Langzi Tan’s research while affiliated with Central South University and other places

Aims The gradient captures the continuous transitions in connectivity, representing an intrinsic hierarchical architecture of the brain. Previous works hinted at the dynamics of the gradient but did not verify them. Cognitive impairment is a common comorbidity of temporal lobe epilepsy (TLE). Gradient techniques provide a framework that could promote the understanding of the neural correlations of cognitive decline. Methods Thirty patients with TLE and hippocampal sclerosis and 29 matched healthy controls (HC) were investigated with verbal fluency task‐based functional MRI and gradient techniques. The correlation between task‐based activation/deactivation and healthy gradients, task‐based gradients, and dynamic features calculated with sliding window approaches was compared between HC and TLE. Results The allegiance in the real data of HC and TLE was more widespread compared to static null models. TLE has lower dynamic recruitment of gradient, atypical activation‐gradient correlation, and contracted principal gradient. Correlation analysis proved that the reconfiguration of principal gradient did not drive the reorganization of activation. The atypical activation pattern and impaired recruitment were correlated with cognition scales in TLE. Discussion The principal gradient is dynamic. TLE disrupted activation/deactivation patterns, the principal gradient, and the dynamics of the gradient, which were correlated with cognitive decline.

To test a Chinese character version of the phonemic verbal fluency task in patients with temporal lobe epilepsy (TLE) and assess the verbal fluency deficiency pattern in TLE with and without hippocampal sclerosis, a cross-sectional study was conducted including 30 patients with TLE and hippocampal sclerosis (TLE-HS), 28 patients with TLE and without hippocampal sclerosis (TLE-NHS), and 29 demographically matched healthy controls (HC). Both sexes were enrolled. Participants finished a Chinese character verbal fluency (VFC) task during functional MRI. The activation/deactivation maps, functional connectivity, degree centrality, and community features of the left frontal and temporal regions were compared. A neural network classification model was applied to differentiate TLE-HS and TLE-NHS using functional statistics. The VFC scores were correlated with semantic fluency in HC while correlated with phonemic fluency in TLE-NHS. Activation and deactivation deficiency was observed in TLE-HS and TLE-NHS ( p < 0.001, k ≥ 10). Functional connectivity, degree centrality, and community features of anterior inferior temporal gyri were impaired in TLE-HS and retained or even enhanced in TLE-NHS ( p < 0.05, FDR-corrected). The functional connectivity was correlated with phonemic fluency ( p < 0.05, FDR-corrected). The neural network classification reached an area under the curve of 0.90 in diagnosing hippocampal sclerosis. The VFC task is a Chinese phonemic verbal fluency task suitable for clinical application in TLE. During the VFC task, functional connectivity of phonemic circuits was impaired in TLE-HS and was enhanced in TLE-NHS, representing a compensative phonemic searching strategy applied by patients with TLE-NHS.

Background Cerebellar functional alterations are common in patients with mesial temporal lobe epilepsy (MTLE), which contribute to cognitive decline. This study aimed to deepen our knowledge of cerebellar functional alterations in patients with MTLE. Methods In this study, participants were recruited from an ongoing prospective cohort of 13 patients with left TLE (LTLE), 17 patients with right TLE (RTLE), and 30 healthy controls (HCs). Functional magnetic resonance imaging data were collected during a Chinese verbal fluency task. Group independent component (IC) analysis (group ICA) was applied to segment the cerebellum into six functionally separated networks. Functional connectivity was compared among cerebellar networks, cerebellar activation maps, and the centrality parameters of cerebellar regions. For cerebellar functional profiles with significant differences, we calculated their correlation with clinical features and neuropsychological scores. Result Compared to HCs and patients with LTLE, patients with RTLE had higher cerebellar functional connectivity between the default mode network (DMN) and the oculomotor network and lower cerebellar functional connectivity from the frontoparietal network (FPN) to the dorsal attention network (DAN) (p < 0.05, false discovery rate- (FDR-) corrected). Cerebellar degree centrality (DC) of the right lobule III was significantly higher in patients with LTLE compared to HC and patients with RTLE (p < 0.05, FDR-corrected). Higher cerebellar functional connectivity between the DMN and the oculomotor network, as well as lower cerebellar degree centrality of the right lobule III, was correlated with worse information test performance. Conclusion Cerebellar functional profiles were altered in MTLE and correlated with long-term memory in patients.

Aim Temporal lobe epilepsy is a neurological network disease in which genetics played a greater role than previously appreciated. This study aimed to explore shared functional network abnormalities in patients with sporadic temporal lobe epilepsy and their unaffected siblings. Methods Fifty‐eight patients with sporadic temporal lobe epilepsy, 13 unaffected siblings, and 30 healthy controls participated in this cross‐sectional study. We examined the task‐based whole‐brain functional network topology and the effective functional connectivity between networks identified by group‐independent component analysis. Results We observed increased global efficiency, decreased clustering coefficiency, and decreased small‐worldness in patients and siblings (p < 0.05, false discovery rate‐corrected). The effective network connectivity from the ventral attention network to the limbic system was impaired (p < 0.001, false discovery rate‐corrected). These features had higher prevalence in unaffected siblings than in normal population and was not correlated with disease burden. In addition, topological abnormalities had a high intraclass correlation between patients and their siblings. Conclusion Patients with temporal lobe epilepsy and their unaffected siblings showed shared topological functional disturbance and the effective functional network connectivity impairment. These abnormalities may contribute to the pathogenesis that promotes the susceptibility of seizures and language decline in temporal lobe epilepsy.

Objective This work was undertaken to study the functional connectivity differences between non‐seizure‐free and seizure‐free patients with temporal lobe epilepsy (TLE) and to identify imaging predictors for drug responsiveness in TLE. Methods In this prospective study, 52 patients with TLE who presented undetermined antiseizure medication responsiveness and 55 demographically matched healthy controls were sequentially recruited from Xiangya Hospital. Functional magnetic resonance imaging data were acquired during a Chinese version of the verbal fluency task. The patients were followed up until the outcome could be classified. The subject groups were compared in terms of activation profile, task‐residual functional connectivity (trFC), and generalized psychophysiological interaction (gPPI) analyses. Moreover, we extracted imaging characteristics for logistic regression and receiver operating characteristic evaluation. Results With a mean follow‐up of 1.1 years, we identified 27 non‐seizure‐free patients and 19 seizure‐free patients in the final analyses. The Chinese character verbal fluency task successfully activated the language network and cognitive control network (CCN) and deactivated the default mode network (DMN). In the non‐seizure‐freedom group, the trFC between the hippocampus and bilateral brain networks was attenuated (p < .05, familywise error corrected). For the gPPI analysis, group differences were mainly located in the precuneus, middle frontal gyrus, and inferior parietal lobule (p < .001, uncorrected; k ≥ 10). The regression model presented high accuracy when predicting non‐seizure‐free patients (area under the curve = .879, 95% confidence interval = .761–.998). Significance In patients with TLE who would not achieve seizure freedom with current antiseizure medications, the functional connectivity between the hippocampus and central nodes of the DMN, CCN, and language network was disrupted, leading to language decline. Independent of hippocampal sclerosis, abnormalities, especially the effective connectivity from the hippocampus to the DMN, were predictive biomarkers of drug responsiveness in patients with TLE.

Objectives: To comprehensively analyze the characteristics of cognitive impairment of temporal lobe epilepsy (TLE), and to explore the effects of different lateral patients' cognitive impairment and different clinical factors on cognitive impairment of TLE. Methods: A total of 84 patients, who met the diagnostic criteria for TLE in the Department of Neurology, Xiangya Hospital, were collected as a patient group, with 36 cases of left TLE and 48 cases of right TLE. A total of 79 healthy volunteers with matching gender, age and education level were selected as a control group. The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and the scores of Arithmetic Test, Information Test, Digit Symbol Substitution Test (DSST), Block Design Test (BDT), Hayling Test and Verbal Fluency Test (VFT) of the revised Chinese Adult Wechsler Intelligence scale were retrospectively analyzed in the 2 groups.Multiple regression analysis was used to analyze the relationship between the clinical factors and the cognitive impairment score. Results: Compared with the control group, the TLE patient group had low scores in all neuropsychological tests, with significant difference (all P<0.05). Compared with the control group, there was significant difference in different neuropsychological tests in the patients with TLE on different sides (all P<0.05). In the left TLE, there were low scores in Information Test, arithmetic, VFT, the completion time of Hayling Test part A, the completion time of Hayling Test part B, the correct number of Hayling Test part A, the correct number of Hayling Test part B, BDT, Forward Digit Span Test (FDST) and Backward Digit Span Test (BDST). While in the right TLE, there were low scores in Information Test, arithmetic, DSST, VFT, the completion time of Hayling Test part A, the correct number of Hayling Test part A, the completion time of Hayling Test part B, the correct number of Hayling Test part B, BDT, FDST and BDST. Conclusions: There are multiple cognitive domain dysfunctions in TLE, including language, short-term memory, long-term memory, attention, working memory, executive function and visual space function. Left TLE has greater impairment of executive function and right TLE has greater damage in working memory. Long pathography of disease, hippocampal sclerosis and a history of febrile convulsions may lead to more severe cognitive impairment. Earlier identification and earlier intervention are needed to improve prognosis of patients.

The present study was performed to investigate the clinical manifestations and pathogenic variants in three large families with autosomal dominant paroxysmal kinesigenic dyskinesia (PKD) and/or benign familial infantile epilepsy (BFIE) in China. Detailed clinical data and family history were collected. Genomic DNA was isolated from the peripheral blood samples of all available members. The genetic diagnosis was made by whole-exome sequencing on the three probands and the candidate variants were verified by PCR-Sanger sequencing. The pathogenicity of variants was predicted by bioinformatics analyses and classified according to the American College of Medical Genetics criteria. A total of three causative heterozygous variants were identified in the proline-rich transmembrane protein 2 (PRRT2) gene by DNA sequencing: A novel c.324_334del(p.Val109Argfs*21) deletion variant in Family A, as well as the previously known c.510_513del(p.Ser172Argfs*3) deletion variant in Family B and c.649dupC(p.Arg217Profs*8) duplication variant in Family C. The three variants of PRRT2 co-segregated with the phenotype and genotype in the family members. The present results deepen the current understanding of PKD/BFIE and extend the genotypic-phenotypic spectrum of PKD/BFIE.

Purpose Patients with temporal lobe epilepsy (TLE) are at high risk of cognitive impairment. In addition to persistent seizures and antiepileptic drugs (AEDs), genetic factors also play an important role in the progression of cognitive deficits in TLE patients. Defining a cognitive endophenotype for TLE can provide information on the risk of cognitive impairment in patients. This study investigated the cognitive endophenotype of TLE by comparing neuropsychological function between patients with TLE, their unaffected siblings, and healthy control subjects. Patients and Methods A total of 46 patients with TLE, 26 siblings, and 33 control subjects were recruited. Cognitive function (ie, general cognition, short- and long-term memory, attention, visuospatial and executive functions, and working memory) was assessed with a battery of neuropsychological tests. Differences between groups were evaluated by analysis of covariance, with age and years of education as covariates. The Kruskal–Wallis test was used to evaluate data that did not satisfy the homogeneity of variance assumption. Pairwise comparisons were adjusted by Bonferroni correction, with a significance threshold of P<0.05. Results Patients with TLE showed deficits in the information test (P<0.001), arithmetic test (P=0.003), digit symbol substitution test (P=0.001), block design test (BDT; P=0.005), and backward digit span test (P=0.001) and took a longer time to complete the Hayling test Part A (P=0.011) compared to controls. Left TLE patients tended to have worse executive function test scores than right TLE patients. The siblings of TLE patients showed deficits in the BDT (P=0.006, Bonferroni-corrected) relative to controls. Conclusion Patients with TLE exhibit cognitive impairment. Executive function is worse in patients with left TLE than in those with right TLE. Siblings show impaired visuospatial function relative to controls. Thus, cognitive deficits in TLE patients have a genetic component and are independent of seizures or AED use.