Semantic Processing Impairment in Patients with Temporal Lobe Epilepsy

Temporal lobe epilepsy (TLE) may determine memory difficulties not explained by episodic memory impairment. The present study was aimed to verify the presence of specific semantic memory dysfunctions in TLE and to explore their relations to epilepsy variables. Forty-seven patients with lateralized temporal (n = 26) or extra-temporal lobe epilepsy (n = 21) and 23 healthy subjects were compared. Picture Naming and Pointing to a Picture were used to explore expressive and receptive vocabulary and the Semantic Questionnaire evaluated semantic judgment of verbally presented items. The Selective Reminding Procedure for word list learning and Story Recall were used to assess episodic memory. Spontaneous speech and the Token Test controlled for language disturbances, and Raven's Coloured Progressive Matrices were used to evaluate abstract reasoning ability. Multivariate analysis of variance of test scores showed significant impairment of semantic memory in patients with left TLE compared to healthy controls, whereas episodic memory was impaired in left temporal and extra-temporal epilepsy (as measured by word learning) and all epilepsy groups (as measured by Story Recall). In the TLE groups, naming abilities were more compromised than single-word comprehension and semantic judgment - which were not significantly affected. No deficits in language abilities or in abstract reasoning were found in any patient group. Factor analysis of memory tests scores in the patients produced two factors, one semantic and the other episodic. Regression analysis revealed that the semantic factor was related to abstract reasoning, left hemisphere lateralization of seizures, and age of seizure onset; while the episodic factor was related to age. Left TLE may determine significant verbal semantic memory compromise, maybe due to impaired access to the semantic-lexical storage. In non-aphasic epilepsy patients, comparison of performance on semantic and episodic memory tests may be useful for assessing the nature of memory failures, and may complement clinical and neurophysiological means for defining the epileptic center.

Do recurrent seizures cause neuronal damage? A series of studies with MRI volumetry in adults with partial epilepsy

To the Editor.— The report by Herzog and colleagues, Neuroendocrine Dysfunction in Temporal Lobe Epilepsy (Archives1982;39:133-135), offers a potential neuroendocrinologic basis for impaired fertility in epileptic women 1 and the frequent occurrence of hyposexuality—primarily erectile dysfunction—in men with temporal lobe epilepsy (TLE). 2 We would be interested to know whether the patient who had an elevated serum prolactin level had recently experienced a seizure. Although we agree that interictal prolactin studies are normal in this clinical population, we found postictal hyperprolactinemia after complex partial seizures in all cases studied 3 ; thus, the temporal relationship between serum prolactin determinations and the occurrence of seizures is critical. Although the clinical consequences of episodic hyperprolactinemia are uncertain, impotence and decreased libido are the most common accompaniments of sustained hyperprolactinemia in men. 4 Further studies of prolactin secretion in TLE seem warranted. Using an intravenous (IV) bolus of luteinizing hormone-releasing hormone (LH-RH) in

Epilepsy patients face significantly elevated cardiovascular risks, with cardiac arrhythmias occurring 2-3 times more frequently than in the general population. Current knowledge of brain-heart functional coupling abnormalities in epilepsy, particularly during interictal periods, remains limited. We investigated brain-heart interplay characteristics in temporal lobe epilepsy through synchronized electroencephalographic-electrocardiographic analysis using a synthetic data generation model and microstate analysis. We enrolled 52 patients with temporal lobe epilepsy (mean age = 33.4 ± 12.7 years) and 42 age-matched healthy controls (mean age = 31.95 ± 11.03 years). Twenty-minute artifact-free electroencephalographic segments were analyzed during resting states. Four directional brain-heart coupling sequences were extracted: CBrain→HF, CBrain→LF, CHF→Brain, and CLF→Brain, representing bidirectional interactions between brain activity and cardiac components. Six microstate topologies were consistently identified across all brain-heart interplay sequences, with temporal lobe epilepsy patients demonstrating significantly more complex and unstable topological characteristics compared to healthy controls. For CBrain→HF coupling, patients exhibited significantly reduced mean duration of microstate 3 (.34 ± .09 s vs. .38 ± .07 s, p = .02), increased occurrence rates of microstates 3 and 4 (both p < .001), and altered temporal coverage patterns. Similar abnormalities were observed across all sequences, with patients showing shortened microstate durations, altered occurrence rates, and disrupted temporal coverage. Spatial dissimilarity analysis revealed significant topological abnormalities across all microstates. A logistic regression model incorporating microstate parameters achieved 94.7% diagnostic accuracy for temporal lobe epilepsy, with an F1 score of .952 and an area under the curve of .932. Temporal lobe epilepsy is characterized by profound disruptions in brain-heart functional coupling during interictal periods, manifesting as altered microstate topographies and temporal dynamics. These findings establish microstate-based analysis as a promising framework for characterizing brain-heart axis dysfunction in epilepsy.

SummaryTemporal lobe epilepsy (TLE) is typically associated with long-term memory dysfunction. The frontal lobes support high-level cognition comprising executive skills and working memory that is vital for daily life functioning. Deficits in these functions have been increasingly reported in TLE. Evidence from both the neuropsychological and neuroimaging literature suggests both executive function and working memory are compromised in the presence of TLE. In relation to executive impairment, particular focus has been paid to set shifting as measured by the Wisconsin Card Sorting Task. Other discrete executive functions such as decision-making and theory of mind also appear vulnerable but have received little attention. With regard to working memory, the medial temporal lobe structures appear have a more critical role, but with emerging evidence of hippocampal dependent and independent processes. The relative role of underlying pathology and seizure spread is likely to have considerable bearing upon the cognitive phenotype and trajectory in TLE. The identification of the nature of frontal lobe dysfunction in TLE thus has important clinical implications for prognosis and surgical management. Longitudinal neuropsychological and neuroimaging studies assessing frontal lobe function in TLE patients pre- and postoperatively will improve our understanding further.

Epilepsy CurrentsVolume 3, Issue 1 p. 31-32 Widespread Neuronal Dysfunction in Temporal Lobe Epilepsy Gregory D. Cascino M.D., Gregory D. Cascino M.D.Search for more papers by this author Gregory D. Cascino M.D., Gregory D. Cascino M.D.Search for more papers by this author First published: 18 September 2008 https://doi.org/10.1046/j.1535-7597.2003.03113.xRead the full textAboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume3, Issue1January 2003Pages 31-32 RelatedInformation

Category-specific naming impairment in temporal lobe epilepsy through cortical electrical stimulation: Case report

The goal of this work was to evaluate the relationship between neuronal injury/loss in the hippocampus, thalamus, and putamen in temporal lobe epilepsy (TLE) patients using (1)H magnetic resonance spectroscopic imaging. (1)H spectroscopic images from the hippocampus and thalamus of controls and patients with TLE were acquired at 4 T. The spectroscopic imaging data were reconstructed using an automated voxel-shifting method based on anatomic landmarks providing four, six, and three loci for the hippocampus, thalamus, and putamen, respectively. For correlation analysis, the hippocampal and striatal loci were averaged to provide single estimates of the entire structure, whereas the thalamus was divided into two regions, an anterior and posterior measure, using the average of three loci each. The ratio of N-acetyl aspartate to creatine (NAA/Cr), a measure of neuronal injury/loss, was significantly reduced in both the ipsilateral and contralateral hippocampi and thalami. NAA/Cr in the ipsilateral hippocampus was significantly correlated with the ipsilateral and contralateral anterior and posterior thalami, putamen, and contralateral hippocampus. In control subjects, the hippocampi were only correlated with each other. The data demonstrate that there is significant neuronal injury/loss in both the ipsilateral and contralateral thalami in temporal lobe epilepsy patients, with greater impairment in the anterior portions of the ipsilateral thalamus. The degree of injury/loss in the ipsilateral and contralateral thalamus and putamen is directly correlated with that of the ipsilateral hippocampus. This is consistent with the hypothesis that the impairment and damage associated with recurrent seizures as measured by N-acetyl aspartate originating in the hippocampus results in injury and impairment in other subcortical structures.

SummaryNeural stem cells (NSCs) are one of the candidates for grafting in the realm of cell‐based therapy for temporal lobe epilepsy (TLE). Because NSCs can produce neurons synthesizing the inhibitory neurotransmitter γ‐aminobutyric acid (GABA) and cells secreting multiple neurotrophic factors, NSC grafting therapy has promise for restraining seizures and easing cognitive dysfunction in TLE. For an expanded treatment of this topic see Jasper’s Basic Mechanisms of the Epilepsies, Fourth Edition (Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado‐Escueta AV, eds) published by Oxford University Press (available on the National Library of Medicine Bookshelf [NCBI] at http://www.ncbi.nlm.nih.gov/books).

Hijacking of hippocampal–cortical oscillatory coupling during sleep in temporal lobe epilepsy

SummaryPurpose: Anterior temporal lobe resection (ATLR) controls seizures in up to 70% of patients with intractable temporal lobe epilepsy (TLE) but, in the language dominant hemisphere, may impair language function, particularly naming. Functional reorganization can occur within the ipsilateral and contralateral hemispheres. We investigated reorganization of language in left-hemisphere–dominant patients before and after ATLR; whether preoperative functional magnetic resonance imaging (fMRI) predicts postoperative naming decline; and efficiency of postoperative language networks.Methods: We studied 44 patients with TLE due to unilateral hippocampal sclerosis (24 left) on a 3T GE-MRI scanner. All subjects performed language fMRI and neuropsychological testing preoperatively and again 4 months after left or right ATLR.Key Findings: Postoperatively, individuals with left TLE had greater bilateral middle/inferior frontal fMRI activation and stronger functional connectivity from the left inferior/middle frontal gyri to the contralateral frontal lobe than preoperatively, and this was not observed in individuals with right TLE. Preoperatively, in left and right TLE, better naming correlated with greater preoperative left hippocampal and left frontal activation for verbal fluency (VF). In left TLE, stronger preoperative left middle frontal activation for VF was predictive of greater decline in naming after ATLR. Postoperatively, in left TLE with clinically significant naming decline, greater right middle frontal VF activation correlated with better postoperative naming. In patients without postoperative naming decline, better naming correlated with greater activation in the remaining left posterior hippocampus. In right TLE, naming ability correlated with left hippocampal and left and right frontal VF activation postoperatively.Significance: In left TLE, early postoperative reorganization to the contralateral frontal lobe suggests multiple systems support language function. Postoperatively, ipsilateral recruitment involving the posterior hippocampal remnant is important for maintaining language, and reorganization to the contralateral hemisphere is less effective. Preoperative left middle frontal activation for VF was predictive of naming decline in left TLE after ATLR.

Background: Semantic and phonological processing deficits are often present in aphasia. The degree of interdependence between the deficits has been widely studied with variable findings. Semantic variables such as category and typicality have been found to influence semantic processing in healthy individuals and persons with aphasia (PWA), but their influence on phonological processing is unknown.Aims: This study examined the nature of semantic and phonological access in aphasia by comparing adults with aphasia to healthy control participants. Semantic and phonological tasks were used to assess the difference in processing requirements between and within each group as well as examine the effects of category and typicality on different stages of semantic and phonological processing.Methods & Procedures: Thirty-two PWA and 10 neurologically healthy adults were administered nine tasks: Category Superordinate, Category Coordinate, Semantic Feature, Rhyme Judgment (No-Name), Syllable Judgment (No-Name), Phoneme Verification (No-Name), Rhyme Judgment (Name-Provided), Syllable Judgment (Name-Provided), and Phoneme Verification (Name-Provided). Accuracy and reaction time (RT) data were collected for each of these tasks and between-group and within-group differences were analysed via MANOVA/MANCOVA and hierarchical clustering analyses.Outcomes & Results: PWA performed with significantly lower accuracy than controls on phonological tasks but performed comparably on semantic tasks. Participants with aphasia were significantly slower than controls on all semantic and phonological tasks. Clustering of the nine tasks by accuracy revealed different processing requirements in the participants with aphasia compared to the control group while clustering by RT revealed similar trends in both groups in that phonological (no-name) items required the most processing time. Significant effects of category and typicality were noted in the semantic tasks but not in any of the phonological tasks.Conclusions: Individuals with aphasia demonstrated overall impaired phonological processing with relatively preserved semantic processing as compared to controls. Per accuracy and RT measures, distinct trends in processing load for semantic tasks versus phonological tasks were seen in the individuals with aphasia whereas only speed of processing and not accuracy was impacted by phonological processing load in the control group. The results align most closely with discrete serial processing models of lexical processing as category and typicality effects were robust in the semantic tasks but not in any of the phonological tasks. Alternative explanations for these results also are discussed.

The relationship between episodic and semantic memory systems has long been debated. Some authors argue that episodic memory is contingent on semantic memory (Tulving 1984), while others postulate that both systems are independent since they can be selectively damaged (Squire 1987). The interaction between these memory systems is particularly important in the elderly, since the dissociation of episodic and semantic memory defects characterize different aging-related pathologies. Here, we investigated the interaction between semantic knowledge and episodic memory processes associated with faces in elderly subjects using an experimental paradigm where the semantic encoding of famous and unknown faces was compared to their episodic recognition. Results showed that the level of semantic awareness of items affected the recognition of those items in the episodic memory task. Event-related magnetic fields confirmed this interaction between episodic and semantic memory: ERFs related to the old/new effect during the episodic task were markedly different for famous and unknown faces. The old/new effect for famous faces involved sustained activities maximal over right temporal sensors, showing a spatio-temporal pattern partly similar to that found for famous versus unknown faces during the semantic task. By contrast, an old/new effect for unknown faces was observed on left parieto-occipital sensors. These findings suggest that the episodic memory for famous faces activated the retrieval of stored semantic information, whereas it was based on items' perceptual features for unknown faces. Overall, our results show that semantic information interfered markedly with episodic memory processes and suggested that the neural substrates of these two memory systems overlap.

Impaired consciousness requires altered cortical function. This can occur either directly from disorders that impair widespread bilateral regions of the cortex or indirectly through effects on subcortical arousal systems. It has therefore long been puzzling why focal temporal lobe seizures so often impair consciousness. Early work suggested that altered consciousness may occur with bilateral or dominant temporal lobe seizure involvement. However, other bilateral temporal lobe disorders do not impair consciousness. More recent work supports a 'network inhibition hypothesis' in which temporal lobe seizures disrupt brainstem-diencephalic arousal systems, leading indirectly to depressed cortical function and impaired consciousness. Indeed, prior studies show subcortical involvement in temporal lobe seizures and bilateral frontoparietal slow wave activity on intracranial electroencephalography. However, the relationships between frontoparietal slow waves and impaired consciousness and between cortical slowing and fast seizure activity have not been directly investigated. We analysed intracranial electroencephalography recordings during 63 partial seizures in 26 patients with surgically confirmed mesial temporal lobe epilepsy. Behavioural responsiveness was determined based on blinded review of video during seizures and classified as impaired (complex-partial seizures) or unimpaired (simple-partial seizures). We observed significantly increased delta-range 1-2 Hz slow wave activity in the bilateral frontal and parietal neocortices during complex-partial compared with simple-partial seizures. In addition, we confirmed prior work suggesting that propagation of unilateral mesial temporal fast seizure activity to the bilateral temporal lobes was significantly greater in complex-partial than in simple-partial seizures. Interestingly, we found that the signal power of frontoparietal slow wave activity was significantly correlated with the temporal lobe fast seizure activity in each hemisphere. Finally, we observed that complex-partial seizures were somewhat more common with onset in the language-dominant temporal lobe. These findings provide direct evidence for cortical dysfunction in the form of bilateral frontoparietal slow waves associated with impaired consciousness in temporal lobe seizures. We hypothesize that bilateral temporal lobe seizures may exert a powerful inhibitory effect on subcortical arousal systems. Further investigations will be needed to fully determine the role of cortical-subcortical networks in ictal neocortical dysfunction and may reveal treatments to prevent this important negative consequence of temporal lobe epilepsy.

In order to evaluate the possible consequences of temporal lobe epilepsy on reading acquisition, we first compared the reading skills and phonological awareness abilities in a set of 13-year-old identical twins, one of whom is affected by temporal lobe epilepsy (LB). We then compared their performances to those of an age- and IQ-matched control group. Both siblings have an intellectual quotient above average as well as normal memory and linguistic abilities. Results showed that the reading age of LB (assessed by the Lefabvrais French reading test) was more than two years behind expectations whereas that of her sister was above average. Further, in contrast to her sister and healthy control subjects, LB exhibited specific deficits in elaborate metaphonological awareness abilities (non-word repetition, rhyme production, phonemic segmentation and syllabic inversion). These could be linked to temporal lobe dysfunction, thus confirming the important role of the temporal lobes in reading acquisition.