Tinnitus distress is linked to enhanced resting-state functional connectivity from the limbic system to the auditory cortex

Abstract

The phantom sound of tinnitus is believed to be triggered by aberrant neural activity in the central auditory pathway, but since this debilitating condition is often associated with emotional distress and anxiety, these comorbidities likely arise from maladaptive functional connections to limbic structures such as the amygdala and hippocampus. To test this hypothesis, resting-state functional magnetic resonance imaging (fMRI) was used to identify aberrant effective connectivity of the amygdala and hippocampus in tinnitus patients and to determine the relationship with tinnitus characteristics. Chronic tinnitus patients (n = 26) and age-, sex-, and education-matched healthy controls (n = 23) were included. Both groups were comparable for hearing level. Granger causality analysis utilizing the amygdala and hippocampus as seed regions were used to investigate the directional connectivity and the relationship with tinnitus duration or distress. Relative to healthy controls, tinnitus patients demonstrated abnormal directional connectivity of the amygdala and hippocampus, including primary and association auditory cortex, and other non-auditory areas. Importantly, scores on the Tinnitus Handicap Questionnaires were positively correlated with increased connectivity from the left amygdala to left superior temporal gyrus (r = 0.570, P = 0.005), and from the right amygdala to right superior temporal gyrus (r = 0.487, P = 0.018). Moreover, enhanced effective connectivity from the right hippocampus to left transverse temporal gyrus was correlated with tinnitus duration (r = 0.452, P = 0.030). The results showed that tinnitus distress strongly correlates with enhanced effective connectivity that is directed from the amygdala to the auditory cortex. The longer the phantom sensation, the more likely acute tinnitus becomes permanently encoded by memory traces in the hippocampus. Hum Brain Mapp 38:2384-2397, 2017. © 2017 Wiley Periodicals, Inc.

Keywords: effective connectivity; functional connectivity; limbic system; resting-state fMRI; tinnitus.

Figure 1

Altered effective connectivity from the amygdala to the whole brain regions in tinnitus patients compared with healthy controls. (A) From the left amygdala to the other brain regions. (B) From the right amygdala to the other brain regions. Thresholds were set at a corrected P < 0.05, determined by Monte Carlo simulation. Note that the left side corresponds to the right hemisphere.

Figure 2

Altered effective connectivity from the whole brain regions to the amygdala in tinnitus patients compared with healthy controls. (A) From the other brain regions to the left amygdala. (B) From the other brain regions to the right amygdala. Thresholds were set at a corrected P < 0.05, determined by Monte Carlo simulation. Note that the left side corresponds to the right hemisphere.

Figure 3

Altered effective connectivity from the hippocampus to the whole brain regions in tinnitus patients compared with healthy controls. (A) From the left hippocampus to the other brain regions. (B) From the right hippocampus to the other brain regions. Thresholds were set at a corrected P < 0.05, determined by Monte Carlo simulation. Note that the left side corresponds to the right hemisphere.

Figure 4

Altered effective connectivity from the whole brain regions to the hippocampus in tinnitus patients compared with healthy controls. (A) From the other brain regions to the left hippocampus. (B) From the other brain regions to the right hippocampus. Thresholds were set at a corrected P < 0.05, determined by Monte Carlo simulation. Note that the left side corresponds to the right hemisphere.

Figure 5

Correlations between abnormal effective connectivity and tinnitus characteristics. (A) Correlations between the THQ scores and the increased effective connectivity from the left amygdala to the left STG (r = 0.570, P = 0.005). (B) Correlations between the THQ scores and the increased effective connectivity from the right amygdala to the right STG (r = 0.487, P = 0.018). (C) Correlations between the tinnitus duration and the enhanced effective connectivity from the right hippocampus to the left TTG (r = 0.452, P = 0.030). The correlations were corrected for age, sex, and education. THQ, Tinnitus Handicap Questionnaires; STG, Superior Temporal Gyrus; TTG, Transverse Temporal Gyrus.