Sambucus williamsii Hance: A comprehensive review of traditional uses, processing specifications, botany, phytochemistry, pharmacology, toxicology, and pharmacokinetics.

OBJECTIVE: Sambucus williamsii Hance, belonging to the Sambucus L. family (Viburnaceae), possesses medicinal properties in its roots, stems, leaves, flowers, and fruits. It is recognized for its ability to facilitate bone reunion, enhance blood circulation, remove stasis, and dispel wind and dampness. This traditional Chinese medicine holds significant potential for development and practical use. Hence, this paper offers an in-depth review of S. williamsii, covering traditional uses, processing guidelines, botany, phytochemistry, pharmacology, toxicology, and pharmacokinetics, aiming to serve as a reference for its further development and utilization. MATERIALS AND METHODS: Information for this study was gathered from various books, bibliographic databases, and literature sources such as Google Scholar, Web of Science, PubMed, Chinese National Knowledge Infrastructure, Baidu Scholar, VIP Database for Chinese Technical Periodicals, and Wanfang Data. RESULTS: Phytochemical investigations have identified approximately 238 compounds within the root bark, stem branches, leaves, and fruits of S. williamsii. These compounds encompass flavonoids, sugars, glycosides, terpenoids, phenylpropanoids, alkaloids, phenols, phenolic glycosides, and other chemical constituents, with phenylpropanoids being the most prevalent. S. williamsii exhibits a wide range of pharmacological effects, particularly in promoting osteogenesis and fracture healing. CONCLUSION: This comprehensive review delves into the traditional uses, processing guidelines, botany, phytochemistry, pharmacology, toxicology, and pharmacokinetics of S. williamsii. It provides valuable insights into this plant, which will prove beneficial for future research involving S. williamsii.

Polygonum ciliinerve (Nakai) Ohwi: a review of its botany, traditional uses, phytochemistry, pharmacology, pharmacokinetics and toxicology.

Polygonum ciliinerve (Nakai) Ohwi is a perennial twining vine plant from the Polygonaceae family, which is a Chinese herbal medicine with great value for development and utilization. The purpose of this paper is to provide a systematic review of the botany, traditional uses, phytochemistry, pharmacology, pharmacokinetics, and toxicology of Polygonum ciliinerve (Nakai) Ohwi, as well as an outlook on the future research directions and development prospects of the plant. Data on Polygonum ciliinerve (Nakai) Ohwi were obtained from different databases, including China National Knowledge Infrastructure, Baidu Academic, Wanfang Database, Google Academic, PubMed, Web of Science, SpringerLink, Wiley; books; standards; and Ph.D. and MSc theses. So far, 86 compounds have been identified from Polygonum ciliinerve (Nakai) Ohwi, including anthraquinones, stilbenes, flavonoids, tannins, chromogenic ketones, organic acids and esters, lignans, isobenzofurans, alkaloids, naphthols, and others. Studies have found that Polygonum ciliinerve (Nakai) Ohwi has a wide range of pharmacological effects, including antiviral, antibacterial, anti-inflammatory and analgesic, antitumor, immunomodulatory, hypoglycemic, and antioxidant effects. Clinically, Polygonum ciliinerve (Nakai) Ohwi is very effective in the treatment of gastritis and chronic gastritis. Based on its traditional use, chemical composition, and pharmacological activity, Polygonum ciliinerve (Nakai) Ohwi is a promising source of natural medicine in drug development.

Quality markers of Guchang Zhixie pills based on multicomponent qualitative and quantitative analysis combined with network pharmacology and chemometric analysis.

Traditional Chinese medicine Guchang Zhixie pills(GCZX) is one of the famous varieties of "Qin medicine" that has been extensively applied to treating irritable bowel syndrome(IBS). However, despite the acknowledged clinical advantages of GCZX there are significant constraints on its quality control and evaluation. The present study utilized UHPLC-Q-Exactive-Orbitrap-MS to analyze the chemical composition of GCZX. Additionally, network pharmacology approaches were utilized to explore the underlying mechanism by which blood components exert therapeutic effects in the treatment of IBS. Furthermore, the GCZX samples were evaluated for their quality on the basis of the qualitative results obtained from 25 batches of GCZX samples using fingerprinting; subsequently, multivariate statistical analysis methods were employed for further analysis. The results indicated the presence of 198 individual components. Among them, 17 prototype compounds were detected in the serum of rats that were administered with GCZX. The potential therapeutic mechanism of GCZX in the treatment of IBS may be associated with the modulation of the neurological system, the immunological system, and the inflammatory response. Moreover, a total of seven prominent peaks were identified after fingerprint analysis. The range of fingerprint similarity among the 25 batches of samples varied from 0.843 to 1.000. The application of chemometrics analysis successfully facilitated the categorical classification of 25 batches of GCZX into three distinct groups. Seven components hold significant importance and should be duly considered during the quality control process of GCZX. The present study can establish the Q-Markers of GCZX for IBS, thereby providing a foundation for investigating the theoretical underpinnings and elucidating the mechanisms underlying the therapeutic effects of GCZX in the treatment of IBS.

Automatic auditory processing features in distinct subtypes of patients at clinical high risk for psychosis: Forecasting remission with mismatch negativity.

Individuals at clinical high risk (CHR) for psychosis exhibit a compromised mismatch negativity (MMN) response, which indicates dysfunction of pre-attentive deviance processing. Event-related potential and time-frequency (TF) information, in combination with clinical and cognitive profiles, may provide insight into the pathophysiology and psychopathology of the CHR stage and predict the prognosis of CHR individuals. A total of 92 individuals with CHR were recruited and followed up regularly for up to 3 years. Individuals with CHR were classified into three clinical subtypes demonstrated previously, specifically 28 from Cluster 1 (characterized by extensive negative symptoms and cognitive deficits), 31 from Cluster 2 (characterized by thought and behavioral disorganization, with moderate cognitive impairment), and 33 from Cluster 3 (characterized by the mildest symptoms and cognitive deficits). Auditory MMN to frequency and duration deviants was assessed. The event-related spectral perturbation (ERSP) and inter-trial coherence (ITC) were acquired using TF analysis. Predictive indices for remission were identified using logistic regression analyses. As expected, reduced frequency MMN (fMMN) and duration MMN (dMMN) responses were noted in Cluster 1 relative to the other two clusters. In the TF analysis, Cluster 1 showed decreased theta and alpha ITC in response to deviant stimuli. The regression analyses revealed that dMMN latency and alpha ERSP to duration deviants, theta ITC to frequency deviants and alpha ERSP to frequency deviants, and fMMN latency were significant MMN predictors of remission for the three clusters. MMN variables outperformed behavioral variables in predicting remission of Clusters 1 and 2. Our findings indicate relatively disrupted automatic auditory processing in a certain CHR subtype and a close affinity between these electrophysiological indexes and clinical profiles within different clusters. Furthermore, MMN indexes may serve as predictors of subsequent remission from the CHR state. These findings suggest that the auditory MMN response is a potential neurophysiological marker for distinct clinical subtypes of CHR.

Characterizing thalamic and basal ganglia nuclei in medically intractable focal epilepsy by MR fingerprinting.

OBJECTIVES: Magnetic resonance fingerprinting (MRF) is a novel, quantitative, and noninvasive technique to measure brain tissue properties. We aim to use MRF for characterizing normal-appearing thalamic and basal ganglia nuclei in the epileptic brain. METHODS: A three-dimensional (3D) MRF protocol (1 mm3 isotropic resolution) was acquired from 48 patients with unilateral medically intractable focal epilepsy and 39 healthy controls (HCs). Whole-brain T1 and T2 maps (containing T1 and T2 relaxation times) were reconstructed for each subject. Ten subcortical nuclei in the thalamus and basal ganglia were segmented as regions of interest (ROIs), within which the mean T1 and T2 values, as well as their coefficient of variation (CV) were compared between the patients and HCs at the group level. Subgroup and correlation analyses were performed to examine the relationship between significant MRF measures and various clinical characteristics. Using significantly abnormal MRF measures from the group-level analyses, support vector machine (SVM) and logistic regression machine learning models were built and tested with 5-fold and 10-fold cross-validations, to separate patients from HCs, and to separate patients with left-sided and right-sided epilepsy, at the individual level. RESULTS: MRF revealed increased T1 mean value in the ipsilateral thalamus and nucleus accumbens; increased T1 CV in the bilateral thalamus, bilateral pallidum, and ipsilateral caudate; and increased T2 CV in the ipsilateral thalamus in patients compared to HCs (p < .05, false discovery rate [FDR] corrected). The SVM classifier produced 78.2% average accuracy to separate individual patients from HCs, with an area under the curve (AUC) of 0.83. The logistic regression classifier produced 67.4% average accuracy to separate patients with left-sided and right-sided epilepsy, with an AUC of 0.72. SIGNIFICANCE: MRF revealed bilateral tissue-property changes in the normal-appearing thalamus and basal ganglia, with ipsilateral predominance and thalamic preference, suggesting subcortical involvement/impairment in patients with medically intractable focal epilepsy. The individual-level performance of the MRF-based machine-learning models suggests potential opportunities for predicting lateralization.

Opsonized nanoparticles target and regulate macrophage polarization for osteoarthritis therapy: A trapping strategy.

Osteoarthritis (OA) is a chronic disease caused by joint inflammation. Its occurrence and development depend on a continuous inflammation environment. The activated M1 macrophages play a critical role in the inflammatory response of OA. Regulating the pro-inflammatory M1 to anti-inflammatory M2 macrophages in the OA articular cavity could be a rational strategy for OA treatment. It has been acknowledged that activated macrophages could proactively capture opsonized nanoparticles in the bloodstream and then accumulate into the reticuloendothelial system (RES) organs. Based on this fact, a trapping strategy is proposed, which transforms a normal nanoparticle into an opsonized attractant to target and regulate macrophage polarization. In this study, the opsonized nanoparticle (IgG/Bb@BRPL) had several key features, including an immunoglobulin IgG (the opsonized layer), an anti-inflammatory agent berberine (Bb), and an oxidative stress-responsive bilirubin grafted polylysine biomaterial (BR-PLL) for drug loading (the inner nanocore). In vitro studies confirmed that IgG/Bb@BRPL prefer to be phagocytosed by M1 macrophage, not M0. And the internalized IgG/Bb@BRPL effectively promoted macrophage polarization toward the M2 phenotype and protected nearby chondrocytes. In vivo studies suggested that IgG/Bb@BRPL significantly enhanced therapeutic outcomes by suppressing inflammation and promoting cartilage repair while not prolonging the retention period compared to non-opsonized counterparts. This proof-of-concept study provided a novel opsonization trapping strategy for OA drug delivery and treatment.

Test-retest reliability of mismatch negativity and gamma-band auditory steady-state response in patients with schizophrenia.

Patients with schizophrenia show widespread impairments in clinical, cognitive and psychosocial functioning. Mismatch negativity (MMN) and gamma-band auditory steady-state response (ASSR) are two neurophysiological biomarkers widely used to inform diagnosis, guide treatments and track response to interventions in schizophrenia. However, evidence for the test-retest reliability of these indices across multiple sessions in schizophrenia patients remains scarce. In the present study, we included 34 schizophrenia patients (17 females) and obtained duration MMN (dMMN), frequency MMN (fMMN) and 40-Hz ASSR data across three sessions with intervals of 2 days. Event-related spectrum perturbation (ERSP) and inter-trial coherence (ITC) were calculated following Morlet wavelet time-frequency decomposition of ASSR data. The intra-class correlation coefficient (ICC) was used to quantify the reliability of MMN and ASSR measures among the three sessions. We found fair to good reliability for dMMN amplitudes but poor reliability for fMMN amplitudes. For the ASSR measures, ERSP showed good to excellent test-retest reliability while ITC had poor to fair test-retest reliability. In addition, the average of dMMN amplitudes was significantly correlated with that of ERSP across the three sessions. In summary, we established for the first time the short-term test-retest reliability of MMN and ASSR measures in schizophrenia patients. These findings demonstrate that dMMN amplitudes and ERSP of ASSR are reliable indices which may be used in longitudinal observational studies.

Temporal and time-frequency features of auditory oddball response in distinct subtypes of patients at clinical high risk for psychosis.

Individuals at clinical high risk (CHR) for psychosis exhibit a reduced P300 oddball response, which indicates deficits in attention and working memory processes. Previous studies have mainly researched these responses in the temporal domain; hence, non-phase-locked or induced neural activities may have been ignored. Event-related potential (ERP) and time-frequency (TF) information, combined with clinical and cognitive profiles, may provide an insight into the pathophysiology and psychopathology of the CHR stage. The 104 CHR individuals who completed cognitive assessments and ERP tests were recruited and followed up between 2016 and 2018. Individuals with CHR were classified by three clinical subtypes demonstrated before, specifically 32 from Cluster-1 (characterized by extensive negative symptoms and cognitive deficits, at the highest risk for conversion to psychosis), 34 from Cluster-2 (characterized by thought and behavioral disorganization, with moderate cognitive impairment), and 38 from Cluster-3 (characterized by the mildest symptoms and cognitive deficits). Electroencephalograms were recorded during the auditory oddball paradigm. The P300 ERPs were analyzed in the temporal domain. The event-related spectral perturbation (ERSP) and inter-trial coherence (ITC) were acquired by TF analysis. A reduced P300 response to target tones was noted in Cluster-1 relative to the other two clusters. Moreover, the P300 amplitude of Cluster-1 was associated with speed of processing (SoP) scores. Furthermore, the P300 amplitude of Cluster-3 was significantly correlated with verbal and visual learning scores. In the TF analysis, decreased delta ERSP and ITC were observed in Cluster-1; delta ITC was associated with SoP scores in Cluster-3. The results indicate relatively disrupted oddball responses in a certain CHR subtype and a close affinity between these electrophysiological indexes and attention, working memory, and declarative memory within different CHR clusters. These findings suggest that the auditory oddball response is a potential neurophysiological marker for distinct clinical subtypes of CHR.

The lateralization and reliability of spatial mismatch negativity elicited by auditory deviants with virtual spatial location.

Mismatch negativity (MMN) is an intensively studied event-related potential component that reflects pre-attentive auditory processing. Existing spatial MMN (sMMN) studies usually use loud-speakers in different locations or deliver sound with binaural localization cues through earphones to elicit MMN, which either was practically complicated or sounded unnatural to the subjects. In the present study, we generated head related transfer function (HRTF)-based spatial sounds and verified that the HRTF-based sounds retained the left and the right spatial localization cues. We further used them as deviants to elicit sMMN with conventional oddball paradigm. Results showed that sMMN was successfully elicited by the HRTF-based deviants in 18 of 21 healthy subjects in two separate sessions. Furthermore, the left deviants elicited higher sMMN amplitudes in the right hemisphere compared to the left hemisphere, while the right deviants elicited sMMN with similar amplitudes in both hemispheres, which supports a combination of contralateral and right-hemispheric dominance in spatial auditory information processing. In addition, the sMMN in response to the right deviants showed good test-retest reliability, while the sMMN in response to the left deviants had weak test-retest reliability. These findings implicate that HRTF-based sMMN could be a robust paradigm to investigate spatial localization and discrimination abilities.

Preparative separation of high-purity trans- and cis-ferulic acid from wheat bran by pH-zone-refining counter-current chromatography.

Ferulic acid stereoisomers are the most abundant phenolic acids in cereal bran. However, it is challenging to separate them because of the similar structures and properties. In this study, a preparative separation method of ferulic acid stereoisomers from the crude extract of wheat bran was successfully developed. The method contained a two-step separation, the traditional counter-current chromatography (CCC, hexane: ethyl acetate: methanol: water = 2:5:2:4) was followed with a pH-zone-refining CCC (hexane: ethyl acetate: acetonitrile: water = 2:5:2:2, 10 mmol L-1 trifluoroacetic acid in organic stationary phase and 10 mmol L-1 ammonia in aqueous mobile phase). Trans-ferulic acid and cis-ferulic acid with HPLC high purity over than 99% and 98% can be yielded in large-scale separation. Moreover, it is found that different proton affinity, deprotonation ability and interaction site of hydrogen bond result in distinct partition behavior of stereoisomers, which is illustrated by quantitative analysis of molecular surface. This contributes to our in-depth understanding of the separation mechanism toward pH-zone refining CCC. The developed method can be applied in the exploitation of ferulic acids and related phenolic acids from other resources.

Altered functional connectivity of the thalamus induced by modified electroconvulsive therapy for schizophrenia.

BACKGROUND: Electroconvulsive therapy (ECT) has been shown to be effective in schizophrenia (SZ), particularly in drug-refractory cases or when rapid symptom relief is needed. However, its precise mechanisms of action remain largely unclear. To clarify the mechanisms underlying modified electroconvulsive therapy (mECT) for SZ, we conducted a longitudinal cohort study evaluating functional connectivity of the thalamus before and after mECT treatment using sub-regions of thalamus as regions of interest (ROIs). METHODS: Twenty-one SZ individuals taking only antipsychotics (DSZ group) for 4 weeks and 21 SZ patients receiving a regular course of mECT combining with antipsychotics (MSZ group) were observed in parallel. All patients underwent magnetic resonance imaging scans at baseline (t1) and follow-up (t2, ~4 weeks) time points. Data were compared to a matched healthy control group (HC group) consisting of 23 persons who were only scanned at baseline. Group differences in changes of thalamic functional connectivity between two SZ groups over time, as well as in functional connectivity among two SZ groups and HC group were assessed. RESULTS: Significant interaction of group by time was found in functional connectivity of the right thalamus to right putamen during the course of about 4-week treatment. Post-hoc analysis showed a significantly enhanced functional connectivity of the right thalamus to right putamen in the MSZ group contrasting to the DSZ group. In addition, a decreased and an increased functional connectivity of the thalamus to sensory cortex were observed within the MSZ and DSZ group after 4-week treatment trial, respectively. CONCLUSION: Our findings suggest that changes in functional connectivity of the thalamus may be associated with the brain mechanisms of mECT for schizophrenia.

Aberrant resting-state functional connectivity of salience network in first-episode schizophrenia.

The disruption of salience network (SN) has been consistently found in patients with schizophrenia and thought to give rise to specific symptoms. However, the functional dysconnectivity pattern of SN remains unclear in first-episode schizophrenia (FES). Sixty-five patients with FES and sixty-six health controls (HC) were enrolled in this study and underwent resting-state functional magnetic resonance imaging (rs-fMRI). The eleven regions of interest (ROIs) within SN were derived from the peaks of the group independent component analysis (gICA). Seed-based whole-brain functional connectivity (FC) analyses were performed with all SN ROIs as the seeds. Both hyper- and hypo-connectivity of SN were found in the FES. Specifically, the increased FC mainly existed between the SN and cortico-cerebellar sub-circuit and prefrontal cortex, while the reduced FC mainly existed within cortico-striatal-thalamic-cortical (CSTC) sub-circuit. Our findings suggest that FES is associated with pronounced dysregulation of SN, characterized prominently by hyperconnectivity of SN-prefrontal cortex and cerebellum, as well as hypoconnectivity of CSTC sub-circuit of the SN.

Functional characterization of ABCC9 variants identified in sudden unexpected natural death.

BACKGROUND: Genetic variation in ion channel genes ('channelopathies') are often associated with inherited arrhythmias and sudden death. Genetic testing ('molecular autopsies') of channelopathy genes can be used to assist in determining the likely causes of sudden unexpected death. However, different in silico approaches can yield conflicting pathogenicity predictions and assessing their impact on ion channel function can assist in this regard. METHODS AND RESULTS: We performed genetic testing of cases of sudden expected death in the New York City metropolitan area and found four rare or novel variants in ABCC9, which codes for the regulatory SUR2 subunit of KATP channels. All were missense variants, causing amino acid changes in the protein. Three of the variants (A355S, M941V, and K1379Q) were in cases of infants less than six-months old and one (H1305Y) was in an adult. The predicted pathogenicities of the variants were conflicting. We have introduced these variants into a human SUR2A cDNA, which we coexpressed with the Kir6.2 pore-forming subunit in HEK-293 cells and subjected to patch clamp and biochemical assays. Each of the four variants led to gain-of-function phenotypes. The A355S and M941V variants increased in the overall patch current. The sensitivity of the KATP channels to inhibitory 'cytosolic' ATP was repressed for the M941V, H1305Y and K1379Q variants. None of the variants had any effect on the unitary KATP channel current or the surface expression of KATP channels, as determined with biotinylation assays, suggesting that all of the variants led to an enhanced open state. CONCLUSIONS: All four variants caused a gain-of-function phenotype. Given the expression of SUR2-containing KATP channels in the heart and specialized cardiac conduction, vascular smooth muscle and respiratory neurons, it is conceivable that electrical silencing of these cells may contribute to the vulnerability element, which is a component of the triple risk model of sudden explained death in infants. The gain-of-function phenotype of these ABCC9 variants should be considered when assessing their potential pathogenicity.

Abnormal auditory-evoked gamma band oscillations in first-episode schizophrenia during both eye open and eye close states.

Abnormal auditory steady state response (ASSR) is a typical finding among schizophrenia patients, which is thought to directly reflect deficient gamma band oscillations in the brain. However, whether these ASSR alterations are state dependent, e.g. during eye-open or eye-closed conditions, has not yet been carefully elucidated in schizophrenia. Our study aimed to explore whether the abnormality of ASSR in patients with first-episode schizophrenia (FEP) is altered under eye-open (EO) and eye-closed (EC) states. ASSR was elicited using 40 Hz click trains under EO and EC states. Twenty-eight healthy control subjects (HC) and thirty-three FEP individuals, 17 of whom were medication-naïve, were recruited. The event-related spectrum perturbation (ERSP) and intertrial coherence (ITC) in response to 40 Hz click sounds were quantified. Compared to HC group, FEP group showed a lower ITC and ERSP during EO state, as well as a decreased ITC during EC state. Our results suggest that abnormalities in gamma band oscillations among first-episode schizophrenia patients are present under both eye open and eye close states. Although differences in gamma band oscillations between EO and EC states within the FEP group were not observed, exploratory results suggest that state-sensitivity may be contingent on medication use.

Periconceptional folic acid supplementation among pregnant women with epilepsy in a developing country: a retroprospective survey in China.

OBJECTIVE: The aims of this study were to investigate the implementation of guidelines on periconceptional folic acid supplementation among pregnant women with epilepsy (WWE) in China and to identify its potential correlations with selected sociodemographic and clinical factors. METHODS: A detailed investigation was conducted in China using a structured questionnaire from December 2013 to May 2014. Data on the awareness and use of folic acid supplementation, as well as sociodemographic and clinical characteristics, were collected from 153 pregnant WWE. Descriptive analysis, followed by univariate and multivariate logistic regression analyses, was applied to the data from this survey. RESULTS: Among the enrolled subjects, 67.3% became pregnant after the promulgation of the relevant guidelines. Only 26.2% of them knew the exact effects of folic acid, and 73.8% had taken folic acid at some point during periconception. In addition, the folic acid intake of most of these women (67.1%) did not exceed that of the average pregnant woman. The prevalence of folic acid supplementation for pregnant WWE three months before pregnancy was only 15.5%. There has been almost no improvement in the level of additional awareness and use of folic acid supplementation for WWE since the relevant guidelines were established in China. Pregnant WWE with higher education levels, those with a planned pregnancy, or those who live in urban areas were more likely to know about and implement folic acid supplementation during periconception. Moreover, pregnant WWE with a planned pregnancy or those living in cities seemed to have a higher folic acid intake and started folic acid supplementation earlier before conception. CONCLUSION: The extent of awareness and use of folic acid supplementation in pregnant WWE remains low in China. More efforts are needed to promote periconceptional folic acid supplementation for WWE, especially those with low education levels and those who live in rural areas. Planned pregnancy should be encouraged for WWE.

A resting-state functional connectivity study in patients at high risk for sudden unexpected death in epilepsy.

OBJECTIVE: Seizure-related respiratory and cardiac dysfunctions were once thought to be the direct cause of sudden unexpected death in epilepsy (SUDEP), but both may be secondary to postictal cerebral inhibition. An important issue that has not been explored to date is the neural network basis of cerebral inhibition. Our aim was to investigate the features of neural networks in patients at high risk for SUDEP using a blood oxygen level-dependent (BOLD) resting-state functional connectivity (FC) approach. SUBJECTS AND METHODS: Resting-state functional magnetic resonance imaging (Rs-fMRI) data were recorded from 13 patients at high risk for SUDEP and 12 patients at low risk for SUDEP. Thirteen cerebral regions that are closely related to cardiorespiratory activity were selected as regions of interest (ROIs). The ROI-wise resting-state FC analysis was compared between the two groups. RESULTS: Compared with patients at low risk for SUDEP, patients at high risk exhibited significant reductions in the resting-state FC between the pons and the right thalamus, the midbrain and the right thalamus, the bilateral anterior cingulate cortex (ACC) and the right thalamus, and the left thalamus and the right thalamus. CONCLUSIONS: This investigation is the first to use neuroimaging methods in research on the mechanism of SUDEP and demonstrates the abnormally decreased resting-state FC in the ACC-thalamus-brainstem circuit in patients at high risk for SUDEP. These findings highlight the need to understand the fundamental neural network dysfunction in SUDEP, which may fill the missing link between seizure-related cardiorespiratory dysfunction and SUDEP, and provide a promising neuroimaging biomarker for risk prediction of SUDEP.