**6. Conclusion**

84 Hearing Loss

al., 1996). The similarity of age-dependent changes in gap detection by humans and gerbils emphasises the usefulness of the gerbil model for the analysis of impaired auditory

Forward masking is a phenomenon through which threshold for a probe that follows a signal (masker) is elevated (masked) and recovers with time (≈ 100 ms) following the end of the masker. Increased masking and delayed recovery from preceding acoustic stimulation interferes with the detection of fluctuations and transients in sound signals and might contribute to age-dependent impairment of speech perception. In the analysis of the effect of age on forward masking in gerbils (Gleich et al., 2007a) a 2.85 kHz masker presented at 40 dBSPL and repeated continuously every 1.6 seconds served as a constant background signal. Animals had to detect trials where a short 2.85 kHz probe signal (20 ms) was presented 2.5 ms after the end of the masker. In addition to the masked threshold, the threshold for the probe signal without a masker was determined to characterise peripheral hearing. In a sample of 15 gerbils between 5 and 36 months of age, threshold for the probe in quiet was independent of age (mean 12 dBSPL). These animals showed no sign of peripheral hearing loss. In contrast, the masked thresholds of these gerbils increased from around 33 dB SPL at 1 year of age to 48 dBSPL at an age of 3 years. The efficacy of the masker increased by 15 dB between 1 and 3 years of age. The increased degree of forward masking in old gerbils in the absence of elevated thresholds in the condition without a masker suggests a deficit in central, rather than peripheral, auditory processing. An analysis of forward masking using ABR in humans also demonstrated increased forward masking in old subjects with normal audiometric thresholds and led to the conclusion that this was likely due to changes in central auditory processing (Walton et al., 1999). Thus, gerbils appear to be a useful model

Age-dependent structural changes in auditory nuclei involved in binaural processing have been discussed above (see headings 4.2.3-4.2.5). Consistent with the pathology in MNTB, MSO and LSO, auditory spatial resolution was impaired in old gerbils (Maier et al., 2008). The minimum resolvable angle in a sound lateralisation task showed a higher degree of inter-animal variability in old (32 to 51 months), as compared to young (3-8 months), gerbils. The angle for pure tones (0.5 and 8 kHz) and narrowband noise centred at 0.5 and 2 kHz was ≈ 50-60° in old gerbils, approximately twice the angle found in young gerbils. Maier et al. (2008) suggest that spongiform lesions in the VCN compromise the excitatory input, while pathology of the MNTB affects the inhibitory input to LSO and MSO and contribute to

The available data indicate that ageing is associated with a loss of inhibition in the central auditory pathway, which could contribute to impaired auditory temporal processing (Caspary et al., 2008). Age-dependent changes in neurotransmitter systems might be influenced by pharmacotherapy and the similarity of age-dependent deficits between

for the analysis of the interaction of age and forward masking.

impaired auditory spatial resolution in old gerbils.

**5.5 Auditory spatial resolution** 

**5.6 Pharmacotherapy** 

temporal processing.

**5.4 Forward masking** 

At the level of the cochlea, pathology begins to affect the marginal cells of the stria vascularis and eventually leads to a reduction of the endocochlear potential in old gerbils. Loss of hair cells and loss of auditory nerve fibres and spiral ganglion cells are not major contributors to age-dependent peripheral hearing loss. Consequently, gerbils can be regarded as a good model for strial or metabolic presbyacusis.

Behavioural and evoked potential (CAP, ABR) measures of auditory sensitivity are useful to characterise hearing status; however, the degree of age-dependent threshold elevation depends on the method used: the discrepancy between thresholds determined psychoacoustically and by evoked potentials increases with age; evoked potentials indicate more threshold loss than behavioural methods in old gerbils and old humans.

Auditory nuclei in the ascending auditory pathway of gerbils show specific and distinct agedependent structural changes, where some nuclei appear more affected than others. Structural changes in nuclei involved in binaural processing are associated with impaired auditory spatial resolution in old gerbils. For LSO and MSO, the degree of age-dependent pathology in gerbils can be correlated with age-dependent changes in human performance

The Mongolian Gerbil as a Model for

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in sound lateralisation tasks, which are based on inter-aural level and inter-aural time difference cues. This suggests a causal relationship between structural and functional agedependent changes.

The age-dependent decline of auditory temporal resolution determined by gap detection and forward masking in gerbils and humans is very similar and probably due to loss of inhibition or age-dependent disturbance of neurotransmitter balance in the auditory pathway. Augmentation of the GABA system by vigabatrin was effective in the treatment of impaired gap detection in gerbils and demonstrates that pharmacotherapy of central auditory processing deficits appears feasible, in principle. The challenge is to identify appropriate substances that act on the disturbed neurotransmitter balance in advanced age. The available data show that the gerbil is a suitable model to evaluate the efficacy of potential therapies for the treatment of impaired central auditory processing.
