Prefrontal-Temporal Pathway Mediates the Cross-Modal and Cognitive Reorganization in Sensorineural Hearing Loss With or Without Tinnitus: A Multimodal MRI Study

Ying Luan, Congxiao Wang, Yun Jiao, Tianyu Tang, Jian Zhang, Gao-Jun Teng, Ying Luan, Congxiao Wang, Yun Jiao, Tianyu Tang, Jian Zhang, Gao-Jun Teng

Abstract

Objective: Hearing loss, one main risk factor of tinnitus and hyperacusis, is believed to involve significant central functional abnormalities. The recruitment of the auditory cortex in non-auditory sensory and higher-order cognitive processing has been demonstrated in the hearing-deprived brain. The dorsolateral prefrontal cortex (dlPFC), which has dense anatomical connections with the auditory pathway, is known to play a crucial role in multi-sensory integration, auditory regulation, and cognitive processing. This study aimed to verify the role of the dlPFC in the cross-modal reorganization and cognitive participation of the auditory cortex in long-term sensorineural hearing loss (SNHL) by combining functional and structural measurements. Methods: Thirty five patients with long-term bilateral SNHL and 35 matched healthy controls underwent structural imaging, resting-state functional magnetic resonance imaging (rs-fMRI), diffusion tensor imaging (DTI), and neuropsychological assessments. Ten SNHL patients were with subjective tinnitus. Results: No differences in gray matter volume, spontaneous neural activity, or diffusion characteristics in the dlPFC were found between the SNHL and control groups. The functional connectivity (FC) between the dlPFC and the auditory cortex and visual areas, such as the cuneus, fusiform, lingual cortex, and calcarine sulcus was increased in patients with SNHL. ANOVA and post hoc tests revealed similar FC alterations in the SNHL patients with and without tinnitus when compared with the normal hearing controls, and SNHL patients with and without tinnitus showed no difference in the dlPFC FC. The FC in the auditory cortex was associated with the symbol digit modality test (SDMT) scores in the SNHL patients, which reflect attentional function, processing speed, and visual working memory. Hearing-related FC with the dlPFC was found in the lingual cortex. A tract-based spatial statistics (TBSS) analysis revealed decreased fractional anisotropy (FA) values, mainly in the temporal inferior fronto-occipital fasciculus (IFOF), which showed remarkable negative correlations with the mean hearing thresholds in SNHL. Conclusion: Higher functional coupling between the dlPFC and auditory and visual areas, accompanied by decreased FA along the IFOF connecting the frontal cortex and the occipito-temporal area, might mediate cross-modal plasticity via top-down regulation and facilitate the involvement of the auditory cortex in higher-order cognitive processing following long-term SNHL.

Keywords: cognition; cross-modal reorganization; dorsolateral prefrontal cortex; multimodal MRI; resting-state functional connectivity; sensorineural hearing loss; tinnitus; tract-based spatial statistics.

Figures

FIGURE 1
FIGURE 1
The hearing thresholds of (A) right side and (B) left side at 250, 500, 1000, 2000, 4000, and 8000 Hz in the control and SNHL groups. (C) No side differences in mean hearing thresholds are shown for either group. The mean hearing thresholds for each side in patients with SNHL are significantly higher than in healthy controls. The data are shown as mean ± standard deviation. ∗∗∗∗p < 0.0001.
FIGURE 2
FIGURE 2
(A) The between-group difference distribution map of FC with the seed set to the left and right dlPFC independent of age, sex, or education (p < 0.05, corrected by FDR). Significantly increased FC is present in the red-yellow heat scales. The color bar below shows the t-scores obtained from the between-group comparisons. The SDMT scores are positively correlated with the left dlPFC-seeded FC in the right cuneus (B), left dlPFC-seeded FC in the right STG (C), and the right dlPFC-seeded FC in the right STG (D) in patients with SNHL, after controlling for age, sex, and education. FC, functional connectivity; dlPFC, dorsolateral prefrontal cortex; FDR, false discovery rate; SDMT, Symbol Digit Modalities Test; STG, superior temporal gyrus; ROI, region of interest; L, left; R, right.
FIGURE 3
FIGURE 3
Receiver operating characteristic curves for differentiating patients with SNHL and healthy controls based on the significant FC with the left dlPFC (A) and right dlPFC (B). AUC, area under the receiver operating characteristic curve.
FIGURE 4
FIGURE 4
The between-group difference distribution map of FC with the seed set to the left and right dlPFC among the SNHL without tinnitus, SNHL with tinnitus, and healthy controls, independent of age, sex, or education (p < 0.05/3, corrected by FDR). Significantly increased FC is present in the red-yellow heat scales. The color bars show the t scores obtained from the between-group comparisons.
FIGURE 5
FIGURE 5
(A) Voxel-wise hearing-related FC patterns with the left and right dlPFC in patients with SNHL, independent of age, sex, and education. Significant positive correlations are presented in the red-yellow heat scales. The color bar below shows the z-scores. The scatterplots show the correlations in the patients with SNHL between the binaural mean hearing thresholds with the mean left dlPFC-seeded FC in the left lingual gyrus (B) and the mean right dlPFC-seeded FC in the right lingual gyrus (C), which were shown to be significant by the voxel-wise correlation analysis, after controlling for the effects of age, sex, and education.
FIGURE 6
FIGURE 6
(A) Distribution map of the FA value that was significantly lower in the SNHL group compared with the control group based on the TBSS analysis. The mean FA skeleton (green) is overlaid with the blue clusters denoting significantly decreased FA values in patients with SNHL. The color bar on the left presents the p-value. The mean FA values in the significant cluster of the right temporal lobe are positively correlated with the binaural mean hearing thresholds in patients with SNHL, after controlling for the effects of the age, sex, and education (B). FA, fractional anisotropy; IFOF, inferior fronto-occipital fasciculus; ILF, inferior longitudinal fasciculus; SLF, superior longitudinal fasciculus.

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