Treatment of 10 days of rTMS over auditory cortex in 116 patients with chronic tinnitus resulted in a near significant, but very small reduction of RMT (1% stimulator output) for the whole group. Since stimulation intensity in most rTMS treatment studies is adjusted to the resting motor threshold (RMT) several earlier studies investigated whether rTMS treatment changes the RMT [5, 14–16, 31–42]. Findings in these studies are not entirely consistent and it also remains unclear whether observed fluctuations of RMT during the course of rTMS treatment rather reflect variations of cortical excitability or rather an inherent inaccuracy of the measurement procedure of the RMT . Despite these uncertainties there are recommendations to re-measure the RMT over the course of treatment and to adjust the stimulation intensity accordingly . However, the mean reduction by about 1% of the stimulator output in our sample rather suggests that the induced changes in RMT are negligible. Changes in cortical excitability would be meaningful if RMT were shown to be reliable and if stimulation intensity was falling above safe intensity or below effective targeting the brain due to changes of RMT.
Treatment responders as identified by a 5-point reduction in the TQ showed increased SICI at the beginning of the treatment and a reduction over the course of the treatment. Non-responders showed the reverse pattern. Because of the lack of a placebo group we cannot definitively conclude that the observed reduction of SICI during treatment in the responder-group is related to successful rTMS treatment. Theoretically the SICI change could also reflect tinnitus reduction alone, independently of the kind of intervention. However the fact that the responder and non-responder group also differed in their baseline values of SICI makes the latter explanation extremely unlikely.
A relationship between treatment response and a reduction of SICI has not yet been reported before. The discrepancy to previous results may be related to statistical power since the here presented data are from the biggest sample so far. Two studies in healthy controls found no effects of temporal rTMS on SICI [14, 15]; in a small sample of tinnitus patients low frequency temporal rTMS increased SICI  and also high frequency prefrontal rTMS in patients with major depression increased SICI . However, authors stimulated the left dorso-lateral prefrontal cortex with 20Hz. We used three different treatments all including temporal 1Hz stimulation of the auditory cortex with one treatment including a 20Hz stimulation of left dorso-lateral prefrontal cortex before the temporal stimulation. We did not find any treatment specific effects. One could speculate that opposite effects on SICI after low frequency (decrease of SICI in the present study) and high-frequency rTMS [increase of SICI in 31] may reflect the well-established frequency-dependency of the direction of rTMS treatment effects . However, it is unclear, whether the findings from motor cortex can be directly transferred to non-motor areas since the exact mechanism of the observed cross-modal interaction still remains to be elucidated.
Nevertheless, our findings of altered SICI add further evidence to the notion of cross-modal plasticity of motor cortex in context of stimulation of non-motor areas. Considered mechanisms as indicated by studies in synaesthesia and sensory deprivation (e.g. deafness or blindness) may take place via multi-sensory association areas, via direct cortico-cortical connections, or via subcortical interplay of the corresponding sensory systems at the thalamic level [44–47]. In tinnitus and other neuropsychiatric disorders, the model of thalamocortical dysrhythmia considers altered thalamic activity due to deprived afferent input as the core of the pathology. This altered thalamic activity is generating altered cortical activity which in turn induces symptoms such as phantom perceptions . Based on this concept one could assume that the observed effects on motor cortex excitability in treatment responders are mediated via rTMS induced modulation of thalamic activity. The exact mechanism which underlies the observed cross-modal plasticity effect in this study might be best evaluated by future connectivity studies. Dynamic causal modelling would enable the modelling of the direction of information flow of assumed network hubs. Such studies could elucidate, whether our findings may reflect region-specific changes mediated via specific cross-modal pathways or rather global changes as an unspecific response to local stimulation.
Beside anatomical considerations of cross-modal plasticity, our findings can also be discussed in the context of trans-synaptic chemical signalling. Both antidepressant effects  and tinnitus reduction , are mediated by the inhibitory-acting γ-aminobutyric acid (GABA). GABA is also involved in motor cortex excitability and plasticity for an overview [50, 51]. Especially SICI is mediated by GABAergic interneurons within the primary motor cortex [50, 52]. For tinnitus, evidence for GABAergic involvement comes from pharmacological treatments [for an overview 49], animal models , and genetic analyses e.g., . Recent studies in animal models of tinnitus identified deficient inhibitory function in input-deprived auditory regions . If low frequency rTMS reduces tinnitus by renormalizing inhibitory function in the auditory cortex, the observed reduction of SICI in treatment responders could reflect the subsequent reduction of a compensatory global inhibitory effort. Following this reasoning the increased baseline SICI may then reflect reduced inhibitory tone in the auditory system. It seems reasonable that rTMS can only exert an effect on tinnitus, if the inhibitory function in the auditory system is altered. In this study we found no effects for other excitability measures. Since RMT, ICF and CSP are rather modulated by other neurotransmitters and -receptors, our findings highlight the role of GABAA mediated neurotansmission in rTMS treatment effects in tinnitus [41, 42]. We are well aware that this interpretation is highly speculative and needs to be confirmed by further studies, before further conclusions can be drawn.
On a functional level auditory-motor connectivity might be related to functions of speech or music perception. The motor theory of speech perception links vocal tract gestures to the perception of speech . Beat induction and rhythm perception helps to identify regular patterns in music with the aim to get synchronised by clapping, dancing, or singing . Electrophysiological markers of this transfer may be grounded in the existence of rhythmic oscillatory activity of mu or alpha-like frequencies . Based on these considerations the anatomical, neurotransmitter, and functional association of treatment response to temporal stimulation in tinnitus with SICI highlights the role of auditory-motor connectivity in rTMS treatment of tinnitus. Future clinical approaches might be the identification of responders of daily rTMS based on measurements of SICI changes after single rTMS sessions.