Yu- Chen

Altered Spontaneous Brain Activity in Type 2 Diabetes: A Resting-State Functional MRI Study

Previous research has shown that type 2 diabetes mellitus (T2DM) is associated with an increased risk of cognitive impairment. Patients with impaired cognition often show decreased spontaneous brain activity on resting-state functional magnetic resonance imaging (rs-fMRI). This study used rs-fMRI to investigate changes in spontaneous brain activity among patients with T2DM and to determine the relationship of these changes with cognitive impairment. T2DM patients (n = 29) and age-, sex-, and education-matched healthy control subjects (n = 27) were included in this study. Amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) values were calculated to represent spontaneous brain activity. Brain volume and cognition were also evaluated among these participants. Compared with healthy control subjects, patients with T2DM had significantly decreased ALFF and ReHo values in the occipital lobe and postcentral gyrus. Patients performed worse on several cognitive tests; this impaired cognitive performance was correlated with decreased activity in the cuneus and lingual gyrus in the occipital lobe. Brain volume did not differ between the two groups. The abnormalities of spontaneous brain activity reflected by ALFF and ReHo measurements in the absence of structural changes in T2DM patients may provide insights into the neurological pathophysiology underlying diabetes-associated cognitive decline.

Aberrant Brain Functional Connectivity Related to Insulin Resistance in Type 2 Diabetes: A Resting-State fMRI Study

OBJECTIVE Type 2 diabetes is characterized by insulin resistance, which is involved in the development of Alzheimer disease. This study aims to investigate the relationship between abnormal resting-state brain functional connectivity and insulin resistance in type 2 diabetes. RESEARCH DESIGN AND METHODS A total of 30 patients with type 2 diabetes and 31 healthy well-matched volunteers were prospectively examined. Resting-state brain functional connectivity analysis was used to examine the correlation between the posterior cingulate cortex (PCC) and whole-brain regions. The possible relationships between functional connectivity measures and insulin resistance were evaluated using the homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS Compared with healthy controls, we observed significantly decreased functional connectivity of the PCC within some selected regions, including the right middle temporal gyrus (MTG), left lingual gyrus, left middle occipital gyrus, and left precentral gyrus; increased functional connectivity of the PCC was detected in the left cerebellum posterior lobe, right superior frontal gyrus, and right middle frontal gyrus. A significant negative correlation was found between the PCC-right MTG connectivity and HOMA-IR in type 2 diabetic patients (P = 0.014; r = −0.446). CONCLUSIONS Type 2 diabetic patients develop aberrant functional connectivity of the PCC, which is associated with insulin resistance in selected brain regions. Resting-state connectivity disturbance of PCC–MTG may be a central role for evaluating the cognitive dysfunction in type 2 diabetes.

Tinnitus and hyperacusis involve hyperactivity and enhanced connectivity in auditory-limbic-arousal-cerebellar network

Hearing loss often triggers an inescapable buzz (tinnitus) and causes everyday sounds to become intolerably loud (hyperacusis), but exactly where and how this occurs in the brain is unknown. To identify the neural substrate for these debilitating disorders, we induced both tinnitus and hyperacusis with an ototoxic drug (salicylate) and used behavioral, electrophysiological, and functional magnetic resonance imaging (fMRI) techniques to identify the tinnitus–hyperacusis network. Salicylate depressed the neural output of the cochlea, but vigorously amplified sound-evoked neural responses in the amygdala, medial geniculate, and auditory cortex. Resting-state fMRI revealed hyperactivity in an auditory network composed of inferior colliculus, medial geniculate, and auditory cortex with side branches to cerebellum, amygdala, and reticular formation. Functional connectivity revealed enhanced coupling within the auditory network and segments of the auditory network and cerebellum, reticular formation, amygdala, and hippocampus. A testable model accounting for distress, arousal, and gating of tinnitus and hyperacusis is proposed. DOI: http://dx.doi.org/10.7554/eLife.06576.001

Aberrant spontaneous brain activity in chronic tinnitus patients revealed by resting-state functional MRI.

Objective The neural mechanisms that give rise to the phantom sound of tinnitus are poorly understood. This study aims to investigate whether aberrant spontaneous brain activity exists in chronic tinnitus patients using resting-state functional magnetic resonance imaging (fMRI) technique. Materials and methods A total of 31 patients with chronic tinnitus patients and 32 healthy age-, sex-, and education-matched healthy controls were prospectively examined. Both groups had normal hearing thresholds. We calculated the amplitude of low-frequency fluctuations (ALFFs) of fMRI signals to measure spontaneous neuronal activity and detect the relationship between fMRI information and clinical data of tinnitus. Results Compared with healthy controls, we observed significant increased ALFF within several selected regions including the right middle temporal gyrus (MTG), right superior frontal gyrus (SFG), and right angular gyrus; decreased ALFF was detected in the left cuneus, right middle occipital gyrus and bilateral thalamus. Moreover, tinnitus distress correlated positively with increased ALFF in right MTG and right SFG; tinnitus duration correlated positively with higher ALFF values in right SFG. Conclusions The present study confirms that chronic tinnitus patients have aberrant ALFF in many brain regions, which is associated with specific clinical tinnitus characteristics. ALFF disturbance in specific brain regions might be used to identify the neuro-pathophysiological mechanisms in chronic tinnitus patients.

Enhancement of the sensitivity of surface plasmon resonance biosensor with colloidal gold labeling technique

Abstract In our experiment colloidal gold was used to enhance the signal obtained from the surface-plasmonresonance biosensor. Fab′ fragments of human IgG molecules were immobilized on the gold surface and reacted with the sheep-anti-human IgG(SAH-IgG) molecules in solution. It was found that when the colloidal gold labeling technique was introduced the sensitivity of surface plasmon resonance instruments increased by a factor of about 300.

Altered Intra- and Interregional Synchronization in Resting-State Cerebral Networks Associated with Chronic Tinnitus

Objective. Subjective tinnitus is hypothesized to arise from aberrant neural activity; however, its neural bases are poorly understood. To identify aberrant neural networks involved in chronic tinnitus, we compared the resting-state functional magnetic resonance imaging (fMRI) patterns of tinnitus patients and healthy controls. Materials and Methods. Resting-state fMRI measurements were obtained from a group of chronic tinnitus patients (n = 29) with normal hearing and well-matched healthy controls (n = 30). Regional homogeneity (ReHo) analysis and functional connectivity analysis were used to identify abnormal brain activity; these abnormalities were compared to tinnitus distress. Results. Relative to healthy controls, tinnitus patients had significant greater ReHo values in several brain regions including the bilateral anterior insula (AI), left inferior frontal gyrus, and right supramarginal gyrus. Furthermore, the left AI showed enhanced functional connectivity with the left middle frontal gyrus (MFG), while the right AI had enhanced functional connectivity with the right MFG; these measures were positively correlated with Tinnitus Handicap Questionnaires (r = 0.459, P = 0.012 and r = 0.479, P = 0.009, resp.). Conclusions. Chronic tinnitus patients showed abnormal intra- and interregional synchronization in several resting-state cerebral networks; these abnormalities were correlated with clinical tinnitus distress. These results suggest that tinnitus distress is exacerbated by attention networks that focus on internally generated phantom sounds.

Magnetic resonance and near-infrared imaging using a novel dual-modality nano-probe for dendritic cell tracking in vivo.

BACKGROUND AIMS The effect of cellular-based immunotherapy is highly correlated with the success of dendritic cells (DCs) homing to the draining lymph nodes (LNs) and interacting with antigen-specific CD4(+) T cells. In this study, a novel magneto-fluorescent nano-probe was used to track the in vivo migration of DCs to the draining LNs. METHODS A dual-modality nano-probe composed of superparamagnetic iron oxide (SPIO) and near-infrared fluorescent (NIRF) dye (NIR797) was developed, and its magnetic and optical contrasting properties were characterized. DCs generated from mouse bone marrow were co-cultured with the probe at a lower concentration of 10 μg/mL. The cell phenotype and function of DCs were also investigated by fluorescence-activated cell sorting analysis and mixed leukocyte reactivity assay. Labeled DCs were injected into the footpad of C57BL/6 mice. Afterward, magnetic resonance imaging, NIRF imaging, Perls staining and CD11c immunofluorescence were used to observe the migration of the labeled DCs into draining LNs. RESULTS The synthetic SPIO-NIR797 nano-probe had a desirable superparamagnetic and near-infrared behavior. Perls staining showed perfect labeling efficiency. The cell phenotypes, including CD11c, CD80, CD86 and major histocompatibility complex class II, as well as the T-cell activation potential of the mature DCs were insignificantly affected after incubation (P > 0.05). Labeled DCs migrating into LNs could be detected by both magnetic resonance imaging and NIRF imaging simultaneously, which was further confirmed by Perls staining and immunofluorescence. CONCLUSIONS The novel dual-modality SPIO-NIR797 nano-probe has highly biocompatible characteristics for labeling and tracking DCs, which can be used to evaluate cancer immunotherapy in clinical applications.

Impairments of thalamic resting-state functional connectivity in patients with chronic tinnitus.

PURPOSE The phantom sound of tinnitus is believed to arise from abnormal functional coupling between the thalamus and cerebral cortex. To explore this hypothesis, we used resting-state functional magnetic resonance imaging (fMRI) to compare the degree of thalamocortical functional connectivity in chronic tinnitus patients and controls. MATERIALS AND METHODS Resting-state fMRI scans were obtained from 31 chronic tinnitus patients and 33 well-matched healthy controls. Thalamocortical functional connectivity was characterized using a seed-based whole-brain correlation method. The resulting thalamic functional connectivity measures were correlated with other clinical data. RESULTS We found decreased functional connectivity between the seed region in left thalamus and right middle temporal gyrus (MTG), right middle orbitofrontal cortex, left middle frontal gyrus, right precentral gyrus, and bilateral calcarine cortex. Decreased functional connectivity was detected between the seed in the right thalamus and the left superior temporal gyrus (STG), left amygdala, right superior frontal gyrus, left precentral gyrus, and left middle occipital gyrus. Tinnitus distress correlated negatively with thalamic functional connectivity in right MTG; tinnitus duration correlated negatively with thalamic functional connectivity in left STG. Increased functional connectivity between the bilateral thalamus and a set of regions were also observed. CONCLUSIONS Chronic tinnitus patients have disrupted thalamocortical functional connectivity to selected brain regions which is associated with specific tinnitus characteristics. Resting-state thalamic functional connectivity disturbances may play an important role in neuropathological features of tinnitus.

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.

Altered Interhemispheric Functional Coordination in Chronic Tinnitus Patients

Purpose. Recent studies suggest that tinnitus may be due in part to aberrant callosal structure and interhemispheric interaction. To explore this hypothesis we use a novel method, voxel-mirrored homotopic connectivity (VMHC), to examine the resting-state interhemispheric functional connectivity and its relationships with clinical characteristics in chronic tinnitus patients. Materials and Methods. Twenty-eight chronic tinnitus patients with normal hearing thresholds and 30 age-, sex-, education-, and hearing threshold-matched healthy controls were included in this study and underwent the resting-state fMRI scanning. We computed the VMHC to analyze the interhemispheric functional coordination between homotopic points of the brain in both groups. Results. Compared to the controls, tinnitus patients showed significantly increased VMHC in the middle temporal gyrus, middle frontal gyrus, and superior occipital gyrus. In tinnitus patients, a positive correlation was found between tinnitus duration and VMHC of the uncus. Moreover, correlations between VMHC changes and tinnitus distress were observed in the transverse temporal gyrus, superior temporal pole, precentral gyrus, and calcarine cortex. Conclusions. These results show altered interhemispheric functional connectivity linked with specific tinnitus characteristics in chronic tinnitus patients, which may be implicated in the neuropathophysiology of tinnitus.