Alterations in brain activity and functional connectivity originating residual inhibition of tinnitus induced by tailor-made notched music training

Tinnitus arises from the intricate interplay of multiple, parallel but overlapping networks, involving neuroplastic changes in both auditory and non-auditory activity. Tailor-made notched music training (TMNMT) has emerged as a promising therapeutic approach for tinnitus. Residual inhibition (RI) represents one of the rare interventions capable of temporarily alleviating tinnitus, offering a valuable tool that can be applied to tinnitus research to explore underlying tinnitus mechanisms. To our knowledge, this study is the first to investigate the neural mechanisms underlying the RI effect of TMNMT through analysis of neural source activity and functional connectivity of EEG. Forty-four participants with tinnitus were divided into TMNMT group (twenty-two participants; ECnm, NMnm, RInm represented that EEG recordings with eyes closed stimuli-pre, stimuli-ing, stimuli-post by TMNMT music, respectively) and Placebo control group (twenty-two participants; ECpb, PBpb, RIpb represented that EEG recordings with eyes closed stimuli-pre, stimuli-ing, stimuli-post by Placebo music, respectively) in a single-blind manner. Source localization analysis revealed that RI effect of TMNMT significantly increased in current density at the delta band in the insula, subgenual anterior cingulate cortex (sgACC), parahippocampus (PHC), and secondary auditory cortex (AⅡ), and significantly increased in current density at the theta band in the sgACC, and significantly decreased in current density at the alpha band in the precuneus, PHC, primary (AI) and secondary (AII) auditory cortex. Meanwhile, RI effect of Placebo significantly decreased in current density at the alpha band in the PHC. Functional connectivity analysis demonstrated that RI effect of TMNMT significantly increased in phase coherence between the left AⅡ and the right sgACC; and between the left PHC and the left retrosplenial cortex (RSC) at the theta band. It significantly decreased in phase coherence between the left PHC and the right precuneus, the right posterior cingulate cortex (PCC), the right AⅡ; between the right PHC and the right PCC; and between the right PCC and the right AⅡ at the alpha band. RI effect of Placebo significantly increased in phase coherence between the left insula and the right precuneus, the left PHC, the right PHC, the left AⅠ, the left AⅡ; between the left sgACC and the right PHC; between the left AⅡ and the right PHC, the left PCC at the delta band. It was found that the current density of sgACC was significantly positively correlated with the tinnitus evaluation indicators (Loudness, VAS, THI, TFI) at the alpha band in TMNMT group. These findings indicated that TMNMT, a novel music therapy for tinnitus, revealed a robust RI effect, and RI effect of TMNMT was not only involved in the activity of auditory networks (AⅠ, AⅡ), but also extended to non-auditory networks, particularly higher-level auditory association cortices, such as the sgACC, PHC and PCC. The current study provides valuable experimental evidence and promising practical prospects for the potential applications of TMNMT in tinnitus treatment.