Specific brain network predictors of interventions with different mechanisms for tinnitus patients

BACKGROUND: The aberrant brain network that gives rise to the phantom sound of tinnitus is believed to determine the effectiveness of tinnitus therapies involving neuromodulation with repetitive transcranial magnetic stimulation (rTMS) and sound therapy utilizing tailor-made notch music training (TMNMT). To test this hypothesis, we determined how effective rTMS or TMNMT were in ameliorating tinnitus in patients with different functional brain networks. METHODS: Resting-state functional MRI was used to construct brain functional networks in patients with tinnitus (41 males/45 females, mean age 49.53±11.19 years) and gender-matched healthy controls (22 males/35 females, mean age 46.23±10.23 years) with independent component analysis (ICA). A 2 × 2 analysis of variance with treatment outcomes (Effective group, EG/Ineffective group, IG) and treatment types (rTMS/TMNMT) was used to test the interaction between outcomes and treatment types associated with functional network connections (FNCs). FINDINGS: The optimal neuroimaging indicator for responding to rTMS (AUC 0.804, sensitivity 0.700, specificity 0.913) was FNCs in the salience network-right frontoparietal network (SN-RFPN) while for responding to TMNMT (AUC 0.764, sensitivity 0.864, specificity 0.667) was the combination of FNCs in the auditory network- salience network (AUN-SN) and auditory network-cerebellar network (AUN-CN). INTERPRETATION: Tinnitus patients with higher FNCs in the SN-RFPN is associated with a recommendation for rTMS whereas patients with lower FNCs in the AUN-SN and AUN-CN would suggest TMNMT as the better choice. These results indicate that brain network-based measures aid in the selection of the optimal form of treatment for a patient contributing to advances in precision medicine. FUNDING: Yuexin Cai is supported by Key R&D Program of Guangdong Province, China (Grant No. 2018B030339001), National Natural Science Foundation of China (82071062), Natural Science Foundation of Guangdong province (2021A1515012038), the Fundamental Research Funds for the Central Universities (20ykpy91), and Sun Yat-Sen Clinical Research Cultivating Program (SYS-Q-201903). Yu-Chen Chen is supported by Medical Science and Technology Development Foundation of Nanjing Department of Health (No. ZKX20037), and Natural Science Foundation of Jiangsu Province (No. BK20211008).