Tinnitus, commonly known as “ringing of the ears”, is one of the largest health challenges in the world (1). According to a recent large survey, approximately 6.4% of Americans experience persistent tinnitus (2). Every tenth patient experiences a most extreme and debilitating form of tinnitus. Sleep deprivation, anxiety, and depression often accompany tinnitus and severely affect the patient’s quality of life (3–5). In turn, this places a huge burden on society, healthcare costs, and decreases productivity (6).
Subjective tinnitus has a multifactorial origin with heterogeneous patient profiles, which makes it a highly complex condition. The absence of an underlying medical cause in most cases leaves many patients without an available curative evidence-based treatment (7, 8). Tinnitus combined with sensorineural hearing loss might benefit from hearing aids. However, somewhere between 22% and 80% of affected patients are adequately served by using hearing aids (9, 10). Current clinical practice primarily aims at reducing the impact of tinnitus by providing psychoeducation and improving coping strategies via various psychological interventions (11, 12).
The etiological and pathophysiological mechanisms of subjective tinnitus are complex and not fully understood. Many investigators feel that in nearly all tinnitus cases, there is some degree of cochlear impairment, leading to diminished auditory nerve activity reaching the cochlear nuclei (13). Much evidence implicates the head and neck somatosensory system as a separate major factor in the development of tinnitus. It is likely that most tinnitus develops as a result of CNS interactions between these two systems (14). According to current theories, tinnitus is associated with increased neural activity in auditory cortices, possibly resulting from maladaptive gating (15, 16) and/or increase in central gain (17). Specific neural correlates described in tinnitus models are enhanced neuronal synchrony, increased spontaneous firing, and changes in tonotopic organization (18). The medial geniculate body (MGB) of the thalamus is a major relay and gateway between midbrain and cortex, and a core structure in tinnitus pathophysiology (19, 20). Preclinically, at multiple levels of the central auditory pathway from cochlear nuclei to auditory cortex and including the MGB, tinnitus related neuronal activity is similar to subthalamic nucleus activity in Parkinson’s disease, i.e., enhanced spontaneous activity and burst firing (21–24). The primary role of auditory thalamic neurons is to actively and dynamically shape neural representations of information and to control which information reaches the cerebral cortex (25). Furthermore, integration of auditory and limbic information occurs within the MGB (26). Connected limbic structures, such as the amygdala and nucleus accumbens, are related to emotional and attentional symptoms of tinnitus (27). Hence, the MGB acts as a central hub in involved tinnitus networks, which makes it a promising structure for neuromodulatory approaches.
A commonly applied neuromodulation technique is deep brain stimulation (DBS). This therapy has been widely used in neurologic and neuropsychiatric disorders such as Parkinson’s disease. DBS is generally applied using high frequency stimulation (> 100Hz), to disrupt pathological neuronal activity and oscillations (28, 29). Hypothetically, this results in alteration of tinnitus perception and related distress. Further, patients, treated with DBS for a movement disorder sometimes also suffered from tinnitus. DBS of non-auditory structures in these patients led to diminished or completely suppressed tinnitus (30–32). Moreover, preclinical studies support the beneficial effects of DBS on tinnitus when applied in auditory brain areas. A reduction in tinnitus-like behavior was shown when DBS was applied in several structures along the classical auditory pathway, including the dorsal cochlear nucleus (33, 34), inferior colliculus (35), and MGB (36). Importantly, no undesired side-effects occurred. DBS of the MGB did not lead to anxiety or disturbed locomotor activity. DBS of the inferior colliculi did not cause any detectable hearing impairment (37). Therefore, DBS seems to be a promising treatment for severe, refractory tinnitus (38–40). The MGB is a preferred target area next to other auditory subcortical structures (39), as the auditory thalamus is readily accessible in stereotactic surgery. Consequently, targeting the auditory thalamus bears smaller surgical risks and complications such as bleeding and potential neurological deficit. Currently, MGB DBS has not been applied in humans. The majority of patients with tinnitus can be treated with non-invasive methods, and only a small number of patients can be considered as a candidate for DBS.
The primary objective of the proposed study is to assess the safety and feasibility (acceptability) of bilateral MGB DBS in severe tinnitus. Patients with severe tinnitus who are refractory to the standard treatment program will be included. Secondary outcomes will provide data on the potential efficacy of MGB DBS on tinnitus severity (Tinnitus Functional Index), tinnitus loudness, and distress (Visual Analogue Scales). Additionally, hearing (audiometry), cognition (neuropsychological test battery), quality of life, and psychological functioning (questionnaires) will be assessed. Furthermore, electrophysiological data will assess fundamental aspects of auditory function and tinnitus pathophysiology. After successful evaluation of the primary and secondary outcomes in this pilot study, MGB DBS could potentially be further developed as a novel treatment option in severe, refractory tinnitus.