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Aims: This study systematically investigated structural and functional alterations in the thalamus and its subregions using multimodal magnetic resonance imaging (MRI) and examined its clinical relevance in tinnitus patients with different outcomes after sound therapy (narrowband noise). Methods: In total, 60 patients with persistent tinnitus and 57 healthy controls (HCs) were recruited. Based on treatment efficacy, 28 patients were categorized into the effective group and 32 into the ineffective group. Five MRI measurements of the thalamus and its seven subregions, including gray matter volume, fractional anisotropy, fractional amplitude of low‐frequency fluctuation, and functional connectivity (FC), were obtained for each participant and compared between the groups. Results: Patients in both the groups exhibited widespread functional and diffusion abnormalities in the whole thalamus and several subregions, with more obvious changes observed in the effective group. All tinnitus patients had abnormal FC compared with the HCs; FC differences between the two patient groups were only observed in the striatal network, auditory‐related cortex, and the core area of the limbic system. We combined the multimodal quantitative thalamic alterations and used it as an imaging indicator to evaluate prognosis before sound therapy and achieved a sensitivity of 71.9% and a specificity of 85.7%. Conclusion: Similar patterns of thalamic alterations were identified in tinnitus patients with different outcomes, with more obvious changes observed in the effective group. Our findings support the tinnitus generation hypothesis of frontostriatal gating system dysfunction. A combination of multimodal quantitative thalamic properties may be used as indicators to predict tinnitus prognosis before sound therapy. [ABSTRACT FROM AUTHOR]

Previous resting-state functional magnetic resonance imaging (fMRI) studies have shown neural connectivity alterations after the treatment of tinnitus. We aim to study the value of the baseline functional connectivity features of neural network nodes to predict outcomes of sound therapy through adjusted narrow band noise. The fMRI data of 27 untreated tinnitus patients and 27 matched healthy controls were analyzed. We calculated the graph-theoretical metric degree centrality (DC) to characterize the functional connectivity of the neural network nodes. Therapeutic outcomes are determined by the changes in the Tinnitus Handicap Inventory (THI) score after a 12-week intervention. The connectivity of 10 brain nodes in tinnitus patients was significantly increased at baseline. The functional connectivity of right insula, inferior parietal lobule (IPL), bilateral thalami, and left middle temporal gyrus was significantly modified with the sound therapy, and such changes correlated with THI changes in tinnitus patients. Receiver operating characteristic curve analyses revealed that the measurements from the five brain regions were effective at classifying improvement after therapy. After age, gender, and education correction, the adjusted area under the curve (AUC) values for the bilateral thalami were the highest (left, 0.745; right, 0.708). Our study further supported the involvement of the fronto-parietal-cingulate network in tinnitus and found that the connectivity of the thalamus at baseline is an object neuroimaging-based indicator to predict clinical outcome of sound therapy through adjusted narrow band noise.

Topological properties, which serve as the core of the neural network, and their couplings can reflect different therapeutic effects in tinnitus patients. We hypothesized that tinnitus patients with different outcomes after sound therapy (narrowband noise) would have distinct brain network topological alterations. Diffusion tensor imaging and resting‐state functional magnetic resonance imaging (fMRI) were prospectively performed in 60 patients with idiopathic tinnitus and 57 healthy controls (HCs). Graph‐theoretical network analyses of structural connectivity (SC), functional connectivity (FC), and SC and FC coupling were performed. Associations between clinical performance and graph‐theoretical features were also analyzed. Treatment was effective (effective group; EG) in 28 patients and ineffective (ineffective group; IG) in 32 patients. For FC, the patients in the EG showed higher local efficiency than patients in the IG. For SC, patients in both the EG and IG displayed lower normalized characteristic path length, characteristic path length, and global efficiency than the HCs. More importantly, patients in the IG had higher coupling than the HCs, whereas there was no difference in coupling between patients in the EG and HCs. Additionally, there were significant associations between the SC features and clinical performance in patients in the EG. Our findings demonstrate that tinnitus patients exhibited significant brain network topological alterations, especially in the structural brain network. More importantly, patients who demonstrated different curative effects showed distinct SC‐FC topological coupling properties. SC‐FC coupling could be an indicator that could be used to predict prognoses in patients with idiopathic tinnitus before sound therapy. [ABSTRACT FROM AUTHOR]

This study aimed to investigate abnormal tinnitus activity by evaluating brain surface-based amplitude of low-frequency fluctuation (ALFF) changes detected by resting-state functional magnetic resonance imaging (RS-fMRI) in patients with idiopathic tinnitus before and after 24 weeks of sound therapy. We hypothesized that sound therapy could gradually return cortical local brain function to a relatively normal range. In this prospective observational study, we recruited thirty-three tinnitus patients who had undergone 24 weeks of sound therapy and 26 matched healthy controls (HCs). For the two groups of subjects, we analyzed the spontaneous neural activity of tinnitus patients by cortical ALFF and detected its correlation with clinical indicators of tinnitus. Patients' Tinnitus Handicap Inventory (THI) scores were assessed to determine the severity of their tinnitus before and after treatment. Two-way mixed model analysis of variance and Pearson's correlation analysis were used in the statistical analysis. Student–Newman–Keuls tests were used in the post hoc analysis. Interaction effects between the two groups and between the two scans revealing local neural activity as assessed by ALFF were observed in the bilateral dorsal stream visual cortex (DSVC), bilateral posterior cingulate cortex (PCC), bilateral anterior cingulate and medial prefrontal cortex (ACC and MPC), left temporo-parieto-occipital junction (TPOJ), left orbital and polar frontal cortex (OPFC), left paracentral lobular and mid cingulate cortex (PCL and MCC), right insular and frontal opercular cortex (IFOC), and left early visual cortex (EVC). Importantly, local functional activity in the left TPOJ and right PCC in the patient group was significantly lower than that in the HCs at baseline and was increased to relatively normal levels after treatment. The 24-week sound therapy tinnitus group demonstrated significantly higher ALFF in the left TPOJ and right PCC than in the tinnitus baseline group. Also, compared with the HC baseline group and the 24-week HC group, the 24-week sound therapy tinnitus group demonstrated slightly lower or higher ALFF in the left TPOJ and right PCC, and there were no differences between the 24-week sound therapy tinnitus and HC groups. Decreased THI scores and ALFF changes in the abovementioned brain regions were not correlated. Taken together, surface-based RS-fMRI can provide more subtle local functional activity to explain the mechanism of tinnitus treatment, and long-term sound therapy had a normalizing effect on tinnitus patients. [ABSTRACT FROM AUTHOR]

Previous studies demonstrated that brain morphological differences and distinct patterns of neural activation exist in tinnitus patients with different prognoses after sound therapy. This study aimed to explore possible differences in intrinsic network‐level functional connectivity (FC) in patients with different outcomes after sound therapy (narrow band noise). We examined intrinsic FC using resting‐state functional magnetic resonance imaging in 78 idiopathic tinnitus patients (including 35 effectively treated and 43 ineffectively treated) and 52 healthy controls (HCs) via independent component analysis. We also investigated the associations between the differences in FC and clinical variables. Analyses revealed significantly altered intranetwork connectivity in the auditory network (AUN) and some nonauditory‐related networks in the EG/IG patients compared to HCs; compared with EG patients, IG patients showed decreased intranetwork connectivity in the anterior default mode network (aDMN) and AUN. Meanwhile, robust differences were also evident in internetwork connectivity between some nonauditory‐related networks (salience network and executive control network; posterior default mode network and dorsal attention network) in the EG relative to IG patients. We combined intranetwork connectivity in the aDMN and AUN as an imaging indicator to evaluate patient outcomes and screen patients before treatment; this approach reached a sensitivity of 94.3% and a specificity of 76.7%. Our study suggests that tinnitus patients with different outcomes show distinct network‐level functional reorganization patterns. Intranetwork connectivity in the aDMN and AUN may be indicators that can be used to predict prognoses in patients with idiopathic tinnitus and screen patients before sound therapy. [ABSTRACT FROM AUTHOR]

Sound therapy is one of the most common first-line treatments for idiopathic tinnitus. We aimed to investigate the brain structural and functional alterations between patients with idiopathic tinnitus without hearing loss (HL) and healthy controls (HCs) and between patients before and after sound therapy (narrow band noise). Structural and resting-state functional images were acquired from 13 tinnitus patients without HL and 18 HCs before and after 6 months of narrow band sound therapy (only patients received the treatment). Voxel-based morphometry (VBM) and independent component analysis (ICA) were conducted to separately investigate the brain structural and functional changes. Associations between brain changes and clinical variables were also performed. After the treatment, the % improvement of THI score was −1.30% (± 63.40%). Compared with HCs, tinnitus patients showed gray matter and white matter atrophy in the left middle temporal gyrus at baseline, and the gray matter volume was further reduced after the treatment. The patients also showed increased white matter volume in the cingulum (cingulate), right calcarine, left rolandic operculum, and left parietal and frontal lobes. Additionally, compared with HCs, tinnitus patients exhibited positive [medial visual network (mVN) and sensorimotor network (SMN), mVN and auditory network (AN)] and negative [mVN and lateral visual network (lVN)] internetwork functional connectivity (FC) at baseline and negative [left frontoparietal network (LFPN) and dorsal attention network (DAN), AN and posterior default mode network (pDMN)] internetwork FC after the narrow band sound therapy. The patients also showed negative [LFPN and right frontoparietal network (RFPN), LFPN and RFPN, anterior default mode network (aDMN) and AN, aDMN and DAN] internetwork FC after the treatment when compared with baseline. Our findings suggest that although the outcomes of idiopathic tinnitus patients without HL were not very good when the improvement of THI scores was used as an evaluation indicator, the patients experienced significant differences in auditory-related and non-auditory-related brain reorganization before and after the narrow band sound therapy, that is, sound therapy may have a significant effect on brain reorganization in patients with idiopathic tinnitus. This study may provide some new useful information for the understanding of mechanisms underlying idiopathic tinnitus. [ABSTRACT FROM AUTHOR]

This study aimed to explore brain surface-based morphometry cortical thickness changes in patients with idiopathic tinnitus before and after 24 weeks of sound therapy. In this prospective observational study, we recruited 33 tinnitus patients who had undergone 24 weeks of sound therapy and 26 matched healthy controls. For the two groups of subjects, a 3D-BRAVO pulse sequence was acquired both at baseline and at the 24th week. Structural image data preprocessing was performed using the DPABISurf toolbox. The Tinnitus Handicap Inventory (THI) score was assessed to determine the severity of tinnitus before and after treatment. Two-way mixed-model analysis of variance (ANOVA) and Pearson's correlation analysis were used in the statistical analysis. Student–Newman–Keuls (SNK) tests were used in the post hoc analysis. Significantly lower cortical thickness was found in the left somatosensory and motor cortex (SMC), left posterior cingulate cortex (PCC), and right orbital and polar frontal cortex (OPFC) of the participants in the tinnitus group at baseline than in the participants in the HC group at baseline and after 24 weeks; in the tinnitus group, significantly higher cortical thickness was found after the 24 weeks sound therapy in comparison to the baseline in the left SMC, bilateral superior parietal cortex (SPC), left inferior parietal cortex (IPC), left PCC, and right OPFC. In the HC group, no statistically significant difference in cortical thickness was found after the 24 weeks treatment in comparison to the baseline in the bilateral SMC, bilateral SPC, left IPC, left PCC, or right OPFC. The changes in cortical thickness before and after sound therapy can provide certain reference values for clinical tinnitus treatment. These brain regions could serve as potential targets for neuroimaging. [ABSTRACT FROM AUTHOR]

This study aimed to explore brain structural and white matter microstructural reorganization in the early stage of tinnitus and identify brain alterations that contribute to its relief after 6 months of sound therapy. We studied 64 patients with idiopathic tinnitus, including 29 patients who were categorized into an effective group (EG) and 35 who were categorized into an ineffective group (IG) according to the 6‐month follow‐up improvement of the Tinnitus Handicap Inventory score, along with 63 healthy controls (HCs). All participants underwent structural and diffusion tensor imaging scanning on a 3‐T magnetic resonance system. Differences in brain gray/white matter volume and white matter microstructure were evaluated using voxel‐based morphometry analysis and tract‐based spatial statistics among the three groups. Associations between brain reorganization and the improvement of tinnitus symptoms were also investigated. Compared with EG patients, IG patients experienced a significant gray matter volume decrease in the right middle frontal gyrus (MFG)/right precentral gyrus (PreCG). Meanwhile, both EG and IG patients showed significant changes (decrease or increase) in brain white matter integrity in the auditory‐related or nonauditory‐related white matter fiber tracts compared with HCs, while EG patients showed decreased axial diffusivity in the bilateral middle cerebellar peduncle (MCP) compared with IG patients. We combined the gray matter change of the MFG/PreCG and the white matter integrity of the bilateral MCP as an imaging indicator to evaluate the patient's prognosis and screen patients before treatment; this approach reached a sensitivity of 77.1% and a specificity of 82.8%. Our study suggests that there was a close relationship between brain reorganization and tinnitus improvement. The right MFG/PreCG and bilateral MCP may be indicators that can be used to predict prognoses in patients with idiopathic tinnitus and may be used to screen patients before sound therapy. These findings may provide new useful information that can lead to a better understanding of the tinnitus mechanism. [ABSTRACT FROM AUTHOR]

Many neuroanatomical alterations have been detected in patients with tinnitus in previous studies. However, little is known about the morphological and structural covariance network (SCN) changes before and after long-term sound therapy. This study aimed to explore alterations in brain anatomical and SCN changes in patients with idiopathic tinnitus using voxel-based morphometry (VBM) analysis 24 weeks before and after sound therapy. Thirty-three tinnitus patients underwent magnetic resonance imaging scans at baseline and after 24 weeks of sound therapy. Twenty-six age- and sex-matched healthy control (HC) individuals also underwent two scans over a 24-week interval; 3.0T MRI and high-resolution 3D structural images were acquired with a 3D-BRAVO pulse sequence. Structural image data preprocessing was performed using the VBM8 toolbox. The Tinnitus Handicap Inventory (THI) score was assessed for the severity of tinnitus before and after treatment. Two-way mixed model analysis of variance (ANOVA) and post hoc analyses were performed to determine differences between the two groups (patients and HCs) and between the two scans (at baseline and on the 24th week). Student-Newman-Keuls (SNK) tests were used in the post hoc analysis. Interaction effects between the two groups and the two scans demonstrated significantly different gray matter (GM) volume in the right parahippocampus gyrus, right caudate, left superior temporal gyrus, left cuneus gyrus, and right calcarine gyrus; we found significantly decreased GM volume in the above five brain regions among the tinnitus patients before sound therapy (baseline) compared to that in the HC group. The 24-week sound therapy group demonstrated significantly greater brain volume compared with the baseline group among these brain regions. We did not find significant differences in brain regions between the 24-week sound therapy and HC groups. The SCN results showed that the left superior temporal gyrus and left rolandic operculum were significantly different in nodal efficiency, nodal degree centrality, and nodal betweenness centrality after FDR correction. This study characterized the effect of sound therapy on brain GM volume, especially in the left superior temporal lobe. Notably, sound therapy had a normalizing effect on tinnitus patients. [ABSTRACT FROM AUTHOR]

According to previous studies, many neuroanatomical alterations have been detected in patients with tinnitus. However, few studies have reported on the morphological changes observed following sound therapy. To explore the brain anatomical alterations in patients with idiopathic tinnitus using voxel-based morphometry (VBM) analysis before and after effective 12 weeks sound therapy. The protocol was registered on ClinicalTrials.gov, ID: NCT02774122. In this study, we collected data from 27 matched healthy control (HC) individuals and 27 idiopathic tinnitus patients before and after 12 weeks of sound therapy by using adjusted narrow band sound. 3.0T MRI system and high-resolution 3D structural images were acquired with a 3D-BRAVO pulse sequence. Structural image data preprocessing was performed using the VBM8 toolbox. The Tinnitus Handicap Inventory (THI) score was acquired in the tinnitus group to assess the severity of tinnitus and tinnitus-related distress. Mann–Whitney U Test, Wilcoxon Signed-Ranks test, and Pearson's correlation analysis were used in the statistical analysis. We found significantly decreased gray matter (GM) volume in the left thalami, right thalami, and cochlear nucleus among the tinnitus patients before sound therapy (baseline) compared to the HC group. However, we did not find significant differences in brain regions between the 12-week treatment and HC groups. According to the results of Wilcoxon Signed-Ranks test, the 12-week sound therapy group demonstrated significant greater brain volume compared with the baseline group among these brain regions. Decreased THI score and changed GM volume were not correlated. This is a useful study for observing the characteristics of neuroanatomical changes in patients with idiopathic tinnitus before and after sound treatment. The study characterized the effect of sound therapy on brain volume. It found that sound therapy had a normalizing effect on the bilateral thalami and cochlear nucleus. Clinical Trial Registration: www.ClinicalTrials.gov, NCT02774122. [ABSTRACT FROM AUTHOR]

The functional connectivity of the auditory network is considered to be important in the development of tinnitus. We hypothesized that sound therapy, as a commonly used effective treatment for tinnitus, can modulate the functional connectivity of the auditory network. In this prospective observational study, we recruited 27 tinnitus patients who had undergone 12 weeks of sound therapy and 27 matched healthy controls. For the two groups of subjects, resting-state functional magnetic resonance imaging was acquired both at baseline and at the 12th week. We utilized independent component analysis and seed-based functional connectivity analysis to characterize the connectivity features of the auditory network. Interaction effects between the two groups and the two scans within the auditory network were observed, which were driven by increased functional connectivity in the left primary auditory cortex (PAC) and decreased values in the secondary auditory cortex (SAC) in tinnitus patients after treatment. Increased connections between the auditory network and limbic network, as well as decreased values with the bilateral thalami, were identified. The effects were mainly driven by the functional connectivity alterations of the SAC rather than that of the PAC. Significant positive correlations between the percent improvement in the Tinnitus Handicap Inventory (THI) score and the percentage change rates of functional connectivity between the SAC and bilateral thalami were observed. Our study contributes to the understanding of the mechanism of tinnitus and effective sound therapy, providing evidence to support the theory of a gain adaptation mechanism that quantifies the recovered gating function of the thalamus in tinnitus patients. • We hypothesized that sound therapy can modulate the functional connectivity (FC) of the auditory network. • This is the first longitudinal investigation that specifically analyzed the FC of the auditory network after therapy. • Results supported the theory of a gain adaptation mechanism of the tinnitus onset. • Secondary auditory cortex may be a better candidate for therapies applying neural suppression techniques. [ABSTRACT FROM AUTHOR]