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Abstract Background The mechanistic effects of gamma transcranial alternating current stimulation (tACS) on hippocampal gamma oscillation activity in Alzheimer’s Disease (AD) remains unclear. This study aimed to clarify beneficial effects of gamma tACS on cognitive functioning in AD and to elucidate effects on hippocampal gamma oscillation activity. Methods This is a double-blind, randomized controlled single-center trial. Participants with mild AD were randomized to tACS group or sham group, and underwent 30 one-hour sessions of either 40 Hz tACS or sham stimulation over consecutive 15 days. Cognitive functioning, structural magnetic resonance imaging (MRI), and simultaneous electroencephalography–functional MRI (EEG-fMRI) were evaluated at baseline, the end of the intervention and at 3-month follow-up from the randomization. Results A total of 46 patients were enrolled (23 in the tACS group, 23 in the sham group). There were no group differences in the change of the primary outcome, 11-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-Cog) score after intervention (group*time, p = 0.449). For secondary outcomes, compared to the control group, the intervention group showed significant improvement in MMSE (group*time, p = 0.041) and MoCA scores (non-parametric test, p = 0.025), which were not sustained at 3-month follow-up. We found an enhancement of theta-gamma coupling in the hippocampus, which was positively correlated with improvements of MMSE score and delayed recall. Additionally, fMRI revealed increase of the local neural activity in the hippocampus. Conclusion Effects on the enhancement of theta-gamma coupling and neural activity within the hippocampus suggest mechanistic models for potential therapeutic mechanisms of tACS. Trial registration ClinicalTrials.gov, NCT 03920826; Registration Date: 2019-04-19.

Abstract Background Temporal lobe epilepsy (TLE) is among the most common types of epilepsy and often leads to cognitive, emotional, and psychiatric issues due to the frequent seizures. A notable pathological change related to TLE is hippocampal sclerosis (HS), which is characterized by neuronal loss, gliosis, and an increased neuron fibre density. The mechanisms underlying TLE-HS development remain unclear, but the reactive transcriptomic changes in glial cells and neurons of the hippocampus post-epileptogenesis may provide insights. Methods To induce TLE, 200 nl of kainic acid (KA) was stereotactically injected into the hippocampal CA1 region of mice, followed by a 7-day postinjection period. Single-cell RNA sequencing (ScRNA-seq), single-nucleus RNA sequencing (SnRNA-seq), and Xenium-based spatial transcriptomics analyses were employed to evaluate the changes in mRNA expression in glial cells and neurons. Results From the ScRNA-seq and SnRNA-seq data, 31,390 glial cells and 48,221 neuronal nuclei were identified. Analysis of the differentially expressed genes (DEGs) revealed significant transcriptomic alterations in the hippocampal cells of mice with TLE, affecting hundreds to thousands of mRNAs and their signalling pathways. Enrichment analysis indicated notable activation of stress and inflammatory pathways in the TLE hippocampus, while pathways related to axonal development and neural support were suppressed. Xenium analysis demonstrated the expression of all 247 genes across mouse brain sections, revealing the spatial distributions of their expression in 27 cell types. Integrated analysis of the DEGs identified via the three sequencing techniques revealed that Spp1, Trem2, and Cd68 were upregulated in all glial cell types and in the Xenium data; Penk, Sorcs3, and Plekha2 were upregulated in all neuronal cell types and in the Xenium data; and Tle4 and Sipa1l3 were downregulated in all glial cell types and in the Xenium data. Conclusion In this study, a high-resolution single-cell transcriptomic atlas of the hippocampus in mice with TLE was established, revealing potential intrinsic mechanisms driving TLE-associated inflammatory activation and altered cell interactions. These findings provide valuable insights for further exploration of HS development and epileptogenesis.

Abstract Objective Stereo‐electroencephalography‐guided three‐dimensional radiofrequency thermocoagulation (SEEG‐3D RFTC) is a minimally invasive treatment for mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE‐HS). This study aimed to investigate the long‐term prognosis after SEEG‐3D RFTC treatment in patients with MTLE‐HS. Methods This single‐center retrospective study included 28 patients with MTLE‐HS treated with SEEG‐3D RFTC from January 2016 to May 2018. Postoperative curative effects were evaluated using the Engel classification, and the patients were followed up for 5 years. Results The proportions of patients categorized as Engel I between 1 and 5 years after surgery were 72.41% (12 months after surgery), 67.86% (18 months after surgery), 62.07% (24 months after surgery), 50.00% (36 months after surgery), 42.86% (48 months after surgery), and 42.86% (60 months after surgery), respectively. Regarding long‐term efficacy, based on the Engel classification, SEEG‐3D RFTC showed room for improvement. Significance This was the first study to evaluate the efficacy of SEEG‐3D RFTC for MTLE‐HS with long‐term follow‐up. SEEG‐3D RFTC is a promising alternative for patients with MTLE‐HS. Plain Language Summary This study explored the potential of stereoelectroencephalography‐guided three‐dimensional radiofrequency thermocoagulation, a minimally invasive approach, for treating medial temporal lobe epilepsy with hippocampal sclerosis. Involving 28 patients, the research tracked the treatment’s success over five years using the Engel classification. Initial results were promising, with 72.41% of patients achieving the most favorable outcome (Engel I) at one year. While there was a gradual decrease in this proportion over time, 42.86% of patients maintained this positive outcome at five years, highlighting the treatment's potential for long‐term efficacy.

Epilepsy is characterized by abnormal synchronous electrical activity of neurons in the brain. The blood-brain barrier, which is mainly composed of endothelial cells, pericytes, astrocytes and other cell types and is formed by connections between a variety of cells, is the key physiological structure connecting the blood and brain tissue and is critical for maintaining the microenvironment in the brain. Physiologically, the blood-brain barrier controls the microenvironment in the brain mainly by regulating the passage of various substances. Disruption of the blood-brain barrier and increased leakage of specific substances, which ultimately leading to weakened cell junctions and abnormal regulation of ion concentrations, have been observed during the development and progression of epilepsy in both clinical studies and animal models. In addition, disruption of the blood-brain barrier increases drug resistance through interference with drug trafficking mechanisms. The changes in the blood-brain barrier in epilepsy mainly affect molecular pathways associated with angiogenesis, inflammation, and oxidative stress. Further research on biomarkers is a promising direction for the development of new therapeutic strategies.

Abstract The brain-computer interface (BCI) is a technology that involves direct communication with parts of the brain and has evolved rapidly in recent years; it has begun to be used in clinical practice, such as for patient rehabilitation. Patient electroencephalography (EEG) datasets are critical for algorithm optimization and clinical applications of BCIs but are rare at present. We collected data from 50 acute stroke patients with wireless portable saline EEG devices during the performance of two tasks: 1) imagining right-handed movements and 2) imagining left-handed movements. The dataset consists of four types of data: 1) the motor imagery instructions, 2) raw recording data, 3) pre-processed data after removing artefacts and other manipulations, and 4) patient characteristics. This is the first open dataset to address left- and right-handed motor imagery in acute stroke patients. We believe that the dataset will be very helpful for analysing brain activation and designing decoding methods that are more applicable for acute stroke patients, which will greatly facilitate research in the field of motor imagery-BCI.

ObjectiveNeuromodulation has been proven to be a promising alternative treatment for adult patients with drug-resistant epilepsy (DRE). Deep brain stimulation (DBS) and responsive neurostimulation (RNS) were approved by many countries for the treatment of DRE. However, there is a lack of systematic studies illustrating the differences between them. This meta-analysis is performed to assess the efficacy and clinical characteristics of DBS and RNS in adult patients with DRE.MethodsPubMed, Web of Science, and Embase were retrieved to obtain related studies including adult DRE patients who accepted DBS or RNS. The clinical characteristics of these patients were compiled for the following statistical analysis.ResultsA total of 55 studies (32 of DBS and 23 of RNS) involving 1,568 adult patients with DRE were included in this meta-analysis. There was no significant difference in seizure reduction and responder rate between DBS and RNS for DRE. The seizure reduction of DBS and RNS were 56% (95% CI 50–62%, p > 0.05) and 61% (95% CI 54–68%, p > 0.05). The responder rate of DBS and RNS were 67% (95% CI 58–76%, p > 0.05) and 71% (95% CI 64–78%, p > 0.05). Different targets of DBS did not show significant effect on seizure reduction (p > 0.05). Patients with DRE who accepted DBS were younger than those of RNS (32.9 years old vs. 37.8 years old, p 0.05).ConclusionBoth DBS and RNS are beneficial and alternative therapies for adult DRE patients who are not eligible to accept resection surgery. Further and larger studies are needed to clarify the characteristics of different targets and provide tailored treatment for patients with DRE.

BackgroundPrimary central nervous system post-transplant lymphoproliferative disorder (PCNS-PTLD) is a rare condition, posing diagnostic and treatment challenges, with histological biopsy essential for diagnosis. Standardized treatment protocols are lacking. This disease requires urgent attention due to the increasing number of organ transplant surgeries and the use of immunosuppressive agents.MethodsFrom 2020 to 2023, our center diagnosed five patients with PCNS-PTLD. We reviewed their clinical records and conducted a comprehensive analysis of 22 literatures on PCNS-PTLD cases following renal transplantation or allogeneic hematopoietic stem cell transplantation (HSCT).ResultsFour patients had previously received a kidney transplant, one had undergone allogeneic HSCT. The median time from the last transplant surgery to the diagnosis of PCNS-PTLD differs between kidney transplant (21.5 years) and allogeneic HSCT (9 months). Common symptoms included motor weakness (n = 4), headache (n = 2), confusion (n = 2), and nausea (n = 2), with ring-enhancing (n = 5), typically solitary (n = 3) and supratentorial (n = 3) lesions on imaging. Diagnosis involved robot-assisted stereotactic brain biopsy (n = 4) or craniotomy (n = 1), all showing Epstein-Barr virus and CD20 positivity. Most cases (n = 4) were monomorphic diffuse large B-cell lymphoma. Treatment included rituximab (n = 3), surgical resection (n = 2), zanubrutinib (n = 1), whole-brain radiation (n = 1), and methotrexate (n = 1). At the last follow-up, the median duration of follow-up for all patients was 19 months. During this time, 3 patients had died and 2 patients were still alive.ConclusionIn patients with a history of kidney transplantation or allogeneic HSCT who are on long-term immunosuppressive therapy, any neurological symptoms, particularly the presence of supratentorial ring-enhancing masses in the brain on imaging, whether solitary or multiple, should raise high suspicion for this disease, warranting a timely brain biopsy. Additionally, we found that besides reducing immunosuppressants, zanubrutinib may be a potential, safe, and effective treatment for this condition. Moreover, post-surgical administration of rituximab in conjunction with whole-brain radiotherapy also appears to be a potentially safe and effective approach.

BackgroundAt the intersection of neural monitoring and decoding, event-related potential (ERP) based on electroencephalography (EEG) has opened a window into intrinsic brain function. The stability of ERP makes it frequently employed in the field of neuroscience. However, project-specific custom code, tracking of user-defined parameters, and the large diversity of commercial tools have limited clinical application.MethodsWe introduce an open-source, user-friendly, and reproducible MATLAB toolbox named EPAT that includes a variety of algorithms for EEG data preprocessing. It provides EEGLAB-based template pipelines for advanced multi-processing of EEG, magnetoencephalography, and polysomnogram data. Participants evaluated EEGLAB and EPAT across 14 indicators, with satisfaction ratings analyzed using the Wilcoxon signed-rank test or paired t-test based on distribution normality.ResultsEPAT eases EEG signal browsing and preprocessing, EEG power spectrum analysis, independent component analysis, time-frequency analysis, ERP waveform drawing, and topological analysis of scalp voltage. A user-friendly graphical user interface allows clinicians and researchers with no programming background to use EPAT.ConclusionThis article describes the architecture, functionalities, and workflow of the toolbox. The release of EPAT will help advance EEG methodology and its application to clinical translational studies.

ObjectiveMesial temporal lobe epilepsy (mTLE) is a complex neurological disorder that has been recognized as a widespread global network disorder. The group-level structural covariance network (SCN) could reveal the structural connectivity disruption of the mTLE but could not reflect the heterogeneity at the individual level.MethodsThis study adopted a recently proposed individual structural covariance network (IDSCN) method to clarify the alternated structural covariance connection mode in mTLE and to associate IDSCN features with the clinical manifestations and regional brain atrophy.ResultsWe found significant IDSCN abnormalities in the ipsilesional hippocampus, ipsilesional precentral gyrus, bilateral caudate, and putamen in mTLE patients than in healthy controls. Moreover, the IDSCNs of these areas were positively correlated with the gray matter atrophy rate. Finally, we identified several connectivities with weak associations with disease duration, frequency, and surgery outcome.SignificanceOur research highlights the role of hippo-thalamic-basal-cortical circuits in the pathophysiologic process of disrupted whole-brain morphological covariance networks in mTLE, and builds a bridge between brain-wide covariance network changes and regional brain atrophy.

IntroductionAccurately and objectively quantifying the clinical features of Parkinson's disease (PD) is crucial for assisting in diagnosis and guiding the formulation of treatment plans. Therefore, based on the data on multi-site motor features, this study aimed to develop an interpretable machine learning (ML) model for classifying the “OFF” and “ON” status of patients with PD, as well as to explore the motor features that are most associated with changes in clinical symptoms.MethodsWe employed a support vector machine with a recursive feature elimination (SVM-RFE) algorithm to select promising motion features. Subsequently, 12 ML models were constructed based on these features, and we identified the model with the best classification performance. Then, we used the SHapley Additive exPlanations (SHAP) and the Local Interpretable Model agnostic Explanations (LIME) methods to explain the model and rank the importance of those motor features.ResultsA total of 96 patients were finally included in this study. The naive Bayes (NB) model had the highest classification performance (AUC = 0.956; sensitivity = 0.8947, 95% CI 0.6686–0.9870; accuracy = 0.8421, 95% CI 0.6875–0.9398). Based on the NB model, we analyzed the importance of eight motor features toward the classification results using the SHAP algorithm. The Gait: range of motion (RoM) Shank left (L) (degrees) [Mean] might be the most important motor feature for all classification horizons.ConclusionThe symptoms of PD could be objectively quantified. By utilizing suitable motor features to construct ML models, it became possible to intelligently identify whether patients with PD were in the “ON” or “OFF” status. The variations in these motor features were significantly correlated with improvement rates in patients' quality of life. In the future, they might act as objective digital biomarkers to elucidate the changes in symptoms observed in patients with PD and might be used to assist in the diagnosis and treatment of patients with PD.

BackgroundThyroid hormones (THs) play a crucial role in regulating various biological processes, particularly the normal development and functioning of the central nervous system (CNS). Epilepsy is a prevalent neurological disorder with multiple etiologies. Further in-depth research on the role of thyroid hormones in epilepsy is warranted.MethodsGenome-wide association study (GWAS) data for thyroid function and epilepsy were obtained from the ThyroidOmics Consortium and the International League Against Epilepsy (ILAE) Consortium cohort, respectively. A total of five indicators of thyroid function and ten types of epilepsy were included in the analysis. Two-sample Mendelian randomization (MR) analyses were conducted to investigate potential causal relations between thyroid functions and various epilepsies. Multiple testing correction was performed using Bonferroni correction. Heterogeneity was calculated with the Cochran’s Q statistic test. Horizontal pleiotropy was evaluated by the MR-Egger regression intercept. The sensitivity was also examined by leave-one-out strategy.ResultsThe findings indicated the absence of any causal relationship between abnormalities in thyroid hormone and various types of epilepsy. The study analyzed the odds ratio (OR) between thyroid hormones and various types of epilepsy in five scenarios, including free thyroxine (FT4) on focal epilepsy with hippocampal sclerosis (IVW, OR = 0.9838, p = 0.02223), hyperthyroidism on juvenile absence epilepsy (IVW, OR = 0.9952, p = 0.03777), hypothyroidism on focal epilepsy with hippocampal sclerosis (IVW, OR = 1.0075, p = 0.01951), autoimmune thyroid diseases (AITDs) on generalized epilepsy in all documented cases (weighted mode, OR = 1.0846, p = 0.0346) and on childhood absence epilepsy (IVW, OR = 1.0050, p = 0.04555). After Bonferroni correction, none of the above results showed statistically significant differences.ConclusionThis study indicates that there is no causal relationship between thyroid-related disorders and various types of epilepsy. Future research should aim to avoid potential confounding factors that might impact the study.

Summary: Background: Drug-resistant epilepsy (DRE) is associated with distributed laminar disruptions due to cytoarchitectonic pathologies, which may be characterized by multimodal MRI approaches such as morphometric similarity networks (MSNs). However, the genetic and histological underpinning of MSN alterations in DRE remains poorly understood, hampering its clinical application. Methods: We enrolled 60 patients with DRE and 23 controls, acquiring T1 and diffusion spectrum imaging data with a 3.0T GE SIGNA Premier scanner. Morphometric similarity networks (MSNs) were constructed and analyzed to identify microstructure similarity differences between patients and controls. Subsequently, patient-specific MSN alteration patterns were associated with gene expression using the GAMBA tool, and layer-specific neuronal signature mapping were also applied. During these analyses, sex and age were adjusted as covariates and multiple comparisons corrections were applied when appropriate. Findings: We observed widespread MSN changes in patients with DRE and identified five distinct MSN alteration patterns. Major patterns presented pattern-specific associations with expressions of epilepsy-related genes, particularly involving the mTOR pathway. Histological analysis confirmed the presence of cortical microstructure changes in areas with MSN alterations and revealed cellular abnormalities matching the aforementioned genetic risks. Interpretation: Our findings highlight the potential of quantifying laminar-related microstructure integrity using MSN to uncover the cytoarchitectonic changes in the pathophysiology of DRE. This approach may facilitate the identification of genetic and histological underpinnings of MSN alterations in DRE, ultimately aiding in the development of targeted therapeutic strategies. Fundings: The National Natural Science Foundation of China, the Ministry of Science and Technology of the People's Republic of China, and the Beijing Municipal Health Commission.

Summary: Background: China has the highest prevalence of spontaneous intracerebral hemorrhage (sICH) worldwide. To date, no national-level report has revealed sICH surgical performance. We aimed to investigate the current status and short-term outcomes of patients who underwent surgical treatment for sICH between 2019 and 2021. Methods: Data from 7451 patients undergoing sICH surgical treatment in China between 2019 and 2021, including demographic information, disease severity, surgical treatments for sICH, complications, and follow-up information, were retrieved from the Bigdata Observatory Platform for Stroke of China. Propensity score matching (PSM) was applied to balance the baseline characteristics. The surgical treatment performance on 3-month mortality and functional outcome were then explored by regression analysis. The influence of stroke center level and region on surgical performance was then explored. Findings: The numbers of sICH patients undergoing open craniotomy (OC), cranial puncture (CP), decompressive craniectomy (DC) and endoscopic evacuation (EE) were 2404 (32.3%), 3030 (40.7%), 1700 (22.8%) and 317 (4.3%), respectively. The 3-month mortality rate was 20.2%. Among the surviving patients, the 3-month poor functional prognosis (mRS 3–5) rate was 46.5%. After PSM, regression analysis showed that DC was associated with a higher mortality risk (OR = 1.31, 95% CI 1.06–1.61) than OC. CP was associated with a lower risk of poor mRS scores than OC (OR = 0.84, 95% CI 0.70–1.01), especially in stroke prevention centers and specific regions. Interpretation: Outcome improvements in Chinese sICH patients undergoing surgical treatment are worth expecting. Inconsistent surgical performance, especially functional outcome, affected by inhomogeneity of the hospital should be addressed. Funding: This work was supported by the Beijing Hospitals Authority Youth Programme (QML20230804), the National Natural Science Foundation of China (81701796, 82030037, 81871009), Capital Health Research and Development of Special Fund (2020-2Z-2019), Science and Technology Innovation 2030-Major Project (2021ZD0201801), and the Translational and Application Project of Brain-inspired and Network Neuroscience on Brain Disorders (11000022T000000444685).

Abstract Background Hemispherectomy is an effective treatment option for patients with drug-resistant epilepsy caused by hemispheric lesions. However, patients often have deterioration of their motor functions postoperatively. Diffusion spectrum imaging (DSI) was reliable in presenting the natural shape of the white matter fibers. At the same time, the natural sprawl pyramid tract (PT) might be more intuitive for predicting postoperative motor functions. Therefore, we assessed the motor functions by the natural shape revealed by DSI tractography. Methods Ten children with drug-resistant epilepsy who were candidates for hemispherectomy performed DSI PTs tractography and transcranial magnetic stimulation (TMS) for motor mapping. The motor function was evaluated with muscle strength and hand grasping capability. Pyramidal tract (PT) structural integrity and TMS mapping results were compared between patients who remained stable and those with deteriorated motor functions. Receiver operating characteristic (ROC) curves with PTs asymmetric ratio were analyzed to evaluate DSI tractography diagnostic value. Results All patients underwent DSI acquisition, while four patients successfully performed TMS. One patient had no response to TMS until the maximal machine output was reached. Four patients failed to perform TMS due to lacking cooperation. One patient was contraindicated to TMS. DSI successfully reconstructed the sharp angle fan-shaped PTs within the hemisphere. The accurate fiber distribution with fiber termination and thickness within the lesioned hemisphere was replicated with DSI tractography. No significance was found in patients’ age, sex, seizure frequency, or medication between patients with stable or deteriorated postoperative motor functions. DSI effectively predicted postoperative motor function as stable with damaged PTs, mild deterioration with atrophied PTs, and intact PTs with contralateral innervation confirmed by intracranial stimulation. The area under the curve (AUC) of DSI tractography was 0.84. According to ROC, the cut-off value of PTs asymmetric ratio was 11.5% with 100% sensitivity and 75% specificity. The sensitivity and specificity of TMS were 2/3 and 1/2, respectively. Conclusions The anatomic integrity of PTs with DSI tractography could effectively predict postoperative motor function after hemispherectomy. This enables neurosurgeons to inform patients and relatives about postoperative motor functions with direct morphological evidence of PTs to help them with their surgical decisions.

ObjectiveTo explore the development context, research hotspots and frontiers in the glymphatic system (GS) field from 2012 to 2022 by bibliometric analysis.MethodsThe Web of Science Core Collection (WoSCC) database was searched for articles published between 2012 and 2022. Microsoft Excel was used to manage the data. VOSviewer, CiteSpace, GraphPad Prism, the Web of Science, and an online analysis platform for bibliometrics (http://bibliometric.com/) were used to analyze the countries, institutions, journals, and collaboration networks among authors and the types of articles, developmental directions, references, and top keywords of published articles.ResultsA total of 412 articles were retrieved, including 39 countries/regions, 223 research institutes and 171 academic journals. The subject classifications related to the GS were Neuroscience, Clinical Neuroscience and Radiology/Nuclear Medicine/Medical Imaging. The United States has maintained its dominant and most influential position in GS research. Among research institutions and journals, the Univ Rochester and Journal of Cerebral Blood Flow and Metabolism had the highest number of academic articles, respectively. Nedergaard M had the most published article, and Iliff JJ had the most co-citations. The top two keywords with the highest frequency were “glymphatic system” and “cerebrospinal fluid.”ConclusionThis research provides valuable information for the study of the GS. The bibliometric analysis of this area will encourage potential collaborations among researchers, defining its frontiers and directions for development.

Direct electrical stimulation of the basal ganglia using implanted SEEG electrodes produced a variety of motor and non-motor effects in human participants, providing insight into the functional architecture of this key brain region.

BackgroundHypothalamic hamartoma (HH) is a rare intracranial disease whose manifestations include gelastic seizures and precocious puberty. The diagnosis and treatment of HH have changed substantially over the past three decades as medical care has improved. Bibliometrics can reveal the evolution and development of a scientific field.MethodsDocuments on HH were retrieved from the Web of Science Core Collection (WoSCC) database on September 8, 2022. The search terms were as follows: “hypothalamic hamartoma” or “hamartoma of the hypothalamus” or “hypothalamic hamartomas.” The types of documents were restricted to articles, case reports, and reviews. VOSviewer, CiteSpace, and the R package “bibliometrix” were used for a bibliometric analysis.ResultsA total of 667 independent documents on HH were obtained from the WoSCC database. The most common types of documents were articles (n = 498, 75%) and reviews (n = 103, 15%). The number of annual publications fluctuated but showed an upward trend overall, and the annual growth rate was 6.85%. The cumulative publication data indicated that the most influential journals in the HH field include Epilepsia, Epileptic Disorders, Child’s Nervous System, Neurosurgery, and the Journal of Neurosurgery. Kerrigan JF, Ng YT, Rekate HL, Regis J, and Kameyama S were among the most prominent authors in the field of HH, with numerous publications and citations. American research institutions, especially the Barrow Neurological Institute, occupied a pivotal position in HH research. Other countries and institutions were catching up and producing considerable research results. Research on HH has steadily switched its emphasis from Pallister-Hall syndrome (PHS) and precocious puberty to epilepsy and new diagnostic and therapeutic techniques, including Gamma Knife, laser ablation, and interstitial thermal therapy.ConclusionHH remains a special neurological disease with significant research prospects. The development of novel technologies, including MRI-guided laser-induced thermal therapy (MRg-LiTT) and stereotactic radiofrequency thermocoagulation (RF-TC), has enabled the efficient treatment of gelastic seizures in HH while minimizing the risks associated with craniotomies. Through bibliometric analysis, this study points out the direction for future HH research.

Abstract Background Corpus callosotomy (CC) is appropriate for patients with seizures of a bilateral or diffuse origin, or those with seizures of a unilateral origin with rapid spread to the contralateral cerebral hemisphere. The efficiency of CC in patients with drug‐resistant epilepsy is a long‐term concern because most articles reporting the surgical results of CC arise from small case series, and the durations of follow‐up vary. Methods PubMed, Embase, Cochrane Library, and Web of Science were searched to identify papers published before November 8, 2021. The systematic review was completed following PRISMA guidelines. Outcomes were analyzed by meta‐analysis of the proportions. Results A total of 1644 patients with drug‐resistant epilepsy (49 retrospective or prospective case series studies) underwent CC, and the follow‐up time of all patients was at least 1 year. The rate of complete seizure freedom (SF) was 12.38% (95% confidence interval [CI], 8.17%–17.21%). Meanwhile, the rate of complete SF from drop attacks was 61.86% (95% CI, 51.87%–71.41%). The rates of complete SF after total corpus callosotomy (TCC) and anterior corpus callosotomy (ACC) were 11.41% (95% CI, 5.33%–18.91%) and 6.75% (95% CI, 2.76%–11.85%), respectively. Additionally, the rate of complete SF from drop attacks after TCC was significantly higher than that after ACC (71.52%, 95% CI, 54.22%–86.35% vs. 57.11%, 95% CI, 42.17%–71.49%). The quality of evidence for the three outcomes by GRADE assessment was low to moderate. Conclusion There was no significant difference in the rate of complete SF between TCC and ACC. TCC had a significantly higher rate of complete SF from drop attacks than did ACC. Furthermore, CC for the treatment of drug‐resistant epilepsy remains an important problem for further investigation because there are no universally accepted standardized guidelines for the extent of CC and its benefit to patients. In future research, we will focus on this issue.

Abstract Objective Little is known about the intrinsic electrophysiological properties of hypothalamic hamartoma (HH) in vivo and seizure network since only few cases using stereoelectroencephalography (SEEG) electrodes exploring both cortex and HH have been published. To elucidate these issues, we analyzed simultaneous SEEG recordings in HH and cortex systematically. Methods We retrospectively investigated data from 15 consecutive patients with SEEG electrodes into the HH for the treatment purpose of radiofrequency thermocoagulation treatment. Additional SEEG electrodes were placed into the cortex in 11 patients to assess extra‐HH involvement. Interictal discharges within the HH and anatomo‐electroclinical correlations during seizures of each patient were qualitatively and quantitatively analyzed. Results Overall, 77 electrodes with 719 contacts were implanted, and 33 spontaneous seizures were recorded during long‐term SEEG monitoring. Interictally, distinct electrophysiological patterns, including isolated intermittent spikes/sharp waves, burst spike and wave trains, paroxysmal fast discharges, periodic discharges, and high‐frequency oscillations, were identified within the HH. Notably, synchronized or independent interictal discharges in the cortex were observed. Regarding the ictal discharges, the electrical onset pattern within the HH always started with abrupt giant shifts superimposed on low‐voltage fast activity across patients. The gelastic seizure network mainly involved the HH, orbitofrontal areas, and cingulate gyrus. Seizures with automatisms and impaired awareness primarily propagated to mesial temporal lobes. Moreover, independent ictal discharges arising from the mesial temporal lobe were detected in three out of nine patients. Interpretation This study comprehensively reveals intrinsic electrophysiological patterns and epileptogenic networks in vivo, providing new insights into the mechanisms underlying cortical and subcortical epileptogenesis.

Successful surgery on drug-resistant epilepsy patients (DRE) needs precise localization of the seizure onset zone (SOZ). Previous studies analyzing this issue still face limitations, such as inadequate analysis of features, low sensitivity and limited generality. Our study proposed an innovative and effective SOZ localization method based on multiple epileptogenic biomarkers (spike and HFOs), and analysis of single-contact (MEBM-SC) to address the above problems. We extracted contacts epileptic features from signal distributions and signal energy based on machine learning and end-to-end deep learning. Among them, a normalized pathological ripple rate was designed to reduce the disturbance of physiological ripple and enhance the performance of SOZ localization. Then, a feature selection algorithm based on Shapley value and hypothetical testing (ShapHT+) was used to limit interference from irrelevant features. Moreover, an attention mechanism and a focal loss algorithm were used on the classifier to learn significant features and overcome the unbalance of SOZ/nSOZ contacts. Finally, we provided an SOZ prediction and visualization on magnetic resonance imaging (MRI). Ten patients with DRE were selected to verify our method. The experiment performed cross-validation and revealed that MEBM-SC obtains higher sensitivity. Additionally, the spike has better sensitivity while HFOs have better specificity, and the combination of these biomarkers can achieve the best performance. The study confirmed that MEBM-SC can increase the sensitivity and accuracy of SOZ localization and help clinicians to perform a precise and reliable preoperative evaluation based on interictal SEEG.

Abstract Introduction Recently, transcranial alternating current stimulation (tACS), which can interact with ongoing neuronal activity, has emerged as a potentially effective and promising treatment for Alzheimer's disease (AD), and the 40 Hz gamma frequency was suggested as a suitable stimulation frequency for AD. Methods The TRANSFORM‐AD study is a double‐blind, randomized‐controlled trial that will include 40 individuals with mild AD. Eligible patients need to have amyloid β (Aβ) loads examined by Pittsburgh compound B (PiB) positron emission tomography (PET) or decreased Aβ level in cerebrospinal fluid. Participants will be randomized into either a 40 Hz tACS group or a sham stimulation group. Both groups will undergo 30 one‐hour sessions across 3 weeks (21 days). The outcome measures will be assessed at baseline, at the end of the intervention, and 3 months after the first session. The primary outcome is global cognitive function, assessed by the 11‐item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS‐Cog), and the secondary outcomes include changes in other neuropsychological assessments and in PiB‐PET, structural magnetic resonance imaging (MRI), resting electroencephalography (EEG), and simultaneous EEG–functional MRI (EEG‐fMRI) results. Results The trial is currently ongoing, and it is anticipated that recruitment will be completed in June 2021. Discussion This trial will evaluate the efficacy and safety of 40 Hz tACS in patients with AD, and further explore the potential mechanisms by analyzing amyloid deposits using PiB‐PET, brain volume and white matter integrity by structural MRI, and neural activity by EEG and EEG‐fMRI.

Substantial studies of human amygdala function have revealed its importance in processing emotional experience, autonomic regulation, and sensory information; however, the neural substrates and circuitry subserving functions have not been directly mapped at the level of the subnuclei in humans. We provide a useful overview of amygdala functional characterization by using direct electrical stimulation to various amygdala regions in 48 patients with drug-resistant epilepsy undergoing stereoelectroencephalography recordings. This stimulation extends beyond the anticipated emotional, neurovegetative, olfactory, and somatosensory responses to include visual, auditory, and vestibular sensations, which may be explained by the functional connectivity with cortical and subcortical regions due to evoked amygdala-cortical potentials. Among the physiological symptom categories for each subnucleus, the most frequently evoked neurovegetative symptoms were distributed in almost every subnucleus. Laterobasal subnuclei are mainly associated with emotional responses, somatosensory responses, and vestibular sensations. Superficial subnuclei are mainly associated with emotional responses and olfactory and visual hallucinations. Our findings contribute to a better understanding of the functional architecture of the human amygdala at the subnuclei level and as a mechanistic basis for the clinical practice of amygdala stimulation in treating patients with neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]