Hemodynamics derived from computational fluid dynamics based on magnetic resonance angiography is associated with functional outcomes in atherosclerotic middle cerebral artery stenosis.

BACKGROUND: To investigate the relationship between fluid-attenuated inversion recovery (FLAIR) vascular hyperintensity (FVH), hemodynamics, and functional outcome in atherosclerotic middle cerebral artery (MCA) stenosis using a computational fluid dynamics (CFD) model based on magnetic resonance angiography (MRA), according to a modified Rankin Scale (mRS) at 3 months. METHODS: A total of 120 patients with 50-99% atherosclerotic MCA stenosis were included. The training and internal validation groups were composed of 99 participants and 21 participants, respectively. Demographic, imaging data, and functional outcome (mRS at 3 months) were collected. Hemodynamic parameters were obtained from the CFD model. The FVH score was based on the number of territories where FVH is positive, according to the spatial distribution in the Alberta Stroke Program Early Computed Tomography Score (ASPECTS). The prediction models were constructed according to clinical and hemodynamic parameters using multivariate logistic analysis. The DeLong test compared areas under the curves (AUCs) of the models. RESULTS: The multivariable logistic regression analysis showed that the National Institute of Health Stroke Scale (NIHSS) at admission, hypertension, hyperlipidemia, the ratio of wall shear stress before treatment (WSSRbefore), and difference in the ratio of wall shear stress (WSSR) were independently associated with functional outcome (all P<0.05). In the training group before treatment, the AUC of model 1a (only clinical variables) and 2a (clinical variables with addition of WSSRbefore) were 0.750 and 0.802. After treatment, the AUC of model 1b (only clinical variables) and 2b (clinical variables with addition of difference in WSSR) were 0.815 and 0.883, respectively. The AUC of models with hemodynamic parameters was significantly higher than the models based on clinical variables only (all P<0.05, DeLong test). In the internal validation group before treatment, the AUC of the model (clinical variables) was 0.782, and that of the model (clinical variables and WSSRbefore) was 0.800. After treatment, the AUC of the model (clinical variables) was 0.833, and that of the model (clinical variables and difference in WSSR) was 0.861. There were no significant differences between the good and the poor functional outcome group concerning FVHbefore scores before treatment (0.30±0.81 vs. 0.26±0.97; P=0.321) and FVHafter scores after treatment (0.08±0.39 vs. 0.00±0.00; P=0.244). CONCLUSIONS: Hemodynamics was associated with functional outcomes in patients with ischemic stroke attributed to atherosclerotic MCA stenosis, while FVH was not. Hemodynamic parameters were of great importance in the prediction models.

Assessment of normalized cerebral blood flow and its connectivity with migraines without aura during interictal periods by arterial spin labeling.

BACKGROUND: Migraine constitutes a global health burden, and its pathophysiology is not well-understood; research evaluating cerebral perfusion and altered blood flow between brain areas using non-invasive imaging techniques, such as arterial spin labeling, have been scarce. This study aimed to assess cerebral blood flow (CBF) and its connectivity of migraine. METHODS: This study enrolled 40 patients with episodic migraine without aura (MwoA), as well as 42 healthy patients as control (HC). Two groups of normalized CBF and CBF connectivity were compared, and the relationship between CBF variation and clinical scale assessment was further evaluated. RESULTS: In comparison to HC subjects, MwoA patients exhibited higher CBF in the right middle frontal orbital gyrus (ORBmid.R) and the right middle frontal gyrus, while that in Vermis_6 declined. The increased CBF of ORBmid.R was positively correlated with both the Visual Light Sensitivity Questionnaire-8 (VLSQ-8) and the monthly attack frequency score. In MwoA, significantly decreased CBF connectivity was detected between ORBmid.R and the left superior frontal gyrus, the right putamen, the right caudate, as well as the right angular gyrus. In addition, increased CBF connectivity was observed between the left calcarine cortex and ORBmid.R. CONCLUSIONS: Our results indicate that migraine patients exhibit abnormalities in regional CBF and feature CBF connection defects at the resting state. The affected areas involve information perception, information integration, and emotional, pain and visual processing. Our findings might provide important clues for the pathophysiology of migraine.

Increased thalamo-cortical functional connectivity in patients with diabetic painful neuropathy: A resting-state functional MRI study.

Functional changes in the brain of patients with painful diabetic neuropathy (PDN) have remained largely elusive. The aim of the present study was to explore changes in thalamo-cortical functional connectivity (FC) of patients with PDN using resting-state functional MRI. A total of 20 patients with type 2 diabetes mellitus (T2DM) with non-painful diabetic neuropathy (Group NDN), 19 patients with T2DM with PDN (Group-PDN) and 13 age-, sex- and education-matched healthy controls were recruited. The differences in thalamo-cortical FC among the three groups were compared. Patients in Group PDN had increased FC in the left thalamus, the right angular gyrus and the occipital gyrus as compared to those in Group NDN. Furthermore, patients in Group PDN had increased FC in the right thalamus and angular gyrus as compared to those in Group NDN. In conclusion, the present results suggested that the thalamo-cortical FC is increased in patients with T2DM and PDN. Furthermore, the increased FC in the thalamic-parietal-occipital connectivity may be a central pathophysiological mechanism for PDN. The study was retrospectively registered at ClinicalTrials.gov on 3 October 2018 (identifier no. NCT03700502).

Altered amygdala effective connectivity in migraine without aura: evidence from resting-state fMRI with Granger causality analysis.

BACKGROUND: Granger causality analysis (GCA) has been used to investigate the pathophysiology of migraine. Amygdala plays a key role in pain modulation of migraine attack. However, the detailed neuromechanism remained to be elucidated. We applied GCA to explore the amygdala-based directional effective connectivity in migraine without aura (MwoA) and to determine the relation with clinical characteristics. METHODS: Forty-five MwoA patients and forty age-, sex-, and years of education-matched healthy controls(HCs) underwent resting-state functional magnetic resonance imaging (fMRI). Bilateral amygdala were used as seed regions in GCA to investigate directional effective connectivity and relation with migraine duration or attack frequency. RESULTS: MwoA patients showed significantly decreased effective connectivity from right amygdala to right superior temporal gyrus, left superior temporal gyrus and right precentral gyrus compared with HCs. Furthermore, MwoA patients demonstrated significantly decreased effective connectivity from the left amygdala to the ipsilateral superior temporal gyrus. Also, MwoA patients showed enhanced effective connectivity from left inferior frontal gyrus to left amygdala. Effective connectivity outflow from right amygdala to right precentral gyrus was negatively correlated to disease duration. CONCLUSIONS: Altered directional effective connectivity of amygdala demonstrated that neurolimbic pain networks contribute to multisensory integration abnormalities and deficits in pain modulation of MwoA patients.

Magnetic Resonance Imaging has Better Accuracy in Detecting New-Onset Rib Fractures as Compared to Computed Tomography.

BACKGROUND The aim of this study was to explore the magnetic resonance imaging (MRI) manifestations of new-onset rib fractures and determine the utility of MRI through a comparative study of MRI and computed tomography (CT). MATERIAL AND METHODS Twenty-one patients with mild chest trauma who sought medical care from February 2019 to June 2020 were included in this study. The patients were subjected to CT and MRI scanning within 2 weeks after the trauma, and CT rescanning was scheduled 4-8 weeks later to classify rib fractures and determine the diagnostic accuracy of MRI and CT for new-onset rib fractures. RESULTS Seventy-seven rib fractures were confirmed by CT rescanning, of which 72 (93.51%) were type I fractures and 5 (6.49%) were type II. MRI identified 76 fractures, of which 3 were false positive, with the diagnostic accuracy rate of 91.25% and sensitivity rate of 94.81%. Among them, type I fractures (n=71, 3 were false positive) showed the MRI "sandwich" sign (heterogeneous high-signal shadow within bone marrow of the inner layer, low-signal bony cortex of the middle layer, and high-signal subperiosteal effusion of the outer layer) in T2-weighted fat-suppressed sequences; type II fractures (n=5) displayed intramedullary high-signal intensities and no subperiosteal effusion. Forty-four fractures (all type I) were discovered in the initial CT examination, and the corresponding diagnostic accuracy rate and sensitivity rate were 57.14%, which were lower than that of MRI. CONCLUSIONS MRI is highly sensitive for new-onset rib fractures, especially type I, so it is a preferred method for patients with mild chest trauma.

Altered lateral geniculate nucleus functional connectivity in migraine without aura: a resting-state functional MRI study.

OBJECTIVES: To investigate the structural and functional connectivity changes of lateral geniculate nucleus (LGN) and their relationships with clinical characteristics in patients without aura. METHODS: Conventional MRI, 3D structure images and resting state functional MRI were performed in 30 migraine patients without aura (MwoA) and 22 healthy controls (HC). The lateral geniculate nucleus volumes and the functional connectivity (FC) of bilateral lateral geniculate nucleus were computed and compared between groups. RESULTS: The lateral geniculate nucleus volumes in patient groups did not differ from the controls. The brain regions with increased FC of the left LGN mainly located in the left cerebellum and right lingual gyrus in MwoA compared with HC. The increased FC of right LGN located in left inferior frontal gyrus in MwoA compared with HC. The correlation analysis showed a positive correlation between VLSQ-8 score and the increased FC of left cerebellum and right lingual gyrus. CONCLUSIONS: Photophobia in MwoA could be mediated by abnormal resting state functional connectivity in visual processing regions, the pain perception regulatory network and emotion regulation network. This result is valuable to further understanding about the clinical manifestation and pathogenesis of migraine.

Chemotherapy-induced functional changes of the default mode network in patients with lung cancer.

Previous studies have demonstrated that cognitive impairment is associated with neurophysiological changes in lung cancer following chemotherapy. This study aimed to investigate the intrinsic functional connectivity (FC) pattern within the default mode network (DMN) and its associations with cognitive impairment in patients with lung cancer revealed by resting-state functional magnetic resonance imaging (fMRI). Resting-state fMRI scans were acquired from 21 post-chemotherapy and 27 non-chemotherapy lung cancer patients and 30 healthy controls. All groups were age, gender and education-matched. The posterior cingulate cortex (PCC) was chosen as the seed region to detect the FC patterns and then determine whether these changes were related with specific cognitive performance. Compared with non-chemotherapy lung cancer patients, chemotherapy patients revealed decreased FC between the PCC and the right anterior cingulate cortex (ACC), left inferior parietal lobule (IPL), and left medial prefrontal cortex (mPFC), as well as increased FC with the left postcentral gyrus (PoCG). Relative to healthy controls, post-chemotherapy patients exhibited reduced FC between the PCC and the left ACC and left temporal lobe, as well as increased FC with the right PoCG. Moreover, the decreased FC of the PCC to bilateral ACC in post-chemotherapy patients was positively associated with reduced MoCA scores (left: r = 0.529, p = 0.029; right: r = 0.577, p = 0.015). The current study mainly demonstrated reduced resting-state FC pattern within the DMN regions that was linked with impaired cognitive function in lung cancer patients after chemotherapy. These findings illustrated the potential role of the DMN in lung cancer patients that will provide novel insight into the underlying neuropathological mechanisms in chemotherapy-induced cognitive impairment.

Altered functional connectivity of the red nucleus and substantia nigra in migraine without aura.

BACKGROUND: Functional connectivity (FC) has been used to investigate the pathophysiology of migraine. Accumulating evidence is pointing toward malfunctioning of brainstem structures, i.e., the red nucleus (RN) and substantia nigra (SN), as an important factor in migraine without aura (MwoA). We aimed to identify atypical FC between the RN and SN and other brain areas in patients with MwoA and to explore the association between RN and SN connectivity changes and performance on neuropsychological tests in these patients. METHODS: Resting-state functional magnetic resonance imaging (fMRI) data were obtained from 30 patients with MwoA and 22 age-, sex-, and years of education-matched healthy controls (HC). The FC of the brainstem structures was analyzed using a standard seed-based whole-brain correlation method. The results of the brainstem structure FC were assessed for correlations with other clinical features. RESULTS: Patients with MwoA exhibited reduced left RN-based FC with the left middle frontal gyrus, reduced right RN-based FC with the ipsilateral superior parietal lobe, and increased FC with the ipsilateral cerebellum. Additionally, patients with MwoA demonstrated significantly decreased right SN-based FC with the right postcentral gyrus, left parietal lobule, and left superior frontal gyrus. Hypo-connectivity between the right SN and right postcentral gyrus was negatively correlated with disease duration (r = - 0.506, P = 0.004). Additionally, increased connectivity of the right RN to the ipsilateral cerebellar lobes was positively correlated with the Headache Impact Test-6 scores (r = 0.437, P = 0.016). CONCLUSIONS: The present study suggested that patients with MwoA have disruption in their RN and SN resting-state networks, which are associated with specific clinical characteristics. The changes focus on the regions associated with cognitive evaluation, multisensory integration, and modulation of perception and pain, which may be associated with migraine production, feedback, and development. Taken together, these results may improve our understanding of the neuropathological mechanism of migraine.

A Single-Blinded Trial Using Resting-State Functional Magnetic Resonance Imaging of Brain Activity in Patients with Type 2 Diabetes and Painful Neuropathy.

About two-thirds of patients with painful diabetic neuropathy (PDN) suffer from anxiety and/or depression disorders. However, the pathogenesis of PDN is unclear, in particular with respect to the mechanism associated with the central nervous system. We used the neuroimaging techniques of fraction amplitude of low-frequency fluctuation (fALFF) and regional homogeneity of resting-state functional magnetic resonance imaging (fMRI) to explore the brain activity in patients with PDN. The symptoms, signs and mental conditions of 19 patients with PDN and of 18 patients with non-pain neuropathy were assessed separately and compared. Blood oxygenation level-dependent resting-state fMRI scans of the brain were performed in all 37 patients with neuropathy and in 15 gender- and age-matched healthy controls. Our data showed that patients with PDN had increased insulin resistance (p = 0.03), increased depression (p = 0.02) and increased anxiety (p < 0.001) compared with the controls and that all of these conditions were associated with abnormal spontaneous activities in several regions of the brain, including the somatosensory, cognitive and emotional regions. The duration of diabetes, level of glycated hemoglobin, homeostasis model assessment of insulin resistance and estimated glomerular filtration rate were significantly correlated to abnormal spontaneous activity in patients' brains. These results lead to the conclusion that patients with PDN have abnormal brain activity, indicating that the central nervous system may contribute to painful diabetic neuropathy. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03700502.

One-step analysis of brain perfusion and function for acute stroke patients after reperfusion: A resting-state fMRI study.

BACKGROUND: Resting-state functional magnetic resonance imaging (rs-fMRI) can noninvasively estimate the perfusion and function of the brain. PURPOSE: To investigate the perfusion and functional status using rs-fMRI in acute ischemic stroke (AIS) patients after reperfusion therapy. STUDY TYPE: Prospective. SUBJECTS: Twenty-five AIS patients who underwent dynamic susceptibility contrast (DSC) upon hospital admission and both rs-fMRI and DSC scans at 24 hours after reperfusion therapy. FIELD STRENGTH/SEQUENCE: 3T; DSC, rs-fMRI. ASSESSMENT: The time delay of the blood oxygenation level-dependent (BOLD) signal was calculated using time-shift-analysis (TSA) and compared with the time to peak (TTP) derived from the DSC. For patients who exhibited partial or complete reperfusion in the supratentorial hemisphere, we quantified the function of different regions (healthy tissue, reperfused tissue, not reperfused tissue) by using three rs-fMRI measurements (functional connectivity, the amplitude of low-frequency fluctuation [ALFF] and regional homogeneity [ReHo]). Correlations between the functional measurements and modified Rankin Scale (mRS) scores were calculated. STATISTICAL TESTS: Dice coefficient (DC) analysis, two-sample t-tests, Pearson correlation coefficient. RESULTS: Twelve patients who exhibited complete reperfusion on their TTP maps showed no time-delayed areas on the TSA maps. For the remaining 13 patients with partial reperfusion (5/13) or no reperfusion (8/13) on the TTP maps, the TSA detected comparable time-delayed areas. Eleven out of 13 patients showed moderate to good overlap (mean DC, 0.58 ± 0.1) between the TTP and TSA results. Fourteen patients were chosen for functional analyses and most patients (12/14) showed abnormal functional connectivity in the reperfused regions. The reperfused and not reperfused tissues had lower mean ReHo values than those of the healthy tissue (both P < 0.001). The mRS scores showed negative correlation with mean ReHo values of reperfused region (R = -0.523, P = 0.027). DATA CONCLUSION: rs-fMRI might be a useful way to estimate both the perfusion and functional status for AIS patients after reperfusion therapy. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:221-229.

Decreased functional connectivity within the default-mode network in acute brainstem ischemic stroke.

PURPOSE: Ischemic stroke within the brainstem is associated with an increased risk of cognitive dysfunction. This study aimed to explore the integrity of a default-mode network (DMN) and its relationship with clinical variables in patients with acute ischemic brainstem stroke using an independent component analysis (ICA) approach. MATERIALS AND METHODS: Twenty-one patients with acute ischemic brainstem stroke and 25 well-matched healthy subjects were enrolled in this study and underwent resting-state functional magnetic resonance imaging. The ICA was adopted to extract the DMN, including its anterior and posterior components. Pearson correlation analyses were performed to investigate the relationship between DMN connectivity and clinical variables. RESULTS: Compared with healthy controls, patients with acute ischemic stroke showed significantly decreased functional connectivity in the right medial prefrontal cortex (mPFC) and right precuneus within the anterior and posterior DMN, respectively. After correcting for age, sex, and education, hypoconnectivity in the right mPFC and right precuneus was negatively correlated with higher homocysteine in patients with stroke (r = -0.592, p = 0.010 and r = -0.491, p = 0.039, respectively). CONCLUSION: The finding of decreased functional connectivity within the DMN of patients with acute brainstem stroke provides novel insight into the neural mechanisms that underlie cognitive impairment following ischemic insult to this brain region.

Increased Resting-State Cerebellar-Cerebral Functional Connectivity Underlying Chronic Tinnitus.

Purpose: Chronic subjective tinnitus may arise from aberrant functional coupling between the cerebellum and the cerebral cortex. To explore this hypothesis, we used resting-state functional magnetic resonance imaging (fMRI) to illuminate the functional connectivity network of the cerebellar regions in chronic tinnitus patients and controls. Methods: Resting-state fMRI scans were obtained from 28 chronic tinnitus patients and 29 healthy controls (well matched for age, sex and education) in this study. Cerebellar-cerebral functional connectivity was characterized using a seed-based whole-brain correlation method. The resulting cerebellar functional connectivity measures were correlated with each clinical tinnitus characteristic. Results: Chronic tinnitus patients demonstrated increased functional connectivity between the cerebellum and several cerebral regions, including the superior temporal gyrus (STG), parahippocampal gyrus (PHG), inferior occipital gyrus (IOG), and precentral gyrus. The enhanced functional connectivity between the left cerebellar Lobule VIIb and the right STG was positively correlated with the Tinnitus Handicap Questionnaires (THQ) score (r = 0.577, p = 0.004). Furthermore, the increased functional connectivity between the cerebellar vermis and the right STG was also associated with the THQ score (r = 0.432, p = 0.039). Conclusions: Chronic tinnitus patients have greater cerebellar functional connectivity to certain cerebral brain regions which is associated with specific tinnitus characteristics. Resting-state cerebellar-cerebral functional connectivity disturbances may play a pivotal role in neuropathological features of tinnitus.

Presbycusis Disrupts Spontaneous Activity Revealed by Resting-State Functional MRI.

Purpose: Presbycusis, age-related hearing loss, is believed to involve neural changes in the central nervous system, which is associated with an increased risk of cognitive impairment. The goal of this study was to determine if presbycusis disrupted spontaneous neural activity in specific brain areas involved in auditory processing, attention and cognitive function using resting-state functional magnetic resonance imaging (fMRI) approach. Methods: Hearing and resting-state fMRI measurements were obtained from 22 presbycusis patients and 23 age-, sex- and education-matched healthy controls. To identify changes in spontaneous neural activity associated with age-related hearing loss, we compared the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) of fMRI signals in presbycusis patients vs. controls and then determined if these changes were linked to clinical measures of presbycusis. Results: Compared with healthy controls, presbycusis patients manifested decreased spontaneous activity mainly in the superior temporal gyrus (STG), parahippocampal gyrus (PHG), precuneus and inferior parietal lobule (IPL) as well as increased neural activity in the middle frontal gyrus (MFG), cuneus and postcentral gyrus (PoCG). A significant negative correlation was observed between ALFF/ReHo activity in the STG and average hearing thresholds in presbycusis patients. Increased ALFF/ReHo activity in the MFG was positively correlated with impaired Trail-Making Test B (TMT-B) scores, indicative of impaired cognitive function involving the frontal lobe. Conclusions: Presbycusis patients have disrupted spontaneous neural activity reflected by ALFF and ReHo measurements in several brain regions; these changes are associated with specific cognitive performance and speech/language processing. These findings mainly emphasize the crucial role of aberrant resting-state ALFF/ReHo patterns in presbycusis patients and will lead to a better understanding of the neuropathological mechanisms underlying presbycusis.

A High-Resolution MRI Study of Relationship between Remodeling Patterns and Ischemic Stroke in Patients with Atherosclerotic Middle Cerebral Artery Stenosis.

Purpose: Recently, high-resolution magnetic resonance imaging (HR-MRI) has been used to depict the wall characteristics of the intracranial arteries. The aim of this study was to explain the relationship between the remodeling patterns and acute ischemic stroke in patients with atherosclerotic middle cerebral artery (MCA) stenosis using HR-MRI. Materials and Methods: From August 2015 to May 2016, we prospectively screened 33 consecutive patients with unilateral MCA stenosis using time-to-flight MR angiography, including 15 patients with symptomatic MCA stenosis and 18 patients with asymptomatic MCA stenosis. Among them, 14 patients were diagnosed as positive remodeling (PR) and 19 as negative remodeling or non-remodeling. The cross-sectional images of the stenotic MCA wall on HR-MRI including T1WI, T2WI, and PDWI were compared between the symptomatic group and the asymptomatic group as well as the PR group and the non-PR group, based on the vessel area, lumen area, wall area, plaque area, degree of stenosis, remodeling index, and NIHSS score. Results: The symptomatic group had larger wall area (P = 0.040), plaque area (P<0.001), degree of stenosis (P = 0.038), remodeling index (P < 0.001), and NIHSS score (P = 0.003) as well as smaller lumen area (P = 0.001) than the asymptomatic group. In addition, more PR patients were observed in symptomatic group. The PR group had larger plaque area (P = 0.014) and NIHSS score (P = 0.037) than the non-PR group. Demographic and clinical characteristics between the symptomatic group and the asymptomatic group, the PR group and the non-PR group showed no statistical difference. Conclusion: The current study suggests that the HR-MRI has emerged as a promising tool to detect the characteristics of intracranial arteries wall and reveal the relationship between remodeling patterns and ischemic stroke. The PR is an unsafe remodeling way and is prone to cause acute ischemic stroke.

Disrupted Brain Functional Network Architecture in Chronic Tinnitus Patients.

PURPOSE: Resting-state functional magnetic resonance imaging (fMRI) studies have demonstrated the disruptions of multiple brain networks in tinnitus patients. Nonetheless, several studies found no differences in network processing between tinnitus patients and healthy controls (HCs). Its neural bases are poorly understood. To identify aberrant brain network architecture involved in chronic tinnitus, we compared the resting-state fMRI (rs-fMRI) patterns of tinnitus patients and HCs. MATERIALS AND METHODS: Chronic tinnitus patients (n = 24) with normal hearing thresholds and age-, sex-, education- and hearing threshold-matched HCs (n = 22) participated in the current study and underwent the rs-fMRI scanning. We used degree centrality (DC) to investigate functional connectivity (FC) strength of the whole-brain network and Granger causality to analyze effective connectivity in order to explore directional aspects involved in tinnitus. RESULTS: Compared to HCs, we found significantly increased network centrality in bilateral superior frontal gyrus (SFG). Unidirectionally, the left SFG revealed increased effective connectivity to the left middle orbitofrontal cortex (OFC), left posterior lobe of cerebellum (PLC), left postcentral gyrus, and right middle occipital gyrus (MOG) while the right SFG exhibited enhanced effective connectivity to the right supplementary motor area (SMA). In addition, the effective connectivity from the bilateral SFG to the OFC and SMA showed positive correlations with tinnitus distress. CONCLUSIONS: Rs-fMRI provides a new and novel method for identifying aberrant brain network architecture. Chronic tinnitus patients have disrupted FC strength and causal connectivity mostly in non-auditory regions, especially the prefrontal cortex (PFC). The current findings will provide a new perspective for understanding the neuropathophysiological mechanisms in chronic tinnitus.