Processing In Temporal Lobe Epilepsy Research Articles

Structure-function coupling increases during interictal spikes in temporal lobe epilepsy: A graph signal processing study

ObjectiveStructure-function coupling remains largely unknown in brain disorders. We studied this coupling during interictal epileptic discharges (IEDs), using graph signal processing in temporal lobe epilepsy (TLE). MethodsWe decomposed IEDs of 17 patients on spatial maps, i.e. network harmonics, extracted from a structural connectome. Harmonics were split in smooth maps (long-range interactions reflecting integration) and coarse maps (short-range interactions reflecting segregation) and were used to reconstruct the part of the signal coupled (Xc) and decoupled (Xd) from the structure, respectively. We analysed how Xc and Xd embed the IED energy over time, at global and regional level. ResultsFor Xc, the energy was smaller than for Xd before the IED onset (p < .001), but became larger around the first IED peak (p < .05, cluster 2, C2). Locally, the ipsilateral mesial regions were significantly coupled to the structure over the whole epoch. The ipsilateral hippocampus increased its coupling during C2 (p < .01). ConclusionsAt whole-brain level, segregation gives way to integrative processes during the IED. Locally, brain regions commonly involved in the TLE epileptogenic network increase their reliance on long-range couplings during IED (C2). SignificanceIn TLE, integration mechanisms prevail during the IED and are localized in the ipsilateral mesial temporal regions.

Multiple-brain systems dynamically interact during tonic and phasic states to support language integrity in temporal lobe epilepsy

An epileptogenic focus in the dominant temporal lobe can result in the reorganization of language systems in order to compensate for compromised functions. We studied the compensatory reorganization of language in the setting of left temporal lobe epilepsy (TLE), taking into account the interaction of language (L) with key non-language (NL) networks such as dorsal attention (DAN), fronto-parietal (FPN) and cingulo-opercular (COpN), with these systems providing cognitive resources helpful for successful language performance.We applied tools from dynamic network neuroscience to functional MRI data collected from 23 TLE patients and 23 matched healthy controls during the resting state (RS) and a sentence completion (SC) task to capture how the functional architecture of a language network dynamically changes and interacts with NL systems in these two contexts.We provided evidence that the brain areas in which core language functions reside dynamically interact with non-language functional networks to carry out linguistic functions. We demonstrated that abnormal integrations between the language and DAN existed in TLE, and were present both in tonic as well as phasic states. This integration was considered to reflect the entrainment of visual attention systems to the systems dedicated to lexical semantic processing. Our data made clear that the level of baseline integrations between the language subsystems and certain NL systems (e.g., DAN, FPN) had a crucial influence on the general level of task integrations between L/NL systems, with this a normative finding not unique to epilepsy. We also revealed that a broad set of task L/NL integrations in TLE are predictive of language competency, indicating that these integrations are compensatory for patients with lower overall language skills.We concluded that RS establishes the broad set of L/NL integrations available and primed for use during task, but that the actual use of those interactions in the setting of TLE depended on the level of language skill. We believe our analyses are the first to capture the potential compensatory role played by dynamic network reconfigurations between multiple brain systems during performance of a complex language task, in addition to testing for characteristics in both the phasic/task and tonic/resting state that are necessary to achieve language competency in the setting of temporal lobe pathology. Our analyses highlighted the intra- versus inter-system communications that form the basis of unique language processing in TLE, pointing to the dynamic reconfigurations that provided the broad multi-system support needed to maintain language skill and competency.

Experimental study on the expression of ubiquitin-specific protease-25 in temporal cortex of epileptic rats

Objective To study the expression of ubiquitin-specific protease 25 (USP25) in the temporal cortex of the kainic acid (KA) induced epilepsy rat model. Methods Fifty-two male SD rats were randomly divided into the epilepsy model group (n=39) and sham-operated control group (n=13) with the random number table. The epilepsy model group was established by injecting KA into the amygdala, then the epileptic rats were randomly divided into 3 groups according to the modeling success time: 1 day for acute period, 7 days for latent period and 30 days for chronic period (13 rats in each group). Those rats were sampled at the end of observation. Rats in the control group were injected with normal saline into the amygdala and sampled together with those in the experimental group. Immunohistochemistry and immunofluorescence double labeling was used to test USP25 expression and its co-expression with neurons (NeuN) and astrocytes (GFAP). Quantitative real-time PCR and Western blot were used to assess the change of USP25 in the temporal cortex of rats. Results In the ipsilateral temporal cortex, the positive cells of co-expression of USP25 and NeuN were increased in the later stage of epilepsy in the epilepsy model group, and the expression levels of USP25 mRNA and protein in different stages of epilepsy varied significantly (F= 25.48 and 7.68 respectively, both P<0.05). Compared with the control group (mRNA level: 1.00±0.36, protein level: 1.00±0.46), the expression of USP25 in the latent group (mRNA level: 10.80±4.82, protein level: 1.88±0.32) and the chronic group (mRNA level: 12.97±4.48, protein level: 1.92±0.26) were increased significantly (all P<0.05). In the contralateral temporal cortex, the expression levels of USP25 mRNA and protein in different stages of epilepsy also varied significantly (F=86.86 and 6.65 respectively, both P<0.05). Conclusions The increased expression of USP25 in the temporal cortex after the latent period has suggested that the deubiquitination pathway is involved in the chronic pathological process of temporal lobe epilepsy. Key words: Epilepsy, temporal lobe; Ubiquitin-specific protease 25; Rats

Does neuronal-glia interaction involve depression as a behavioral comorbidity related to epileptogenic process in temporal lobe epilepsy?

Does neuronal-glia interaction involve depression as a behavioral comorbidity related to epileptogenic process in temporal lobe epilepsy?

Hippocampal MRS and subfield volumetry at 7T detects dysfunction not specific to seizure focus

Ultra high-field 7T MRI offers sensitivity to localize hippocampal pathology in temporal lobe epilepsy (TLE), but has rarely been evaluated in patients with normal-appearing clinical MRI. We applied multimodal 7T MRI to assess if focal subfield atrophy and deviations in brain metabolites characterize epileptic hippocampi. Twelve pre-surgical TLE patients (7 MRI-negative) and age-matched healthy volunteers were scanned at 7T. Hippocampal subfields were manually segmented from 600μm isotropic resolution susceptibility-weighted images. Hippocampal metabolite spectra were acquired to determine absolute concentrations of glutamate, glutamine, myo-inositol, NAA, creatine and choline. We performed case-controls analyses, using permutation testing, to identify abnormalities in hippocampal imaging measures in individual patients, for evaluation against clinical evidence of seizure lateralisation and neuropsychological memory test scores. Volume analyses identified hippocampal subfield atrophy in 9/12 patients (75%), commonly affecting CA3. 7/8 patients had altered metabolite concentrations, most showing reduced glutamine levels (62.5%). However, neither volume nor metabolite deviations consistently lateralized the epileptogenic hippocampus. Rather, lower subiculum volumes and glutamine concentrations correlated with impaired verbal memory performance. Hippocampal subfield and metabolic abnormalities detected at 7T appear to reflect pathophysiological processes beyond epileptogenesis. Despite limited diagnostic contributions, these markers show promise to help elucidate mnemonic processing in TLE.

Wnt/β-catenin signalling pathway mediated aberrant hippocampal neurogenesis in kainic acid-induced epilepsy.

Temporal lobe epilepsy is a chronic disorder of nerve system, mainly characterized by hippocampal sclerosis with massive neuronal loss and severe gliosis. Aberrant neurogenesis has been shown in the epileptogenesis process of temporal lobe epilepsy. However, the molecular mechanisms underlying aberrant neurogenesis remain unclear. The roles of Wnt signalling cascade have been well established in neurogenesis during multiple aspects. Here, we used kainic acid-induced rat epilepsy model to investigate whether Wnt/β-catenin signalling pathway is involved in the aberrant neurogenesis in temporal lobe epilepsy. Immunostaining and western blotting results showed that the expression levels of β-catenin, Wnt3a, and cyclin D1, the key regulators in Wnt signalling pathway, were up-regulated during acute epilepsy induced by the injection of kainic acids, indicating that Wnt signalling pathway was activated in kainic acid-induced temporal lobe epilepsy. Moreover, BrdU labelling results showed that blockade of the Wnt signalling by knocking down β-catenin attenuated aberrant neurogenesis induced by kainic acids injection. Altogether, Wnt/β-catenin signalling pathway mediated hippocampal neurogenesis during epilepsy, which might provide new strategies for clinical treatment of temporal lobe epilepsy. Temporal lobe epilepsy is a chronic disorder of nerve system, mainly characterized by hippocampal sclerosis. Aberrant neurogenesis has been shown to involve in the epileptogenesis process of temporal lobe epilepsy. In the present study, we discovered that Wnt3a/β-catenin signalling pathway serves as a link between aberrant neurogenesis and underlying remodelling in the hippocampus, leading to temporal lobe epilepsy, which might provide new strategies for clinical treatment of temporal lobe epilepsy.

An event-related potentials study of lexico-semantic processing in temporal lobe epilepsy

An event-related potentials study of lexico-semantic processing in temporal lobe epilepsy

The Role of Wnt/β-Catenin Signaling Pathway in Disrupted Hippocampal Neurogenesis of Temporal Lobe Epilepsy: A Potential Therapeutic Target?

Temporal lobe epilepsy is one of the most common clinical neurological disorders. One of the major pathological findings in temporal lobe epilepsy is hippocampal sclerosis, characterized by massive neuronal loss and severe gliosis. The epileptogenesis process of temporal lobe epilepsy usually starts with initial precipitating insults, followed by neurodegeneration, abnormal hippocampus circuitry reorganization, and the formation of hypersynchronicity. Experimental and clinical evidence strongly suggests that dysfunctional neurogenesis is involved in the epileptogenesis. Recent data demonstrate that neurogenesis is induced by acute seizures or precipitating insults, whereas the capacity of neuronal recruitment and proliferation substantially decreases in the chronic phase of epilepsy. Participation of the Wnt/β-catenin signaling pathway in neurogenesis reveals its importance in epileptogenesis; its dysfunction contributes to the structural and functional abnormality of temporal lobe epilepsy, while rescuing this pathway exerts neuroprotective effects. Here, we summarize data supporting the involvement of Wnt/β-catenin signaling in the epileptogenesis of temporal lobe epilepsy. We also propose that the Wnt/β-catenin signaling pathway may serve as a promising therapeutic target for temporal lobe epilepsy treatment.

Resting-state functional connectivity predicts the strength of hemispheric lateralization for language processing in temporal lobe epilepsy and normals.

In temporal lobe epilepsy (TLE), determining the hemispheric specialization for language before surgery is critical to preserving a patient's cognitive abilities post-surgery. To date, the major techniques utilized are limited by the capacity of patients to efficiently realize the task. We determined whether resting-state functional connectivity (rsFC) is a reliable predictor of language hemispheric dominance in right and left TLE patients, relative to controls. We chose three subregions of the inferior frontal cortex (pars orbitalis, pars triangularis, and pars opercularis) as the seed regions. All participants performed both a verb generation task and a resting-state fMRI procedure. Based on the language task, we computed a laterality index (LI) for the resulting network. This revealed that 96% of the participants were left-hemisphere dominant, although there remained a large degree of variability in the strength of left lateralization. We tested whether LI correlated with rsFC values emerging from each seed. We revealed a set of regions that was specific to each group. Unique correlations involving the epileptic mesial temporal lobe were revealed for the right and left TLE patients, but not for the controls. Importantly, for both TLE groups, the rsFC emerging from a contralateral seed was the most predictive of LI. Overall, our data depict the broad patterns of rsFC that support strong versus weak left hemisphere language laterality. This project provides the first evidence that rsFC data may potentially be used on its own to verify the strength of hemispheric dominance for language in impaired or pathologic populations.

The impact of temporal lobe epilepsy on musical ability

PurposePatients with temporal lobe epilepsy (TLE) often show impairment of cognitive processing in different domains. We aimed to evaluate whether also musical ability is impaired in TLE. MethodsWe enrolled patients with lesional TLE and without any other neurological or psychiatric disorder. The side and the etiology of the epilepsy were confirmed by EEG and by MRI. We applied a self-developed test of musical ability which evaluates the ability to identify melodies, pitch, rhythm, and emotional content of music. In addition, we compared the results of the patients to the results of age and sex matched healthy control subjects. All patients and subjects were without specific musical training. ResultsPatients with left TLE showed a significantly lower score in melody recognition, patients with right TLE showed a significantly lower score in identification of emotion in music. In all other aspects of music ability, no significant difference between left and right TLE could be found. We observed a significantly lower total score in patients with left TLE, but not with right TLE, as compared to healthy subjects. There were no differences with respect to sex. ConclusionOur data confirm that the recognition of melodies shows left hemisphere dominance whereas the identification of emotions in music shows right hemisphere dominance in patients without musical training. Furthermore, our data show that the impairment of cognitive processing in TLE is reflected even in higher cognitive functions such as music processing. However, this impairment was mild.

Changes in the duration and frequency of deviant stimuli engender different mismatch negativity patterns in temporal lobe epilepsy

Mismatch negativity (MMN) is an event-related potential (ERP) component that reflects preattentive sensory memory functions. Previous research revealed that MMN is generated by distinct sources in the frontal and temporal lobes. Event-related potential abnormalities have been shown in the vicinity of seizure foci in epilepsy. Additionally, no published study has investigated the MMN in response to variations in both frequency and duration deviants in patients with temporal lobe epilepsy (TLE). The aims of this study were to compare MMN changes between the frontocentral sites and the mastoid sites and to compare MMNs related to deviant stimuli with different durations and frequencies in patients with TLE. We recorded MMNs elicited by duration and frequency changes of deviant stimuli from 15 patients with TLE and 15 healthy control subjects. We found that mean MMN amplitudes related to duration deviants were lower in patients with TLE at the mastoid sites relative to controls, whereas the MMN amplitudes at the frontocentral sites did not differ between the two groups. There were no MMN differences related to frequency deviants between TLE subjects and controls at the frontocentral sites or the mastoid sites. Mismatch negativity parameters related to duration deviants did not correlate with those related to deviant frequencies in the group with TLE. The present findings suggest selective impairments among multiple mismatch generators in TLE and suggest that processing of temporal information of auditory stimuli is selectively disturbed in TLE. Changes in MMN amplitudes related to duration deviants at the mastoid sites may represent deficits in time-dependent processing in TLE.

Induction of sodium channel Nax (SCN7A) expression in rat and human hippocampus in temporal lobe epilepsy

In a recent large-scale gene-expression study in a rat model of temporal lobe epilepsy (TLE) a persistent up-regulation in the expression of the SCN7A gene was revealed. The SCN7A gene encodes an atypical sodium channel (Na(x) ), which is involved in osmoregulation via a sensing mechanism for the extracellular sodium concentration. Herein we investigated the expression and cellular distribution of SCN7A mRNA and protein in normal and epileptic rat and human hippocampus. SCN7A/Na(x) expression analysis was performed by polymerase chain reaction (PCR), immunocytochemistry, and western blot analysis. Increased expression of SCN7A/Na(x) mRNA/protein was observed during epileptogenesis and in the chronic epileptic phase in the post-status epilepticus (SE) model of TLE. The up-regulation was confirmed in human hippocampal tissue resected from pharmacoresistant patients with hippocampal sclerosis (HS). In both epileptic rat and human hippocampus, increased Na(x) expression was observed in neurons and reactive astrocytes compared to control tissue. The increased and persistent expression of SCN7A/Na(x) in the epileptic rat and human hippocampus supports the possible involvement of this channel in the complex reorganization occurring within the hippocampus during the epileptogenic process in TLE. Further studies are needed for a complete understanding of the functional role of SCN7A in epilepsy.

Postoperative speech processing in temporal lobe epilepsy: Functional relationship between object naming, semantics and phonology

Deficits in confrontation naming ability can occur after epilepsy surgery in the left temporal lobe. This study addresses the functional relationship between postoperative object naming and semantic and phonological speech processing in patients with epilepsy. Fifty-eight consecutive patients with temporal lobe epilepsy from our epilepsy surgery program (24 patients with left temporal lobe epilepsy, 34 patients with right temporal lobe epilepsy) were investigated using the Boston Naming Test and comprehensive semantic and phonological speech testing. Language dominance was evaluated in all patients with the preoperative intracarotid sodium amytal test. Naming decline was observed exclusively in patients with left temporal lobe epilepsy. Regression analysis with semantic processing and phonological input/output processing as independent variables, and naming change in the Boston Naming Test (preoperative–postoperative score) as a dependent variable, revealed a significant association between postoperative naming decline and impaired semantic functions. Accordingly, patients exhibited deficits in the category-related differentiation of objects. It is hypothesized that naming deficits arise from the functional specialization of the left temporal lobe for semantic interpretation of visual input.

深部前梨状葉皮質の間欠的電気刺激によるてんかん発作重積モデル

Hippocampal damage induced by status epilepticus (SE) has been suggested as the developmental pathway of temporal lobe epilepsy. We developed an experimental model of SE induced by massed electrical stimulations into the deep prepiriform cortex. Stimulations under aminophylline pretreatment more effectively induced SE than those in the absence of aminophylline. Most SE episodes included secondary generalized seizures. Cresyl violet staining indicated neuronal degeneration in CA1 and CA3, 1-2 weeks after the SE. Mild neuronal loss was observed 8 weeks after the SE, although there were no obvious histological changes in the hilus. Immunoreactivity for GluR1, a subunit of the AMPA receptors, was reduced in CA3 and the hilus starting 1 week after SE, indicating a discrepancy between the distributions of neuronal damage and the GluR1 decrement. The present model serves as a useful model of SE. Further improvement of this method will make it an effective tool for understanding the developmental process of temporal lobe epilepsy.

Investigation of social and emotion information processing in temporal lobe epilepsy with ictal fear

This study examined whether patients with temporal lobe epilepsy (TLE) and ictal fear (IF) show emotion recognition deficits similar to those associated with amygdala damage. Three groups of patients (13 with TLE and IF, 14 with TLE and nonfear auras (non-IF), and 10 with idiopathic generalized epilepsy (IGE)) completed tests of visual and face processing, face emotion recognition and social judgment, together with measures of psychological adjustment (Hospital Anxiety and Depression Scale; SCL-90-R) and Quality of Life (QOLIE-31). All three epilepsy groups had fear recognition deficits, with relatively greater impairments in the IF group. Fear recognition deficits were associated with impaired social judgment of trustworthiness, duration of epilepsy, and a measure of quality of life. Social cognition impairments previously associated with amygdala dysfunction are also a feature of the neuropsychology of TLE, and extend the hypothesis in that they may additionally play a role in IGE.

Functional MRI of phonological and semantic processing in temporal lobe epilepsy.

Phonological and semantic aspects of language were examined in patients with unilateral temporal lobe epilepsy (TLE) and healthy controls using functional MRI. We expected to replicate previous findings in healthy individuals showing relatively greater activation in frontal regions for phonological compared with semantic processing, and greater activation in temporal regions for semantic compared with phonological processing. We hypothesized that differences between patients with left TLE and healthy controls would be found in the pattern of left temporal cortical activation associated specifically with semantic processing. Patients with right TLE were included as a seizure control group. All TLE patients previously showed left hemisphere language dominance on intracarotid sodium amytal studies. Greater blood oxygen level dependent activation was found during phonological processing compared with semantic processing in frontal regions for healthy participants but, contrary to expectation, semantic processing did not lead to increased temporal lobe activity relative to phonological processing. Furthermore, no differences between left temporal patients and controls were found specifically in left temporal cortex. Rather, patients with left temporal seizure foci showed significantly greater left dorsolateral prefrontal activity compared with controls, as well as increased signal change in left inferior frontal and right middle temporal gyrus. Surprisingly, patients with right, but not left, TLE showed poorer performance on the linguistic tasks compared with controls, as well as a decrease in right superior temporal activation. The results converge with studies of dyslexic patients showing increased left frontal activity in the presence of left temporal dysfunction and are suggestive of both inter- and intra-hemispheric functional reorganization of language representation in left TLE.

A mathematical model of internal time processing in temporal lobe epilepsy

Based on known relationships between epileptic and nonepileptic cortical cerebral blood flow, electrocorticographic factors and epileptogenicity, a mathematical model for internal time processing is derived. The model suggests that the human brain has mechanisms for internal processing of real, reverse and imaginary time.

Disturbance of semantic processing in temporal lobe epilepsy demonstrated with scalp ERPs

We investigated event-related potentials (N400, LPC and CNV) elicited in temporal lobe epilepsy (TLE) patients and control subjects from scalp electrodes, using a word-pair category matching paradigm. Each prime consisted of a Japanese noun (constructed from 2–4 characters of the Hiragana) followed by a Chinese character (Kanji) as the target, the latter representing one of five semantic categories. There were two equally probable target conditions: match or mismatch. Each target was preceded by a prime, either belonging to, or not belonging to, the same semantic category. The subjects were required to respond with a specified button press to the given target, according to the condition. We found RTs to be longer under the mismatch condition in both subject groups. The N400 amplitude was reduced in TLE subjects under both conditions, although LPC and CNV amplitudes showed no significant differences. These results suggest that scalp N400 is capable of demonstrating disturbance of semantic processing in TLE non-invasively.

Disturbance of visual information processing in temporal lobe epilepsy: in comparison with idiopathic generalized epilepsy.

Disturbance of visual information processing in temporal lobe epilepsy: in comparison with idiopathic generalized epilepsy.