Neurological diseases, often caused by irreversible loss of terminally differentiated neurons, present considerable challenges to treatment due to the limited regenerative capacity of these neurons. Although induced pluripotent stem cells hold promise for neuronal regeneration, their clinical application is constrained by risks, including tumorigenicity, incomplete neuronal maturation, and immune rejection. Recent advancements in direct neuronal reprogramming, which bypasses the intermediate pluripotent stage by directly converting non-neuronal cells into functional neurons, offer a compelling alternative for in situ neuronal replacement in neurodegenerative diseases. Key transcription factors, such as NeuroD1, Ascl1, Sox2, as well as CRISPR activation (CRISPRa) of NGN2 and ISL1, have been explored to convert glial cells into neurons. However, several challenges remain. This review discusses the current applications of direct neuronal reprogramming technology in several neurological diseases. We further highlight the potential contamination issues in adeno-associated virus (AAV) delivery systems and propose a code of conduct to avoid artifacts and pitfalls. Finally, we point out future directions for expanding direct reprogramming targets, integrating organoid-based disease modeling, and advancing reprogramming regulation techniques.

Localization of the epileptogenic zone (EZ) requires further refinement. We identified a unique ictal spectral structure, the “harmonic pattern” (H pattern), which potentially serves as a novel biomarker for localizing the EZ. This study aimed to analyze the clinical significance of the H pattern and to explore its underlying waveform features. Seventy patients with drug-resistant focal epilepsy, undergoing stereo-EEG (SEEG) evaluation and surgery, were included. Time–frequency maps (TFM) were generated using Morlet wavelet transform analysis. The H pattern was defined as multiple equidistant, high-density bands with varying frequencies on TFM. The upper quartile was employed to confirm contacts expressing dominant H pattern (dH pattern). Bispectral analysis and transfer function modeling were employed to assess nonlinear properties and signal propagation, respectively. The performance of the dH pattern in evaluating the EZ was compared with other ictal biomarkers. Regardless of seizure onset patterns, the H pattern commonly occurred during early or late seizure propagation among 57 patients (81.4

BACKGROUND:Thalamic recordings are increasingly incorporated into stereo-electroencephalography (SEEG) evaluations of drug-resistant focal epilepsy to guide neuromodulation targeting. Human thalamic electrophysiology, however, is poorly defined, limiting the distinction between pathological and physiological activity. Here, we characterised interictal epileptic and non-epileptic events during non-rapid eye movement (NREM) sleep across multiple thalamic nuclei and examined their associations to seizure outcomes. METHODS:We analysed NREM sleep SEEG recordings from 64 patients with drug-resistant focal epilepsy. Electrodes sampled four thalamic nuclei: centromedian (CM), pulvinar (Pu), ventral lateral (VL), and ventral posterolateral (VPL). Patients were classified into three outcome groups: favourable, unfavourable, and surgically non-remediable. Rates of thalamic spikes, high-frequency oscillations (HFOs), spike-fast activity, and sleep spindles were analysed and compared across nuclei and outcomes. FINDINGS:Recordings of the thalamus revealed both pathological and physiological interictal events. Interictal epileptic events were infrequent. Only ∼0.2% of seizure-onset zone spikes propagated to the thalamus. Thalamic spike-fast activity was indicative of unfavourable surgical outcomes (CM: p = 0.047, d = 0.46) or surgically non-remediable epilepsy (VL: p = 0.002, d = 0.84). In contrast, thalamic sleep spindles were ubiquitous but reduced in surgically non-remediable patients (CM: p = 0.031, d = -0.58; VL: p = 0.005, d = -0.79). Finally, unique thalamic SEEG patterns were identified, including spikes concomitant with spindles, isolated spikes, and physiological fast ripples. INTERPRETATION:This study provides a comprehensive characterisation of thalamic interictal events during NREM sleep, enriching our understanding of thalamic pathophysiology and highlighting the value of thalamic recordings in presurgical evaluation. FUNDING:Start-up funding of Duke University; National Natural Science Foundation of China (82471469, 82301636); Zhejiang Provincial Natural Science Foundation (LD24H090003); Canadian Institutes of Health Research funding (PJT-175056).

Abstract Objective To investigate how etiology and seizure localization influence ictal scalp electroencephalographic (EEG) patterns in temporal lobe epilepsy (TLE). Methods We retrospectively analyzed ictal EEG features from 504 focal seizures recorded in 189 TLE patients with various etiologies who underwent resective surgery. Results For seizure onset patterns (SOPs), α/β onset was more common in the low‐grade tumor group (38.4%) than in the hippocampal sclerosis (HS) group (14.1%, p < 0.001). The ictal EEG duration was shorter in the tumor group compared to the focal cortical dysplasia (FCD), HS, and non‐specific groups (p < 0.05). Among mesial TLE patients, SOPs varied depending on the etiology. Within both the tumor and non‐specific groups, SOPs and the spreading time to the contralateral hemisphere differed between mesial and neocortical origins. Ictal pattern (87.7%) and ictal theta activity (83.9%) correctly lateralized the seizure in most cases. Significance The ictal scalp pattern in TLE is influenced by both etiology and seizure localization. TLE associated with low‐grade tumors exhibits distinct ictal EEG characteristics. Furthermore, ictal pattern and ictal theta activity are equally effective in lateralizing seizures, regardless of etiology. Plain Language Summary This research examined how brain activity during seizures in people with temporal lobe epilepsy can be different based on what caused the epilepsy and where in the brain the seizure starts. We found that seizures caused by brain tumors have unique patterns in the brain's electrical activity. Additionally, we discovered that specific patterns and types of brain waves can help determine which side of the brain the seizure is occurring on, regardless of its cause.

AIMS:Sustained neuroinflammation following ischemic stroke impedes post-injury tissue repairment and neurological functional recovery. Developing innovative therapeutic strategies that simultaneously suppress detrimental inflammatory cascades and facilitate neurorestorative processes is critical for improving long-term rehabilitation outcomes. METHODS:We employed a microglia depletion-repopulation paradigm by administering PLX5622 for 7 days post-ischemia; followed by a 7-day withdrawal period to allow microglia repopulation. Single-cell transcriptomics, behavioral testing, cytokine arrays, flow cytometry, and immunofluorescence were used to assess the effects of microglia repopulation and delineate the transition of reshaped immune microenvironment. RESULTS:PLX5622 administration reshaped the poststroke immune microenvironment, promoting neurofunctional recovery. Repopulated microglia adopted a homeostatic phenotype, increasing homeostatic states by ~14.36% and reducing pro-inflammatory states by ~20.17%. This reshaped environment suppressed T cell exhaustion, limited neutrophil terminal differentiation, and promoted a phagocytic macrophage phenotype. Furthermore, we identified that these transitions in infiltrating immune cells may be driven by reduced chemokine production, enhanced blood-brain barrier (BBB) integrity, and transcriptional reprogramming. CONCLUSION:Transient microglial depletion and repopulation via PLX5622 during the acute phase post stroke facilitate the recovery of neurological function. This immunomodulatory strategy offers a promising and clinically translationally relevant approach to enhance functional recovery following ischemic brain injury.

OBJECTIVES:Conventional deep brain stimulation (cDBS) is an established treatment for Parkinson's disease (PD), whereas adaptive DBS (aDBS) represents a promising approach with potential advantages in minimizing stimulation-induced side effects and enhancing quality of life. This study evaluated the safety and efficacy of a newly developed aDBS closed-loop neurostimulation (CNS) device for one year across multiple centers, with the primary objective of comparing the outcomes of aDBS and cDBS. MATERIALS AND METHODS:This retrospective study included 62 patients with PD who underwent bilateral subthalamic nucleus (STN) DBS. Outcomes were assessed using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Parkinson's Disease Questionnaire-39 (PDQ-39), and Schwab and England Activities Scale, whereas the levodopa-equivalent daily dose (LEDD) and adverse events were monitored. This two-phase trial randomized participants into Stim-on or Stim-off groups for 90-day postoperative comparison followed by nonrandomized evaluation of aDBS vs cDBS at 360 days after surgery. RESULTS:At 90 days postoperatively, the Stim-on group exhibited superior outcomes to those in the Stim-off group except for LEDD and speech in the medication-on state. At the 360-day postoperative assessment, the aDBS group showed significantly greater improvements than did the cDBS group in MDS-UPDRS II (57.29% vs 33.02%, p = 0.022), MDS-UPDRS IV (59.83% vs 36.69%, p = 0.026), PDQ-39 (56.91% vs 27.37%, p = 0.031), and LEDD reduction (53.35% vs 29.16%, p = 0.002). CNS aDBS recorded clear STN-beta signals, which could be adopted as a biomarker. CONCLUSIONS:Both aDBS and cDBS significantly alleviate motor symptoms and enhance quality of life in patients with PD. Although comparable in motor symptom control, aDBS indicated advantages over cDBS across LEDD reduction, MDS-UPDRS II, MDS-UPDRS IV, and PDQ-39 over the long term. Further studies with extended follow-up and larger sample sizes are required to validate these results.

Background The pathophysiology of idiopathic normal pressure hydrocephalus (iNPH) remains unclear, and the treatment strategy remains suboptimal. This study aims to identify biomarkers for shunt prognosis by cerebrospinal fluid (CSF) proteomic profiling. Methods CSF samples collected from 37 iNPH patients from the discovery cohort and 12 iNPH patients from an independent validation cohort (71.9 ± 6.1 years (mean ± SD)), and 16 age-balanced controls (69.9 ± 7.6 years (mean ± SD)) were collected from September 2020 to December 2023. 53 CSF samples were analyzed using a mass spectrometry-based proteomic workflow. Clinical evaluations were performed on all iNPH patients, and 44 patients underwent ventriculoperitoneal shunting. Postoperative CSF were also collected from 10 iNPH patients who underwent shunting surgery. Bioinformatics, machine learning, and enzyme-linked immunosorbent assay (ELISA) were performed to identify CSF proteome changes related to pathophysiology in iNPH, and screen for biomarkers associated with shunt response. Results 39 and 285 proteins significantly increased and decreased in iNPH CSF compared to the control group. Gene ontology analysis revealed that the noticeably increased proteins were mainly associated with myeloid leukocyte migration and extracellular matrix organization, and significantly decreased proteins were primarily associated with axon development and synapse organization. Machine learning identified 6 candidate biomarkers that potentially predicted the response to shunt surgery. Among these, QPCT levels were found to be elevated in non-responders, while RBP4 levels were decreased, and both of these changes were validated through ELISA. Conclusions Our findings provide support for the hypothesis that the pathophysiology of iNPH is characterized by a state of neuroinflammation, extracellular matrix remodeling, and neurodegeneration, and CSF shunting can reverse such pathological state. Machine learning using preoperative proteomic profiles satisfactorily predicted the clinical outcome of the shunt procedure in iNPH. Future research targeting specific proteins in iNPH may be warranted to better comprehend the disease mechanism and design patient-tailored treatments.

OBJECTIVE:Low-grade epilepsy-associated neuroepithelial tumors (LEATs) often cause drug-resistant epilepsy. Despite complete resection of these lesions, approximately 20% of patients continue to experience suboptimal seizure control. This study aims to investigate the predictive value of quantitative features in determining the surgical outcomes for LEAT patients. METHODS:We retrospectively analyzed 44 temporal LEAT patients who underwent gross-total lesionectomy. EEG features, including power spectral density (PSD) and weighted phase lag index (wPLI), were compared between patients with good (Engel I) and poor (Engel II-IV) outcomes. Significant EEG features were identified through these analyses. Domain Adversarial Neural Network (DANN) was employed to assess the predictive value of these features for surgical outcomes. RESULTS:No significant PSD differences were found, but patients with good outcomes had higher alpha-band wPLI (p = 0.008). LEATnet, predicted outcomes with an AUC of 0.81and correctly classified 8 of 11 patients in the independent validation cohort. CONCLUSIONS:Alpha-band functional connectivity is a key predictor of surgical outcomes in LEAT patients. SIGNIFICANCE:EEG-based connectivity analysis may improve prognostic accuracy and aid clinical decision-making in LEAT epilepsy.

OBJECTIVE:Rhythmic epileptiform discharges (REDs) are a prevalent interictal pattern on scalp electroencephalogram (EEG) in patients with focal cortical dysplasia (FCD). The study aims to assess the relationship between REDs and epileptogenicity by investigating their clinical and pathological correlations. METHODS:We retrospectively included patients who underwent resective surgeries with confirmed FCD. Presurgical scalp EEGs were evaluated regarding the presence or absence of REDs. Associations between REDs and clinical variables were analyzed. Furthermore, we investigated the pathological substrates of REDs in patients with FCD type 2 by comparing densities of abnormal chloride transporters and pathological cells in the patients with and without REDs. RESULTS:Our results demonstrated that REDs were more common in patients with an earlier onset (P < 0.0001), FCD type 2 (P < 0.0001) and were more likely recorded in the extratemporal region (P < 0.0001). REDs predicted a favorable surgical outcome in FCD patients (Odds ratio = 4.35, P = 0.02). In patients with FCD type 2, presence of REDs was associated with increased cytoplasmic expressions of potassium-chloride-co-transporter 2 (P = 0.048). CONCLUSION:REDs are associated with favorable surgical outcomes in patients with FCD. Abnormal expressions of the chloride transporters may underlie the RED generation. SIGNIFICANCE:Our results expand the clinical significance of REDs and provide further insights into its pathogenesis.

OBJECTIVE:This study evaluated the association between temporal piriform cortex (tPC) resection and long-term postoperative outcomes in temporal lobe epilepsy (TLE). METHODS:We conducted a retrospective analysis of patients with TLE undergoing surgery between 2012 and 2022, with a minimum follow-up of 2 years. The extent of resection, including the tPC, hippocampal head/body, and amygdala, was assessed using magnetic resonance imaging scans. These measurements, along with demographic data and other presurgical evaluations, were analyzed for their associations with Engel class postoperative outcomes and antiseizure medications (ASMs) withdrawal across different TLE subtypes. RESULTS:Among 216 included patients, 158 had mesial TLE (MTLE). At the final follow-up, 131 MTLE and 35 neocortical TLE (NTLE) patients were seizure-free. Multivariable logistic regression revealed that unresected tPC significantly predicted seizure recurrence (p < .001, odds ratio [OR] = 4.415, 95% confidence interval [CI] = 2.032-9.594), along with older age at surgery (p = .018, OR = 1.034, 95% CI = 1.006-1.063) and nonspecific pathology (p = .017, OR = 3.899, 95% CI = 1.278-11.894). In NTLE, tPC resection did not significantly affect outcomes. However, in MTLE, unresected tPC was strongly associated with poorer seizure outcomes at both 2-year (p = .012, OR = 3.362, 95% CI = 1.311-8.621) and 5-year (p = .014, OR = 5.750, 95% CI = 1.423-23.242) follow-ups. Among seizure-free MTLE patients, those with tPC resection had higher rates of ASMs reduction and withdrawal after 5 years (p < .05). In hippocampal sclerosis (HS) patients, unresected tPC correlated with seizure recurrence (p < .05), whereas no such association was observed in non-HS cases. SIGNIFICANCE:Our findings suggest that tPC involvement in the epileptogenic zone varies by TLE subtype, with tPC resection strongly linked to favorable outcomes in MTLE, particularly in HS patients. These results reinforce the understanding of the hippocampus-amygdala-piriform complex as crucial to the epileptogenic zone in MTLE.

Objectives: The study aims to investigate the predictive performance of preoperative imaging features combined with tap test for the outcomes of ventriculoperitoneal (VP) shunt in idiopathic normal pressure hydrocephalus (iNPH). Methods: In this multicenter retrospective study, 166 iNPH patients who underwent VP shunt surgery between August 2019 and November 2023 were included. Preoperative clinical characteristics and imaging features were collected. Preoperative clinical assessment and at least 3 months of postoperative follow-up were performed. Multivariable logistic regression, sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC) were used to evaluate predictive performance. Results: Out of 166 total patients, 96 were responders and 70 non-responders. The tap test showed significant difference between two group (p < 0.01). Multivariable logistic regression identified that a positive disproportionately enlarged subarachnoid space (DESH) sign (OR = 0.09, 95% CI: 0.04-0.22, p < 0.001) and a sharper callosal angle (CA) (OR = 0.97, 95% CI: 0.95-1.00, p = 0.02) were associated with symptom improvement after shunt. The sensitivity, specificity, and AUC of tap test were 0.64, 0.60, and 0.62, respectively. Combining CA and the tap test increased sensitivity to 0.85, while combining DESH, CA, and the tap test improved specificity and AUC to 0.67 and 0.72, respectively. Conclusion: The findings suggest that the imaging features DESH and CA, when combined with the tap test, enhance the prediction of VP shunt outcomes in iNPH patients. Despite the improved predictive capability, further research focusing on innovative biomarkers for VP shunt is warranted.

This work proposes a supervised machine learning algorithm for target localization in deep brain stimulation (DBS). DBS is a recognized treatment for movement disorders, such as essential tremor. The effects of DBS significantly depends on the precise choice of target location. Recent research on diffusion tensor imaging (DTI) shows that the optimal target is related to the dentato-rubro-thalamic tract (DRTT), thus DRTT analysis has become a promising approach. This technique is more accurate than conventional ones, but still too complicated for clinical scenarios, where only magnetic resonance imaging (MRI) data is available. In order to improve efficiency and utility, we consider target localization as a non-linear regression problem in a reduced-reference learning framework, and solve it with convolutional neural networks. The proposed method is light-weight, and consists of two image-based networks: one for classification and the other for localization. We model the basic workflow as an image retrieval process and define relevant performance metrics. Using DRTT analysis as groundtruths, we show that DTI-based optimal targets can be inferred from MRI data with high accuracy. For 280x220 (0.7 mm slice thickness) MRI input, our model achieves an average posterior localization error of 2.3 mm, and a median of 1.7 mm. The proposed framework is the first in the DBS domain. It is a successful application of reduced-reference learning, and may serve as a baseline for general target localization problems in DBS.

Abstract Metacognition, the ability to introspectively monitor confidence prior to decision-making, remains an area with unclear neural mechanisms, particularly concerning the intercommunication among various brain regions. Recently, the precuneus has emerged as a key player in mnemonic metacognitive tasks, while the hippocampus's involvement in memory function is well-established. Our study sought to examine the roles of the precuneus and hippocampus in mnemonic metacognition, employing intracranial electrode recordings from patients with intractable epilepsy to analyze the regulatory and correlational dynamics between these regions. We identified distinct communication patterns between the precuneus and hippocampus during metacognition and confidence generation. Furthermore, we conducted a quantitative assessment of the temporal dynamics involved in metacognition and the generation of confidence. Our observations reveal that introspective judgments typically occur subsequent to the generation of confidence. Our study sheds light on the neural underpinnings of metacognition and the genesis of confidence, focusing on the interplay between the hippocampus and the precuneus. This investigation lays the groundwork for deepening our comprehension of the nuances distinguishing confidence from metacognition.

IntroductionLanguage impairments often result from severe neurological disorders, driving the development of neural prosthetics utilizing electrophysiological signals to restore comprehensible language. Previous decoding efforts primarily focused on signals from the cerebral cortex, neglecting subcortical brain structures’ potential contributions to speech decoding in brain-computer interfaces.MethodsIn this study, stereotactic electroencephalography (sEEG) was employed to investigate subcortical structures’ role in speech decoding. Two native Mandarin Chinese speakers, undergoing sEEG implantation for epilepsy treatment, participated. Participants read Chinese text, with 1–30, 30–70, and 70–150 Hz frequency band powers of sEEG signals extracted as key features. A deep learning model based on long short-term memory assessed the contribution of different brain structures to speech decoding, predicting consonant articulatory place, manner, and tone within single syllable.ResultsCortical signals excelled in articulatory place prediction (86.5% accuracy), while cortical and subcortical signals performed similarly for articulatory manner (51.5% vs. 51.7% accuracy). Subcortical signals provided superior tone prediction (58.3% accuracy). The superior temporal gyrus was consistently relevant in speech decoding for consonants and tone. Combining cortical and subcortical inputs yielded the highest prediction accuracy, especially for tone.DiscussionThis study underscores the essential roles of both cortical and subcortical structures in different aspects of speech decoding.

AbstractObjectiveThe ictalHarmonicpattern (Hpattern), produced by the non-linear characteristics of EEG waveforms, may hold significant potential for localizing the epileptogenic zone (EZ) in focal epilepsy. However, further validation is needed to establish theHpattern’s effectiveness as a biomarker for measuring the EZ.MethodsWe retrospectively enrolled 131 patients diagnosed with drug-resistant focal epilepsy, all of whom had complete stereo-electroencephalographic (SEEG) data. From this cohort, we selected 85 patients for outcome analysis. We analyzed the morphological and time-frequency (TF) features of theHpattern using TF plots. A third quartile (Q3) threshold was applied to classify channels expressing either dominant (ChanneldHpattern) or non-dominantHpatterns (Channelnon-dHpattern). We then examined associations between the morphological features of theHpattern and patients’ clinical characteristics, as well as the correlations between the extent of channel removal and seizure outcomes.ResultsWe found no significant correlations between the morphological features of the ictalHpattern and clinical factors, including lesional MRI findings, epileptic onset patterns, epilepsy type, pathology, or surgical outcomes. The non-localizableHpattern appeared exclusively in patients with non-focal onset patterns. Notably, the proportion ofChanneldHpatternwas higher in the seizure-onset zone (SOZ) compared to the early propagation zone. The seizure-free group demonstrated significantly higher removal proportions ofChanneldHpattern, both within and outside the SOZ (p= 0.014;p= 0.036), with AUCs of 0.606 and 0.660, respectively, in a seizure freedom prediction model. Survival analysis confirmed that complete removal of these regions correlated with long-term seizure freedom (p= 0.008;p= 0.028). Further subgroup analysis showed a significant correlation in neocortical epilepsy (p= 0.0004;p= 0.011), but not in mesial temporal lobe epilepsy. Additionally, multivariate analysis identified the complete removal ofChanneldHpatternas the only independent predictor for seizure freedom (p= 0.022; OR 6.035, 95% CI 1.291-28.211).ConclusionsOur study supports the notion that the dominance of the ictalHpattern, regardless of its morphology, serves as a novel biomarker for the EZ in focal epilepsy. The non-linearity in EEG waveforms provides new insights into understanding ictal spreading propagation and offers potential improvements for surgical planning in neocortical epilepsy.

The blood-brain barrier (BBB) is a selectively semi-permeable layer, crucial in shielding the brain from external pathogens and toxic substances while maintaining ionic homeostasis and sufficient nutrient supply. However, it poses a significant challenge for drugs to penetrate the BBB in order to effectively target brain tumors. Magnetic resonance-guided laser interstitial thermal therapy (MRg-LITT) is a minimally invasive technique that employs thermal energy to cauterize intracranial lesions with the potential to temporarily disrupt the BBB. This further opens a possible therapeutic window to enhance patient outcomes. Here, we review the impact of MRg-LITT on BBB and blood tumor barrier (BTB) and the duration of the BBB disruption. Studies have shown that MRg-LITT is effective due to its minimally invasive nature, precise tumor targeting, and low complication rates. Although the disruption duration varies across studies, the average peak disruption is within the initial two weeks post-ablation period and subsequently exhibits a gradual decline. However, further research involving larger groups with extended follow-up periods is required to determine disruption duration more accurately. In addition, evaluating toxicity and glymphatic system disruption is crucial to circumvent potential risks associated with this procedure.

The ictal EEG biomarkers of the epileptogenic zone (EZ) need to be better defined. The power and structure of ictal fast activity are important in EZ localization, but EEG onset patterns are heterogeneous and initial fast activity is absent in many patients. Here we defined a unique spectral structure of "harmonic pattern" (H pattern) on stereo-EEG (SEEG), characterized by multiple equidistant, high-density bands with varying frequency on time frequency map. H pattern was commonly observed among 57 (81.4%) out of 70 patients with focal onset pattern on SEEG. It was presented in seizures with various ictal onset patterns with or without fast activity, and during early or late stage of seizures. H pattern usually expressed at very close time point across the seizure onset zone (SOZ), primary propagation zone and sometimes other areas, with the same fundamental difference, reflecting an inter-regional synchronization within the ictal network during this time. Notably, SOZ showed the highest proportion of channels expressing H-pattern, and also highest band number of H-pattern. At patient level, the dominant H pattern was defined as those with high rank in band numbers (the third quartile, Q3). Resection of the region expressing dominant H pattern, but not SOZ, independently predicted seizure freedom after surgery, suggesting it is an ictal marker of EZ. How H pattern was produced was then investigated. It only embedded into two types of EEG segments: fast activity with a frequency >25Hz (FA-H pattern) at early seizure propagation (mean 13.3 sec after onset), and irregular polyspikes (> 5 Hz, PS-H pattern) during late propagation (mean 23.3 sec after onset). Nonlinear analysis was used to unravel the mechanism underlying H pattern generation. Our data showed it was produced by specific nonlinear phenomena rather than intermodulation of frequencies or purely methodological artefact. The nonlinearity was stronger for dominant compared to non-dominant H pattern. According to the spectral parameters, we postulate that FA-H pattern may be supported by a predominant and synchronized firing of GABAergic neurons, while excitatory neuron firing is more important for PS-H pattern. As a distinctive and common ictal spectral feature, H pattern conveys unique information of ictal neural dynamics and provides new insights into the EZ. Our study also provides evidence that there is an elongated time-window to measure EZ using quantitative EEG.### Competing Interest StatementThe authors have declared no competing interest.### Funding StatementThis work was supported by the National Natural Science Foundation of China (grant numbers: 82171437, 82001365 and 82272112).### Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:This study was approved by the Medical Ethics Committee of the Second Affiliated Hospital, Zhejiang University School of Medicine (Study No. 2020-910).I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesThe data that support the findings of this study are available upon reasonable request from the corresponding author. The data are not publicly available to protect the privacy of research participants.

Background and purpose: In light of the ongoing COVID-19 pandemic, vaccination has emerged as the primary and most effective solution. The aim of this study was to examine compliance rates of vaccination and explore the factors that predict vaccine uptake among patients with epilepsy (PWE) who have undergone resection surgery.Method: To examine the variations in vaccination coverage, safety concerns, and factors influencing vaccination hesitancy among PWE who have undergone resection surgery, this study recruited patients with at least one-year follow-up. We utilized questionnaires to gather clinical characteristics and obtain information regarding COVID-19 vaccines.Results: Among the 303 patients included in the study, a majority of 229 (75.58%) achieved a seizure-free outcome (Engel Ia). Of these patients, 178 (58.75%) received at least one dose of COVID-19 vaccine, and the vaccination rate has remained relatively consistent over the past six months. Nearly 94.95% of those who received the vaccine completed the full vaccination regimen, with the majority (n = 174, 97.75%) opting for an inactivated vaccine. Only three patients reported side effects unrelated to epilepsy, and one patient experienced a worsening of typical aura seizures within one month after vaccination. Notably, significant positive associations were observed between COVID-19 vaccine acceptance and adulthood (age 18 years or older) (OR = 1.820, 95% CI = 1.018-3.252, p = 0.043) as well as achieving a seizure-free outcome (OR = 2.823, 95% CI = 1.619-4.921, p < 0.001). Regarding the unvaccinated patients, approximately one-fifth expressed willingness to receive a future COVID-19 vaccine, while the remainder were hesitant (41.60%) or unsure (39.20%) about vaccination. These reservations mainly stemmed from concerns about the potential worsening of seizures and vaccine safety.Conclusions: Inactivated vaccines can be considered safe for individuals with epilepsy who have undergone resection surgery. The likelihood of being vaccinated was found to be comparatively higher among the cohort with seizure-free status or adults. To promote COVID-19 vaccination among children, it is crucial to implement comprehensive education and public awareness campaigns that emphasize the safety of vaccines. These efforts will help encourage widespread acceptance of vaccination and ensure the wellbeing of individuals with epilepsy.& COPY; 2023 Elsevier Inc. All rights reserved.

Subcallosal cingulate gyrus (SCG) is a target of deep brain stimulation (DBS) for treatment-resistant depression. However, previous randomized controlled trials report that approximately 42% of patients are responders to this therapy of last resort, and suboptimal targeting of SCG is a potential underlying factor to this unsatisfactory efficacy. Tractography has been proposed as a supplementary method to enhance targeting strategy. We performed a connectivity-based segmentation in the SCG region via probabilistic tractography in 100 healthy volunteers from the Human Connectome Project. The SCG voxels with maximum connectivity to brain regions implicated in depression, including Brodmann Area 10 (BA10), cingulate cortex, thalamus, and nucleus accumbens were identified, and the conjunctions were deemed as tractography-based targets. We then performed deterministic tractography using these targets in additional 100 volunteers to calculate streamline counts compassing to relevant brain regions and fibers. We also evaluated the intra- and inter-subject variance using test-retest dataset. Two tractography-based targets were identified. Tractography-based target-1 had the highest streamline counts to right BA10 and bilateral cingulate cortex, while tractography-based target-2 had the highest streamline counts to bilateral nucleus accumbens and uncinate fasciculus. The mean linear distance from individual tractography-based target to anatomy-based target was 3.2 +/- 1.8 mm and 2.5 +/- 1.4 mm in left and right hemispheres. The mean +/- SD of targets between intra- and inter-subjects were 2.2 +/- 1.2 and 2.9 +/- 1.4 in left hemisphere, and 2.3 +/- 1.4 and 3.1 +/- 1.7 in right hemisphere, respectively. Individual heterogeneity as well as inherent variability from diffusion imaging should be taken into account during SCG-DBS target planning procedure.