Figure 1.
Patients underwent five sessions with five different rTMS protocols (including Sham). In each session, tinnitus loudness and oscillatory brain activity were measured before and after rTMS. The right upper panel illustrates the different stimulation protocols.
Figure 2.
Consistent changes in tinnitus loudness after the four active TMS protocols compared to sham.
The upper panel displays tinnitus loudness modulations that were measured with a matched-intensity approach (TIM), while the lower panel illustrates tinnitus loudness modulations that were quantified with a visual analogue scale (VAS). Sham effects are visualised in the right panel. Shown are the 95% confidence intervals. The small bars display the median. The asterisk indicates significant modulations, while the cross points to marginally significant modulations. According to the TIM, tinnitus loudness was reduced after 1-Hz rTMS. A trend pointing to a tinnitus reduction was revealed after 1-Hz rTMS and cTBS, while tinnitus loudness was marginally enhanced after IAF rTMS.
Figure 3.
Consistent changes in oscillatory activity after the four active TMS protocols compared to sham.
The upper panel displays alpha power modulations, while the lower panel illustrates modulations of high gamma power at the stimulated auditory cortex. The stimulated region and region of interest are displayed on the right side. Shown are the 95% confidence intervals. The small bars display the median while the asterisks indicate that the modulations were significant. Alpha power was significantly reduced after IAF rTMS and iTBS, while gamma power was significantly decreased by 1-Hz rTMS and iTBS (uncorrected).
Figure 4.
Changes in tinnitus loudness after application of the individually most effective stimulation protocol.
The upper panel displays tinnitus loudness modulations that were measured with the tinnitus intensity matching procedure (TIM), while the lower panel illustrates tinnitus loudness modulations that were quantified with a visual analogue scale (VAS). The 99% confidence intervals are shown on the left side. The small bars display the median. The asterisks indicate significant modulations. As expected tinnitus loudness was significantly reduced after application of the individually selected protocol that was best in reducing tinnitus. The distribution of these protocols is displayed on the right side. Note that, as the ambiguous cases (when selecting the most effective protocol with VAS) were included for this illustration, the summed frequency of occurrence can be higher than the total number of patients.
Figure 5.
Changes in tinnitus loudness after application of the stimulation protocol that enhanced tinnitus loudness.
The upper panel displays tinnitus loudness modulations that were measured with the tinnitus intensity matching procedure (TIM), while the lower panel illustrates tinnitus loudness modulations that were quantified using a visual analogue scale (VAS). The 95% confidence intervals are shown on the left side. The small bars display the median. The asterisks indicate significant modulations. As expected tinnitus loudness was significantly reduced after application of the individually selected protocol that worsened tinnitus. The distribution of these protocols is displayed on the right side. Note that, as the ambiguous cases (when selecting the most effective protocol with VAS) were included for this illustration, the summed frequency of occurrence can be higher than the total number of patients.
Figure 6.
Modulation of oscillatory activity for the most effective TMS protocols.
Shown are changes in oscillatory activity at the stimulated auditory cortex after application of the rTMS protocols that were best in reducing (black bars) and enhancing (grey bars) tinnitus loudness. The upper panel displays power modulations that were associated with the tinnitus intensity matching procedure (TIM), while the lower panel illustrates power modulations that were related to the visual analogue scale (VAS). Displayed are the 95% confidence intervals for power modulations in the stimulated auditory cortex and the different frequency bands (delta, theta, alpha, low gamma, high gamma). The small bars show the median, while the asterisk indicates the power modulations as significant. Note that we observed too many ambiguous cases for the VAS with respect to an increase in tinnitus loudness; we could thus not specify the according signature in oscillatory activity. Alpha power was significantly enhanced when tinnitus loudness was most effectively reduced by rTMS.
Figure 7.
Modulation of auditory alpha power in the individual patients.
Depicted are modulations of auditory alpha power in the individual patients and for the four active TMS protocols (black bars) and sham (grey bars). Shown are the 95% confidence intervals (uncorrected). The small bars display the median. The asterisks indicate significant modulations from pre to post TMS. The orange boxes point to significant modulations against sham stimulation. TMS modulates alpha activity significantly already in individual patients: 1 Hz rTMS (4 of 10, against Sham: 2 of 10), cTBS (10 of 10, against sham 5 of 10), IAF rTMS (4 of 10, against sham 4 of 10), iTBS (2 of 10, against Sham 3 of 10), however, not consistently into the same direction (increase vs decrease of alpha power).
Figure 8.
Modulation of oscillatory activity for the most effective TMS protocols and the individual patients.
Shown are the changes in oscillatory activity at the stimulated auditory cortex for the individual patients after application of the rTMS protocols that were best in reducing (upper panel) and enhancing (lower panel) tinnitus loudness. Shown are the 95% confidence intervals for the individual patients. The small bars display the median. Patients are ordered according to the strength of the tinnitus loudness decrease (upper panel) or increase (lower panel). The grey line illustrates the correlation between the extent of the alpha power modulation and the extent of the tinnitus loudness modulation (ordered from 1 to 10). When tinnitus loudness is maximally reduced (range of TIM values: −0.63–0) the extent of the alpha power modulation is negatively correlated with the extent of the loudness reduction (RHO: –.61, p<. 05), thus the patients with the strongest alpha power increase were the patients with the strongest tinnitus loudness decrease. In contrast, When tinnitus loudness was maximally increased no such correlation was evident (RHO: –.37, p not significant).
Figure 9.
Changes in oscillatory activity in non-auditory brain areas for the most effective stimulation protocols.
Shown are the changes in oscillatory activity in non-auditory brain areas after application of the rTMS protocols that were most effective in enhancing tinnitus loudness. The upper panel displays brain regions with power modulations in the alpha band, while the lower panel illustrates the areas exhibiting modulations in gamma power. Displayed are comparisons from pre to post rTMS and are quantified in t-values. Gamma power was significantly (p<.01; corrected) reduced in a left prefrontal, a left precentral and a left parieto-temporo-occipital region. Alpha power was reduced (p<.01; corrected) in a left superior frontal area.