Abnormalities In Temporal Lobe Epilepsy Research Articles

Quantitative analysis of visually normal EEG reveals spectral power abnormalities in temporal lobe epilepsy

ObjectiveTo compare quantitative spectral parameters of visually-normal EEG between Mesial Temporal Lobe Epilepsy (MTLE) patients and healthy controls (HC). MethodWe enrolled 26 MTLE patients and 26 HC. From each recording we calculated total power of all frequency bands and determined alpha-theta (ATR) and alpha-delta (ADR) power ratios in different brain regions. Group-wise differences between spectral parameters were investigated (p < 0.05). To test for associations between spectral-power and cognitive status, we evaluated correlations between neuropsychological tests and quantitative EEG (qEEG) metrics. ResultsIn all comparisons, ATR and ADR were significantly decreased in MTLE patients compared to HC, particularly over the hemisphere ipsilateral to epileptic activity. A positive correlation was seen in MTLE patients between ATR in ipsilateral temporal lobe, and results of neuropsychological tests of auditory verbal learning (RAVLT and RAVLT-D), short term verbal memory (Digit span backwards), and executive function (Weigl's sorting test). ADR values in the contralateral posterior region correlated positively with RAVLT-D and Digit span backwards tests. DiscussionResults confirmed that the power spectrum of qEEG is shifted towards lower frequencies in MTLE patients compared to HC. ConclusionOf note, our results were found in visually-normal recordings, providing further evidence of the value of qEEG for longitudinal monitoring of MTLE patients over time. Exploratory analysis of associations between qEEG and neuropsychological data suggest this could be useful for investigating effects of antiseizure medications on cognitive integrity in patients.

Cerebellar white and gray matter abnormalities in temporal lobe epilepsy: a voxel-based morphometry study.

Previous structural neuroimaging studies linked cerebellar deficits to temporal lobe epilepsy (TLE). The functions of various cerebellar regions are increasingly being valued, and their changes in TLE patients warrant further in-depth investigation. In this study, we used the Spatially Unbiased Infratentorial (SUIT) toolbox with a new template to evaluate the cerebellar structural abnormalities in patients with TLE, and further explored the relationship between the changes of different cerebellar regions and cognition. Thirty-two patients with TLE were compared with 39 healthy controls (HC) matched according to age, gender, handedness, and education level. All participants underwent a high-resolution T1-weighted MRI scan on a 3.0 Tesla scanner. We used a voxel-based morphometry (VBM) approach utilizing the SUIT toolbox to provide an optimized and fine-grained exploration of cerebellar structural alterations associated with TLE. Compared with HC, TLE patients showed a significant reduction in the volume of gray matter in the Left lobule VI and white matter in the Right Crus II. In the TLE patient group, we conducted partial correlation analysis between the volumes of different cerebellar regions and cognitive rating scale scores, such as MMSE and MoCA. The volume of the Left lobule VI (GM) exhibited a positive correlation with the MMSE score, but no significant correlation was found with the MoCA score. On the other hand, there was no significant correlation observed between the volume of the Right Crus II (WM) and the two cognitive scale scores mentioned above. Furthermore, it was observed that the MMSE was more effective than the MoCA in identifying epilepsy patients with cognitive impairment. This study supported previous research indicating that temporal lobe epilepsy (TLE) is linked to structural changes in the cerebellum, specifically affecting the volume of both gray and white matter. These findings offer valuable insights into the neurobiology of TLE and hold potential to inform the development of enhanced diagnostic methods and more effective treatment approaches.

Structural-functional coupling abnormalities in temporal lobe epilepsy.

Nowadays, researchers are using advanced multimodal neuroimaging techniques to construct the brain network connectome to elucidate the complex relationship among the networks of brain functions and structure. The objective of this study was to evaluate the coupling of structural connectivity (SC) and functional connectivity (FC) in the entire brain of healthy controls (HCs), and to investigate modifications in SC-FC coupling in individuals suffering from temporal lobe epilepsy (TLE). We evaluated 65 patients with TLE matched for age and gender with 48 healthy controls. The SC-FC coupling between regions was determined, based on which whole-brain nodes were clustered. Differences in the coupling among the three groups of nodes were compared. To further validate the results obtained, the within-cluster coupling indices of the three groups were compared to determine the inter-group differences. Nodes were divided into five clusters. Cluster 1 was primarily located in the limbic system (n = 9/27), whereas cluster 5 was mainly within the visual network (n = 12/29). By comparing average cluster SC-FC coupling in each cluster of the three groups, we identified marked discrepancies within the three cohorts in Cluster 3 (p = 0.001), Cluster 4 (p < 0.001), and Cluster 5 (p < 0.001). Post-hoc analysis revealed that the SC-FC coupling strengths in LTLE and RTLE were significantly lower than that in HCs in Cluster 3 (PL = 0.001/PR = 0.003), Cluster 4 (PL = 0.001/PR < 0.001), and Cluster 5 (PL < 0.001/PR < 0.001). We also observed that the within-cluster SC-FC coupling in cluster 5 of left- and right TLE was significantly lower than in HCs (PL = 0.0001, PR = 0.0005). The SC and FC are inconsistently coupled across the brain with spatial heterogeneity. In the fifth cluster with the highest degree of coupling in HCs, the average SC-FC coupling index of individuals with TLE was notably less than that of HCs, manifesting that brain regions with high coupling may be more delicate and prone to pathological disruption.

Association of neighborhood deprivation with white matter connectome abnormalities in temporal lobe epilepsy.

Social determinants of health, including the effects of neighborhood disadvantage, impact epilepsy prevalence, treatment, and outcomes. This study characterized the association between aberrant white matter connectivity in temporal lobe epilepsy (TLE) and disadvantage using a US census-based neighborhood disadvantage metric, the Area Deprivation Index (ADI), derived from measures of income, education, employment, and housing quality. Participants including 74 TLE patients (47 male, mean age = 39.2 years) and 45 healthy controls (27 male, mean age = 31.9 years) from the Epilepsy Connectome Project were classified into ADI-defined low and high disadvantage groups. Graph theoretic metrics were applied to multishell connectome diffusion-weighted imaging (DWI) measurements to derive 162 × 162 structural connectivity matrices (SCMs). The SCMs were harmonized using neuroCombat to account for interscanner differences. Threshold-free network-based statistics were used for analysis, and findings were correlated with ADI quintile metrics. A decrease in cross-sectional area (CSA) indicates reduced white matter integrity. Sex- and age-adjusted CSA in TLE groups was significantly reduced compared to controls regardless of disadvantage status, revealing discrete aberrant white matter tract connectivity abnormalities in addition to apparent differences in graph measures of connectivity and network-based statistics. When comparing broadly defined disadvantaged TLE groups, differences were at trend level. Sensitivity analyses of ADI quintile extremes revealed significantly lower CSA in the most compared to least disadvantaged TLE group. Our findings demonstrate (1) the general impact of TLE on DWI connectome status is larger than the association with neighborhood disadvantage; however, (2) neighborhood disadvantage, indexed by ADI, revealed modest relationships with white matter structure and integrity on sensitivity analysis in TLE. Further studies are needed to explore this relationship and determine whether the white matter relationship with ADI is driven by social drift or environmental influences on brain development. Understanding the etiology and course of the disadvantage-brain integrity relationship may serve to inform care, management, and policy for patients.

Relationship between visuoperceptual functions and parietal structural abnormalities in temporal lobe epilepsy.

Progressive gray matter volume reductions beyond the epileptogenic area has been described in temporal lobe epilepsy. There is less evidence regarding correlations between gray and white matter volume changepres and multi-domain cognitive performance in this setting. We aimed to investigate correlations between volume changes in parietal structures and visuospatial performance in temporal lobe epilepsy patients. we performed a cross-sectional study comparing global and regional brain volume data from 34 temporal lobe epilepsy patients and 30 healthy controls. 3D T1-weighted sequences were obtained on a 3.0 T magnet, and data were analyzed using age and sex-adjusted linear regression models. Global and regional brain volumes and cortical thickness in patients were correlated with standardized visual memory, visuoperceptual, visuospatial, and visuoconstructive parameters obtained in a per-protocol neuropsychological assessment. temporal lobe epilepsy patients had smaller volume fractions of the deep gray matter structures, putamen and nucleus accumbens, and larger cerebrospinal fluid volume fraction than controls. Correlations were found between: 1) visual memory and precuneus and inferior parietal cortical thickness; 2) visuoperceptual performance and precuneus and supramarginal white matter volumes; 3) visuospatial skills and precuneus, postcentral, and inferior and superior parietal white matter volumes; 4) visuoconstructive performance and inferior parietal white matter volume. Brain volume loss is widespread in temporal lobe epilepsy. Volumetric reductions in parietal lobe structures were associated with visuoperceptual cognitive performance.

Role of NODDI in the MRI Characterization of Hippocampal Abnormalities in Temporal Lobe Epilepsy: Clinico-histopathologic Correlations.

The identification of possible hippocampal alterations is a crucial point for the diagnosis and therapy of patients with unilateral temporal lobe epilepsy (TLE). This study aims to investigate the role of neurite orientation dispersion and density imaging (NODDI) compared to diffusion tensor imaging (DTI) in the comprehension of hippocampal microstructure in TLE. DTI and NODDI metrics were calculated in the hippocampi of adult patients with TLE, with and without histology-confirmed hippocampal sclerosis (HS), and in age/sex-matched healthy controls (HC). Diffusion metrics and hippocampal volumes of the pathologic side were compared within participants and between participants among the HS, non-HS, and HC groups. Diffusion metrics were also correlated with hippocampal volume and patients' clinical features. After surgery, hippocampal specimens were processed for neuropathology examinations. Fifteen patients with TLE (9 with and 6 without HS) and 11 HC were included. Hippocampal analyses resulted in a significant increase in fractional anisotropy (FA) and mean diffusivity (MD; mm2/s × 10-3) and decrease in orientation dispersion index (ODI) comparing the pathologic side of patients with HS and their relative nonpathologic side (0.203 vs 0.183, 0.825 vs 0.724, 0.366 vs 0.443, respectively), the pathologic side of patients without HS (0.203 vs 0.169, 0.825 vs 0.745, 0.366 vs 0.453, respectively), and HC (0.203 vs 0.172, 0.825 vs 0.729, 0.366 vs 0.447, respectively). Moreover, neurite density (ND) was significantly decreased comparing both hippocampi of patients with HS (0.416 vs 0.460). A significant increase in free-water isotropic volume fraction (fiso) was found in the comparison of pathologic hippocampi of patients with HS and nonpathologic hippocampi of patients with HS (0.323 vs 0.258) and HC (0.323 vs 0.226). Hippocampal volume of all patients with TLE negatively correlated with MD (r = -0.746, p = 0.0145) and positively correlated with ODI (r = 0.719, p = 0.0145). Fiso and ND of sclerotic hippocampi positively correlated with disease duration (r = 0.684, p = 0.0424 and r = 0.670, p = 0.0486, respectively). Immunohistochemistry in sclerotic hippocampal specimens revealed neuronal loss in the pyramidal layer and fiber reorganization at the level of stratum lacunosum-moleculare, confirming ODI and ND metrics. This study shows the capability of diffusion MRI metrics to detect hippocampal microstructural alterations. Among them, ODI seems to better highlight the fiber reorganization observed by neuropathology in sclerotic hippocampi.

Network topology of the cognitive phenotypes of temporal lobe epilepsy

PurposeThe neuropsychological complications of temporal lobe epilepsy are characterized by a spectrum of reproducible cognitive phenotypes that vary in the presence, type and degree of impairment. The nature of the disruptions to the neuropsychological networks that underlie these phenotypes remain to be characterized and represent the subject of this investigation. MethodsParticipants included 30 healthy controls and 104 patients with temporal lobe epilepsy who fell into three cognitive phenotypes (intact, focal impairment, generalized impairment). Eighteen neuropsychological measures representing multiple cognitive domains (language, memory, executive function, visuoperception, motor speed) were examined by graph theory techniques within the control and each epilepsy cognitive phenotype group to characterize their global and local network properties. ResultsAcross the control and epilepsy cognitive phenotype groups (intact to focal to generalized impairment), there was: 1) an orderly breakdown in the positive manifold reflected by a stepwise reduction of positive associations among the neuropsychological tests, 2) stepwise abnormal increases in global measures including the normalized clustering coefficient and modularity index, 3) stepwise abnormal decreases in normalized global efficiency, 4) a community structure demonstrating well organized modules within the control group while each epilepsy group showed deviations from controls, and 5) lower strength, compared to controls, across 8 nodes in the focal and generalized impairment groups compared to only 3 nodes in the no-impairment epilepsy group, pointing to the superior integration of local connections in controls. DiscussionThe cognitive phenotypes of temporal lobe epilepsy are characterized by orderly abnormalities in their underlying neuropsychological networks. These findings inform the network perturbations that underlie the taxonomy of cognitive abnormality in temporal lobe epilepsy and provide a model for examination of similar issues in other focal and generalized epilepsies.

Focal to bilateral tonic-clonic seizures are associated with widespread network abnormality in temporal lobe epilepsy.

ObjectiveOur objective was to identify whether the whole‐brain structural network alterations in patients with temporal lobe epilepsy (TLE) and focal to bilateral tonic–clonic seizures (FBTCS) differ from alterations in patients without FBTCS.MethodsWe dichotomized a cohort of 83 drug‐resistant patients with TLE into those with and without FBTCS and compared each group to 29 healthy controls. For each subject, we used diffusion‐weighted magnetic resonance imaging to construct whole‐brain structural networks. First, we measured the extent of alterations by performing FBTCS‐negative (FBTCS−) versus control and FBTCS‐positive (FBTCS+) versus control comparisons, thereby delineating altered subnetworks of the whole‐brain structural network. Second, by standardizing each patient's networks using control networks, we measured the subject‐specific abnormality at every brain region in the network, thereby quantifying the spatial localization and the amount of abnormality in every patient.ResultsBoth FBTCS+ and FBTCS− patient groups had altered subnetworks with reduced fractional anisotropy and increased mean diffusivity compared to controls. The altered subnetwork in FBTCS+ patients was more widespread than in FBTCS− patients (441 connections altered at t > 3, p < .001 in FBTCS+ compared to 21 connections altered at t > 3, p = .01 in FBTCS−). Significantly greater abnormalities—aggregated over the entire brain network as well as assessed at the resolution of individual brain areas—were present in FBTCS+ patients (p < .001, d = .82, 95% confidence interval = .32–1.3). In contrast, the fewer abnormalities present in FBTCS− patients were mainly localized to the temporal and frontal areas.SignificanceThe whole‐brain structural network is altered to a greater and more widespread extent in patients with TLE and FBTCS. We suggest that these abnormal networks may serve as an underlying structural basis or consequence of the greater seizure spread observed in FBTCS.

Artificial intelligence for classification of temporal lobe epilepsy with ROI-level MRI data: A worldwide ENIGMA-Epilepsy study

Artificial intelligence has recently gained popularity across different medical fields to aid in the detection of diseases based on pathology samples or medical imaging findings. Brain magnetic resonance imaging (MRI) is a key assessment tool for patients with temporal lobe epilepsy (TLE). The role of machine learning and artificial intelligence to increase detection of brain abnormalities in TLE remains inconclusive. We used support vector machine (SV) and deep learning (DL) models based on region of interest (ROI-based) structural (n = 336) and diffusion (n = 863) brain MRI data from patients with TLE with (“lesional”) and without (“non-lesional”) radiographic features suggestive of underlying hippocampal sclerosis from the multinational (multi-center) ENIGMA-Epilepsy consortium. Our data showed that models to identify TLE performed better or similar (68–75%) compared to models to lateralize the side of TLE (56–73%, except structural-based) based on diffusion data with the opposite pattern seen for structural data (67–75% to diagnose vs. 83% to lateralize). In other aspects, structural and diffusion-based models showed similar classification accuracies. Our classification models for patients with hippocampal sclerosis were more accurate (68–76%) than models that stratified non-lesional patients (53–62%). Overall, SV and DL models performed similarly with several instances in which SV mildly outperformed DL. We discuss the relative performance of these models with ROI-level data and the implications for future applications of machine learning and artificial intelligence in epilepsy care.

Temporal Lobe Epilepsy Surgical Outcomes Can Be Inferred Based on Structural Connectome Hubs: A Machine Learning Study.

Medial temporal lobe epilepsy (TLE) is the most common form of medication-resistant focal epilepsy in adults. Despite removal of medial temporal structures, more than one-third of patients continue to have disabling seizures postoperatively. Seizure refractoriness implies that extramedial regions are capable of influencing the brain network and generating seizures. We tested whether abnormalities of structural network integration could be associated with surgical outcomes. Presurgical magnetic resonance images from 121 patients with drug-resistant TLE across 3 independent epilepsy centers were used to train feed-forward neural network models based on tissue volume or graph-theory measures from whole-brain diffusion tensor imaging structural connectomes. An independent dataset of 47 patients with TLE from 3 other epilepsy centers was used to assess the predictive values of each model and regional anatomical contributions toward surgical treatment results. The receiver operating characteristic area under the curve based on regional betweenness centrality was 0.88, significantly higher than a random model or models based on gray matter volumes, degree, strength, and clustering coefficient. Nodes most strongly contributing to the predictive models involved the bilateral parahippocampal gyri, as well as the superior temporal gyri. Network integration in the medial and lateral temporal regions was related to surgical outcomes. Patients with abnormally integrated structural network nodes were less likely to achieve seizure freedom. These findings are in line with previous observations related to network abnormalities in TLE and expand on the notion of underlying aberrant plasticity. Our findings provide additional information on the mechanisms of surgical refractoriness. ANN NEUROL 2020;88:970-983.

Chronically reduced IL-10 plasma levels are associated with hippocampal sclerosis in temporal lobe epilepsy patients

BackgroundIncreasing evidence supports the role of soluble inflammatory mediators in the pathogenesis of refractory temporal lobe epilepsy (TLE). Hippocampal sclerosis (HS) is a well-described pathohistological abnormality in TLE. The association of proinflammatory cytokines with epileptic disease profiles is well established; however, the potential significance of circulating interleukin 10 (IL-10), particularly in TLE-associated HS, is still poorly understood. Therefore, taking into consideration the neuroprotective and anticonvulsive effects of IL-10, we performed this study to examine the role of the plasma levels of IL-10 in patients with TLE with HS (TLE + HS), TLE without HS (TLE-HS) and with other types of epilepsy.MethodsThis study included 270 patients with refractory epilepsy who were classified into four groups: i) 34 patients with TLE + HS, ii) 105 patients with TLE-HS, iii) 95 patients with extra-TLE (XLE) and iv) 36 patients with idiopathic generalized epilepsy (IGE). The plasma IL-10 levels were quantified using a commercially available enzyme-linked immunosorbent assay (ELISA).ResultsIL-10 levels were significantly lower in TLE + HS than in TLE-HS (p = 0.013). In a subgroup of TLE-HS patients who had seizures 1 month before sampling, patients with seizures had significantly higher IL-10 levels than patients who were seizure-free (p = 0.039). Among a small group (n = 15) of non-refractory TLE-HS patients, IL-10 levels showed a moderate negative correlation with the duration of epilepsy (r = − 0.585, p = 0.023).ConclusionsThis study demonstrated that chronically reduced levels of plasma IL-10 were associated with HS in TLE patients, suggesting that there was an inadequate systemic anti-inflammatory immune response. These results could provide new biological insights into the pathophysiology of HS in TLE. We also found that the production of IL-10 could be affected by the seizure frequency and declined concomitantly with increased disease durations. Therefore, the measurement of plasma IL-10 may have diagnostic value as a biomarker for stratifying TLE + HS from other epilepsy types or as a marker of disease progression towards a progressive form of epilepsy.

Investigation of microstructural abnormalities in white and gray matter around hippocampus with diffusion tensor imaging (DTI) in temporal lobe epilepsy (TLE)

ObjectiveThe objective of this study was to apply diffusion tensor imaging (DTI) to investigate microstructural abnormalities in temporal lobe epilepsy (TLE) with and without hippocampal sclerosis (HS). MaterialsTotally, 19 patients with TLE with HS and 23 patients with TLE without HS were included. Fiber tracking fibers focused on the parahippocampal cingulum (PHC), cingulate gyrus (CG), and fornix (FORX). Fractional anisotropy (FA) and mean diffusivity (MD) values were obtained, and hippocampal volumes were measured. ResultsCompared with the contralateral side, for the HS group, FA values of ipsilateral CG and FORX were significantly decreased, and MD value of ipsilateral hippocampus was significantly higher, with significantly declined ipsilateral hippocampal volume. For the MRI-Neg group, FA values of ipsilateral CG, FORX, and hippocampus were significantly decreased, while MD values of ipsilateral FORX and hippocampus were significantly higher. Moreover, for the MRI-Neg group, the FA value of contralateral PHC was significantly decreased. Fractional anisotropy values of ipsilateral CG for both groups were significantly decreased, and FA value of ipsilateral FORX for the HS group was significantly decreased. Furthermore, MD value of ipsilateral hippocampus for the HS group was significantly higher, and FA value of ipsilateral hippocampus for the MRI-Neg group was significantly decreased. In addition, ipsilateral hippocampal volumes for both groups were significantly decreased. Fractional anisotropy value of ipsilateral CG and FORX had a correlation with the seizure frequency. ConclusionDiffusion tensor imaging can detect microstructural abnormalities in brain from patients with TLE, which might be hard to find with routine Magnetic Resonance Imaging (MRI) sequence.

Gray Matter and White Matter Abnormalities in Temporal Lobe Epilepsy Patients with and without Hippocampal Sclerosis.

The presentation and distribution of gray matter (GM) and white matter (WM) abnormalities in temporal lobe epilepsy (TLE) have been widely studied. Here, we investigated the GM and WM abnormalities in TLE patients with and without hippocampal sclerosis (HS) in five groups of participants: healthy controls (HCs) (n = 28), right TLE patients with HS (n = 26), right TLE patients without HS (n = 30), left TLE patients with HS (n = 25), and left TLE patients without HS (n = 27). We performed a flexible factorial statistical test in a whole-brain voxel-based morphometry analysis to identify significant GM and WM abnormalities and analysis of variance of hippocampal and amygdala regions among the five groups using the FreeSurfer procedure. Furthermore, we conducted multiple regression analysis to assess regional GM and WM changes with disease duration. We observed significant ipsilateral mesiotemporal GM and WM volume reductions in TLE patients with HS compared with HCs. We also observed a slight GM amygdala swelling in right TLE patients without HS. The regression analysis revealed significant negative GM and WM changes with disease duration specifically in left TLE patients with HS. The observed GM and WM abnormalities may contribute to our understanding of the root of epilepsy mechanisms.

Comparing CAT12 and VBM8 for Detecting Brain Morphological Abnormalities in Temporal Lobe Epilepsy.

The identification of the brain morphological alterations that play important roles in neurodegenerative/neurological diseases will contribute to our understanding of the causes of these diseases. Various automated software programs are designed to provide an automatic framework to detect brain morphological changes in structural magnetic resonance imaging (MRI) data. A voxel-based morphometry (VBM) analysis can also be used for the detection of brain volumetric abnormalities. Here, we compared gray matter (GM) and white matter (WM) abnormality results obtained by a VBM analysis using the Computational Anatomy Toolbox (CAT12) via the current version of Statistical Parametric Mapping software (SPM12) with the results obtained by a VBM analysis using the VBM8 toolbox implemented in the older software SPM8, in adult temporal lobe epilepsy (TLE) patients with (n = 51) and without (n = 57) hippocampus sclerosis (HS), compared to healthy adult controls (n = 28). The VBM analysis using CAT12 showed that compared to the healthy controls, significant GM and WM reductions were located in ipsilateral mesial temporal lobes in the TLE-HS patients, and slight GM amygdala swelling was present in the right TLE-no patients (n = 27). In contrast, the VBM analysis via the VBM8 toolbox showed significant GM and WM reductions only in the left TLE-HS patients (n = 25) compared to the healthy controls. Our findings thus demonstrate that compared to VBM8, a VBM analysis using CAT12 provides a more accurate volumetric analysis of the brain regions in TLE. Our results further indicate that a VBM analysis using CAT12 is more robust and accurate against volumetric alterations than the VBM8 toolbox.

Mismatch negativity is abnormal but not lateralizing in temporal lobe epilepsy.

We investigated the changes of mismatch negativity (MMN) in patients with temporal lobe epilepsy (TLE) and explored the possible role of MMN in lateralizing their seizure focus. Thirty patients with TLE and thirty healthy controls were included. MMN was elicited in each subject. Patients with TLE were divided into three subgroups: unilateral left TLE; unilateral right TLE, and bilateral TLE. MMN amplitudes and latencies were compared between the patients with TLE and the control group, and also among the three subgroups of TLE, using repeated measures analyses of variance (ANOVA). To assess the lateralizing value of MMN, MMN latencies and amplitudes at the mastoid sites between the ipsilateral and contralateral sides of epileptic focus in patients with unilateral TLE were compared using t-test. Compared with controls, each subgroup of patients with TLE had longer latencies of MMN at both fronto-central and mastoid sites, but the amplitudes of MMN were not significantly different. The amplitudes and latencies of MMN were not significantly different between the ipsilateral and contralateral sides of seizure focus at mastoid sites. The present findings of prolonged latencies of MMN are suggestive of cognitive impairment in TLE. Both the mastoid sites and the fronto-central sites are involved, which likely reflect widespread cortical abnormalities in TLE. However, the changes of MMN during the interictal phase are not useful for lateralizing the seizure focus in patients with TLE.

The spectrum of structural and functional imaging abnormalities in temporal lobe epilepsy.

Although most temporal lobe epilepsy (TLE) patients show marked hippocampal sclerosis (HS) upon pathological examination, 40% present with no significant cell loss but gliotic changes only. To evaluate effects of hippocampal pathology on brain structure and functional networks, we aimed at dissociating multimodal magnetic resonance imaging (MRI) characteristics in patients with HS (TLE-HS) and those with gliosis only (TLE-G). In 20 TLE-HS, 19 TLE-G, and 25 healthy controls, we carried out a novel MRI-based hippocampal subfield surface analysis that integrated volume, T2 signal intensity, and diffusion markers with seed-based hippocampal functional connectivity. Compared to controls, TLE-HS presented with marked ipsilateral atrophy, T2 hyperintensity, and mean diffusivity increases across all subfields, whereas TLE-G presented with dentate gyrus hypertrophy, focal increases in T2 intensity and mean diffusivity. Multivariate assessment confirmed a more marked ipsilateral load of anomalies across all subfields in TLE-HS, whereas anomalies in TLE-G were restricted to the subiculum. A between-cohort dissociation was independently suggested by resting-state functional connectivity analysis, revealing marked hippocampal decoupling from anterior and posterior default mode hubs in TLE-HS, whereas TLE-G did not differ from controls. Back-projection connectivity analysis from cortical targets revealed consistently decreased network embedding across all subfields in TLE-HS, while changes in TLE-G were limited to the subiculum. Hippocampal disconnectivity strongly correlated to T2 hyperintensity and marginally to atrophy. Multimodal MRI reveals diverging structural and functional connectivity profiles across the TLE spectrum. Pathology-specific modulations of large-scale functional brain networks lend novel evidence for a close interplay of structural and functional disruptions in focal epilepsy. Ann Neurol 2016;80:142-153.

Gray Matter Abnormalities in Temporal Lobe Epilepsy: Relationships with Resting-State Functional Connectivity and Episodic Memory Performance.

Temporal lobe epilepsy (TLE) affects multiple brain regions through evidence from both structural (gray matter; GM) and functional connectivity (FC) studies. We tested whether these structural abnormalities were associated with FC abnormalities, and assessed the ability of these measures to explain episodic memory impairments in this population. A resting-state and T1 sequences were acquired on 94 (45 with mesial temporal pathology) TLE patients and 50 controls, using magnetic resonance imaging (MRI) technique. A voxel-based morphometry analysis was computed to determine the GM volume differences between groups (right, left TLE, controls). Resting-state FC between the abnormal GM volume regions was computed, and compared between groups. Finally, we investigated the relation between EM, GM and FC findings. Patients with and without temporal pathology were analyzed separately. The results revealed reduced GM volume in multiple regions in the patients relative to the controls. Using FC, we found the abnormal GM regions did not display abnormal functional connectivity. Lastly, we found in left TLE patients, verbal episodic memory was associated with abnormal left posterior hippocampus volume, while in right TLE, non-verbal episodic memory was better predicted by resting-state FC measures. This study investigated TLE abnormalities using a multi-modal approach combining GM, FC and neurocognitive measures. We did not find that the GM abnormalities were functionally or abnormally connected during an inter-ictal resting state, which may reflect a weak sensitivity of functional connectivity to the epileptic network. We provided evidence that verbal and non-verbal episodic memory in left and right TLE patients may have distinct relationships with structural and functional measures. Lastly, we provide data suggesting that in the setting of occult, non-lesional right TLE pathology, a coupling of structural and functional abnormalities in extra-temporal/non-ictal regions is necessary to produce reductions in episodic memory recall. The latter, in particular, demonstrates the complex structure/function interactions at work when trying to understand cognition in TLE, suggesting that subtle network effects can emerge bearing specific relationships to hemisphere and the type of pathology.

Resting-state fMRI abnormalities in temporal lobe epilepsy

Automaticity, the ability to perform a task rapidly with minimal effort, plays a key role in reading fluency and is indexed by rapid automatized naming (RAN) and processing speed. Yet little is known about automaticity's neurophysiologic underpinnings. The more efficiently sound is encoded, the more automatic sound processing can be. In turn, this automaticity could free up cognitive resources such as attention and working memory to help build an integrative reading network. Therefore, we hypothesized that automaticity and reading fluency correlate with stable neural representation of sounds, given a larger body of literature suggesting the close relationship between neural stability and the integrative function in the central auditory system. To test this hypothesis, we recorded the frequency-following responses (FFR) to speech syllables and administered cognitive and reading measures to school-aged children. We show that the stability of neural responses to speech correlates with RAN and processing speed, but not phonological awareness. Moreover, the link between neural stability and RAN mediates the previously-determined link between neural stability and reading ability. Children with a RAN deficit have especially unstable neural responses. Our neurophysiological approach illuminates a potential neural mechanism specific to RAN, which in turn indicates a relationship between synchronous neural firing in the auditory system and automaticity critical for reading fluency.

Temporal pole abnormalities in temporal lobe epilepsy with hippocampal sclerosis: Clinical significance and seizure outcome after surgery

PurposeTo assess the clinical significance of temporal pole abnormalities (temporopolar blurring, TB, and temporopolar atrophy, TA) in patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS) with a long post-surgical follow-up. MethodsWe studied 60 consecutive patients with TLE–HS and 1.5 preoperative MRI scans who underwent surgery and were followed up for at least 5 years (mean follow-up 7.3 years). Based on findings of pre-surgical MRI, patients were classified according to the presence of TB or TA. Groups were compared on demographic, clinical, neuropsychological data, and seizure outcome. ResultsTB was found in 37 (62%) patients, while TA was found in 35 (58%) patients, always ipsilateral to HS, with a high degree of overlap (83%) between TB and TA (p<0.001). Patients with TB did not differ from those without TB with regard to history of febrile convulsions, GTCSs, age of epilepsy onset, side of surgery, seizure frequency, seizure outcome, and neuropsychological outcome. On the other hand, they were significantly older, had a longer duration of epilepsy, and displayed lower preoperative scores on several neuropsychological tests. Similar findings were observed for TA. Multivariate analysis corroborated the association between temporopolar abnormalities and age at onset, age at surgery (for TB only), and lower preoperative scores on some neuropsychological tests. ConclusionsTemporopolar abnormalities are frequent in patients with TLE–HS. Our data support the hypothesis that TB and TA are caused by seizure-related damages. These abnormalities did not influence seizure outcome, even after a long-term post-surgical follow-up.

Olfactory abnormalities in temporal lobe epilepsy

We studied olfactory function in a cohort of 25 temporal lobe epilepsy (TLE) patients and 25 healthy controls. Our objectives were to measure olfactory acuity in patients with right, left or bilateral TLE and compare them with age and sex matched controls, and to correlate olfactory acuity with duration of seizure, baseline seizure control and the number of drugs used. Olfactory impairment is common in neurological disorders and dysfunction of the temporo-limbic neural substrates involved in olfactory perception is noted in TLE. We measured olfactory acuity in 25 patients with TLE, nine with right, 10 with left and six with bilateral temporal lobe seizure activity, and compared them to the controls. Odor identification was assessed using the University of Pennsylvania Smell Identification Test (UPSIT) which is a 40 item olfactory test used to diagnose olfactory deficits. Our results showed that patients with TLE exhibited significant impairment in UPSIT performance compared to the controls. There was no significant difference in scores between the right and left TLE patients. The severity of olfactory impairment did not correlate with the duration of seizures, baseline seizure control and number of drugs used. We concluded that significant olfactory impairment is seen in both right and left TLE patients, unrelated to the duration and baseline frequency of seizures or drugs used.