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Abstract Abnormal brain aging is suggested in epilepsy. Given the brain network dysfunction in epilepsy, the white matter tracts, which primarily interconnect brain regions, could be of special importance. We focused on white matter brain aging in diverse forms of epilepsy and comorbid psychosis. We obtained brain diffusion tensor imaging (DTI) data at 3 T-MRI in 257 patients with epilepsy and 429 healthy subjects. The tract-based fractional anisotropy values of the healthy subjects were used to build a brain-age prediction model, and we calculated the brain-predicted age difference (brain-PAD: predicted age—chronological age) of all subjects. As a result, almost all epilepsy categories showed significantly increased brain-PAD (p

IntroductionLow-grade epilepsy-associated tumors are the second most common histopathological diagnoses in cases of drug-resistant focal epilepsy. However, the connection between neuroimaging features and genetic alterations in these tumors is unclear, prompting an investigation into genotype-relevant neuroimaging characteristics.MethodsThis study retrospectively analyzed neuroimaging and surgical specimens from 46 epilepsy patients with low-grade epilepsy-associated neuroepithelial tumors that had genetic mutations identified through panel sequencing to investigate their relationship to genotypes.ResultsThree distinct neuroimaging groups were established: Group 1 had indistinct borders and iso T1-weighted and slightly high or high T2-weighted signal intensities without a diffuse mass effect, associated with 93.8% sensitivity and 100% specificity to BRAF V600E mutations; Group 2 exhibited sharp borders and very or slightly low T1-weighted and very high T2-weighted signal intensities with a diffuse mass effect and 100% sensitivity and specificity for FGFR1 mutations; and Group 3 displayed various characteristics. Histopathological diagnoses including diffuse low-grade glioma and ganglioglioma showed no clear association with genotypes. Notably, postoperative seizure-free rates were higher in Group 1 tumors (BRAF V600E) than in Group 2 tumors (FGFR1).DiscussionThese findings suggest that tumor genotype may be predicted by neuroimaging before surgery, providing insights for personalized treatment approaches.

Background/Objectives: Although the involvement of progressive brain alterations in epilepsy was recently suggested, individual patients’ trajectories of white matter (WM) disruption are not known. Methods: We investigated the disease progression patterns of WM damage and its associations with clinical metrics. We examined the cross-sectional diffusion tensor imaging (DTI) data of 155 patients with unilateral temporal lobe epilepsy (TLE) and 270 age/gender-matched healthy controls, and we then calculated the average fractional anisotropy (FA) values within 20 WM tracts of the whole brain. We used the Subtype and Stage Inference (SuStaIn) program to detect the progression trajectory of FA changes and investigated its association with clinical parameters including onset age, disease duration, drug-responsiveness, and the number of anti-seizure medications (ASMs). Results: The SuStaIn algorithm identified a single subtype model in which the initial damage occurs in the ipsilateral uncinate fasciculus (UF), followed by damage in the forceps, superior longitudinal fasciculus (SLF), and anterior thalamic radiation (ATR). This pattern was replicated when analyzing TLE with hippocampal sclerosis (n = 50) and TLE with no lesions (n = 105) separately. Further-progressed stages were associated with longer disease duration (p < 0.001) and a greater number of ASMs (p = 0.001). Conclusions: the disease progression model based on WM tracts may be useful as a novel individual-level biomarker.

Mild malformation of cortical development with oligodendroglial hyperplasia (MOGHE) is a recently proposed epileptogenic entity that is difficult to detect on MRI. We present a case of MOGHE that was successfully detected on T1WI-chemical shift-selective saturation (CHESS) MRI. The clinical presentation, MRI including T1WI-CHESS, functional images, and pathology findings of a 14-year-old Japanese girl diagnosed with MOGHE are described. T1WI-CHESS revealed an abnormal high signal along the affected lesion, whereas the findings shown by the other MR sequences were less obvious; interictal fluorodeoxyglucose-positron emission tomography indicated slightly decreased accumulation in the lesion, and subtraction ictal single photon emission computed tomography co-registered to MRI showed an increased blood flow. Together these observations suggest that T1WI-CHESS may be a useful MR sequence for detecting the lesions in patients with MOGHE.

Abstract Objective Psychosis is an important comorbidity in epilepsy, but its pathophysiology is still unknown. The imaging modality 18F‐fluorodeoxyglucose‐positron emission tomography (18F‐FDG PET) is widely used to measure brain glucose metabolism, and we speculated that 18F‐FDG PET may detect characteristic alteration patterns in individuals with temporal lobe epilepsy (TLE) and psychosis. Methods We enrolled 13 patients with TLE and interictal psychosis (TLE‐P) and 21 patients with TLE without psychosis (TLE‐N). All underwent interictal 18F‐FDG‐PET scanning. Statistical Parametric Mapping (SPM)12 software was used for the normalization process, and we performed a voxel‐wise comparison of the TLE‐P and TLE‐N groups. Results Cerebral hypometabolic areas were observed in the ipsilateral temporal pole to hippocampus in both patient groups. In the TLE‐P group, the voxel‐wise comparison revealed significantly increased 18F‐FDG signals in the upper cerebellum, superior cerebellar peduncle, and midbrain. There were no significant between‐group metabolic differences around the focus or other cerebral areas. Significance Our results demonstrated significant hypermetabolism around the upper cerebellum in patients with TLE and interictal psychosis compared to patients with TLE without psychosis. These findings may reflect the involvement of the cerebellum in the underlying neurobiology of interictal psychosis and could contribute to a better understanding of this disorder.

Background: Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system that causes the damage to the myelin sheath as well as axonal degeneration. Individuals with MS appear to have changes in the numbers and functions of T-cell subsets, leading to an immunological imbalance accompanied by enhanced autoreactivity. In previous preclinical studies, (2 S,3 S,4R)-1-O-(α-D-Galactopyranosyl)-N-tetracosanoyl-2-amino-1,3,4-nonanetriol (OCH), a synthetic analog of α-galactosylceramide stimulatory for invariant NKT (iNKT) cells, has shown therapeutic or disease-preventive immunoregulatory effects in autoimmune disease models such as experimental autoimmune encephalomyelitis (EAE). Objectives: This study is the first-in-human study of oral OCH to evaluate the pharmacokinetics and to examine the effects on immune cells as well as related gene expression profiles. Methods: Fifteen healthy volunteers and 13 MS patients who met the study criteria were enrolled. They were divided into five cohorts and received oral administration of various doses of granulated powder of OCH (0.3–30 mg), once per week for 4 or 13 weeks. Plasma OCH concentrations were measured by high-performance liquid chromatography. Frequencies of lymphocyte subsets in peripheral blood were evaluated by flow cytometry, and microarray analysis was performed to determine OCH-induced changes in gene expression. Results: Oral OCH was well tolerated, and its bioavailability was found to be sufficient. Six hours after a single dose of OCH, increased frequencies of Foxp3 + regulatory T-cells were observed in some cohorts of healthy subjects and MS patients. Furthermore, gene expression analysis demonstrated an upregulation of several immunoregulatory genes and downregulation of pro-inflammatory genes following OCH administration. Conclusion: This study has demonstrated immunomodulatory effects of the iNKT cell-stimulatory drug OCH in human. Safety profiles together with the presumed anti-inflammatory effects of oral OCH encouraged us to conduct a phase II trial.

Abstract Background Chemoradiotherapy (CRT) is the standard treatment for c-stage IIIB non-small cell lung cancer (NSCLC); however, patients who respond to CRT are at risk of developing fatal complications such as massive hemoptysis or infection. In such cases, surgery is an alternative option. Currently, there are limited reports on surgery for complications arising during definitive CRT for locally advanced NSCLC. We report a case of hemoptysis after definitive CRT for c-T4N2M0 stage IIIB NSCLC that was successfully treated with lower bilobectomy combined with left atrial resection. Case presentation A 72-year-old man with c-T4N2M0 stage IIIB NSCLC with left atrial invasion developed hemoptysis during CRT, which was discontinued to control hemoptysis. Chest computed tomography revealed a regressed and cavitated tumor. Three weeks after discontinuation of CRT, surgery was performed to avoid fatal complications and secure radicality. We performed lower bilobectomy combined with partial left atrial resection, which was performed using an automatic tri-stapler. The bronchial stump was covered with an omental flap. The resected specimen pathologically showed complete response with fistula between the intermediate bronchus and necrotic cavity in the tumor. His postoperative course was uneventful, and the patient was disease free at 10 months after surgery. Conclusions We successfully performed surgery after definitive CRT in a patient with c-T4N2M0 stage IIIB NSCLC. Partial left atrial resection was safely performed with an automatic tri-stapler. A complete pathological response to CRT was achieved. In a case with a chance of complete (R0) resection, when the risk of developing fatal complications might outweigh the risk of post-CRT surgery perioperative complications, surgery should be considered as a treatment option.

Abstract Introduction Free‐water (FW) imaging, a new analysis method for diffusion magnetic resonance imaging (MRI), can indicate neuroinflammation and degeneration. We evaluated FW in Alzheimer's disease (AD) using tau/inflammatory and amyloid positron emission tomography (PET). Methods Seventy‐one participants underwent multi‐shell diffusion MRI, 18F‐THK5351 PET, 11C‐Pittsburgh compound B PET, and neuropsychological assessments. They were categorized into two groups: healthy controls (HCs) (n = 40) and AD‐spectrum group (AD‐S) (n = 31) using the Centiloid scale with amyloid PET and cognitive function. We analyzed group comparisons in FW and PET, correlations between FW and PET, and correlation analysis with neuropsychological scores. Results In AD‐S group, there was a significant positive correlation between FW and 18F‐THK5351 in the temporal lobes. In addition, there were negative correlations between FW and cognitive function in the temporal lobe and cingulate gyrus, and negative correlations between 18F‐THK5351 and cognitive function in the same regions. Discussion FW imaging could be a biomarker for tau in AD alongside clinical correlations.

Abstract Backgrounds Although neurofibrillary tangles (NFTs) mainly accumulate in the medial temporal lobe with human aging, only a few imaging studies have investigated correlations between NFT accumulation and gray matter (GM) volume in cognitively normal older adults. Here, we investigated the correlations between 18F-THK5351 accumulation and GM volume at the voxel level. Material and methods We recruited 47 amyloid-negative, cognitively normal, older adults (65.0 ± 7.9 years, 26 women), who underwent structural magnetic resonance imaging, 11C-Pittsburgh compound-B and 18F-THK5351 PET scans, and neuropsychological assessment. The magnetic resonance and 18F-THK5351 PET images were spatially normalized using Statistical Parametric Mapping 12. Voxel-wise correlations between 18F-THK5351 accumulation and GM volume were evaluated using the Biological Parametric Mapping toolbox. Results A significant negative correlation (p

Background: Recent studies detected the aberrant myelination of the central nervous system (CNS) in Alzheimer’s disease (AD). Here, we compared the change of myelination between patients with AD and controls by a novel magnetic resonance imaging modality, “q-space myelin map (MM) imaging.” Methods: Twenty patients with AD and 18 healthy subjects underwent MM imaging. We compared the MM metric between the 2 groups and examined the relationships between the metric and the clinical symptoms of AD. Results: AD patients showed a significant reduction of MM metric in the hippocampus, insula, precuneus, and anterior cingulate regions. There was also a significant negative correlation between the duration of illness and the MM metric in the temporoparietal region. Conclusion: Our findings suggest that MM imaging could be a clinically proper modality to estimate the myelination changes in AD patients.

Objective: The aim of this study was to evaluate tau-related structural network metrics derived from gray matter magnetic resonance imaging (MRI) scans in cognitively normal (CN) older adults. Methods: We recruited 47 amyloid-negative CN older adults (mean age ± standard deviation, 65.0 ± 7.9 years; 26 women). All participants underwent 3D T1-weighted MRI and 11C-Pittsburgh compound-B and 18F-THK5351 positron emission tomography scans. Four local network metrics (betweenness centrality, clustering coefficient, characteristic path length, and degree) were computed and rendered on individual brain images. We then evaluated the correlations between 18F-THK5351 positron emission tomography images and local network metric images at the voxel level. Results: Significant positive correlations of the four local network metrics with 18F-THK5351 were detected in the bilateral caudate. Conclusion: Our findings suggest that tau and neuroinflammation in CN older adults may influence the gray matter structural network in the caudate.

Objective: This study aimed to examine the alterations in gray matter networks related to tau retention in Alzheimer's disease (AD) patients and cognitively normal (CN) older individuals. Methods: Eighteen amyloid-positive AD patients and 30 age- and sex-matched amyloid-negative CN controls were enrolled. All underwent 3D T1-weighted MRI, amyloid positron-emission tomography imaging (PET) with 11C-Pittsburgh Compound B (PiB), and tau PET with 18F-THK5351. The structural networks extracted from the T1-weighted MRI data based on cortical similarities within single subjects were analyzed. Based on graph theoretical approach, global and local network properties across the whole brain were computed. Group comparisons of global and local network properties were evaluated between the groups. Then, we correlated the global and local network measures with total cerebral 18F-THK5351 retention. Results: AD patients moved toward more randomized global network compared to controls and regional differences were observed in the default mode network (DMN) area. No significant correlations existed between global network properties and tau retention. On a local level, AD and controls showed opposite relationships between network properties and tau retention mainly in the DMN areas; CN controls showed positive correlations, whereas AD showed negative correlations. Conclusion: We found opposite relationships between local network properties and tau retention between amyloid-positive AD patients and amyloid-negative controls. Our findings suggest that the presence of amyloid and induced exacerbated tau retention alter the relationship of local network properties and tau retention.

Objective: In this study, we investigated the ability of fluid-attenuated inversion recovery (FLAIR) data coupled with machine-leaning algorithms to differentiate normal and epileptic brains and identify the laterality of focus side in temporal lobe epilepsy (TLE) patients with visually negative MRI.Materials and Methods: The MRI data were acquired on a 3-T MR system (Philips Medical Systems). After pre-proceeding stage, the FLAIR signal intensities were extracted from specific regions of interest, such as the amygdala, cerebral white matter, inferior temporal gyrus, middle temporal gyrus, parahippocampal gyrus, superior temporal gyrus, and temporal pole, and fed into a classification framework followed by a support vector machine as classifier. The proposed lateralization framework was assessed in a group of MRI-negative unilateral TLE patients (N = 42; 23 left TLE and 19 right TLE) and 34 healthy controls (HCs) based on a leave-one-out cross-validation strategy.Results: Using the FLAIR data, we obtained a 75% accuracy for discriminating the three groups, as well as 87.71, 83.01, and 76.19% accuracies for HC/right TLE, HC/left TLE, and left TLE/right TLE tasks, respectively.Interpretation: The experimental results show that FLAIR data can potentially be considered an informative biomarker for improving the pre-surgical diagnostic confidence in patients with MRI-negative TLE.

Background: Despite the importance of psychosis as a comorbidity of temporal lobe epilepsy (TLE), the underlying neural mechanisms are still unclear. We aimed to investigate abnormalities specific to psychosis in TLE, using diffusion MRI parameters and graph-theoretical network analysis.Material and Methods: We recruited 49 patients with TLE (20 with and 29 without interictal schizophrenia-like psychosis) and 42 age-/gender-matched healthy controls. We performed 3-tesla MRI scans including 3D T1-weighted imaging and diffusion tensor imaging in all participants. Among the three groups, fractional anisotropy (FA), mean diffusivity (MD), and global network metrics were compared by analyses of covariance. Regional connectivity strength was compared by network-based statistics.Results: Compared to controls, TLE patients showed significant temporal and extra-temporal changes in FA, and MD, which were more severe and widespread in patients with than without psychosis. We observed distinct differences between TLE patients with and without psychosis in the anterior thalamic radiation (ATR), inferior fronto-occipital fasciculus (IFOF), and inferior longitudinal fasciculus (ILF). Similarly, for network metrics, global, and local efficiency and increased path length were significantly reduced in TLE patients compared to controls, but with more severe changes in TLE with psychosis than without psychosis. Network-based statistics detected significant differences between TLE with and without psychosis mainly involving the left limbic and prefrontal areas.Conclusion: TLE patients with interictal schizophrenia-like psychosis showed more widespread and severe white matter impairment, involving the ATR, IFOF and ILF, as well as disrupted network connectivity, particularly in the left limbic and prefrontal cortex, than patients without psychosis.

Background: Despite recent advances in diffusion MRI (dMRI), there is still limited information on neurite orientation dispersion and density imaging (NODDI) in temporal lobe epilepsy (TLE). This study aimed to demonstrate neurite density and dispersion in TLE with and without hippocampal sclerosis (HS) using whole-brain voxel-wise analyses. Material and methods: We recruited 33 patients with unilateral TLE (16 left, 17 right), including 14 patients with HS (TLE-HS) and 19 MRI-negative 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)-positive patients (MRI-/PET+ TLE). The NODDI toolbox calculated the intracellular volume fraction (ICVF) and orientation dispersion index (ODI). Conventional dMRI metrics, that is, fractional anisotropy (FA) and mean diffusivity (MD), were also estimated. After spatial normalization, all dMRI parameters (ICVF, ODI, FA, and MD) of the patients were compared with those of age- and sex-matched healthy controls using Statistical Parametric Mapping 12 (SPM12). As a complementary analysis, we added an atlas-based region of interest (ROI) analysis of relevant white matter tracts using tract-based spatial statistics. Results: We found decreased neurite density mainly in the ipsilateral temporal areas of both right and left TLE, with the right TLE showing more severe and widespread abnormalities. In addition, etiology-specific analyses revealed a localized reduction in ICVF (i.e., neurite density) in the ipsilateral temporal pole in MRI-/PET+ TLE, whereas TLE-HS presented greater abnormalities, including FA and MD, in addition to a localized hippocampal reduction in ODI. The results of the atlas-based ROI analysis were consistent with the results of the SPM12 analysis. Conclusion: NODDI may provide clinically relevant information as well as novel insights into the field of TLE. Particularly, in MRI-/PET+ TLE, neurite density imaging may have higher sensitivity than other dMRI parameters. The results may also contribute to better understanding of the pathophysiology of TLE with HS. Keywords: Temporal lobe epilepsy, Neurite orientation dispersion and density imaging, Diffusion MRI, MRI-negative focal epilepsy, Hippocampal sclerosis

Background: White matter hyperintensities (WMH) in the cholinergic pathways are associated with cognitive performance in Alzheimer's disease. This study aimed to evaluate the relationship between the volume reduction of cholinergic pathways and cognitive function in patients with multiple sclerosis (MS). Methods: Thirty-two MS patients underwent a brain MRI and cognitive measurements including the Mini-Mental State Examination (MMSE) and the Japanese version of the Montreal Cognitive Assessment (MoCA-J). The extent of WMH within the cholinergic pathways was assessed using the Cholinergic Pathways Hyperintensities Scale (CHIPS). Computerized WMH volumes were also obtained. FreeSurfer was used to measure regional volumes including the cortical and subcortical volumes. The correlations among the CHIPS, the WMH volume, and the clinical data were assessed, in addition to the correlations between the cognitive scores and regional volumes measured by FreeSurfer. Results: The CHIPS score and the WMH volume were strongly positively correlated with each other (r=0.87, P

Background: Despite the increasing use of arterial spin labeling (ASL) in patients with epilepsy, little is known about its brain regional distribution pattern, including diaschisis, and its correspondence with FDG-PET. Here, we investigated the regional match and mismatch between FDG-PET and ASL in temporal lobe epilepsy (TLE).Methods: We recruited 27 patients with unilateral TLE, who underwent inter-ictal ASL and FDG-PET scans. These images were spatially normalized using Statistical Parametric Mapping 12, and the regional values in both ASL and FDG-PET were calculated using PMOD software within 20 volumes of interest (VOIs), including the temporal lobe, adjacent cortices, subcortical structures, and cerebellum. ASL images of 37 healthy controls were also analyzed and compared.Results: Whereas, ASL showed significant side differences, mainly in the temporal and frontal lobes, the significant abnormalities in FDG-PET were more widespread and included the insula and supramarginal gyrus. Ipsilateral thalamic reduction was found in FDG-PET only. The detectability of the focus side compared with the contralateral side was generally higher in FDG-PET. The discriminative values in ASL compared with healthy controls were higher in temporal neocortex and amygdala VOIs.Conclusions: There are similar and differing regional distributions between FDG-PET and ASL in TLE, possibly reflecting regional match and mismatch of cerebral blood flow and metabolism. At this stage, it seems that ASL couldn't present comparable clinical usefulness with FDG-PET. These findings deepen our knowledge of ASL imaging and are potentially useful for its further application.

PurposeThe pathophysiology of idiopathic generalized epilepsy (IGE) is still unclear, but graph theory may help to understand it. Here, we examined the graph-theoretical findings of the gray matter network in IGE using anatomical covariance methods.Materials and methodsWe recruited 33 patients with IGE and 35 age- and sex-matched healthy controls. Gray matter images were obtained by 3.0-T 3D T1-weighted MRI and were normalized using the voxel-based morphometry tools of Statistical Parametric Mapping 12. The normalized images were subjected to graph-theoretical group comparison using the Graph Analysis Toolbox with two different parcellation schemes. Initially, we used the Automated Anatomical Labeling template, whereas the Hammers Adult atlas was used for the second analysis.ResultsThe resilience analyses revealed significantly reduced resilience of the IGE gray matter networks to both random failure and targeted attack. No significant between-group differences were found in global network measures, including the clustering coefficient and characteristic path length. The IGE group showed several changes in regional clustering, including an increase mainly in wide areas of the bilateral frontal lobes. The second analysis with another region of interest (ROI) parcellation generated the same results in resilience and global network measures, but the regional clustering results differed between the two parcellation schemes.ConclusionThese results may reflect the potentially weak network organization in IGE. Our findings contribute to the accumulation of knowledge on IGE.

Background and purpose: Automated subfield volumetry of hippocampus is desirable for use in temporal lobe epilepsy (TLE), but its utility has not been established. Automatic segmentation of hippocampal subfields (ASHS) and the new version of FreeSurfer software (ver.6.0) using high-resolution T2-weighted MR imaging are candidates for this volumetry. The aim of this study was to evaluate hippocampal subfields in TLE patients using ASHS as well as the old and new versions of FreeSurfer. Materials and methods: We recruited 50 consecutive unilateral TLE patients including 25 with hippocampal sclerosis (TLE-HS) and 25 without obvious etiology (TLE-nonHS). All patients and 45 healthy controls underwent high-resolution T2-weighted and 3D-volume T1-weighted MRI scanning. We analyzed all of their MR images by FreeSurfer ver.5.3, ver.6.0 and ASHS. For each subfield, normalized z-scores were calculated and compared among groups. Results: In TLE-HS groups, ASHS and FreeSurfer ver.6.0 revealed maximal z-scores in ipsilateral cornu ammonis (CA) 1, CA4 and dentate gyrus (DG), whereas in FreeSurfer ver.5.3 ipsilateral subiculum showed maximal z-scores. In TLE-nonHS group, there was no significant volume reduction by either ASHS or FreeSurfer. Conclusions: ASHS and the new version of FreeSurfer may have an advantage in compatibility with existing histopathological knowledge in TLE patients with HS compared to the old version of FreeSurfer (ver.5.3), although further investigations with pathological findings and/or surgical outcomes are desirable.

This study aimed to investigate abnormalities in structural covariance network constructed from gray matter volume in myotonic dystrophy type 1 (DM1) patients by using graph theoretical analysis for further clarification of the underlying mechanisms of central nervous system involvement. Twenty-eight DM1 patients (4 childhood onset, 10 juvenile onset, 14 adult onset), excluding three cases from 31 consecutive patients who underwent magnetic resonance imaging in a certain period, and 28 age- and sex- matched healthy control subjects were included in this study. The normalized gray matter images of both groups were subjected to voxel based morphometry (VBM) and Graph Analysis Toolbox for graph theoretical analysis. VBM revealed extensive gray matter atrophy in DM1 patients, including cortical and subcortical structures. On graph theoretical analysis, there were no significant differences between DM1 and control groups in terms of the global measures of connectivity. Betweenness centrality was increased in several regions including the left fusiform gyrus, whereas it was decreased in the right striatum. The absence of significant differences between the groups in global network measurements on graph theoretical analysis is consistent with the fact that the general cognitive function is preserved in DM1 patients. In DM1 patients, increased connectivity in the left fusiform gyrus and decreased connectivity in the right striatum might be associated with impairment in face perception and theory of mind, and schizotypal-paranoid personality traits, respectively.

Psychosis is one of the most important psychiatric comorbidities in temporal lobe epilepsy (TLE), and its pathophysiology still remains unsolved. We aimed to explore the connectivity differences of structural neuroimaging between TLE with and without psychosis using a graph theoretical analysis, which is an emerging mathematical method to investigate network connections in the brain as a small-world system.We recruited 11 TLE patients with unilateral hippocampal sclerosis (HS) presenting psychosis or having a history of psychosis (TLE-P group). As controls, 15 TLE patients with unilateral HS without any history of psychotic episodes were also recruited (TLE-N group). For graph theoretical analysis, the normalized gray matter images of both groups were subjected to Graph Analysis Toolbox (GAT). As secondary analyses, each group was compared to 14 age- and gender-matched healthy subjects.The hub node locations were found predominantly in the ipsilateral hemisphere in the TLE-N group, and mainly on the contralateral side in the TLE-P group. The TLE-P group showed significantly higher characteristic path length, transitivity, lower global efficiency, and resilience to random or targeted attack than those of the TLE-N group. The regional comparison in betweenness centrality revealed significantly decreased connectivity in the contralateral temporal lobe, ipsilateral middle frontal gyrus, and bilateral postcentral gyri in the TLE-P group. The healthy subjects showed well-balanced nodes/edges distributions, similar metrics to TLE-N group except for higher small-worldness/modularity/assortativity, and various differences of regional betweenness/clustering.In TLE with psychosis, graph theoretical analysis of structural imaging revealed disrupted connectivity in the contralateral hemisphere. The network metrics suggested that the existence of psychosis can bring vulnerability and decreased efficiency of the whole-brain network. The sharp differences in structural networks between morphologically homogeneous groups are remarkable and may contribute to a better understanding of psychosis in TLE.