Aberrant functional hubs and related networks attributed to cognitive impairment in patients with anti­N­methyl­D­aspartate receptor encephalitis.

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.

Impaired interhemispheric synchrony and effective connectivity in right temporal lobe epilepsy.

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.

Cerebral gray matter volume changes in patients with anti-N-methyl-D-aspartate receptor encephalitis: A voxel-based morphometry study.

Background: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disease with typical clinical features. Whether and how cerebral gray matter structural damage inherent to the disorder affects cognitive function in patients is still unclear. Therefore, this study aimed to explore the changes in cerebral gray matter volume and whether these alterations contribute to cognitive impairment and mood disorders. Methods: Forty patients with anti-NMDAR encephalitis and forty healthy controls (HCs) matched for gender, age, and education were recruited. All participants underwent attention network tests (ANT), neuropsychological tests and magnetic resonance imaging (MRI). Voxel-based morphological analysis (VBM) and correlation analysis was performed on all participants. Finally, according to the course of disease, patients were divided into two groups: NMDARE_SD (short duration; course ≤ 2 years since diagnosis) and NMDARE_LD (long duration; course >2 years since diagnosis), to evaluate gray matter volume changes that differ as a function of disease course. Results: Compared to HCs, patients with anti-NMDAR encephalitis showed decreased executive control ability and lower MoCA score, while increased anxiety and depression as reflected by HAMA and HAMD24 scores (all P < 0.05). In VBM analysis, patients showed decreased gray matter volume in bilateral thalamus, left medial prefrontal cortex (mPFC_L), left superior temporal gyrus (STG_L), and left rectus gyrus. In the analysis stratified by disease course, the NMDARE_LD group exhibited decreased gray matter volume in the left precuneus and right posterior cerebellar lobe compared to the NMDARE_SD group. Conclusions: Patients with anti-NMDAR encephalitis have cognitive, executive, and emotional dysfunction, and the sites of gray matter atrophy are concentrated in the thalamus, frontal lobe, and temporal lobe. These abnormalities may be involved in the process of cognitive and affective dysfunction.Patients with different courses of anti-NMDAR encephalitis have different brain atrophy sites. These results may help to clarify the contradiction between clinical and imaging manifestations of anti NMDAR encephalitis, which is worthy of further longitudinal studies.

Disruption in Surface-Based Functional Connectivity in the Right Posterior Hippocampal CA3 Subfield: A Probable Neural Basis of Visuospatial Working Memory Impairment in Patients With Right Temporal Lobe Epilepsy.

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).

Altered interhemispheric functional homotopy and connectivity in temporal lobe epilepsy based on fMRI and multivariate pattern analysis.

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.

The Insula Is a Hub for Functional Brain Network in Patients With Anti-N-Methyl-D-Aspartate Receptor Encephalitis.

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.