Abstract Mutations in the SHANK3B gene have been strongly implicated in the pathogenesis of autism spectrum disorder (ASD). The medial prefrontal cortex (mPFC) is integral to emotional processing and social behavior, and its atypical development is closely associated with ASD pathogenesis. However, the electrophysiological characteristics of pyramidal neurons within the mPFC and the mechanisms of their synaptic transmission remain inadequately characterized. In the present study, we conducted whole-cell patch-clamp recordings on mPFC pyramidal neurons in Shank3b knockout mice. We observed significant alterations in the membrane properties and excitability of mPFC pyramidal neurons in Shank3b knockout mice; these were accompanied by reduced inhibitory postsynaptic currents and deficiencies in γ-aminobutyric acid (GABA) release or GABAA receptor transport. Additionally, RNA sequencing analysis of PFC tissue revealed differentially expressed genes in Shank3b knockout mice compared with WT mice, with these genes enriched in synaptic function and calcium channel signaling pathways. These findings are consistent with our ultrastructural observations of a reduced postsynaptic density at excitatory synapses, which may further contribute to the impaired number and morphology of pyramidal neurons in the mPFC. Our research offers new insights into the disruption of PFC circuitry that is caused by Shank3b deficiency and establishes connections between the pathophysiological mechanisms underlying ASD and synaptic structural anomalies, ion channel dysregulation, and excitatory/inhibitory imbalances. Together, these findings highlight the importance of Shank3b-mediated regulation of GABA signaling and modulation of intrinsic excitability as prospective therapeutic targets for ASD.

OBJECTIVE:Although the hippocampus is critical for memory processes, recent studies have suggested that amnesic patients with hippocampal lesions can still acquire some types of memory by distributed learning rather than by massed learning. However, as these studies recruited patients with developmental amnesia, whether lesion onset influenced the spacing effect was unclear. In addition, the extent to which the prefrontal cortex (PFC) supports the spacing effect has not been explored. METHOD:Patients with hippocampal lesions at early onset and late onset and PFC lesions were enrolled. The participants learned face-scene pairs under single learning (i.e., once in 1 day), massed learning (i.e., four times in 1 day), and distributed learning (i.e., four times in 2 days, twice per day). Then, they performed associative recognition tasks 20 min and 1 day later. RESULTS:The results showed that the spacing effect was significantly higher than baseline (d = 2.91) and comparable with the control groups for hippocampal lesions at early onset patients at 1 day. However, the spacing effect was significantly impaired for hippocampal lesions at late onset (d = -1.84) and PFC patients (d = -1.48) when compared with the normal groups. The repetition effect (massed vs. single learning) was significantly impaired for PFC patients at 20 min when compared with the controls (d = -1.15). CONCLUSIONS:These findings clarified the roles of the hippocampus and PFC in distributed learning and repetitive learning and suggest that early-onset hippocampal damage induces a significant reorganization in the human brain to support memory formation and retention. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

PURPOSE:Anti-AMPAR encephalitis is a rare antibody-mediated disorder, and its clinicoradiological profile is incompletely defined. We aimed to characterize the clinical presentation and cerebral metabolic patterns of Chinese adults with anti-AMPAR encephalitis using 18F-FDG PET/CT. METHODS:From August 2016 to August 2022, we retrospectively identified patients from two neurology centers who were positive for anti-AMPAR antibodies in serum and/or cerebrospinal fluid. Demographic data, presenting symptoms, MRI and 18F-FDG PET/CT findings (Discovery Elite, GE Healthcare), treatment regimens, and outcomes were extracted and analyzed. RESULTS:Eight patients (four women) were included; median age was 53 years (range 37-63). Anti-AMPA2R antibodies were detected in seven cases and anti-AMPA1R antibodies in one. Limbic manifestations dominated, particularly cognitive decline and abnormal behavior; severe disease necessitated intensive care support in one patient, who nonetheless achieved a good outcome. Malignancy was documented in three individuals (lung carcinoma, hepatocellular carcinoma, and thymoma), and three harbored additional neural autoantibodies. MRI was abnormal in five patients (62.5%). All five subjects who underwent 18F-FDG PET/CT displayed prefrontal hypometabolism; three also showed posterior cingulate hypometabolism. Focal hypermetabolism was observed in the right temporal lobe (one case) and in the left thalamus (one case). CONCLUSION:Anti-AMPAR encephalitis usually presents as limbic encephalitis and is marked by prefrontal and posterior cingulate hypometabolism on 18F-FDG PET/CT. In some instances, hypermetabolism was observed in the basal ganglia or temporal lobes, possibly reflecting the local blood flow.

BackgroundAutism Spectrum Disorders (ASD) are a collection of neurodevelopmental diseases characterized by poor social interaction and communication, a limited range of interests, and stereotyped behavior. High-functioning autism (HFA) indicates a subgroup of individuals with autism who possess cognitive and/or language skills that are within the average to above-normal range for their age. Transcutaneous auricular vagus nerve stimulation (taVNS) holds promise in children with HFA. However, few studies have used randomized controlled trials to validate the effectiveness of taVNS. Therefore, in this study, we intend to provide a study protocol to examine the therapeutic effects of taVNS in individuals diagnosed with HFA and to investigate the process of brain network remodeling in individuals with ASD using functional imaging techniques to observe alterations in large-scale neural networks.Methods and designWe planned to employ a randomized, double-blind experimental design, including 40 children receiving sham stimulation and 40 children receiving real stimulation. We will assess clinical scales and perform functional imaging examinations before and after the stimulation. Additionally, we will include age- and gender-matched healthy children as controls and conduct functional imaging examinations. We plan first to observe the therapeutic effects of taVNS. Furthermore, we will observe the impact of taVNS stimulation on the brain network.DiscussiontaVNS was a low-risk, easy-to-administer, low-cost, and portable option to modulate the vagus system. taVNS may improve the social performance of HFA. Changes in the network properties of the large-scale brain network may be related to the efficacy of taVNS.Clinical trial registrationhttp://www.chictr.org.cn, identifier ChiCTR2300074035.

BackgroundPantothenate kinase-associated neurodegeneration (PKAN) is a type of inherited metabolic disorder caused by mutation in the PANK2 gene. The metabolic disorder mainly affects the basal ganglia region and eventually manifests as dystonia. For patients of dystonia, their dystonic symptom may progress to life-threatening emergency--status dystonicus.ObjectiveWe described a case of a child with PKAN who had developed status dystonicus and was successfully treated with deep brain stimulation (DBS). Based on this rare condition, we analysed the clinical features of PKAN with status dystonicus and reviewed the reasonable management process of this condition.ConclusionThis case confirmed the rationality of choosing DBS for the treatment of status dystonicus. Meanwhile, we found that children with classic PKAN have a cluster of risk factors for developing status dystonicus. Once children diagnosed with similar neurodegenerative diseases are under status dystonicus, DBS can be active considered because it has showed high control rate of this emergent condition.

Neurogenesis, play a vital role in neuronal plasticity of adult mammalian brains, and its dysregulation is present in the pathophysiology of Parkinson’s disease (PD). While subthalamic nucleus deep brain stimulation (STN-DBS) at various frequencies has been proven effective in alleviating PD symptoms, its influence on neurogenesis remains unclear. This study aimed to investigate the effects of 1-week electrical stimulation at frequencies of 60Hz, 130Hz, and 180Hz on neurogenesis in the subventricular zone (SVZ) of PD rats. A hemiparkinsonian rat model was established using 6-hydroxydopamine and categorized into six groups: control, PD, sham stimulation, 60Hz stimulation, 130Hz stimulation, and 180Hz stimulation. Motor function was assessed using the open field test and rotarod test after one week of STN-DBS at different frequencies. Tyrosine hydroxylase (TH) expression in brain tissue was analyzed via western blot and immunohistochemistry. Immunofluorescence analysis was conducted to evaluate the expression of BrdU/Sox2, BrdU/GFAP, Ki67/GFAP, and BrdU/DCX in bilateral SVZ and the rostral migratory stream (RMS). Our findings revealed that high-frequency STN-DBS improved motor function. Specifically, stimulation at 130Hz increased dopaminergic neuron survival in the PD rat model, while significantly enhancing the proliferation of neural stem cells (NSCs) and neuroblasts in bilateral SVZ. Moreover, this stimulation effectively facilitated the generation of new NSCs in the ipsilateral RMS and triggered the emergence of fresh neuroblasts in bilateral RMS, with notable presence within the lesioned striatum. Conversely, electrical stimulation at 60Hz and 180Hz did not exhibit comparable effects. The observed promotion of neurogenesis in PD rats following STN-DBS provides valuable insights into the mechanistic basis of this therapeutic approach for PD.

Focal cortical dysplasia (FCD) is a major cause of drug‐resistant paediatric epilepsy and is amenable to successful neurosurgical resection. FCD ILAE Type IIb is the most common FCD subtype, and brain somatic mutations affecting the mTOR pathway play a major pathogenic role. The aim of this study was to comprehensively describe the genotype–phenotype association of 20 patients with histopathologically confirmed FCDIIb using next generation sequencing (NGS) of paired blood–brain samples.

Introduction:Hypersalivation has been associated with Rolandic epilepsy and other childhood epilepsy syndromes. However, pure salivatory seizures are a rare type of focal seizure in which ictal hypersalivation is the dominant feature throughout the seizures.Case presentation:We present a case of pure salivatory seizures originating from the right post-central operculum cortex, confirmed by the favorable surgical outcome. We attempt to analyze the symptom from behavioral and neural network perspectives and propose a possible mechanism to generate ictal hypersalivation and pure salivatory seizures.Conclusion:Based on previous reports in the literature and our case, we emphasize the importance of the operculum in patients with ictal hypersalivation, particularly in patients with pure salivatory seizures.

Objective: Although clinical trials have demonstrated that cathodal transcranial direct current stimula-tion (tDCS) is effective for seizure reduction, its long-term efficacy is unknown. This study aimed to deter-mine the long-term effects of repeated cathodal long tDCS sessions on seizure suppression in patients with refractory epilepsy. Methods: Patients were recruited to participate in an extended phase of a previous randomized, double-blind, sham-controlled, three-arm, parallel, multicenter study on tDCS. The patients were divided into an active tDCS group (20 min of tDCS per day) and an intensified tDCS group (2 x 20 min of tDCS per day). Each tDCS session lasted 2 weeks and the patients underwent repeated sessions at intervals of 2 to 6 months. The cathode was placed over the epileptogenic focus with the current intensity set as 2 mA. Seizure frequency reduction from baseline was analyzed using the Wilcoxon signed-rank test for two related samples. A generalized estimating equation model was used to estimate group, time, and inter-action effects. Results: Among the 19 patients who participated in the extended phase, 11 were in the active tDCS group and underwent 2-16 active tDCS sessions, and eight were in the intensified tDCS group and underwent 3-11 intensified tDCS sessions. Seizure reduction was significant from the first to the seventh follow-up, with a median seizure frequency reduction of 41.7%-83.3% (p < 0.05). Compared to the regular tDCS pro-tocol, each intensified tDCS session substantially decreased seizure frequency by 0.3680 (p < 0.05). One patient experienced an increase of 8.5%-232.8% in the total number of seizures during three treatment sessions and follow-ups. Conclusion: Repeated long cathodal tDCS sessions yielded significant and progressive long-term seizure reductions in patients with refractory focal epilepsy. (c) 2022 Published by Elsevier Inc.

Epilepsy affects more than 70 million people in the world. It is characterized by recurrent spontaneous seizures, and it is related to many neurological, cognitive, and psychosocial consequences. Glutamate neurotransmitter dysfunction has essential functions in the pathophysiology of epilepsy. In this work, bibliometric analysis was conducted to explore the trends, frontiers, and hotspots of the global scientific output of glutamate in epilepsy research in the past 20 years. The Science Citation Index Expanded of the Web of Science Core Collection (WoSCC) was searched to obtain information on publications and records published between 2002 and 2021. VOSviewer and CiteSpace were used to conduct bibliometric and visual analyses on the overall distribution of annual output, major countries, active institutions, journals, authors, commonly cited literature, and keywords. The impact and quality of the papers were assessed using the global citation score (GCS). Four thousand eight hundred ninety-one publications were retrieved in total. During the past two decades, the number of publications (Np) associated with glutamate in epilepsy has risen yearly. The United States has published the most papers; its H-index and number of citations are also the highest. The League of European Research Universities (LERU) was the most productive institution. In 2016, the total score of the paper written by Zhang Y was 854, ranking first. The keywords that appear most frequently are "epilepsy," "glutamate," "temporal lobe epilepsy (TLE)," "hippocampus," and "seizures." This study showed that although the publications related to epileptic glutamate fluctuated slightly, the Np increased overall. The United States is a great creator and influential country in this field. The first three authors are Eid, T., Aronica, E., and Smolders, I. "spectrum," "animal model," "inflammation," "mutation," "dysfunction," and "prefrontal cortex" are increasing research hotspots. By recognizing the most critical indicators (researchers, countries, research institutes, and journals of glutamate release in epilepsy research), the research hotspot of glutamate in epilepsy could help countries, scholars, and policymakers in this field enhance their understanding of the role of glutamate in epilepsy and make decisions.

• Ictal embarrassment (IE) and ictal appeasement behavior (IAB) are rare and unusual. • IAB following IE complies with the natural embarrassment process. • The pregenual anterior cingulate cortex plays a crucial role in IE and IAB. • The network of IE and IAB overlaps with natural embarrassment processing network.

Objectives: To compare the levels of plasma glutamate and glutamine in drug-resistant or drug-responsive symptomatic focal epilepsy. Dysfunctional glutamate neurotransmission plays an essential role in epilepsy pathophysiology. Methods: This cross-sectional study included 80 drug-resistant and 42 drug-responsive symptomatic focal epileptic patients and 132 healthy controls from June 2017 to February 2018. Plasma glutamate and glutamine levels were assessed via high-performance liquid chromatography. Results: Patients with drug-resistant symptomatic focal epilepsy had significantly higher plasma glutamate levels than healthy controls, whereas those with the drug-responsive disease had higher plasma glutamine levels than healthy controls. These results indicate that plasma glutamate and glutamine levels can discriminate patients with drug-resistant and drug-responsive symptomatic focal epilepsy from control individuals with the areas under the curve values of 0.931 and 0.72, respectively. Conclusion: Elevated plasma glutamate levels are associated with drug-resistant symptomatic focal epilepsy and may aid the diagnosis of drug-resistant symptomatic focal epilepsy.

Purpose: Delineation of subtle lesions in magnetic resonance imaging (MRI)-negative patients is of great importance in preoperative epilepsy evaluation. The aim of our study was to explore the diagnostic value of the novel fluid and white matter suppression (FLAWS) sequence in comparison with a voxel-based MRI postprocessing morphometric analysis program (MAP) in a consecutive cohort of non-lesional patients. Methods: Surgical candidates with a negative finding on an official neuroradiology report were enrolled. High-resolution FLAWS image and MAP maps generated based on high-resolution three-dimensional (3D) T1 image were visually inspected for each patient. The findings of FLAWS or MAP-positive (FLAWS/MAP+) regions were compared with the surgical resection cavity in correlation with surgical outcome and pathology. Results: Forty-five patients were enrolled; the pathological examination revealed focal cortical dysplasia (FCD) in 32 patients and other findings in 13 patients. The positive rate, sensitivity, and specificity were 48.9%, 0.43, and 0.87, respectively, for FLAWS and 64.4%, 0.57, and 0.8, respectively, for MAP. Concordance between surgical resection and FLAWS+ or MAP+ regions was significantly associated with a seizure-free outcome (FLAWS: p = 0.002; MAP: p = 0.0003). A positive finding in FLAWS and MAP together with abnormalities in the same gyrus (FLAWS–MAP gyral+) was detected in 31.1% of patients. FLAWS+ only and MAP+ only were found in 7 (15.5%) and 14 (31.1%) patients, respectively. Conclusions: FLAWS showed a promising value for identifying subtle epileptogenic lesions and can be used as a complement to current MAP in patients with MRI-negative epilepsy.

Objective: Diagnostic challenges exist in the presurgical evaluation of patients with magnetic resonance imaging (MRI) negative cingulate epilepsy (CE) because of the heterogeneity in clinical semiology and lack of localizing findings on scalp electroencephalographic (EEG) recordings. We aimed to examine the neuroimaging characteristics in a consecutive cohort of patients with MRI-negative CE with a focus on two image post-processing methods, including the MRI post-processing morphometric analysis program (MAP) and F-18-fluorodeoxyglucose-positron emission tomography-MRI (PET/MRI) co-registration. Methods: Included in this retrospective study were patients with MRI-negative CE who met the following criteria: negative on preoperative MRI, invasive EEG (iEEG) confirmed cingulate gyrus-onset seizures, surgical resection of the cingulate gyrus with/without adjacent cortex, and seizure-free for more than 12 months. MAP and PET/MRI co-registration were performed and investigated by comparison to ictal intracranial EEG findings. Other characteristics obtained from scalp EEG, magnetoencephalography (MEG), iEEG, and pathological study were also reported. Results: Ten patients were included, of which eight were diagnosed with anterior CE, one with middle CE, and one with posterior CE. The semiology included fear, embarrassment, vocalization, ictal pouting, asymmetric tonic posture, hypermotor, and automatism. Scalp EEG revealed unilateral or bilateral frontal-temporal onset. MEG localized the dipoles correctly in one patient (1/10). MAP detected subtle abnormalities in regions concordant with iEEG onset in seven patients (7/10) while PET/MRI co-registration revealed focal concordant hypometabolism in five patients (5/10). Combining MAP with PET/MRI co-registration improved the detection rate to 90 % in this cohort. The pathology was focal cortical dysplasia (FCD), including FCD type IIA in three, type IIB in three, and type I in four. Conclusion: MAP and PET/MRI co-registration show promising results in identifying subtle FCD abnormalities in CE with negative results on conventional MRI, which can be otherwise challenging. More importantly, a combination of MRI post-processing and PET/MRI co-registration can greatly improve the identification of epileptic abnormalities, which can be used as surgical target. MAP and PET/MRI co-registration should be incorporated into the routine presurgical evaluation.