Visualization of the auditory pathway in rats with 18F-FDG PET activation studies based on different auditory stimuli and reference conditions including cochlea ablation.

Martin Mamach,Jens P Bankstahl,Lilli Geworski,Mariella Kessler,Frank M Bengel,Florian Wilke,Simone Kurt,Georg Berding,Manuel S Malmierca

doi:10.1371/journal.pone.0205044

Martin Mamach, Jens P Bankstahl + Show 7 more

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https://doi.org/10.1371/journal.pone.0205044

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Journal: PloS one	Publication Date: Oct 2, 2018
Citations: 2	License type: CC BY 4.0

Affiliation: Hannover Medical School, Hearing4all, Saarland University

Abstract

Activation studies with positron emission tomography (PET) in auditory implant users explained some of the mechanisms underlying the variability of achieved speech comprehension. Since future developments of auditory implants will include studies in rodents, we aimed to inversely translate functional PET imaging to rats. In normal hearing rats, activity in auditory and non-auditory regions was studied using 18F-fluorodeoxyglucose (18F-FDG) PET with 3 different acoustic conditions: sound attenuated laboratory background, continuous white noise and rippled noise. Additionally, bilateral cochlea ablated animals were scanned. 3D image data were transferred into a stereotaxic standard space and evaluated using volume of interest (VOI) analyses and statistical parametric mapping (SPM). In normal hearing rats alongside the auditory pathway consistent activations of the nucleus cochlearis (NC), olivary complex (OC) and inferior colliculus (IC) were seen comparing stimuli with background. In this respect, no increased activation could be detected in the auditory cortex (AC), which even showed deactivation with white noise stimulation. Nevertheless, higher activity in the AC in normal hearing rats was observed for all 3 auditory conditions against the cochlea ablated status. Vice versa, in ablated status activity in the olfactory nucleus (ON) was higher compared to all auditory conditions in normal hearing rats. Our results indicate that activations can be demonstrated in normal hearing animals based on 18F-FDG PET in nuclei along the central auditory pathway with different types of noise stimuli. However, in the AC missing activation with respect to the background advises the need for more rigorous background noise attenuation for non-invasive reference conditions. Finally, our data suggest cross-modal activation of the olfactory system following cochlea ablation–underlining, that 18F-FDG PET appears to be well suited to study plasticity in rat models for cochlear implantation.

Highlights

Since their first clinical application in the early 1960s cochlear implants (CI) enabled a remarkable success story in the treatment of inner ear deafness [1]
Higher normalized 18F-FDG uptake could be visually assessed for RN(95dB) stimulation in inferior colliculus (IC) and auditory cortex (AC), while no distinct difference to other conditions was detected in medial geniculate body (MGB), nucleus cochlearis (NC) or olivary complex (OC)
This study demonstrates the usefulness of small animal positron emission tomography (PET) with 18F-FDG to image auditory system activations along nuclei of the central auditory pathway in normal hearing rats

Summary

Introduction

Since their first clinical application in the early 1960s cochlear implants (CI) enabled a remarkable success story in the treatment of inner ear deafness [1]. In 30% of the cases, despite early implantation in childhood, the expected hearing performance is not achieved–without explanation in 78% of these [2,3,4] In this context, functional neuroimaging after implantation using positron emission tomography (PET) improved already the pathophysiologic understanding of underlying plasticity in specialized auditory regions as well as at the level of neuronal circuits required for a successful outcome [5,6,7]. Auditory and visual stimuli as well as cochlea ablation and tinnitus condition have been investigated [8, 13,14,15] These were pioneering studies, demonstrating the general potential of the methodology, but including shortcomings with respect to the development of 18F-FDG PET as a standardized quantitative diagnostic method to serve in the further development of treatment options for hearing loss in particular via rat models of cochlear implantation. Shortcomings include for example: (i) no consideration of adaptation to stimulation paradigms, (ii) lack of standardization of environment with background or reference conditions, (iii) lack of comparison to bilateral complete hearing loss as absolute reference in order to estimate observed effects sizes and (iv) no exclusion / proof of effects due to auditory stimulation in non-auditory regions (including potential cross-modal activations)

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