Convergent Neuroimaging and Molecular Signatures in Mild Cognitive Impairment and Alzheimer's Disease: A Data-Driven Meta-Analysis with N = 3,118.

The current study aimed to evaluate the susceptibility to regional brain atrophy and its biological mechanism in Alzheimer's disease (AD). We conducted data-driven meta-analyses to combine 3,118 structural magnetic resonance images from three datasets to obtain robust atrophy patterns. Then we introduced a set of radiogenomic analyses to investigate the biological basis of the atrophy patterns in AD. Our results showed that the hippocampus and amygdala exhibit the most severe atrophy, followed by the temporal, frontal, and occipital lobes in mild cognitive impairment (MCI) and AD. The extent of atrophy in MCI was less severe than that in AD. A series of biological processes related to the glutamate signaling pathway, cellular stress response, and synapse structure and function were investigated through gene set enrichment analysis. Our study contributes to understanding the manifestations of atrophy and a deeper understanding of the pathophysiological processes that contribute to atrophy, providing new insight for further clinical research on AD.

Profiling functional networks identify activation of corticostriatal connectivity in ET patients after MRgFUS thalamotomy.

BACKGROUND: MR-guided focused ultrasound (MRgFUS) thalamotomy is a novel and effective treatment for medication-refractory tremor in essential tremor (ET), but how the brain responds to this deliberate lesion is not clear. OBJECTIVE: The current study aimed to evaluate the immediate and longitudinal alterations of functional networks after MRgFUS thalamotomy. METHODS: We retrospectively obtained preoperative and postoperative 30-day, 90-day, and 180-day data of 31 ET patients subjected with MRgFUS thalamotomy from 2018 to 2020. Their archived resting-state functional MRI data were used for functional network comparison as well as graph-theory metrics analysis. Both partial least squares (PLS) regression and linear regression were conducted to associate functional features to tremor symptoms. RESULTS: MRgFUS thalamotomy dramatically abolished tremors, while global functional network only sustained immediate fluctuation within one week after the surgery. Network-based statistics have identified a long-term enhanced corticostriatal subnetwork by comparison between 180-day and preoperative data (P = 0.019). Within this subnetwork, network degree, global efficiency and transitivity were significantly recovered in ET patients right after MRgFUS thalamotomy compared to the pre-operative timepoint (P < 0.05), as well as hemisphere lateralization (P < 0.001). The PLS main component significantly accounted for 33.68 % and 34.16 % of the total variances of hand tremor score and clinical rating scale for tremor (CRST)-total score (P = 0.037 and 0.027). Network transitivity of this subnetwork could serve as a reliable biomarker for hand tremor score control prediction at 180-day after the surgery (ß = 2.94, P = 0.03). CONCLUSION: MRgFUS thalamotomy promoted corticostriatal connectivity activation correlated with tremor improvement in ET patient after MRgFUS thalamotomy.

Tumor characteristics, brain functional activity, and connectivity of tinnitus in patients with vestibular schwannoma: a pilot study.

Background: The mechanism underlying tinnitus remains unclear, and when it coexists with vestibular schwannoma (VS), it can significantly diminish the quality of life for affected patients. This study aimed to determine the correlation between preoperative clinical characteristics of VS, postoperative changes in brain function, and tinnitus in patients with VS through a cohort study. Methods: We collected data from 80 patients with VS preoperatively and 28 patients with VS preoperatively and postoperatively, and recruited 28 healthy controls. We used Chi-squared tests and unpaired t-tests to identify clinical characteristics with a significant preoperative effect. We used paired t-tests to identify brain regions where patients demonstrated significant changes in amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) postoperatively. Tinnitus severity was evaluated using the Tinnitus Handicap Inventory (THI) and Visual Analogue Scale (VAS). Pearson correlation coefficients were applied to assess the relationship between the changes in ALFF and ReHo and the changes in THI and VAS scores postoperatively. We also conducted seed- and region of interest (ROI)-based functional connectivity (FC) analyses. Results: Before surgery, patients with VS with tinnitus (n=49) had smaller tumors (t=3.293; P<0.001), more solid tumor (χ2=4.559; P=0.033), and less extrusion into the cerebellum brain stem (χ2=10.345; P=0.001) than those without tinnitus (n=31). After surgery, the 28 patients with VS showed a significant reduction in ALFF in the left Cerebellum_Crus2 (a lobule in the cerebellum anatomy) (ROI 1) and a significant reduction in ReHo in the left Cerebellum_Crus1 (a lobule in the cerebellum anatomy) (ROI 2) and the right precuneus (ROI 3). Conversely, ReHo was significantly increased in the right precentral gyrus (ROI 4) [cluster-level P value family-wise error (PFWE) <0.05]. The changes in ALFF values were negatively correlated with changes in the VAS score (r=-0.32; P<0.05). The FC strengths of patients between ROI 2 and the left and right posterior cingulate gyrus were significantly decreased postoperatively [false discovery rate (FDR) correction; P<0.05]. Conclusions: Preoperative tinnitus in patients with VS may be influenced by tumor characteristics. The functional activities of brain regions are possibly altered postoperatively, which may be involved in the maintenance of postoperative tinnitus. Notably, the changes in ALFF are correlated with tinnitus.

Genetic screen identified PRMT5 as a neuroprotection target against cerebral ischemia.

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.

Disrupted topological properties of structural brain networks present a glutamatergic neuropathophysiology in people with narcolepsy.

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.

Alteration of White Matter Connectivity for MR-Guided Focused Ultrasound in the Treatment of Essential Tremor.

BACKGROUND: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy has been implemented as a therapeutic alternative for the treatment of drug-refractory essential tremor (ET). However, its impact on the brain structural network is still unclear. PURPOSE: To investigate both global and local alterations of the white matter (WM) connectivity network in ET after MRgFUS thalamotomy. STUDY TYPE: Retrospective. SUBJECTS: Twenty-seven ET patients (61 ± 11 years, 19 males) with MRgFUS thalamotomy and 28 healthy controls (HC) (61 ± 11 years, 20 males) were recruited for comparison. FIELD STRENGTH/SEQUENCE: A 3 T/single shell diffusion tensor imaging by using spin-echo-based echo-planar imaging, three-dimensional T1 weighted imaging by using gradient-echo-based sequence. ASSESSMENT: Patients were undergoing MRgFUS thalamotomy and their clinical data were collected from pre-operation to 6-month post-operation. Network topological metrics, including rich-club organization, small-world, and efficiency properties were calculated. Correlation between the topological metrics and tremor scores in ET groups was also calculated to assess the role of neural remodeling in the brain. STATISTICAL TESTS: Two-sample independent t-tests, chi-squared test, ANOVA, Bonferroni test, and Spearman's correlation. Statistical significance was set at P < 0.05. RESULTS: For ET patients, the strength of rich-club connection and clustering coefficient significantly increased vs. characteristic path length decreased at 6-month post-operation compared with pre-operation. The distribution pattern of rich-club regions was different in ET groups. Specifically, the order of the rich-club regions was changed according to the network degree value after MRgFUS thalamotomy. Moreover, the altered nodal efficiency in the right temporal pole of the superior temporal gyrus (R = 0.434-0.596) and right putamen (R = 0.413-0.436) was positively correlated with different tremor improvement. DATA CONCLUSION: These findings might improve understanding of treatment-induced modulation from a network perspective and may work as an objective marker in the assessment of ET tremor control with MRgFUS thalamotomy. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 4.

Generative Adversarial Network-based Noncontrast CT Angiography for Aorta and Carotid Arteries.

Background Iodinated contrast agents (ICAs), which are widely used in CT angiography (CTA), may cause adverse effects in humans, and their use is time-consuming and costly. Purpose To develop an ICA-free deep learning imaging model for synthesizing CTA-like images and to assess quantitative and qualitative image quality as well as the diagnostic accuracy of synthetic CTA (Syn-CTA) images. Materials and Methods A generative adversarial network (GAN)-based CTA imaging model was trained, validated, and tested on retrospectively collected pairs of noncontrast CT and CTA images of the neck and abdomen from January 2017 to June 2022, and further validated on an external data set. Syn-CTA image quality was evaluated using quantitative metrics. In addition, two senior radiologists scored the visual quality on a three-point scale (3 = good) and determined the vascular diagnosis. The validity of Syn-CTA images was evaluated by comparing the visual quality scores and diagnostic accuracy of aortic and carotid artery disease between Syn-CTA and real CTA scans. Results CT scans from 1749 patients (median age, 60 years [IQR, 50-68 years]; 1057 male patients) were included in the internal data set: 1137 for training, 400 for validation, and 212 for testing. The external validation set comprised CT scans from 42 patients (median age, 67 years [IQR, 59-74 years]; 37 male patients). Syn-CTA images had high similarity to real CTA images (normalized mean absolute error, 0.011 and 0.013 for internal and external test set, respectively; peak signal-to-noise ratio, 32.07 dB and 31.58 dB; structural similarity, 0.919 and 0.906). The visual quality of Syn-CTA and real CTA images was comparable (internal test set, P = .35; external validation set, P > .99). Syn-CTA showed reasonable to good diagnostic accuracy for vascular diseases (internal test set: accuracy = 94%, macro F1 score = 91%; external validation set: accuracy = 86%, macro F1 score = 83%). Conclusion A GAN-based model that synthesizes neck and abdominal CTA-like images without the use of ICAs shows promise in vascular diagnosis compared with real CTA images. Clinical trial registration no. NCT05471869 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Zhang and Turkbey in this issue.

Magnetic Resonance-Guided Focused Ultrasound Thalamotomy Rebalances Atypical Functional Hierarchy in Patients with Essential Tremor.

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 ([Formula: see text] ET6m vs. [Formula: see text] ETpre: Cohen d = 0.87, P = 0.048). Compared with matched health controls (HCs), its gradient distances to primary communities were significantly increased in [Formula: see text] 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.

Multi-frequency therapeutic ultrasound: A review.

Focused ultrasound is a noninvasive, radiation-free and real-time therapeutic approach to treat deep-seated targets, which benefits numerous diseases otherwise requiring surgeries. Treatment efficiency is one of the key factors determining therapeutic outcomes, but improving it solely by increasing the total power can be limited by the performance of general ultrasound devices. To address this, multi-frequency therapeutic ultrasound, using additional ultrasound waves of different frequencies on top of the standard single-frequency wave, provides a promising method for treatment efficiency enhancement with limited power. Several applications and numerical works have demonstrated its superiority on treatment enhancement. This paper presents an overview of the mechanisms, implementations, applications and decisive parameters of the multi-frequency therapeutic ultrasound, which could help to pave the way for better understanding and further developing this technology in the future.

Gray matter alterations in tremor-dominant Parkinson's disease after MRgFUS thalamotomy are correlated with tremor improvement: a pilot study.

Background: Regional differences in gray matter volume (GMV) have been reported to be a reliable marker for diagnosing Parkinson's disease (PD). This study aimed to explore the clinical value of GMV to assess magnetic resonance imaging-guided focused ultrasound (MRgFUS) thalamotomy as a treatment for tremor-dominant PD (TDPD). Methods: Nine TDPD patients with MRgFUS thalamotomy were recruited for structural magnetic resonance image (MRI) scanning and clinical score evaluation. GMV was calculated. To investigate changes after treatment, voxel- and region of interest (ROI)-wise GMV analyses were performed. Then, GMV with significant differences was extracted from patients to investigate its dynamic alterations by one-way repeated-measures analysis of variance (ANOVA). The nonparametric Spearman rank correlation analysis was used to evaluate the relationship between GMV alterations and tremor improvement after thalamotomy. Results: Tremors were significantly relieved after MRgFUS thalamotomy in nine patients (P<0.05). The treated hand tremor scores improved 74.82% on average in patients from pre-operation to 12 months post-operation. Voxel-wise analysis at the cluster level showed a significant decrease in GMV in the left middle occipital gyrus (MOG) [t=11.81, voxel-level P<0.001, cluster-level Pfamily-wise error (FWE) <0.05] and an increase in GMV in the left precentral gyrus (PreCG) (t=7.99, voxel-level P<0.001, cluster-level PFWE <0.05) in TDPD patients from preoperative to 12 months post-operation, which was significantly correlated with tremor scores (rho =0.346-0.439, P<0.05). ROI-wise analysis showed that GMV related to MRgFUS thalamotomy was associated with long-term structural alterations (P<0.05 with Bonferroni correction), including specific basal ganglia and related nuclei and cerebellum subregions. Conclusions: GMV can be used to reflect tremor improvement after MRgFUS thalamotomy and be helpful to better understand the distant effect of MRgFUS thalamotomy and the involvement of GMV in tremor control in TDPD. Trial Registration: ClinicalTrials.gov identifier: NCT04570046.

Corrigendum: Atypical functional hierarchy contributed to the tinnitus symptoms in patients with vestibular schwannoma.

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

Coupling of the spatial distributions between sMRI and PET reveals the progression of Alzheimer's disease.

Amyloid-beta (Aß) 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 Aß 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, Aß, and Tau subgroups. R2SN coupling was probed for relationships with neuropsychiatric measures and peripheral biomarkers. Kaplan-Meier analysis showed that lower global coupling scores could reveal worse clinical progression of dementia. The R2SN coupling scores derived from the coupling between Aß and atrophy over individual brain regions could reflect the specific pathway of AD progression, which would be a reliable biomarker for AD.

Atypical functional hierarchy contributed to the tinnitus symptoms in patients with vestibular schwannoma.

Objective: Tinnitus is frequently found in patients with vestibular schwannoma (VS), but its underlying mechanisms are currently unclear. Methods: Both preoperative (VS pre ) and postoperative (VS post ) 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. Results: 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 pre were rescued after tumor resection, while the gradient performance in the postcentral gyrus continues to maintain (VS post vs. HC : P = 0.016). The gradient features of the postcentral gyrus were not only significantly decreased in patients with tinnitus (P FDR = 0.022), but also significantly correlated with tinnitus handicap inventory (THI) score (r = -0.30, P = 0.013), THI level (r = -0.31, P = 0.010), and visual analog scale (VAS) rating (r = -0.31, P = 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. Conclusion: Altered functional plasticity in the central nervous system is involved in the maintenance of VS tinnitus.

Nomogram for predicting the risk of postoperative myasthenic crisis in patients with thymectomy.

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.

Evaluation of postcontrast images of intracranial tumors at 7T and 3T MRI: An intra-individual comparison study.

AIM: This study aimed to evaluate the diagnostic value of ultrahigh-field magnetic resonance imaging (MRI) for brain tumors in clinical practice. METHODS: Thirty patients with brain tumors underwent 7- and 3-T MRI. The performance and diagnostic confidence of 7- and 3-T MRI in the visualization of tumor details such as internal structure and feeding artery were evaluated by radiologists. Contrast-enhanced region performance and tumor detail diagnostic confidence score (DCS) were calculated and compared between 7 and 3T using Wilcoxon rank sum test. RESULTS: In 19 with obvious enhancement and 11 cases without obvious enhancement, 7- and 3-T MRI showed similar performance. The tumors' internal structure and feeding artery were more clearly depicted by 7-T MRI (62.2% and 54.4%, respectively) than by 3-T MRI (2.2% and 6.7%, respectively). Furthermore, the mean DCSs of both internal structure and feeding artery were higher at 7T than at 3T (internal structure: 16.29 ± 9.67 vs. -5.79 ± 4.12, p = 0.028; feeding artery: 21.96 ± 6.93 vs. 4.46 ± 7.07, p = 0.028). The DCS was more significantly improved in the senior radiologist group. CONCLUSION: Better visualization of brain tumor details and higher tumor detail diagnostic confidence can be obtained with 7-T MRI.

Assessing the impact of MR-guided focused ultrasound thalamotomy on brain activity and connectivity in patients with essential tremor.

OBJECTIVE: Although magnetic resonance-guided focused ultrasound (MRgFUS) at the ventral intermediate (VIM) thalamic nucleus is a novel and effective treatment for medication-refractory essential tremor (ET), it is unclear how the ablation lesion affects functional activity. The current study sought to evaluate the functional impact of MRgFUS thalamotomy in patients with ET, as well as to investigate the relationship between neuronal activity changes and tremor control. METHODS: This study included 30 patients with ET who underwent MRgFUS thalamotomy with a 6-month follow-up involving MRI and clinical tremor rating. Additional sex- and age-matched healthy people were recruited for the healthy control group. The fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity were used to identify functional alteration regions of interest (ROIs). To investigate changes after treatment, ROI- and seed-based functional connectivity (FC) analyses were performed. RESULTS: Patients with ET had significantly increased fALFF in the right postcentral gyrus (PoCG; ROI 1), regional homogeneity in the left PoCG (ROI 2), and regional homogeneity in the right PoCG (ROI 3, cluster-level p value family-wise error [pFWE] < 0.05), which were recovered and normalized at 6 months after MRgFUS thalamotomy. FCs between ROI 2 and the right supramarginal gyrus, ROI 2 and the right superior parietal gyrus, and ROI 3 and the left precentral gyrus were also found to be increased after treatment (cluster-level pFWE < 0.05). Furthermore, changes in fALFF, regional homogeneity, and FC values were significantly correlated with tremor relief (p < 0.05). Preoperative FC strengths were found to be inversely related to the postoperative tremor control ratio (p < 0.05). CONCLUSIONS: In patients with ET, the VIM lesion of MRgFUS thalamotomy resulted in symptom-related regional functional recovery associated with sensorimotor and attention networks. Preoperative FC strengths may reflect the postoperative tremor control ratio, implying that this metric could be a useful neuroimaging biomarker for predicting symptom relief in patients with ET following thalamotomy.

Treatment-Specific Network Modulation of MRI-Guided Focused Ultrasound Thalamotomy in Essential Tremor : Modulation of ET-Related Network by 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.

Gray Matter Volume Abnormality in Chronic Pain Patients With Depressive Symptoms: A Systemic Review and Meta-Analysis of Voxel-Based Morphometry Studies.

Background: Gray matter volume (GMV) alteration in specific brain regions has been widely regarded as one of the most important neuroplasticity features in chronic pain patients with depressive symptoms (CP-D). However, the consistent and significant results were still lacking. Thus, further exploration was suggested to be performed. Objectives: This study aimed to comprehensively collect the voxel-based morphometry (VBM) studies on GMV alteration between CP-D and healthy controls (HCs). And a systemic review and meta-analysis were made to explore the characteristic brain regions in chronic pain and depression comorbidity. Methods: Search of PubMed, MEDLINE, Web of Science, and Cochrane Library databases updated to July 13, 2021. The altered GMV between CP-D and HCs in VBM studies was included in this meta-analysis. In total, 18 studies (20 datasets) and 1320 participants (520 patients and 800 HCs) were included. The significant coordinate information (x, y, z) reported in standard space and the effect size (t-value or z-score) were extracted and analyzed by anisotropic effect size-signed differential mapping (AES-SDM) 5.15 software. Results: According to the main analysis results, CP-D showed significant and consistent increased GMV in the left hippocampus (HIP. L) and decreased GMV in the medial part of the left superior frontal gyrus (SFG. L, BA 10) compared to HCs. Subgroup analysis showed significant decreased GMV in the medial orbital part of SFG.R (BA 10) in neuropathic pain, as well as significant increased GMV in the right parahippocampal gyrus (PHG.R, BA 35), left hippocampus (HIP.L, BA 20), and right middle frontal gyrus (MFG.R) in musculoskeletal pain. Furthermore, meta-regression showed a positive relationship between the decreased GMV in the medial part of SFG.L and the percentage of female patients. Conclusion: GMV abnormality in specific brain areas (e.g., HIP.L and SFG) was robust and reproducible, which could be significantly involved in this comorbidity disease. The findings in this study may be a valuable reference for future research. Systematic Review Registration: [www.crd.york.ac.uk/prospero/].

Regulatory B Cells Are Decreased and Functionally Impaired in Myasthenia Gravis Patients.

Myasthenia gravis (MG) is an autoimmune disease mediated by B cells secreting autoantibodies. Regulatory B (Breg) cells confirmed to have an immunosuppressive function play an important role in many autoimmune diseases. However, what about the changes in Breg cells in the thymus and peripheral blood of MG patients? The changes in the proportion of Breg cells in the peripheral blood of 41 MG patients without any drug treatment and 30 healthy controls were detected by flow cytometry. We found that the proportions of CD19+ IL-10+ cells and CD19+CD24hiCD38hi cell subsets in MG patients were significantly lower than those in healthy controls. Then, we detected the proportion of CD19+ IL-10+ cells in thymus tissues of 10 healthy children, 4 healthy adults, and 12 MG patients by flow cytometry. However, the percentage of CD19+ IL-10+ cells was highest in healthy children (~8%), followed by healthy adults (~3%), and was lowest in MG patients (~0.5%). CD19+CD24hiCD38hi B cells exerted immunosuppressive functions in healthy people but were refractory in MG patients. Moreover, p-STAT3 downstream of CD40 may be impaired in CD24hiCD38hi B cells from the peripheral blood of MG patients.

Pretherapeutic functional connectivity of tractography-based targeting of the ventral intermediate nucleus for predicting tremor response in patients with Parkinson's disease after thalamotomy with MRI-guided focused ultrasound.

OBJECTIVE: Tractography-based direct targeting of the ventral intermediate nucleus (T-VIM) is a novel method that provides patient-specific VIM coordinates. This study aimed to explore the accuracy and predictive value of using T-VIM in combination with tractography and resting-state functional connectivity techniques to perform magnetic resonance imaging-guided focused ultrasound (MRgFUS) thalamotomy as a treatment of Parkinson's disease (PD). METHODS: PD patients underwent MRgFUS thalamotomy and were recruited for functional MRI scanning. A subscore of the Clinical Rating Scale for Tremor was used to evaluate tremor improvement. T-VIM and surgical VIM (S-VIM) were defined on preoperative diffusion tensor MRI and 24-hour postoperative T1-weighted imaging, respectively. The overlapping volume and center distance between S-VIM and T-VIM were measured to determine their correlations with 12-month postoperative tremor improvement. Moreover, pretherapeutic functional connectivity of T-VIM or S-VIM, based on region-of-interest connectivity and whole-brain seed-to-voxel connectivity, was measured with the resting-state functional connectivity technique to investigate their correlations with tremor improvement. RESULTS: All patients had excellent tremor improvement (mean [range] tremor improvement 74.82% [50.00%-94.44%]). The authors found that both overlapping volume and center distance between T-VIM and S-VIM were significantly correlated with tremor improvement (r = 0.788 and p = 0.012 for overlapping volume; r = -0.696 and p = 0.037 for center distance). Pretherapeutic functional connectivity of T-VIM with the ipsilateral sensorimotor cortex (r = 0.876 and p = 0.002), subthalamic nucleus (r = 0.700 and p = 0.036), and visual area (r = 0.911 and p = 0.001) was significantly and positively correlated with tremor improvement. CONCLUSIONS: T-VIM may improve the clinical application of MRgFUS thalamotomy as a treatment of PD. Pretherapeutic functional connectivity of T-VIM with the ipsilateral sensorimotor cortex, subthalamic nucleus, and visual area may predict PD tremor responses after MRgFUS thalamotomy.