Networks In Temporal Lobe Epilepsy Research Articles

Olfactory Dysfunction and Limbic Hypoactivation in Temporal Lobe Epilepsy.

The epileptogenic network in temporal lobe epilepsy (TLE) contains structures of the primary and secondary olfactory cortex such as the piriform and entorhinal cortex, the amygdala, and the hippocampus. Olfactory auras and olfactory dysfunction are relevant symptoms of TLE. This study aims to characterize olfactory function in TLE using olfactory testing and olfactory functional magnetic resonance imaging (fMRI). We prospectively enrolled 20 individuals with unilateral TLE (age 45 ± 20 years [mean ± SD], 65% female, 90% right-handed) and 20 healthy individuals (age 33 ± 15 years [mean ± SD], 35% female, 90% right-handed). In the TLE group, the presumed seizure onset zone was left-sided in 75%; in 45% of the individuals with TLE limbic encephalitis was the presumed etiology; and 15% of the individuals with TLE reported olfactory auras. Olfactory function was assessed with a Screening Sniffin' Sticks Test (Burkhart, Wedel, Germany) during a pre-assessment. During a pre-testing, all individuals were asked to rate the intensity, valence, familiarity, and associated memory of five different odors (eugenol, vanillin, phenethyl alcohol, decanoic acid, valeric acid) and a control solution. During the fMRI experiment, all individuals repeatedly smelled eugenol (positively valenced odor), valeric acid (negatively valenced odor), and the control solution and were asked to rate odor intensity on a five-point Likert scale. We acquired functional EPI sequences and structural images (T1, T2, FLAIR). Compared to healthy individuals, individuals with TLE rated the presented odors as more neutral (two-sided Mann-Whitney U tests, FDR-p < 0.05) and less familiar (two-sided Mann-Whitney U tests, FDR-p < 0.05). fMRI data analysis revealed a reduced response contrast in secondary olfactory areas (e.g., hippocampus) connected to the limbic system when comparing eugenol and valeric acid in individuals with TLE when compared with healthy individuals. However, no lateralization effect was obtained when calculating a lateralization index by the number of activated voxels in the olfactory system (two-sided Mann-Whitney U test; U = 176.0; p = 0.525). TLE is characterized by olfactory dysfunction and associated with hypoactivation of secondary olfactory structures connected to the limbic system. These findings contribute to our understanding of the pathophysiology of TLE. This study was preregistered on OSF Registries (www.osf.io).

Non-classical event-related potentials reveal attention network alteration in patients with temporal lobe epilepsy

ObjectiveTo explore the characteristic changes of multiple ERP components associated with attention impairments in patients with temporal lobe epilepsy (TLE). MethodsA total of 92 patients diagnosed with TLE at Xiangya Hospital during May 2022 and January 2023 and 85 healthy controls were included in this study. Participants were asked to complete attention network test with recording of electroencephalogram. ResultsCompared with healthy controls, significant lower amplitudes (cue-related N1, N2 and CNV) and longer latencies (target-related N2) were found in TLE patients. Besides classical components, other components could also reveal the impairments of attention function. Cue-related N1 (p ≤ 0.007) and N2 (p ≤ 0.01) components indicated impaired alerting and orienting network in TLE. And cue-related CNV-E component (p = 0.003) promoted the alerting network was damaged and target-related N2 component (p = 0.008) indicated the executive control network was impaired. ConclusionThese findings consummate the non-classical ERP features of attention impairments in TLE patients. SignificanceThe above findings have strong clinical guiding significance for early identification and intervention.

Altered structural network in temporal lobe epilepsy with focal to bilateral tonic-clonic seizures.

This study aims to investigate whether alterations in white matter topological networks are associated with focal to bilateral tonic-clonic seizures (FBTCS) in temporal lobe epilepsy (TLE). Additionally, we investigated the variables contributing to memory impairment in TLE. This cross-sectional study included 88 unilateral people with TLE (45 left/43 right), and 42 healthy controls. Graph theory analysis was employed to compare the FBTCS (+) group (n = 51) with the FBTCS (-) group (n = 37). The FBTCS (+) group was subcategorized into current-FBTCS (n = 31) and remote-FBTCS (n = 20), based on the history of FBTCS within 1 year or longer than 1 year before scanning, respectively. We evaluated the discriminatory power of topological network properties by receiver operating characteristic (ROC) analysis. Generalized linear models (GLMs) were employed to investigate variables associated with memory impairment in TLE. Global efficiency (Eg) was significantly reduced in the FBTCS (+) group, especially in the current-FBTCS subgroup. Greater disruption of regional properties in the ipsilateral occipital and temporal association cortices was observed in the FBTCS (+) group. ROC analysis revealed that Eg, normalized characteristic shortest path length, and nodal efficiency of the ipsilateral middle temporal gyrus could distinguish between FBTCS (+) and FBTCS (-) groups. Additionally, GLMs linked the occurrence of current FBTCS with poorer verbal memory outcomes in TLE. Our study suggests that abnormal networks could be the structural basis of seizure propagation in FBTCS. Strategies aimed at reducing the occurrence of FBTCS could potentially improve the memory outcomes in people with TLE.

Associations of Cerebral Blood Flow Patterns With Gray and White Matter Structure in Patients With Temporal Lobe Epilepsy.

Neuroimaging studies in patients with temporal lobe epilepsy (TLE) show widespread brain network alterations beyond the mesiotemporal lobe. Despite the critical role of the cerebrovascular system in maintaining whole-brain structure and function, changes in cerebral blood flow (CBF) remain incompletely understood in the disease. Here, we studied whole-brain perfusion and vascular network alterations in TLE and assessed its associations with gray and white matter compromises and various clinical variables. We included individuals with and without pharmaco-resistant TLE who underwent multimodal 3T MRI, including arterial spin labelling, structural, and diffusion-weighted imaging. Using surface-based MRI mapping, we generated individualized cortico-subcortical profiles of perfusion, morphology, and microstructure. Linear models compared regional CBF in patients with controls and related alterations to morphological and microstructural metrics. We further probed interregional vascular networks in TLE, using graph theoretical CBF covariance analysis. The effects of disease duration were explored to better understand the progressive changes in perfusion. We assessed the utility of perfusion in separating patients with TLE from controls using supervised machine learning. Compared with control participants (n = 38; mean ± SD age 34.8 ± 9.3 years; 20 females), patients with TLE (n = 24; mean ± SD age 35.8 ± 10.6 years; 12 females) showed widespread CBF reductions predominantly in fronto-temporal regions (Cohen d -0.69, 95% CI -1.21 to -0.16), consistent in a subgroup of patients who remained seizure-free after surgical resection of the seizure focus. Parallel structural profiling and network-based models showed that cerebral hypoperfusion may be partially constrained by gray and white matter changes (8.11% reduction in Cohen d) and topologically segregated from whole-brain perfusion networks (area under the curve -0.17, p < 0.05). Negative effects of progressive disease duration further targeted regional CBF profiles in patients (r = -0.54, 95% CI -0.77 to -0.16). Perfusion-derived classifiers discriminated patients from controls with high accuracy (71% [70%-82%]). Findings were robust when controlling for several methodological confounds. Our multimodal findings provide insights into vascular contributions to TLE pathophysiology affecting and extending beyond mesiotemporal structures and highlight their clinical potential in epilepsy diagnosis. As our work was cross-sectional and based on a single site, it motivates future longitudinal studies to confirm progressive effects, ideally in a multicentric setting.

Alterations in DNA 5-hydroxymethylation patterns in the hippocampus of an experimental model of chronic epilepsy

Temporal lobe epilepsy (TLE) is a type of focal epilepsy characterized by spontaneous recurrent seizures originating from the hippocampus. The epigenetic reprogramming hypothesis of epileptogenesis suggests that the development of TLE is associated with alterations in gene transcription changes resulting in a hyperexcitable network in TLE. DNA 5-methylcytosine (5-mC) is an epigenetic mechanism that has been associated with chronic epilepsy. However, the contribution of 5-hydroxymethylcytosine (5-hmC), a product of 5-mC demethylation by the Ten-Eleven Translocation (TET) family proteins in chronic TLE is poorly understood. 5-hmC is abundant in the brain and acts as a stable epigenetic mark altering gene expression through several mechanisms. Here, we found that the levels of bulk DNA 5-hmC but not 5-mC were significantly reduced in the hippocampus of human TLE patients and in the kainic acid (KA) TLE rat model. Using 5-hmC hMeDIP-sequencing, we characterized 5-hmC distribution across the genome and found bidirectional regulation of 5-hmC at intergenic regions within gene bodies. We found that hypohydroxymethylated 5-hmC intergenic regions were associated with several epilepsy-related genes, including Gal, SV2, and Kcnj11 and hyperdroxymethylation 5-hmC intergenic regions were associated with Gad65, TLR4, and Bdnf gene expression. Mechanistically, Tet1 knockdown in the hippocampus was sufficient to decrease 5-hmC levels and increase seizure susceptibility following KA administration. In contrast, Tet1 overexpression in the hippocampus resulted in increased 5-hmC levels associated with improved seizure resiliency in response to KA. These findings suggest an important role for 5-hmC as an epigenetic regulator of epilepsy that can be manipulated to influence seizure outcomes.

Macroscale intrinsic dynamics are associated with microcircuit function in focal and generalized epilepsies

Epilepsies are a group of neurological disorders characterized by abnormal spontaneous brain activity, involving multiscale changes in brain functional organizations. However, it is not clear to what extent the epilepsy-related perturbations of spontaneous brain activity affect macroscale intrinsic dynamics and microcircuit organizations, that supports their pathological relevance. We collect a sample of patients with temporal lobe epilepsy (TLE) and genetic generalized epilepsy with tonic-clonic seizure (GTCS), as well as healthy controls. We extract massive temporal features of fMRI BOLD time-series to characterize macroscale intrinsic dynamics, and simulate microcircuit neuronal dynamics used a large-scale biological model. Here we show whether macroscale intrinsic dynamics and microcircuit dysfunction are differed in epilepsies, and how these changes are linked. Differences in macroscale gradient of time-series features are prominent in the primary network and default mode network in TLE and GTCS. Biophysical simulations indicate reduced recurrent connection within somatomotor microcircuits in both subtypes, and even more reduced in GTCS. We further demonstrate strong spatial correlations between differences in the gradient of macroscale intrinsic dynamics and microcircuit dysfunction in epilepsies. These results emphasize the impact of abnormal neuronal activity on primary network and high-order networks, suggesting a systematic abnormality of brain hierarchical organization.

Topological regularization of networks in temporal lobe epilepsy: a structural MRI study.

Patients with temporal lobe epilepsy (TLE) often exhibit neurocognitive disorders; however, we still know very little about the pathogenesis of cognitive impairment in patients with TLE. Therefore, our aim is to detect changes in the structural connectivity networks (SCN) of patients with TLE. Thirty-five patients with TLE were compared with 47 normal controls (NC) matched according to age, gender, handedness, and education level. All subjects underwent thin-slice T1WI scanning of the brain using a 3.0 T MRI. Then, a large-scale structural covariance network was constructed based on the gray matter volume extracted from the structural MRI. Graph theory was then used to determine the topological changes in the structural covariance network of TLE patients. Although small-world networks were retained, the structural covariance network of TLE patients exhibited topological irregularities in regular architecture as evidenced by an increase in the small world properties (p < 0.001), normalized clustering coefficient (p < 0.001), and a decrease in the transfer coefficient (p < 0.001) compared with the NC group. Locally, TLE patients showed a decrease in nodal betweenness and degree in the left lingual gyrus, right middle occipital gyrus and right thalamus compared with the NC group (p < 0.05, uncorrected). The degree of structural networks in both TLE (Temporal Lobe Epilepsy) and control groups was distributed exponentially in truncated power law. In addition, the stability of random faults in the structural covariance network of TLE patients was stronger (p = 0.01), but its fault tolerance was lower (p = 0.03). The objective of this study is to investigate the potential neurobiological mechanisms associated with temporal lobe epilepsy through graph theoretical analysis, and to examine the topological characteristics and robustness of gray matter structural networks at the network level.

Altered spread of waves of activities at large scale is influenced by cortical thickness organization in temporal lobe epilepsy: a magnetic resonance imaging-high-density electroencephalography study.

Temporal lobe epilepsy is a brain network disorder characterized by alterations at both the structural and the functional levels. It remains unclear how structure and function are related and whether this has any clinical relevance. In the present work, we adopted a novel methodological approach investigating how network structural features influence the large-scale dynamics. The functional network was defined by the spatio-temporal spreading of aperiodic bursts of activations (neuronal avalanches), as observed utilizing high-density electroencephalography in patients with temporal lobe epilepsy. The structural network was modelled as the region-based thickness covariance. Loosely speaking, we quantified the similarity of the cortical thickness of any two brain regions, both across groups and at the individual level, the latter utilizing a novel approach to define the subject-wise structural covariance network. In order to compare the structural and functional networks (at the nodal level), we studied the correlation between the probability that a wave of activity would propagate from a source to a target region and the similarity of the source region thickness as compared with other target brain regions. Building on the recent evidence that large-waves of activities pathologically spread through the epileptogenic network in temporal lobe epilepsy, also during resting state, we hypothesize that the structural cortical organization might influence such altered spatio-temporal dynamics. We observed a stable cluster of structure-function correlation in the bilateral limbic areas across subjects, highlighting group-specific features for left, right and bilateral temporal epilepsy. The involvement of contralateral areas was observed in unilateral temporal lobe epilepsy. We showed that in temporal lobe epilepsy, alterations of structural and functional networks pair in the regions where seizures propagate and are linked to disease severity. In this study, we leveraged on a well-defined model of neurological disease and pushed forward personalization approaches potentially useful in clinical practice. Finally, the methods developed here could be exploited to investigate the relationship between structure-function networks at subject level in other neurological conditions.

Dynamic causal modeling of reorganization of memory and language networks in temporal lobe epilepsy.

To evaluate the alterations of language and memory functions using dynamic causal modeling, in order to identify the epileptogenic hemisphere in temporal lobe epilepsy (TLE). Twenty-two patients with left TLE and 13 patients with right TLE underwent functional magnetic resonance imaging (fMRI) during four memory and four language mapping tasks. Dynamic causal modeling (DCM) was employed on fMRI data to examine effective directional connectivity in memory and language networks and the alterations in people with TLE compared to healthy individuals. DCM analysis suggested that TLE can influence the memory network more widely compared to the language network. For memory mapping, it demonstrated overall hyperconnectivity from the left hemisphere to the other cranial regions in the picture encoding, and from the right hemisphere to the other cranial regions in the word encoding tasks. On the contrary, overall hypoconnectivity was seen from the brain hemisphere contralateral to the seizure onset in the retrieval tasks. DCM analysis further manifested hypoconnectivity between the brain's hemispheres in the language network in patients with TLE compared to controls. The CANTAB® neuropsychological test revealed a negative correlation for the left TLE and a positive correlation for the right TLE cohorts for the connections extracted by DCM that were significantly different between the left and right TLE cohorts. In this study, dynamic causal modeling evidenced the reorganization of language and memory networks in TLE that can be used for a better understanding of the effects of TLE on the brain's cognitive functions.

The role of the thalamus in modular functional networks in temporal lobe epilepsy with cognitive impairment.

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. 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. 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. The thalamus plays a prominent role in modular networks and potentially represents a key neural mechanism underlying cognitive impairment in TLE.

ID:16474 Relating Neurocognition and Connectivity Between Arousal Structures and Intrinsic Connectivity Networks in Temporal Lobe Epilepsy

Despite temporal lobe epilepsy (TLE) being a focal syndrome, patients experience widespread brain deficits. It has been shown previously that intrinsic connectivity networks (ICNs) have abnormal connectivity in epilepsy patients. Additionally, we have previously shown abnormal connectivity in arousal structures in TLE. Arousal structures may modulate these ICNs. Here, we investigate if patients with TLE have perturbations in functional connectivity (non-directed and directed) between arousal structures and ICNs.

Disruption of Cerebellar-Cerebral Functional Connectivity in Temporal Lobe Epilepsy and the Connection to Language and Cognitive Functions.

ObjectiveTo 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.Methods30 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.ResultsCompared 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.ConclusionOur 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.

Structure and function of language networks in temporal lobe epilepsy.

Individuals with temporal lobe epilepsy (TLE) may have significant language deficits. Language capabilities may further decline following temporal lobe resections. The language network, comprising dispersed gray matter regions interconnected with white matter fibers, may be atypical in individuals with TLE. This review explores the structural changes to the language network and the functional reorganization of language abilities in TLE. We discuss the importance of detailed reporting of patient's characteristics, such as, left- and right-sided focal epilepsies as well as lesional and nonlesional pathological subtypes. These factors can affect the healthy functioning of gray and/or white matter. Dysfunction of white matter and displacement of gray matter function could concurrently impact their ability, in turn, producing an interactive effect on typical language organization and function. Surgical intervention can result in impairment of function if the resection includes parts of this structure-function network that are critical to language. In addition, impairment may occur if language function has been reorganized and is included in a resection. Conversely, resection of an epileptogenic zone may be associated with recovery of cortical function and thus improvement in language function. We explore the abnormality of functional regions in a clinically applicable framework and highlight the differences in the underlying language network. Avoidance of language decline following surgical intervention may depend on tailored resections to avoid critical areas of gray matter and their white matter connections. Further work is required to elucidate the plasticity of the language network in TLE and to identify sub-types of language representation, both of which will be useful in planning surgery to spare language function.

Characterization of Hippocampal-Thalamic-Cortical Morphometric Reorganization in Temporal Lobe Epilepsy.

IntroductionBrain cortico-subcortical connectivity has been investigated in epilepsy using the functional MRI (MRI). Although structural images cannot demonstrate dynamic changes, they provide higher spatial resolution, which allows exploration of the organization of brain in greater detail.MethodsWe used high-resolution brain MRI to study the hippocampal-thalamic-cortical networks in temporal lobe epilepsy (TLE) using a volume-based morphometric method. We enrolled 22 right-TLE, 33 left-TLE, and 28 age/gender-matched controls retrospectively. FreeSurfer software was used for the thalamus segmentation.ResultsAmong the 50 subfields, ipsilateral anterior, lateral, and parts of the intralaminar and medial nuclei, as well as the contralateral parts of lateral nuclei had significant volume loss in both TLE. The anteroventral nucleus was most vulnerable. Most thalamic subfields were susceptible to seizure burden, especially the left-TLE. SPM12 was used to conduct an analysis of the gray matter density (GMD) maps. Decreased extratemporal GMD occurred bilaterally. Both TLE demonstrated significant GMD loss over the ipsilateral inferior frontal gyrus, precentral gyrus, and medial orbital cortices.SignificanceThalamic subfield atrophy was related to the ipsilateral inferior frontal GMD changes, which presented positively in left-TLE and negatively in right-TLE. These findings suggest prefrontal-thalamo-hippocampal network disruption in TLE.

Association Between Anatomical Location of Surgically Induced Lesions and Postoperative Seizure Outcome in Temporal Lobe Epilepsy.

To determine the association between surgical lesions of distinct gray and white structures and connections with favorable postoperative seizure outcomes. Patients with drug-resistant temporal lobe epilepsy (TLE) from 3 epilepsy centers were included. We employed a voxel-based and connectome-based mapping approach to determine the association between favorable outcomes and surgery-induced temporal lesions. Analyses were conducted controlling for multiple confounders, including total surgical resection/ablation volume, hippocampal volumes, side of surgery, and site where the patient was treated. The cohort included 113 patients with TLE (54 women; 86 right-handed; mean age at seizure onset 16.5 years [SD 11.9]; 54.9% left) who were 61.1% free of disabling seizures (Engel Class 1) at follow-up. Postoperative seizure freedom in TLE was associated with (1) surgical lesions that targeted the hippocampus as well as the amygdala-piriform cortex complex and entorhinal cortices; (2) disconnection of temporal, frontal, and limbic regions through loss of white matter tracts within the uncinate fasciculus, anterior commissure, and fornix; and (3) functional disconnection of the frontal (superior and middle frontal gyri, orbitofrontal region) and temporal (superior and middle pole) lobes. Better postoperative seizure freedom is associated with surgical lesions of specific structures and connections throughout the temporal lobes. These findings shed light on the key components of epileptogenic networks in TLE and constitute a promising source of new evidence for future improvements in surgical interventions. This study provides Class II evidence that for patients with TLE, postoperative seizure freedom is associated with surgical lesions of specific temporal lobe structures and connections.

Identification and Validation of a Dysregulated miRNA-Associated mRNA Network in Temporal Lobe Epilepsy.

Objectives This study is aimed at exploring the relationships between miRNAs and mRNAs and to characterize their biological functions in temporal lobe epilepsy (TLE). Methods Novel clinical significant miRNAs and target genes and their potential underlying mechanisms have been discovered and explored by mining miRNAs and mRNA expression data of TLE patients using various bioinformatics methods. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to validate the bioinformatic analysis results. Results A total of 6 dysregulated miRNAs and 442 differentially expressed genes (DEGs) related to TLE were obtained from GEO database (GSE114701 and GSE127871 datasets). A protein-protein interaction (PPI) network containing the 442 DEGs was established. mRNA response elements from the 6 dysregulated miRNAs were predicted using the miRDB and TargetScan bioinformatic tools. By merging the identified targets of the dysregulated miRNAs and the 247 downregulated DEGs, a miRNA-mRNA network was constructed revealing the interaction of miR-484 with eight mRNAs (ABLIM2, CEP170B, CTD-3193O13.9, EFNA5, GAP43, PRKCB, FXYD7, and NCAN). A weighted correlation network analysis (WGCNA) based on the eight genes was established and demonstrated that these mRNAs, except FXYD7 and NCAN, were hub genes in the network. Gene Oncology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that the six hub genes were mainly involved in cellular-related biological functions and the neurotransmitter synapse pathway. The differences in expression levels of the miR-484 and the three hub genes (CTD-3193O13.9, EFNA5, and PRKCB) observed experimentally in TLE patients compared to those of healthy controls were consistent with the WGCNA prediction. Conclusion Our study suggests that understanding the miRNA-mRNA interactions will provide insights into the epilepsy pathogenesis. In addition, our results indicate that miR-484 may be a promising novel biomarker for TLE.

Decoupling of functional and structural language networks in temporal lobe epilepsy.

ObjectiveTo identify functional and structural alterations in language networks of people with temporal lobe epilepsy (TLE), who frequently present with naming and word‐finding difficulties.MethodsFifty‐five patients with unilateral TLE (29 left) and 16 controls were studied with auditory and picture naming functional magnetic resonance imaging (fMRI) tasks. Activation maxima in the left posterobasal temporal lobe were used as seed regions for whole‐brain functional connectivity analyses (psychophysiological interaction). White matter language pathways were investigated using diffusion tensor imaging and neurite orientation dispersion and density imaging metrics extracted along fiber bundles starting from fMRI‐guided seeds. Regression analyses were performed to investigate the correlation of functional connectivity with diffusion MRI metrics.ResultsIn the whole group of patients and controls, weaker functional connectivity from the left posterobasal temporal lobe (1) to the bilateral anterior temporal lobe, precentral gyrus, and lingual gyrus during auditory naming and (2) to the bilateral occipital cortex and right fusiform gyrus during picture naming was associated with decreased neurite orientation dispersion and higher free water fraction of white matter tracts. Compared to controls, TLE patients exhibited fewer structural connections and an impaired coupling of functional and structural metrics.SignificanceTLE is associated with an impairment and decoupling of functional and structural language networks. White matter damage, as evidenced by diffusion abnormalities, may contribute to impaired functional connectivity and language dysfunction in TLE.

Intrinsic Thalamic Network in Temporal Lobe Epilepsy With Hippocampal Sclerosis According to Surgical Outcomes.

Background: The aim of this study was to identify the differences of intrinsic amygdala, hippocampal, or thalamic networks according to surgical outcomes in temporal lobe epilepsy (TLE) patients with hippocampal sclerosis (HS).Methods: We enrolled 69 pathologically confirmed TLE patients with HS. All patients had pre-operative three-dimensional T1-weighted MRI using a 3.0 T scanner. We obtained the structural volumes of the amygdala nuclei, hippocampal subfields, and thalamic nuclei. Then, we investigated the intrinsic networks based on volumes of these structures using structural covariance and graph theoretical analysis.Results: Of the 69 TLE patients with HS, 21 patients (42.1%) had poor surgical outcomes, whereas 40 patients (57.9%) had good surgical outcomes. The volumes in the amygdala nuclei, hippocampal subfields, and thalamic nuclei were not different according to surgical outcome. In addition, the intrinsic amygdala and hippocampal networks were not different between the patients with poor and good surgical outcomes. However, there was a significant difference in the intrinsic thalamic network in the ipsilateral hemisphere between them. The eccentricity and small-worldness index were significantly increased, whereas the characteristic path length was decreased in the patients with poor surgical outcomes compared to those with good surgical outcomes.Conclusion: We successfully demonstrated significant differences in the intrinsic thalamic network in the ipsilateral hemisphere between TLE patients with HS with poor and good surgical outcomes. This result suggests that the pre-operative intrinsic thalamic network can be related with surgical outcomes in TLE patients with HS.

Seizure Freedom After Epilepsy Surgery and Higher Baseline Cognition May Be Associated With a Negatively Correlated Epilepsy Network in Temporal Lobe Epilepsy.

Background: Brain regions positively correlated with the epileptogenic zone in patients with temporal lobe epilepsy vary in spread across the brain and in the degree of correlation to the temporal lobes, thalamus, and limbic structures, and these parameters have been associated with pre-operative cognitive impairment and seizure freedom after epilepsy surgery, but negatively correlated regions have not been as well studied. We hypothesize that connectivity within a negatively correlated epilepsy network may predict which patients with temporal lobe epilepsy will respond best to surgery.Methods: Scalp EEG and resting state functional MRI (rsfMRI) were collected from 19 patients with temporal lobe epilepsy and used to estimate the irritative zone. Using patients’ rsfMRI, the negatively correlated epilepsy network was mapped by determining all the brain voxels that were negatively correlated with the voxels in the epileptogenic zone and the spread and average connectivity within the network was determined.Results: Pre-operatively, connectivity within the negatively correlated network was inversely related to the spread (diffuseness) of that network and positively associated with higher baseline verbal and logical memory. Pre-operative connectivity within the negatively correlated network was also significantly higher in patients who would go on to be seizure free.Conclusion: Patients with higher connectivity within brain regions negatively correlated with the epilepsy network had higher baseline memory function, narrower network spread, and were more likely to be seizure free after surgery.

The impact of hippocampal impairment on task-positive and task-negative language networks in temporal lobe epilepsy

ObjectiveTo study hippocampal integration within task-positive and task-negative language networks and the impact of a diseased left and right hippocampus on the language connectome in temporal lobe epilepsy (TLE). MethodsWe used functional magnetic resonance imaging (fMRI) to study a homogenous group of 32 patients with TLE (17 left) and 14 healthy controls during a verb-generation task. We performed functional connectivity analysis and quantified alterations within the language connectome and evaluated disruptions of the functional dissociation along the anterior-posterior axis of the hippocampi. ResultsConnectivity analysis revealed significant differences between left and right TLE compared to healthy controls. Left TLE showed widespread impairment of task-positive language networks, while right TLE showed less pronounced alterations. Particularly right TLE showed altered connectivity for cortical regions that were part of the default mode network (DMN). Left TLE showed a disturbed functional dissociation pattern along the left hippocampus to left and right inferior frontal language regions, while left and right TLE revealed an altered dissociation pattern along the right hippocampus to regions associated with the DMN. ConclusionsOur results showed an impaired hippocampal integration into active language and the default mode networks, which both may contribute to language impairment in TLE. SignificanceOur results emphasize the direct role of the left hippocampus in language processing, and the potential role of the right hippocampus as a modulator between DMN and task-positive networks.