Elsevier

Biosystems

Volume 136, October 2015, Pages 113-119
Biosystems

Altered intensity coding in the salicylate-overdose animal model of tinnitus

https://doi.org/10.1016/j.biosystems.2015.06.010Get rights and content

Abstract

Tinnitus is one of the leading disorders of hearing with no effective cure as its pathophysiological mechanisms remain unclear. While the sensitivity to sound is well-known to be affected, exactly how intensity coding per se is altered remains unclear. To address this issue, we used a salicylate-overdose animal model of tinnitus to measure auditory cortical evoked potentials at various stimulus levels, and analyzed on single-trial basis the response strength and its variance for the computation of the lower bound of Fisher information. Based on Fisher information profiles, we compared the precision or efficiency of intensity coding before and after salicylate-treatment. We found that after salicylate treatment, intensity coding was unexpectedly improved, rather than impaired. Also, the improvement varied in a sound-dependent way. The observed changes are likely due to some central compensatory mechanisms that are activated during tinnitus to bring out the full capacity of intensity coding which is expressed only in part under normal conditions.

Introduction

Tinnitus is one of the leading disorders of hearing with a high prevalent rate (review see Roberts et al., 2010). In extreme cases, it can be disabling to normal life. Symptoms of this disorder, besides some degree of hearing loss, include: (a) the perception of phantom sound (i.e., in clinical terms, tinnitus); and/or (b) the overly-loud perception of sounds at moderate levels (i.e., in clinical terms, hyperacusis) (Baguley, 2003, Wang et al., 2008). May or may not be related to hyperacusis, a number of electrophysiological recordings from auditory cortex in awake rats showed enhanced responses during experimental tinnitus (e.g., with salicylate overdose or acoustic trauma) (Eggermont, 2013, Lu et al., 2011, Sun et al., 2009, Stolzberg et al., 2012a, Stolzberg et al., 2012b). No effective cure, but only behavioral management is available to treat tinnitus as the underlying pathophysiology still remains unclear (Cazals, 2000, Jastreboff, 2007, Møller, 2007). Research on experimental tinnitus in animals has led to theories of its pathogenesis. The prevailing one is that an initial hearing loss leads to the activation of a central gain control system in order to compensate for the impaired sensory input (Qiu et al., 1999, Norena, 2011). The key issue is therefore the compensation for an altered intensity coding.

One fundamental question in tinnitus regarding the phenomenon of intensity compensation is how the efficiency or precision of intensity coding is altered (i.e., better, no change, or worse). To address this issue, we studied a reversible model of tinnitus that involves salicylate-overdose in rats (Jastreboff et al., 1988, Bauer et al., 1999). Specifically we measured, in their awake state, single-trial auditory evoked responses from the cortex before and after tinnitus-induction. Based on single-trial response strength and its variance, we computed the lower bound of Fisher information at different stimulus levels for an estimation of the coding efficiency of sound intensity (Bethge et al., 2002, Kostal et al., 2013, Roy, 2004).

Below is a brief account of Fisher information with relevance to this study. Fisher information is a measure of the amount of information that an observable random variable (in our case, the strength of evoked potential integral, EPI) carries about an unknown parameter (in our case, the stimulus sound pressure level, or SPL). The probability function for EPI, which is also the likelihood function for SPL, is a function f(EPI; SPL), which describes the probability that we would observe a sample of EPI given a known value of SPL. If f(EPI; SPL) is sharply peaked (or large in size) with respect to SPL, that means it contains a lot of information about SPL, since it is easy to predict the correct value of SPL given the EPI data. Otherwise, if the function is flat (or small in size), it would need more samples of EPI to estimate the correct SPL, and hence the EPI data has less information about SPL (please see Supplementary Text 1 for details).

Section snippets

Animals

Ten adult Sprague Dawley rats (∼6 weeks old, ∼250 g b.w.) were obtained from the Animal Center of National Cheng Kung University (NCKU). Experimental procedures have been approved by the Animal Ethics Committee, NCKU.

Recording electrodes

Bipolar recording electrodes custom-made of Teflon-coated silver wires (125 μm ID, 175 μm OD; A-M Systems, USA) were soldered at one end to miniature strip male-sockets (model 520200; A-M Systems, USA). The recording electrodes contain an active lead and two reference leads which were

Results

Depending on animals, the auditory evoked responses could be of very good signal to noise ratio as shown in Fig. 1. Here the average EP showed clear incremental changes from the control (pre-drug) to the salicylate-treated (post-drug) conditions, with minimal changes in the shape of the response waveform.

From the total of 10 rats studied, 3 of them reached the criterion of good signal-to-noise ratio, and showed significant correspondence with the four-parameter logistic regression function (see

Conclusions and discussion

The principal finding of this study is that during the experimental tinnitus, there is an increase in the efficiency or precision of intensity coding. Furthermore, the increase in J2 is not the same for different sounds (apart from daily variations with identical stimuli, as expected from such behavioral paradigms of passive listening).

First, for tones of different frequencies, high frequency tones (16 kHz in particular) showed significant changes of the response-level function (including an

Acknowledgements

Supported by grants from NCKU, Ministry of Science and Technology, Taiwan, grants 99-2320-B-006-020,100-2923-006-001, 101-2911-I-006-511; as well as by grants from Czech Science Foundation, P303/11/J005, P304/12/1342, 15-08066S.

References (36)

Cited by (5)

  • Functional data analysis of single-trial auditory evoked potentials recorded in the awake rat

    2017, BioSystems
    Citation Excerpt :

    In rats, the experimental tinnitus after a single SS-overdose can last for several hours, providing a good opportunity to study SS-induced changes in auditory EP in a reversible way on a daily basis, often over extended periods up to weeks. In the previous study on awake rats, we have reported the changes of auditory EP during SS-induced tinnitus using intra-cranially near-field electrodes implanted over the cortex (Wan et al., 2015). What we found of interest are the large daily variations in EP to sound particularly after SS treatment.

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