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

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.

Activation in the auditory pathway of the gerbil studied with 18F-FDG PET: effects of anesthesia.

Here, we present results from an 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) study in the Mongolian gerbil, a preferred animal model in auditory research. One major issue in preclinical nuclear imaging, as well as in most of the neurophysiological methods investigating auditory processing, is the need of anesthesia. We compared the usability of two types of anesthesia which are frequently employed in electrophysiology, ketamine/xylazine (KX), and fentanyl/midazolam/medetomidine (FMM), for valid measurements of auditory activation with 18F-FDG PET. Gerbils were placed in a sound-shielding box and injected with 18F-FDG. Two acoustic free-field conditions were used: (1) baseline (no stimulation, 25 dB background noise) and (2) 90 dB frequency-modulated tones (FM). After 40 min of 18F-FDG uptake, a 30 min acquisition was performed using a small animal PET/CT system. Blood glucose levels were measured after the uptake phase before scanning. Standardized uptake value ratios for relevant regions were determined after implementing image and volume of interest templates. Scans demonstrated a significantly higher uptake in the inferior colliculus with FM stimulation compared to baseline in awake subjects (+ 12%; p = 0.02) and with FMM anesthesia (+ 13%; p = 0.0012), but not with KX anesthesia. In non-auditory brain regions, no significant difference was detected. Blood glucose levels were significantly higher under KX compared to FMM anesthesia (17.29 ± 0.42 mmol/l vs. 14.30 ± 1.91 mmol/l; p = 0.024). These results suggest that valid 18F-FDG PET measurements of auditory activation comparable to electrophysiology can be obtained from gerbils during opioid-based anesthesia due to its limited effects on interfering blood glucose levels.

Positron Emission Tomography Imaging Reveals Auditory and Frontal Cortical Regions Involved with Speech Perception and Loudness Adaptation.

Considerable progress has been made in the treatment of hearing loss with auditory implants. However, there are still many implanted patients that experience hearing deficiencies, such as limited speech understanding or vanishing perception with continuous stimulation (i.e., abnormal loudness adaptation). The present study aims to identify specific patterns of cerebral cortex activity involved with such deficiencies. We performed O-15-water positron emission tomography (PET) in patients implanted with electrodes within the cochlea, brainstem, or midbrain to investigate the pattern of cortical activation in response to speech or continuous multi-tone stimuli directly inputted into the implant processor that then delivered electrical patterns through those electrodes. Statistical parametric mapping was performed on a single subject basis. Better speech understanding was correlated with a larger extent of bilateral auditory cortex activation. In contrast to speech, the continuous multi-tone stimulus elicited mainly unilateral auditory cortical activity in which greater loudness adaptation corresponded to weaker activation and even deactivation. Interestingly, greater loudness adaptation was correlated with stronger activity within the ventral prefrontal cortex, which could be up-regulated to suppress the irrelevant or aberrant signals into the auditory cortex. The ability to detect these specific cortical patterns and differences across patients and stimuli demonstrates the potential for using PET to diagnose auditory function or dysfunction in implant patients, which in turn could guide the development of appropriate stimulation strategies for improving hearing rehabilitation. Beyond hearing restoration, our study also reveals a potential role of the frontal cortex in suppressing irrelevant or aberrant activity within the auditory cortex, and thus may be relevant for understanding and treating tinnitus.