Sensory gating describes a filter mechanism
‘Sensory gating’ describes a filter mechanism protecting the central nervous system from sensory overload by inhibiting behaviorally irrelevant input (Boutros et al., 2004, 2008). This permits Fluorescein TSA where to a changing contextual environment (Fruhstorfer et al., 1970; Grunwald et al., 2003). Auditory gating has been anatomically linked to the auditory cortex (AUD), hippocampus, parahippocampus (PHC), and cingulate cortices (Boutros et al., 2008; Grunwald et al., 2003; Majic et al., 2011); prefrontal cortex (PFC) dopamine is also involved in auditory gating (Grunwald et al., 2003). A direct relationship was recently shown between the COMT polymorphism and poor auditory gating via a PFC–AUD mechanism (Majic et al., 2011). Indeed, this study shows that COMT Met carrying is associated with a poor sensory gating of the N100 component - a mid-latency component of auditory evoked potentials with a peak between 80 and 120 ms after the presentation of an acoustic stimulus, suggesting that a high prefrontal processing capacity allows a pronounced afferent input of sensory information form the AUD as reflected by poor sensory gating (Majic et al., 2011).
Tinnitus is the perception of simple sound (pure tones and/or noise) in the absence of a corresponding external sound source, and is considered an auditory phantom percept analogous to phantom pain (Eggermont et al., 2004; Jastreboff, 1990). Tinnitus is proposed to be an emergent property of network activity (De Ridder et al., 2014b) most commonly related to auditory deafferentation with or without hearing loss (Vanneste et al., 2016). The deafferentation is commonly due to noise trauma, presbyacusis, or other causes of auditory deprivation (Hesse et al., 2016). It has been postulated that tinnitus, based on the pain literature, can be the result of a deficient auditory gating mechanism (Leaver et al., 2011; Rauschecker et al., 2010). One line of research, although no consistently replicated, shows that structural deficits and functional changes in the ventromedial PFC, pregenual anterior cingulate cortex (pgACC), and the nucleus accumbens are associated with a deficient frontostriatal auditory gating mechanism (Leaver et al., 2011; Rauschecker et al., 2010, 2015). This mechanism is central gatekeeper that evaluates the relevance and affective meaning of sensory stimuli and modulates information via descending inhibitory pathways to the thalamic reticular nucleus which modulates the information flow between the thalamus and the AUD by inhibiting specific thalamic neurons in a highly selective and frequency-specific manner (Rauschecker et al., 2015; Yu et al., 2009).
Some preliminary evidence from pharmacological interventions in humans have demonstrated that a decrease in dopamine activity could reduce tinnitus perception (Lopez-Gonzalez et al., 2007; Meeus et al., 2011). As the COMT polymorphism is especially prominent in PFC and has been associated with auditory gating, we hypothesize that tinnitus patients with this polymorphism have altered activity in the ventromedial PFC/anterior cingulate cortex that modulate the tinnitus percept.
Discussion The current study aimed to understand the influence of the COMT polymorphism and the neurogenetic architecture of hearing loss induced tinnitus. Our data identify that Met carriers in combination with severe hearing loss are a good predictor for the loudness of the tinnitus percept. This is mainly driven by increased activity in the pgACC and decreased pgACC–PHC functional connectivity in Met carriers. Furthermore, the connectivity is increased from the left PHC to the pgACC, while decreased from the pgACC to the left PHC in tinnitus patients who are Met carriers with severe hearing loss. The result indicates that the pgACC, which has been associated with sensory gating in tinnitus, is mediating the percept loudness (see Fig. 12). To our knowledge, this is the first study investigating the clinical and associated electrophysiological effects, both in activity and connectivity, of COMT Val158Met polymorphism in tinnitus.