Temporal Lobe Epilepsy Subjects Research Articles

Development of an objective method to quantify hippocampal dentation.

Hippocampal dentation (HD) refers to a series of ridges (dentes) seen on the inferior aspect of the hippocampus. The degree of HD varies dramatically across healthy individuals, and hippocampal pathology may result in loss of HD. Existing studies show associations between HD and memory performance in healthy adults as well as temporal lobe epilepsy (TLE) patients. However, until now studies relied on visual assessment of HD as no objective methods to quantify HD have been described. In this work, we describe a method to objectively quantify HD by transforming the characteristic 3D surface morphology of HD into a simplified 2D plot for which area under the curve (AUC) was calculated. This was applied to T1w scans of 59 TLE subjects, each with one epileptic hippocampus and one normal appearing hippocampus. Results showed that AUC significantly correlated with the number of dentes based on visual inspection (p < .05) and correctly sorted a set of hippocampi from least to most prominently dentated. Intra- and inter-rater reliability was nearly perfect (ICC ≥ 0.99). AUC values were significantly lower in epileptic hippocampi compared to contralateral hippocampi (p=.00019), consistent with previously published findings. In the left TLE group, the AUC values from the contralateral hippocampi showed a positive trend (p=.07) with verbal memory acquisition scores but was not statistically significant. The proposed approach is the first objective, quantitative measurement of dentation described in the literature. The AUC values numerically capture the complex surface contour information of HD and will enable future study of this interesting morphologic feature.

Lateralization of temporal lobe epileptic foci with automated chemical exchange saturation transfer measurements at 3Tesla.

Magnetic Resonance Imaging (MRI) is an indispensable tool for the diagnosis of temporal lobe epilepsy (TLE). However, about 30% of TLE patients show no lesion on structural MRI (sMRI-negative), posing a significant challenge for presurgical evaluation. This study aimed to investigate whether chemical exchange saturation transfer (CEST) MRI at 3 Tesla can lateralize the epileptic focus of TLE and study the metabolic contributors to the CEST signal measured. Forty TLE subjects (16 males and 24 females) were included in this study. An automated data analysis pipeline was established, including segmentation of the hippocampus and amygdala (HA), calculation of four CEST metrics and quantitative relaxation times (T1 and T2), and construction of prediction models by logistic regression. Furthermore, a modified two-stage Bloch-McConnell fitting method was developed to investigate the molecular imaging mechanism of 3T CEST in identifying epileptic foci of TLE. The mean CEST ratio (CESTR) metric within 2.25-3.25ppm in the HA was the most powerful index in predicting seizure laterality, with an area under the receiver-operating characteristic curve (AUC) of 0.84. And, the combination of T2 and CESTR further increased the AUC to 0.92. Amine and guanidinium moieties were the two leading contributors to the CEST contrast between the epileptogenic HA and the normal HA. CEST at 3 Tesla is a powerful modality that can predict seizure laterality with high accuracy. This study can potentially facilitate the clinical translation of CEST MRI in identifying the epileptic foci of TLE or other localization-related epilepsies. National Natural Science Foundation of China, Science Technology Department of Zhejiang Province, and Zhejiang University.

Dorsal bed nucleus of stria terminalis in depressed and nondepressed temporal lobe epilepsy patients.

Temporal lobe epilepsy (TLE) and depression are common comorbid disorders whose underlying shared neural network has yet to be determined. Although animal studies demonstrate a role for the dorsal bed nucleus of the stria terminalis (dBNST) in both seizures and depression, and human clinical studies demonstrate a therapeutic effect of stimulating this region on treatment-resistant depression, the role of the dBNST in depressed and nondepressed TLE patients is still unclear. Here, we tested the hypothesis that this structure is morphologically abnormal in these epilepsy patients, with an increased abnormality in TLE patients with comorbid depression. In this case-controlled study, 3-T structural magnetic resonance imaging scans were obtained from TLE patients with no depression (TLEonly), TLE patients with depression (TLEdep), and healthy control (HC) subjects. TLE subjects were recruited from the Yale University Comprehensive Epilepsy Center, diagnosed with the International League Against Epilepsy 2014 Diagnostic Guidelines, and confirmed by video-electroencephalography. Diagnosis of major depressive disorder was confirmed by a trained neuropsychologist through a Mini International Neuropsychiatric Interview based on the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. The dBNST was delineated manually by reliable raters using Bioimage Suite software. The number of patients and subjects included 35 TLEonly patients, 20 TLEdep patients, and 102 HC subjects. Both TLEonly and TLEdep patients had higher dBNST volumes compared to HC subjects, unilaterally in the left hemisphere in the TLEonly patients (p= .003) and bilaterally in the TLEdep patients (p< .0001). Furthermore, the TLEdep patients had a higher dBNST volume than the TLEonly patients in the right hemisphere (p= .02). Here, we demonstrate an abnormality of the dBNST in TLE patients, both without depression (left enlargement) and with depression (bilateral enlargement). Our results demonstrate this region to underlie TLE both with and without depression, implicating it as a target in treating the comorbidity between these two disorders.

The role of the temporal pole in temporal lobe epilepsy: A diffusion kurtosis imaging study

This study aimed to evaluate the use of diffusion kurtosis imaging (DKI) to detect microstructural abnormalities within the temporal pole (TP) and its temporopolar cortex in temporal lobe epilepsy (TLE) patients. DKI quantitative maps were obtained from fourteen lesional TLE and ten non-lesional TLE patients, along with twenty-three healthy controls. Data collected included mean (MK); radial (RK) and axial kurtosis (AK); mean diffusivity (MD) and axonal water fraction (AWF). Automated fiber quantification (AFQ) was used to quantify DKI measurements along the inferior longitudinal (ILF) and uncinate fasciculus (Unc). ILF and Unc tract profiles were compared between groups and tested for correlation with disease duration. To characterize temporopolar cortex microstructure, DKI maps were sampled at varying depths from superficial white matter (WM) towards the pial surface. Patients were separated according to the temporal lobe ipsilateral to seizure onset and their AFQ results were used as input for statistical analyses. Significant differences were observed between lesional TLE and controls, towards the most temporopolar segment of ILF and Unc proximal to the TP within the ipsilateral temporal lobe in left TLE patients for MK, RK, AWF and MD. No significant changes were observed with DKI maps in the non-lesional TLE group. DKI measurements correlated with disease duration, mostly towards the temporopolar segments of the WM bundles. Stronger differences in MK, RK and AWF within the temporopolar cortex were observed in the lesional TLE and noticeable differences (except for MD) in non-lesional TLE groups compared to controls. This study demonstrates that DKI has potential to detect subtle microstructural alterations within the temporopolar segments of the ILF and Unc and the connected temporopolar cortex in TLE patients including non-lesional TLE subjects. This could aid our understanding of the extrahippocampal areas, more specifically the temporal pole role in seizure generation in TLE and might inform surgical planning, leading to better seizure outcomes.

Metabolic Brain Network and Surgical Outcome in Temporal Lobe Epilepsy: A Graph Theoretical Study Based on 18F-fluorodeoxyglucose PET

Drug-resistant temporal lobe epilepsy (TLE) is a potential candidate for surgery; however, nearly one-third subjects had a poor surgical prognosis. We studied the underlying neuromechanism related to the surgical prognosis using graph theory based on metabolic brain network. Sixty-four unilateral TLE subjects with preoperative 18F-fluorodeoxyglucose (FDG) PET scanning were retrospectively enrolled and divided into Ia (Engel class Ia, n = 32) and non-Ia (Engel class Ib-IV, n = 32) groups according to more than 3-year follow-up after unilateral anterior temporal lobectomy (ATL). The metabolic brain network was constructed and the changed metabolic connectivity of Ia and non-Ia was detected compared with 15 matched healthy controls (HCs). Further, the network properties, including small-worldness and global efficiency, were calculated and hub nodes were also identified for the 3 groups respectively. Non-Ia group exhibited increased connectivity between contralateral fusiform gyrus and contralateral lingual gyrus; while Ia showed decreased connectivity mainly among bilateral frontal, temporal and parietal cortex. Graph theoretical analysis revealed that non-Ia group showed increased small-worldness (35%<s < 55%, P ≤ 0.05) compared to HCs; and elevated global efficiency (P = 0.05) and decreased Lp (P = 0.05) compared to Ia group. Ia group showed reduced Cp (55%<s < 63%, P < 0.05) and increased small-worldness (35%<s < 37%, P < 0.05) compared to HCs; Furthermore, disrupted hub nodes distribution pattern with the midcingulate gyrus disappeared, was also found in non-Ia group compared with the Ia group. All those results revealed that elevated network integration and metabolic connectivity, redistributed hub nodes pattern is associated with ongoing postoperative seizures in subjects with intractable TLE.

Algebraic relationship between the structural network’s Laplacian and functional network’s adjacency matrix is preserved in temporal lobe epilepsy subjects

The relationship between anatomic and resting state functional connectivity of large-scale brain networks is a major focus of current research. In previous work, we introduced a model based on eigen decomposition of the Laplacian which predicts the functional network from the structural network in healthy brains. In this work, we apply the eigen decomposition model to two types of epilepsy; temporal lobe epilepsy associated with mesial temporal sclerosis, and MRI-normal temporal lobe epilepsy. Our findings show that the eigen relationship between function and structure holds for patients with temporal lobe epilepsy as well as normal individuals. These results suggest that the brain under TLE conditions reconfigures and rewires the fine-scale connectivity (a process which the model parameters are putatively sensitive to), in order to achieve the necessary structure-function relationship.

Dynamic functional connectivity in temporal lobe epilepsy: a graph theoretical and machine learning approach.

Functional magnetic resonance imaging (fMRI) in resting state can be used to evaluate the functional organization of the human brain in the absence of any task or stimulus. The functional connectivity (FC) has non-stationary nature and consented to be varying over time. By considering the dynamic characteristics of the FC and using graph theoretical analysis and a machine learning approach, we aim to identify the laterality in cases of temporal lobe epilepsy (TLE). Six global graph measures are extracted from static and dynamic functional connectivity matrices using fMRI data of 35 unilateral TLE subjects. Alterations in the time trend of the graph measures are quantified. The random forest (RF) method is used for the determination of feature importance and selection of dynamic graph features including mean, variance, skewness, kurtosis, and Shannon entropy. The selected features are used in the support vector machine (SVM) classifier to identify the left and right epileptogenic sides in patients with TLE. Our results for the performance of SVM demonstrate that the utility of dynamic features improves the classification outcome in terms of accuracy (88.5% for dynamic features compared with 82% for static features). Selecting the best dynamic features also elevates the accuracy to 91.5%. Accounting for the non-stationary characteristics of functional connectivity, dynamic connectivity analysis of graph measures along with machine learning approach can identify the temporal trend of some specific network features. These network features may be used as potential imaging markers in determining the epileptogenic hemisphere in patients with TLE.

Reduced synaptic vesicle protein 2A binding in temporal lobe epilepsy: A [11 C]UCB-J positron emission tomography study.

In this positron emission tomography (PET) study with [11 C]UCB-J, we evaluated synaptic vesicle glycoprotein 2A (SV2A) binding, which is decreased in resected brain tissues from epilepsy patients, in subjects with temporal lobe epilepsy (TLE) and compared the regional binding pattern to [18 F]fluorodeoxyglucose (FDG) uptake. Twelve TLE subjects and 12 control subjects were examined. Regional [11 C]UCB-J binding potential (BPND ) values were estimated using the centrum semiovale as a reference region. [18 F]FDG uptake in TLE subjects was quantified using mean radioactivity values. Asymmetry in outcome measures was assessed by comparison of ipsilateral and contralateral regions. Partial volume correction (PVC) with the iterative Yang algorithm was applied based on the FreeSurfer segmentation. In 11 TLE subjects with medial temporal lobe sclerosis (MTS), the hippocampal volumetric asymmetry was 25±11%. After PVC, [11 C]UCB-J BPND asymmetry indices were 37±19% in the hippocampus, with very limited asymmetry in other brain regions. Reductions in [11 C]UCB-J BPND values were restricted to the sclerotic hippocampus when compared to control subjects. The corresponding asymmetry in hippocampal [18 F]FDG uptake was 22±7% and correlated with that of [11 C]UCB-J BPND across subjects (R2 =.38). Hippocampal asymmetries in [11 C]UCB-J binding were 1.7-fold larger than those of [18 F]FDG uptake. [11 C]UCB-J binding is reduced in the seizure onset zone of TLE subjects with MTS. PET imaging of SV2A may be a promising biomarker approach in the presurgical selection and evaluation of TLE patients and may improve the sensitivity of molecular imaging for seizure focus detection.

Graph Theory Analysis of Functional Connectivity Combined with Machine Learning Approaches Demonstrates Widespread Network Differences and Predicts Clinical Variables in Temporal Lobe Epilepsy.

Understanding how global brain networks are affected in epilepsy may elucidate the pathogenesis of seizures and its accompanying neurobehavioral comorbidities. We investigated functional changes within neural networks in temporal lobe epilepsy (TLE) using graph theory analysis of resting-state connectivity. Twenty-seven TLE presurgical patients (age 41.0 ± 12.3 years) and 85 age, gender, and handedness equivalent healthy controls (HCs; age 39.7 ± 16.9 years) were enrolled. Eyes-closed resting-state functional magnetic resonance image scans were analyzed to compare network properties and functional connectivity (FC) changes. TLE subjects showed significantly higher global efficiency, lower clustering coefficient ratio, and lower shortest path lengths ratio than HCs, as an indication of a more synchronized, yet less segregated network. A trend of functional reorganization with a shift of network hubs to the contralateral hemisphere was noted in TLE subjects. Support vector machine (SVM) with linear kernel was trained to separate between neural networks in TLE and HC subjects based on graph measurements. SVM analysis allowed separation between TLE and HC networks with 80.66% accuracy using eight features of graph measurements. Support vector regression (SVR) was used to predict neurocognitive performance from graph metrics. An SVR linear predictor showed discriminative prediction accuracy for four key neurocognitive variables in TLE (absolute R value range: 0.61-0.75). Despite TLE, our results showed both local and global network topology differences that reflect widespread alterations in FC in TLE. Network differences are discriminative between TLE and HCs using data-driven analysis and predicted severity of neurocognitive sequelae in our cohort.

Neuropsychological assessment and clinical evaluation in temporal lobe epilepsy with associated cortical dysplasia

Temporal Lobe Epilepsy (TLE) is a chronic neurological disorder, often associated to cognitive deficits. Focal cortical dysplasia (FCD), frequently associated to high risk of epilepsy, can lead to abnormalities in cognition. The aim of this study was to explore neuropsychological performance and to identify potential risk factors for cognitive impairment in TLE subjects with associated FCD. Our sample was composed by 46 TLE patients with FCD (37.76 ± 12.60 years; 29 females and 16 males) and 44 healthy controls (41.05 ± 9.74 years; 25 females and 19 males). All subjects performed a neuropsychological battery associated to a measurement of depression and anxiety. Results showed a poor performance of all domains of cognitive functioning and identified age of epilepsy onset as potential risk factor of cognitive impairment. These findings support the importance to focus on cognitive impairment in TLE patients with FCD to better clarify the impact of epilepsy features and FCD in therapeutic and everyday management.

Influences of temporal lobe epilepsy and temporal lobe resection on olfaction.

Although temporal lobe epilepsy (TLE) and resection (TLR) impact olfactory eloquent brain structures, their influences on olfaction remain enigmatic. We sought to more definitively assess the influences of TLE and TLR on olfaction using three well-validated olfactory tests and measuring the tests' associations with the volume of numerous temporal lobe brain structures. The University of Pennsylvania Smell Identification Test and an odor detection threshold test were administered to 71 TLE patients and 71 age- and sex-matched controls; 69 TLE patients and controls received an odor discrimination/memory test. Fifty-seven patients and 57 controls were tested on odor identification and threshold before and after TLR; 27 patients and 27 controls were similarly tested for odor detection/discrimination. Scores were compared using analysis of variance and correlated with pre- and post-operative volumes of the target brain structures. TLE was associated with bilateral deficits in all test measures. TLR further decreased function on the side ipsilateral to resection. The hippocampus and other structures were smaller on the focus side of the TLE subjects. Although post-operative volumetric decreases were evident in most measured brain structures, modest contralateral volumetric increases were observed in some cases. No meaningful correlations were evident pre- or post-operatively between the olfactory test scores and the structural volumes. In conclusion, we demonstrate that smell dysfunction is clearly a key element of both TLE and TLR, impacting odor identification, detection, and discrimination/memory. Whether our novel finding of significant post-operative increases in the volume of brain structures contralateral to the resection side reflects plasticity and compensatory processes requires further study.

Alterations of theta oscillation in executive control in temporal lobe epilepsy patients

Attention dysfunction, especially executive control has been investigated within many types of diseases of the central nervous system. The present study aims to clarify alterations of the executive control (EC) network in patients with temporal lobe epilepsy (TLE).Twenty patients with TLE and 20 matched healthy control subjects participated in the attention network test (ANT), and scalp electroencephalogram (EEG) recordings were set up. The ANT was used to evaluate attention network behavior deficits. Power spectral density (PSD), coherence and correlation were used to detect power and oscillation alterations of attention network in patients with TLE.The most significant differences in executive control were found between patients with TLE and healthy control subjects. Power spectral density in the theta band, and coherence and correlation in the theta band in the frontal area were decreased in patients with TLE.Our results indicate that patients with TLE have severe attention dysfunction, especially in executive control. In addition, brain theta oscillation impairment in frontal area might be connected with poor executive control behavior. These findings will provide new insight into diagnosing and treating patients with temporal lobe epilepsy.

Brain region and epilepsy-associated differences in inflammatory mediator levels in medically refractory mesial temporal lobe epilepsy.

BackgroundEpilepsy patients have distinct immune/inflammatory cell profiles and inflammatory mediator levels in the blood. Although the neural origin of inflammatory cells and mediators has been implied, few studies have measured these inflammatory components in the human brain itself. This study examines the brain levels of chemokines (8), cytokines (14), and vascular injury mediators (3) suspected of being altered in epilepsy.MethodsSoluble protein extracts of fresh frozen resected hippocampus, entorhinal cortex, and temporal cortex from 58 medically refractory mesial temporal lobe epilepsy subjects and 4 nonepileptic neurosurgical subjects were assayed for 25 inflammation-related mediators using ultrasensitive low-density arrays.ResultsBrain mediator levels were compared between regions and between epileptic and nonepileptic cases, showing a number of regional and possible epilepsy-associated differences. Eotaxin, interferon-γ, interleukin (IL)-2, IL-4, IL-12 p70, IL-17A, tumor necrosis factor-α, and intercellular adhesion molecule (ICAM)-1 levels were highest in the hippocampus, the presumptive site of epileptogenesis. Surprisingly, IL-1β and IL-1α were lowest in the hippocampus, compared to cortical regions. In the temporal cortex, IL-1β, IL-8, and MIP-1α levels were highest, compared to the entorhinal cortex and the hippocampus.The most pronounced epilepsy-associated differences were decreased levels of eotaxin, IL-1β, C-reactive protein, and vascular cell adhesion molecule (VCAM)-1 and increased IL-12 p70 levels. Caution must be used in interpreting these results, however, because nonepileptic subjects were emergent neurosurgical cases, not a control group.Correlation analyses of each mediator in each brain region yielded valuable insights into the regulation of these mediator levels in the brain. Over 70 % of the associations identified were between different mediators in a single brain region, providing support for local control of mediator levels. Correlations of different mediators in different brain regions suggested more distributed control mechanisms, particularly in the hippocampus. Interestingly, only four mediators showed robust correlations between the brain regions, yet levels in three of these were significantly different between regions, indicating both global and local controls for these mediators.ConclusionsBoth brain region-specific and epilepsy-associated changes in inflammation-related mediators were detected. Correlations in mediator levels within and between brain regions indicated local and global regulation, respectively. The hippocampus showed the majority of interregional associations, suggesting a focus of inflammatory control between these regions.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-016-0727-z) contains supplementary material, which is available to authorized users.

70. Rehabilitation of verbal and visuospatial memory by oscillatory tDCS and sleep consolidation

Temporal lobe epilepsy (TLE) is often associated with memory deficits. Given the putative role for sleep spindles in learning and encoding, the distribution of spindle generators skewed toward the affected lobe in TLE subjects may be a neurophysiological marker of defective memory. Slow-oscillatory transcranial direct current stimulation (sotDCS) has been shown to improve memory possibly by increasing slow-wave sleep and modulating sleep spindles. To test if excitatory anodal sotDCS over the affected temporal lobe affects sleep spindles, thus improving memory performance. In this randomized controlled cross-over study 12 people with TLE underwent either sotDCS (0.75 Hz; 0–250 μV, 30 min) or a sham procedure before a daytime nap. Declarative verbal and visuospatial learning were tested. Fast and slow spindle signals were recorded by 256-channel EEG during sleep. In both study arms, we used electrical source imaging (ESI) to localize cortical generators. Neuropsychological data were analyzed with general linear model statistics or the Kruskal–Wallis test (p or Z < 0.05), and neurophysiological data were tested with the Mann–Whitney t test and a binomial distribution test (p or Z < 0.05). An improvement in declarative (p = 0.05) and visuospatial memory performance (p = 0.048) was noted after sotDCS. SotDCS increased the current density of slow spindle generators (Z = 0.001), with a shift to the anterior cortical areas. Anodal sotDCS delivered over the affected temporal lobe can improve declarative and, to a lesser extent, visuospatial memory performance by modulating cortical source generators of slow sleep spindles. SotDCS appears to be a promising tool for memory rehabilitation in people with TLE.

Relating Cortical Atrophy in Temporal Lobe Epilepsy with Graph Diffusion-Based Network Models.

Mesial temporal lobe epilepsy (TLE) is characterized by stereotyped origination and spread pattern of epileptogenic activity, which is reflected in stereotyped topographic distribution of neuronal atrophy on magnetic resonance imaging (MRI). Both epileptogenic activity and atrophy spread appear to follow white matter connections. We model the networked spread of activity and atrophy in TLE from first principles via two simple first order network diffusion models. Atrophy distribution is modeled as a simple consequence of the propagation of epileptogenic activity in one model, and as a progressive degenerative process in the other. We show that the network models closely reproduce the regional volumetric gray matter atrophy distribution of two epilepsy cohorts: 29 TLE subjects with medial temporal sclerosis (TLE-MTS), and 50 TLE subjects with normal appearance on MRI (TLE-no). Statistical validation at the group level suggests high correlation with measured atrophy (R = 0.586 for TLE-MTS, R = 0.283 for TLE-no). We conclude that atrophy spread model out-performs the hyperactivity spread model. These results pave the way for future clinical application of the proposed model on individual patients, including estimating future spread of atrophy, identification of seizure onset zones and surgical planning.

P65. Memory rehabilitation in temporal lobe epilepsy: Slow-oscillatory transcranial direct current stimulation modulates memory by altering sleep spindle generators

Background Temporal lobe epilepsy (TLE) is often associated with memory deficits. Given the putative role for sleep spindles in learning and encoding, the distribution of spindle generators skewed toward the affected lobe in TLE subjects may be a neurophysiological marker of defective memory. Slow-oscillatory transcranial direct current stimulation (sotDCS) has been shown to improve memory possibly by increasing slow-wave sleep and modulating sleep spindles. Objective/Hypothesis To test if excitatory anodal sotDCS over the affected temporal lobe affects sleep spindles, thus improving memory performance. Methods In this randomized controlled cross-over study 12 people with TLE underwent either sotDCS (0.75 Hz; 0–250 μV, 30 min) or a sham procedure before a daytime nap. Declarative verbal and visuospatial learning were tested. Fast and slow spindle signals were recorded by 256-channel EEG during sleep. In both study arms, we used electrical source imaging (ESI) to localize cortical generators. Neuropsychological data were analyzed with general linear model statistics or the Kruskal–Wallis test (p or Z). Results An improvement in declarative (p = 0.05) and visuospatial memory performance (p = 0.048) was noted after sotDCS. SotDCS increased the current density of slow spindle generators (Z = 0.001), with a shift to the anterior cortical areas. Conclusions Anodal sotDCS delivered over the affected temporal lobe can improve declarative and, to a lesser extent, visuospatial memory performance by modulating cortical source generators of slow sleep spindles. SotDCS appears to be a promising tool for memory rehabilitation in people with TLE ( Fig. 1 , Table 1 , Table 2 ).

Cortical reorganization for calculation in patients with left temporal lobe epilepsy

Objective To observe the brain regions activated during calculation in patients with left temporal lobe epilepsy (TLE) and in normal subjects. Methods Functional magnetic resonance imaging (fMRI) was applied. Sixteen right-handed persons with left TLE were selected as the left TLE group, and sixteen healthy volunteers were recruited as a control group. The fMRI data was collected as each subject performed simple additions, subtractions and abdication subtractions. Statistical parametric mapping was used to compare the activated brain regions between the two groups. Results The error rate in the calculations was significantly higher in the left TLE group, and their average reaction time was significantly longer. There were aslo significant differences between the two groups in terms of brain activation patterns. Compared with the control group, the left TLE group exhibited hypo-activity in regions such as the left paracentral lobule, the posterior central gyrus, the bilateral inferior parietal lobule, the left angular gyrus, the bilateral supramarginal gyrus, the left middle frontal gyrus, the left superior gyrus, and also in the bilateral posterior cingulate, insular lobule, superior and inferior temporal gyrus, right hippocampus, parahippocampal gyrus, thalamus and cerebellum. The TLE subjects exhibited hyper-activity in the bilateral superior parietal lobule, the bilateral anterior cingulate, as well as in the right, middle and inferior frontal gyrus. Conclusion Our results support a significant functional reorganization of calculation-related neuronal networks within and between the hemispheres in TLE patients. The frontal and parietal lobes may play a compensatory role in the reorganization of the calculation function. Task-related fMRI technology can provide useful information for non-invasive assessment of mathematical computing and cognitive function in TLE patients. Key words: Temporal lobe epilepsy; Computation; Cognition; Functional magnetic resonance imaging

Slow-oscillatory Transcranial Direct Current Stimulation Modulates Memory in Temporal Lobe Epilepsy by Altering Sleep Spindle Generators: A Possible Rehabilitation Tool.

Temporal lobe epilepsy (TLE) is often associated with memory deficits. Given the putative role for sleep spindles memory consolidation, spindle generators skewed toward the affected lobe in TLE subjects may be a neurophysiological marker of defective memory. Slow-oscillatory transcranial direct current stimulation (sotDCS) during slow waves sleep (SWS) has previously been shown to enhance sleep-dependent memory consolidation by increasing slow-wave sleep and modulating sleep spindles. To test if anodal sotDCS over the affected TL prior to a nap affects sleep spindles and whether this improves memory consolidation. Randomized controlled cross-over study. 12 people with TLE underwent sotDCS (0.75 Hz; 0-250 μV, 30 min) or sham before daytime nap. Declarative verbal and visuospatial learning were tested. Fast and slow spindle signals were recorded by 256-channel EEG during sleep. In both study arms, electrical source imaging (ESI) localized cortical generators. Neuropsychological data were analyzed with general linear model statistics or the Kruskal-Wallis test (P or Z < 0.05), and neurophysiological data tested with the Mann-Whitney t test and binomial distribution test (P or Z < 0.05). An improvement in declarative (P = 0.05) and visuospatial memory performance (P = 0.048) emerged after sotDCS. SotDCS increased slow spindle generators current density (Z = 0.001), with a shift to the anterior cortical areas. Anodal sotDCS over the affected temporal lobe improves declarative and visuospatial memory performance by modulating slow sleep spindles cortical source generators. SotDCS appears a promising tool for memory rehabilitation in people with TLE.

Low levels of maximal aerobic power impair the profile of mood state in individuals with temporal lobe epilepsy.

To investigate the correlation between cardiorespiratory fitness and mood state in individuals with temporal lobe epilepsy (TLE). Individuals with TLE (n = 20) and healthy control subjects (C, n = 20) were evaluated. Self-rating questionnaires were used to assess mood (POMS) and habitual physical activity (BAECKE). Cardiorespiratory fitness was evaluated by a maximal incremental test. People with TLE presented lower cardiorespiratory fitness; higher levels of mood disorders; and lower levels of vigor when compared to control health subjects. A significant negative correlation was observed between the levels of tension-anxiety and maximal aerobic power. Low levels of cardiorespiratory fitness may modify the health status of individuals with TLE and it may be considered a risk factor for the development of mood disorders.

Expression and activity of thimet oligopeptidase (TOP) are modified in the hippocampus of subjects with temporal lobe epilepsy (TLE)

Thimet oligopeptidase (TOP) is a metalloprotease that has been associated with peptide processing in several nervous system structures, and its substrates include several peptides such as bradykinin, amyloid beta (Aβ), and major histocompatibility complex (MHC) class I molecules. As shown previously by our research group, patients with temporal lobe epilepsy (TLE) have a high level of kinin receptors as well as kallikrein, a kinin-releasing enzyme, in the hippocampus. In this study, we evaluated the expression, distribution, and activity of TOP in the hippocampus of patients with TLE and autopsy-control tissues, through reverse-transcription polymerase chain reaction (RT-PCR), enzymatic activity, Western blot, and immunohistochemistry. In addition, hippocampi of rats were analyzed using the pilocarpine-induced epilepsy model. Animals were grouped according to the epilepsy phases defined in the model as acute, silent, and chronic. Increased TOP mRNA expression, decreased protein levels and enzymatic activity were observed in tissues of patients, compared to control samples. In addition, decreased TOP distribution was also visualized by immunohistochemistry. Similar results were observed in tissues of rats during the acute phase of epilepsy model. However, increased TOP mRNA expression and no changes in immunoreactivity were found in the silent phase, whereas increased TOP mRNA expression and increased enzymatic activity were observed in the chronic phase. The results show that these alterations could be related to a failure in the mechanisms involved in clearance of inflammatory peptides in the hippocampus, suggesting an accumulation of potentially harmful substances in nervous tissue such as Aβ, bradykinin, and antigenic peptides. These accumulations could be related to hippocampal inflammation observed in TLE subjects.