Explore the vast range of titles available.

MRgFUS has just been made available for the 1.7 million Parkinson's disease patients in China. Despite its non-invasive and rapid therapeutic advantages for involuntary tremor, some concerns have emerged about outcomes variability, non-specificity, and side-effects, as little is known about its impact on the long-term plasticity of brain structure. We sought to dissect the characteristics of long-term changes in brain structure caused by MRgFUS lesion and explored potential biological mechanisms. One-year multimodal imaging follow-ups were conducted for nine tremor-dominant Parkinson's disease patients undergoing unilateral MRgFUS thalamotomy. A structural connectivity map was generated for each patient to analyze dynamic changes in brain structure. The human brain transcriptome was extracted and spatially registered for connectivity vulnerability. Genetic functional enrichment analysis was performed and further clarified using in vivo emission computed tomography data. MRgFUS not only abolished tremors but also significantly disrupted the brain network topology. Network-based statistics identified a U-shape MRgFUS-sensitive subnetwork reflective of hand tremor recovery and surgical process, accompanied by relevant cerebral blood flow and gray matter alteration. Using human brain gene expression data, we observed that dopaminergic signatures were responsible for the preferential vulnerability associated with these architectural alterations. Additional PET/SPECT data not only validated these gene signatures, but also suggested that structural alteration was significantly correlated with D1 and D2 receptors, DAT, and F-DOPA measures. There was a long-term dynamic loop between structural alteration and dopaminergic signature for MRgFUS thalamotomy, which may be closely related to the long-term improvements in clinical tremor.

Epigenetic regulators present novel opportunities for both ischemic stroke research and therapeutic interventions. While previous work has implicated that they may provide neuroprotection by potentially influencing coordinated sets of genes and pathways, most of them remain largely uncharacterized in ischemic conditions. In this study, we used the oxygen-glucose deprivation (OGD) model in the immortalized mouse hippocampal neuronal cell line HT-22 and carried out an RNAi screen on epigenetic regulators. PRMT5 was identified as a novel negative regulator of neuronal cell survival after OGD, which presented a phenotype of translocation from the cytosol to the nucleus upon oxygen and energy depletion both in vitro and in vivo. PRMT5 bound to the chromatin and a large number of promoter regions to repress downstream gene expression. Silencing Prmt5 significantly dampened the OGD-induced changes for a large-scale of genes, and gene ontology analysis showed that PRMT5-target genes were highly enriched for Hedgehog signaling. Encouraged by the above observation, mice were treated with middle cerebral artery occlusion with the PRMT5 inhibitor EPZ015666 and found that PRMT5 inhibition sustains protection against neuronal death in vivo. Together, these findings revealed a novel epigenetic mechanism of PRMT5 in cerebral ischemia and uncovered a potential target for neuroprotection.

Tinnitus is frequently found in patients with vestibular schwannoma (VS), but its underlying mechanisms are currently unclear. Both preoperative (VS ) and postoperative (VS ) functional MR images were collected from 32 patients with unilateral VS and matched healthy controls (HCs). Connectome gradients were generated for the identification of altered regions and perturbed gradient distances. Tinnitus measurements were conducted for predictive analysis with neuroimaging-genetic integration analysis. There were 56.25% of preoperative patients and 65.63% of postoperative patients suffering from ipsilateral tinnitus, respectively. No relevant factors were identified including basic demographics info, hearing performances, tumor features, and surgical approaches. Functional gradient analysis confirmed atypical functional features of visual areas in VS were rescued after tumor resection, while the gradient performance in the postcentral gyrus continues to maintain (VS vs. HC : = 0.016). The gradient features of the postcentral gyrus were not only significantly decreased in patients with tinnitus ( = 0.022), but also significantly correlated with tinnitus handicap inventory (THI) score ( = -0.30, = 0.013), THI level ( = -0.31, = 0.010), and visual analog scale (VAS) rating ( = -0.31, = 0.0093), which could be used to predict VAS rating in the linear model. Neuropathophysiological features linked to the tinnitus gradient framework were linked to Ribosome dysfunction and oxidative phosphorylation. Altered functional plasticity in the central nervous system is involved in the maintenance of VS tinnitus.

[This corrects the article DOI: 10.3389/fnins.2023.1084270.].

Amyloid-beta (Aβ) deposition and altered brain structure are the most relevant neuroimaging biomarkers for Alzheimer’s disease (AD). However, their spatial inconsistency was always confusing and misleading. Furthermore, the relationship between this spatial inconsistency and AD progression is unclear. The current study introduced a regional radiomics similarity network (R2SN) to map structural MRI and Aβ positron emission tomography (PET) images to study their cross-modal interregional coupling. A total of 790 participants (248 normal controls, 390 mild cognitive impaired patients, and 152 AD patients) with their structural MRI and PET images were studied. The results showed that global and regional R2SN coupling significantly decreased according to the severity of cognitive decline, from mild cognitive impairment to AD dementia. The global coupling patterns are discriminative between different APOE ε4, Aβ, and Tau subgroups. R2SN coupling was probed for relationships with neuropsychiatric measures and peripheral biomarkers. Kaplan–Meier analysis showed that lower could reveal worse clinical progression of dementia. The R2SN coupling scores derived from the coupling between Aβ and atrophy over individual brain regions could reflect the specific pathway of AD progression, which would be a reliable biomarker for AD. Amyloid-beta (Aβ) deposition and altered brain structure are the most relevant neuroimaging biomarkers for Alzheimer’s disease (AD). We introduced a novel network coupling measure based on the regional radiomics similarity network (R2SN) to explore the potential association between the spatial distributions of brain structure and Aβ based on sMRI and Aβ positron emission tomography (PET) imaging. In this study, we systematically demonstrated that the alteration of the coupling between brain networks of brain structure and Aβ accumulation could serve as a predictor for revealing the distinct progression of AD.

Objective This study aimed to develop and validate internally a clinical predictive model, for predicting myasthenic crisis within 30 days after thymectomy in patients with myasthenia gravis. Methods Eligible patients were enrolled between January 2015 and May 2019. The primary outcome measure was postoperative myasthenic crisis (POMC). A predictive model was constructed using logistic regression and presented in a nomogram. The area under the receiver operating characteristic curve (AUC) was calculated to examine the performance. The study population was divided into high‐ and low‐risk groups according to Youden index. Calibration curves with 1000 replications bootstrap resampling were plotted to visualize the calibration of the nomogram. Decision curve analyses (DCA) with 1000 replications bootstrap resampling were performed to evaluate the clinical usefulness of the model. Results A total of 445 patients were enrolled. Five variables were screened including thymus imaging, onset age, MGFA classification, preoperative treatment regimen, and surgical approach. The model exhibited moderate discriminative ability with AUC value 0.771. The threshold probability was 0.113, which was used to differentiate between high‐ and low‐risk groups. The sensitivity and specificity were 72.1% and 77.1%, respectively. The high‐risk group had an 8.70‐fold higher risk of POMC. The calibration plot showed that when the probability was between 0 and 0.5, the deviation calibration curve of the model was consistent with the ideal curve. Interpretation This nomogram could assist in identifying patients at higher risk of POMC and determining the optimal surgical time for these patients.

MRI-guided focused ultrasound (MRgFUS) thalamotomy is a novel, effective, and non-invasive treatment for essential tremor (ET). However, the network mediating MRgFUS in treating ET is not precisely known. This study aimed to identify the disease-specific network associated with the therapeutic effects of MRgFUS thalamotomy on ET and investigate its regional characteristics and genetic signatures to gain insights into the neurobiological mechanism of ET and MRgFUS thalamotomy. Twenty-four ET patients treated with MRgFUS thalamotomy underwent resting-state functional MRI at baseline and postoperative 6 months to measure the fractional amplitude of low-frequency fluctuation (fALFF). Ordinal trends canonical variates analysis (OrT/CVA) was performed on the within-subject fALFF data to identify the ET-related network. Genetic functional enrichment analysis was conducted to study the genetic signatures of this ET-related network using brain-wide gene expression data. OrT/CVA analysis revealed a significant ET-related network for which subject expression showed consistent increases after surgery. The treatment-induced increases in subject expression were significantly correlated with concurrent tremor improvement. This network was characterized by increased activity in the sensorimotor cortex and decreased activity in the posterior cingulate cortex. It was correlated with an expression map of a weighted combination genes enriched for mitochondria relevant ontology terms. This study demonstrates that the therapeutic effects of MRgFUS thalamotomy on ET are associated with modulating a distinct ET-related network which may be driven by mitochondria relevant neurobiological mechanism. Quantification of treatment-induced modulation on the ET-related network can provide an objective marker for evaluating the efficacy of MRgFUS thalamotomy.

MRI-guided focused ultrasound (MRgFUS) thalamotomy is a novel, effective, and non-invasive treatment for essential tremor (ET). However, the network mediating MRgFUS in treating ET is not precisely known. This study aimed to identify the disease-specific network associated with the therapeutic effects of MRgFUS thalamotomy on ET and investigate its regional characteristics and genetic signatures to gain insights into the neurobiological mechanism of ET and MRgFUS thalamotomy. Twenty-four ET patients treated with MRgFUS thalamotomy underwent resting-state functional MRI at baseline and postoperative 6 months to measure the fractional amplitude of low-frequency fluctuation (fALFF). Ordinal trends canonical variates analysis (OrT/CVA) was performed on the within-subject fALFF data to identify the ET-related network. Genetic functional enrichment analysis was conducted to study the genetic signatures of this ET-related network using brain-wide gene expression data. OrT/CVA analysis revealed a significant ET-related network for which subject expression showed consistent increases after surgery. The treatment-induced increases in subject expression were significantly correlated with concurrent tremor improvement. This network was characterized by increased activity in the sensorimotor cortex and decreased activity in the posterior cingulate cortex. It was correlated with an expression map of a weighted combination genes enriched for mitochondria relevant ontology terms. This study demonstrates that the therapeutic effects of MRgFUS thalamotomy on ET are associated with modulating a distinct ET-related network which may be driven by mitochondria relevant neurobiological mechanism. Quantification of treatment-induced modulation on the ET-related network can provide an objective marker for evaluating the efficacy of MRgFUS thalamotomy.

Abstract Study Objectives Growing evidences have documented various abnormalities of the white matter bundles in people with narcolepsy. We sought to evaluate topological properties of brain structural networks, and their association with symptoms and neuropathophysiological features in people with narcolepsy. Methods Diffusion tensor imaging was conducted for people with narcolepsy (n = 30) and matched healthy controls as well as symptoms assessment. Structural connectivity for each participant was generated to analyze global and regional topological properties and their correlations with narcoleptic features. Further human brain transcriptome was extracted and spatially registered for connectivity vulnerability. Genetic functional enrichment analysis was performed and further clarified using in vivo emission computed tomography data. Results A wide and dramatic decrease in structural connectivities was observed in people with narcolepsy, with descending network degree and global efficiency. These metrics were not only correlated with sleep latency and awakening features, but also reflected alterations of sleep macrostructure in people with narcolepsy. Network-based statistics identified a small hyperenhanced subnetwork of cingulate gyrus that was closely related to rapid eye movement sleep behavior disorder (RBD) in narcolepsy. Further imaging genetics analysis suggested glutamatergic signatures were responsible for the preferential vulnerability of connectivity alterations in people with narcolepsy, while additional PET/SPECT data verified that structural alteration was significantly correlated with metabotropic glutamate receptor 5 (mGlutR5) and N-methyl-D-aspartate receptor (NMDA). Conclusions People with narcolepsy endured a remarkable decrease in the structural architecture, which was not only closely related to narcolepsy symptoms but also glutamatergic signatures. Graphical Abstract Graphical Abstract

Magnetic resonance-guided focused ultrasound (MRgFUS) has brought thalamotomy back to the frontline for essential tremor (ET). As functional organization of human brain strictly follows hierarchical principles which are frequently deficient in neurological diseases, whether additional damage from MRgFUS thalamotomy induces further disruptions of ET functional scaffolds are still controversial. This study was to examine the alteration features of brain functional frameworks following MRgFUS thalamotomy in patients with ET. We retrospectively obtained preoperative (ETpre) and postoperative 6-month (ET6m) data of 30 ET patients underwent MRgFUS thalamotomy from 2018 to 2020. Their archived functional MR images were used to functional gradient comparison. Both supervised pattern learning and stepwise linear regression were conducted to associate gradient features to tremor symptoms with additional neuropathophysiological analysis. MRgFUS thalamotomy relieved 78.19% of hand tremor symptoms and induced vast global framework alteration (ET6m vs. ETpre: Cohen d = − 0.80, P < 0.001). Multiple robust alterations were identified especially in posterior cingulate cortex (ET6m ET6m vs. ETpre ETpre: Cohen d = 0.87, P = 0.048). Compared with matched health controls (HCs), its gradient distances to primary communities were significantly increased in ETpre ETpre patients with anomalous stepwise connectivity (P < 0.05 in ETpre vs. HCs), which were restored after MRgFUS thalamotomy. Both global and regional gradient features could be used for tremor symptom prediction and were linked to neuropathophysiological features of Parkinson disease and oxidative phosphorylation. MRgFUS thalamotomy not only suppress tremor symptoms but also rebalances atypical functional hierarchical architecture of ET patients.