Introduction
Tinnitus – the perception of a sound without external physical source
– is commonly believed to be the result of an interaction of a damage
to the peripheral auditory system and central neuroplastic adaptations
to the new, changed auditory input (Nelson & Chen, 2004). We already
put forward a bottom-up model for tinnitus development in which these
neuroplastic adaptations – after a mild hearing loss – start in the
dorsal cochlear nuclei (DCN) after losing a part of the neuronal
information not transmitted from the damaged cochlea anymore (Krausset al. , 2016; Krauss et al. , 2017; Schilling et
al. , 2021). In a nutshell, this Erlangen model of tinnitus development
(Schulze et al. , 2023) assumes that a neurophysiological
mechanism detects a drop in information after a hearing loss by
computing the autocorrelation of the signal of the cochlear nerve
(Schulze & Tziridis, 2023), as less temporally structured spike trains
reach the DCN neurons (Schulze & Tziridis, 2023). By disinhibition of
neuronal noise, most probably coming from the somatosensory system
(Schilling et al. , 2021), a reduced – but still information
containing – input signal plus that noise can reach the threshold and
activate the DCN neurons, a mechanism known as stochastic resonance. As
a consequence, otherwise sub-threshold activity from the cochlea can now
be further transmitted along the auditory pathway, thereby optimizing
information transmission within the auditory system. This comes at the
cost of co-propagation of the noise up to the auditory cortex, where the
activity is then perceived as a sound, namely tinnitus. based on that
model we were able to predict and explain several tinnitus related
effects on hearing loss, e.g., that the hearing thresholds in patients
with mild to moderate hearing loss and tinnitus are better than in
matched patients without tinnitus (Gollnast et al. , 2017).
Furthermore, we were able to develop a new therapeutic approach based on
that model which allows a causative reduction of tinnitus loudness in
tinnitus patients (Schilling et al. , 2020; Tziridis et
al. , 2022). However, the original model failed to describe the effects
of chronic manifestation of tinnitus and made no predictions on tinnitus
related plasticity in the auditory cortex. To overcome these drawbacks,
in a previous paper, the stochastic resonance model was unified with the
predictive coding model of auditory phantom perception (Sedley et
al. , 2016; Schilling et al. , 2023b). in this view, tinnitus
might be induced and chronically manifested through an interplay of two
feedback loops – the stochastic resonance loop in the brainstem and the
predictive coding circuit in the cortex (Sedley et al. , 2016;
Schilling et al. , 2023b).
In the present study we aim to investigate tinnitus related adaptations
in the auditory cortex (AC) after an assumed chronic manifestation of
the phantom percept. Based on electrophysiological recordings in animals
(Engineer et al. , 2011; Tziridis et al. , 2015) and e.g.,
imaging methods or EEG recordings in humans (Haab et al. , 2009;
Schoisswohl et al. , 2021), it is already known that tinnitus
before and after chronification has different neurophysiological
manifestations within the AC of mammals. While before chronification the
neurophysiology of the AC seems to undergo profound changes in, e.g.,
tonotopy (e.g., Eggermont, 2006), the normal processing in the AC seems
to be recovered after the new percept is developed, with the addition of
the phantom sound activity in the affected frequency range (Ahlfet al. , 2012; Langers et al. , 2012).
Neuronal plasticity in the cortex can be assessed using several
different methods (Ohl & Scheich, 2005; Peters et al. , 2017;
Irvine, 2018). One of them is the investigation of the density of the
extracellular matrix (ECM) by using immunofluorescence luminance of
Wisteria floribunda lectin-fluoresceine-5-isothiocyanate (WFA-FITC) on
histological slices (e.g., Happel et al. , 2014). The higher the
density (WFA-FITC luminance) of the ECM, the more stable are the
synapses connecting the neurons and therefore the less likely it is that
a once formed pattern can be changed by new information (Dityatevet al. , 2010; Gundelfinger et al. , 2010). With that in
mind, we asked, how the ECM density of the primary AC – and indirectly
the potential for neuroplasticity of that area – is affected by
tinnitus after its chronification in our animal model, the Mongolian
gerbil (Meriones unguiculatus ).