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

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.

Divergent Responses in the Gap Prepulse Inhibition of the Acoustic Startle Reflex in Two Different Guinea Pig Colonies

“…One possible explanation for the results is that a large proportion of animals in colony 2 have pre-existing idiopathic tinnitus as a passed PPI with a failed GPIAS result is the criterion generally applied to identify the presence of tinnitus in animal models 8,11,21,22 . However, we consider this to be unlikely for several reasons.…”

“…Data were taken from animals used in different experiments taking place in our laboratory over a period of approximately 18 months. Animals which showed good PPI and GPIAS (see section 2 for details) were used for tinnitus inducing experiments by acoustic trauma 22 and manuscript in preparation. The guinea pigs were derived from 2 different colonies bred at the University of Western Australia.…”

“…Because GPIAS has been validated against behavioural tests of tinnitus in animals 8 and is a convenient tool to quickly screen animals, its use has become widespread amongst research groups investigating tinnitus 14 . Studies have shown that GPIAS can be used in rats 8,15,16 , mice [17][18][19][20] and guinea pigs 11,21,22 . In addition, it has been used after a variety of tinnitus-inducing methods such as after salicylate or quinine 15,23 as well as after acoustic overexposure 16 .…”

“…In our laboratory we use guinea pig models to explore the neural substrate of tinnitus 21,22 . Before any tinnitus inducing treatment we always establish stable baseline suppression in the GPIAS and PPI test for each animal.…”

“…The PPI test is conducted together with the GPIAS test as it establishes that the animal can hear both the prepulse and the background noise (we use background noise in the GPIAS test with the exact same characteristics as the prepulse in the PPI test). This is essential because an animal may show reduced suppression in the GPIAS test not only due to the presence of tinnitus, but also when it cannot hear the background noise and hence would be unable to detect a silent gap 11,21,22 . The guinea pigs used in our laboratory are derived from two tricolour outbred guinea pig colonies.…”