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Abstract
Purpose
One of the suggested potential mechanisms of tinnitus is an alteration in perception in the neural auditory pathway. The aim of this study was to investigate the difference in laterality in functional connectivity between tinnitus patients and healthy controls using resting state functional MRI (rs-fMRI).
Materials and Methods
Thirty-eight chronic tinnitus subjects and 45 age-matched healthy controls were enrolled in this study. Connectivity was investigated using independent component analysis, and the laterality index map was calculated based on auditory (AN) and dorsal attention (DAN), default mode (DMN), sensorimotor, salience (SalN), and visual networks (VNs). The laterality index (LI) of tinnitus subjects was compared with that of normal controls using region-of-interest (ROI) and voxel-based methods and a two-sample unpaired t-test. Pearson correlation was conducted to assess the associations between the LI in each network and clinical variables.
Results
The AN and VN showed significant differences in LI between the two groups in ROI analysis (P < 0.05), and the tinnitus group had clusters with significantly decreased laterality of AN, SalN, and VN in voxel-based comparisons. The AN was positively correlated with tinnitus distress (tinnitus handicap inventory), and the SalN was negatively correlated with symptom duration (P < 0.05).
References
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Fig. 1.
Spatial maps of the six independent components of interest, grouped by network in tinnitus patients (right column) and controls (left column). Auditory (AN), dorsal attention network (DAN), default mode network (DMN), sensorimotor (SMN), salience network (SalN), and visual (VN) networks. Spatial maps are plotted as the t-statistics thresholded over two standard deviations. Background images are bilaterally symmetric gray-matter templates created from specific subjects.
Fig. 2.
Box and whisker plots showing the laterality index (a), and volumetric laterality ratio values (b) of the auditory (AN), dorsal attention network (DAN), default mode network (DMN), sensorimotor (SMN), salience network (SalN) and visual (VN) networks in the tinnitus and control groups. The grey bar represents the control group, and the white bar represents the tinnitus group. Positive value of Y-axis means left laterality.
Fig. 3.
Regions showing significant differences in laterality index (LI) between tinnitus patients and healthy controls. Thresholds were set at corrected P < 0.01, with a voxel-level of P < 0.001 and a minimum cluster size of 21 voxels using AlphaSim. The LI of the auditory network (AN) in the tgPCS and postcentral gyrus were lower in tinnitus subjects than in controls (left column; cluster with blue color). The LI of the salience network (SalN) in the supplemental motor cortex and middle frontal gyrus (middle column), and the LI of the visual network (VN) in the precuneus (right column) are higher in tinnitus subjects than in controls (cluster with yellow to red color). Note that significant clusters are shown only in the left cerebral hemisphere.
Fig. 4.
Scatter plots of the correlations between clinical variables (THI, duration) and the laterality of networks (auditory and salience networks) in the tinnitus group. The navy and red circles represent right-sided and left-sided tinnitus, respectively. The regression line is also shown. (a) Scatter plots between tinnitus distress (THI) and the LI values of tgPCS of the auditory network. The X-axis is THI scores, and the Y-axis is LI values extracted from ROI (shown in Fig. 3, left column). The correlation coefficient was 0.4098 (95% CI, 0.1037 to 0.6450; P < 0.05). (b) Scatter plots between tinnitus duration (month) and the LI values for middle frontal gyrus of the salience network. The X-axis is symptom duration (months), and the Y-axis is LI values extracted from ROI (shown in Fig. 3, middle column). The correlation coefficient was −0.3539 (95% CI, −0.6051 to −0.03855; P < 0.05).
Table 1.
Clinical Variables of Left- and Right-Sided Tinnitus
Table 2.
ROI Comparison of Laterality Index and Lateralized Volume Ratio between Tinnitus and Control Groups
| Network |
Tinnitus (38) |
Controls (45) |
Unpaired t-test |
||||||
|---|---|---|---|---|---|---|---|---|---|
| Mean | 95% CI | Dominance | Mean | 95% CI | Dominance | t | P-value | ||
| AN | LI | 0.0536 | 0.0247 to 0.0825 | Left | 0.0979 | 0.0741 to 0.1217 | Left | –2.414 | 0.0181* |
| LvR | 0.5735 | 0.5343 to 0.6127 | 0.6436 | 0.6076 to 0.6796 | –2.661 | 0.0094* | |||
| DAN | LI | –0.0889 | –0.1207 to −0.0572 | Right | –0.1122 | –0.1410 to −0.0835 | Right | 1.101 | 0.2741 |
| LvR | 0.3737 | 0.3282 to 0.4193 | 0.3471 | 0.3089 to 0.3853 | 0.439 | 0.3645 | |||
| DMN | LI | –0.0257 | –0.0659 to 0.0146 | Indeterminate | –0.0365 | –0.0672 to −0.00575 | Indeterminate | 6.499 | 0.6618 |
| LvR | 0.4636 | 0.4025 to 0.5246 | 0.4639 | 0.4168 to 0.5110 | –0.009 | 0.9928 | |||
| SalN | LI | –0.0187 | –0.0437 to 0.0063 | Indeterminate | –0.0483 | –0.0724 to −0.0241 | Right | –1.711 | 0.0909 |
| LvR | 0.4805 | 0.4460 to 0.5149 | 0.4296 | 0.3955 to 0.4637 | –2.106 | 0.0383* | |||
| SMN | LI | 0.0260 | –0.0150 to 0.0669 | Indeterminate | 0.0003 | –0.0406 to 0.0411 | Indeterminate | –0.892 | 0.3753 |
| LvR | 0.5256 | 0.4601 to 0.5911 | 0.5130 | 0.4473 to 0.5788 | 0.272 | 0.7860 | |||
| vN | LI | –0.0985 | –0.1283 to −0.0687 | Right | –0.1441 | –0.1733 to −0.1148 | Right | –2.190 | 0.0314* |
| LvR | 0.3427 | 0.2868 to 0.3986 | 0.3087 | 0.2642 to 0.3533 | –0.972 | 0.3338 | |||
Table 3.
Voxel-Based Comparison of Laterality Index between Tinnitus Subjects and Healthy Controls
| Network | Region (Nearest Brodmann's area) | Number of voxels | Peak intensity |
MNI coordinate** |
||
|---|---|---|---|---|---|---|
| X* | Y | Z | ||||
| AN | Postcentral gyrus (43) | 93 | –4.0807 | |62| | –6 | 18 |
| tgPCS (6) | 22 | –3.6249 | |50| | –3 | 38 | |
| SalN | Supplemental motor area (6) | 76 | 3.9689 | |10| | 2 | 56 |
| Middle frontal gyrus (6) | 24 | 3.8871 | |50| | 2 | 44 | |
| VN | Precuneus (19) | 89 | 4.4266 | |10| | –76 | 26 |
| Lingual gyrus (18) | 208 | 4.2507 | |18| | –54 | –4 | |
| Lingual gyrus (18) | 66 | 3.6009 | |8| | –76 | –4 | |
Table 4.
Voxel-Based Analysis of Correlation between Laterality Index and Clinical Variables in Tinnitus Patients
| Network | Region (Nearest Brodmann's area) | Number of voxels | s Peak intensity |
MNI coordinate** |
||
|---|---|---|---|---|---|---|
| X* | Y | Z | ||||
| AN-THI | Superior temporal gyrus (42) | 67 | 0.6038 | |52| | –32 | 10 |
| Superior temporal gyrus (22) | 22 | 0.5627 | |68| | –8 | 2 | |
| SalN-duration | Inferior parietal lobule (40) | 29 | –0.5078 | |58| | 36 | 50 |
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