Left or right ear? A neuroimaging study using combined taVNS/fMRI to understand the interaction between ear stimulation target and lesion location in chronic stroke.

BACKGROUND: Implanted vagus nerve stimulation (VNS) and transcutaneous auricular VNS (taVNS) have been primarily administered clinically to the unilateral-left vagus nerve. This left-only convention has proved clinically beneficial in brain disorders. However, in stroke survivors, the presence of a lesion in the brain may complicate VNS-mediated signaling, and it is important to understand the laterality effects of VNS in stroke survivors to optimize the intervention. OBJECTIVE: To understand whether taVNS delivered to different ear targets relative to the lesion (ipsilesional vs contralesional vs bilateral vs sham) impacts blood oxygenation level dependent (BOLD) signal propagation in stroke survivors. METHODS: We enrolled 20 adults with a prior history of stroke. Each participant underwent a single visit, during which taVNS was delivered concurrently during functional magnetic resonance imaging (fMRI) acquisition. Each participant received three discrete active stimulation conditions (ipsilesional, contralesional, bilateral) and one sham condition in a randomized order. Stimulation-related BOLD signal changes in the active conditions were compared to sham conditions to understand the interaction taVNS and laterality effects. RESULTS: All active taVNS conditions deactivated the contralesional default mode network related regions compared to sham, however only ipsilesional taVNS enhanced the activations in the ipsilesional visuomotor and secondary visual cortex. Furthermore, we reveal an interaction in task activations between taVNS and cortical visuomotor areas, where ipsilesional taVNS significantly increased ipsilesional visuomotor activity and decreased contralesional visuomotor activity compared to sham. CONCLUSION: Laterality of taVNS relative to the lesion is a critical factor in optimizing taVNS in a stroke population, with ipsilesional stimulation providing largest direct brain activation and should be explored further when designing taVNS studies in neurorehabilitation.

Free zinc determines the formability of the vesicular dense core in diabetic beta cells.

During the progression of type 2 diabetes, total body zinc deficiency disrupts the formability of the electron-dense core in beta-cell vesicles, but the mechanism is unclear. Using fluorescence imaging, transmission electron microscopy and pharmacokinetics assays, we established a strong link between an increasing concentration of free zinc and the formability enhancement of the dense core electron density. Thus, our results highlight a mechanism by which zinc supplementation enhances the maturation of dense cores and restores the secretion of insulin in two diabetic mouse models both in vitro and in vivo. This study provides a potential research direction for investigating the etiology and nutrition of zinc in the management of type 2 diabetes.

Functional brain connectome and its relation to mild cognitive impairment in cerebral small vessel disease patients with thalamus lacunes: A cross-sectional study.

To investigate the functional connectome alterations in cerebral small-vessel disease (CSVD) patients with thalamus lacunes and its relation to cognitive impairment.This case-control study was approved by the local research ethics committee, and all participants provided informed consent. There were 14 CSVD patients with thalamus lacunes (CSVDw.), 27 without (CSVDwo.), and 34 healthy controls (HC) recruited matched for age, sex, and education to undergo a 3T resting-state functional MR examination. The whole-brain functional connectome was constructed by thresholding the Pearson correlation matrices of 90 brain regions, and the topologic properties were analyzed by using graph theory approaches. Networks were compared between CSVD patients and HC, and associations between network measures and cognitive function were tested.Compared with HC, the functional connectome in CSVDw. patients showed abnormalities at the global level and at the nodal level (P < .05, false discovery rate corrected). The network-based statistics method identified a significantly altered network consisting 6 nodes and 13 connections. Among all the 13 connections, only two connections had significant correlation with episodic memory (EM) and processing speed (PS) respectively (P < .05). The CSVDwo. patients showed no significant network alterations relative to controls (P > .05).The configurations of brain functional connectome in CSVDw. patients were perturbed but not obvious for those without, and correlated with the mild cognitive impairment, especially for EM and PS. This study suggested that lacunes on thalamus played a vital role in mediating the neural functional changes of CSVD patients.

Amid proton transfer (APT) and magnetization transfer (MT) MRI contrasts provide complimentary assessment of brain tumors similarly to proton magnetic resonance spectroscopy imaging (MRSI).

OBJECTIVES: Using MRSI as comparison, we aimed to explore the difference between amide proton transfer (APT) MRI and conventional semi-solid magnetization transfer ratio (MTR) MRI, and to investigate if molecular APT and structural MTR can provide complimentary information in assessing brain tumors. METHODS: Seventeen brain tumor patients and 17 age- and gender-matched volunteers were included and scanned with anatomical MRI, APT and MT-weighted MRI, and MRSI. Multi-voxel choline (Cho) and N-acetylaspartic acid (NAA) signals were quantified from MRSI and compared with MTR and MTRasym(3.5ppm) contrasts averaged from corresponding voxels. Correlations between contrasts were explored voxel-by-voxel by pooling values from all voxels into Pearson's correlation analysis. Differences in correlation coefficients were tested with the Z-test (set at p<0.05). RESULTS: APT and MT provide good contrast and quantitative parameters in tumor imaging, as do the metabolite (Cho and NAA) maps. MTRasym(3.5ppm) significantly correlated with MTR (R=-0.61, p<0.0001), Cho (R=0.568, p<0.0001) and NAA (R=-0.619, p<0.0001) in tumors, and MTR also significantly correlated with Cho (R=-0.346, p<0.0001) and NAA (R=0.624, p<0.0001). In healthy volunteers, MTRasym(3.5ppm) was non-significantly correlated with MTR (R=-0.049, p=0.239), Cho (R=0.030, p=0.478) and NAA (R=-0.083, p=0.046). Significant correlations were found among MTR with Cho (R=0.199, p<0.0001) and NAA (R=0.263, p<0.0001) in the group of healthy volunteers with lower correlation R values than those in tumor patients. CONCLUSIONS: APT and MT could provide independent and supplementary information for the comprehensive assessment of molecular and structural changes due to brain tumor cancerogenesis. KEY POINTS: • MTR asym(3.5ppm) positively correlated with Cho while negatively with NAA in tumors. • MTR positively correlated with NAA while negatively with Cho in tumors. • Combining APT/MT provides molecular and structural information similarly to MRSI.

A DOPA-functionalized chondroitin sulfate-based adhesive hydrogel as a promising multi-functional bioadhesive.

Great progress has been achieved on the study of hydrogels, which were presented for the first time in 1960 by Otto Wichterle and Drahoslav Lím. The two crucial properties of hydrogels, namely high water content and biocompatibility, have made hydrogels ideal compositions in the development of bioadhesives in recent years. Chondroitin sulfate (CS), a sulfated glycosaminoglycan (GAG), is distributed throughout animal bodies, including cartilage and the extracellular matrix (ECM), and it has been widely utilized in the dietary supplement and pharmaceutical industries. Besides, CS has been reported to have excellent pain-relief and anti-inflammation properties. Some studies have even reported CS's wound healing promoting ability. In this study, taking advantage of CS's excellent physical and chemical properties, DOPA groups were functionalized onto CS backbones. After that, the potential of the newly established CS-DOPA (CSD) hydrogel to work as a bioadhesive in multiple internal medical conditions was evaluated through in vitro and in vivo means. The outcomes of the in vivo assessments demonstrated CSD's promising potential to be further commercialized into an adhesive hydrogel product, and to be utilized in diverse clinical medications in the future.

Role of diffusion tensor imaging or magnetic resonance spectroscopy in the diagnosis and disability assessment of amyotrophic lateral sclerosis.

OBJECTIVE: To compare the results of magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI) in amyotrophic lateral sclerosis (ALS) patients. METHODS: Nineteen ALS patients and thirteen age-matched healthy controls underwent MRS and DTI between October 2013 and July 2014. Fractional anisotropy (FA), apparent diffusion coefficient (ADC), N-acetylaspartate (NAA), choline (Cho), and creatine (Cr) were collected as the quantitative results of the imaging study. The ALS functional rating scale-revised (ALSFRS-R) and disease progression rate were evaluated to assess patients' disability. The imaging study results were compared between ALS patients and healthy controls. The relationship between disability assessment and imaging study results was analyzed. RESULTS: NAA/Cr in the motor cortex and FA in the corticospinal tract (CST) of both sides were significantly lower in patients than controls. There was no significant difference between the two groups in Cho/Cr, tract length, tract volume, ADC or NAA. No relationship was found between ALSFRS-R and FA (r=0.243, p=0.316) in the right CST; NAA (r=0.095, p=0.699) or NAA/Cr (r=0.172, p=0.481) in the left motor cortex; or NAA (r=0.320, p=0.182) or NAA/Cr (r=0.193, p=0.492) in the right motor cortex. There was no relationship between the disease progression rate and FA, NAA, or NAA/Cr on either side. CONCLUSION: NAA/Cr and FA can help diagnose ALS. Regional brain NAA/Cr and FA values could not assess the ALSFRS-R or disease progression rate.

Proton magnetic resonance spectroscopy in neonates with hypoxic-ischemic injury and its prognostic value.

It is difficult to predict the neurologic outcome of neonates with hypoxic-ischemic encephalopathy (HIE). Our goal was to investigate the prognostic values of magnetic resonance spectroscopy (MRS) in neonatal HIE. During this study, 46 neonates with HIE underwent magnetic resonance imaging (MRI) and proton MRS ((1)HMRS). The sample included 25 cases of mild HIE, 11 cases of moderate HIE, and 10 cases of severe HIE. Nine healthy neonates without asphyxia served as controls. (1)HMRS techniques included single-voxel MRS and 2-D-point-resolved spatially localized spectroscopy (PRESS) multivoxel chemical shift spectroscopy imaging. Then, 31 of 46 neonates with HIE were divided into 3 groups according to their prognosis: dead, abnormal, and normal outcome. Abnormal and normal outcome were defined by follow-up MRI. Metabolic changes were analyzed and compared with HIE grading and prognosis. As a result, the GLx-alpha peak was markedly increased in the moderate and severe HIE groups. The GLx-alpha/Cr ratio in the control, mild, moderate, and severe HIE groups was 0.18, 0.21, 0.64, 1.31, respectively. The Lac/Cr ratio was 0.12, 0.14, 0.19, and 0.26, respectively. A Spearman rank correlation test confirmed that the ratio of GLx-alpha/Cr and Lac/Cr had significant positive correlation with clinical grading of HIE (P < 0.01). The GLx-alpha/Cr ratio in the dead, abnormal, and normal outcome groups was 1.28, 0.82, and 0.25, respectively; the Lac/Cr ratio was 0.34, 0.19, and 0.14, respectively. An anaylsis of variance demonstrated that the differences were significant (both P < 0.01). A Spearman rank correlation test confirmed that the ratio of GLx-alpha/Cr and Lac/Cr had significant negative correlation with prognosis of HIE; GLx-alpha/Cr showed a much stronger correlation than the Lac/Cr ratio (P < 0.01). The formula of the relationship between the poor prognosis of HIE and the ratio of GLx-alpha/Cr in basal ganglia was established by the logistic regression model. In conclusion, (1)HMRS is a useful tool for evaluating the severity and prognosis of HIE. The higher ratio of GLx-alpha/Cr in the basal ganglia and thalamus may predict a poor outcome in neonates with HIE.