Source-Space Cross-Frequency Amplitude-Amplitude Coupling in Tinnitus

Abstract

The thalamocortical dysrhythmia (TCD) model has been influential in the development of theoretical explanations for the neurological mechanisms of tinnitus. It asserts that thalamocortical oscillations lock a region in the auditory cortex into an ectopic slow-wave theta rhythm (4-8 Hz). The cortical area surrounding this region is hypothesized to generate abnormal gamma (>30 Hz) oscillations ("edge effect") giving rise to the tinnitus percept. Consequently, the model predicts enhanced cross-frequency coherence in a broad range between theta and gamma. In this magnetoencephalography study involving tinnitus and control cohorts, we investigated this prediction. Using beamforming, cross-frequency amplitude-amplitude coupling (AAC) was computed within the auditory cortices for frequencies (f1, f2) between 2 and 80 Hz. We find the AAC signal to decompose into two distinct components at low (f1, f2 < 30 Hz) and high (f1, f2 > 30 Hz) frequencies, respectively. Studying the correlation of AAC with several key covariates (age, hearing level (HL), tinnitus handicap and duration, and HL at tinnitus frequency), we observe a statistically significant association between age and low-frequency AAC. Contrary to the TCD predictions, however, we do not find any indication of statistical differences in AAC between tinnitus and controls and thus no evidence for the predicted enhancement of cross-frequency coupling in tinnitus.

Figure 1

Subject-averaged AAC comodulograms for (a) controls and (b) tinnitus participants.

Figure 2

Comodulograms after removing AAC through reshuffling. (a) Single-subject comodulogram after averaging over voxels. (b) Average of single-subject comodulograms (as in (a)) over all controls. (c) Histogram of maximum AAC in control-averaged comodulograms for 1000 realizations.

Figure 3

Frequency-resolved correlation maps between AAC and (a) age and (b) hearing level. The correlation at a frequency pair (f ₁, f ₂) is between the AAC values at that frequency combination and the respective covariate across all subjects.

Figure 4

Frequency-resolved maps of (a) partial correlations between AAC and group assignment controlling for age and (b) t statistics for the group comparison between tinnitus and control subjects.

Figure 5

(a) Mean difference in AAC between the auditory cortices ipsilateral and contralateral to the tinnitus, in subjects with unilateral tinnitus. (b) Thresholded map of the corresponding pairwise t statistic showing the observed clusters used in the permutation test.

Figure 6

Frequency-resolved correlation maps between AAC and (a) the THI score, (b) tinnitus duration, and (c) the hearing threshold at the tinnitus frequency.