EEG spectral and microstate analysis originating residual inhibition of tinnitus induced by tailor-made notched music training

Abstract

Tailor-made notched music training (TMNMT) is a promising therapy for tinnitus. Residual inhibition (RI) is one of the few interventions that can temporarily inhibit tinnitus, which is a useful technique that can be applied to tinnitus research and explore tinnitus mechanisms. In this study, RI effect of TMNMT in tinnitus was investigated mainly using behavioral tests, EEG spectral and microstate analysis. To our knowledge, this study is the first to investigate RI effect of TMNMT. A total of 44 participants with tinnitus were divided into TMNMT group (22 participants; ECnm, NMnm, RInm represent that EEG recordings with eyes closed stimuli-pre, stimuli-ing, stimuli-post by TMNMT music, respectively) and Placebo control group (22 participants; ECpb, PBpb, RIpb represent that EEG recordings with eyes closed stimuli-pre, stimuli-ing, stimuli-post by Placebo music, respectively) in a single-blind manner. Behavioral tests, EEG spectral analysis (covering delta, theta, alpha, beta, gamma frequency bands) and microstate analysis (involving four microstate classes, A to D) were employed to evaluate RI effect of TMNMT. The results of the study showed that TMNMT had a stronger inhibition ability and longer inhibition time according to the behavioral tests compared to Placebo. Spectral analysis showed that RI effect of TMNMT increased significantly the power spectral density (PSD) of delta, theta bands and decreased significantly the PSD of alpha2 band, and microstate analysis showed that RI effect of TMNMT had shorter duration (microstate B, microstate C), higher Occurrence (microstate A, microstate C, microstate D), Coverage (microstate A) and transition probabilities (microstate A to microstate B, microstate A to microstate D and microstate D to microstate A). Meanwhile, RI effect of Placebo decreased significantly the PSD of alpha2 band, and microstate analysis showed that RI effect of Placebo had shorter duration (microstate C, microstate D), higher occurrence (microstate B, microstate C), lower coverage (microstate C, microstate D), higher transition probabilities (microstate A to microstate B, microstate B to microstate A). It was also found that the intensity of tinnitus symptoms was significant positively correlated with the duration of microstate B in five subgroups (ECnm, NMnm, RInm, ECpb, PBpb). Our study provided valuable experimental evidence and practical applications for the effectiveness of TMNMT as a novel music therapy for tinnitus. The observed stronger residual inhibition (RI) ability of TMNMT supported its potential applications in tinnitus treatment. Furthermore, the temporal dynamics of EEG microstates serve as novel functional and trait markers of synchronous brain activity that contribute to a deep understanding of the neural mechanism underlying TMNMT treatment for tinnitus.

Keywords: EEG; microstate; residual inhibition; spectral analysis; tailor-made notched music training; tinnitus.

Figure 1

Experimental pipeline. ECnm, NMnm, RInm subgroups in TMNMT group and ECpb, PBpb, RIpb subgroups in Placebo group. ECnm, EEG recordings with eyes closed stimuli-pre by TMNMT music; NMnm, EEG recordings with eyes closed stimuli-ing by TMNMT music; RInm, EEG recordings with eyes closed stimuli-post by TMNMT music; ECpb, EEG recordings with eyes closed stimuli-pre by Placebo music; PBpb, EEG recordings with eyes closed stimuli-ing by Placebo music; RIpb, EEG recordings with eyes closed stimuli-post by Placebo music.

Figure 2

A standard procedure of EEG microstate analysis. Based on (A) the preprocessed EEG data, (B) candidate topographies with high signal-to-noise ratios were extracted from the local maxima of the GFP curve, (C) four templates were obtained after AAHC Clustering. (D) The final detected EEG microstate templates were then fitted back into the preprocessed EEG data by assigning each time point to a predominant microstate. After EEG microstates back-fitting, the original EEG time series were re-represented into EEG microstate sequences covering whole-brain spontaneous spatial–temporal activities. (E) A several of microstate feature metrics were calculated for quantitative measurement, including duration, occurrence, coverage, transition probability.

Figure 3

The intensity and duration of residual inhibition (RI) between TMNMT and Placebo groups. (A) TMNMT: −3.6 ± 1.3; Placebo: −1.1 ± 1.6, p = 0.0257; (B) TMNMT: 403 ± 215 s; Placebo: 96 ± 123 s, p = 0.0045; *p < 0.05, **p < 0.01.

Figure 4

Waveforms of spectral analysis in TMNMT group. (A) The power spectral density (PSD) waveform of full frequency bands in ECnm, NMnm, RInm subgroups of TMNMT group. (B–G) The PSD of delta (B), theta (C), alpha2 (D), beta2 (E), beta3 (F), gamma2 (G) bands in ECnm, NMnm, RInm subgroups of TMNMT group. ECnm, EEG recordings with eyes closed stimuli-pre by TMNMT music; NMnm, EEG recordings with eyes closed stimuli-ing by TMNMT music; RInm, EEG recordings with eyes closed stimuli-post by TMNMT music. *p < 0.05, **p < 0.01, ***p < 0.001.

Figure 5

Waveforms of spectral analysis in Placebo group. (A) The power spectral density (PSD) waveform of full frequency bands in ECpb, PBpb, RIpb subgroups of Placebo group. (B–G) The PSD of delta (B), theta (C), alpha2 (D), beta2 (E), beta3 (F), gamma2 (G) bands in ECpb, PBpb, RIpb subgroups of Placebo group. ECpb, EEG recordings with eyes closed stimuli-pre by Placebo music; PBpb, EEG recordings with eyes closed stimuli-ing by Placebo music; RIpb, EEG recordings with eyes closed stimuli-post by Placebo music. *p < 0.05, **p < 0.01.

Figure 6

Scalp topographies of spectral analysis in TMNMT group. (A–F) Comparison of ECnm, NMnm, RInm of delta (A), theta (B), alpha2 (C), beta2 (D), beta3 (E), and gamma2 (F) bands. The first column showed the PSD across the whole brain within each subgroup, the second and third column showed the uncorrected p values and corrected p values for multiple comparisons of a false discovery rate (FDR) across the whole brain within each two subgroups, respectively. ECnm, EEG recordings with eyes closed stimuli-pre by TMNMT music; NMnm, EEG recordings with eyes closed stimuli-ing by TMNMT music; RInm, EEG recordings with eyes closed stimuli-post by TMNMT music.

Figure 7

Scalp topographies of spectral analysis in Placebo group. (A–F) Comparison of ECpb, PBpb, RIpb of delta (A), theta (B), alpha2 (C), beta2 (D), beta3 (E), and gamma2 (F) bands. The first column showed the PSD across the whole brain within each subgroup, the second and third column showed the uncorrected p values and corrected p values for multiple comparisons of a false discovery rate (FDR) across the whole brain within each two subgroups, respectively. ECpb, EEG recordings with eyes closed stimuli-pre by Placebo music; PBpb, EEG recordings with eyes closed stimuli-ing by Placebo music; RIpb, EEG recordings with eyes closed stimuli-post by Placebo music.

Figure 8

The spatial configuration of the four microstate topographies, separately for (A) TMNMT group and (B) Placebo group. Each row showed the three subgroups of TMNMT group and Placebo group. Each column showed the four topographic configurations (microstate A, B, C, D) for each subgroup. ECnm, EEG recordings with eyes closed stimuli-pre by TMNMT music; NMnm, EEG recordings with eyes closed stimuli-ing by TMNMT music; RInm, EEG recordings with eyes closed stimuli-post by TMNMT music; ECpb, EEG recordings with eyes closed stimuli-pre by Placebo music; PBpb, EEG recordings with eyes closed stimuli-ing by Placebo music; RIpb, EEG recordings with eyes closed stimuli-post by Placebo music.

Figure 9

Microstate analysis of temporal metrics results: duration, occurrence, and coverage. Violin plots show each microstate class in the three subgroups of TMNMT and Placebo groups. (A) Microstate B of RInm had a shorter duration compared to ECnm, microstate C of RInm had a shorter duration compared to NMnm. (B) Microstate A of RInm had a higher occurrence compared to ECnm and NMnm, microstate C of NMnm had a higher occurrence compared to ECnm, and microstate D of RInm had a higher occurrence compared to NMnm. (C) microstate A of RInm had a higher coverage compared to ECnm and NMnm, microstate C of RInm had a lower coverage compared to NMnm. (D) Microstate C of PBpb had a shorter duration compared to ECpb, and microstate D of RIpb had a shorter duration compared to PBpb. (E) Microstate B of RIpb had a higher occurrence compared to ECpb and PBpb, microstate C of RIpb had a higher occurrence compared to PBpb. (F) Microstate C of PBpb had a lower coverage compared to ECpb and RIpb had a higher coverage compared to PBpb, microstate D of RIpb had a lower coverage compared to PBpb. ECnm, EEG recordings with eyes closed stimuli-pre by TMNMT music; NMnm, EEG recordings with eyes closed stimuli-ing by TMNMT music; RInm, EEG recordings with eyes closed stimuli-post by TMNMT music; ECpb, EEG recordings with eyes closed stimuli-pre by Placebo music; PBpb, EEG recordings with eyes closed stimuli-ing by Placebo music; RIpb, EEG recordings with eyes closed stimuli-post by Placebo music. *p < 0.05, **p < 0.01.

Figure 10

Schematic view of microstate syntax analysis results. A significant difference in transition probabilities for each pair of microstate class between ECnm subgroup and RInm subgroup (A), ECpb subgroup and RIpb subgroup (B). ECnm, EEG recordings with eyes closed stimuli-pre by TMNMT music; RInm, EEG recordings with eyes closed stimuli-post by TMNMT music; ECpb, EEG recordings with eyes closed stimuli-pre by Placebo music; RIpb, EEG recordings with eyes closed stimuli-post by Placebo music.

Figure 11

Correlation between the duration of microstate B and each subgroup. ECnm, EEG recordings with eyes closed stimuli-pre by TMNMT music; NMnm, EEG recordings with eyes closed stimuli-ing by TMNMT music; RInm, EEG recordings with eyes closed stimuli-post by TMNMT music; ECpb, EEG recordings with eyes closed stimuli-pre by Placebo music; PBpb, EEG recordings with eyes closed stimuli-ing by Placebo music; RIpb, EEG recordings with eyes closed stimuli-post by Placebo music.

Figure 12

Waveforms of spectral analysis in ECnm vs. ECpb subgroups. (A–F) The PSD of delta (A), theta (B), alpha2 (C), beta2 (D), beta3 (E), gamma2 (F) bands in ECnm vs. ECpb subgroups. ECnm, EEG recordings with eyes closed stimuli-pre by TMNMT music; ECpb, EEG recordings with eyes closed stimuli-pre by Placebo music.

Figure 13

Scalp topographies of spectral analysis in ECnm vs. ECpb subgroups. (A–F) Comparison of ECnm, ECpb of delta (A), theta (B), alpha2 (C), beta2 (D), beta3 (E), and gamma2 (F) bands. The first column showed the PSD across the whole brain within each subgroup, the first and second rows of the second column showed the uncorrected p values and corrected p values for multiple comparisons of a false discovery rate (FDR) across the whole brain within each two subgroups, respectively. ECnm, EEG recordings with eyes closed stimuli-pre by TMNMT music; ECpb, EEG recordings with eyes closed stimuli-pre by Placebo music.