Chaorong Liu’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.

Aims This study aimed to comprehensively explore the cerebellar structural and functional changes in temporal lobe epilepsy (TLE) and its association with clinical information. Methods The SUIT toolbox was utilized to perform cerebellar volume and diffusion analysis. In addition, we extracted the average diffusion values of cerebellar peduncle tracts to investigate microstructure alterations. Seed-based whole-brain analysis was used to investigate cerebellar–cerebral functional connectivity (FC). Subgroup analyses were performed to identify the cerebellar participation in TLE with/without hippocampal sclerosis (HS)/focal-to-bilateral tonic–clonic seizure (FBTCS) and TLE with different lateralization. Results TLE showed widespread gray matter atrophy in bilateral crusII, VIIb, VIIIb, left crusI, and left VIIIa. Both voxel and tract analysis observed diffusion abnormalities in cerebellar afferent peduncles. Reduced FC between the right crus II and the left parahippocampal cortex was found in TLE. Additionally, TLE showed increased FCs between left lobules VI–VIII and cortical nodes of the dorsal attention and visual networks. Across all patients, decreased FC was associated with poorer cognitive function, while increased FCs appeared to reflect compensatory effects. The cerebellar structural changes were mainly observed in HS and FBTCS subgroups and were regardless of seizure lateralization, while cerebellar–cerebral FC alterations were similar in all subgroups. Conclusion TLE exhibited microstructural changes in the cerebellum, mainly related to HS and FBTCS. In addition, altered cerebellar–cerebral functional connectivity is associated with common cognitive alterations in TLE.

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 Cortical tremor/myoclonus is the hallmark feature of benign adult familial myoclonic epilepsy (BAFME), the mechanism of which remains elusive. A hypothesis is that a defective control in the preexisting cerebellar‐motor loop drives cortical tremor. Meanwhile, the basal ganglia system might also participate in BAFME. This study aimed to discover the structural basis of cortical tremor/myoclonus in BAFME. Methods Nineteen patients with BAFME type 1 (BAFME1) and 30 matched healthy controls underwent T1‐weighted and diffusion tensor imaging scans. FreeSurfer and spatially unbiased infratentorial template (SUIT) toolboxes were utilized to assess the motor cortex and the cerebellum. Probabilistic tractography was generated for two fibers to test the hypothesis: the dentato‐thalamo‐(M1) (primary motor cortex) and globus pallidus internus (GPi)‐thalamic projections. Average fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD) of each tract were extracted. Results Cerebellar atrophy and dentate nucleus alteration were observed in the patients. In addition, patients with BAFME1 exhibited reduced AD and FA in the left and right dentato‐thalamo‐M1 nondecussating fibers, respectively false discovery rate (FDR) correction q < .05. Cerebellar projections showed negative correlations with somatosensory‐evoked potential P25‐N33 amplitude and were independent of disease duration and medication. BAFME1 patients also had increased FA and decreased MD in the left GPi‐thalamic projection. Higher FA and lower RD in the right GPi‐thalamic projection were also observed (FDR q < .05). Significance The present findings support the hypothesis that the cerebello‐thalamo‐M1 loop might be the structural basis of cortical tremor in BAFME1. The basal ganglia system also participates in BAFME1 and probably serves a regulatory role.

Neurodevelopmental disorders (NDD) are complex and multifaceted diseases involving genetic and environmental science. The rapid development of sequencing techniques makes it possible to dig new disease‐causing genes. Our study was aimed to discover novel genes linked to NDD. Trio whole‐exome sequencing was performed to evaluate potential variants of NDD, identifying three unrelated patients with compound heterozygous variants in DNAH14. The detailed clinical information and genetic results of the recruited patients were obtained and systematically reviewed. Three compound heterozygous DNAH14 variants were identified (c.6100C>T(p.Arg2034Ter) and (c.5167A>G(p.Arg1723Gly), c.12640_12641delAA (p.Lys4214Valfs*7) and (c.4811T>A(p.Leu1604Gln), c.7615C>A(p.Pro2539Thr) and c.11578G>A (p.Gly3860Ser)), including one nonsense variant, one frameshift variant and four missense variants, which were all not exist or with low minor allele frequency based on the gnomAD database. The missense variants were all assumed to be damaging or probably damaging by multiple bioinformatics tools. Four of these variants were located in the AAA+ ATPase domain and two were located in the C‐terminal domain. Most affected amino acids were highly conserved in various species. A spectrum of neurological and developmental phenotypes was observed including seizure, global developmental delay, microcephaly and hypotonia. Our findings indicate that variants in DNAH14 could lead to previously unrecognized neurodevelopmental disorders. This article is protected by copyright. All rights reserved.

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.