Name: a free-breathing fmri method to study human olfactory function
Uploaded: 2017-07-30T13:00:00
Description: Watch this Scientific Journal Video about A Free-breathing fMRI Method to Study Human Olfactory Function at JoVE.com

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以下の実験プロトコールは、ペンシルバニア州立大学医科大学のInstitutional Review Boardのガイドラインに従っており、ヒト被験者は研究に参加する前に書面による同意を得た。 注意：デモンストレーションの目的のために、市販のMRIコンパチブルオルファクトメーターを用いた簡単な臭い刺激のパラダイムを提示する。このパラダイムは習慣化効果を低下させるのに有効で...

<ol>
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P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Functional+neuroanatomy+of+different+olfactory+judgments.">Functional neuroanatomy of different olfactory judgments.</a> Neuroimage. 13 (3), 506-519 (2001).</li><li>Doty, R. 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実験手順は、信頼できる嗅覚活性化データを収集するために慎重に検討し、適切に実施すべきである。プロトコル内の重要なステップには、臭気の伝達を画像取得と同期させるための呼吸トリガのパラダイムの実装、精神物理応答の制御のための臭気物質の適切な濃度の準備、安定した呼吸信号と一定の空気流を伴う嗅覚器の設定、 ONSETを使用して臭気開始ベクトルを遡及的に調整するため?...

人間の嗅覚系は、嗅覚が恒常性の調節および感情においても重要な役割を果たすため、感覚系以上のものであると理解されている。臨床的には、人間の嗅覚系は、アルツハイマー病、パーキンソン病、心的外傷後ストレス障害、およびうつ病1、2、3、4、5のように多くの流行の神経疾患や精神疾患の攻撃に対して脆弱であることが知られています。現在、血液酸素レベル依存性（BOLD）コントラストを有する機能的磁気共鳴イメージング（fMRI）は、人間の脳の機能をマッピングするための最も貴重な技術である。この技術により、中心嗅覚構造（ 例えば 、梨状皮質、眼窩前頭皮質、扁桃体、膵島皮質）の特定の機能に関する重要な知識が得られているIQUE 6、7、8、9、10。 しかしながら、ヒトの中枢嗅覚系および関連疾患の研究へのfMRIの適用は、BOLDシグナルの迅速な慣れと呼吸による可変調節という2つの主要な障害によって妨げられている。日常生活では、一定期間において匂いに曝されると、すぐに香りに慣れます。嗅覚のfMRIを用いて調べたときに、実際には、臭い誘発性のfMRI信号が急速に刺激パラダイムデザイン8、10、11、12、13、14上の課題を提起慣れによって減衰されます。一次嗅覚野の初期の有意なBOLDシグナルは持続するだけである臭いが発症してから数秒間。したがって、嗅覚的fMRIパラダイムは、短期間で長期または頻繁な匂い刺激を避けるべきである。習慣化効果を減少させるために、fMRIパラダイムに交互の臭気を提示する試みがいくつかなされている。しかしながら、このアプローチは、各付臭剤が独立した刺激事象として扱われることができるので、データ解析を複雑にする可能性がある。 被験者の呼吸パターンにばらつきがある場合、別の技術的問題が生じる。固定タイミングのパラダイムの間に、匂いの投与と吸入が常に同期するとは限りません。嗅覚刺激の発症および持続時間は、個々の呼吸によって調節され、fMRIデータの質および分析を混乱させる。いくつかの研究では、呼吸と匂いの発症を同期させるための視覚的または聴覚的手がかりを用いてこの問題を緩和しようと試みたが、被験者のコンプライアンスは特に臨床集団において変動する。 wiに関連する脳活性化特定のアプリケーションでは、これらの手がかりもデータ分析を複雑にする可能性があります。したがって、臭気物質送達と吸入を同期させることは、嗅覚fMRI研究15にとって重要であり得る。 嗅覚fMRIに不可欠な追加の考慮事項、特にデータ分析プロセスでは、匂い選択が重要です。認識された強度に関して適切なニオイ物質の濃度を見つけることは、様々な実験条件または疾患の下での脳における活性化レベルの定量化および比較のために重要である。また、匂いの選択は、匂いの価数や心地よさを考慮しなければならない。これは嗅覚学習16、17で発散時間プロファイルを引き起こすことが知られています。この理由から、このデモンストレーションではラベンダーの香りが部分的に選択されました。特定の研究の目的に応じて、異なる匂い物質がより良い選択肢になる可能性があります。さらに、三叉神経刺激を最小限に抑えて、直接的に嗅覚に関連しない活性化18 。 この報告では、磁気共鳴環境において嗅覚計を用いて呼吸によって引き起こされるパラダイムを設定し実行するためのfMRI技術を実証する。また、データ収集中に発生したタイミングエラーを減らし、データ分析をさらに改善するためのポスト処理ツールも提供しています。

<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>
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a free-breathing fmri method to study human olfactory function

ヒトの嗅覚の研究は、生物医学的研究から臨床評価までの応用分野を持つ非常に複雑で貴重な分野です。現在、機能的磁気共鳴イメージング（fMRI）を用いたヒト中心嗅覚システムの機能の評価は、いくつかの技術的困難のために依然として課題である。適切な匂い選択、匂い提示と呼吸との相互作用、および匂い物質への潜在的期待または慣れを含む、fMRIを用いた中枢嗅覚システムの機能をマッピングするための効果的な方法を検討する際に考慮すべきいくつかの重要な変数がある。事象に関連した、呼吸によって誘発される嗅覚fMRI技術は、潜在的な干渉を最小限に抑えながら臭い物質を正確に投与して嗅覚系を刺激することができる。我々のデータ後処理法を用いて、原発性嗅覚野におけるfMRI信号の正確なオンセットを効果的に捕捉することができる。テクニック・プレ信頼できる嗅覚fMRIの結果を得るための効率的で実用的な手段を提供する。そのような技術は、アルツハイマー病およびパーキンソン病を含む嗅覚変性に関連する疾患の診断ツールとして臨床領域で最終的に適用することができ、ヒトの嗅覚系の複雑さをさらに理解し始める。

図1は、MR-適合性を考慮して、磁石室の内部および外部の嗅覚fMRIのセットアップを示す。 図2aは標準的な固定タイミングパラダイムを示し、 図2bは「呼吸トリガ」が臭気の送達と吸入の同期を可能にするパラダイムを示す 。 明確な?...

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

我々は、人間の中心嗅覚系から信頼できる機能的磁気共鳴イメージング（fMRI）データを得るための技術的課題と解決策を提示する。これには、嗅覚fMRIパラダイム設計における特別な考慮事項、MRI適合オルファクトメーターによるfMRIデータ収集、匂い選択、およびデータ後処理のための特別なソフトウェアツールの記述が含まれる。

ヒトの嗅覚機能を研究する自由呼吸fMRI法

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

デフォルトモードのネットワークを検査する経頭蓋磁気刺激とfMRIを組み合わせ

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 ...

神経科学

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

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

嗅神経細胞のレンチウイルスを介した遺伝子操作と可視化 in vivoで</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

人間の前頭前野皮質からfMRI信号への行動応答の相関：タスク分析を用いた認知プロセスを調べる

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

fMRIと拡散強調画像を用いた脳の構造と機能の同時分析

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

レーザーキャプチャーマイクロダイセクションで鼻生検併用して得られた嗅覚ニューロン：精神疾患における治療応答を研究するために潜在的なアプローチ

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

モデルとしての嗅覚系は、軸索の成長パターンと形態を研究する<em&gt;インビボ</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

管理のリアルタイム fMRI ニューロフィード バック トレーニングのプロトコル

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

味覚コーディングを研究する新しい方法

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

嗅覚ニューロンの光刺激に対する応答のショウジョウバエ幼虫の行動を追跡

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

坐骨神経クラッシュ損傷のラットモデルにおける機能的評価のための3D運動学的解析

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