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53 result(s) for "Zhao, Hulin"
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Intracranial neural representation of phenomenal and access consciousness in the human brain
•We first provide the direct intracranial evidence in the human brain that supports the framework of phenomenon and access consciousness.•We further characterize the spatiotemporal dynamics and the relationship of the two different NCCs more precisely.•Our results show that lateral PFC may be a key node linking phenomenon and access consciousness. After more than 30 years of extensive investigation, impressive progress has been made in identifying the neural correlates of consciousness (NCC). However, the functional role of spatiotemporally distinct consciousness-related neural activity in conscious perception is debated. An influential framework proposed that consciousness-related neural activities could be dissociated into two distinct processes: phenomenal and access consciousness. However, though hotly debated, its authenticity has not been examined in a single paradigm with more informative intracranial recordings. In the present study, we employed a visual awareness task and recorded the local field potential (LFP) of patients with electrodes implanted in cortical and subcortical regions. Overall, we found that the latency of visual awareness-related activity exhibited a bimodal distribution, and the recording sites with short and long latencies were largely separated in location, except in the lateral prefrontal cortex (lPFC). The mixture of short and long latencies in the lPFC indicates that it plays a critical role in linking phenomenal and access consciousness. However, the division between the two is not as simple as the central sulcus, as proposed previously. Moreover, in 4 patients with electrodes implanted in the bilateral prefrontal cortex, early awareness-related activity was confined to the contralateral side, while late awareness-related activity appeared on both sides. Finally, Granger causality analysis showed that awareness-related information flowed from the early sites to the late sites. These results provide the first LFP evidence of neural correlates of phenomenal and access consciousness, which sheds light on the spatiotemporal dynamics of NCC in the human brain.
The involvement of the human prefrontal cortex in the emergence of visual awareness
Exploring the neural mechanisms of awareness is a fundamental task of cognitive neuroscience. There is an ongoing dispute regarding the role of the prefrontal cortex (PFC) in the emergence of awareness, which is partially raised by the confound between report- and awareness-related activity. To address this problem, we designed a visual awareness task that can minimize report-related motor confounding. Our results show that saccadic latency is significantly shorter in the aware trials than in the unaware trials. Local field potential (LFP) data from six patients consistently show early (200–300ms) awareness-related activity in the PFC, including event-related potential and high-gamma activity. Moreover, the awareness state can be reliably decoded by the neural activity in the PFC since the early stage, and the neural pattern is dynamically changed rather than being stable during the representation of awareness. Furthermore, the enhancement of dynamic functional connectivity, through the phase modulation at low frequency, between the PFC and other brain regions in the early stage of the awareness trials may explain the mechanism of conscious access. These results indicate that the PFC is critically involved in the emergence of awareness.
Detecting focal cortical dysplasia lesions from FLAIR-negative images based on cortical thickness
Background Focal cortical dysplasia (FCD) is a neuronal migration disorder and is a major cause of drug-resistant epilepsy. However, many focal abnormalities remain undetected during routine visual inspection, and many patients with histologically confirmed FCD have normal fluid-attenuated inversion recovery (FLAIR-negative) images. The aim of this study was to quantitatively evaluate the changes in cortical thickness with magnetic resonance (MR) imaging of patients to identify FCD lesions from FLAIR-negative images. Methods We first used the three-dimensional (3D) Laplace method to calculate the cortical thickness for individuals and obtained the cortical thickness mean image and cortical thickness standard deviation (SD) image based on all 32 healthy controls. Then, a cortical thickness extension map was computed by subtracting the cortical thickness mean image from the cortical thickness image of each patient and dividing the result by the cortical thickness SD image. Finally, clusters of voxels larger than three were defined as the FCD lesion area from the cortical thickness extension map. Results The results showed that three of the four lesions that occurred in non-temporal areas were detected in three patients, but the detection failed in three patients with lesions that occurred in the temporal area. The quantitative analysis of the detected lesions in voxel-wise on images revealed the following: specificity (99.78%), accuracy (99.76%), recall (67.45%), precision (20.42%), Dice coefficient (30.01%), Youden index (67.23%) and area under the curve (AUC) (83.62%). Conclusion Our studies demonstrate an effective method to localize lesions in non-temporal lobe regions. This novel method automatically detected FCD lesions using only FLAIR-negative images from patients and was based only on cortical thickness feature. The method is noninvasive and more effective than a visual analysis for helping doctors make a diagnosis.
Oncolytic Viruses in Glioblastoma: Clinical Progress, Mechanistic Insights, and Future Therapeutic Directions
High-grade gliomas-particularly glioblastoma (GBM)-remain refractory to standard-of-care surgery followed by chemoradiation, with a median overall survival of ~15 months. Oncolytic viruses (OVs), which selectively infect and lyse tumor cells while engaging antitumor immunity, offer a mechanistically distinct therapeutic modality. This review synthesizes clinical progress of OVs in GBM, with emphasis on oncolytic herpes simplex virus (oHSV) and coverage of other vectors (adenovirus, reovirus, Newcastle disease virus, vaccinia virus) across phase I-III trials, focusing on efficacy and safety. Key observations include the encouraging clinical trajectory of oHSV exemplars-T-VEC (approved for melanoma) and G47Δ (approved in Japan for recurrent GBM)-the multi-center exploration of the adenovirus DNX-2401 combined with programmed death-1 (PD-1) blockade, and the early-stage status of reovirus (pelareorep) and Newcastle disease virus programs. Emerging evidence indicates that oHSV therapy augments immune infiltration within the tumor microenvironment and alleviates immunosuppression, with synergy when combined with chemotherapy or immune checkpoint inhibitors. Persistent challenges include GBM's inherently immunosuppressive milieu, limitations imposed by the blood-brain barrier, intrapatient viral delivery and biodistribution, and concerns about viral shedding. Future directions encompass programmable vector design, optimization of systemic delivery, biomarker-guided patient selection, and rational combination immunotherapy. Collectively, OVs represent a promising immunotherapeutic strategy in GBM; further gains will hinge on vector engineering and precision combinations to translate mechanistic promise into durable clinical benefit.
Comparison of children and adults in deep brain stimulation for Tourette Syndrome: a large-scale multicenter study of 102 cases with long-term follow-up
Background Deep brain stimulation (DBS) is a promising therapy for refractory Gilles de la Tourette syndrome (GTS). However, its long-term efficacy, safety, and recommended surgical age remain controversial, requiring evidence to compare different age categories. Methods This retrospective cohort study recruited 102 GTS patients who underwent DBS between October 2006 and April 2022 at two national centers. Patients were divided into two age categories: children (aged < 18 years; n  = 34) and adults (aged ≥ 18 years; n  = 68). The longitudinal outcomes as tic symptoms were assessed by the YGTSS, and the YBOCS, BDI, and GTS-QOL were evaluated for symptoms of obsessive–compulsive disorder (OCD), depression, and quality of life, respectively. Results Overall, these included patients who finished a median 60-month follow-up, with no significant difference between children and adults ( p  = 0.44). Overall, the YGTSS total score showed significant postoperative improvements and further improved with time (improved 45.2%, 51.6%, 55.5%, 55.6%, 57.8%, 61.4% after 6, 12, 24, 36, 48, and ≥ 60 months of follow-up compared to baseline, respectively) in all included patients (all p  < 0.05). A significantly higher improvement was revealed in children than adults at ≥ 60 months of follow-up in the YGTSS scores (70.1% vs 55.9%, p  = 0.043), and the time to achieve 60% improvement was significantly shorter in the children group (median 6 months vs 12 months, p  = 0.013). At the last follow-up, the mean improvements were 45.4%, 48.9%, and 55.9% and 40.3%, 45.4%, and 47.9% in YBOCS, BDI, and GTS-QOL scores for children and adults, respectively, which all significantly improved compared to baseline (all p  < 0.05) but without significant differences between these two groups (all p  > 0.05), and the children group received significantly higher improvement in GTS-QOL scores than adults (55.9% vs. 47.9%, p  = 0.049). Conclusions DBS showed acceptable long-term efficacy and safety for both children and adults with GTS. Surgeries performed for patients younger than 18 years seemed to show acceptable long-term efficacy and safety and were not associated with increased risks of loss of benefit compared to patients older than 18 at the time of surgery. However, surgeries for children should also be performed cautiously to ensure their refractoriness and safety.
The surgical interval between robot-assisted SEEG and epilepsy resection surgery is an influencing factor of SSI
Background In recent years, the development of robotic neurosurgery has brought many benefits to patients, but there are few studies on the occurrence of surgical site infection (SSI) after robot-assisted stereoelectroencephalography (SEEG). The purpose of this study was to collect relevant data from robot-assisted SEEG over the past ten years and to analyze the influencing factors and economic burden of surgical site infection. Methods Basic and surgical information was collected for all patients who underwent robot-assisted SEEG from January 2014 to December 2023. Logistic regression was used to analyze the factors influencing SSI according to different subgroups (radiofrequency thermocoagulation or epilepsy resection surgery). Results A total of 242 subjects were included in this study. The risk of SSI in the epilepsy resection surgery group (18.1%) was 3.5 times greater than that in the radiofrequency thermocoagulation group (5.1%) (OR 3.49, 95% CI 1.39 to 9.05); this difference was statistically significant. SSI rates in the epilepsy resection surgery group were associated with shorter surgical intervals (≤ 9 days) and higher BMI (≥ 23 kg/m 2 ) (6.1 and 5.2 times greater than those in the control group, respectively). Hypertension and admission to the intensive care unit (ICU) were risk factors for SSI in the radiofrequency thermocoagulation group. Patients with SSIs had $21,231 more total hospital costs, a 7-day longer hospital stay, and an 8-day longer postoperative hospital stay than patients without SSI. Conclusions The incidence of SSI in patients undergoing epilepsy resection after stereoelectroencephalography was higher than that in patients undergoing radiofrequency thermocoagulation. For patients undergoing epilepsy resection surgery, prolonging the interval between stereoelectroencephalography and epilepsy resection surgery can reduce the risk of SSI; At the same time, for patients receiving radiofrequency thermocoagulation treatment, it is not recommended to enter the ICU for short-term observation if the condition permits.
Correction to: Detecting focal cortical dysplasia lesions from FLAIR-negative images based on cortical thickness
It was highlighted that the original article [1] contained an error in the Quantitative evaluation of Methods. A bracket was misplaced in the formula. This Correction article shows the incorrect and correct formula.
Genetic Analysis of the ts-Lethal Mutant Δpa0665/pTS-pa0665 Reveals Its Role in Cell Morphology and Oxidative Phosphorylation in Pseudomonas aeruginosa
Pa0665 in Pseudomonas aeruginosa shares homologous sequences with that of the essential A-type iron–sulfur (Fe-S) cluster insertion protein ErpA in Escherichia coli. However, its essentiality in P. aeruginosa and its complementation with E. coli erpA has not been experimentally examined. To fulfill this task, we constructed plasmid-based ts-mutant Δpa0665/pTS-pa0665 using a three-step protocol. The mutant displayed growth defects at 42 °C, which were complemented by expressing ec.erpA. Microscopic observations indicated a petite cell phenotype for Δpa0665/pTS-pa0665 at 42 °C, correlated with the downregulation of the oprG gene. RNA sequencing revealed significant transcriptional changes in genes associated with the oxidative phosphorylation (OXPHOS) system, aligning with reduced ATP levels in Δpa0665/pTS-pa0665 under 42 °C. Additionally, the ts-mutant showed heightened sensitivity to H2O2 at 42 °C. Overall, our study demonstrates the essential role of pa0665 for OXPHOS function and is complemented by ec.erpA. We propose that the plasmid-based ts-allele is useful for genetic analysis of essential genes of interest in P. aeruginosa.
Genetic Analysis of the ts-Lethal Mutant IΔpa0665/I/IpTS-pa0665/I Reveals Its Role in Cell Morphology and Oxidative Phosphorylation in IPseudomonas aeruginosa/I
Pa0665 in Pseudomonas aeruginosa shares homologous sequences with that of the essential A-type iron–sulfur (Fe-S) cluster insertion protein ErpA in Escherichia coli. However, its essentiality in P. aeruginosa and its complementation with E. coli erpA has not been experimentally examined. To fulfill this task, we constructed plasmid-based ts-mutant Δpa0665/pTS-pa0665 using a three-step protocol. The mutant displayed growth defects at 42 °C, which were complemented by expressing ec.erpA. Microscopic observations indicated a petite cell phenotype for Δpa0665/pTS-pa0665 at 42 °C, correlated with the downregulation of the oprG gene. RNA sequencing revealed significant transcriptional changes in genes associated with the oxidative phosphorylation (OXPHOS) system, aligning with reduced ATP levels in Δpa0665/pTS-pa0665 under 42 °C. Additionally, the ts-mutant showed heightened sensitivity to H[sub.2]O[sub.2] at 42 °C. Overall, our study demonstrates the essential role of pa0665 for OXPHOS function and is complemented by ec.erpA. We propose that the plasmid-based ts-allele is useful for genetic analysis of essential genes of interest in P. aeruginosa.