Xindao Yin

Tinnitus distress is linked to enhanced resting‐state functional connectivity from the limbic system to the auditory cortex

The phantom sound of tinnitus is believed to be triggered by aberrant neural activity in the central auditory pathway, but since this debilitating condition is often associated with emotional distress and anxiety, these comorbidities likely arise from maladaptive functional connections to limbic structures such as the amygdala and hippocampus. To test this hypothesis, resting‐state functional magnetic resonance imaging (fMRI) was used to identify aberrant effective connectivity of the amygdala and hippocampus in tinnitus patients and to determine the relationship with tinnitus characteristics. Chronic tinnitus patients (n = 26) and age‐, sex‐, and education‐matched healthy controls (n = 23) were included. Both groups were comparable for hearing level. Granger causality analysis utilizing the amygdala and hippocampus as seed regions were used to investigate the directional connectivity and the relationship with tinnitus duration or distress. Relative to healthy controls, tinnitus patients demonstrated abnormal directional connectivity of the amygdala and hippocampus, including primary and association auditory cortex, and other non‐auditory areas. Importantly, scores on the Tinnitus Handicap Questionnaires were positively correlated with increased connectivity from the left amygdala to left superior temporal gyrus (r = 0.570, P = 0.005), and from the right amygdala to right superior temporal gyrus (r = 0.487, P = 0.018). Moreover, enhanced effective connectivity from the right hippocampus to left transverse temporal gyrus was correlated with tinnitus duration (r = 0.452, P = 0.030). The results showed that tinnitus distress strongly correlates with enhanced effective connectivity that is directed from the amygdala to the auditory cortex. The longer the phantom sensation, the more likely acute tinnitus becomes permanently encoded by memory traces in the hippocampus. Hum Brain Mapp 38:2384–2397, 2017.

Resting-State Brain Abnormalities in Chronic Subjective Tinnitus: A Meta-Analysis

Purpose: The neural mechanisms that give rise to the phantom sound of tinnitus have not been fully elucidated. Neuroimaging studies have revealed abnormalities in resting-state activity that could represent the neural signature of tinnitus, but there is considerable heterogeneity in the data. To address this issue, we conducted a meta-analysis of published neuroimaging studies aimed at identifying a common core of resting-state brain abnormalities in tinnitus patients. Methods: A systematic search was conducted for whole-brain resting-state neuroimaging studies with SPECT, PET and functional MRI that compared chronic tinnitus patients with healthy controls. The authors searched PubMed, Science Direct, Web of Knowledge and Embase databases for neuroimaging studies on tinnitus published up to September 2016. From each study, coordinates were extracted from clusters with significant differences between tinnitus subjects and controls. Meta-analysis was performed using the activation likelihood estimation (ALE) method. Results: Data were included from nine resting-state neuroimaging studies that reported a total of 51 distinct foci. The meta-analysis identified consistent regions of increased resting-state brain activity in tinnitus patients relative to controls that included, bilaterally, the insula, middle temporal gyrus (MTG), inferior frontal gyrus (IFG), parahippocampal gyrus, cerebellum posterior lobe and right superior frontal gyrus. Moreover, decreased brain activity was only observed in the left cuneus and right thalamus. Conclusions: The current meta-analysis is, to our knowledge, the first to demonstrate a characteristic pattern of resting-state brain abnormalities that may serve as neuroimaging markers and contribute to the understanding of neuropathophysiological mechanisms for chronic tinnitus.

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.

Amygdala functional disconnection with the prefrontal-cingulate-temporal circuit in chronic tinnitus patients with depressive mood

Chronic tinnitus is often accompanied with depressive symptom, which may arise from aberrant functional coupling between the amygdala and cerebral cortex. To explore this hypothesis, resting-state functional magnetic resonance imaging (fMRI) was used to investigate the disrupted amygdala-cortical functional connectivity (FC) in chronic tinnitus patients with depressive mood. Chronic tinnitus patients with depressive mood (n=20), without depressive mood (n=20), and well-matched healthy controls (n=23) underwent resting-state fMRI scanning. Amygdala-cortical FC was characterized using a seed-based whole-brain correlation method. The bilateral amygdala FC was compared among the three groups. Compared to non-depressed patients, depressive tinnitus patients showed decreased amygdala FC with the prefrontal cortex and anterior cingulate cortex as well as increased amygdala FC with the postcentral gyrus and lingual gyrus. Relative to healthy controls, depressive tinnitus patients revealed decreased amygdala FC with the superior and middle temporal gyrus, anterior and posterior cingulate cortex, and prefrontal cortex, as well as increased amygdala FC with the postcentral gyrus and lingual gyrus. The current study identified for the first time abnormal resting-state amygdala-cortical FC with the prefrontal-cingulate-temporal circuit in chronic tinnitus patients with depressive mood, which will provide novel insight into the underlying neuropathological mechanisms of tinnitus-induced depressive disorder.

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.

Corticospinal tract changes in acute brainstem ischemic stroke patients: A diffusion kurtosis imaging study

Purpose: The present study aimed to investigate the corticospinal tract (CST) changes in patients with brainstem ischemic stroke by using the diffusion kurtosis imaging (DKI) approach.. Materials and Methods: Twenty-one patients with brainstem stroke and 21 group-matched healthy controls underwent brain DKI with 3.0 T magnetic resonance imaging (MRI). The DKI was obtained by using three b values of 0, 1,000, 2,000 s/mm2 with 15 diffusion directions. Regions of interest (ROIs) were placed at four levels: the pons, posterior limb of the internal capsule (PLIC), corona radiata, and precentral gyrus. The DKI parameters, including fractional anisotropy (FA), mean diffusivity (MD), and mean kurtosis (MK) values, in these regions were measured from the contralateral to the ipsilateral side of patients and both the left and right sides of healthy controls at all the four selected levels. Results: The ipsilateral side of the ischemic lesion showed a decrease in FA and MD and an increase in MK when compared with the contralateral normal region at all the four selected levels with statistically differences (P < 0.05). At these four selected levels, there were no differences between the left and right sides in healthy controls with MD, FA, and MK (P > 0.05). The MD values of the contralateral side of the ischemic lesion in patients at the four selected levels were significantly higher than those in the corresponding side of the healthy controls (P < 0.05). Compared to the healthy controls, there was a decrease at the posterior limb of the internal capsule (PLIC) in FA of the contralateral side of the ischemic lesion in stroke patients (P < 0.05). However, no significant differences were observed for MK values between the groups (P > 0.05). Conclusion: The current results suggest that the DKI technique could identify the early microstructural changes along the motor pathway and that these changes were not limited to the ipsilateral side of the ischemic lesion; in fact, the contralateral changes also occurred, especially at the PLIC.

Disrupted spontaneous neural activity related to cognitive impairment in postpartum women

Purpose: Prior research has demonstrated that the postpartum period is associated with an increased risk of cognitive impairment. This study aims to investigate whether disrupted spontaneous neural activity exists in postpartum women without depression using resting-state functional magnetic resonance imaging (rs-fMRI) and to detect the relationship between these abnormalities and cognitive impairment. Materials and Methods: Postpartum women (n = 22) were compared with age- and education-matched nulliparous women (n = 23) using rs-fMRI. We calculated the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) values to evaluate spontaneous neural activity and detect the relationship between rs-fMRI data and cognitive performance. Results: Relative to nulliparous women, postpartum women had significantly decreased ALFF and ReHo values primarily in the left posterior cingulate cortex (PCC) and prefrontal cortex and increased ALFF values in left cerebellar posterior lobe. We found a positive correlation between the ALFF and ReHo values in the PCC and the complex figure test (CFT)-delayed scores in postpartum women (r = 0.693, p = 0.001; r = 0.569, p = 0.011, respectively). Moreover, the clock-drawing test (CDT) scores showed positive correlations with the ALFF and ReHo values in the right superior frontal gyrus (SFG; r = 0.492, p = 0.033; r = 0.517, p = 0.023, respectively). Conclusion: Our combined ALFF and ReHo analyses revealed decreased spontaneous neural activity, mainly in the PCC and prefrontal cortex, which was correlated with specific impaired cognitive functioning in postpartum women. This study may elucidate the neurophysiological mechanisms underlying postpartum cognitive impairment and enhance our understanding of the neurobiological aspects of the postpartum period.

Abnormal Resting-State Functional Connectivity of the Anterior Cingulate Cortex in Unilateral Chronic Tinnitus Patients

Purpose: The anterior cingulate cortex (ACC) has been suggested to be involved in chronic subjective tinnitus. Tinnitus may arise from aberrant functional coupling between the ACC and cerebral cortex. To explore this hypothesis, we used resting-state functional magnetic resonance imaging (fMRI) to illuminate the functional connectivity (FC) network of the ACC subregions in chronic tinnitus patients. Methods: Resting-state fMRI scans were obtained from 31 chronic right-sided tinnitus patients and 40 healthy controls (age, sex, and education well-matched) in this study. Rostral ACC and dorsal ACC were selected as seed regions to investigate the intrinsic FC with the whole brain. The resulting FC patterns were correlated with clinical tinnitus characteristics including the tinnitus duration and tinnitus distress. Results: Compared with healthy controls, chronic tinnitus patients showed disrupted FC patterns of ACC within several brain networks, including the auditory cortex, prefrontal cortex, visual cortex, and default mode network (DMN). The Tinnitus Handicap Questionnaires (THQ) scores showed positive correlations with increased FC between the rostral ACC and left precuneus (r = 0.507, p = 0.008) as well as the dorsal ACC and right inferior parietal lobe (r = 0.447, p = 0.022). Conclusions: Chronic tinnitus patients have abnormal FC networks originating from ACC to other selected brain regions that are associated with specific tinnitus characteristics. Resting-state ACC-cortical FC disturbances may play an important role in neuropathological features underlying chronic 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.

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.