Deep brain stimulation of the inferior colliculus in the rodent suppresses tinnitus

Highlights

• Noise-trauma induced tinnitus was assessed using gap induced prepulse inhibition.

• Deep brain stimulation was applied in the external cortex of inferior colliculus.

• Tinnitus-like behavior was significantly reduced during deep brain stimulation.

• Hearing seems not to be affected by deep brain stimulation.

Abstract

In animal models of tinnitus pathological neuronal activity has been demonstrated. Deep brain stimulation disrupts pathological neuronal activity and might therefore be a potential treatment for patients who suffer severely from tinnitus. In this study, the effect of DBS in the inferior colliculi is investigated in an animal model of tinnitus. The external cortex of the inferior colliculus was targeted because of the key position of the inferior colliculus within the auditory network and the relation of the external cortex with the limbic system. In this study we show the effect of DBS in the inferior colliculus on tinnitus using a within-subject experimental design. After noise trauma, rats showed a significant increase in gap:no gap ratio of the gap-induced prepulse inhibition at 16 and 20 kHz (p<0.05), indicating the presence of tinnitus in these frequency bands. During DBS the gap:no gap ratio returned back to baseline (p<0.05). Hearing thresholds before and during DBS did not differ, indicating that hearing function is probably not impaired by electrical stimulation. In summary, this study shows that DBS of the inferior colliculi is effective in reducing behavioral signs of tinnitus in an animal model. Impaired hearing function could not be objectified as a side effect of stimulation.

Introduction

Tinnitus, also known as ringing of the ears, has a prevalence ranging from 10% to 15% in the general population (Sanchez, 2004). While tinnitus is not bothersome in the majority of the patients, 2.4% of the whole population suffers daily from severely debilitating symptoms (Axelsson and Ringdahl, 1989). Often tinnitus is accompanied by psychological symptoms such as anxiety and depressive symptoms (Andersson et al., 1999, Shargorodsky et al., 2010, Milerova et al., 2013).

To date, there is consensus among the majority of researchers that noise-induced tinnitus is the result of maladaptive plasticity after damage to the peripheral auditory system (Eggermont, 2003). The decrease in auditory nerve activity leads to an increased activity in auditory as well as in non-auditory brain structures (Norena and Farley, 2013). Measurements in animal models of tinnitus show increased spontaneous neuronal firing rate, neural synchrony, bursting activity and tonotopic reorganization (Eggermont, 2003, Kaltenbach, 2011, Norena, 2011). At least some of these changes in neuronal activity have been found in the cochlear nucleus, inferior colliculus, medial geniculate body of thalamus and auditory cortex (Smit et al., 2015).

Increased bursting activity, neural synchrony and tonotopic reorganization are all demonstrated in the IC in preclinical tinnitus studies (Bauer et al., 2008, Chen and Jastreboff, 1995, Robertson et al., 2013, Wang et al., 2002). The IC integrates neuronal input from a variety of auditory nuclei. An interesting substructure within the IC is the external nucleus of the IC (ICx), which shows increased spontaneous activity and bursting activity in an animal model of tinnitus (Chen and Jastreboff, 1995) and changes in neuronal excitability following noise exposure due to neuronal plasticity (Szczepaniak and Moller, 1996). The ICx is considered part of the non-classical auditory pathway and projects via the dorsal and medial parts of the thalamic auditory nucleus to the secondary auditory cortex and auditory association cortices. Furthermore, the dorsal and medial connections from the thalamic nuclei make connections to limbic structures such as the amygdala. The limbic system reflects emotional reaction to tinnitus and might play an extended role in tinnitus (Rauschecker et al., 2010).

Currently, deep brain stimulation (DBS) is successfully applied in several central neurological conditions like Parkinson's disease and essential tremor (Larson, 2014). Via a pulse generator, electrical impulses are sent to electrodes which are surgically placed in a specific brain area with high precision. The exact mechanism of DBS is unknown but it is clear that DBS is able to modulate pathological neuronal activity patterns (McIntyre and Hahn, 2010), possibly by silencing neurons. This hypothesis is based on the fact that high-frequency stimulation results in a similar functional effect as performing a lesion of the area (Benabid et al., 2002, Hamani and Temel, 2012). The nucleus subthalamicus is a hyperactive target in Parkinson's disease and is the main target for DBS (Janssen et al., 2014, Rodriguez-Oroz et al., 2001). DBS of the ICx, which is found to be a hyperactive area in tinnitus, might reduce the tinnitus signal (Smit et al., 2015).

The main objective of this study was to assess the efficacy of DBS in the ICx in an animal model of tinnitus.