Connectome reorganization associated with temporal lobe pathology and its surgical resection.

Network neuroscience offers a unique framework to understand the organizational principles of the human brain. Despite recent progress, our understanding of how the brain is modulated by focal lesions remains incomplete. Resection of the temporal lobe is the most effective treatment to control seizures in pharmaco-resistant temporal lobe epilepsy (TLE), making this syndrome a powerful model to study lesional effects on network organization in young and middle-aged adults. Here, we assessed the downstream consequences of a focal lesion and its surgical resection on the brain's structural connectome, and explored how this reorganization relates to clinical variables at the individual patient level. We included adults with pharmaco-resistant TLE (n = 37) who underwent anterior temporal lobectomy between two imaging time points, as well as age- and sex-matched healthy controls who underwent comparable imaging (n = 31). Core to our analysis was the projection of high-dimensional structural connectome data-derived from diffusion MRI tractography from each subject-into lower-dimensional gradients. We then compared connectome gradients in patients relative to controls before surgery, tracked surgically-induced connectome reconfiguration from pre- to postoperative time points, and examined associations to patient-specific clinical and imaging phenotypes. Before surgery, individuals with TLE presented with marked connectome changes in bilateral temporo-parietal regions, reflecting an increased segregation of the ipsilateral anterior temporal lobe from the rest of the brain. Surgery-induced connectome reorganization was localized to this temporo-parietal subnetwork, but primarily involved postoperative integration of contralateral regions with the rest of the brain. Using a partial least-squares analysis, we uncovered a latent clinical-imaging signature underlying this pre- to postoperative connectome reorganization, showing that patients who displayed postoperative integration in bilateral fronto-occipital cortices also had greater preoperative ipsilateral hippocampal atrophy, lower seizure frequency, and secondarily generalized seizures. Our results bridge the effects of focal brain lesions and their surgical resections with large-scale network reorganization and inter-individual clinical variability, thus offering new avenues to examine the fundamental malleability of the human brain.

Protein-based bioactive coatings: from nanoarchitectonics to applications.

Protein-based bioactive coatings have emerged as a versatile and promising strategy for enhancing the performance and biocompatibility of diverse biomedical materials and devices. Through surface modification, these coatings confer novel biofunctional attributes, rendering the material highly bioactive. Their widespread adoption across various domains in recent years underscores their importance. This review systematically elucidates the behavior of protein-based bioactive coatings in organisms and expounds on their underlying mechanisms. Furthermore, it highlights notable advancements in artificial synthesis methodologies and their functional applications in vitro. A focal point is the delineation of assembly strategies employed in crafting protein-based bioactive coatings, which provides a guide for their expansion and sustained implementation. Finally, the current trends, challenges, and future directions of protein-based bioactive coatings are discussed.

Dual functional antifouling and bactericidal proteinaceous coating.

Coatings with both anti-fouling and bactericidal functions are used in many fields. In this work, lysozyme (Lyso) and poly (2-Methylallyloxyethyl phosphorylcholine) (PMPC) conjugate (Lyso-PMPC) is successfully designed and synthesized for the first time. A new nanofilm (PTL-PMPC) is then obtained by phase transition of lysozyme via the reduction of disulfide bonds in Lyso-PMPC. Benefit from lysozyme amyloid-like aggregates as surface anchors, the nanofilm shows excellent stability, it remains unchanged after treatment under extreme conditions such as ultrasonic and 3 M tape peeling. Due to the presence of zwitterionic polymer (PMPC) brush, the PTL-PMPC film has excellent antifouling properties against cell, bacterium, fungi, proteins, biofluids, phosphatide, polyose, esters, and carbohydrates. Meanwhile, the PTL-PMPC film is colourless and transparent. Further, a new coating (PTL-PMPC/PHMB) is fabricated by hybridizing PTL-PMPC with poly (hexamethylene biguanide) (PHMB). This coating had excellent antibacterial properties, and the antibacterial rate against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) is more than 99.99%. In addition, the coating exhibit good hemocompatibility and low cytotoxicity.

Lipid-accumulated reactive astrocytes promote disease progression in epilepsy.

Reactive astrocytes play an important role in neurological diseases, but their molecular and functional phenotypes in epilepsy are unclear. Here, we show that in patients with temporal lobe epilepsy (TLE) and mouse models of epilepsy, excessive lipid accumulation in astrocytes leads to the formation of lipid-accumulated reactive astrocytes (LARAs), a new reactive astrocyte subtype characterized by elevated APOE expression. Genetic knockout of APOE inhibited LARA formation and seizure activities in epileptic mice. Single-nucleus RNA sequencing in TLE patients confirmed the existence of a LARA subpopulation with a distinct molecular signature. Functional studies in epilepsy mouse models and human brain slices showed that LARAs promote neuronal hyperactivity and disease progression. Targeting LARAs by intervention with lipid transport and metabolism could thus provide new therapeutic options for drug-resistant TLE.

Amyloid-Mediated Nanoarchitectonics with Biomimetic Mineralization of Polyetheretherketone for Enhanced Osseointegration.

Polyetheretherketone (PEEK), a widely used implant material, has attracted the attention of scientific researchers because of its bone-matched elastic modulus, radiolucency, and chemical resistance. However, the bioinert chemical properties of PEEK do not promote bone apposition once implanted. In this study, using a phase-transitioned lysozyme (PTL) nanofilm as a sandwiched layer, a robust hydroxyapatite (HAp) coating on PEEK (HAp@PTL@PEEK) is constructed. The PTL nanofilm shows strong adhesion to the PEEK surface and induces biomimetic mineralization to form a compact HAp coating on PEEK in simulated body fluids. This HAp coating not only shares a higher adhesion strength and better stability but can also be applied to implants with complex 3D structures. HAp@PTL@PEEK showed significantly enhanced osteogenic capacity when cultured with rat bone marrow mesenchymal stem cells by promoting initial cell adhesion, proliferation, and osteogenic differentiation in vitro. In vivo evaluations utilizing models of femoral condyle defects and skull defects confirm that the HAp coating substantially augments bone remodeling and osseointegration ability. Compared with the traditional method, our modified method is simpler, more environmentally friendly, and uses less hazardous components. Furthermore, the obtained HAp coating shares a higher adhesion strength to PEEK and a better osteogenic capacity. The study offers a novel method to improve the osseointegration of PEEK-based implants in biointerfaces and tissue engineering.

Altered spontaneous brain activity as a potential imaging biomarker for generalized and focal to bilateral tonic-clonic seizures: A resting-state fMRI study.

OBJECTIVE: We aimed to determine whether alterations in spontaneous regional brain activity in those with generalized tonic-clonic seizures (GTCS) and focal to bilateral tonic-clonic seizures (FBTCS) and explore whether the alterations could be used as biomarkers to classify disease subtypes through support vector machine analysis (SVM). METHODS: The fractional amplitude of low-frequency fluctuations (fALFF) and regional homogeneity (ReHo) from resting-state functional magnetic resonance imaging (rs-fMRI) data were extracted from 57 patients with GTCS, 35 patients with FBTCS, and 50 age-matched and sex-matched normal controls (NCs) using the DPARSF 5.0 toolbox. Between-group comparisons were adjusted for covariates (age, sex, and equipment). Correlation analyses between imaging biomarkers and the frequency or duration of seizure activity were calculated using partial correlations. The differential imaging indicators, age, and sex were considered as the discriminative features in the SVM to evaluate classification performance. RESULTS: The patients with GTCS showed lower fALFF values (voxel p < 0.001, cluster p < 0.05, Gaussian random field corrected, GRF corrected) in the right postcentral gyrus and precentral gyrus and lower ReHo values (GRF corrected) in the middle temporal gyrus than the NCs. The patients with FBTCS showed higher fALFF (GRF corrected) values in the right postcentral and precentral gyrus and higher ReHo (GRF corrected) values in the right postcentral gyrus. Both fALFF (GRF corrected) and ReHo (GRF corrected) values were lower in the right postcentral gyrus and precentral gyrus in the GTCS group than in the FBTCS group. In patients with FBTCS, fALFF values in the right postcentral and precentral gyrus were positively correlated with duration (r = 0.655, p = 0.008, Bonferroni corrected) in the low-duration group, and ReHo values in the right postcentral gyrus were positively correlated with frequency (r = 0.486, p = 0.022, uncorrected) in the low-frequency group. SVM results showed receiver operating characteristic curves of 0.89, 0.87, and 0.76 for the classification between GTCS and NC, between FBTCS and NC, and GTCS and FBTCS, respectively. SIGNIFICANCE: This study detected alterations in fALFF and ReHo in the postcentral gyrus and precentral gyrus in patients with GTCS and FBTCS, which might contribute to understanding the pathogenesis, disease classification, and clinical targeted therapy.

Predicting MGMT Promoter Methylation in Diffuse Gliomas Using Deep Learning with Radiomics.

This study aimed to investigate the feasibility of predicting oxygen 6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in diffuse gliomas by developing a deep learning approach using MRI radiomics. A total of 111 patients with diffuse gliomas participated in the retrospective study (56 patients with MGMT promoter methylation and 55 patients with MGMT promoter unmethylation). The radiomics features of the two regions of interest (ROI) (the whole tumor area and the tumor core area) for four sequences, including T1 weighted image (T1WI), T2 weighted image (T2WI), apparent diffusion coefficient (ADC) maps, and T1 contrast-enhanced (T1CE) MR images were extracted and jointly fed into the residual network. Then the deep learning method was developed and evaluated with a five-fold cross-validation, where in each fold, the dataset was randomly divided into training (80%) and validation (20%) cohorts. We compared the performance of all models using area under the curve (AUC) and average accuracy of validation cohorts and calculated the 10 most important features of the best model via a class activation map. Based on the ROI of the whole tumor, the predictive capacity of the T1CE and ADC model achieved the highest AUC value of 0.85. Based on the ROI of the tumor core, the T1CE and ADC model achieved the highest AUC value of 0.90. After comparison, the T1CE combined with the ADC model based on the ROI of the tumor core exhibited the best performance, with the highest average accuracy (0.91) and AUC (0.90) among all models. The deep learning method using MRI radiomics has excellent diagnostic performance with a high accuracy in predicting MGMT promoter methylation in diffuse gliomas.

Preparation of a reusable and pore size controllable porous polymer monolith and its catalysis of biodiesel synthesis.

A sulfonated porous polymer monolith (PPM-SO3H) has been prepared via the polymerisation of styrene (St) and divinyl benzene (DVB) with organic microspheres as pore-forming agents, followed by sulfonation with concentrated sulfuric acid. It was characterized by acid-base titration in order to determine its acid density, scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared (FT-IR) spectroscopy, mercury intrusion porosimetry (MIP) and thermogravimetric analysis (TG). The PPM-SO3H showed an acid density of 1.89 mmol g-1 and pore cavities with an average diameter of 870 nm. The catalytic activity of PPM-SO3H in practical biodiesel synthesis from waste fatty acids was investigated and the main reaction parameters were optimized through orthogonal experiment. The best reaction conditions obtained for the optimization of methanol to oil ratio, catalyst concentration, reaction temperature and reaction time were 1 : 1, 20%, 80 °C and 8 h, respectively. PPM-SO3H showed excellent catalytic activity. In biodiesel synthesis, the esterification rate of PPM-SO3H is 96.9%, which is much higher than that of commercial poly(sodium-p-styrenesulfonate) (esterification rate 29.0%). The PPM-SO3H can be reused several times without significant loss of catalytic activity; the esterification rate was still 90.8% after 6 cycles. The pore size of this porous polymer monolith can be controlled. The dimension and shape of this porous polymer monolith were also adjustable by choosing a suitable polymerisation container.

Causal structural covariance network revealing atrophy progression in Alzheimer's disease continuum.

The structural covariance network (SCN) has provided a perspective on the large-scale brain organization impairment in the Alzheimer's Disease (AD) continuum. However, the successive structural impairment across brain regions, which may underlie the disrupted SCN in the AD continuum, is not well understood. In the current study, we enrolled 446 subjects with AD, mild cognitive impairment (MCI) or normal aging (NA) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The SCN as well as a casual SCN (CaSCN) based on Granger causality analysis were applied to the T1-weighted structural magnetic resonance images of the subjects. Compared with that of the NAs, the SCN was disrupted in the MCI and AD subjects, with the hippocampus and left middle temporal lobe being the most impaired nodes, which is in line with previous studies. In contrast, according to the 194 subjects with records on CSF amyloid and Tau, the CaSCN revealed that during AD progression, the CaSCN was enhanced. Specifically, the hippocampus, thalamus, and precuneus/posterior cingulate cortex (PCC) were identified as the core regions in which atrophy originated and could predict atrophy in other brain regions. Taken together, these findings provide a comprehensive view of brain atrophy in the AD continuum and the relationships among the brain atrophy in different regions, which may provide novel insight into the progression of AD.

Atrophy in the Left Amygdala Predicted Drug Responses in Idiopathic Generalized Epilepsy Patients With Tonic-Clonic Seizures.

We aimed to determine the alterations in the subcortical structures of patients with idiopathic generalized epilepsy with tonic-clonic seizures (IGE-GTCS) via MRI volumetry and vertex-based shape analysis and to evaluate the relationships between MRI measures and drug responses. In a follow-up sample of 48 patients with IGE-GTCS and 48 matched normal controls (NCs), high-resolution 3D T1WI was performed at baseline. After 1 year of follow-up, 31 patients were classified as seizure free (SF) and 17 as drug resistant (DR). The volumes of subcortical structures were extracted, and vertex-based shape analysis was performed using FSL-Integrated Registration and Segmentation Toolbox (FSL-FIRST). Comparisons among groups were calculated adjusting for covariates [age, sex, and intracranial volume (ICV)]. Analysis of the relationships among imaging biomarkers along with frequency and duration was assessed using partial correlations. The differential imaging indicators were used as features in a linear support vector machine (LSVM). The DR group displayed significant regional atrophy in the volume of the left amygdala compared with NCs (p = 0.004, false discovery rate corrected) and SF patients (p = 0.029, uncorrected). Meanwhile, vertex-based shape analysis showed focal inward deformation in the basolateral subregion of the left amygdala in DR compared with the results for SF and NC (p < 0.05, FWE corrected). There were significant correlations between the volume changes and seizure frequency (r = -0.324, p = 0.030) and between shape (r = -0.438, p = 0.003) changes and seizure frequency. Moreover, the volume of the left thalamus in the DR group was significantly correlated with seizure frequency (r = -0.689, p = 0.006). The SVM results revealed areas under the receiver operating characteristic curve of 0.82, 0.68, and 0.88 for the classification between SF and DR, between SF and NC, and between DR and NC, respectively. This study indicates the presence of focal atrophy in the basolateral region of the left amygdala in patients with IGE drug resistance; this finding may help predict drug responses and suggests a potential therapeutic target.

Functional connectome contractions in temporal lobe epilepsy: Microstructural underpinnings and predictors of surgical outcome.

OBJECTIVE: Temporal lobe epilepsy (TLE) is the most common drug-resistant epilepsy in adults. Although it is commonly related to hippocampal pathology, increasing evidence suggests structural changes beyond the mesiotemporal lobe. Functional anomalies and their link to underlying structural alterations, however, remain incompletely understood. METHODS: We studied 30 drug-resistant TLE patients and 57 healthy controls using multimodal magnetic resonance imaging (MRI) analyses. All patients had histologically verified hippocampal sclerosis and underwent postoperative imaging to outline the extent of their surgical resection. Our analysis leveraged a novel resting-state functional MRI framework that parameterizes functional connectivity distance, consolidating topological and physical properties of macroscale brain networks. Functional findings were integrated with morphological and microstructural metrics, and utility for surgical outcome prediction was assessed using machine learning techniques. RESULTS: Compared to controls, TLE patients showed connectivity distance reductions in temporoinsular and prefrontal networks, indicating topological segregation of functional networks. Testing for morphological and microstructural associations, we observed that functional connectivity contractions occurred independently from TLE-related cortical atrophy but were mediated by microstructural changes in the underlying white matter. Following our imaging study, all patients underwent an anterior temporal lobectomy as a treatment of their seizures, and postsurgical seizure outcome was determined at a follow-up at least 1 year after surgery. Using a regularized supervised machine learning paradigm with fivefold cross-validation, we demonstrated that patient-specific functional anomalies predicted postsurgical seizure outcome with 76 ± 4% accuracy, outperforming classifiers operating on clinical and structural imaging features. SIGNIFICANCE: Our findings suggest connectivity distance contractions as a macroscale substrate of TLE. Functional topological isolation may represent a microstructurally mediated network mechanism that tilts the balance toward epileptogenesis in affected networks and that may assist in patient-specific surgical prognostication.

Clinical characteristics of patients with anti-EJ antisynthetase syndrome associated interstitial lung disease and literature review.

AIM: Interstitial lung disease (ILD) is an extra-muscular manifestation of antisynthetase syndrome (ASS). The aim of this study is to analyze the clinical characteristics of anti-EJ associated ILD in a large cohort of patients. METHODS: Retrospective cohort study of patients with anti-EJ associated ILD. All available data of clinical and laboratory characteristics, pulmonary function tests, laboratory parameters, high resolution computed tomography (HRCT) and treatment were collected and analyzed from medical records. RESULTS: We identified 51 subjects. Average age at diagnosis was 55.6 years. Thirty-two of 51 patients were female. Concurrent autoantibodies against Ro52 were seen in 92.2% patients studied. HRCT patterns were mainly non-specific interstitial pneumonia (NSIP). The predominant myositis subset was amyopathic dermatomyositis (ADM) (41.2%) followed by dermatomyositis and polymyositis. Thirty-four patients improved on corticosteroids alone or in combination with immunosuppressive drugs as treatment and ten patients were stabilized. However, eleven patients (21.6%) initially improved during 12.0 ± 4.4 months, then progressively recurred despite steroid treatment (mean prednisone dose 11.6 ± 3.5 mg). The recurrence group included a significantly higher proportion of patients with NSIP pattern (p < 0.05). In the literature review the most common manifestations of anti-EJ ASS were ILD (89.3%) and myositis (58.9%). CONCLUSION: ILD are common features of the anti-EJ ASS. Patients with anti-EJ ILD often had an onset of ILD with lower lung-predominant opacities and NSIP. Although the disease responded well to the initial combination therapy of corticosteroid and immunosuppressant, recurrence was frequent. NSIP pattern was significantly more frequent in the recurrence group.

Interaction of COMT and KIBRA modulates the association between hippocampal structure and episodic memory performance in healthy young adults.

Genetic variations of COMT and KIBRA, which were reported to be expressed in the hippocampus, have been linked to memory function. However, their interaction on the hippocampal structure remains unknown. This study aimed to explore the interaction effects of COMT rs4680 and KIBRA rs17070145 on the hippocampal subfield volumes and test their associations with hippocampus-memory relationship in 187 healthy young adults. Two-way analysis of covariance was applied to the alterations in hippocampal subfield volumes among COMT and KIBRA genotypes. Significant interaction effects of these two genes were found in the right CA1 and CA3 subfields. Among KIBRA C-allele carriers, COMT Val/Val homozygotes showed greater volume in these regions than COMT Met-allele carriers. Furthermore, the slope of the correlation between right CA1 volume and immediate recall on the California Verbal Learning Test-II (CVLT-II) (F = 4.36, p = 0.041) as well as CVLT-II delayed recall (F = 6.44, p = 0.014) were significantly different between COMT Val/Val homozygotes and Met-allele carriers, which were positive or tend to be positive in COMT Val/Val group (CVLT immediate recall, r = 0.319, p = 0.040; CVLT delayed recall, r = 0.304, p = 0.051), but absent in COMT Met-allele carriers (CVLT immediate recall, r = -0.263, p = 0.205; CVLT delayed recall, r = -0.351, p = 0.086). These findings may provide a novel insight into the genetic effects upon the hippocampal structure and suggest that the conjoint effects of COMT and KIBRA played a modulatory role in the hippocampus-episodic memory correlation.

Community-informed connectomics of the thalamocortical system in generalized epilepsy.

OBJECTIVE: To study the intrinsic organization of the thalamocortical circuitry in patients with generalized epilepsy with tonic-clonic seizures (GTCS) via resting-state fMRI (rs-fMRI) connectome analysis and to evaluate its relation to drug response. METHODS: In a prospectively followed-up sample of 41 patients and 27 healthy controls, we obtained rs-fMRI and structural MRI. After 1 year of follow-up, 27 patients were classified as seizure-free and 14 as drug-resistant. We examined connectivity within and between resting-state communities in cortical and thalamic subregions. In addition to comparing patients to controls, we examined associations with seizure control. We assessed reproducibility in an independent cohort of 21 patients. RESULTS: Compared to controls, patients showed a more constrained network embedding of the thalamus, while frontocentral neocortical regions expressed increased functional diversity. Findings remained significant after regressing out thalamic volume and cortical thickness, suggesting independence from structural alterations. We observed more marked network imbalances in drug-resistant compared to seizure-free patients. Findings were similar in the reproducibility dataset. CONCLUSIONS: Our findings suggest a pathoconnectomic mechanism of generalized epilepsy centered on diverging changes in cortical and thalamic connectivity. More restricted thalamic connectivity could reflect the tendency to engage in recursive thalamocortical loops, which may contribute to hyperexcitability. Conversely, increased connectional diversity of frontocentral networks may relay abnormal activity to an extended bilateral territory. Network imbalances were observed shortly after diagnosis and related to future drug response, suggesting clinical utility.

Impaired hippocampal functional connectivity in patients with drug resistant, generalized tonic-clonic seizures.

The aim of this study was to better understand the imaging features of drug-resistant epilepsy (DRE), especially in idiopathic generalized tonic-clonic seizure (GTCS), as well as to discover the associated mechanisms and functional connectivity (FC). A total of 31 idiopathic generalized epilepsy-GTCS patients and 17 healthy controls were enrolled. For each patient, resting-state functional MRI was performed. After a 12-month follow-up observation, patients were further divided into either drug-resistant (DR) or drug-sensitive (DS) groups. Compared to the DS group, DR patients had previously received more types of antiepileptic drugs and had taken more types of failed antiepileptic drugs. There were distinct FC changes toward the left thalamus, left putamen, left precuneus, and right precentral gyrus in the left hippocampus between DR and DS patients. FCs in the DR group largely decreased or remained unchanged, while DS patients exhibited compensatory enhancement. Disease duration was negatively correlated with FC between the left hippocampus and the left thalamus-putamen in patients with DRE. Further, DRE patients had an extremely high area under the curve (0.978) and a cut-off FC between the left hippocampus and thalamus-putamen of 0.282. Together, hippocampal FCs in patients with DR GTCS were impaired and time-dependently correlated with disease duration. Hippocampal FCs in DS patients showed overall compensatory enhancement, which could be used as a sensitive and specific marker to identify and predict DR GTCS.

Functional Connectome before and following Temporal Lobectomy in Mesial Temporal Lobe Epilepsy.

As mesial temporal lobe epilepsy (mTLE) has been recognized as a network disorder, a longitudinal connectome investigation may shed new light on the understanding of the underlying pathophysiology related to distinct surgical outcomes. Resting-state functional MRI data was acquired from mTLE patients before (n = 37) and after (n = 24) anterior temporal lobectomy. According to surgical outcome, patients were classified as seizure-free (SF, n = 14) or non-seizure-free (NSF, n = 10). First, we found higher network resilience to targeted attack on topologically central nodes in the SF group compared to the NSF group, preoperatively. Next, a two-way mixed analysis of variance with between-subject factor 'outcome' (SF vs. NSF) and within-subject factor 'treatment' (pre-operation vs. post-operation) revealed divergent dynamic reorganization in nodal topological characteristics between groups, in the temporoparietal junction and its connection with the ventral prefrontal cortex. We also correlated the network damage score (caused by surgical resection) with postsurgical brain function, and found that the damage score negatively correlated with postoperative global and local parallel information processing. Taken together, dynamic connectomic architecture provides vital information for selecting surgical candidates and for understanding brain recovery mechanisms following epilepsy surgery.

Connectome Reorganization Associated With Surgical Outcome in Temporal Lobe Epilepsy.

To identify the distinct pattern of anatomical network reorganization in surgically refractory mesial temporal lobe epilepsy (MTLE) patients using a longitudinal design. We collected longitudinal diffusion-weighted images of 19 MTLE patients before and after anterior temporal lobectomy. Patients were classified as seizure-free (SF) or nonseizure-free (NSF) at least 1 year after surgery. We constructed whole-brain anatomical networks derived from white matter tractography and evaluated network connectivity measures by graph theoretical analysis. The reorganization trajectories of network measures in SF and NSF patients were investigated by two-way mixed analysis of variance, with factors "group" (SF vs NSF) and "treatment" (presurgery vs postsurgery). Widespread brain structures showed opposite reorganization trajectories in FS and NSF groups (interaction effect). Most of them showed group difference before surgery and then converge after surgery, suggesting that surgery remodeled these structures into a similar status. Conversly, contralateral amygdala-planum-temporale and thalamic-parietal tracts showed higher connectivity strength in NSF than in SF patients after surgery, indicating maladaptive neuroplastic responses to surgery in NSF patients. Our findings suggest that surgical outcomes are associated not only with the preoperative pattern of anatomical connectivity, but also with connectome reconfiguration following surgery. The reorganization of contralateral temporal lobe and corticothalamic tracts may be particularly important for seizure control in MTLE.

Frequency-Specific Alterations of Local Synchronization in Idiopathic Generalized Epilepsy.

Recurrently and abnormally hypersynchronous discharge is a striking feature of idiopathic generalized epilepsy (IGE). Resting-state functional magnetic resonance imaging has revealed aberrant spontaneous brain synchronization, predominately in low-frequency range (<0.1 Hz), in individuals with IGE. Little is known, however, about these changes in local synchronization across different frequency bands. We examined alterations to frequency-specific local synchronization in terms of spontaneous blood oxygen level-dependent (BOLD) fluctuations across 5 bands, spanning 0 to 0.25 Hz. Specifically, we compared brain activity in a large cohort of IGE patients (n = 86) to age- and sex-matched normal controls (n = 86). IGE patients showed decreased local synchronization in low frequency (<0.073 Hz), primarily in the default mode network (DMN). IGE patients also exhibited increased local synchronization in high-frequency (>0.073 Hz) in a "conscious perception network," which is anchored by the pregenual and dorsal anterior cingulate cortex, as well as the bilateral insular cortices, possibly contributing to impaired consciousness. Furthermore, we found frequency-specific alternating local synchronization in the posterior portion of the DMN relative to the anterior part, suggesting an interaction between the disease and frequency bands. Importantly, the aberrant high-frequency local synchronization in the middle cingulate cortex was associated with disease duration, thus linking BOLD frequency changes to disease severity. These findings provide an overview of frequency-specific local synchronization of BOLD fluctuations, and may be helpful in uncovering abnormal synchronous neuronal activity in patients with IGE at specific frequency bands.

Pathological uncoupling between amplitude and connectivity of brain fluctuations in epilepsy.

Amplitude and functional connectivity are two fundamental parameters for describing the spontaneous brain fluctuations. These two parameters present close coupling in physiological state, and present different alteration patterns in epilepsy revealed by functional MRI (fMRI). We hypothesized that the alteration of coupling between these two imaging parameters may be underpinned by specific pathological factors of epilepsy, and can be employed to improve the capability for epileptic focus detection. Forty-seven patients (26 left- and 21 right-sided) with mesial temporal lobe epilepsy (mTLE) and 32 healthy controls underwent resting-state fMRI scans. All patients were detected to have interictal epileptic discharges on simultaneous electroencephalograph (EEG) recordings. Amplitude-connectivity coupling was calculated by correlating amplitude and functional connectivity density of low-frequency brain fluctuations. We observed reduced amplitude-connectivity coupling associated with epileptic discharges in the mesial temporal regions in both groups of patients, and increased coupling associated with epilepsy durations in the posterior regions of the default-mode network in the right-sided patients. Moreover, we proposed a new index of amplitude subtracting connectivity, which elevated imaging contrast for differentiating the patients from the controls. The findings indicated that epileptic discharges and chronic damaging effect of epilepsy might both contribute to alterations of amplitude-connectivity coupling in different pivotal regions in mTLE. Investigation on imaging coupling provides synergistic approach for describing brain functional changing features in epilepsy.

Brain iron redistribution in mesial temporal lobe epilepsy: a susceptibility-weighted magnetic resonance imaging study.

BACKGROUND: The roles of iron in epilepsy and its pathophysiological significance are poorly understood, especially whether iron levels are abnormal in subcortcal structures. This study aims to demonstrate whole-brain iron alterations and its clinical relevancies in mesial temporal lobe epilepsy (mTLE) in vivo, using susceptibility-weighted magnetic resonance imaging (SWI). METHODS: We studied 62 patients with mTLE and 62 healthy controls. Brain iron concentration was quantified using SWI phase values. Voxel-wise analysis was carried out to compare iron levels between mTLE and controls, and to assess the relationship between altered iron concentration and clinical parameters in mTLE. RESULTS: Patients with mTLE showed decreases of iron levels in the subcortical structures such as substantia nigra, red nucleus, and basal ganglia. Conversely, iron levels were decreased in the cortex. Subcortical iron levels were negatively correlated to those in the cortex. Moreover, cortical and basal ganglia iron levels were related to clinical variables including epilepsy duration, age at seizures onset, and histories of precipitating factors. CONCLUSIONS: Our SWI findings suggest a redistribution of iron between subcortical and cortical structures in mTLE. The degree of redistribution is affected by both progression of epilepsy and precipitating factors. Investigation on brain iron redistribution offers new insights into the pathogenesis of mTLE, and may be a potential biomarker for monitoring the clinical progression of epilepsy.