Changes of oscillatory activity in pitch processing network and related tinnitus relief induced by acoustic CR neuromodulation

Abstract

Chronic subjective tinnitus is characterized by abnormal neuronal synchronization in the central auditory system. As shown in a controlled clinical trial, acoustic coordinated reset (CR) neuromodulation causes a significant relief of tinnitus symptoms along with a significant decrease of pathological oscillatory activity in a network comprising auditory and non-auditory brain areas, which is often accompanied with a significant tinnitus pitch change. Here we studied if the tinnitus pitch change correlates with a reduction of tinnitus loudness and/or annoyance as assessed by visual analog scale (VAS) scores. Furthermore, we studied if the changes of the pattern of brain synchrony in tinnitus patients induced by 12 weeks of CR therapy depend on whether or not the patients undergo a pronounced tinnitus pitch change. Therefore, we applied standardized low-resolution brain electromagnetic tomography (sLORETA) to EEG recordings from two groups of patients with a sustained CR-induced relief of tinnitus symptoms with and without tinnitus pitch change. We found that absolute changes of VAS loudness and VAS annoyance scores significantly correlate with the modulus, i.e., the absolute value, of the tinnitus pitch change. Moreover, as opposed to patients with small or no pitch change we found a significantly stronger decrease in gamma power in patients with pronounced tinnitus pitch change in right parietal cortex (Brodmann area, BA 40), right frontal cortex (BA 9, 46), left temporal cortex (BA 22, 42), and left frontal cortex (BA 4, 6), combined with a significantly stronger increase of alpha (10-12 Hz) activity in the right and left anterior cingulate cortex (ACC; BA 32, 24). In addition, we revealed a significantly lower functional connectivity in the gamma band between the right dorsolateral prefrontal cortex (BA 46) and the right ACC (BA 32) after 12 weeks of CR therapy in patients with pronounced pitch change. Our results indicate a substantial, CR-induced reduction of tinnitus-related auditory binding in a pitch processing network.

Keywords: coordinated reset neuromodulation; electroencephalography; gamma band activity; phantom perception; pitch; tinnitus.

FIGURE 1

Changes in VAS-L (A) and VAS-A (B) as a function of a tinnitus pitch change ratio. Patients are divided into two groups: (1) tinnitus pitch decrease (blue, n = 46); (2) tinnitus pitch increase (green, n = 13 or red dashed line after removal of an outlier, n = 12). An outlier patient is marked by the red circle.

FIGURE 2

Changes in VAS-L (A) and VAS-A (B) as a function of the modulus tinnitus pitch change ratio with all patients included (n = 59, solid red line) or with the outlier (marked by the red circle) excluded from the analysis (n = 58, dashed blue line).

FIGURE 3

EEG source localization (sLORETA) power maps for the PC–NPC paired-groups comparison. (A) Alpha2 (10–12 Hz) increased (color-coded red) in the right and left anterior cingulate cortex (BA 24, 32). (B) Gamma band power decreased (color-coded blue) with pitch change in the left parietal (BA 40), left temporal (BA 22, 42), right frontal (BA 9, 46), and left frontal (BA 4, 6) cortex.

FIGURE 4

Significant negative partial correlation between relative change of CSD gamma power and modulus of tinnitus pitch change ratio (A) with all patients included (r = -0.31, p = 0.02, solid red line) or with the outlier excluded (r = -0.29, p = 0.03, dashed blue line). The outlier patient is marked by the red circle. A significant negative correlation (r = -0.33, p = 0.01, n = 59) between relative change of anterior cingulate CSD alpha power and difference in VAS-A (B).

FIGURE 5

Connectivity contrast analysis between PC and NPC patients. rmANOVA analysis was applied to those brain areas which showed differential effects of CR therapy depending on whether or not tinnitus pitch changed strongly (see Figure 3). Decreased gamma lagged linear connectivity can be seen in PC patients between right ACC (BA 32) and DLPFC (BA 46).