The effects of repetitive transcranial magnetic stimulation in an animal model of tinnitus.

Wilhelmina H. A. M. Mulders,Alex D. Tang,Kalina Makowiecki,Jennifer Rodger,Vanessa Vooys

doi:10.1038/srep38234

Wilhelmina H. A. M. Mulders, Alex D. Tang + Show 3 more

Open Access

https://doi.org/10.1038/srep38234

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Journal: Scientific Reports	Publication Date: Dec 1, 2016
Citations: 16	License type: CC BY 4.0

Affiliation: University of Western Australia

Abstract

Tinnitus (phantom auditory perception associated with hearing loss) can seriously affect wellbeing. Its neural substrate is unknown however it has been linked with abnormal activity in auditory pathways. Though no cure currently exists, repetitive transcranial magnetic stimulation (rTMS) has been shown to reduce tinnitus in some patients, possibly via induction of cortical plasticity involving brain derived neurotrophic factor (BDNF). We examined whether low intensity rTMS (LI-rTMS) alleviates signs of tinnitus in a guinea pig model and whether this involves changes in BDNF expression and hyperactivity in inferior colliculus. Acoustic trauma was used to evoke hearing loss, central hyperactivity and tinnitus. When animals developed tinnitus, treatment commenced (10 sessions of 10 minutes 1 Hz LI-rTMS or sham over auditory cortex over 14 days). After treatment ceased animals were tested for tinnitus, underwent single-neuron recordings in inferior colliculus to assess hyperactivity and samples from cortex and inferior colliculus were taken for BDNF ELISA. Analysis revealed a significant reduction of tinnitus after LI-rTMS compared to sham, without a statistical significant effect on BDNF levels or hyperactivity. This suggests that LI-rTMS alleviates behavioural signs of tinnitus by a mechanism independent of inferior colliculus hyperactivity and BDNF levels and opens novel therapeutic avenues for tinnitus treatment.

Highlights

We have developed a guinea pig model of tinnitus, using unilateral exposure to a loud tone to damage the cochlea, leading to a small hearing loss and development of increased spontaneous firing rates of central auditory neurons[10,30,31]
In 5 animals the gap prepulse inhibition of acoustic startle (GPIAS) deficit appeared at the background noise of 14 kHz, in another 5 animals at the background noise of 8 kHz and in the final 2 animals the deficit occurred at both frequencies
The significant interaction was followed by Sidak corrected post-hoc tests and this revealed a significant decrease in percentage GPIAS at the tinnitus frequency after acoustic trauma (p < 0.0001) and a significant difference after acoustic trauma between the tinnitus frequency and the non-tinnitus frequency (p < 0.001)

Summary

Introduction

We have developed a guinea pig model of tinnitus, using unilateral exposure to a loud tone to damage the cochlea, leading to a small hearing loss and development of increased spontaneous firing rates (hyperactivity) of central auditory neurons[10,30,31]. We use our model to investigate whether rTMS can reduce behavioural evidence of tinnitus and the associated hyperactivity in inferior colliculus (IC). Upon behavioural evidence of tinnitus, we commenced treatment (10 minutes of 1 Hz low intensity rTMS (LI-rTMS) or sham stimulation over auditory cortex contralateral to the affected cochlea for 10 daily sessions over 14 days) using a custom-built coil[38,39]. This coil approximates the coil to brain-size ratio used in humans providing improved focality[40]. BDNF plays important roles in neural plasticity[41] and was upregulated in other neural systems in rodents following rTMS16,42

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