Table 2.
Overview of the eight studies included in the review.
| Reference, country | Study design | Sample | Outcome measures | Main results |
|---|---|---|---|---|
| Tass et al. (27), Germany | Computer analysis | None | Coordinated reset (CR) neuromodulation: model presentation illustrating the concept of CR in a simplified neuronal model, considering neurons with spike timing-dependent plasticity transformation of the concept of deep brain stimulation into non-invasive, acoustic CR stimulation | Non-invasive acoustic CR neuromodulation may be a novel therapy for tinnitus |
| Tass et al. (23), Germany | Prospective, randomized, single blind, placebo-controlled trial: RESET | 63 | Visual analog scale (VAS) | CR neuromodulation caused a significant decrease of tinnitus loudness and symptoms, and reversed tinnitus-related EEG alterations |
| Tinnitus Questionnaire (TQ) | ||||
| Tinnitus frequency | ||||
| Spontaneous EEG | ||||
| Adamchic et al. (28), Germany | Part of RESET | 59 | Tinnitus pitch change versus tinnitus loudness and/or annoyance (VAS score) | VAS scores significantly correlated with the absolute value of the CR neuromodulation-induced tinnitus pitch change (r = 0.92 baseline to 12 weeks, p < 0.01) |
| Changes of brain synchrony induced by CR neuromodulation versus tinnitus pitch change | Significant changes in brain activity were associated with a pronounced tinnitus pitch change | |||
| Adamchic et al. (29), Germany | Part of RESET | 28 | EEG pattern in the tinnitus patients after CR neuromodulation versus EEG pattern in healthy controls | Tinnitus patients significantly deviated from healthy controls concerning oscillatory brain activity |
| EEG in tinnitus patients before and after acoustic CR neuromodulation | CR neuromodulation significantly normalized patient’s brain oscillations in all frequency bands | |||
| Relationship between CR neuromodulation-induced changes of different resting EEG parameters and tinnitus symptoms | CR neuromodulation-induced normalization of EEG power was significantly associated with reduction of tinnitus severity | |||
| Silchenko et al. (30), Germany | Part of RESET | 28 | Comparison of EEG in tinnitus patients before and after CR neuromodulation | CR neuromodulation significantly normalized both power and causal interactions within a tinnitus-related network |
| Comparison of EEG in tinnitus patients with healthy controls | CR neuromodulation specifically counteracted an imbalance of excitation and inhibition in tinnitus patients | |||
| CR neuromodulation qualitatively changed the spectral response of the tinnitus network by modifying the shape of the averaged transfer function, so that the latter became similar to the control group | ||||
| Adamchic et al. (31), Germany, USA | Re-analysis of existing dataset from RESET | 59 | To investigate how the oscillations in the various frequency bands interact | Identification of changes of cross-frequency coupling (CFC) |
| Phase–amplitude CFC increased in tinnitus patients within the auditory cortex and the dorsolateral prefrontal regions between the phase of delta-theta and the amplitude of gamma oscillations | ||||
| Theta phase in the anterior cingulate region modulated gamma in the auditory and dorsolateral prefrontal regions | ||||
| Hauptmann et al. (26), Germany, UK, USA | Prospective open-label, non-randomized, non-controlled multicenter clinical study | 200 | TQ (TBF-12) | TBF-12 (total score) showed a mean reduction of 4.1 points (−37.9%) compared to baseline (p < 0.01) |
| 23 study centers | Global Clinical Improvement-Impression Scale (CGI-I7) | CGI-I7 revealed that 66.9% of the patients reported an improvement of tinnitus [very much improved (8.7%), much improved (25%), or slightly improved (33.2%)] (p < 0.01) | ||
| Numeric Rating Scale (NRS) (0–100) | Tinnitus-related loudness and annoyance were reduced by 11.1 points (18.9%) and 14.7 points (25.2%), respectively, compared to baseline (p < 0.01) on the NRS | |||
| Williams et al. (32), UK, Germany | Clinical case study, open-label, non-randomized, non-controlled | 66 | Tinnitus Handicap Questionnaire (THQ) score | VAS scores were significantly improved: 25.8% mean reduction in tinnitus loudness, 32% mean reduction in tinnitus annoyance (p < 0.01 compared to baseline) |
| VAS for tinnitus annoyance and loudness | A clinically significant reduction in tinnitus loudness and annoyance was recorded in 59.1 and 72.7% of the patient group, respectively | |||
| THQ scores were significantly improved by an average of 19.4% (p < 0.01) | ||||
| 58.8% of patients experienced a clinically significant reduction in THQ score | ||||