometer with similar capabilities is acceptable.</td>
		</tr>
		<tr>
			<td>6-channel odorant carrier</td>
			<td>Emerging Tech Trans, LLC</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Nosepiece/applicator</td>
			<td>Emerging Tech Trans, LLC</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>PTFE tubing</td>
			<td>Emerging Tech Trans, LLC</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>TTL convertor box</td>
			<td>Emerging Tech Trans, LLC</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Respiratory sensor belt</td>
			<td>Emerging Tech Trans, LLC</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Lavender oil</td>
			<td>Givaudan Flavors Corporation</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>1,2 propanediol</td>
			<td>Sigma</td>
			<td>P6209</td>
			<td></td>
		</tr>
		<tr>
			<td>ONSET</td>
			<td></td>
			<td></td>
			<td>www.pennstatehershey.org/web/nmrlab/resources/software/onset</td>
		</tr>
		<tr>
			<td>SPM8&#160;</td>
			<td>Wellcome Trust Center for Neuroimaging, University College London, London, UK&#160;</td>
			<td></td>
			<td></td>
		</tr>
	</tbody>
</table>

a free-breathing fmri method to study human olfactory function

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。

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?...

Watch this Scientific Journal Video about A Free-breathing fMRI Method to Study Human Olfactory Function at JoVE.com

A Free-breathing fMRI Method to Study Human Olfactory Function

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。

一种免费呼吸功能磁共振成像方法研究人类嗅觉功能

The study of human olfaction is a highly complex and valuable field with applications ranging from biomedical research to clinical evaluation. Currently, ...

The overall goal of this video is to present and explain an efficient and easily adaptable method of fMRI in order to effectively explore the mapping of the human olfactory system without interference of natural breathing. One obstacle of using olfactory fMRI to study the brain activation responding to odor and stimulation, is the inconsistency of repetitive odor stimulation, which is caused by the asynchrony of respiration and odor delivery. As illustrated here, when the odor presentation in a fixed timing odor stimulation paradigm is not synchronized with respiration, the repetitive odor stimulation can happen at different phases of respiration.A solution to this problem is to set up a respiration-triggered olfactory fMRI paradigm. Effective olfactory fMRI data collection is accomplished by first designing an event related respiration-triggered olfactory stimulation paradigm on the olfactometer that is resist to habituation and inconsistent inhalation patterns. The second step is to prepare odorants for the olfactory stimulation, taking care to use odorants that minimize trigeminal stimulation and habituation effects.The third step is to set up and run the experiment in the MRI environment by assembling the olfactometer with the capability of running a respiration-triggered paradigm. The final step is to process the data using the program ONSET to define the actual onset and the duration vectors of the stimuli. Ultimately, this technique has the potential to facilitate more sensitive exploration and connections of the human olfactory system.Here, we will demonstrate how to set up a respiration-triggered olfactory fMRI experiment using an ETT Olfactometer. To create a paradigm, assign the odorant channels to specific odorants. There are six odorant channels available in this olfactometer system.Input and edit the sequence and timing of open and close of these channels. Push the Paradigm Setting button on the touchscreen. To input or edit the sequence of the open and close of the odorant channels, push the Edit button for the Valve Sequence.When finished, push the Edit button again to exit the editing mode. To input or edit the timing parameters for the open and close of the odorant channels, push the Set button for Time Sequence. When finished, push the Set button again to exit the editing mode.After finishing the Paradigm Setting, push the Return button to return to the main window. Demonstrated in this video is a simple stimulation paradigm of the same odorant in the same concentration. Each odorant presentation is interleaved with the presentation of fresh air.In this paradigm, the same odor is presented 12 times. Each time, the odorant presentation lasts for six seconds with variable amounts of time between the odor presentations. Set the Valve Open and Valve Close durations, accordingly.In this demonstration, one concentration of lavender oil is prepared. We use lavender oil because of its minimal trigeminal stimulation and activation of certain brain areas. The odorant concentrations can be varied depending on the odorant selected.Choose the concentrations based upon the ideal perception threshold of the odor. By varying the concentration, we lessen the likelihood of habituation to an odorant. To prepare the concentrations, mix the lavender oil with propylene glycol.Propylene glycol is a commonly used solvent for odorants and is stable and nearly odorless. After mixing all solutions as outlined in the paradigm design, pour the same amount of odorants into each container bottle. Then, attach the bottles to the odorant carrier in the correct order.To set up the olfactometer in the MRI, place the odorant carrier in the magnet room next to the machine. Run the tubes through the wave guide to connect to the carrier, taking care that the order of tubes matches the order connecting to the olfactometer. For ease, we color code our tubings to match the odorant channels.Turn the machine on. Adjust the main airflow, as necessary, as well as the individual flow rates for the carrier and flush. Then, connect the respiration belt to the olfactometer and run the belt through the wave guide.The belt will record the subject's respiration activity, as well as the utilization of the respiration trigger. Bring the subject into the magnet room and place the face mask on the subject. When the subject is lying down, place the respiratory belt around their chest or abdomen where there is clear respiration event.Check the respiration pattern on the screen of the olfactometer. If the waves plateau, the belt is fastened too tightly and the respiration trigger will not work properly. Adjust the belt until a complete respiration trace can be seen, as clear respiration peak signals are critical for a successful execution of a respiration-triggered paradigm.Create a data folder on the olfactometer to store the respiration data. The synchrony of the odor presentation with respiration should be tested for accuracy by using the Paradigm Check and adjusting the Trigger Delay time, as necessary. Push the Paradigm Check button on the touchscreen and monitor if odor delivery happens during the inhalation phase of the respiration cycle.The odor delivery period is highlighted in the color pink on the respiration trace. If odor delivery starts during the exhalation phase, to back to Paradigm Setting, adjust the Trigger Delay in the time sequence and then redo the Paradigm Check. Set the paradigm to Trigger In mode so that the execution of the odor stimulation paradigm will be triggered by MRI scanning.Then select the Respiration Trigger Start function. The paradigm is now ready to be run. Once the odor stimulation paradigm is completed, check the respiration data saved in the olfactometer.This file includes the respiration trace and the time stamp of each functional MRI image, respiration trigger, open and close of each odor channel, and the subject response, using a response device. It can be processed using the program ONSET to acquire the actual stimulation onset vectors and durations for fMRI data processing. ONSET can be run in the IDL Virtual Machine.To get the odor stimulation onset vectors and durations, click Respiration Validation. Load the respiration data file that's saved from the olfactometer and set the post processing parameters for ONSET processing. Run ONSET.The actual stimulation onset vectors, the start of each inhalation during odor delivery, will automatically be detected based on the timing of odor presentation and the respiration trace. The results, including the onset and duration vectors, can be utilized in fMRI data processing. Process the fMRI data following standard procedures.Here is an example of data processing using SPM8. Use either the image numbers or the onset vectors and durations in seconds from the onset output, depending on the timing unit chosen for the SPM paradigm design. Generate a statistical parametric map at the individual level by fitting the stimulation paradigm using the actual onset and duration vectors to the functional data with the canonical hemodynamic response function.Here is an example of the primary olfactory cortex activation responding to the odor stimulation. In contrast to the respiration-triggered odor stimulation paradigm, for example, a fixed timing paradigm which we can see here from the same subject, the odor delivery is not triggered by respiration activity. Since there is no control of the subject's respiration, there is significant variability in the amount of odorant that is inhaled.Following the standard procedure to process these fMRI data with the same statistical threshold as that used for the previous respiration-triggered fMRI data, no significant activation was detected in the primary olfactory cortex. However, when a respiration trigger is implemented, odorant presentation is always synchronized with inhalation, improving the consistency and accuracy of odor stimulation. After watching this video, you should have a good understanding of the current practice of olfactory fMRI using an event related respiration-triggered paradigm.Once the technique demonstrated in this video has been mastered, further olfactory stimulation paradigm design and analysis methods can be applied to map the functions of the human central olfactory system and to further explore the olfactory deficits in neurodegenerative diseases.

Research

JoVE Journal

Neuroscience

Combining Transcranial Magnetic Stimulation and fMRI to Examine the Default Mode Network

结合经颅磁刺激和功能磁共振成像检查默认模式网络

The default mode network is a group of brain regions that are active when an individual is not focused on the outside world and the brain is at "wakeful ...

科研

神经科学

Lentivirus-mediated Genetic Manipulation and Visualization of Olfactory Sensory Neurons in vivo

Lentivirus-mediated Genetic Manipulation and Visualization of Olfactory Sensory Neurons in vivo

嗅觉感官神经元的慢病毒介导的遗传操作和可视化在体内</em

Development of a precise olfactory circuit relies on accurate projection of olfactory sensory neuron (OSN) axons to their synaptic 
targets in the ...

Correlating Behavioral Responses to fMRI Signals from Human Prefrontal Cortex: Examining Cognitive Processes Using Task Analysis

关联从人类前额叶皮层的fMRI信号的行为反应：检查的认知过程，使用任务分析

The aim of this methods paper is to describe how to implement a neuroimaging technique to examine complementary brain processes engaged by two similar ...

Co-analysis of Brain Structure and Function using fMRI and Diffusion-weighted Imaging

使用功能磁共振成像和弥散加权成像脑结构与功能分析

The study of complex computational systems is facilitated by network maps, such as circuit diagrams. Such mapping is particularly informative when ...

Olfactory Neurons Obtained through Nasal Biopsy Combined with Laser-Capture Microdissection: A Potential Approach to Study Treatment Response in Mental Disorders

通过鼻腔活检获得联合激光捕获显微切割的嗅觉神经元：一种可能的方法来研究治疗反应的精神障碍

Bipolar disorder (BD) is a severe neuropsychiatric disorder with poorly understood pathophysiology and typically treated with the mood stabilizer, lithium ...

The Olfactory System as a Model to Study Axonal Growth Patterns and Morphology In Vivo

The Olfactory System as a Model to Study Axonal Growth Patterns and Morphology In Vivo

嗅觉系统作为模型来研究轴突生长的模式和形态<em&gt;在体内</em

The olfactory system has the unusual capacity to generate new neurons throughout the lifetime of an organism. Olfactory stem cells in the basal portion of ...

A Protocol for the Administration of Real-Time fMRI Neurofeedback Training

实时 fMRI 神经训练管理协议

Neurologic disorders are characterized by abnormal cellular-, molecular-, and circuit-level functions in the brain. New methods to induce and control ...

New Methods to Study Gustatory Coding

研究风味编码的新方法

The sense of taste allows animals to detect chemicals in the environment, giving rise to behaviors critical for survival. When Gustatory Receptor Neurons ...

Tracking Drosophila Larval Behavior in Response to Optogenetic Stimulation of Olfactory Neurons

Tracking Drosophila Larval Behavior in Response to Optogenetic Stimulation of Olfactory Neurons

跟踪果蝇幼虫行为对嗅神经元 Optogenetic 刺激的反应

The ability of insects to navigate toward odor sources is based on the activities of their first-order olfactory receptor neurons (ORNs). While a ...

3D Kinematic Analysis for the Functional Evaluation in the Rat Model of Sciatic Nerve Crush Injury

坐骨神经粉碎损伤大鼠模型中功能评估的3D运动学分析

Compared to the Sciatic Functional Index (SFI), kinematic analysis is a more reliable and sensitive method for performing functional evaluations of ...