Presbycusis and tinnitus are the two most common hearing related pathologies. Although both of these conditions presumably originate in the inner ear, there are several reports concerning their central components. Interestingly, the onset of presbycusis coincides with the highest occurrence of tinnitus. The aim of this study was to identify age, hearing loss, and tinnitus related functional changes, within the auditory system and its associated structures. Seventy-eight participants were selected for the study based on their age, hearing, and tinnitus, and they were divided into six groups: young controls (Y-NH-NT), subjects with mild presbycusis (O-NH-NT) or expressed presbycusis (O-HL-NT), young subjects with tinnitus (Y-NH-T), subjects with mild presbycusis and tinnitus (O-NH-T), and subjects with expressed presbycusis and tinnitus (O-HL-T). An MRI functional study was performed with a 3T MRI system, using an event related design (different types of acoustic and visual stimulations and their combinations). The amount of activation of the auditory cortices (ACs) was dependent on the complexity of the stimuli; higher complexity resulted in a larger area of the activated cortex. Auditory stimulation produced a slightly greater activation in the elderly, with a negative effect of hearing loss (lower activation). The congruent audiovisual stimulation led to an increased activity within the default mode network, whereas incongruent stimulation led to increased activation of the visual cortex. The presence of tinnitus increased activation of the AC, specifically in the aged population, with a slight prevalence in the left AC. The occurrence of tinnitus was accompanied by increased activity within the insula and hippocampus bilaterally. Overall, we can conclude that expressed presbycusis leads to a lower activation of the AC, compared to the elderly with normal hearing; aging itself leads to increased activity in the right AC. The complexity of acoustic stimuli plays a major role in the activation of the AC, its support by visual stimulation leads to minimal changes within the AC. Tinnitus causes changes in the activity of the limbic system, as well as in the auditory AC, where it is bound to the left hemisphere.

• Klíčová slova
• auditory system, functional MRI, limbic system, presbycusis, tinnitus,
• Publikační typ
• časopisecké články MeSH

The LIM homeodomain transcription factor ISL1 is essential for the different aspects of neuronal development and maintenance. In order to study the role of ISL1 in the auditory system, we generated a transgenic mouse (Tg) expressing Isl1 under the Pax2 promoter control. We previously reported a progressive age-related decline in hearing and abnormalities in the inner ear, medial olivocochlear system, and auditory midbrain of these Tg mice. In this study, we investigated how Isl1 overexpression affects sound processing by the neurons of the inferior colliculus (IC). We recorded extracellular neuronal activity and analyzed the responses of IC neurons to broadband noise, clicks, pure tones, two-tone stimulation and frequency-modulated sounds. We found that Tg animals showed a higher inhibition as displayed by two-tone stimulation; they exhibited a wider dynamic range, lower spontaneous firing rate, longer first spike latency and, in the processing of frequency modulated sounds, showed a prevalence of high-frequency inhibition. Functional changes were accompanied by a decreased number of calretinin and parvalbumin positive neurons, and an increased expression of vesicular GABA/glycine transporter and calbindin in the IC of Tg mice, compared to wild type animals. The results further characterize abnormal sound processing in the IC of Tg mice and demonstrate that major changes occur on the side of inhibition.

• Klíčová slova
• auditory system, inferior colliculus, inhibition, sound processing, transcription factor ISL1,
• MeSH
• colliculus inferior metabolismus   fyziologie   MeSH
• exprese genu genetika   MeSH
• lidé MeSH
• mozek fyziologie   MeSH
• myši transgenní MeSH
• myši MeSH
• neurony fyziologie   MeSH
• promotorové oblasti (genetika) genetika   MeSH
• proteiny s homeodoménou LIM genetika   metabolismus   MeSH
• sluch MeSH
• sluchová percepce genetika   fyziologie   MeSH
• sluchové kmenové evokované potenciály fyziologie   MeSH
• sluchový práh fyziologie   MeSH
• transkripční faktor PAX2 genetika   MeSH
• transkripční faktory genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• insulin gene enhancer binding protein Isl-1 MeSH Prohlížeč
• PAX2 protein, human MeSH Prohlížeč
• Pax2 protein, mouse MeSH Prohlížeč
• proteiny s homeodoménou LIM MeSH
• transkripční faktor PAX2 MeSH
• transkripční faktory MeSH

Age related hearing loss (presbycusis) is a natural process represented by elevated auditory thresholds and decreased speech intelligibility, especially in noisy conditions. Tinnitus is a phantom sound that also potentially leads to cortical changes, with its highest occurrence coinciding with the clinical onset of presbycusis. The aim of our project was to identify age, hearing loss and tinnitus related structural changes, within the auditory system and associated structures. Groups of subjects with presbycusis and tinnitus (22 subjects), with only presbycusis (24 subjects), young tinnitus patients with normal hearing (10 subjects) and young controls (17 subjects), underwent an audiological examination to characterize hearing loss and tinnitus. In addition, MRI (3T MR system, analysis in Freesurfer software) scans were used to identify changes in the cortical and subcortical structures. The following areas of the brain were analyzed: Heschl gyrus (HG), planum temporale (PT), primary visual cortex (V1), gyrus parahippocampus (PH), anterior insula (Ins), amygdala (Amg), and hippocampus (HP). A statistical analysis was performed in R framework using linear mixed-effects models with explanatory variables: age, tinnitus, laterality and hearing. In all of the cortical structures, the gray matter thickness decreased significantly with aging without having an effect on laterality (differences between the left and right hemispheres). The decrease in the gray matter thickness was faster in the HG, PT and Ins in comparison with the PH and V1. Aging did not influence the surface of the cortical areas, however there were differences between the surface size of the reported regions in the left and right hemispheres. Hearing loss caused only a borderline decrease of the cortical surface in the HG. Tinnitus was accompanied by a borderline decrease of the Ins surface and led to an increase in the volume of Amy and HP. In summary, aging is accompanied by a decrease in the cortical gray matter thickness; hearing loss only has a limited effect on the structure of the investigated cortical areas and tinnitus causes structural changes which are predominantly within the limbic system and insula, with the structure of the auditory system only being minimally affected.

• Klíčová slova
• auditory system, limbic system, morphometry, presbycusis, tinnitus,
• Publikační typ
• časopisecké články MeSH

Fischer 344 (F344) rats represent a strain that is frequently used as a model for fast aging. In this study, we systematically compare the hearing function during aging in male and female F344 rats, by recording auditory brainstem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs). In addition to this, the functional parameters are correlated with the cochlear histology. The parameters of the hearing function were not different in the young (3-month-old) male and female F344 rats; the gender differences occurred only in adult and aged animals. In 8-24-month-old males, the ABR thresholds were higher and the ABR amplitudes were smaller than those measured in females of the same age. There were no gender differences in the neural adaptation tested by recording ABRs, elicited by a series of clicks with varying inter-click interval (ICI). Amplitudes of DPOAEs in both the males and females decreased with age, but in the males, the decrease of DPOAE amplitudes was faster. In males older than 20 months, the DPOAEs were practically absent, whereas in 20-24-month-old females, the DPOAEs were still measurable. There were no gender differences in the number of surviving outer hair cells (OHC) and the number of inner hair cell ribbon synapses in aged animals. The main difference was found in the stria vascularis (SV). Whereas the SV was well preserved in females up to the age of 24 months, in most of the age-matched males the SV was evidently deteriorated. The results demonstrate more pronounced age-related changes in the cochlear morphology, hearing thresholds, ABR amplitudes and DPOAE amplitudes in F344 males compared with females.

• Klíčová slova
• Fischer 344 rats, aging, cochlear morphology, gender differences, hearing function, stria vascularis,
• Publikační typ
• časopisecké články MeSH