Name: a free-breathing fmri method to study human olfactory function
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Das folgende experimentelle Protokoll folgte den Richtlinien des Institutional Review Board der Pennsylvania State University College of Medicine, und das menschliche Subjekt gab schriftlich informierte Zustimmung vor der Teilnahme an der Studie. Anmerkung: Zur Demonstration wird ein einfaches Geruchsstimulations-Paradigma mit einem handelsüblichen MRI-kompatiblen Olfaktometer vorgestellt. Dieses Paradigma hat sich bewährt bei der Verringerung der Gewöhnungseffekt und hat zuverlässige ol...

<ol>
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Experimentelle Verfahren sollten sorgfältig geprüft und ordnungsgemäß für die Erfassung von zuverlässigen olfaktorischen Aktivierungsdaten durchgeführt werden. Die kritischen Schritte innerhalb des Protokolls beinhalten die Implementierung eines respirationsgesteuerten Paradigmas zur Synchronisation der Geruchsabgabe mit der Bilderfassung, die Vorbereitung geeigneter Konzentrationen von Geruchsstoffen zur Kontrolle psychophysikalischer Reaktionen, die Einrichtung des Olfaktometers mit zuverlässigem stabilen Atmu...

Das menschliche olfaktorische System wird viel mehr als ein sensorisches System verstanden, da die Orangenheit auch eine wichtige Rolle bei der homöostatischen Regulation und Emotionen spielt. Klinisch ist bekannt, dass das menschliche olfaktorische System anfällig für Angriffe vieler vorherrschender neurologischer Erkrankungen und psychiatrischer Erkrankungen wie Alzheimer-Krankheit, Parkinson-Krankheit, posttraumatischer Belastungsstörung und Depression 1 , 2 , 3 , 4 , 5 ist . Derzeit ist die funktionelle Magnetresonanztomographie (fMRI) mit dem Blut-Sauerstoff-Niveau-abhängigen (BOLD) -Kontrast die wertvollste Technik für die Abbildung von Funktionen des menschlichen Gehirns. In dieser Technik wurde ein erheblicher Wissenswert über spezifische Funktionen zentraler olfaktorischer Strukturen ( zB piriforme Kortex, orbitofrontale Kortex, Amygdala und Inselrinde) erworbenIque 6 , 7 , 8 , 9 , 10 Die Anwendung von fMRI auf Studien des menschlichen zentralen olfaktorischen Systems und damit verbundenen Krankheiten wurde jedoch durch zwei große Hindernisse behindert: schnelle Gewöhnung des BOLD-Signals und variable Modulation durch Atmung. Im Alltag, wenn sie für einen Zeitraum von einem Riechstoff ausgesetzt sind, haben wir schnell den Duft gewohnt. In der Tat, wenn man mit olfaktorischem fMRI studiert, wird das geruchsinduzierte fMRI-Signal durch Gewöhnung schnell abgeschwächt, was eine Herausforderung für die Stimulations-Paradigmen-Designs 8 , 10 , 11 , 12 , 13 , 14 darstellt . Das anfängliche signifikante BOLD-Signal im primären olfaktorischen Kortex bleibt nur bestehenS für einige Sekunden nach dem geruchlichen Beginn. Daher sollten olfaktorische fMRI-Paradigmen längere oder häufige Geruchsstimulationen in kurzer Zeit vermeiden. Um den Gewöhnungseffekt zu reduzieren, haben einige Studien versucht, abwechselnde Gerüche in einem fMRI-Paradigma zu präsentieren. Dieser Ansatz kann jedoch die Datenanalyse erschweren, da jedes Odorant als ein unabhängiges Stimulationsereignis behandelt werden kann. Ein weiteres technisches Problem ergibt sich aus der Variabilität der Atmungsmuster der Subjekte; Inhalation synchronisiert sich nicht immer mit einer geruchlosen Verabreichung während eines Festzeit-Paradigmas. Der Beginn und die Dauer der olfaktorischen Stimulation werden durch die Atmung jedes Individuums moduliert, was die Datenqualität und -analyse von fMRI verwechselt. Einige Studien haben versucht, dieses Problem mit visuellen oder auditiven Stichwörtern zu mildern, um Atmung und Geruchsbefall zu synchronisieren, aber die Einhaltung von Themen ist variabel, vor allem in der klinischen Population. Die Gehirnaktivierungen assoziiert wiDiese Cues könnten auch die Datenanalyse in bestimmten Anwendungen komplizieren. Somit kann die Synchronisierung Inhalation mit Riechstoff Lieferung von entscheidenden Bedeutung seines für olfaktorischen fMRI 15 Studien. Eine zusätzliche Betrachtung, die für das olfaktorische fMRI entscheidend ist, insbesondere im Datenanalyseverfahren, ist eine Geruchsauswahl. Die Suche nach einer geeigneten Odorierungskonzentration in Bezug auf die wahrgenommene Intensität ist wichtig für die Quantifizierung und den Vergleich von Aktivierungsniveaus im Gehirn unter verschiedenen experimentellen Bedingungen oder Krankheiten. Die Geruchsauswahl muss auch die Geruchsvalenz oder die Annehmlichkeit berücksichtigen. Dies ist bekannt, um divergierende zeitliche Profile im olfaktorischen Lernen 16 , 17 zu verursachen . Lavendelgeruch wurde für diese Demonstration teilweise aus diesem Grund gewählt. Je nach dem Zweck einer bestimmten Studie können verschiedene Geruchsstoffe bessere Entscheidungen treffen. Darüber hinaus muss die Trigeminusstimulation minimiert werden, um zu reduzierenE Aktivierung nicht direkt mit der Auflösung verknüpft 18 . In diesem Bericht zeigen wir eine fMRI-Technik zur Einrichtung und Durchführung eines respirationsgesteuerten Paradigmas mit einem Olfaktometer in der Magnetresonanzumgebung. Wir stellen auch ein Nachbearbeitungswerkzeug vor, das einige Zeitfehler beeinträchtigen kann, die bei der Datenerfassung aufgetreten sind, um die Datenanalyse weiter zu verbessern.

<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

Das Studium der menschlichen Olfusion ist ein hochkomplexes und wertvolles Feld mit Anwendungen von der biomedizinischen Forschung bis zur klinischen Evaluation. Derzeit ist die Auswertung der Funktionen des menschlichen zentralen olfaktorischen Systems mit funktioneller Magnetresonanztomographie (fMRI) aufgrund vieler technischer Schwierigkeiten immer noch eine Herausforderung. Es gibt einige signifikante Variablen, die bei der Betrachtung einer wirksamen Methode zur Abbildung der Funktion des zentralen olfaktorischen Systems unter Verwendung von fMRI berücksichtigt werden, einschließlich der richtigen Odorantauswahl, der Wechselwirkung zwischen Geruchsdarstellung und Atmung und der möglichen Vorwegnahme oder Gewöhnung an Geruchsstoffe. Eine ereignisbezogene, atmungsgesteuerte olfaktorische fMRI-Technik kann die Geruchsstoffe genau anregen, um das olfaktorische System zu stimulieren und gleichzeitig mögliche Störungen zu minimieren. Es kann effektiv die genauen Onsets von fMRI-Signalen in der primären olfaktorischen Kortex mit unserer Daten nach der Verarbeitung Methode zu erfassen. Die Technik vorHier finden Sie ein effizientes und praktisches Mittel zur Erstellung zuverlässiger olfaktorischer fMRI-Ergebnisse. Eine solche Technik kann letztlich im klinischen Bereich als diagnostisches Werkzeug für Krankheiten angewendet werden, die mit einer olfaktorischen Degeneration, einschließlich der Alzheimer- und Parkinson-Krankheit, verbunden sind, da wir beginnen, die Komplexität des menschlichen Geruchsystems weiter zu verstehen.

Abbildung 1 zeigt den Aufbau von olfaktorischen fMRI innerhalb und außerhalb des Magnetraums unter Berücksichtigung der MR-Kompatibilität. Abbildung 2a zeigt ein standardmäßiges Festzeit-Paradigma, während Abbildung 2b ein Paradigma zeigt, in dem der &quot;Atmungsauslöser&quot; die Synchronisation der Geruchsabgabe und des Inhalierens ermöglicht. <p class="jove_content" fo:keep-together....

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

Wir stellen die technischen Herausforderungen und Lösungen für den Erhalt zuverlässiger funktioneller Magnetresonanztomographie (fMRI) Daten aus dem menschlichen zentralen olfaktorischen System vor. Dazu gehören besondere Überlegungen im olfaktorischen fMRI-Paradigmen-Design, Beschreibungen der fMRI-Datenerfassung mit einem MRI-kompatiblen Olfaktometer, Odorant-Auswahl und einem speziellen Software-Tool für die Daten-Nachbearbeitung.

Eine frei atmende fMRI-Methode zur Untersuchung der menschlichen olfaktorischen Funktion

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

Die Kombination TMS und fMRT dem Standard-Modus Netzwerk Untersuchen

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 ...

Forschung

Neurowissenschaften

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

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

Lentivirus-vermittelte Gen-Manipulation und Visualisierung von Riechzellen In vivo</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

Korrelation von Verhaltensreaktionen auf fMRI Signalen von Human präfrontalen Kortex: Untersuchung kognitiver Prozesse mit dem Task Analysis

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

Co-Analyse von Hirnstruktur und-funktion mittels fMRT und Diffusionsgewichtete Imaging

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

Riechzellen durch nasale Biopsie Combined Erhalten mit Laser-Mikrodissektion: Ein möglicher Ansatz zum Behandlungserfolg bei Mental Disorders Studieren

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

Das olfaktorische System als Modell zur Axonal Wachstumsmuster und Morphologie Studieren<em&gt; In Vivo</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

Ein Protokoll für die Verwaltung von Real-Time-fMRT Neurofeedback Training

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

Neue Methoden zum Studieren der Gustatory Coding

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

Tracking von Drosophila Larven Verhalten als Reaktion auf optogenetische Stimulation der olfaktorischen Neuronen

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

3D Kinematische Analyse zur funktionellen Bewertung im Rattenmodell von Ischias-Nerven-Crush-Verletzungen

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