Astrocyte-derived SerpinA3N promotes neuroinflammation and epileptic seizures by activating the NF-κB signaling pathway in mice with temporal lobe epilepsy.

Impaired activation and regulation of the extinction of inflammatory cells and molecules in injured neuronal tissues are key factors in the development of epilepsy. SerpinA3N is mainly associated with the acute phase response and inflammatory response. In our current study, transcriptomics analysis, proteomics analysis, and Western blotting showed that the expression level of Serpin clade A member 3N (SerpinA3N) is significantly increased in the hippocampus of mice with kainic acid (KA)-induced temporal lobe epilepsy, and this molecule is mainly expressed in astrocytes. Notably, in vivo studies using gain- and loss-of-function approaches revealed that SerpinA3N in astrocytes promoted the release of proinflammatory factors and aggravated seizures. Mechanistically, RNA sequencing and Western blotting showed that SerpinA3N promoted KA-induced neuroinflammation by activating the NF-κB signaling pathway. In addition, co-immunoprecipitation revealed that SerpinA3N interacts with ryanodine receptor type 2 (RYR2) and promotes RYR2 phosphorylation. Overall, our study reveals a novel SerpinA3N-mediated mechanism in seizure-induced neuroinflammation and provides a new target for developing neuroinflammation-based strategies to reduce seizure-induced brain injury.

Ruthenium red attenuates acute pancreatitis by inhibiting MCU and improving mitochondrial function.

Acute pancreatitis (AP) is a common inflammatory disease of the digestive system. Mitochondrial calcium uniporter (MCU) mediates mitochondrial uptake of Ca2+ and plays an important role in calcium homeostasis. However, it is undefined whether AP can be relieved by inhibiting MCU. This study aimed to study the therapeutic potential of Ruthenium red (RuR), a MCU inhibitor, in AP mice model and primary acinar cells. Cell injury and AP mice model was induced by caerulein. RuR alleviated CER-AP evidenced by reduced serum lipase, TNF-α, and pancreatic MPO levels, less severe pancreatic pathology damage, and decreased inflammatory cell infiltration. In freshly isolated pancreatic acinar cells, RuR diminished cell necrosis with effect on suppressing the expression of MCU. RuR also decreased levels of cytosolic calcium and ROS, preventing mitochondrial membrane potential loss, ATP depletion and MPTP opening. The present findings indicate that inhibit MCU by RuR has a beneficial effect in AP by preventing calcium overload, mitochondrial dysfunction, and cell necrosis.

Preoperative acute lung injury and oxygenation impairment occurred in the patients with acute aortic dissection.

Acute lung injury (ALI) and oxygenation impairment (OI) frequently occur in the patients with acute aortic dissection (AAD), which may necessitate mechanical ventilation and result in adverse outcomes. This paper aims to increase clinicians' awareness of the severe respiratory complications in the patients with AAD, and provide the overview of the epidemiology, adverse outcomes, pathogenesis, predictive markers and therapeutic modalities of the concurrent conditions. Currently, it is considered that inflammatory response plays a great role in the pathogenesis of ALI and OI in the patients with AAD, but the definite pathogenesis remains unclear. Given the great importance of the prediction of the occurrence of the severe respiratory complication at a very early stage, some inflammatory biomarkers have been investigated to predict the occurrence of ALI and OI in several studies. C-reactive protein was found to have a significant predictive effect for the development of ALI and OI. Early use of beta-blockers and the use of bindarit could prevent the occurrence of OI and ALI. Ulinastatin could also improve oxygenation in the patients with type-A AAD. Prevention and management of ALI and OI in AAD remain a great challenge. The definite pathogenesis should be clearly clarified and further studies should be performed to look for potential effective way to predict and manage the severe respiratory conditions.

A novel localization technique for peripheral ground glass opacity using geometric parameters measured on CT images.

BACKGROUND: Currently no optimal localization technique has been established for localization of ground glass opacity (GGO). We aimed to introduce a localization technique using geometric localization for peripheral GGO. METHODS: We delineated the location of pulmonary GGO using geometric method which was similar with localization of a point in a spatial coordinate system. The localization technique was based on the anatomical landmarkers (ribs or intercostal spaces, capitulum costae and sternocostal joints). The geometric parameters were measured on preoperative CT images and the targeted GGO could be identified intraoperatively according to the parameters. We retrospectively collected the data of the patients with peripheral GGOs which were localized using this method and were wedge resected between June 2019 and July 2020. The efficacy and feasibility of the localization technique were assessed. RESULTS: There were 93 patients (male 34, median = 55 years) with 108 peripheral GGOs in the study. All the targeted GGOs were successfully wedge resected in the operative field with negative surgical margin at the first attempt. For each GGO, the localization parameters could be measured in 2-4 min (median = 3 min) on CT images before operation, and surgical resection could be completed in 5-10 min (median = 7 min). A total of 106 (98.15%) GGOs achieved sufficient resection margin. No complications and deaths occurred related to the localization and surgical procedure. CONCLUSIONS: The localization technique can achieve satisfactory localization success rate and good safety profile. It can provide an easy-to-use alternative to localize peripheral GGO.

Hair as a noninvasive biomarker of human exposure to the endocrine disruptors polybrominated diphenyl ethers: a meta-analysis.

Several epidemiological studies with small sample sizes have suggested that hair is a promising biomarker of exposure to polybrominated diphenyl ethers (PBDEs). We reanalyzed the data from human studies to investigate correlations between the concentrations of the five main congeners in hair and serum. We searched medical article databases for articles that reported correlation coefficients for concentrations of PBDEs in hair and serum. The methodological quality of the included articles was fully assessed. Then, the correlation coefficients were used for our analysis. Seven epidemiological studies were included in our analysis using the random-effects model. Significant positive relationships were found between the concentrations of the five congeners (BDE28, BDE47, BDE99, BDE100, BDE209) in serum and hair. The results of this study show that hair may be a promising biomarker for the biomonitoring human exposure to the five congeners of PBDEs within a certain detection range. Studies with a larger sample size are needed to explore the detection range.

Predictors for the development of preoperative oxygenation impairment in acute aortic dissection in hypertensive patients.

BACKGROUND: Acute aortic dissection (AAD) is an acute life-threatening cardiovascular disease, which is frequently complicated with oxygenation impairment (OI). We aim to investigate predictors of the development of OI in the patients with AAD. METHODS: We retrospectively collected clinical data of AAD in hypertensive patients from July 2012 to March 2020. The patients included in this study were divided into OI (+) group (oxygenation index≤200) and OI (-) group (oxygenation index> 200). Both groups were compared according to demographic and clinical characteristics, and laboratory findings. Characteristics of hypertension in the patients with AAD were described. Predictors for the development of OI were assessed. And cutoff values were determined by receiver operating characteristics (ROC) curve. RESULTS: A total of 208 patients were included in this study and the incidence of OI was 32.2%. In OI (+) group, patients had significantly higher peak body temperature (37.85 ± 0.60 vs 37.64 ± 0.44 °C, P = .005), higher levels of CRP (42.70 ± 28.27 vs 13.90 ± 18.70 mg/L, P = .000) and procalcitonin (1.07 ± 3.92 vs 0.31 ± 0.77µg/L, P = .027), and lower levels of albumin (34.21 ± 5.65 vs 37.73 ± 4.70 g/L, P = .000). Spearman's rank correlation test showed that the minimum oxygenation index was positively correlated with albumin, and was negatively correlated with the peak body temperature, serum CRP, procalcitonin, BNP and troponin. The stepwise multiple linear regression analysis showed that the peak body temperature, serum CRP and albumin were independently associated with development of OI. An optimal cutoff value for CRP for predicting OI was ≥9.20 mg/L, with a sensitivity of 91.0% and a specificity of 61.0%. CONCLUSIONS: The peak body temperature, serum CRP and albumin were independent predictors of OI development in the patients with AAD. The serum CRP on admission≥9.20 mg/L might be a valuable and reliable indicator in predicting the development of OI.

Association between Serum 25-Hydroxyvitamin D Level and Cognitive Impairment in Patients with White Matter Lesions: A Cross-Sectional Study.

OBJECTIVES: We aimed to observe the relationship between serum 25-hydroxyvitamin D (25-[OH] D) and different cognitive domains, and to evaluate the predictive value of 25-(OH) D level for cognitive impairment in patients with white matter lesions (WML). METHODS: The differences in clinical data including 25-(OH) D were analyzed between cognitive normality (n = 87) and impairment (n = 139) groups, and variant cognitive domains were analyzed between groups of different levels of serum 25-(OH) D. Risk factors for cognitive impairments were evaluated with multivariate logistic regression analysis; a receiver operating characteristic (ROC) curve of 25-(OH) D levels was used to examine the association between 25-(OH) D and WML with cognitive dysfunction. RESULTS: As the severity of WML increased, the proportion of patients with a low level of serum 25-(OH) D increased (p < 0.05). The total MoCA (Montreal Cognitive Assessment) scores and all domain scores except naming were significantly lower in patients with low levels of serum 25-(OH) D than in patients with high levels of serum 25-(OH) D (p < 0.05). Multivariate logistic regression analyses showed that serum 25-(OH) D levels were independently correlated with cognitive impairment. In the ROC analysis, the optimal cut-off value for 25-(OH) D was 17.53 with 76% sensitivity and 70% specificity (AUC =0.751, 95% CI: 0.674-0.819, p < 0.05). CONCLUSION: We observed that vitamin D deficiency is associated with multiple areas of cognitive impairment and that it is an independent risk factor for cognitive impairment in WML.

LncRNA H19 contributes to hippocampal glial cell activation via JAK/STAT signaling in a rat model of temporal lobe epilepsy.

BACKGROUND: Astrocyte and microglia activation are well-known features of temporal lobe epilepsy that may contribute to epileptogenesis. However, the mechanisms underlying glia activation are not well understood. Long non-coding RNA (lncRNA) H19 has diverse functions depending on physiological or pathological state, and its role in epilepsy is unknown. We previously demonstrated that H19 was significantly upregulated in the latent period of epilepsy and may be associated with cell proliferation and immune and inflammatory responses. We therefore speculated that H19 is involved in the hippocampal glial cell activation during epileptogenesis. METHODS: H19 was overexpressed or knocked down using an adeno-associated viral vector delivery system. A rat status epilepticus model was induced by intra-amygdala kainic acid injection. Astrocyte and microglia activation were assessed by immunofluorescence and western blot analyses. Expression of proinflammatory cytokines and components of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathways were evaluated with western blotting. RESULTS: H19 overexpression induced the activation of astrocytes and microglia and the release of proinflammatory cytokines (interleukin-1ß and interleukin-6 and tumor necrosis factor-α) in the hippocampus, whereas H19 knockdown inhibited status epilepticus-induced glial cell activation. Moreover, H19 activated JAK/STAT signaling by promoting the expression of Stat3 and c-Myc, which is thought to be involved in astrocyte activation. CONCLUSIONS: LncRNA H19 contributes to hippocampal glial cell activation via modulation of the JAK/STAT pathway and could be a therapeutic tool to prevent the development of epilepsy.

Whole-transcriptome screening reveals the regulatory targets and functions of long non-coding RNA H19 in epileptic rats.

Understanding the molecular mechanisms mediating epileptogenesis may lead to the development of preventative therapies against epilepsy. Our previous study demonstrated that the long non-coding RNA H19 contributes to epileptogenesis by aggravating status epilepticus-induced neuronal loss, glial cell activation, mossy fiber sprouting, and cognitive impairments in epileptic rats. However, the systematic functions and downstream targets of H19 associated with epileptogenesis are still unknown. In the present study, high-throughput microarray analysis was used to explore the influence of H19 on gene expression in an epileptic rat model. A large number of genes were differentially expressed at the transcriptional level when H19 was overexpressed or knocked down. Series test of cluster analysis further distinguished genes associated with H19. Function and pathway analyses demonstrated that H19 has diverse functions related to epileptogenesis, including demyelination, immune and inflammatory responses, cell apoptosis, and activation of MAPK. This study implicates H19 in a broad spectrum of epileptogenic processes, thereby providing a range of targets for further mechanistic investigations.

Role of the tumour necrosis factor-like weak inducer of apoptosis (TWEAK)/fibroblast growth factor-inducible 14 (Fn14) axis in autoimmune thyroid disease.

BACKGROUND: TNF-like weak inducer of apoptosis (TWEAK), its receptor fibroblast growth factor-inducible 14 (Fn14) and its scavenger receptor CD163 (sCD163) have known associations with many autoimmune diseases. However, the role of the TWEAK axis in autoimmune thyroid disease (AITD) remains unclear. Therefore, the aim of this study was to investigate the role of the TWEAK-Fn14 axis in the pathogenesis of AITD. METHODS: Serum levels of soluble TWEAK (sTWEAK) and sCD163 were measured in 38 patients with Graves' disease (GD), 40 patients with Hashimoto's thyroiditis (HT) and 40 healthy controls (HCs). Additionally, the mRNA expression of TWEAK and Fn14 in peripheral blood mononuclear cells (PBMCs) was explored, and the protein expression of TWEAK and Fn14 in thyroid glands surgically removed from 10 patients with GD, 10 patients with HT and 10 HCs was studied by immunohistochemical staining. RESULTS: The results showed that the serum levels of sTWEAK were significantly reduced in patients with HT and inversely correlated with antithyroid peroxidase antibody (TPOAb) levels. Additionally, high levels of sCD163 and a high sCD163/sTWEAK ratio were positively associated with the TPOAb levels in patients with HT and the thyrotropin receptor antibody (TRAb) levels in patients with GD. TWEAK mRNA expression and protein expression were upregulated in thyroid glands and PBMCs from patients with HT. CONCLUSION: Expression of the TWEAK-Fn14 axis was upregulated in patients with AITD and might play a role in the pathogenesis of AITD.

[Briefly analysis on academic origins of traditional Chinese medicine dispensing].

Through collecting and collating the development process of traditional Chinese medicine dispensing, the development of modern Chinese medicine dispensing on the basis of experience could be promoted. "Heyaofenji", "Hehe", " Heji" in ancient Chinese medicine, herbal medicine literature and law were collected, and then things were sorted out according to traditional Chinese medicine dispensing theory, skills and legal norms. Firstly, "Tang Ye Jing Fa" is the earliest book which marks the rudiment of traditional Chinese medicine dispensing. Secondly, traditional Chinese medicine dispensing theory formed in "Shen Nong's herbal classic". Thirdly, Zhang Zhongjing's "Treatise on Febrile Diseases" marked the formation of Chinese medicine dispensing skills. Lastly, Provisions in Tang Dynasty law marks the development of traditional Chinese medicine dispensing.

Value of C-reactive protein/albumin ratio in predicting the development of preoperative oxygenation impairment in patients with Stanford type-B acute aortic dissection.

Objectives: We aimed to assess the predicting value of C-reactive protein (CRP)/albumin ratio (CAR) in the development of Oxygenation impairment (OI) in the patients with Stanford type-B acute aortic dissection (AAD). Methods: This study included 133 patients (age = 58.8 ± 12.0 years, median age = 61 years, Male/Female = 117/16) diagnosed as Stanford type-B AAD accompanied by hypertension from July 2012 to May 2020. Clinical data were retrospectively extracted from the database. The patients in this study were divided into OI group (oxygenation index ≤ 200) and non-OI group (oxygenation index > 200). Clinical characteristics in both groups were compared, and predicting value of CAR in the development of OI was assessed. Results: Patients in OI group had higher peak body temperature (37.94 ± 0.62 vs. 37.67 ± 0.51 ℃, P =.010), higher levels of serum CRP (41.74 ± 27.71 vs 15.21 ± 19.66 mg/L, P =.000) and plasma B-type natriuretic peptide (292.14 ± 251.11 vs 179.80 ± 241.27 ng/L, P =.016), lower levels of albumin (34.00 ± 5.14 vs 37.72 ± 5.24 g/L, P =.000), and higher CAR (1.27 ± 0.89 vs 0.41 ± 0.53, P =.000). In multivariate regression analysis, CAR (odds ratio: 5.215, 95 % CI: 2.682; 10.137, P =.000) and the peak body temperature (odds ratio: 2.905, 95 % CI: 1.255; 6.724, P =.013) could significantly predict the OI development. The AUC for CAR was 0.831 (95 % CI: 0.756-0.907). An optimal cutoff value for CAR for predicting OI was ≥ 0.70, with a sensitivity of 67.5 % and a specificity of 88.2 %. Conclusions: Compared with CRP or albumin alone, the CAR might be a more accurate marker in predicting OI development in Stanford type-B AAD.

Mendelian randomization analyses for the causal relationship between early age at first sexual intercourse, early age at first live birth, and postpartum depression in pregnant women.

Introduction: There are insufficient epidemiological studies on the impact of age at first sexual intercourse (AFS) and age at first live birth (AFB) on postpartum depression (PPD) in pregnant women, and the conclusions of these studies are inconsistent. Methods: We performed a Mendelian randomization (MR) study to determine the causal relationship between AFS or AFB and the risk of PPD. The summary data were extracted from genome-wide association study (GWAS) summary datasets. We selected the instrumental variables according to the P value of exposure-related single nucleotide polymorphisms (P<5 ×10-9 for AFS and P<5 ×10-8 for AFB) and estimated the linkage disequilibrium using the clump parameter (10,000 kb, r2 < 0.001). Single nucleotide polymorphisms were considered instrumental variables that were significantly associated with exposure factors without linkage disequilibrium. The F-statistics of the instrumental variables should all be larger than 10. A random-effects model of IVW was constructed as the main method in our study. Results and discussion: MR studies based on GWAS data revealed that both AFS (OR = 0.4, P <0.001) and AFB (OR = 0.38, P <0.001) were negatively correlated with the risk of PPD. Early AFS and early AFB should be studied as possible risk factors for PPD in the future. Public health departments should attach importance to sex education for young girls. The results of our TSMR should be verified by high-quality prospective epidemiological studies in the future.

Deep Learning Approaches for Imaging-Based Automated Segmentation of Tuberous Sclerosis Complex.

The present study presents a novel approach for identifying epileptogenic tubers in patients with tuberous sclerosis complex (TSC) and automating tuber segmentation using a three-dimensional convolutional neural network (3D CNN). The study retrospectively included 31 TSC patients whose lesions were manually annotated from multiparametric neuroimaging data. Epileptogenic tubers were determined via presurgical evaluation and stereoelectroencephalography recording. Neuroimaging metrics were extracted and compared between epileptogenic and non-epileptogenic tubers. Additionally, five datasets with different preprocessing strategies were used to construct and train 3D CNNs for automated tuber segmentation. The normalized positron emission tomography (PET) metabolic value was significantly lower in epileptogenic tubers defined via presurgical evaluation (p = 0.001). The CNNs showed high performance for localizing tubers, with an accuracy between 0.992 and 0.994 across the five datasets. The automated segmentations were highly correlated with clinician-based features. The neuroimaging characteristics for epileptogenic tubers were demonstrated, increasing surgical confidence in clinical practice. The validated deep learning detection algorithm yielded a high performance in determining tubers with an excellent agreement with reference clinician-based segmentation. Collectively, when coupled with our investigation of minimal input requirements, the approach outlined in this study represents a clinically invaluable tool for the management of TSC.

Transcriptome sequencing of circular RNA reveals the involvement of hsa-SCMH1_0001 in the pathogenesis of Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease. Exosomes are endosome-derived extracellular vesicles that can take part in intercellular communication. Circular RNAs (circRNAs) are noncoding RNAs characterized by covalently closed-loop structures, which perform a crucial function in many diseases. AIM: To clarify the expression and function of exosomal circRNSs of PD patients and look for circRNAs that might be related to the pathogenesis of PD. MATERIALS AND METHODS: We examined circRNA and mRNA expression profiles in peripheral exosomes from PD patients (n = 23) and healthy controls (n = 15) using next-generation sequencing (NGS) technology, functional annotation, and quantitative polymerase chain reaction. Correlation analysis was performed between the expression levels of the circRNAs and the clinical characteristics of PD patients. The binding miRNAs and target genes were predicted using TargetScanHuman, miRDB, and miRTarBase. The predicted target genes were compared with the differentially expressed mRNAs in sequencing results. RESULTS: According to the NGS, 62 upregulated and 37 downregulated circRNAs in the PD group were screened out. Correlation analysis revealed that hsa-SCMH1_0001 has strong clinical relevance. We identified 17 potential binding miRNAs of hsa-SCMH1_0001 with 149 potential target genes. ARID1A and C1orf115 belong to the intersection of the predicted target genes and the differentially expressed mRNAs obtained by sequencing. CONCLUSION: This study suggested that hsa-SCMH1_0001 and its target genes ARID1A and C1orf115 are downregulated in PD patients and may be involved in the occurrence of PD.

Localizing seizure onset zone by a cortico-cortical evoked potentials-based machine learning approach in focal epilepsy.

OBJECTIVE: We aimed to develop a new approach for identifying the localization of the seizure onset zone (SOZ) based on corticocortical evoked potentials (CCEPs) and to compare the connectivity patterns in patients with different clinical phenotypes. METHODS: Fifty patients who underwent stereoelectroencephalography and CCEP procedures were included. Logistic regression was used in the model, and six CCEP metrics were input as features: root mean square of the first peak (N1RMS) and second peak (N2RMS), peak latency, onset latency, width duration, and area. RESULTS: The area under the curve (AUC) for localizing the SOZ ranged from 0.88 to 0.93. The N1RMS values in the hippocampus sclerosis (HS) group were greater than that of the focal cortical dysplasia (FCD) IIa group (p < 0.001), independent of the distance between the recorded and stimulated sites. The sensitivity of localization was higher in the seizure-free group than in the non-seizure-free group (p = 0.036). CONCLUSIONS: This new method can be used to predict the SOZ localization in various focal epilepsy phenotypes. SIGNIFICANCE: This study proposed a machine-learning approach for localizing the SOZ. Moreover, we examined how clinical phenotypes impact large-scale abnormality of the epileptogenic networks.

3D-QSAR, molecular docking, and molecular dynamics analysis of dihydrodiazaindolone derivatives as PARP-1 inhibitors.

CONTEXT: PARP-1 plays an important role in DNA repair and apoptosis, and PARP-1 inhibitors have shown to be effective in the treatment of several malignancies. To evaluate the function of new PARP-1 inhibitors as anticancer adjuvant medicines, 3D-QSAR, molecular docking, and molecular dynamics (MD) simulations of a sequence of dihydrodiazepinoindolone derivatives PARP-1 inhibitors were undertaken in this study. METHODS: In this paper, 43 PARP-1 inhibitors were studied in a three-dimensional quantitative structure-activity relationship (3D-QSAR) using comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA). CoMFA with q2 of 0.675 and r2 of 0.981 was achieved, as was CoMSIA with q2 of 0.755 and r2 of 0.992. The changed areas of these compounds are shown by steric, electrostatic, hydrophobic, and hydrogen-bonded acceptor field contour maps. Subsequently, molecular docking, and molecular dynamics simulations further confirmed that key residues Gly863 and Ser904 of PARP-1 are vital residues for protein interactions and their binding affinity. The effects of 3D-QSAR, molecular docking and molecular dynamics simulations supply a new route for the search of new PARP-1 inhibitors. Finally, we designed eight new compounds with exact activity and ADME/T properties.

Virtual screening and biological activity evaluation of novel efflux pump inhibitors targeting AdeB.

The AdeABC efflux pump is an important mechanism causing multidrug resistance in Acinetobacter baumannii, and its main component AdeB can recognize carbapenems, aminoglycosides, and other multi-class antibiotics and efflux them intracellularly, which is an ideal target for the development of anti-multidrug resistant bacteria drugs. Here, we combined multiple computer-aided drug design methods to target AdeB to identify promising novel structural inhibitors. Virtual screening was performed by molecular docking and molecular dynamics simulation (MD) and 12 potential compounds were identified from the databases. Meanwhile, their biological activities were validated by in vitro activity assays, and ChemDiv L676-2179 (γ-IFN), ChemDiv L676-1461, and Chembridge 53717615 were confirmed to suppress efflux effects and restore antibiotic susceptibility of resistant bacteria, which are expected to be developed as adjuvant drugs for the treatment of multi-drug resistant Acinetobacter baumannii clinical infections.

Differences in subthalamic oscillatory activity in the two hemispheres associated with severity of Parkinson's disease.

Background: It is well known that motor features of Parkinson's disease (PD) commonly begin on one side of the body and extend to the other side with disease progression. The onset side generally remains more severely affected over the course of the disease. However, the pathophysiology underlying the asymmetry of motor manifestations remains unclear. The purpose of the present study is to examine whether alterations in neuronal activity in the subthalamic nucleus (STN) associate with PD severity. Methods: Microelectrode recording was performed in the STN during targeting for 30 patients in the treatment of deep brain stimulation. The mean spontaneous firing rate (MSFR), power density spectral analysis, and correlations were calculated. Characteristics of subthalamic oscillatory activity were compared between two hemispheres. UPDRS III scores during "Off" and "On" states were obtained for the body side of initial symptoms (BSIS) and the body side of extended symptoms (BSES). Results: There were significant differences of MSFR (41.3 ± 11.0 Hz vs 35.2 ± 10.0 Hz) and percentage of ß frequency oscillatory neurons (51.3% vs 34.9%) between BSIS and BSES. The percentage of ß frequency oscillatory neurons correlated with the bradykinesia/rigidity scores for both sides (p < 0.05). In contrast, the percentage of tremor frequency oscillatory neurons was significantly higher in the BSES than that in the BSIS. In particular, these neurons only correlated with the tremor scores of the BSES (p < 0.05). Conclusion: The results suggest that increased neuronal firing rate and ß frequency oscillatory neurons in the STN are associated with contralateral side motor severity and its progression. Tremor frequency oscillatory neurons are less observed in the STN of the BSIS suggesting that ß oscillatory activity dominates and tremor frequency oscillatory activity reciprocally declines.

Efficient volume-based localization and automatic labeling of intracranial depth electrodes.

Background: The accurate localization and anatomical labeling of intracranial depth electrodes are crucial for stereoelectroencephalography (SEEG) recordings and the interpretation of results in patients with epilepsy. The laborious electrode localization procedure requires an efficient and easy-to-use pipeline. Thus, we developed a useful tool, which we called the depth electrode localizer (DELLO), to automatically identify and label depth electrode contacts with ease. Methods: The DELLO is an open-source package developed in MATLAB (MathWorks). It was specifically fine-tuned to expedite the localization of depth electrodes. The basic procedures include preoperative magnetic resonance imaging (MRI) and postoperative computed tomography coregistration, intensity threshold electrode spatial sampling, the hierarchical clustering of electrode samples, and gray-matter and automatic anatomical labeling (AAL). The DELLO also has a graphical user interface (GUI) that can be used to review the results. The only manual intervention procedures are the identification of the target (tip) and entry point of each electrode and the naming of the clustered electrode contact groups, which generally take ~5 min per case. The coordinates of each contact were recorded in individual spaces and were also transformed in standard space by applying a volume-based deformation field. To validate the performance of the current method, 7 patients with epilepsy were retrospectively included in the analysis. Results: A total of 80 depth electrodes, including 1,030 contacts from the 7 patients with epilepsy, were localized. All the procedures functioned well, and the entire process was robust and intuitive. Among the 1,030 contacts, 746 (72.43%) were labeled as inside the gray matter. The gray-matter and AAL accuracy rates were 95.83% and 90.78%, respectively, over all contacts. Conclusions: The DELLO is an integrated tool that was designed to semi-automatically localize and label intracranial depth electrodes. It is open source and freely available. Given its high accuracy and efficiency, the DELLO could facilitate SEEG interpretation and be used in SEEG-based cognitive neuroscience studies.