Aberrant Intra- and Inter-Network Connectivity in Idiopathic Sudden Sensorineural Hearing Loss with Tinnitus.

BACKGROUND: Idiopathic Sudden Sensorineural Hearing Loss (ISSNHL) is related to alterations in brain cortical and subcortical structures, and changes in brain functional activities involving multiple networks, which is often accompanied by tinnitus. There have been many in-depth research studies conducted concerning ISSNHL. Despite this, the neurophysiological mechanisms of ISSNHL with tinnitus are still under exploration. OBJECTIVE: The study aimed to investigate the neural mechanism in ISSNHL patients with tinnitus based on the alterations in intra- and inter-network Functional Connectivity (FC) of multiple networks. METHODS: Thirty ISSNHL subjects and 37 healthy subjects underwent resting-state functional Magnetic Resonance Imaging (rs-fMRI). Independent Component Analysis (ICA) was used to identify 8 Resting-state Networks (RSNs). Furthermore, the study used a two-sample t-test to calculate the intra-network FC differences, while calculating Functional Network Connectivity (FNC) to detect the inter-network FC differences. RESULTS: By using the ICA approach, tinnitus patients with ISSNHL were found to have FC changes in the following RSNs: CN, VN, DMN, ECN, SMN, and AUN. In addition, the interconnections of VN-SMN, VN-ECN, and ECN-DAN were weakened. CONCLUSION: The present study has demonstrated changes in FC within and between networks in ISSNHL with tinnitus, providing ideas for further study on the neuropathological mechanism of the disease.

Degree centrality and functional connections in presbycusis with and without cognitive impairments.

Presbycusis is a major public issue that affecting elderly adults. However, the neural substrates between normal cognition and cognitive deficits in these patients need to be illustrated. 47 patients with presbycusis and 33 well-matched healthy controls were recruited in present study. Each subject underwent pure-tone audiometry (PTA), MRI scanning and cognition evaluations, then we found 22 patients with cognitive deficits and 25 patients with common cognition. We analyzed the Degree centrality (DC) characteristics among three groups, and try to recognize key nodes which contribute significantly. Subsequent functional connectivity analysis was applied using the key nodes as seeds. Compared with controls, presbycusis without cognitive impairments showed deceased DC in superior temporal gyrus (STG), inferior frontal gyrus (IFG) and supramarginal gyrus (SMG). Additionally, presbycusis with cognitive impairments showed enhanced DC in fusiform gurus (FFG), cerebellum and para-hippocampal gyrus (PHG), while weakened DC in SMG, middle frontal gyrus (IFG) and inferior Parietal lobule (IPL). Compared with normal cognition, increased DC value of cerebellum and STG, as well as decreased DC value of IPL in presbycusis with cognitive impairments were observed. We noticed that SMG may play an important role. Then the left and right SMG were used as seeds in functional connections analysis. With the seed set at left SMG, presbycusis without cognitive impairments showed decreases connections with cerebellum, temporal pole (TP), superior temporal gyrus (STG) and median cingulate cortex (MCC). Presbycusis with cognitive impairments showed weakened connectivity with cerebellum, IFG, IPL and superior frontal gyrus (SFG). The right SMG showed decrease connections with cerebellum, middle temporal gyrus (MTG), STG and increase connection with middle frontal gyrus (MFG) in presbycusis without cognitive impairments. While the right SMG showed enhanced connections with left TP, caudate, anterior cingulate cortex (ACC), angular, SFG and weakened connectivity with right SFG presbycusis with cognitive impairments. In comparison with normal cognition and impaired cognition, MFG, IFG, PHG, rolandic operculum and cerebellum were involved. These findings enriched our understanding of the neural mechanisms underlying cognitive impairments associated with presbycusis and may serve as a potential imaging biomarker for investigating and predicting cognitive difficulties.

Abnormal cerebellar network and effective connectivity in sudden and long-term sensorineural hearing loss.

Sudden sensorineural hearing loss (SSNHL) is a common otology emergency and some SSNHL will develop into a long-term hearing loss (LSNHL). However, whether SSNHL and LSNHL have similar psychiatric patterns remains unknown, as well as the neural substrates. Increasing evidence has proved that the cerebellar network plays a vital role in hearing, cognition processing, and emotion control. Thus, we recruited 20 right SSNHL (RSSNHL), 20 right LSNHL (RLSNHL), and 24 well-matched healthy controls to explore the cerebellar patterns among the three groups. Every participant underwent pure tone audiometry tests, neuropsychological evaluations, and MRI scanning. Independent component analysis (ICA) was carried out on the MRI data and the cerebellar network was extracted. Granger causality analysis (GCA) was conducted using the significant cerebellar region as a seed. Pearson's correlation analysis was computed between imaging characteristics and clinical features. ICA found the effect of group on right cerebellum lobule V for the cerebellar network. Then, we found decreased outflow from right cerebellum lobule V to right middle orbitofrontal cortex, inferior frontal gyrus, anterior cingulate cortex, superior temporal gyrus, and dorsal lateral prefrontal cortex in RSSNHL group in GCA analysis. No significance was found in RLSNHL subjects. Additionally, the RSSNHL group showed increased effective connectivity from the right middle frontal gyrus (MFG) and the RLSNHL group showed increased effective connectivity from the right insula and temporal pole to the right cerebellum lobule V. Moreover, connections between right cerebellum lobule V and mean time series of the cerebellar network was negatively correlated with anxiety score in RSSNHL and negatively correlated with depression scores in RLSNHL. Effective connectivity from right MFG to right cerebellum lobule V could predict anxiety status in RSSNHL subjects. Our results may prove potential imaging biomarkers and treatment targets for hearing loss in future work.

Aberrant Modulations of Neurocognitive Network Dynamics in Migraine Comorbid With Tinnitus.

Purpose: The possible relationship between migraine and tinnitus still remains elusive although migraine is often accompanied by chronic tinnitus. Several neuroimaging studies have reinforced the cognitive network abnormality in migraine and probably as well as tinnitus. The present work aims to investigate the dynamic neurocognitive network alterations of migraine comorbid with tinnitus. Materials and Methods: Participants included migraine patients (n = 32), tinnitus patients (n = 20), migraine with tinnitus (n = 27), and healthy controls (n = 47), matched for age and gender. Resting-state functional magnetic resonance imaging (rs-fMRI) with independent component analysis (ICA), sliding window cross-correlation, and clustering state analysis was used to detect the dynamic functional network connectivity (dFNC) of each group. Correlation analyses illustrated the association between clinical symptoms and abnormal dFNC in migraine as well as tinnitus. Results: Compared with healthy controls, migraine patients exhibited decreased cerebellar network and visual network (CN-VN) connectivity in State 2; migraine with tinnitus patients showed not only decreased CN-VN connectivity in State 2 but also decreased cerebellar network and executive control network (CN-ECN) connectivity in State 2 and increased cerebellar network and somatomotor network (SMN-VN) connectivity in State 1. The abnormal cerebellum dFNC with the executive control network (CN-ECN) was negatively correlated with headache frequency of migraine (rho = -0.776, p = 0.005). Conclusion: Brain network characteristics of migraine with tinnitus patients may indicate different mechanisms for migraine and tinnitus. Our results demonstrated a transient pathologic state with atypical cerebellar-cortical connectivity in migraine with tinnitus patients, which might be used to identify the neuro-pathophysiological mechanisms in migraine accompanied by tinnitus.

Reorganized Brain Functional Network Topology in Presbycusis.

Purpose: Presbycusis is characterized by bilateral sensorineural hearing loss at high frequencies and is often accompanied by cognitive decline. This study aimed to identify the topological reorganization of brain functional network in presbycusis with/without cognitive decline by using graph theory analysis approaches based on resting-state functional magnetic resonance imaging (rs-fMRI). Methods: Resting-state fMRI scans were obtained from 30 presbycusis patients with cognitive decline, 30 presbycusis patients without cognitive decline, and 50 age-, sex-, and education-matched healthy controls. Graph theory was applied to analyze the topological properties of brain functional networks including global and nodal metrics, modularity, and rich-club organization. Results: At the global level, the brain functional networks of all participants were found to possess small-world properties. Also, significant group differences in global network metrics were observed among the three groups such as clustering coefficient, characteristic path length, normalized characteristic path length, and small-worldness. At the nodal level, several nodes with abnormal betweenness centrality, degree centrality, nodal efficiency, and nodal local efficiency were detected in presbycusis patients with/without cognitive decline. Changes in intra-modular connections in frontal lobe module and inter-modular connections in prefrontal subcortical lobe module were found in presbycusis patients exposed to modularity analysis. Rich-club nodes were reorganized in presbycusis patients, while the connections among them had no significant group differences. Conclusion: Presbycusis patients exhibited topological reorganization of the whole-brain functional network, and presbycusis patients with cognitive decline showed more obvious changes in these topological properties than those without cognitive decline. Abnormal changes of these properties in presbycusis patients may compensate for cognitive impairment by mobilizing additional neural resources.

Disrupted Topological Organization of Resting-State Functional Brain Networks in Age-Related Hearing Loss.

Purpose: Age-related hearing loss (ARHL), associated with the function of speech perception decreases characterized by bilateral sensorineural hearing loss at high frequencies, has become an increasingly critical public health problem. This study aimed to investigate the topological features of the brain functional network and structural dysfunction of the central nervous system in ARHL using graph theory. Methods: Forty-six patients with ARHL and forty-five age, sex, and education-matched healthy controls were recruited to undergo a resting-state functional magnetic resonance imaging (fMRI) scan in this study. Graph theory was applied to analyze the topological properties of the functional connectomes by studying the local and global organization of neural networks. Results: Compared with healthy controls, the patient group showed increased local efficiency (Eloc) and clustering coefficient (Cp) of the small-world network. Besides, the degree centrality (Dc) and nodal efficiency (Ne) values of the left inferior occipital gyrus (IOG) in the patient group showed a decrease in contrast with the healthy control group. In addition, the intra-modular interaction of the occipital lobe module and the inter-modular interaction of the parietal occipital module decreased in the patient group, which was positively correlated with Dc and Ne. The intra-modular interaction of the occipital lobe module decreased in the patient group, which was negatively correlated with the Eloc. Conclusion: Based on fMRI and graph theory, we indicate the aberrant small-world network topology in ARHL and dysfunctional interaction of the occipital lobe and parietal lobe, emphasizing the importance of dysfunctional left IOG. These results suggest that early diagnosis and treatment of patients with ARHL is necessary, which can avoid the transformation of brain topology and decreased brain function.

Aberrant Functional Network of Small-World in Sudden Sensorineural Hearing Loss With Tinnitus.

Few researchers investigated the topological properties and relationships with cognitive deficits in sudden sensorineural hearing loss (SNHL) with tinnitus. To explore the topological characteristics of the brain connectome following SNHL from the global level and nodal level, we recruited 36 bilateral SNHL patients with tinnitus and 37 well-matched healthy controls. Every subject underwent pure tone audiometry tests, neuropsychological assessments, and MRI scanning. AAL atlas was employed to divide a brain into 90 cortical and subcortical regions of interest, then investigated the global and nodal properties of "small world" network in SNHL and control groups using a graph-theory analysis. The global characteristics include small worldness, cluster coefficient, characteristic path length, local efficiency, and global efficiency. Node properties include degree centrality, betweenness centrality, nodal efficiency, and nodal clustering coefficient. Interregional connectivity analysis was also computed among 90 nodes. We found that the SNHL group had significantly higher hearing thresholds and cognitive impairments, as well as disrupted internal connections among 90 nodes. SNHL group displayed lower AUC of cluster coefficient and path length lambda, but increased global efficiency. The opercular and triangular parts of the inferior frontal gyrus, rectus gyrus, parahippocampal gyrus, precuneus, and amygdala showed abnormal local features. Some of these connectome alterations were correlated with cognitive ability and the duration of SNHL. This study may prove potential imaging biomarkers and treatment targets for future studies.

Specific brain network predictors of interventions with different mechanisms for tinnitus patients.

BACKGROUND: The aberrant brain network that gives rise to the phantom sound of tinnitus is believed to determine the effectiveness of tinnitus therapies involving neuromodulation with repetitive transcranial magnetic stimulation (rTMS) and sound therapy utilizing tailor-made notch music training (TMNMT). To test this hypothesis, we determined how effective rTMS or TMNMT were in ameliorating tinnitus in patients with different functional brain networks. METHODS: Resting-state functional MRI was used to construct brain functional networks in patients with tinnitus (41 males/45 females, mean age 49.53±11.19 years) and gender-matched healthy controls (22 males/35 females, mean age 46.23±10.23 years) with independent component analysis (ICA). A 2 × 2 analysis of variance with treatment outcomes (Effective group, EG/Ineffective group, IG) and treatment types (rTMS/TMNMT) was used to test the interaction between outcomes and treatment types associated with functional network connections (FNCs). FINDINGS: The optimal neuroimaging indicator for responding to rTMS (AUC 0.804, sensitivity 0.700, specificity 0.913) was FNCs in the salience network-right frontoparietal network (SN-RFPN) while for responding to TMNMT (AUC 0.764, sensitivity 0.864, specificity 0.667) was the combination of FNCs in the auditory network- salience network (AUN-SN) and auditory network-cerebellar network (AUN-CN). INTERPRETATION: Tinnitus patients with higher FNCs in the SN-RFPN is associated with a recommendation for rTMS whereas patients with lower FNCs in the AUN-SN and AUN-CN would suggest TMNMT as the better choice. These results indicate that brain network-based measures aid in the selection of the optimal form of treatment for a patient contributing to advances in precision medicine. FUNDING: Yuexin Cai is supported by Key R&D Program of Guangdong Province, China (Grant No. 2018B030339001), National Natural Science Foundation of China (82071062), Natural Science Foundation of Guangdong province (2021A1515012038), the Fundamental Research Funds for the Central Universities (20ykpy91), and Sun Yat-Sen Clinical Research Cultivating Program (SYS-Q-201903). Yu-Chen Chen is supported by Medical Science and Technology Development Foundation of Nanjing Department of Health (No. ZKX20037), and Natural Science Foundation of Jiangsu Province (No. BK20211008).

Topological features of limbic dysfunction in chronicity of tinnitus with intact hearing: New hypothesis for 'noise-cancellation' mechanism.

PURPOSE: The reorganization of the limbic regions extend to general cognitive network is believed to exist in the chronicity of tinnitus with particular 'hubs' contributing to a 'noise-cancellation' mechanism. To test this hypothesis, we investigated the topological brain network of tinnitus in different periods. METHODS: Resting-state functional magnetic resonance imaging were obtained from 32 patients with acute tinnitus, 41 patients with chronic tinnitus and 60 age- and gender- matched healthy controls (HC). The topological features of their brain networks were explored using graph theory analysis. RESULTS: Common small-world attributes were compared between the three groups, all showed a significantly increased values in Cp, Lp, λ (all p < 0.05). Significantly increased nodal centralities in the left superior frontal gyrus and the right precuneus, significantly decreased nodal centralities in the right inferior temporal gyrus were observed for acute tinnitus patients compared to HC. While for chronic tinnitus patients, there were significant increased nodal centralities in the left hippocampus, amygdala, and temporal pole, but decreased nodal centralities in the right inferior temporal gyrus. Additionally, significant higher nodal centralities were found in bilateral medial superior frontal gyrus for acute tinnitus patients compared to chronic tinnitus patients. Besides, alterations in rich-club organization were found in acute tinnitus patients and chronic tinnitus patients compared with HC, with increased functional connections among rich-club nodes and peripheral nodes in patients with tinnitus. CONCLUSIONS: Brain network topological properties altered across prefrontal-limbic-subcortical regions in tinnitus. The existed hubs in tinnitus might indicate an emotional and cognitive burden in 'noise-cancellation' mechanism.

Cerebral Blood Flow Difference Between Acute and Chronic Tinnitus Perception: A Perfusion Functional Magnetic Resonance Imaging Study.

Purpose: The central nervous mechanism of acute tinnitus is different from that of chronic tinnitus, which may be related to the difference of cerebral blood flow (CBF) perfusion in certain regions. To verify this conjecture, we used arterial spin labeling (ASL) perfusion magnetic resonance imaging (MRI) in this study to compare the CBF alterations of patients with acute and chronic tinnitus. Methods: The current study included patients with chronic tinnitus (n = 35), acute tinnitus (n = 30), and healthy controls (n = 40) who were age-, sex-, and education-matched. All participants underwent MRI scanning and then ASL images were obtained to measure CBF of the entire brain and analyze the differences between groups as well as the correlations with tinnitus characteristics. Results: The chronic tinnitus group showed increased z-CBF in the right superior temporal gyrus (STG) and superior frontal gyrus (SFG) when compared with the acute tinnitus patients. Further connectivity analysis found enhanced CBF connectivity between the right STG and fusiform gyrus (FG), the right SFG and left middle occipital gyrus (MOG), as well as the right parahippocampal gyrus (PHG). Moreover, in the chronic tinnitus group, the tinnitus handicap questionnaire (THQ) score was positively correlated with the normalized z-CBF of right STG (r = 0.440, p = 0.013). Conclusion: Our results confirmed that the CBF changes in some brain regions were different between acute and chronic tinnitus patients, which was correlated with certain tinnitus characteristics. This is of great value to further research on chronicity of tinnitus, and ASL has a promising application in the measurement of CBF.

Arterial Spin Labeling Cerebral Perfusion Changes in Chronic Tinnitus With Tension-Type Headache.

Purpose: Tinnitus is along with tension-type headache that will influence the cerebral blood flow (CBF) and accelerate the tinnitus severity. However, the potential associations between tension-type headache and tinnitus is still unknown. The current study will explore whether abnormal CBF exists in tinnitus patients and examine the effects of headache on CBF in tinnitus patients. Materials and Methods: Resting-state perfusion magnetic resonance imaging was performed in 40 chronic tinnitus patients and 50 healthy controls using pseudocontinuous arterial spin labeling. Regions with CBF differences between tinnitus patients and healthy controls were investigated. The effects of headache on tinnitus for CBF changes were further explored. Correlation analyses revealed the relationship between CBF values and tinnitus distress as well as CBF values and headache degree. Results: Relative to healthy controls, chronic tinnitus showed decreased CBF, mainly in right superior temporal gyrus (STG), left middle frontal gyrus (MFG), and left superior frontal gyrus (SFG); the CBF in the right STG and the left MFG was negatively correlated with THQ scores (r = -0.553, p = 0.001; r = -0.399, p = 0.017). We also observed a significant effect of headache on tinnitus for CBF in the right STG. Furthermore, the headache degree was correlated positively with tinnitus distress (r = 0.594, p = 0.020). Conclusion: Decreased CBF in auditory and prefrontal cortex was observed in chronic tinnitus patients. Headache may accelerate CBF reductions in tinnitus, which may form the basis for the neurological mechanism in chronic tinnitus with tension-type headache.

Aberrant cerebral blood flow in tinnitus patients with migraine: a perfusion functional MRI study.

PURPOSE: Migraine is often accompanied with chronic tinnitus that will affect the cerebral blood flow (CBF) and exacerbate the tinnitus distress. However, the potential relationship between migraine and tinnitus remains unclear. This study will investigate whether aberrant CBF patterns exist in migraine patients with tinnitus and examine the influence of migraine on CBF alterations in chronic tinnitus. MATERIALS AND METHODS: Participants included chronic tinnitus patients (n = 45) and non-tinnitus controls (n = 50), matched for age, sex, education, and hearing thresholds. CBF images were collected and analyzed using arterial spin labeling (ASL) perfusion functional magnetic resonance imaging (fMRI). Regions with major CBF differences between tinnitus patients and non-tinnitus controls were first detected. The effects of migraine on tinnitus for CBF alterations were further examined. Correlation analyses illustrated the association between CBF values and tinnitus severity as well as between CBF and severity of migraine. RESULTS: Compared with non-tinnitus controls, chronic tinnitus patients without migraine exhibited decreased CBF, primarily in right superior temporal gyrus (STG), bilateral middle frontal gyrus (MFG), and left superior frontal gyrus (SFG); decreased CBF in these regions was correlated with tinnitus distress. There was a significant effect of migraine on tinnitus for CBF in right STG and MFG. Moreover, the severity of migraine correlated negatively with CBF in tinnitus patients. CONCLUSIONS: Chronic tinnitus patients exhibited reduced CBF in the auditory and prefrontal cortex. Migraine may facilitate a CBF decrease in the setting of tinnitus, which may underlie the neuropathological mechanisms of chronic tinnitus comorbid with migraine.

The Neural Mechanisms of Tinnitus: A Perspective From Functional Magnetic Resonance Imaging.

Tinnitus refers to sound perception in the absence of external sound stimulus. It has become a worldwide problem affecting all age groups especially the elderly. Tinnitus often accompanies hearing loss and some mood disorders like depression and anxiety. The comprehensive adverse effects of tinnitus on people determine the severity of tinnitus. Understanding the mechanisms of tinnitus and related discomfort may be beneficial to the prevention and treatment, and then getting patients out of tinnitus distress. Functional magnetic resonance imaging (fMRI) is a powerful technique for characterizing the intrinsic brain activity and making us better understand the tinnitus neural mechanism. In this article, we review fMRI studies published in recent years on the neuroimaging mechanisms of tinnitus. The results have revealed various neural network alterations in tinnitus patients, including the auditory system, limbic system, default mode network, attention system, and some other areas involved in memory, emotion, attention, and control. Moreover, changes in functional connectivity and neural activity in these networks are related to the perception, persistence, and severity of tinnitus. In summary, the neural mechanism of tinnitus is a complex regulatory mechanism involving multiple networks. Future research is needed to study these neural networks more accurately to refine the tinnitus models.

Abnormal Static and Dynamic Functional Network Connectivity in Patients With Presbycusis.

Aim: This study aimed to investigate abnormal static and dynamic functional network connectivity (FNC) and its association with cognitive function in patients with presbycusis. Methods: In total, 60 patients with presbycusis and 60 age-, sex-, and education-matched healthy controls (HCs) underwent resting-state functional MRI (rs-fMRI) and cognitive assessments. Group independent component analysis (ICA) was carried out on the rs-fMRI data, and eight resting-state networks (RSNs) were identified. Static and dynamic FNCs (sFNC and dFNC) were then constructed to evaluate differences in RSN connectivity between the patients with presbycusis and the HCs. Furthermore, the correlations between these differences and cognitive scores were analyzed. Results: Patients with presbycusis had differences in sFNC compared with HCs, mainly reflected in decreased sFNC in the default mode network (DMN)-left frontoparietal network (LFPN) and attention network (AN)-cerebellum network (CN) pairs, but they had increased sFNC in the auditory network (AUN) between DMN domains. The decreased sFNC in the DMN-LFPN pair was negatively correlated with their TMT-B score (r = -0.441, p = 0.002). Patients with presbycusis exhibited aberrant dFNCs in State 2 and decreased dFNCs between the CN and AN and the visual network (VN). Moreover, the presbycusis group had a shorter mean dwell time (MDT) and fraction time (FT) in State 3 (p = 0.0027; p = 0.0031, respectively). Conclusion: This study highlighted differences in static and dynamic functional connectivity in patients with presbycusis and suggested that FNC may serve as an important biomarker of cognitive performance since abnormal alterations can better track cognitive impairment in presbycusis.

Aberrant brain functional hubs and causal connectivity in presbycusis.

To investigate resting-state connectivity and further understand directional aspects of implicit alterations in presbycusis patients, we used degree centrality (DC) and Granger causality analysis (GCA) to detect functional hubs of the whole-brain network and then analyze directional connectivity. Resting-state functional magnetic resonance imaging (fMRI) scans were performed on 40 presbycusis patients and 40 healthy controls matched for age, gender, and education. We used DC analysis and GCA to characterize abnormal brain networks in presbycusis patients. The associations of network centrality and directed functional connectivity (FC) with clinical measures of presbycusis were also examined according to the above results. We found that the network centrality of left frontal middle gyrus (MFG) was significantly lower than that of healthy control group. Unidirectionally, the left MFG revealed increased directional connectivity to the left superior frontal gyrus (SFG), while the left MFG exhibited decreased directional connectivity to the left middle temporal gyrus (MTG) and right lingual gyrus (LinG). And the decreased directional connectivity was found from the left precentral gyrus (PrCG) to the left MFG. In addition, the Trail-Making Test B (TMT-B) score was negatively correlated with the decreased DC of the left MFG (r = -0.359, p = 0.032). Resting-state fMRI provides a novel method for identifying aberrant brain network architecture. These results primarily indicate altered functional hubs and abnormal frontal lobe connectivity patterns that may further reflect executive dysfunction in patients with presbycusis.

Glucose Control Has an Impact on Cerebral Blood Flow Alterations in Chronic Tinnitus Patients.

PURPOSE: Both tinnitus and type 2 diabetes mellitus (T2DM) are linked with cognitive decline and brain dysfunction. This study used arterial spin labeling (ASL) perfusion functional magnetic resonance imaging (fMRI) to examine the abnormal cerebral blood flow (CBF) patterns existed in tinnitus patients and potential relationships between the abnormal CBF and cognitive performance. The impact of T2DM on CBF alterations in tinnitus patients was further explored. METHODS: Sixty tinnitus patients and 40 non-tinnitus subjects were recruited. CBF images were collected and analyzed using ASL perfusion fMRI. Brain regions with CBF alterations between tinnitus patients and non-tinnitus controls were identified by one-way analysis of variance. Interaction effects between tinnitus and T2DM for CBF changes were also selected. Then, correlation analyses were calculated to specify the link between CBF changes and cognitive performance and between CBF changes and diabetic characteristics. RESULTS: Tinnitus patients showed decreased CBF, primarily in the auditory area and default mode network (DMN), compared with non-tinnitus controls. Decreased CBF in these regions was correlated with executive function and attention. The interaction effect between tinnitus and T2DM was significant in the right medial prefrontal gyrus. Additionally, CBF in the right medial prefrontal gyrus was correlated with tinnitus distress and cognitive performance. In tinnitus patients, Hemoglobin A1c was associated with CBF in the right medial prefrontal gyrus. CONCLUSION: Tinnitus affects brain perfusion in the auditory area and DMN. T2DM and uncontrolled glucose levels may aggravate a CBF decrease in tinnitus patients. These new findings implied that tinnitus patients may benefit from blood glucose control in terms of their cognitive function and tinnitus distress.

Directed functional connectivity of the hippocampus in patients with presbycusis.

Presbycusis, associated with a diminished quality of life characterized by bilateral sensorineural hearing loss at high frequencies, has become an increasingly critical public health problem. This study aimed to identify directed functional connectivity (FC) of the hippocampus in patients with presbycusis and to explore the causes if the directed functional connections of the hippocampus were disrupted. Presbycusis patients (n = 32) and age-, sex-, and education-matched healthy controls (n = 40) were included in this study. The seed regions of bilateral hippocampus were selected to identify directed FC in patients with presbycusis using Granger causality analysis (GCA) approach. Correlation analyses were conducted to detect the associations of disrupted directed FC of hippocampus with clinical measures of presbycusis. Compared to healthy controls, decreased directed FC between inferior parietal lobule, insula, right supplementary motor area, middle temporal gyrus and hippocampus were detected in presbycusis patients. Furthermore, a negative correlation between TMB score and the decline of directed FC from left inferior parietal lobule to left hippocampus (r = -0.423, p = 0.025) and from right inferior parietal lobule to right hippocampus (r = -0.516, p = 0.005) were also observed. The decreased directed functional connections of the hippocampus were detected in patients with presbycusis, which was associated with specific cognitive performance. This study mainly emphasizes the crucial role of hippocampus in presbycusis and will enhance our understanding of the neuropathological mechanisms of presbycusis.

Chronic Tinnitus Exhibits Bidirectional Functional Dysconnectivity in Frontostriatal Circuit.

PURPOSE: The phantom sound of tinnitus is considered to be associated with abnormal functional coupling between the nucleus accumbens (NAc) and the prefrontal cortex, which may form a frontostriatal top-down gating system to evaluate and modulate sensory signals. Resting-state functional magnetic resonance imaging (fMRI) was used to recognize the aberrant directional connectivity of the NAc in chronic tinnitus and to ascertain the relationship between this connectivity and tinnitus characteristics. METHODS: Participants included chronic tinnitus patients (n = 50) and healthy controls (n = 55), matched for age, sex, education, and hearing thresholds. The hearing status of both groups was comparable. On the basis of the NAc as a seed region, a Granger causality analysis (GCA) study was conducted to investigate the directional connectivity and the relationship with tinnitus duration or distress. RESULTS: Compared with healthy controls, tinnitus patients exhibited abnormal directional connectivity between the NAc and the prefrontal cortex, principally the middle frontal gyrus (MFG), orbitofrontal cortex (OFC), and inferior frontal gyrus (IFG). Additionally, positive correlations between tinnitus handicap questionnaire (THQ) scores and increased directional connectivity from the right NAc to the left MFG (r = 0.357, p = 0.015) and from the right MFG to the left NAc (r = 0.626, p < 0.001) were observed. Furthermore, the enhanced directional connectivity from the right NAc to the right OFC was positively associated with the duration of tinnitus (r = 0.599, p < 0.001). CONCLUSION: In concurrence with expectations, tinnitus distress was correlated with enhanced directional connectivity between the NAc and the prefrontal cortex. The current study not only helps illuminate the neural basis of the frontostriatal gating control of tinnitus sensation but also contributes to deciphering the neuropathological features of tinnitus.

Tinnitus distress is associated with enhanced resting-state functional connectivity within the default mode network.

PURPOSE: The default mode network (DMN) has been confirmed to be involved in chronic tinnitus perception. Tinnitus distress may be associated with abnormal functional connectivity (FC) within the DMN regions. The goal of this study was to determine whether tinnitus disrupted the FC patterns within the DMN as measured by using resting-state functional magnetic resonance imaging approach. PATIENTS AND METHODS: Resting-state functional magnetic resonance imaging scans were acquired from 40 chronic bilateral tinnitus patients and 41 healthy controls. Both were age, sex, and education well-matched with normal hearing. Two important DMN regions, the anterior cingulate cortex and posterior cingulate cortex, were chosen as seed regions to detect the FC patterns within the DMN and then determine whether these changes were linked to clinical measures of tinnitus such as tinnitus duration and tinnitus severity. RESULTS: Compared with healthy controls, chronic tinnitus patients manifested significantly enhanced FC between the anterior cingulate cortex and left precuneus, which was correlated with the tinnitus duration (r=0.451, p=0.007). Moreover, enhanced FC between the posterior cingulate cortex and right medial prefrontal cortex in tinnitus patients was positively correlated with the tinnitus distress (r=0.411, p=0.014). CONCLUSION: Chronic tinnitus patients showed disrupted FC patterns within the DMN regions which are correlated with tinnitus distress. Increased resting-state connectivity pattern of the DMN may play a pivotal role in neuropathological features underlying chronic tinnitus.

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.