Glycogen metabolism-mediated intercellular communication in the tumor microenvironment influences liver cancer prognosis.

Glycogen metabolism plays a key role in the development of hepatocellular carcinoma (HCC), but the function of glycogen metabolism genes in the tumor microenvironment (TME) is still to be elucidated. Single-cell RNA-seq data were obtained from ten HCC tumor samples totaling 64,545 cells, and 65 glycogen metabolism genes were analyzed by a nonnegative matrix factorization (NMF). The prognosis and immune response of new glycogen TME cell clusters were predicted by using HCC and immunotherapy cohorts from public databases. HCC single-cell analysis was divided into fibroblasts, NT T cells, macrophages, endothelial cells, and B cells, which were separately divided into new cell clusters by glycogen metabolism gene annotation. Pseudo-temporal trajectory analysis demonstrated the temporal differentiation trajectory of different glycogen subtype cell clusters. Cellular communication analysis revealed extensive interactions between endothelial cells with glycogen metabolizing TME cell-related subtypes and different glycogen subtype cell clusters. SCENIC analysis of transcription factors upstream of TME cell clusters with different glycogen metabolism. In addition, TME cell clusters of glycogen metabolism were found to be enriched in expression in CAF subtypes, CD8 depleted, M1, and M2 types. Bulk-seq analysis showed the prognostic significance of glycogen metabolism-mediated TME cell clusters in HCC, while a significant immune response was found in the immunotherapy cohort in patients treated with immune checkpoint blockade (ICB), especially for CAFs, T cells, and macrophages. In summary, our study reveals for the first time that glycogen metabolism mediates intercellular communication in the hepatocellular carcinoma microenvironment while elucidating the anti-tumor mechanisms and immune prognostic responses of different subtypes of cell clusters.

Investigating the prognostic role of lncRNAs associated with disulfidptosis-related genes in clear cell renal cell carcinoma.

INTRODUCTION: Renal cell carcinoma (RCC) is a grave malignancy that poses a significant global health burden with over 400,000 new cases annually. Disulfidptosis, a newly discovered programmed cell death process, is linked to the actin cytoskeleton, which plays a vital role in maintaining cell shape and survival. The role of disulfidptosis is poorly depicted in the clear cell histologic variant of RCC (ccRCC). METHODS: Three sets of ccRCC cohorts, ICGC_RECA-EU (n = 91), GSE76207 (n = 32) and TCGA-KIRC (n = 607), were included in our study, the batch effect of which was removed using the "combat" function. Correlation was calculated using the "rcorr" function of the "Hmisc" package for Pearson analysis, which was visualized using the "pheatmap" package. Principal component analysis was performed by the "vegan" package, visualized using the "scatterplot3d" package. Long non-coding RNAs (lncRNAs) associated with disulfidptosis were screened out using least absolute shrinkage and selection operator (LASSO) and COX analysis. Tumor mutation, immune landscaping and immunotherapy prediction were performed for further characterization of two risk groups. RESULTS: A total of 1822 disulfidptosis-related lncRNAs was selected, among which 308 lncRNAs were found to be significantly associated with the clinical outcome of ccRCC patients. We retained 11 disulfidptosis-related lncRNAs, namely, AP000439.3, RP11-417E7.1, RP11-119D9.1, LINC01510, SNHG3, AC156455.1, RP11-291B21.2, EMX2OS, AC093850.2, HAGLR and RP11-389C8.2, through LASSO and COX analysis for prognosis model construction, which displayed satisfactory accuracy (area under the curve, AUC, values all above 0.6 in multiple cohorts) in stratification of ccRCC prognosis. A nomogram model was constructed by integrating clinical factors with risk score, which further enhanced the prediction efficacy (AUC values all above 0.7 in multiple cohorts). We found that patients of male gender, higher clinical stages and advanced pathological T stage were inclined to have higher risk score values. Dactinomycin_1911, Vinblastine_1004, Daporinad_1248 and Vinorelbine_2048 were identified as promising candidate drugs for treating ccRCC patients of higher risk score value. Moreover, patients of higher risk value were prone to be resistant to immunotherapy. CONCLUSION: We developed a prognosis predicting model based on 11 selected disulfidptosis-related lncRNAs, the efficacy of which was verified in different cohorts. Furthermore, we delineated an intricate portrait of tumor mutation, immune topography and pharmacosensitivity evaluations within disparate risk stratifications.

Exploring oncogenes for renal clear cell carcinoma based on G protein-coupled receptor-associated genes.

G protein-coupled receptors (GPCRs) are a class of receptors on cell membranes that regulate various biological processes in cells, such as cell proliferation, differentiation, migration, apoptosis, and metabolism, by interacting with G proteins. However, the role of G protein-coupled receptors in predicting the prognosis of renal clear cell carcinoma is still unknown. The transcriptome data and clinical profiles of renal clear cell carcinoma patients, were downloaded from TCGA databases, and the validation group data were downloaded from number GSE167573, including 63 tumor samples and 14 normal samples. Single-cell RNA sequencing data were downloaded from the GEO database, No. GSE152938 and selected samples were used for GSEA enrichment analysis, WGCNA subgroup analysis, single-cell data analysis, and mutation analysis to explore the role of G protein-coupled receptor-related genes in the diagnosis and prognosis of renal clear cell carcinoma and to verify their reliability with cellular experiments. Finally, this study establishes a disease model based on G protein-coupled receptor-related genes, which may help to propose targeted therapeutic regimens in different strata of renal cell carcinoma patients.Author names: Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author: Given name [Lisa Jia] Last name [Tran].It's ok!

Differential Immune Infiltration Profiles in Colitis-Associated Colorectal Cancer versus Sporadic Colorectal Cancer.

BACKGROUND: Chronic inflammation is a significant factor in colorectal cancer (CRC) development, especially in colitis-associated CRC (CAC). T-cell exhaustion is known to influence inflammatory bowel disease (IBD) progression and antitumor immunity in IBD patients. This study aimed to identify unique immune infiltration characteristics in CAC patients. METHODS: We studied 20 CAC and 20 sporadic CRC (sCRC) patients, who were matched by tumor stage, grade, and location. Immunohistochemical staining targeted various T-cell markers (CD3, CD4, CD8, and FOXP3), T-cell exhaustion markers (TOX and TIGIT), a B-cell marker (CD20), and a neutrophil marker (CD66b) in tumor and tumor-free mucosa from both groups. The quantification of the tumor immune stroma algorithm assessed immune-infiltrating cells. RESULTS: CAC patients had significantly lower TOX+ cell infiltration than sCRC in tumors (p = 0.02) and paracancerous tissues (p < 0.01). Right-sided CAC showed increased infiltration of TOX+ cells (p = 0.01), FOXP3+ regulatory T-cells (p < 0.01), and CD20+ B-cells (p < 0.01) compared to left-sided CAC. In sCRC, higher tumor stages (III and IV) had significantly lower TIGIT+ infiltrate than stages I and II. In CAC, high CD3+ (p < 0.01) and CD20+ (p < 0.01) infiltrates correlated with improved overall survival. In sCRC, better survival was associated with decreased TIGIT+ cells (p < 0.038) and reduced CD8+ infiltrates (p = 0.02). CONCLUSION: In CAC, high CD3+ and CD20+ infiltrates relate to improved survival, while this association is absent in sCRC. The study revealed marked differences in TIGIT and TOX expression, emphasizing distinctions between CAC and sCRC. T-cell exhaustion appears to have a different role in CAC development.

Single-cell transcriptome analysis revealing the intratumoral heterogeneity of ccRCC and validation of MT2A in pathogenesis.

Clear-cell renal cell carcinoma (ccRCC) appears as the most common type of kidney cancer, the carcinogenesis of which has not been fully elucidated. Tumor heterogeneity plays a crucial role in cancer progression, which could be largely deciphered by the implement of scRNA-seq. The bulk and single-cell RNA expression profile is obtained from TCGA and study conducted by Young et al. We utilized UMAP, TSNE, and clustering algorithm Louvain for dimensionality reduction and FindAllMarkers function for determining the DEGs. Monocle2 was utilized to perform pseudo-time series analysis. SCENIC was implemented for transcription factor analysis of each cell subgroup. A series of WB, CFA, CCK-8, and EDU analysis was utilized for the validation of the role of MT2A in ccRCC carcinogenesis. We observed higher infiltration of T/NK and B cells in tumorous tissues, indicating the role of immune cells in ccRCC carcinogenesis. Transcription factor analysis revealed the activation of EOMES and ETS1 in CD8 + T cells, while CAFs were divided into myo-CAFs and i-CAFs, with i-CAFs showing distinct enrichment of ATF3, JUND, JUNB, EGR1, and XBP1. Through cell trajectory analysis, we discerned three distinct stages of cellular evolution, where State2 symbolizes normal renal tubular cells that underwent transitions into State1 and State3 as the CNV score ascended. Functional enrichment examination revealed an amplification of interferon gamma and inflammatory response pathways within tumor cells. The consensus clustering algorithm yielded two molecular subtypes, with cluster 2 being associated with advanced tumor stages and an abundance of infiltrated immune cells. We identified 17 prognostic genes through Cox and LASSO regression models and used them to construct a prognostic model, the efficacy of which was verified in multiple cohorts. Furthermore, we investigated the role of MT2A, one of our hub genes, in ccRCC carcinogenesis, and found it to regulate proliferation and migration of malignant cells. We depicted a detailed single-cell landscape of ccRCC, with special focus on CAFs, endothelial cells, and renal tubular cells. A prognostic model of high stability and accuracy was constructed based on the DEGs. MT2A was found to be actively implicated in ccRCC carcinogenesis, regulating proliferation and migration of the malignant cells.

GADD45B regulates the carcinogenesis process of chronic atrophic gastritis and the metabolic pathways of gastric cancer.

Background: Gastric cancer continues to be a significant global healthcare challenge, and its burden remains substantial. The development of gastric cancer (GC) is closely linked to chronic atrophic gastritis (CAG), yet there is a scarcity of research exploring the underlying mechanisms of CAG-induced carcinogenesis. Methods: In this study, we conducted a comprehensive investigation into the oncogenes involved in CAG using both bulk transcriptome and single-cell transcriptome data. Our approach employed hdWGCNA to identify pathogenic genes specific to CAG, with non-atrophic gastritis (NAG) serving as the control group. Additionally, we compared CAG with GC, using normal gastric tissue as the control group in the single-cell transcriptome analysis. By intersecting the identified pathogenic genes, we pinpointed key network molecules through protein interaction network analysis. To further refine the gene selection, we applied LASSO, SVM-RFE, and RF techniques, which resulted in a set of cancer-related genes (CRGs) associated with CAG. To identify CRGs potentially linked to gastric cancer progression, we performed a univariate COX regression analysis on the gene set. Subsequently, we explored the relationship between CRGs and immune infiltration, drug sensitivity, and clinical characteristics in gastric cancer patients. We employed GSVA to investigate how CRGs regulated signaling pathways in gastric cancer cells, while an analysis of cell communication shed light on the impact of CRGs on signal transmission within the gastric cancer tumor microenvironment. Lastly, we analyzed changes in metabolic pathways throughout the progression of gastric cancer. Results: Using hdWGCNA, we have identified a total of 143 pathogenic genes that were shared by CAG and GC. To further investigate the underlying mechanisms, we conducted protein interaction network analysis and employed machine learning screening techniques. As a result, we have identified 15 oncogenes that are specifically associated with chronic atrophic gastritis. By performing ROC reanalysis and prognostic analysis, we have determined that GADD45B is the most significant gene involved in the carcinogenesis of CAG. Immunohistochemical staining and differential analysis have revealed that GADD45B expression was low in GC tissues while high in normal gastric tissues. Moreover, based on prognostic analysis, high expression of GADD45B has been correlated with poor prognosis in GC patients. Additionally, an analysis of immune infiltration has shown a relationship between GADD45B and the infiltration of various immune cells. By correlating GADD45B with clinical characteristics, we have found that it primarily affects the depth of invasion in GC. Through cell communication analysis, we have discovered that the CD99 signaling pathway network and the CDH signaling pathway network are the main communication pathways that significantly alter the microenvironment of gastric tissue during the development of chronic atrophic gastritis. Specifically, GADD45B-low GC cells were predominantly involved in the network communication of the CDH signaling pathway, while GADD45B-high GC cells played a crucial role in both signaling pathways. Furthermore, we have identified several metabolic pathways, including D-Glutamine and D-glutamate metabolism and N-Glycan biosynthesis, among others, that played important roles in the occurrence and progression of GC, in addition to the six other metabolic pathways. In summary, our study highlighted the discovery of 143 pathogenic genes shared by CAG and GC, with a specific focus on 15 oncogenes associated with CAG. We have identified GADD45B as the most important gene in the carcinogenesis of CAG, which exhibited differential expression in GC tissues compared to normal gastric tissues. Moreover, GADD45B expression was correlated with patient prognosis and is associated with immune cell infiltration. Our findings also emphasized the impact of the CD99 and CDH signaling pathway networks on the microenvironment of gastric tissue during the development of CAG. Additionally, we have identified key metabolic pathways involved in GC progression. Conclusion: GADD45B, an oncogene implicated in chronic atrophic gastritis, played a critical role in GC development. Decreased expression of GADD45B was associated with the onset of GC. Moreover, GADD45B expression levels were closely tied to poor prognosis in GC patients, influencing the infiltration patterns of various cells within the tumor microenvironment, as well as impacting the metabolic pathways involved in GC progression.

FAM family gene prediction model reveals heterogeneity, stemness and immune microenvironment of UCEC.

Background: Endometrial cancer (UCEC) is a highly heterogeneous gynecologic malignancy that exhibits variable prognostic outcomes and responses to immunotherapy. The Familial sequence similarity (FAM) gene family is known to contribute to the pathogenesis of various malignancies, but the extent of their involvement in UCEC has not been systematically studied. This investigation aimed to develop a robust risk profile based on FAM family genes (FFGs) to predict the prognosis and suitability for immunotherapy in UCEC patients. Methods: Using the TCGA-UCEC cohort from The Cancer Genome Atlas (TCGA) database, we obtained expression profiles of FFGs from 552 UCEC and 35 normal samples, and analyzed the expression patterns and prognostic relevance of 363 FAM family genes. The UCEC samples were randomly divided into training and test sets (1:1), and univariate Cox regression analysis and Lasso Cox regression analysis were conducted to identify the differentially expressed genes (FAM13C, FAM110B, and FAM72A) that were significantly associated with prognosis. A prognostic risk scoring system was constructed based on these three gene characteristics using multivariate Cox proportional risk regression. The clinical potential and immune status of FFGs were analyzed using CiberSort, SSGSEA, and tumor immune dysfunction and rejection (TIDE) algorithms. qRT-PCR and IHC for detecting the expression levels of 3-FFGs. Results: Three FFGs, namely, FAM13C, FAM110B, and FAM72A, were identified as strongly associated with the prognosis of UCEC and effective predictors of UCEC prognosis. Multivariate analysis demonstrated that the developed model was an independent predictor of UCEC, and that patients in the low-risk group had better overall survival than those in the high-risk group. The nomogram constructed from clinical characteristics and risk scores exhibited good prognostic power. Patients in the low-risk group exhibited a higher tumor mutational load (TMB) and were more likely to benefit from immunotherapy. Conclusion: This study successfully developed and validated novel biomarkers based on FFGs for predicting the prognosis and immune status of UCEC patients. The identified FFGs can accurately assess the prognosis of UCEC patients and facilitate the identification of specific subgroups of patients who may benefit from personalized treatment with immunotherapy and chemotherapy.

The Role of Microbiota in Liver Transplantation and Liver Transplantation-Related Biliary Complications.

Liver transplantation as a treatment option for end-stage liver diseases is associated with a relevant risk for complications. On the one hand, immunological factors and associated chronic graft rejection are major causes of morbidity and carry an increased risk of mortality due to liver graft failure. On the other hand, infectious complications have a major impact on patient outcomes. In addition, abdominal or pulmonary infections, and biliary complications, including cholangitis, are common complications in patients after liver transplantation and can also be associated with a risk for mortality. Thereby, these patients already suffer from gut dysbiosis at the time of liver transplantation due to their severe underlying disease, causing end-stage liver failure. Despite an impaired gut-liver axis, repeated antibiotic therapies can cause major changes in the gut microbiome. Due to repeated biliary interventions, the biliary tract is often colonized by several bacteria with a high risk for multi-drug resistant germs causing local and systemic infections before and after liver transplantation. Growing evidence about the role of gut microbiota in the perioperative course and their impact on patient outcomes in liver transplantation is available. However, data about biliary microbiota and their impact on infectious and biliary complications are still sparse. In this comprehensive review, we compile the current evidence for the role of microbiome research in liver transplantation with a focus on biliary complications and infections due to multi-drug resistant germs.

Catalytic Reactions Directed by a Structurally Well-Defined Aminomethyl Cyclopalladated Complex.

The introduction of N-containing moieties into feedstock molecules to build nitrogenated functional molecules has always been widely studied by the organic chemistry community. Progress in this field paves new roads to the synthesis of N-containing molecules, which are of significant importance in biological activities and play vital roles in pharmaceuticals and functional materials. Remarkable progress has been achieved in the field of transition metal-catalyzed C-N bond-forming reactions, typified by alkene hydroamination and the aza-Wacker reaction. However, the poisoning effect of electron-donating amine substrates on late transition metal catalysts presents a key impediment to these reactions, thus limiting the scope of amine substrates to electron-deficient amide derivatives. To address this problem, our group developed a palladium-aminomethyl complex with a three-membered palladacycle structure that allowed for the incorporation of electron-rich amine building blocks via C-C bond instead of C-N bond construction. This Account details the discovery of the well-defined aminomethyl cyclopalladated complex and recapitulates its applications for the catalysis of a series of aminomethylation reactions. We highlight how the understanding of the fundamental structural properties of the defined complex guided us toward tuning the reactivity of nucleophiles to initiate aminomethylation in different modes. Moreover, principles of designing and establishing further cascade reactions are also described.Aminomethyl cyclopalladated complexes can be prepared via the oxidative addition of aminals or N,O-acetals to Pd0 species. Thorough structural investigations by single-crystal X-ray diffraction analysis of the cyclopalladated complex suggest the presence of both aminomethylene-PdII (3-membered-ring) and Pd0-iminium (π-ligated) resonance forms, which indicates that both the palladium center and the methylene site are electrophilic. This is further verified by analysis of charge distribution. Two general types of reactions can be established, differing by the selective affinity of the nucleophiles to the two electrophilic positions, which is relevant to the "hardness suitability" of the nucleophiles with each electrophilic site. Softer nucleophiles such as alkenes prefer to attack the palladium center to initiate the reaction, mainly via migratory insertion into the Pd-C bond on the 3-membered ring with high strain. Through tandem ß-hydride or reductive elimination, the Heck-type aminomethylation of styrenes, the aminomethylalkoxylation of electron-rich olefins, and even the aminomethylamination of allenes, dienes, enynes, and carbenoids with full atom-economy have been realized in line with this reaction mode. In contrast, harder nucleophiles tend to attack the harder electrophilic methylene site, leading to the aminomethylation of electron-deficient dienes. For secondary amines, a "C-N bond metathesis" process would be furnished through a reductive elimination, 1,3-proton transfer, and oxidative addition sequence. More intriguingly, when using appropriate "dinucleophile" substrates such as electron-rich amine-tethered dienes, sequential C-N bond metathesis and intramolecular insertion would occur to furnish Pd-catalyzed annulation reactions, which exhibits both the hard and soft nucleophile reactivities mentioned above. These transformations provide convenient methods for the preparation of N-containing molecules, such as amines, diamines, amino acetals, and multiple types of N-heterocycles.

Impact of Mastectomy on Body Image and Sexuality from a LGBTQ Perspective: A Narrative Review.

Although mastectomy could lead to a decrease in sexual performance among patients, only a handful of studies focused on the psychological and sexual behavioral aspects after the surgery. Research on post-mastectomy sexuality has focused mainly on female subjects but barely on lesbian, gay, bisexual, transgender, queer (LGBTQ), and male patients. This narrative review aimed to explore the importance of sexuality after mastectomy from a LGBTQ perspective. Each sexual minority group has been addressed individually. In general, sexual and gender minority breast cancer (BC) patients undergoing bilateral mastectomy expect a complex treatment plan in terms of physical and emotional outcomes. Bilateral mastectomy or top surgery for masculinization reasons was reported to be the most popular procedure among transmen, which resulted in a significant improvement in the quality of life. Heterosexual and lesbian female patients are willing to undergo mastectomy after repeated lumpectomies or to avoid radiation, despite potential post-operative somatic and quality-of-life complications. Transwomen would seek gender-affirming surgery to improve physical satisfaction and psychological well-being. There is not enough evidence for non-oncological reasons and consequences of mastectomy in gay men and cisgender heterosexual men. Establishing the awareness of the sexuality impact of mastectomy will allow the implementation of tailored perioperative psychological care.

Power Modulations of ECoG Alpha/Beta and Gamma Bands Correlate With Time-Derivative of Force During Hand Grasp.

It is well-known that motor cortical oscillatory components are modulated in their amplitude during voluntary and imagined movements. These patterns have been used to develop brain-machine interfaces (BMI) which focused mostly on movement kinematics. In contrast, there have been only a few studies on the relation between brain oscillatory activity and the control of force, in particular, grasping force, which is of primary importance for common daily activities. In this study, we recorded intraoperative high-density electrocorticography (ECoG) from the sensorimotor cortex of four patients while they executed a voluntary isometric hand grasp following verbal instruction. The grasp was held for 2 to 3 s before being instructed to relax. We studied the power modulations of neural oscillations during the whole time-course of the grasp (onset, hold, and offset phases). Phasic event-related desynchronization (ERD) in the low-frequency band (LFB) from 8 to 32 Hz and event-related synchronization (ERS) in the high-frequency band (HFB) from 60 to 200 Hz were observed at grasp onset and offset. However, during the grasp holding period, the magnitude of LFB-ERD and HFB-ERS decreased near or at the baseline level. Overall, LFB-ERD and HFB-ERS show phasic characteristics related to the changes of grasp force (onset/offset) in all four patients. More precisely, the fluctuations of HFB-ERS primarily, and of LFB-ERD to a lesser extent, correlated with the time-course of the first time-derivative of force (yank), rather than with force itself. To the best of our knowledge, this is the first study that establishes such a correlation. These results have fundamental implications for the decoding of grasp in brain oscillatory activity-based neuroprosthetics.

Transition-metal-catalyzed reactions involving reductive elimination between dative ligands and covalent ligands.

Reductive elimination is a crucial bond-forming elementary reaction in various transition-metal mediated reactions. Apart from the well-developed classic reductive elimination, the non-classic reductive elimination occurring between a covalent ligand and a dative ligand, which has been known for over 50 years, has gradually attracted much attention from the organic community. By avoiding pπ-dπ repulsion between the filled metal d-orbital and the filled ligand p-orbital and forming a cationic-type molecule, non-classic reductive elimination could facilitate many catalytic reactions that were difficult to be realized via classic reductive elimination. In this review, transition-metal catalyzed C-P, C-S, C-N, and C-C bond-forming reactions with non-classic reductive elimination as the key elementary step are summarized.

Investigation of the Influence of ECoG Grid Spatial Density on Decoding Hand Flexion and Extension.

Electrocorticogram (ECoG) has been used as a reliable modality to control a brain machine interface (BMI). Recently, promising results of high-density ECoG have shown that non redundant information can be recorded with finer spatial resolution from the cortical surface. In this study, highdensity ECoG was recorded intraoperatively from two patients during awake brain surgery while performing instructed hand flexion and extension. Event related desynchronization (ERD) were found in the low frequency band (LFB: 8-32 Hz) band while event related synchronization (ERS) were found in the high frequency band (HFB: 60-200 Hz). The classification between hand flexion and extension was performed by using common spatial pattern (CSP) as a feature extraction technique and linear discriminant analysis (LDA) as a classifier. In order to compare the high-density ECoG and normal ECoG in terms of classifying between hand flexion and extension, we simulated a typical clinical ECoG (8 mm spacing) by averaging the neural activity of nearest four channels. The same classification methods were applied on the averaged recordings. In HFB, the classification error rate using simulated ECoG greatly increased and lagged the movement onset compared to the original highdensity ECoG. In LFB, the differences between them were not prominent. These results indicated that high-density ECoG is able to capture non-redundant task-related information from the motor cortex and potentially serves as a better modality to drive a neural prosthetic compared to typical clinical electrodes.

Characterization of Hand Clenching in Human Sensorimotor Cortex Using High-, and Ultra-High Frequency Band Modulations of Electrocorticogram.

Functional mapping of eloquent cortex before the resection of a tumor is a critical procedure for optimizing survival and quality of life. In order to locate the hand area of the motor cortex in two patients with low-grade gliomas (LGG), we recorded electrocorticogram (ECoG) from a 113 channel hybrid high-density grid (64 large contacts with diameter of 2.7 mm and 49 small contacts with diameter of 1 mm) while they executed hand clenching movements. We investigated the spatio-spectral characteristics of the neural oscillatory activity and observed that, in both patients, the hand movements were consistently associated with a wide spread power decrease in the low frequency band (LFB: 8-32 Hz) and a more localized power increase in the high frequency band (HFB: 60-280 Hz) within the sensorimotor region. Importantly, we observed significant power increase in the ultra-high frequency band (UFB: 300-800 Hz) during hand movements of both patients within a restricted cortical region close to the central sulcus, and the motor cortical "hand knob." Among all frequency bands we studied, the UFB modulations were closest to the central sulcus and direct cortical stimulation (DCS) positive site. Both HFB and UFB modulations exhibited different timing characteristics at different locations. Power increase in HFB and UFB starting before movement onset was observed mostly at the anterior part of the activated cortical region. In addition, the spatial patterns in HFB and UFB indicated a probable postcentral shift of the hand motor function in one of the patients. We also compared the task related subband modulations captured by the small and large contacts in our hybrid grid. We did not find any significant difference in terms of band power changes. This study shows initial evidence that event-driven neural oscillatory activity recorded from ECoG can reach up to 800 Hz. The spatial distribution of UFB oscillations was found to be more focalized and closer to the central sulcus compared to LFB and HFB. More studies are needed to characterize further the functional significance of UFB relative to LFB and HFB.

Characterization and Decoding the Spatial Patterns of Hand Extension/Flexion using High-Density ECoG.

During awake brain surgeries, electrocorticogram (ECoG) was recorded using a high density electrode grid from the motor cortex of two subjects while they were asked to execute spontaneous hand extension and flexion. Firstly, we characterized the spatio-spectral patterns of high-density ECoG during the hand movements. In both subjects, we observed event related desynchronization (ERD) in low frequency band (LFB: 8-32 Hz) and event related synchronization (ERS) in high frequency band (HFB: 60-200 Hz) where HFB-ERS was more spatially localized and movement specific compared to LFB-ERD. In particular, improved spatial resolution of high density ECoG revealed HFB-ERS patterns with distinct timing in different anatomical regions. A few channels located anterior to the central sulcus were associated with HFB-ERS which started several hundred milliseconds prior to the movement onset. Several channels were associated with HFB-ERS which started close to the movement onset. Most importantly, only a small number of channels in the motor cortex regions exhibited long duration ERS which lasted while the subjects maintained their hand posture. A common spatial pattern (CSP) algorithm fused with linear discriminant analysis (LDA) was used to distinguish between hand extension and flexion at different time points based on subband features. ECoG data recorded from the channels located either anterior or posterior to the central sulcus were tested separately in classification. For both subjects, using channels located in motor area, HFB yielded almost 100% classification accuracy within 150-250 ms after the movement onset. The classification accuracies obtained from sensory areas were poor compared to motor areas and lagged the movement onset. These results suggest that spatial patterns of motor cortex captured with high-density ECoG in HFB can effectively drive a neural prosthetic to perform hand flexion and extension.

Resting state cortical oscillations of patients with Parkinson disease and with and without subthalamic deep brain stimulation: a magnetoencephalography study.

PURPOSE: In this study, we investigate the modification to cortical oscillations of patients with Parkinson disease (PD) by subthalamic deep brain stimulation (STN-DBS). METHODS: Spontaneous cortical oscillations of patients with PD were recorded with magnetoencephalography during on and off subthalamic nucleus deep brain stimulation states. Several features such as average frequency, average power, and relative subband power in regions of interest were extracted in the frequency domain, and these features were correlated with Unified Parkinson Disease Rating Scale III evaluation. The same features were also investigated in patients with PD without surgery and healthy controls. RESULTS: Patients with Parkinson disease without surgery compared with healthy controls had a significantly lower average frequency and an increased average power in 1 to 48 Hz range in whole cortex. Higher relative power in theta and simultaneous decrease in beta and gamma over temporal and occipital were also observed in patients with PD. The Unified Parkinson Disease Rating Scale III rigidity score correlated with the average frequency and with the relative power of beta and gamma in frontal areas. During subthalamic nucleus deep brain stimulation, the average frequency increased significantly when stimulation was on compared with off state. In addition, the relative power dropped in delta, whereas it rose in beta over the whole cortex. Through the course of stimulation, the Unified Parkinson Disease Rating Scale III rigidity and tremor scores correlated with the relative power of alpha over left parietal. CONCLUSIONS: Subthalamic nucleus deep brain stimulation improves the symptoms of PD by suppressing the synchronization of alpha rhythm in somatomotor region.

Local spatial correlation analysis of hand flexion/extension using intraoperative high-density ECoG.

We recorded motor cortical activity using highdensity electrocorticogram (ECoG) from three patients during awake craniotomy. Subjects repeatedly executed hand flexion/extension tasks according to auditory instructions. Clear event-related desynchronization (ERD) in beta band (8-32) Hz and event-related synchronization (ERS) in gamma band (60-200) Hz were observed. High frequency band (HFB: 60-200 Hz) activation was found to be more localized compared to low frequency band (LFB: 8-32 Hz) activation in all subjects. Local spatial correlation maps in LFB and HFB were constructed by computing the correlation between channels. Local spatial correlation dropped more in the ERD/ERS areas consistently in two subjects. The results indicate that ERD/ERS patterns are more spatially uncorrelated and denser ECoG electrode is necessary within these areas to map uncorrelated `sources'. High resolution electrodes might improve both clinical functional mapping and brain machine interface outcomes in the near future.