Study Of Temporal Lobe Epilepsy Research Articles

Surgical Outcomes in Post-Traumatic Temporal Lobe Epilepsy: A Systematic Review and Meta-Analysis.

Epilepsy surgery provides excellent benefits in post-traumatic epilepsy of the temporal lobe (PTE-TL), but outcomes relative to non-traumatic epilepsy of the temporal lobe (NTE-TL) are less favorable. Large well-designed studies are recommended to further clarify the role of epilepsy surgery in PTE. It is unclear whether epilepsy surgery outcomes in PTE are as robust as described for drug resistant epilepsy (DRE) in general. Prior outcome studies in PTE are limited by small numbers, lack of a control group, or both. We performed a meta-analysis of studies in temporal lobe epilepsy (TLE) to evaluate post-surgical outcomes in those with PTE-TL and compare outcomes to those with NTE-TL. PubMed, EMBASE, and Web of Science databases were queried for studies reporting epilepsy surgery outcomes separately for PTE-TL and NTE-TL. Outcomes were divided into favorable (Engel Class I) or unfavorable (Engel Class II-IV) for comparison. Meta-analyses were performed to evaluate: 1) the proportion of Class I outcomes following epilepsy surgery in PTE-TL; and 2) calculate the odds of Class I surgical outcomes in PTE-TL compared with NTE-TL. Of 3669 articles that reported surgical outcomes in epilepsy, nine studies (n = 886) were identified that reported outcomes for both PTE-TL (n = 219) and NTE-TL (n = 667). The weighted proportion of favorable outcomes (Engel Class I) were high for both PTE-TL (70.1%, 95% CI 61.9%-78.3%) and NTE-TL (75.2%, 95% CI 69.4%-80.2%). Patients with PTE-TL were at greater risk of unfavorable (Engel Class II-IV) outcomes (relative risk 1.36, 95% CI 1.04-1.78) compared with NTE-TL.

A resting-state fMRI study of temporal lobe epilepsy using multivariate pattern analysis and Granger causality analysis.

Understanding the pathogenesis of temporal lobe epilepsy (TLE) is essential for its diagnosis and treatment. The study aimed to explore regional homogeneity (ReHo) and changes in effective connectivity (EC) between brain regions in TLE patients, hoping to discover potential abnormalities in certain brain regions in TLE patients. Resting-state functional magnetic resonance data were collected from 23 TLE patients and 32 normal controls (NC). ReHo was used as a feature of multivariate pattern analysis (MVPA) to explore the ability of its alterations in identifying TLE. Based on the results of the MVPA, certain brain regions were selected as seed points to further explore alterations in EC between brain regions using Granger causality analysis. MVPA results showed that the classification accuracy for the TLE and NC groups was 87.27%, and the right posterior cerebellum lobe, right lingual gyrus (LING_R), right cuneus (CUN_R), and left superior temporal gyrus (STG_L) provided significant contributions. Moreover, the EC from STG_L to right fusiform gyrus (FFG_R) and LING_R and the EC from CUN_R to the right occipital superior gyrus (SOG_R) and right occipital middle gyrus (MOG_R) were altered compared to the NC group. The MVPA results indicated that ReHo abnormalities in brain regions may be an important feature in the identification of TLE. The enhanced EC from STG_L to FFG_R and LING_R indicates a shift in language processing to the right hemisphere, and the weakened EC from SOG_R and MOG_R to CUN_R may reveal an underlying mechanism of TLE.

P.013 Stereo-encephalographic presurgical evaluation of temporal lobe epilepsy

Background: Drug resistant epilepsy is present in nearly 30% of patients. Resection of the epileptogenic zone has been found to be the most effective in achieving seizure freedom. The study of temporal lobe epilepsy for surgical treatment is extensive and complex. It involves a multidisciplinary team in decision-making with initial non-invasive studies (Phase I), providing 70% of required information to elaborate a hypothesis and treatment plans. Select cases present more complexity involving bilateral clinical or electrographic manifestations, have contradicting information or may involve deeper structures as a part of the epileptogenic zone. Methods: A review of the literature was done with key terms such as: “temporal lobe epilepsy”and “SEEG”and “intracranial EEG”, “epilepsy surgery”, un Pubmed, EMBASE, Medlink and Scielo. Most cutting edge, controversial subjects surrounding this field were considered. Results: In this comprehensive review, we explore the indications, usefulness, discoveries in interictal and ictal findings, pitfalls, and advances in the science of presurgical stereo-encephalography for temporal lobe epilepsy. Conclusions: Intracranial recording follows original concepts since its development by Bancaud and Talairach, but great advances have been made in the field. Stereo-electroencephalography is a growing field of study, treatment and establishment of seizure pattern complexities.

Stereo-Encephalographic Presurgical Evaluation of Temporal Lobe Epilepsy: An Evolving Science.

Drug-resistant epilepsy is present in nearly 30% of patients. Resection of the epileptogenic zone has been found to be the most effective in achieving seizure freedom. The study of temporal lobe epilepsy for surgical treatment is extensive and complex. It involves a multidisciplinary team in decision-making with initial non-invasive studies (Phase I), providing 70% of the required information to elaborate a hypothesis and treatment plans. Select cases present more complexity involving bilateral clinical or electrographic manifestations, have contradicting information, or may involve deeper structures as a part of the epileptogenic zone. These cases are discussed by a multidisciplinary team of experts with a hypothesis for invasive methods of study. Subdural electrodes were once the mainstay of invasive presurgical evaluation and in later years most Comprehensive Epilepsy Centers have shifted to intracranial recordings. The intracranial recording follows original concepts since its development by Bancaud and Talairach, but great advances have been made in the field. Stereo-electroencephalography is a growing field of study, treatment, and establishment of seizure pattern complexities. In this comprehensive review, we explore the indications, usefulness, discoveries in interictal and ictal findings, pitfalls, and advances in the science of presurgical stereo-encephalography for temporal lobe epilepsy.

Cortical low-frequency power correlates with behavioral impairment in animal model of focal limbic seizures.

Impairment in consciousness is a debilitating symptom during and after seizures; however, its mechanism remains unclear. Limbic seizures have been shown to spread to arousal circuitry to result in a "network inhibition" phenomenon. However, prior animal model studies did not relate physiological network changes to behavioral responses during or following seizures. Focal onset limbic seizures were induced while rats were performing an operant conditioned behavioral task requiring response to an auditory stimulus to quantify how and when impairment of behavioral response occurs. Correct responses were rewarded with sucrose. Cortical and hippocampal electrophysiology measured by local field potential recordings was analyzed for changes in low- and high-frequency power in relation to behavioral responsiveness during seizures. As seen in patients with seizures, ictal (p<.0001) and postictal (p=.0015) responsiveness was variably impaired. Analysis of cortical and hippocampal electrophysiology revealed that ictal (p=.002) and postictal (p=.009) frontal cortical low-frequency 3-6-Hz power was associated with poor behavioral performance. In contrast, the hippocampus showed increased power over a wide frequency range during seizures, and suppression postictally, neither of which were related to behavioral impairment. These findings support prior human studies of temporal lobe epilepsy as well as anesthetized animal models suggesting that focal limbic seizures depress consciousness through remote network effects on the cortex, rather than through local hippocampal involvement. By identifying the cortical physiological changes associated with impaired arousal and responsiveness in focal seizures, these results may help guide future therapies to restore ictal and postictal consciousness, improving quality of life for people with epilepsy.

Preferential susceptibility of limbic cortices to microstructural damage in temporal lobe epilepsy: A quantitative T1 mapping study

The majority of MRI studies in temporal lobe epilepsy (TLE) have utilized morphometry to map widespread cortical alterations. Morphological markers, such as cortical thickness or grey matter density, reflect combinations of biological events largely driven by overall cortical geometry rather than intracortical tissue properties. Because of its sensitivity to intracortical myelin, quantitative measurement of longitudinal relaxation time (qT1) provides and an in vivo proxy for cortical microstructure. Here, we mapped the regional distribution of qT1 in a consecutive cohort of 24 TLE patients and 20 healthy controls. Compared to controls, patients presented with a strictly ipsilateral distribution of qT1 increases in temporopolar, parahippocampal and orbitofrontal cortices. Supervised statistical learning applied to qT1 maps could lateralize the seizure focus in 92% of patients. Intracortical profiling of qT1 along streamlines perpendicular to the cortical mantle revealed marked effects in upper levels that tapered off at the white matter interface. Findings remained robust after correction for cortical thickness and interface blurring, suggesting independence from previously reported morphological anomalies in this disorder. Mapping of qT1 along hippocampal subfield surfaces revealed marked increases in anterior portions of the ipsilateral CA1-3 and DG that were also robust against correction for atrophy. Notably, in operated patients, qualitative histopathological analysis of myelin stains in resected hippocampal specimens confirmed disrupted internal architecture and fiber organization. Both hippocampal and neocortical qT1 anomalies were more severe in patients with early disease onset. Finally, analysis of resting-state connectivity from regions of qT1 increases revealed altered intrinsic functional network embedding in patients, particularly to prefrontal networks. Analysis of qT1 suggests a preferential susceptibility of ipsilateral limbic cortices to microstructural damage, possibly related to disrupted myeloarchitecture. These alterations may reflect atypical neurodevelopment and affect the integrity of fronto-limbic functional networks.

P.3.b.032 Evaluation of preferences of chimeric, reversed and normal self-face in patients with schizophrenia and healthy controls – a pilot study

Temporal lobe epilepsy with hippocampus sclerosis (HS) is the most frequent focal epilepsy and often refractory to anticonvulsant therapy. Secondary structural damage has been reported in several studies of temporal lobe epilepsy and unilateral hippocampal sclerosis. Applying diffusion tensor imaging (DTI) we investigated alterations in white matter following temporal lobe surgery in patients with medial temporal lobe epilepsy. We examined 40 patients who underwent surgery at our hospital for HS between 1996 and 2006 with diffusion tensor imaging (DTI). Images were obtained at a 3 T MRI scanner employing 60 gradient directions. Tract-based spatial statistics (TBSS), a novel voxel-based approach, was applied to analyze the data. Both patients with left- as well as right-sided surgery exhibited widespread degradation of fractional anisotropy (FA) in main fiber tracts not limited to the respective temporal lobe such as the uncinate fasciculus, the fronto-occipital fasciculus, the superior longitudinal fasciculus, the corpus callosum and the corticospinal tract on the respective hemisphere. Patients with left-hemispheric surgery showed more widespread affections ipsilaterally and also FA decrease in the contralateral inferior longitudinal fasciculus. DTI demonstrates widespread clusters of abnormal diffusivity and anisotropy in prominent white matter tracts linking mesial temporal lobe structures with other brain areas. Alterations in the ipsilateral mesial temporal lobe can be attributed to be a result of surgery, whereas extratemporal FA decrease is more likely the result of the underlying seizure disorder.

Detection of temporal lobe epilepsy using support vector machines in multi-parametric quantitative MR imaging

The detection of MRI abnormalities that can be associated to seizures in the study of temporal lobe epilepsy (TLE) is a challenging task. In many cases, patients with a record of epileptic activity do not present any discernible MRI findings. In this domain, we propose a method that combines quantitative relaxometry and diffusion tensor imaging (DTI) with support vector machines (SVM) aiming to improve TLE detection. The main contribution of this work is two-fold: on one hand, the feature selection process, principal component analysis (PCA) transformations of the feature space, and SVM parameterization are analyzed as factors constituting a classification model and influencing its quality. On the other hand, several of these classification models are studied to determine the optimal strategy for the identification of TLE patients using data collected from multi-parametric quantitative MRI.A total of 17 TLE patients and 19 control volunteers were analyzed. Four images were considered for each subject (T1 map, T2 map, fractional anisotropy, and mean diffusivity) generating 936 regions of interest per subject, then 8 different classification models were studied, each one comprised by a distinct set of factors. Subjects were correctly classified with an accuracy of 88.9%. Further analysis revealed that the heterogeneous nature of the disease impeded an optimal outcome. After dividing patients into cohesive groups (9 left-sided seizure onset, 8 right-sided seizure onset) perfect classification for the left group was achieved (100% accuracy) whereas the accuracy for the right group remained the same (88.9%).We conclude that a linear SVM combined with an ANOVA-based feature selection+PCA method is a good alternative in scenarios like ours where feature spaces are high dimensional, and the sample size is limited. The good accuracy results and the localization of the respective features in the temporal lobe suggest that a multi-parametric quantitative MRI, ROI-based, SVM classification could be used for the identification of TLE patients. This method has the potential to improve the diagnostic assessment, especially for patients who do not have any obvious lesions in standard radiological examinations.

Domoic Acid Epileptic Disease

Domoic acid epileptic disease is characterized by spontaneous recurrent seizures weeks to months after domoic acid exposure. The potential for this disease was first recognized in a human case study of temporal lobe epilepsy after the 1987 amnesic shellfish-poisoning event in Quebec, and was characterized as a chronic epileptic syndrome in California sea lions through investigation of a series of domoic acid poisoning cases between 1998 and 2006. The sea lion study provided a breadth of insight into clinical presentations, unusual behaviors, brain pathology, and epidemiology. A rat model that replicates key observations of the chronic epileptic syndrome in sea lions has been applied to identify the progression of the epileptic disease state, its relationship to behavioral manifestations, and to define the neural systems involved in these behavioral disorders. Here, we present the concept of domoic acid epileptic disease as a delayed manifestation of domoic acid poisoning and review the state of knowledge for this disease state in affected humans and sea lions. We discuss causative mechanisms and neural underpinnings of disease maturation revealed by the rat model to present the concept for olfactory origin of an epileptic disease; triggered in dendodendritic synapases of the olfactory bulb and maturing in the olfactory cortex. We conclude with updated information on populations at risk, medical diagnosis, treatment, and prognosis.

Imaging structural and functional brain networks in temporal lobe epilepsy

Early imaging studies in temporal lobe epilepsy (TLE) focused on the search for mesial temporal sclerosis, as its surgical removal results in clinically meaningful improvement in about 70% of patients. Nevertheless, a considerable subgroup of patients continues to suffer from post-operative seizures. Although the reasons for surgical failure are not fully understood, electrophysiological and imaging data suggest that anomalies extending beyond the temporal lobe may have negative impact on outcome. This hypothesis has revived the concept of human epilepsy as a disorder of distributed brain networks. Recent methodological advances in non-invasive neuroimaging have led to quantify structural and functional networks in vivo. While structural networks can be inferred from diffusion MRI tractography and inter-regional covariance patterns of structural measures such as cortical thickness, functional connectivity is generally computed based on statistical dependencies of neurophysiological time-series, measured through functional MRI or electroencephalographic techniques. This review considers the application of advanced analytical methods in structural and functional connectivity analyses in TLE. We will specifically highlight findings from graph-theoretical analysis that allow assessing the topological organization of brain networks. These studies have provided compelling evidence that TLE is a system disorder with profound alterations in local and distributed networks. In addition, there is emerging evidence for the utility of network properties as clinical diagnostic markers. Nowadays, a network perspective is considered to be essential to the understanding of the development, progression, and management of epilepsy.

MRI‐Based Brain Structure Volumes in Temporal Lobe Epilepsy Patients and their Unaffected Siblings: A Preliminary Study

Investigating the heritability of brain structure may be useful in simplifying complicated genetic studies in temporal lobe epilepsy (TLE). A preliminary study is presented to determine if volume deficits of candidate brain structures present at a higher rate in unaffected siblings than controls subjects. T1-weighted MR images was acquired for 28 TLE patients, a same-sex unaffected sibling of 12 of these and 28 normal controls. Selected brain structure volumes were measured using an automated whole brain segmentation technique. Candidate brain structure endophenotypes were determined and group differences were investigated between (1) controls and patients and (2) controls and siblings. ICC's were used to measure the quantitative volumetric association within each sibling pair. TLE patients demonstrated a significantly lower cerebral white matter, bilateral hippocampus, thalamus, and left entorhinal cortex volumes when compared with controls. A significant deficit in cerebral white matter (CWM) was common to patient and nonaffected siblings when compared with controls. Furthermore, a significant correlation was revealed between patients and siblings in CWM and bilateral thalamus. The findings suggest an overlap in the neurodevelopmental genes responsible for both brain structure and the expression of the disease. Further work is ongoing to confirm these findings.

Rapamycin suppresses the recurrent excitatory circuits of dentate gyrus in a mouse model of temporal lobe epilepsy

Recurrent excitatory circuits and abnormal recurrent excitatory inputs are essential in epileptogenesis. Studies in temporal lobe epilepsy have shown that mossy fiber sprouting, which represents synaptic reorganization, renders the formation of abnormal recurrent excitatory circuits and inputs. The mammalian target of rapamycin (mTOR) pathway has recently been proved important in mossy fiber sprouting. In the present study, rapamycin, a mTOR inhibiter, was injected into the mouse of temporal lobe epilepsy. Electrophysiological and histological properties of the hippocampus were investigated by whole cell patch clamp, extracellular recording and Timm staining. Following the development of epilepsy, frequency of spontaneous excitatory postsynaptic currents (EPSCs) and amplitude of antidromically evoked EPSCs in granule cells were remarkably increased, as well as the epileptiform activity and mossy fiber sprouting were detected, which indicated the formation of abnormal recurrent excitatory circuits. By the use of rapamycin, frequency of spontaneous EPSCs, amplitude of antidromically evoked EPSCs, the epileptiform activity and mossy fiber sprouting were all remarkably suppressed. Our findings suggested an anti-epileptogenic role of rapamycin by suppressing the recurrent excitatory circuits of dentate gyrus.

Domoic acid induced seizures progress to a chronic state of epilepsy in rats

The emergence of an epilepsy syndrome in sea lions poisoned by domoic acid (DA) draws striking parallels to the single case study of temporal lobe epilepsy (TLE) that developed in an 84 yr old man one year after being poisoned by DA. To establish a basis for understanding this disease in sea lions and humans that appears to progress from DA poisoning, we have investigated the potential for a single incident of DA poisoning in rats to progress to spontaneous recurrent seizures (SRS), the hallmark of epilepsy. We have developed a DA administration protocol to induce a nonlethal status epilepticus (SE) and monitored the animals for SRS by 6 h/week of video recording. We demonstrate that a single episode of SE leads to SRS in 94% of rats (n = 23) in 6 months. These findings indicate that DA induced SE can efficiently translate to epileptic disease.

An Assessment of MEG Coherence Imaging in the Study of Temporal Lobe Epilepsy

An Assessment of MEG Coherence Imaging in the Study of Temporal Lobe Epilepsy

Contribución diferencial de los estudios preoperatorios al diagnóstico en la cirugía de la epilepsia temporal

It is necessary to know the degree of concordance of preoperative studies in temporal lobe epilepsy (TLE). AIM. To analyze the relative importance of different preoperative tests (vEEG, EEG, SPECT and MRI), the degree of agreement between them, and to develop a Bayesian probability model for diagnosis. We analyzed 73 patients operated by TLE, with a minimum postoperative follow-up of two years. To analyze the localization capability of different test, we used only patients with an Engel's grade I outcome during all the follow-up time (n = 60). Engel's grades percentages at 2 years were 87.7/8.2/3.0/0.0 (I/II/III/IV, respectively). The preoperative correlation was < 50% for three tests and 33% for the four. MRI studies were found normal in 33.3% of cases. According to the localization index, the arrange was vEEG > RM > SPECT > EEG. The conditional probability of correct localization for a test was vEEG (0.950) > EEG (0.719) > SPECT (0.717) > RM (0.683). Concordance for more than two tests, was = 0.587 (vEEG + MRI). The probability of obtaining a priori correct localization was vEEG (0.983) > RM (0.414) > EEG (0.285) > SPECT (0.209). The Bayesian model is highly reliable. Probably it is not always possible to obtain a high degree of agreement among preoperative test, despite this, it is possible to obtain a good functional result. The most effective test is the vEEG.

Widespread affections of large fiber tracts in postoperative temporal lobe epilepsy

Temporal lobe epilepsy with hippocampus sclerosis (HS) is the most frequent focal epilepsy and often refractory to anticonvulsant therapy. Secondary structural damage has been reported in several studies of temporal lobe epilepsy and unilateral hippocampal sclerosis. Applying diffusion tensor imaging (DTI) we investigated alterations in white matter following temporal lobe surgery in patients with medial temporal lobe epilepsy. We examined 40 patients who underwent surgery at our hospital for HS between 1996 and 2006 with diffusion tensor imaging (DTI). Images were obtained at a 3 T MRI scanner employing 60 gradient directions. Tract-based spatial statistics (TBSS), a novel voxel-based approach, was applied to analyze the data. Both patients with left- as well as right-sided surgery exhibited widespread degradation of fractional anisotropy (FA) in main fiber tracts not limited to the respective temporal lobe such as the uncinate fasciculus, the fronto-occipital fasciculus, the superior longitudinal fasciculus, the corpus callosum and the corticospinal tract on the respective hemisphere. Patients with left-hemispheric surgery showed more widespread affections ipsilaterally and also FA decrease in the contralateral inferior longitudinal fasciculus. DTI demonstrates widespread clusters of abnormal diffusivity and anisotropy in prominent white matter tracts linking mesial temporal lobe structures with other brain areas. Alterations in the ipsilateral mesial temporal lobe can be attributed to be a result of surgery, whereas extratemporal FA decrease is more likely the result of the underlying seizure disorder.

E/I balance and GABAA receptor plasticity

GABAA receptors mediate most of the fast inhibitory transmission in the CNS. They form heteromeric complexes assembled from a large family of subunit genes. The existence of multiple GABAA receptor subtypes differing in subunit composition, localization and functional properties underlies their role for fine-tuning of neuronal circuits and genesis of network oscillations. The differential regulation of GABAA receptor subtypes represents a major facet of homeostatic synaptic plasticity and contributes to the excitation/inhibition (E/I) balance under physiological conditions and upon pathological challenges. The purpose of this review is to discuss recent findings highlighting the significance of GABAA receptor heterogeneity for the concept of E/I balance and its relevance for epilepsy. Specifically, we address the following issues: (1) role for tonic inhibition, mediated by extrasynaptic GABAA receptors, for controlling neuronal excitability; (2) significance of chloride ion transport for maintenance of the E/I balance in adult brain; and (3) molecular mechanisms underlying GABAA receptor regulation (trafficking, posttranslational modification, gene transcription) that are important for homoeostatic plasticity. Finally, the relevance of these findings is discussed in light of the involvement of GABAA receptors in epileptic disorders, based on recent experimental studies of temporal lobe epilepsy (TLE) and absence seizures and on the identification of mutations in GABAA receptor subunit genes underlying familial forms of epilepsy.

Cerebral blood flow in temporal lobe epilepsy: a partial volume correction study

Previous studies in temporal lobe epilepsy (TLE) have shown that, owing to brain atrophy, positron emission tomography (PET) can overestimate deficits in measures of cerebral function such as glucose metabolism (CMR(glu)) and neuroreceptor binding. The magnitude of this effect on cerebral blood flow (CBF) is unexplored. The aim of this study was to assess CBF deficits in TLE before and after magnetic resonance imaging-based partial volume correction (PVC). Absolute values of CBF for 21 TLE patients and nine controls were computed before and after PVC. In TLE patients, quantitative CMR(glu) measurements also were obtained. Before PVC, regional values of CBF were significantly (p<0.05) lower in TLE patients than in controls in all regions, except the fusiform gyrus contralateral to the epileptic focus. After PVC, statistical significance was maintained in only four regions: ipsilateral inferior temporal cortex, bilateral insula and contralateral amygdala. There was no significant difference between patients and controls in CBF asymmetry indices (AIs) in any region before or after PVC. In TLE patients, AIs for CBF were significantly smaller than for CMR(glu) in middle and inferior temporal cortex, fusiform gyrus and hippocampus both before and after PVC. A significant positive relationship between disease duration and AIs for CMR(glu), but not CBF, was detected in hippocampus and amygdala, before but not after PVC. PVC should be used for PET CBF measurements in patients with TLE. Reduced blood flow, in contrast to glucose metabolism, is mainly due to structural changes.

Development of 2dTCA for the detection of irregular, transient bold activity

The temporal clustering algorithm (TCA) has been developed in order to detect irregular, transient functional MRI (fMRI) activation signals when the timings of the stimuli are unknown. Unfortunately, such methods are also sensitive to signal changes caused by motion and physiological noise. We have developed a modified TCA technique, 2dTCA, which can detect multiple different timing patterns within a dataset so that signals of interest can be separated from artifacts and those of no interest. The objective of this work was to further develop the 2dTCA methods and evaluate their performance in simulated functional MRI datasets. Comparisons were made with TCA and a freely-distributed independent component analysis algorithm (ICA). We created two different sets of six computer-generated phantoms with one and two different simulated activation time courses present in 10 regions of interest. The phantoms also contained real subject rigid and nonrigid body motion and noise. Sensitivity of detection, defined as the true-positive activation rate at false-positive activation rates varying between 0.0001 and 0.01, was compared between methods. Additionally, specificity of detection of the irregular, transient signal of interest was assessed by comparing the number of signal time courses detected by each algorithm. The results suggest that the increased sensitivity of 2dTCA over TCA in detecting this particular signal of interest is comparable to the detection with ICA, but with fewer other signals detected. A few examples of the successful application of 2dTCA to the localization of interictal activity in preliminary studies of temporal lobe epilepsy are also described.

Hippocampal gene expression analysis using the ORESTES methodology shows that homer 1a mRNA is upregulated in the acute period of the pilocarpine epilepsy model

In the study of temporal lobe epilepsy (TLE) the characterization of genes expressed in the hippocampus is of central importance for understanding their roles in epileptogenic mechanisms. Although several large-scale studies on TLE gene expression have been reported, precise assignment of individual genes associated with this syndrome is still debatable. Here we investigated differentially expressed genes by comparison of mRNAs from normal and epileptic rat hippocampus in the pilocarpine model of epilepsy. For this we used a powerful EST sequencing methodology, ORESTES (Open Reading frame Expressed Sequence Tags), which generates sequence datasets enriched for mRNAs open reading frames (ORFs) rather than simple 5' and 3' ends of mRNAs. Analysis of our sequences shows that ORESTES readily enables the identification of epilepsy associated ORFs. PFAM analysis of protein motifs present in our ORESTES epilepsy database revealed diverse important protein family domains, such as cytoskeletal, cell signaling and protein kinase domains, which could be involved in processes underlying epileptogenesis. More importantly, we show that the expression of homer 1a, known to be coupled to mGluR and NMDA synaptic transmission, is associated with pilocarpine induced status epilepticus (SE). The combined use of the pilocarpine model of epilepsy with the ORESTES technique can significantly contribute to the identification of specific genes and proteins related to TLE. This is the first study applying a large-scale method for rapid shotgun sequencing directed to ORFs in epilepsy research.