Summary

Functionele Beeldvorming van de auditieve cortex in volwassen katten met behulp van High-field fMRI

Published: February 19, 2014
doi:

Summary

Functional studies of the auditory system in mammals have traditionally been conducted using spatially-focused techniques such as electrophysiological recordings. The following protocol describes a method of visualizing large-scale patterns of evoked hemodynamic activity in the cat auditory cortex using functional magnetic resonance imaging.

Abstract

De huidige kennis van sensorische verwerking in het auditief systeem van zoogdieren is voornamelijk afkomstig van elektrofysiologische studies in verschillende diermodellen, zoals apen, fretten, knuppels, knaagdieren en katten. Om geschikte parallellen tussen menselijke en dierlijke modellen van gehoorfunctie trekken, is het belangrijk om een ​​brug tussen menselijke functionele beeldvorming studies en dierlijke elektrofysiologische studies stellen. Functionele magnetische resonantie imaging (fMRI) is een gevestigde, minimaal invasieve methode voor het meten brede patronen van hemodynamische activiteit in verschillende gebieden van de cerebrale cortex. Deze techniek wordt veel gebruikt voor sensorische functie in het menselijk brein sonde is een nuttig instrument koppelen studies auditieve verwerking bij mens en dier en is met succes gebruikt om gehoorfunctie bij apen en knaagdieren onderzoeken. Het volgende protocol beschrijft een experimentele procedure voor het onderzoeken van auditieve functie in verdoofde volwassenkatten door het meten-stimulus opgeroepen hemodynamische veranderingen in de auditieve cortex met behulp van fMRI. Deze methode maakt vergelijking van de hemodynamische responsen in verschillende modellen gehoorfunctie hetgeen leidt tot een beter begrip van species-onafhankelijke eigenschappen van de zoogdieren auditieve cortex.

Introduction

Current understanding of auditory processing in mammals is mainly derived from invasive electrophysiological studies in monkeys1-5, ferrets6-10, bats11-14, rodents15-19, and cats20-24. Electrophysiological techniques commonly utilize extracellular microelectrodes to record the activity of single and multiple neurons within a small area of neural tissue surrounding the electrode tip. Established functional imaging methods, such as optical imaging and functional magnetic resonance imaging (fMRI), serve as useful complements to extracellular recordings by providing a macroscopic perspective of simultaneous driven activity across multiple, spatially distinct regions of the brain. Intrinsic signal optical imaging facilitates visualization of evoked activity in the brain by measuring activity-related changes in the reflectance properties of surface tissue while fMRI utilizes the blood-oxygen level-dependent (BOLD) contrast to measure stimulus-evoked hemodynamic changes in brain regions which are active during a particular task. Optical imaging requires direct exposure of the cortical surface to measures changes in surface tissue reflectance that are related to stimulus-evoked activity25. In comparison, fMRI is noninvasive and exploits the paramagnetic properties of deoxygenated blood to measure both cortical surface26-28 and sulcus-based27,29 evoked activity within an intact skull. Strong correlations between the BOLD signal and neuronal activity in nonhuman primate visual cortex30 and in human auditory cortex31 validate fMRI as a useful tool to study sensory function. Since fMRI has been used extensively to study features of the auditory pathway such as tonotopic organization32-36, lateralization of auditory function37, patterns of cortical activation, identification of cortical regions38, effects of sound intensity on auditory response properties39,40, and characteristics of the BOLD response time course29,41 in human, monkey, and rat models, the development of a suitable functional imaging protocol to study auditory function in the cat would provide a useful complement to the functional imaging literature. While fMRI has also been used to explore various functional aspects of the visual cortex in the anesthetized cat26-28,42, few studies have used this technique to examine sensory processing in cat auditory cortex. The purpose of the present protocol is to establish an effective method of using fMRI to quantify function in the auditory cortex of the anesthetized cat. The experimental procedures outlined in this manuscript have been successfully used to describe the features of the BOLD response time course in the adult cat auditory cortex43.

Protocol

The following procedure can be applied to any imaging experiment in which anesthetized cats are used. Steps which are specifically required for auditory experiments (steps 1.1-1.7, 2.8, 4.1) can be modified to accommodate other sensory stimulus protocols. All experimental procedures received approval from the Animal Use Subcommittee of the University Council on Animal Care at the University of Western Ontario and followed the guidelines specified by the Canadian Council on Animal Care (CCAC)<s…

Representative Results

Representative functional data were acquired in a 7T horizontal bore scanner and analyzed using the Statistical Parametric Mapping toolbox in MATLAB. Robust cortical hemodynamic responses to auditory stimulation have consistently been observed in cats using the described experimental protocol43. Figure 6 illustrates the BOLD activation in 2 animals in response to a 30 sec broadband noise stimulus presented in a block design. T-statistic maps of the broadband noise vs. baseline (no stimulus) co…

Discussion

In designing an fMRI experiment for an anesthetized animal model of auditory function, the following issues should be given careful consideration: (i) the impact of anesthesia on cortical responses, (ii) the effect of background scanner noise, and (iii) the optimization of the data collection phase of the experimental procedure.

While an anesthetized preparation offers the important advantage of producing a prolonged period of sedation and minimizing potential head motion during a functional i…

Declarações

The authors have nothing to disclose.

Acknowledgements

The authors would like to acknowledge the contributions of Kyle Gilbert, who designed the custom RF coil, and Kevin Barker, who designed the MRI-compatible sled. This work was supported by the Canadian Institutes of Health Research (CIHR), Natural Sciences and Engineering Research Council of Canada (NSERC), and Canada Foundation for Innovation (CFI).

Materials

Material
Atropine sulphate injection 0.5 mg/mL Rafter 8 Products
Acepromazine 5 mg/mL Vetoquinol Inc.
Ketamine hydrochloride 100 mg/mL Bimeda-MTC
Dexmedetomidine hydrochloride (Dexdomitor 0.5 mg/mL) Orion Pharma
Isoflurane 99.9% Abbott Laboratories
Lidocaine (Xylocaine endotracheal 10 mg/metered dose) Astra Zeneca
Lubricating opthalmic ointment (Refresh Lacri Lube) Allergan Inc.
Saline 0.95%
IV Catheter 22g (wings)
IV Extension Set Codan US Corp. BC 269
IV Administration Set 10 drips/mL
Endotracheal tube 4.0
Heating pads (Snuggle Safe) Lenric C21 Ltd.
Syringe 60 mL
Equipment
External sound card Roland Corporation Cakewalk UA-25EX
Stereo power amplifier Pyle Audio Inc. Pyle Pro PCAU11
MRI-compatible insert earphone system Sensimetric Corporation Model S14
Foam ear tips for insert earphones E-A-R Auditory Systems Earlink 3B
End-tidal CO2 monitor Nellcor  N-85
MRI-compatible pulse oximeter Nonin Medical Inc. Model 7500
Syringe pump Harvard Apparatus 70-2208

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Brown, T. A., Gati, J. S., Hughes, S. M., Nixon, P. L., Menon, R. S., Lomber, S. G. Functional Imaging of Auditory Cortex in Adult Cats using High-field fMRI. J. Vis. Exp. (84), e50872, doi:10.3791/50872 (2014).

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