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Backgroud: Temporal lobe epilepsy (TLE) is associated with abnormal dynamic functional connectivity patterns, but the dynamic changes in brain activity at each time point remain unclear, as does the potential molecular mechanisms associated with the dynamic temporal characteristics of TLE. Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) was acquired for 84 TLE patients and 35 healthy controls (HCs). The data was then used to conduct HMM analysis on rs-fMRI data from TLE patients and an HC group in order to explore the intricate temporal dynamics of brain activity in TLE patients with cognitive impairment (TLE-CI). Additionally, we aim to examine the gene expression profiles associated with the dynamic modular characteristics in TLE patients using the Allen Human Brain Atlas (AHBA) database. Results: Five HMM states were identified in this study. Compared with HCs, TLE and TLE-CI patients exhibited distinct changes in dynamics, including fractional occupancy, lifetimes, mean dwell time and switch rate. Furthermore, transition probability across HMM states were significantly different between TLE and TLE-CI patients (p < 0.05). The temporal reconfiguration of states in TLE and TLE-CI patients was associated with several brain networks (including the high-order default mode network (DMN), subcortical network (SCN), and cerebellum network (CN). Furthermore, a total of 1580 genes were revealed to be significantly associated with dynamic brain states of TLE, mainly enriched in neuronal signaling and synaptic function. Conclusions: This study provides new insights into characterizing dynamic neural activity in TLE. The brain network dynamics defined by HMM analysis may deepen our understanding of the neurobiological underpinnings of TLE and TLE-CI, indicating a linkage between neural configuration and gene expression in TLE. [ABSTRACT FROM AUTHOR]

Purpose: We decided to track changes in regional brain activity and executive function in temporal lobe epilepsy (TLE) patients based on cross-sectional and longitudinal designs and sought potential imaging features for follow-up observation. Methods: Thirty-two TLE patients and thirty-three healthy controls (HCs) were recruited to detect changes in fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) and to evaluate executive function both at baseline and at two-year (23.3 ± 8.3 months) follow-up. Moreover, multivariate pattern analysis (MVPA) was used for follow-up observation. Results: TLE patients displayed lower fALFF values in the right superior frontal gyrus (SFG) and higher ReHo values in the left putamen (PUT) relative to the HCs. Longitudinal analysis revealed that TLE patients at follow-up exhibited higher fALFF values in the left postcentral gyrus (PoCG), higher ReHo values in the left PoCG and the right middle frontal gyrus (MFG), lower ReHo values in the bilateral PUT and the right fusiform gyrus (FFG) compared with these patients at baseline. The executive function was impaired in TLE patients but didn't deteriorate over time. No correlations were discovered between regional brain activity and executive function. The MVPA based on ReHo performed well in differentiating the follow-up group from the baseline group. Conclusion: We revealed the abnormalities in regional brain activity and executive function as well as their longitudinal trends in TLE patients. The ReHo might be a good imaging feature for follow-up observation. [ABSTRACT FROM AUTHOR]

Background: The brain functional network plays a crucial role in cognitive impairment in temporal lobe epilepsy (TLE). Based on voxel-mirrored homotopic connectivity (VMHC), this study explored how directed functional connectivity changes and is associated with impaired cognition in right TLE (rTLE). Methods: Twenty-seven patients with rTLE and twenty-seven healthy controls were included to perform VMHC and Granger causality analysis (GCA). Correlation analysis was performed based on GCA and cognitive function. Results: Bilateral middle frontal gyrus (MFG), middle temporal gyrus, dorsolateral superior frontal gyrus (SFGdor), and supramarginal gyrus (SMG) exhibited decreased VMHC values in the rTLE group. Brain regions with altered VMHC had abnormal directed functional connectivity with multiple brain regions, mainly belonging to the default mode network, sensorimotor network, and visual network. Besides, the Montreal Cognitive Assessment (MoCA) score was positively correlated with the connectivity from the left SFGdor to the right cerebellum crus2 and was negatively correlated with the connectivity from the left SMG to the right supplementary motor area (SMA) before correction. Before correction, both phasic and intrinsic alertness reaction time were positively correlated with the connectivity from the left MFG to the left precentral gyrus (PreCG), connectivity from the left SMG to the right PreCG, and the connectivity from the left SMG to the right SMA. The executive control effect reaction time was positively correlated with the connectivity from the left MFG to the left calcarine fissure surrounding cortex before correction. Conclusion: The disordered functional network tended to be correlated with cognition impairment in rTLE. [ABSTRACT FROM AUTHOR]

Objective: Cognitive deficit is common in patients with temporal lobe epilepsy (TLE). Here, we aimed to investigate the modular architecture of functional networks associated with distinct cognitive states in TLE patients together with the role of the thalamus in modular networks. Methods: Resting‐state functional magnetic resonance imaging scans were acquired from 53 TLE patients and 37 matched healthy controls. All patients received the Montreal Cognitive Assessment test and accordingly were divided into TLE patients with normal cognition (TLE‐CN, n = 35) and TLE patients with cognitive impairment (TLE‐CI, n = 18) groups. The modular properties of functional networks were calculated and compared including global modularity Q, modular segregation index, intramodular connections, and intermodular connections. Thalamic subdivisions corresponding to the modular networks were generated by applying a 'winner‐take‐all' strategy before analyzing the modular properties (participation coefficient and within‐module degree z‐score) of each thalamic subdivision to assess the contribution of the thalamus to modular functional networks. Relationships between network properties and cognitive performance were then further explored. Results: Both TLE‐CN and TLE‐CI patients showed lower global modularity, as well as lower modular segregation index values for the ventral attention network and the default mode network. However, different patterns of intramodular and intermodular connections existed for different cognitive states. In addition, both TLE‐CN and TLE‐CI patients exhibited anomalous modular properties of functional thalamic subdivisions, with TLE‐CI patients presenting a broader range of abnormalities. Cognitive performance in TLE‐CI patients was not related to the modular properties of functional network but rather to the modular properties of functional thalamic subdivisions. Conclusions: The thalamus plays a prominent role in modular networks and potentially represents a key neural mechanism underlying cognitive impairment in TLE. [ABSTRACT FROM AUTHOR]

This study aimed to explore effective connectivity (EC) of the core networks in cognition impairment associated with temporal lobe epilepsy (CI-TLE) by applying resting state and Granger causality analysis (REST-GCA). The specific brain regions that played a critical role in classification were assessed using multivariate pattern analysis (MVPA). Thirty-two patients with CI-TLE and 29 healthy controls who were matched based on age and gender underwent functional magnetic resonance imaging (fMRI). REST-GCA revealed that patients with CI-TLE displayed decreased GC values in the following brain areas: from the posterior cingulate cortex (PCC) to the left fusiform gyrus (lFFG) and the right parahippocampal gyrus (rPPG); from the right dorsal prefrontal cortex (rDPFC) to the left superior parietal lobule (lSPL); from the left amygdala (lAG) to the PCC. Inhibitory EC was observed from the rDPFC to the PCC compared to HCs. The GC values increased from the right dorsal prefrontal cingulate cortex (rdACC) to the PCC and from the right dorsal forebrain insula (rDAI) to the right middle temporal gyrus (rMTG) in the CI-TLE patients. MVPA showed that the classification yielded an accuracy of 81.91% (78.12%, specificity =85.71%). Our observations indicated that the abnormal EC between the frontal and parietal regions might be associated with the pathophysiological mechanism of CI-TLE. These results also indicated that EC might be play a role as a potential discriminative pattern to detect CI-TLE in patients. [ABSTRACT FROM AUTHOR]

Background and purpose : Limited studies had jointly excavated the structural and functional changes in cognitive deficit in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis patients. We aimed to explore these changes in anti-NMDAR patients and their effect on cognitive function. Methods : Twenty-three patients and 25 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging, diffusion tensor imaging scanning, and neuroethology tests. The significantly differentiated brain regions via the fractional amplitude of low-frequency fluctuation (fALFF) were defined as regions of interest (ROIs). Granger causal, functional connectivity, and tract-based spatial statistical analyses were applied to explore the functional changes in ROIs and assess the structural changes. Results: HCs outperformed patients in Montreal Cognitive Assessment. The fALFF values of right gyrus rectus (RGR) in patients were significantly reduced. The fractional anisotropy (FA) values of WM in the genu of corpus callosum and right superior corona radiata were significantly decreased and positively associated with neuroethology testing scores. The Granger causal connectivity (GCC) from the left inferior parietal lobule to RGR was significantly decreased and positively associated with inherent vigilance. Indicated by the multiple linear regression result, decreased FA value of the right superior corona radiata might be a reliable marker that reflects the cognitive impairment. Conclusions: Significant changes in spontaneous neural activities, GCC, and WM structures in anti-NMDAR encephalitis were reported. These findings promote the understanding of underlying relationships between cerebral function, structural network alterations, and cognitive dysfunction. [ABSTRACT FROM AUTHOR]

Background and Purpose: To investigate the longitudinal alterations of cortical structural‐functional coupling (SF coupling) in patients with temporal lobe epilepsy (TLE) over a 2‐year follow‐up, thereby exploring the neuropathophysiological mechanisms of TLE. Methods: Twenty‐eight TLE patients and 42 age‐ and gender‐matched healthy controls (HCs) were recruited. We used resting‐state functional MRI and diffusion‐weighted imaging to estimate and compare SF coupling at the multiscale network level (whole‐brain, modular, and regional levels). Then, we analyzed the relationships between the spatial patterns of SF coupling, the principal functional connectivity (FC) gradient, and the functional participation coefficient (PC). Finally, we related regional SF coupling changes between baseline and follow‐up to the expression of regional TLE‐specific genes. Results: Compared with HCs, TLE patients showed higher baseline SF couplings within the whole‐brain, limbic, and default‐mode modules. SF couplings within visual and dorsal attention modules were increased at follow‐up compared to baseline. In all three groups, the spatial patterns of SF coupling aligned with the principal FC gradient and the functional PC. The longitudinal change in regional SF coupling in TLE patients was significantly positively correlated with the expression of the CUX2 gene. Conclusions: Aberrant SF coupling was revealed in TLE and related to macroscale cortical hierarchies, functional segregation, and TLE‐specific gene expression; these data help increase our understanding of the neuropathophysiological mechanisms underlying TLE. [ABSTRACT FROM AUTHOR]

Purpose: Previous studies have discovered different neuroimaging features in anti-NMDAR encephalitis associated with cognitive dysfunction. However, it is unknown whether there is a correlation between abnormal homotopic connectivity and cognitive impairment in anti-NMDAR encephalitis. We aim to explore the homotopic connectivity patterns of patients with anti-NMDAR encephalitis and their associations with clinical characteristics. Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) was performed on 29 patients with anti-NMDAR encephalitis and 26 healthy controls (HCs). Voxel-mirrored homotopic connectivity (VMHC) and multivariate pattern analysis (MVPA) were applied to analyze the imaging data. A correlation was also performed between aberrant brain regions and clinical parameters. Results: Compared to HCs, the performance of alertness in the patient group was typically worse (p < 0.05). A significant decrease in VMHC was observed in many regions of the patients in comparison to HCs, including the cerebellar 6, para-hippocampal gyrus, insula, precuneus, and middle frontal gyrus (p < 0.001). The insula and middle frontal gyrus were found to show positive correlations with alertness. The MVPA method achieved a classification accuracy of 74.55% with a sensitivity of 82.76% and a specificity of 65.38% in discriminating patients from HCs. Conclusion: Our findings indicate that interhemispheric functional imbalance may play a significant role in the pathophysiology of cognitive dysfunction in anti-NMDAR encephalitis. The MVPA results suggest that abnormal VMHC may play a crucial role in the identification of patients with anti-NMDAR encephalitis from HCs. [ABSTRACT FROM AUTHOR]

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis results in severe neuropsychiatric symptoms and persistent cognitive impairment; however, the underlying mechanism is still not fully understood. The present study utilized the degree centrality (DC), functional connectivity (FC) and multivariate pattern analysis (MVPA) to further explore neurofunctional symptoms in patients with anti-NMDAR encephalitis. A total of 29 patients with anti-NMDAR encephalitis and 26 healthy controls (HCs) were enrolled for neuropsychological assessment and resting-state functional MRI (rs-fMRI) scans. DC, FC and MVPA were examined to investigate cerebral functional activity and distinguish neuroimaging characteristics between the patient and HC groups based on the rs-fMRI data. Compared with the HCs, the patients exhibited cognitive deficits, anxiety and depression. In the DC analysis, the patients exhibited significantly decreased DC strength in the left rectus gyrus, left caudate nucleus (LCN) and bilateral superior medial frontal gyrus, as well as increased DC strength in the cerebellar anterior lobe, compared with the HCs. In the subsequent FC analysis, the LCN showed decreased FC strength in the bilateral middle frontal gyrus and right precuneus. Furthermore, correlation analysis indicated that disrupted cerebral functional activity was significantly correlated with the alerting effect and Hamilton Depression Scale score. Using DC maps and receiver operating characteristic curve analysis, the MVPA classifier exhibited an area under curve of 0.79, and the accuracy classification rate was 76.36%, with a sensitivity of 79.31% and a specificity of 78.18%. The present study revealed that the disrupted functional activity of hub and related networks in the cerebellum, including the default mode network and executive control network, contributed to deficits in cognition and emotion in patients with anti-NMDAR encephalitis. In conclusion, the present study provided imaging evidence and primary diagnostic markers for pathological and compensatory mechanisms of anti-NMDAR encephalitis, with the aim of improving the understanding of this disease. [ABSTRACT FROM AUTHOR]

Objective: To investigate the changes in the cerebellar-cerebral language network in temporal lobe epilepsy (TLE) patients from the cerebellar perspective, the research analyzes the changes of language and cognitive network in terms of functional connectivity (FC), as well as their efficiency of the reorganization were evaluated basing on relationship between the network metrics and neuropsychological scale scores. Methods: 30 TLE patients and 30 healthy controls were recruited. Brain activity was evaluated by voxel-mirrored homotopic connectivity analysis (VMHC). Two groups were analyzed and compared in terms of language FC using the following methods: Seed-to-Voxel analysis, pairwise correlations [region of interest(ROI)-to-ROI] and graph theory. Correlation analysis was performed between network properties and neuropsychological score. Results: Compared with healthy participants, VMHC values in the Cerebellum Anterior Lobe, Frontal Lobe, Frontal_Sup_R/L, Cingulum_Ant_R/L, and Cingulum_Mid_R/L were decreased in TLE patients. Decreased FC was observed from the Cerebelum_10_R to the left inferior frontal gyrus, from the Cerebelum_6_R to the left Lingual Gyrus, from the Cerebelum_4_5_R to left Lingual Gyrus, left Cuneal Cortex and Precuneous Cortex, from the Cerebelum_3_R to Brain-Stem, and from the Cerebelum_Crus1_L to Cerebelum_6_R in TLE patients. The FC was enhanced between bilateral Cingulum_Mid and angular gyrus and frontoparietal insular cranium, between Frontal_Sup_Med L and left/right superior temporal gyrus (pSTG l/r), while it was decreased between left middle temporal gyrus and pSTG l/r. Compared with controls, the Betweenness Centrality (BC) of the right superior marginal gyrus (SMG), Temporal_Pole_Mid_R and Temporal_Mid_L as well as the Degree Centrality (DC) and Nodal Efficiency (NE) of the right SMG were lower in TLE patients. Further analysis showed that decreased VMHC in bilateral Cerebellum Anterior Lobe was positively correlated with the Boston Naming Test score in TLE patients, but it was negatively correlated with the Verbal Fluency Test score. The NE and DC of SMG_R were both negatively correlated with visual perception score in Montreal Cognitive Assessment. Conclusion: Our results suggest that presence of abnormalities in the static functional connectivity and the language and cognitive network of TLE patients. Cerebellum potentially represents an intervention target for delaying or improving language and cognitive deficits in patients with TLE. [ABSTRACT FROM AUTHOR]

Objectives: Ictal panic (IP) can be observed occasionally in patients with temporal lobe epilepsy (TLE). Such descriptions can be found in previous studies, but the mechanism is still not clear and often confused with panic attacks in patients with panic disorder (PD). We try to use imaging methods (resting-state functional magnetic resonance imaging, rs-fMRI) to study the mechanism of this psychiatric comorbidity in patients with TLE. Methods: Forty right-onset TLE patients were observed, including 28 patients with TLE but without IP and 12 patients with TLEIP along with 30 gender-age matched healthy controls were included. We collected clinical/physiological/neuropsychological and rs-fMRI data. Degree centrality (DC) and functional connectivity (FC) were calculated. For the DC and FC values, analysis of covariance (ANCOVA) was used to find different areas and t -tests were used to compare differences between the TLEIP, TLE without IP, and healthy control(HC)groups. The relationship between brain abnormalities and patient characteristics was explored by correlation analyses. Results: No significant differences in gender and age were found among the three groups, and no significant differences in education level, Montreal Cognitive Assessment (MOCA), Hamilton Depressive Scale (HAMD), Hamilton Anxiety Scale (HAMA), and epilepsy duration (years) between the TLEIP and TLE without IP groups. In addition to fear, other symptoms were observed, including nausea, palpitations, rising epigastric sensation, and dyspnea. There was no correlation between the duration of IP and HAMA. Moreover, all IP durations were <2 min. Compared to the HCs and TLE without IP group, the DC value of the TLEIP group in the left middle temporal gyrus (LMTG) was significantly increased. Compared to the HCs, FC could be found between the LMTG and left inferior temporal gyrus (LITG) in the TLEIP group. In addition, there was FC between the LMTG and cerebellum in the TLEIP group. The difference in the magnitude of FC between the TLEIP vs. HC group was greater than the difference between the TLE vs. HC group. Conclusions: This study describes brain abnormalities in patients with TLEIP. These results will help to preliminarily understand the mechanism of ictal panic and abnormal functional connection in patients with TLE, and further explore the neuroimaging mechanism of ictal panic in patients with TLE. [ABSTRACT FROM AUTHOR]

We aimed to explore the altered functional connectivity patterns within cerebello-cerebral circuits in temporal lobe epilepsy (TLE) patients with and without focal to bilateral tonic–clonic seizures (FBTCS). Forty-two patients with unilateral TLE (21 with and 21 without FBTCS) and 22 healthy controls were recruited. We chose deep cerebellar nuclei as seed regions, calculated static and dynamic functional connectivity (sFC and dFC) in the patients with and without FBTCS and healthy controls, and compared sFC and dFC among the three groups. Correlation analyses were used to assess relationships between the significantly altered imaging features and patient clinical parameters. Compared to the group without FBTCS, the FBTCS group showed decreased sFC between the right dentate nuclei and left hemisphere regions including the middle frontal gyrus, superior temporal gyrus, superior medial frontal gyrus and posterior cingulate gyrus, and significantly increased dFC between the right interposed nuclei and contralateral precuneus. Relative to HCs, the FBTCS group demonstrated prominently decreased sFC between the right dentate nuclei and left middle frontal gyrus. No significant correlations between the altered imaging features and patient clinical parameters were observed. Our results suggest that the disrupted cerebello-cerebral FC might be related to cognitive impairment, epileptogenesis, and propagation of epileptic activities in patients with FBTCS. [ABSTRACT FROM AUTHOR]

Purpose: This retrospective study aimed to investigate the relationship between clinical characteristics, seizure outcomes, and the potential factors influencing the withdrawal of antiepileptic drugs (AEDs) in adult patients with symptomatic seizures secondary to neuronal surface antibody (NSAb)-associated autoimmune encephalitis (AE). Patients and Methods: Eighty-one patients (age ≥ 18 years) diagnosed with NSAb-associated AE were included in this retrospective study. After at least 1 year of follow-up, clinical details, magnetic resonance imaging (MRI) findings, electroencephalography (EEG) data, cerebrospinal fluid parameters, and the therapeutic outcomes were analyzed. Patients who needed long-term AEDs to control seizures were divided into two groups (withdrawal ≤ 1 year and withdrawal > 1 year). Multivariable logistic regression analysis was performed to identify the risk factors affecting the AEDs' withdrawal in patients with seizures secondary to NSAb-associated AE. Results: During the 12-month follow-up after AEDs' withdrawal, 28 (44.4%) patients among the 63 patients who needed long-term AEDs stopped AEDs within 1 year, while 35 (55.6%) patients continued AEDs treatment. Multivariable logistic regression analysis showed that delayed immunotherapy, status epilepticus (SE), and elevated intrathecal Immunoglobulin G synthesis rate of 24 hours (24-h intrathecal IgG) were independent risk factors for delayed withdrawal in patients with seizure secondary to NSAb-associated AE (odds ratios: 1.129, 6.497, 3.415, P< 0.05). The receiver operating characteristics (ROC) curve analysis showed that the area under the curve (AUC) of delayed immunotherapy, SE, and elevated 24-h intrathecal IgG was 0.816 (95% CI=0.711– 0.921, P< 0.001). Conclusion: Delayed immunotherapy, status epilepticus and elevated 24-hour intrathecal IgG synthesis rate are the factors that may influence the decision to delay AEDs' withdrawal. [ABSTRACT FROM AUTHOR]

Objective: Temporal lobe epilepsy (TLE) can be conceptualized as a network disease. However, the network characteristics in lateralization remain controversial. Methods: In this study, resting-state functional MRI scans were acquired from 53 TLE patients [22 with left-side TLE (LTLE) and 31 with right-side TLE (RTLE)] and 37 matched healthy controls. We focused on the characteristics of static and dynamic functional connectivity, including static connectivity patterns and topological properties, as well as temporal properties of the dynamic connectivity state and the variability of the dynamic connectivity and network topological organization. Correlation analyses were conducted between abnormal static and dynamic properties and cognitive performances. Results: The static functional connectivity analysis presented a significantly decreased cortical-cortical connectivity pattern and increased subcortical-cortical connectivity pattern in RTLE. The global-level network in RTLE showed a significant decrease in global efficiency. The dynamic functional connectivity analysis revealed that RTLE patients exhibited aberrant connectivity states, as well as increased variability in the subcortical-cortical connectivity. The global-level network in RTLE revealed increased variance in global efficiency and local efficiency. The static or dynamic functional connectivity in LTLE did not show any significant abnormalities. The altered dynamic properties were associated with worsening cognitive performance in language and conceptual thinking by the TLE patients. Conclusion: Our findings demonstrated the presence of abnormalities in the static and dynamic functional connectivity of TLE patients. RTLE patients exhibited more pronounced aberrant connectivity patterns and topological properties, which might represent a mechanism for reconfiguration of brain networks in RTLE patients. These observations extended our understanding of the pathophysiological network mechanisms of TLE. [ABSTRACT FROM AUTHOR]

Background: Temporal lobe epilepsy (TLE) is commonly refractory. Epilepsy surgery is an effective treatment strategy for refractory epilepsy, but patients with a history of focal to bilateral tonic-clonic seizures (FBTCS) have poor outcomes. Previous network studies on epilepsy have found that TLE and idiopathic generalized epilepsy with generalized tonic-clonic seizures (IGE-GTCS) showed altered global and nodal topological properties. Alertness deficits also were found in TLE. However, FBTCS is a common type of seizure in TLE, and the implications for alertness as well as the topological rearrangements associated with this seizure type are not well understood. Methods: We obtained rs-fMRI data and collected the neuropsychological assessment data from 21 TLE patients with FBTCS (TLE- FBTCS), 18 TLE patients without FBTCS (TLE-non- FBTCS) and 22 controls, and constructed their respective functional brain networks. The topological properties were analyzed using the graph theoretical approach and correlations between altered topological properties and alertness were analyzed. Results: We found that TLE-FBTCS patients showed more serious impairment in alertness effect, intrinsic alertness and phasic alertness than the patients with TLE-non-FBTCS. They also showed significantly higher small-worldness, normalized clustering coefficient (γ) and a trend of higher global network efficiency (gE) compared to TLE-non-FBTCS patients. The gE showed a significant negative correlation with intrinsic alertness for TLE-non-FBTCS patients. Conclusion: Our findings show different impairments in brain network information integration, segregation and alertness between the patients with TLE-FBTCS and TLE-non-FBTCS, demonstrating that impairments of the brain network may underlie the disruptions in alertness functions. [ABSTRACT FROM AUTHOR]

Background: Temporal lobe epilepsy (TLE) is commonly refractory. Epilepsy surgery is an effective treatment strategy for refractory epilepsy, but patients with a history of focal to bilateral tonic-clonic seizures (FBTCS) have poor outcomes. Previous network studies on epilepsy have found that TLE and idiopathic generalized epilepsy with generalized tonic-clonic seizures (IGE-GTCS) showed altered global and nodal topological properties. Alertness deficits also were found in TLE. However, FBTCS is a common type of seizure in TLE, and the implications for alertness as well as the topological rearrangements associated with this seizure type are not well understood.Methods: We obtained rs-fMRI data and collected the neuropsychological assessment data from 21 TLE patients with FBTCS (TLE- FBTCS), 18 TLE patients without FBTCS (TLE-non- FBTCS) and 22 controls, and constructed their respective functional brain networks. The topological properties were analyzed using the graph theoretical approach and correlations between altered topological properties and alertness were analyzed.Results: We found that TLE-FBTCS patients showed more serious impairment in alertness effect, intrinsic alertness and phasic alertness than the patients with TLE-non-FBTCS. They also showed significantly higher small-worldness, normalized clustering coefficient (γ) and a trend of higher global network efficiency (gE) compared to TLE-non-FBTCS patients. The gE showed a significant negative correlation with intrinsic alertness for TLE-non-FBTCS patients.Conclusion: Our findings show different impairments in brain network information integration, segregation and alertness between the patients with TLE-FBTCS and TLE-non-FBTCS, demonstrating that impairments of the brain network may underlie the disruptions in alertness functions. [ABSTRACT FROM AUTHOR]

Background and purpose: Anti‐N‐methyl‐d‐aspartate receptor (NMDAR) encephalitis is characterized by a range of cognitive impairments, especially in executive function. Our study aims to identify the abnormal regional homogeneity (ReHo) in anti‐NMDAR encephalitis patients and its relationship with the executive function. Methods: Forty patients and 42 healthy volunteers undertook an Attention Network Test and a resting‐state functional magnetic resonance imaging scan. ReHo analysis was performed to investigate the neuronal activity synchronization in all subjects. Based on ReHo analysis, a multivariate pattern analysis (MVPA) was carried out to identify the brain regions that differed the most between the two groups. Results: Compared to controls, the patients had higher executive control scores (p < 0.05). The patients presented reduced ReHo values in the bilateral posterior cerebellar lobe, anterior cerebellar lobe, midbrain, bilateral caudate nucleus, right superior frontal gyrus, right middle temporal gyrus, bilateral inferior parietal lobule and the left middle frontal gyrus. The ReHo values of the bilateral inferior parietal lobule in patients were found to be negatively associated with executive control scores. The classification of patients and controls using MVPA had an accuracy of 76.83%, a sensitivity of 82.50%, a specificity of 71.43% and the area under the curve was 0.83. Conclusions: Our study provides evidence of abnormal cerebral function in anti‐NMDAR encephalitis patients, which may contribute to unveiling the neuropathological mechanisms of anti‐NMDAR encephalitis and their influences on executive dysfunction. The MVPA classifier, based on ReHo, is helpful in identifying anti‐NMDAR encephalitis patients from healthy controls. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate how the functional homotopy and further functional connectivity (FC) of whole brain changed in temporal lobe epilepsy (TLE). We also evaluated which brain regions played a decisive role in classification by using functional magnetic resonance imaging (fMRI). Methods: Patients with TLE and matched healthy controls were included to collect the fMRI data and perform the voxel-mirrored homotopic connectivity (VMHC) and FC analyses. The correlation between the changed functional homotopy and neuropsychology tests was examined. Based on VMHC, the weight of each region in the classification was obtained using multivariate pattern analysis (MVPA). Results: The patients exhibited decreased functional coordination in the bilateral inferior temporal gyrus (ITG) and increased functional homotopy in the bilateral lingual gyrus compared with the control group in the VMHC analysis. Compared with healthy controls, the Montreal Cognitive Assessment score was lower, and the scores of Hamilton Anxiety (HAMA) and Hamilton Depression Scales were higher. The score of the HAMA Scale was positively correlated with the altered bilateral ITG. The FC analysis revealed increased connections between the right lingual gyrus and the left superior temporal gyrus/left insula. The MVPA showed that the accuracy, sensitivity, and specificity of classification were 68.49, 66.67 and 70.27%, respectively, and it confirmed that the temporal lobe, cerebellum, and parietal lobe provided significant contributions. Conclusion: These findings demonstrated that the VMHC and FC changed in TLE, and the alterations were correlated with the anxiety state. The MVPA indicated that the abnormal VMHC was a crucial fMRI feature. [ABSTRACT FROM AUTHOR]

Visuospatial working memory (VSWM) impairment is common in patients with right temporal lobe epilepsy (rTLE). The posterior hippocampus is critical for spatial memory, but the contributions of the different subfields to VSWM deficits remain unclear. Forty-six rTLE patients and 42 healthy controls (HCs) were recruited. Resting-state fMRI (rsfMRI) and structural MRI scans were administered, followed by a VSWM_Nback test. The right posterior hippocampus was automatically segmented, and the surface-based functional connectivity (SBFC) of the subiculum (Sub), CA1, CA3, dentate gyrus (DG), hippocampal tail, and right entorhinal cortex (EC) were compared between groups. Correlation analysis was performed between the altered SBFC and VSWM_Nback scores for rTLE patients. The results showed that rTLE patients underperformed in the VSWM_Nback test, with longer mean reaction time of accurate response (ACCmeanRT) in 0back and 2back condition, lower hit rate (HR) and higher false alarm rate (FAR) in 2back condition. Compared with HCs, the rCA3 in the rTLE group exhibited decreased SBFC with inferior parietal cortex (IPC), temporal lateral cortex (TLC), and posterior visual cortex (PVC) in the right hemisphere as well as the bilateral dorsolateral prefrontal cortex (DLPFC). The SBFC of the rEC and right anterior cingulate cortex (rACC) increased in the rTLE group. Within the rTLE group, the decreased SBFC of the rCA3-rIPC and rCA3-rLTC were correlated with worse VSWM performance. Therefore, the decreased SBFC of the rCA3-rIPC and rCA3-rLTC might be the critical aberrant FC pattern reflecting VSWM impairment in rTLE patients. The mechanism might involve functional disruption between the core subsystem and the medial temporal subsystem of the default mode network (DMN). [ABSTRACT FROM AUTHOR]

Background: In recent years, imaging technologies have been rapidly evolving, with an emphasis on the characterization of brain structure changes and functional imaging in patients with autoimmune encephalitis. However, the neural basis of anti- N -methyl-D-aspartate receptor (NMDAR) encephalitis and its linked cognitive decline is unclear. Our research aimed to assess changes in the functional brain network in patients with anti-NMDAR encephalitis and whether these changes lead to cognitive impairment. Methods: Twenty-one anti-NMDAR encephalitis patients and 22 age-, gender-, and education status-matched healthy controls were assessed using resting functional magnetic resonance imaging (fMRI) scanning and neuropsychological tests, including the Hamilton Depression Scale (HAMD24), the Montreal Cognitive Assessment (MoCA), and the Hamilton Anxiety Scale (HAMA). A functional brain network was constructed using fMRI, and the topology of the network parameters was analyzed using graph theory. Next, we extracted the aberrant topological parameters of the functional network as seeds and compared causal connectivity with the whole brain. Lastly, we explored the correlation of aberrant topological structures with deficits in cognitive performance. Results: Relative to healthy controls, anti-NMDAR encephalitis patients exhibited decreased MoCA scores and increased HAMA and HAMD24 scores (p < 0.05). The nodal clustering coefficient and nodal local efficiency of the left insula (Insula_L) were significantly decreased in anti-NMDAR encephalitis patients (p < 0.05 following Bonferroni correction). Moreover, anti-NMDAR encephalitis patients showed a weakened causal connectivity from the left insula to the left inferior parietal lobe (Parietal_Inf_L) compared to healthy controls. Conversely, the left superior parietal lobe (Parietal_sup_L) exhibited an enhanced causal connectivity to the left insula in anti-NMDAR encephalitis patients compared to controls. Unexpectedly, these alterations were not correlated with any neuropsychological test scores. Conclusion: This research describes topological abnormalities in the functional brain network in anti-NMDAR encephalitis. These results will be conducive to understand the structure and function of the brain network of patients with anti-NMDAR encephalitis and further explore the neuropathophysiological mechanisms. [ABSTRACT FROM AUTHOR]

Objective: To analyze the clinical profile and long-term prognosis of relapsing anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis. Method: This is a retrospective, multicenter, self-controlled study of 10 patients with relapsing anti-NMDAR encephalitis. Relapse was defined as new psychiatric or neurologic syndrome unexplainable by other causes that improved after immunotherapy. Results: The main symptoms at first onset and relapse included psychiatric symptoms, cognitive impairment, speech dysfunction, seizures, consciousness disturbance, movement disorders, central hypoventilation, and autonomic dysfunction. There were significantly fewer seizures and consciousness disturbances at relapse. At the first onset, the antibody positivity rate was significantly higher in the cerebrospinal fluid (CSF) than in the serum, and abnormal electroencephalograms results were noted in all patients. The relapse rate was 12.2%. After first-onset discharge, the duration of medication intake was 3.10 ± 2.69 months; the relapse time was 18.3 ± 16.5 months. The Modified Rankin Scale (MRS) score at relapse was significantly lower than that at the first onset. The MRS scores at relapse and first onset after immunotherapy were significantly lower than those before immunotherapy. At follow-up, the average duration of antiepileptic drug (AED) intake was < 1 year; the relapse rate was low. Conclusions: Patients have fewer symptoms and better quality of life at relapse than at the first onset. Active immunotherapy can significantly improve the quality of life during first onset and relapse. Encephalitis antibody testing in the CSF is preferred at first onset and relapse. Increasing antibody titers suggest clinical relapse. Prematurely stopping immunotherapy may lead to relapse, but prolonged AED intake is unnecessary. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairments in temporal lobe epilepsy (TLE) patients has been described as a chronically progressive feature of the disease. However, how severe recurrent seizures modify neuronal circuits in the human brain and subsequently degrade cognitive function, remains largely unknown. Here, we aimed to investigate longitudinal alterations by functional magnetic resonance imaging (fMRI) in TLE patients and to assess how those alterations are related to cognitive function performance. Methods: Sixteen TLE patients and 20 normal controls (NCs) were recruited for a study to observe longitudinal alterations in resting-state functional connectivity (FC) and to estimate alertness, orientation, and executive function both at baseline and at a follow-up time ~3 years later. Results: TLE patients, compared with NCs, showed impaired executive function, intrinsic alertness, and phasic alertness and exhibited lengthened reaction time (RT) in the spatial cue and center cue conditions at baseline. The orienting function of TLE patients was declined at follow-up compared to the baseline. Cross-sectional analysis demonstrated that TLE patients displayed significantly greater positive correlation than NCs between the right dorsolateral prefrontal cortex (DLPFC) and the right inferior parietal lobule (IPL) and right superior frontal gyrus (SFG). Furthermore, among TLE patients, the longitudinal study revealed a decrease in correlation between the right DLPFC and the right SFG compared to the baseline. In addition, there was a significant negative correlation between the longitudinal change in FC and the change in orienting function in TLE subjects. Conclusions: Abnormal connectivity between the DLPFC and the SFG suggests the potential of longitudinal resting-state fMRI to delineate regions relevant to cognitive dysfunction for disease progression. [ABSTRACT FROM AUTHOR]

Objective: We aimed to explore functional connectivity (FC) and effective connectivity (EC) of the executive control networks (ECNs) and the default mode network (DMN) in patients with right-sided TLE (rTLE) by applying independent component analysis (ICA) and Granger causal analysis (GCA). Methods: Twenty-seven patients with rTLE and 20 healthy controls (HCs) matched for age, gender underwent resting-state functional magnetic resonance imaging and Attention Network Test (ANT). Results: The FC analysis showed compared to HCs, patients with rTLE demonstrated reduced FC strength in the right inferior parietal gyrus (IPG) and the right middle temporal gyrus (MTG). The left superior temporal gyrus (STG) displayed reduced FC values whereas the left thalamus revealed increased FC values in rTLE. ROI-wise GCA revealed that patients with rTLE displayed increased EC from the left thalamus to the left STG, and as well as enhanced EC from the right IPG to the right MTG compared to HCs. Voxel-wise GCA showed positive EC from the left thalamus to the left insula while the right middle occipital gyrus (MOG) exhibited increased EC to the right MTG in patients. The ANT results demonstrated executive dysfunction in patients compared to HCs. The increased FC in the left thalamus showed a negative association with ECF in patients. Conclusion: We speculated that recurrent seizures take effect on disruption among the brain networks, and self-modulation occurs simultaneously to compensate for cognitive decline. Our findings revealed new insights on the neuropathophysiological mechanisms of rTLE. [ABSTRACT FROM AUTHOR]

Patients with temporal lobe epilepsy (TLE) have been indicated to exhibit abnormal resting-state functional connectivity (rsFC) of the cingulate cortex. However, it has remained elusive whether cingulate subregions show different connectivity patterns in TLE. The present study aimed to investigate the differences in rsFC of each cingulate subregion between patients with right-sided TLE (rTLE) and healthy controls (HCs), as well as their association with executive control performance in rTLE. A total of 27 patients with rTLE and 20 age-, sex- and education-matched healthy controls were recruited and all participants underwent resting-state functional MRI and an attention network test for the assessment executive control function. In each hemisphere, the cingulate gyrus (CG) was divided into CG-1 (dorsal area 23; A23d), CG-2 (rostroventral area 24; A24rv), CG-3 (pregenual area 32; A32p), CG-4 (ventral area 23; A23v), CG-5 (caudodorsal area 24; A24cd), CG-6 (caudal area 24; A23c) and CG-7 (subgenual area 32; A32sg). Pearson's correlation analysis was performed to assess the correlation between the altered FCs of the cingulate subregions and clinical variables. In patients with rTLE, the majority of the cingulate subregions exhibited decreased rsFC; this was primarily restricted to the right CG-2, the bilateral CG-6 and the bilateral CG-7. Increased rsFC was only detected in rTLE restricted to the left CG-1. Impairments in executive control efficiency were identified in patients with rTLE in comparison with the HCs. Significant alterations in rsFC between the cingulate subregion and the brain regions were mostly decreased (and some slightly increased), suggesting that FC may potentially have a left-side advantage in patients with rTLE. FC variations of the cingulate subregions were indicated to be specific to rTLE. In addition, increased connectivity in the left CG-1 and left superior frontal gyrus were negatively correlated with executive control performance, suggesting a compensatory mechanism on executive control deficits in pathological conditions. This information on differentially altered FC patterns of the cingulate subregions may provide a deeper understanding of the complex neurological mechanisms and executive control dysfunctions underlying rTLE. [ABSTRACT FROM AUTHOR]

Objective: To improve the diagnosis and treatment of anti-GABAB receptor (anti-GABABR) encephalitis and prevent misdiagnosis or non-diagnosis.Methods: We retrospectively examined the chief clinical manifestations, auxiliary examination results, treatment strategies, treatment efficacy, and long-term follow-up results of seven consecutive patients with anti-GABABR encephalitis.Results: Epileptic seizures were the first symptom in 100% of the patients; 85.7% had memory deficit in the hospital, 42.8% had residual symptoms of cognitive impairment at discharge, and 28.6% had cognitive impairment at the end of follow-up; 71.4% of the patients had psychosis in the hospital, 57.1% had residual symptoms of psychosis at discharge, and 14.3% still had psychosis at the end of follow-up. However, the clinical symptoms (psychiatric disorders, cognitive decline) and signs (consciousness disturbance) at onset and after follow-up were not significantly different (P > 0.05). In 71.4% of the patients, anti-GABABR antibody serum levels were higher than those in the cerebrospinal fluid (especially in patients with lung cancer). Magnetic resonance imaging in 71.4% of patients indicated that the marginal lobe demonstrated encephalitis lesions. The average modified Rankin Scale score (2.0 ± 2.31) at follow-up was significantly better than that (3.86 ± 0.90) at the time of admission (P < 0.05).Conclusion: The clinical characteristics of anti-GABABR encephalitis were refractory epilepsy, psychiatric disorders, and cognitive impairment. Multiple antiepileptic drugs are crucial for the treatment of intractable epilepsy. Clinicians should eliminate the possibility of small-cell lung cancer in patients with high anti-GABABR antibody levels. Early active immunotherapy is effective, and the long-term prognosis is good for patients without tumors. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate brain white matter (WM) changes and their relationship to cognition in patients with anti-N-methyl-D-aspartate (anti-NMDA) receptor encephalitis. Multivariate pattern analysis (MVPA) was used to explore brain regions that play an important role in classification. Methods: Fifteen patients and fifteen controls underwent Montreal Cognitive Assessment (MoCA) and diffusion tensor imaging. Based on fractional anisotropy (FA) and mean diffusivity (MD) for MVPA classification, the weights of each brain region were calculated. Results: Compared with the controls, the patients showed an FA reduction in right middle temporal gyrus, left middle cerebellar peduncle, right praecuneus, and an MD increase in left medial temporal gyrus and left frontal lobe. The MoCA score for patients was lower than controls, especially in executive function, fluency, delayed recall and visual perception items. The FA value of right praecuneus was positively correlated with total MoCA score and fluency score. The MD of left frontal lobe was negatively correlated with total MoCA score, and MD of the left medial temporal gyrus was positively correlated with delayed recall. The accuracy, sensitivity and specificity of classification based on FA were 70%, 60% and 80%, respectively. Based on MD, they were each 80%. The brain regions with large weights from FA and MD overlap in temporal lobe, cerebellum and hippocampus. Conclusions: These results suggest that WM changes are associated with cognitive deficits. MVPA based on FA and MD has good classification ability. Our study may provide new insights into the pathophysiological mechanisms of residual cognitive deficits. [ABSTRACT FROM AUTHOR]

Rasagiline mesylate is a highly potent, selective and irreversible monoamine oxidase type B (MAOB) inhibitor and is effective as monotherapy or adjunct to levodopa for patients with Parkinson's disease (PD). However, few studies have evaluated the efficacy and safety of rasagiline in the Chinese population. This study was designed to investigate the safety and efficacy of rasagiline as adjunctive therapy to levodopa treatment in Chinese PD patients. This was a randomized, double-blind, placebo-controlled, parallel-group, multi-centre trial conducted over a 12-wk period that enrolled 244 PD patients with motor fluctuations. Participants were randomly assigned to oral rasagiline mesylate (1 mg) or placebo, once daily. Altogether, 219 patients completed the trial. Rasagiline showed significantly greater efficacy compared with placebo. During the treatment period, the primary efficacy variable – mean adjusted total daily off time – decreased from baseline by 1.7 h in patients treated with 1.0 mg/d rasagiline compared to placebo (p < 0.05). Scores using the Unified Parkinson's Disease Rating Scale also improved during rasagiline treatment. Rasagiline was well tolerated. This study demonstrated that rasagiline mesylate is effective and well tolerated as an adjunct to levodopa treatment in Chinese PD patients with fluctuations. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of transplantation into rats with stroke of bone marrow-derived mesenchymal stem cells (MSCs) induced by brain-derived neurotrophic factor (BDNF). Materials and methods: MSCs were harvested from 6-week-old Sprague-Dawley male rats, and transplanted into adult Sprague-Dawley male rats with transient middle cerebral artery occlusion. At 48 hours after stroke, the adult rats, weighing 250-280 g, were injected via the tail vein with 16107 MSCs or MSCs induced by BDNF (BDNF-MSCs) suspended in 1 ml phosphate-buffered saline. All animals underwent the neurological function test for 14 days. Infarct volume and blood-brain barrier permeability assay were assessed on day 14 post-middle cerebral artery occlusion. Western blotting and immunohistochemical staining were used to detect the protein expression of neuron-specific enolase (NSE). Results: Both BDNF-MSCs and MSCs produced improvement in neurological deficits compared with vehicle controls on day 14 (P,0.05). In particular, the group transplanted with BDNF-MSCs exhibited significant recovery of motor function compared with the group transplanted with MSCs alone (P,0.05). Both BDNF-MSCs and MSCs, but particularly the former, reduced infarct volume, improved blood-brain barrier dysfunction, reduced serum NSE levels, activated the NSE activity, and inhibited neuronal apoptosis in the ischemic boundary zone. Conclusions: BDNF-MSCs might contribute to the motor function improvement partly by reducing neuronal damage via upregulating the NSE expression level and inhibiting neuronal apoptosis. [ABSTRACT FROM AUTHOR]