Theory of mind in epilepsy.

Epilepsy is characterized by recurrent, chronic, and unprovoked seizures. Epilepsy has a significant negative impact on a patient's quality of life even if seizures are well controlled. In addition to the distress caused by seizures, patients with epilepsy (PwE) may suffer from cognitive impairment with serious social consequences such as poor interpersonal relationships, loss of employment, and reduced social networks. Pathological changes and functional connectivity abnormalities observed in PwE can disrupt the neural network responsible for the theory of mind. Theory of mind is the ability to attribute mental states to other people (intentions, beliefs, and emotions). It is a complex aspect of social cognition and includes cognitive and affective constructs. In recent years, numerous studies have assessed the relationship between social cognition, including the theory of mind, in PwE, and suggested impairment in this domain. Interventions targeting the theory of mind can be potentially helpful in improving the quality of life of PwE.

TNF-α: A serological marker for evaluating the severity of hippocampal sclerosis in medial temporal lobe epilepsy?

OBJECTIVE: By analysing the difference in TNF-α levels in the peripheral blood of patients with medial temporal lobe epilepsy (mTLE) with or without hippocampal sclerosis and the correlation between TNF-α and N-acetylaspartate levels in the hippocampus, we explored the relationship between TNF-α and the degree of damage to hippocampal sclerosis neurons in medial temporal lobe epilepsy. METHODS: This is a prospective, population-based study. A total of 71 Patients with medial temporal lobe epilepsy diagnosed by clinical seizures, video-EEG, epileptic sequence MRI, and other imaging examinations were recruited from October 2020 to July 2022 in the Department of Neurology, Affiliated Hospital of Xuzhou Medical University. Twenty age-matched healthy subjects were selected as the control group. The patients were divided into two groups: the medial temporal epilepsy with hippocampal sclerosis group (positive group, mTLE-HS-P group) and the medial temporal epilepsy without hippocampal sclerosis group (negative group, mTLE-HS-N group). The levels of IL-1ß, IL-5, IL-6, IL-8, IL-17, IFN-γ and TNF-α in the peripheral blood of the patients in the three groups were detected by multimicrosphere flow immunofluorescence assay. The level of N-acetylaspartate (NAA) in the hippocampus was measured by 1H-MRS. The differences in cytokine levels among the three groups were analysed, and the correlation between cytokine and NAA levels was analysed. RESULTS: The level of TNF-α in the peripheral blood of the patients in the mTLE-HS-P group was significantly higher than that of the patients in the mTLE-HS-N and healthy control groups, and the level of TNF-α in the patients in the mTLE-HS-N group was significantly higher than that of the patients in the healthy control group. The NAA level in mTLE-HS-P group patients was significantly lower than that of mTLE-HS-N patients and healthy controls, but there was no significant difference between mTLE-HS-N patients and healthy controls (P > 0.05). Spearman correlation analysis showed that TNF-α level (rs = -0.437, P < 0.05) and the longest duration of a single seizure (rs = -0.398, P < 0.05) were negatively correlated with NAA level. Logistic regression analysis showed that there was no significant correlation between the longest duration of a single seizure and hippocampal sclerosis, but TNF-α level was closely related to hippocampal sclerosis in patients with mTLE (OR = 1.315, 95 % CI 1.084-1.595, P = 0.005). CONCLUSION: The level of TNF-α in the peripheral blood of patients with medial temporal lobe epilepsy with hippocampal sclerosis was higher, and it was correlated with NAA and hippocampal sclerosis. The high expression of TNF-α may be of important value in the evaluation of hippocampal sclerosis patients.

Revisiting emotion recognition in different types of temporal lobe epilepsy: The influence of facial expression intensity.

Temporal lobe epilepsy (TLE) can induce various difficulties in recognizing emotional facial expressions (EFE), particularly for negative valence emotions. However, these difficulties have not been systematically examined according to the localization of the epileptic focus. For this purpose, we used a forced-choice recognition task in which faces expressing fear, sadness, anger, disgust, surprise, or happiness were presented in different intensity levels from moderate to high intensity. The first objective of our study was to evaluate the impact of emotional intensity on the recognition of different categories of EFE in TLE patients compared to control participants. The second objective was to assess the effect of localizationof epileptic focus on the recognition of EFE in patients with medial temporal lobe epilepsy (MTLE) associated or not with hippocampal sclerosis (HS), or lateral temporal lobe epilepsy (LTLE). The results showed that the 272 TLE patients and the 68 control participants were not differently affected by the intensity of EFE. However, we obtained group differences within the clinical population when we took into account the localization of the temporal lobe epileptic focus. As predicted, TLE patients were impaired in recognizing fear and disgust relative to controls. Moreover, the scores of these patients varied according to the localization of the epileptic focus, but not according to the cerebral lateralization of TLE. The facial expression of fear was less well recognized by MTLE patients, with or without HS, and the expression of disgust was less well recognized by LTLE as well as MTLE without HS patients. Moreover, emotional intensity modulated differently the recognition of disgust and surprise of the three patient groups underlying the relevance of using moderate emotional intensity to distinguish the effect of epileptic focus localization. These findings should be taken into account for interpreting the emotional behaviors and deserve to befurther investigated before considering TLE surgical treatment or social cognition interventions in TLE patients.

Neocortical and medial temporal seizures have distinct impacts on brain responsiveness.

Focal epileptic seizures are characterized by abnormal neuronal discharges that can spread to other cortical areas and interfere with brain activity, thereby altering the patient's experience and behavior. The origin of these pathological neuronal discharges encompasses various mechanisms that converge toward similar clinical manifestations. Recent studies have suggested that medial temporal lobe (MTL) and neocortical (NC) seizures are often underpinned by two characteristic onset patterns, which, respectively, affect and spare synaptic transmission in cortical slices. However, these synaptic alterations and their effects have never been confirmed or studied in intact human brains. To fill this gap, we here evaluate whether responsiveness of MTL and NC are differentially affected by focal seizures, using a unique data set of cortico-cortical evoked potentials (CCEPs) collected during seizures triggered by single-pulse electrical stimulation (SPES). We find that responsiveness is abruptly reduced by the onset of MTL seizures, despite increased spontaneous activity, whereas it is preserved in the case of NC seizures. The present results provide an extreme example of dissociation between responsiveness and activity and show that brain networks are diversely affected by the onset of MTL and NC seizures, thus extending at the whole brain level the evidence of synaptic alteration found in vitro.

Reflection of the Ictal Electrocorticographic Discharges Confined to the Medial Temporal Lobe to the Scalp-Recorded Electroencephalogram.

Objective: Previous reports on the simultaneous recording of electroencephalography (EEG) and electrocorticography (ECoG) have demonstrated that, in patients with temporal lobe epilepsy (TLE), ictal ECoG discharges with an amplitude as high as 1000 µV originating from the medial temporal lobe could not be recorded on EEG. In contrast, ictal EEG discharges were recorded after ictal ECoG discharges propagated to the lateral temporal lobe. Here, we report a case of TLE in which the ictal EEG discharges, corresponding to ictal ECoG discharges confined to the medial temporal lobe, were recorded. Case report: In the present case, ictal EEG discharges were hardly recognized when the amplitude of the ECoG discharges was less than 1500 µV. During the evolution and burst suppression phase, corresponding to highly synchronized ECoG discharges with amplitudes greater than 1500 to 2000 µV, rhythmic negative waves with the same frequency were clearly recorded both on the lateral temporal lobe and scalp. The amplitude of the lateral temporal ECoG was approximately one-tenth of that of the medial temporal ECoG. The amplitude of the scalp EEG was approximately one-tenth of that of the lateral temporal ECoG. Conclusions: Highly synchronized ictal ECoG discharges with high amplitude of greater than 1500 to 2000 µV in the medial temporal lobe could be recorded on the scalp as ictal EEG discharges via volume conduction.

Changes in heart rate during the peri-ictal period in focal epilepsy

Objective: We explored changes in heart rate during the peri-ictal period in patients with focal epilepsy, and differences in heart rate changes according to epileptic site and side were assessed. Methods: A total of 198 epileptic seizures in 102 patients with focal epilepsy, who had a definite epileptogenic focus and had undergone surgical treatment, were assessed from 2014 to 2019. Heart rate was measured manually during the peri-ictal period. Change in heart rate and the time it occurred were assessed and compared between different epileptic sites and sides. Results: Heart rate increased in 177 (89.4%) of 198 seizures. In 82 (44.8%) of 183 seizures, the change in heart rate occurred before seizure onset. The median period of heart rate change was seven seconds (interquartile range: 3­11 seconds) in seizures with heart rate change before seizure onset. The number of seizures with heart rate increase before seizure onset was significantly greater for medial temporal lobe epilepsy compared to lateral temporal lobe epilepsy (p=0.019) and extratemporal lobe epilepsy (p=0.002). Significance: A change in heart rate prior to seizure onset is more likely to occur in patients with medial temporal lobe epilepsy, compared to those with lateral temporal lobe epilepsy and extratemporal lobe epilepsy. Patients with medial temporal lobe epilepsy may likely benefit from seizure warning and detection devices.

MRI-Negative Medial Temporal Lobe Epilepsy can Benefit from Stereotactic Radiofrequency Thermocoagulation Applied to the Amygdalohippocampal Complex.

BACKGROUND: Seizure control (SC) is often poor in cases of magnetic resonance imaging- negative epilepsy after resection surgery. OBJECTIVE: This study aimed to evaluate the therapeutic efficacy of depth-electrode-guided stereotactic radiofrequency thermocoagulation (RFTC) applied to the amygdalohippocampal complex (AHC) for the treatment of patients with MRI-negative medial temporal lobe epilepsy. METHODS: A total of 62 cases with magnetic resonance imaging-negative medial temporal lobe epilepsy were retrospectively studied after the application of depth-electrode-guided RFTC to the AHC. Single-target coagulations were applied to all patients, and multi-target coagulations were applied to those patients who did not experience significant reductions in discharges after the first target ablation. Bilateral-target coagulations were applied to bilateral medial temporal lobe epilepsy patients, using single target ablation applied to each side. RESULTS: After 24-83 months of follow-up, 32/62 (51.61%) patients became seizure-free, and 35/62 (56.45%) patients reported significant reductions in seizure episodes. The total effective rate was 69.35% (43/62). No significant differences were observed for SC among the single-target, multi-target, and bilateral-target groups. However, a significant difference was observed for the reduction in epileptic discharges after coagulations between those patients who became seizure-free and those who did not. Magnetic resonance imaging-negative medial temporal lobe epilepsy patients can benefit from RFTC applied to the AHC. A significant reduction in epileptic discharges observed during operations after RFTC is applied may predict good SC. CONCLUSION: RFTC applied to the AHC could be considered a promising method for the treatment of magnetic resonance imaging-negative medial temporal lobe epilepsy patients.

Construction and analysis of a competing endogenous RNA network associated with circRNAs dysregulated in medial temporal lobe epilepsy.

The aetiology and pathogenesis of medial temporal lobe epilepsy (MTLE) remain unclear, and effective treatments are lacking. The involvement of a dysregulated competing endogenous RNA (ceRNA) network in MTLE is only partially understood. The purpose of this study was to investigate MTLE regulatory networks composed of messenger RNAs (mRNAs), circular RNAs (circRNAs), long non-coding RNAs (lncRNAs), and microRNAs (miRNAs) through a ceRNA network map. RNA sequencing (RNA-seq) and small RNA-seq were used to detect mRNAs, circRNAs, miRNAs, and lncRNAs differentially expressed between post-operation hippocampal tissues of MTLE patients (n = 3) and paracancer tissues (n = 3). We performed bioinformatics analysis to identify differentially expressed RNAs and construct the corresponding ceRNA network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of differentially expressed RNAs were conducted to explore the biological processes and pathways involved in MTLE. We identified 352 differentially expressed mRNAs, 179 circRNAs, and 42 miRNAs in MTLE. A ceRNA network composed of mRNAs, circRNAs, and miRNAs was constructed. GO and KEGG analysis of the network suggested a key role of synapses and mTOR, cAMP, ErbB, FoxO, and HIF-1 signalling pathways in MTLE. We identify a new circRNA-miRNA-mRNA ceRNA network in MTLE. These results can help clarify the aetiology of MTLE and identify targeted molecular therapies.

Clinical outcome of selective amygdalectomy in a series of patients with resistant temporal lobe epilepsy.

BACKGROUND: Selective amygdalohippocampectomy is one of the main approaches for treating medial temporal lobe epilepsy (TLE). We herewith describe seven cases of amygdala lesions treated with selective amygdalectomy with the hippocampus saving procedure. Furthermore, we explain the trans-middle temporal gyrus transventricular approach for selective amygdalectomy. METHODS: We studied patients with TLE who underwent selective amygdalectomy with hippocampal saving procedure between March 2012 and July 2018. We preferred the trans-middle temporal gyrus transventricular approach. We adopted pterional craniotomy with extensive exposure of the base and posterior of the temporal lobe. The posterior margin of resection in the intraventricular part of the amygdala was considered the inferior choroidal point. Medially anterior part of the uncus was resected until reaching the ambient cistern. We applied the transcortical transventricular approach for selective amygdalectomy in all patients. RESULTS: We present 11 cases having an amygdala lesion in our series, seven of whom underwent selective amygdalectomy with hippocampal sparing. Nine patients had neoplastic lesions, and in two of them, gliosis was evident. Total resection of the lesion was achieved in all cases based on postoperative magnetic resonance imaging. No unusual complication or surgically-related new neurological deficit occurred. CONCLUSION: We consider the resection of the amygdala until the inferior choroidal point sufficient for the disconnection of its circuits, which results in more effective control of seizures and reduction of surgery time and complications.

Two-trajectory laser amygdalohippocampotomy: Anatomic modeling and initial seizure outcomes.

OBJECTIVE: Laser interstitial thermal therapy (LITT) for mesial temporal lobe epilepsy (mTLE) is typically performed with one trajectory to target the medial temporal lobe (MTL). MTL structures such as piriform and entorhinal cortex are epileptogenic, but due to their relative geometry, they are difficult to target with one trajectory while simultaneously maintaining adequate ablation of the amygdala and hippocampus. We hypothesized that a two-trajectory approach could improve ablation of all relevant MTL structures. First, we created large-scale computer simulations to compare idealized one- vs two-trajectory approaches. A two-trajectory approach was then validated in an initial cohort of patients. METHODS: We used magnetic resonance imaging (MRI) from the Human Connectome Project (HCP) to create subject-specific target structures consisting of hippocampus, amygdala, and piriform/entorhinal/perirhinal cortex. An algorithm searched for safe potential trajectories along the hippocampal axis (catheter one) and along the amygdala-piriform axis (catheter two) and compared this to a single trajectory optimized over all structures. The proportion of each structure ablated at various burn radii was evaluated. A cohort of 11 consecutive patients with mTLE received two-trajectory LITT; demographic, operative, and outcome data were collected. RESULTS: The two-trajectory approach was superior to the one-trajectory approach at nearly all burn radii for all hippocampal subfields and amygdala nuclei (p < .05). Two-laser trajectories achieved full ablation of MTL cortical structures at physiologically realistic burn radii, whereas one-laser trajectories could not. Five patients with at least 1 year of follow-up (mean = 21.8 months) experienced Engel class I outcomes; 6 patients with less than 1 year of follow-up (mean = 6.6 months) are on track for Engel class I outcomes. SIGNIFICANCE: Our anatomic analyses and initial clinical results suggest that LITT amygdalohippocampotomy performed via two-laser trajectories may promote excellent seizure outcomes. Future studies are required to validate the long-term clinical efficacy and safety of this approach.

T cell numbers correlate with neuronal loss rather than with seizure activity in medial temporal lobe epilepsy.

OBJECTIVE: Medial temporal lobe epilepsy (MTLE) is a drug-resistant focal epilepsy that can be caused by a broad spectrum of different inciting events, including tumors, febrile seizures, and viral infections. In human epilepsy surgical resections as well as in animal models, an involvement of the adaptive immune system was observed. We here analyzed the presence of T cells in various subgroups of MTLE. We aimed to answer the question of how much inflammation was present and whether the presence of T cells was associated with seizures or associated with hippocampal neurodegeneration. METHODS: We quantified the numbers of CD3+ T cells and CD8+ cytotoxic T cells in the hippocampus of patients with gangliogliomas (GGs; intrahippocampal and extrahippocampal, with and without sclerosis), febrile seizures, and postinfectious encephalitic epilepsy and compared this with Rasmussen encephalitis, Alzheimer disease, and normal controls. RESULTS: We could show that T cell numbers were significantly elevated in MTLE compared to healthy controls. CD3+ as well as CD8+ T cell numbers, however, varied highly among MTLE subgroups. By comparing GG patients with and without hippocampal sclerosis (HS), we were able to show that T-cell numbers were increased in extrahippocampal GG patients with hippocampal neuronal loss and HS, whereas extrahippocampal GG cases without hippocampal neuronal loss (i.e., absence of HS) did not differ from healthy controls. Importantly, T cell numbers in MTLE correlated with the degree of neuronal loss, whereas no correlation with seizure frequency or disease duration was found. Finally, we found that in nearly all MTLE groups, T cell numbers remained elevated even years after the inciting event. SIGNIFICANCE: We here provide a detailed histopathological investigation of the involvement of T cells in various subgroups of MTLE, which suggests that T cell influx correlates to neuronal loss rather than seizure activity.

Brain FDG-PET findings in glutamic acid decarboxylase antibody-associated epilepsy.

BACKGROUND AND PURPOSE: Glutamic acid decarboxylase antibodies (GAD-Ab) are sometimes associated with chronic drug-resistant focal epilepsy. Clinically, it may manifest as mesial temporal lobe epilepsy (mTLE), with GAD-Ab patients difficult to distinguish. Therefore, the aim of this study is to compare brain metabolism of patients with mTLE and high serum titers of GAD-Ab (>2000 UI/ml) to those with mTLE and hippocampal sclerosis (HS) and confirmed GAD-ab negativity. METHODS: Images from PET studies were normalized to an SPM 12 template. Voxel to voxel comparisons were made using a two-sample one-tailed t-test. RESULTS: In both patients with GAD-Ab and controls (mTLE-HS), hypometabolism in mesial temporal lobe areas was observed. When comparing the two groups, GAD-Ab patients had statistically significant reduced metabolism in both insulae and medial inferior frontal-hypothalamus area (p < 0.001). CONCLUSIONS: Hypometabolism in mesial temporal lobe areas together with hypometabolism in insulae and medial inferior frontal-hypothalamus may be characteristic of patients with epilepsy and GAD-ab. This PET pattern could be a useful diagnostic tool to identify GAD-Ab patients.

Auditory Temporal Ordering in Patients with Medial Temporal Lobe Epilepsy with and without Hippocampal Sclerosis.

CONTEXT: Temporal lobe epilepsy can affect central auditory processing (CAP) skills. Auditory temporal ordering (ATO) is a CAP skill that can be evaluated using duration pattern test (DPT). AIM: The aim is to evaluate ATO in patients with medial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (MTLE + HS) and without hippocampal sclerosis (MTLE-HS) and in their subgroups. SETTINGS AND DESIGN: It was a prospective cross-sectional behavioral observational study conducted in a tertiary neuropsychiatric hospital. SUBJECTS AND METHODS: The subjects were patients with refractory MTLE (N = 100), comprising 50 "MTLE + HS" patients and 50 "MTLE-HS". Age-range matched normal healthy subjects (n = 50) formed the control group. Both groups were administered duration pattern test (DPT). STATISTICAL ANALYSIS USED: Analysis of variance (ANOVA) with post hoc analysis, Dunnett's two-sided and Bonferroni, paired sample t-test, Pearson's correlation, and independent t-test. RESULTS: The clinical groups performed significantly poorer than the control group, and however, did not differ significantly between them. The age at onset and the duration of the seizures did not have significant relation with the test measures. CONCLUSIONS: Patients with "MTLE + HS" as well as those with "MTLE-HS" and their respective subgroups revealed abnormal ATO indicating CAP dysfunction.

Central Nervous System Infection-Related Isolated Hippocampal Atrophy as Another Subtype of Medial Temporal Lobe Epilepsy with Hippocampal Atrophy: A Comparison to Conventional Medial Temporal Lobe Epilepsy with Hippocampal Atrophy.

BACKGROUND AND PURPOSE: Hippocampal atrophy (HA) resulting from a central nervous system (CNS) infection might be a relevant lesion responsible for the clinical characteristics of medial temporal lobe epilepsy. METHODS: The clinical characteristics of 54 patients with CNS infection-related medial temporal lobe epilepsy (MTLE) with isolated HA (CNS infection group) and 155 patients with conventional MTLE with HA (conventional group) were compared retrospectively. CNS infection alone and bilateral involvement of the HA were analyzed as prognostic factors, in addition to the detailed clinical characteristics, such as limbic aura and the presence and proportion of each type of automatism, between the two groups, and both medical and surgical prognoses were separately considered. A logistic regression analysis was performed. RESULTS: A statistical analysis including all clinical factors, including CNS infection with bilateral HA, did not reveal significant differences between the two groups. An analysis comparing the prognosis of the two groups based on good or poor prognosis among patients who received medical treatment and good or poor outcomes among patients who received surgical treatment did not produce significant differences. CONCLUSIONS: In addition to bilateral HA, CNS infection alone was not a poor prognostic factor for the CNS infection-related epilepsy with HA group compared with the conventional MTLE with HA group. Based on these negative results, HA is a plausible and relevant lesion with similar clinical characteristics to HA in patients with conventional MTLE. Therefore, CNS infection-related MTLE with isolated HA might represent another subtype of MTLE with HA with a different etiology.

Cognitive and behavioral outcome of stereotactic laser amydalohippocampotomy in a pediatric setting.

We present neuropsychological and functional outcome data in a teenager undergoing stereotactic laser amygdalohippocampotomy (SLAH) who had drug-resistant mesial temporal lobe epilepsy due to left hippocampal sclerosis. Given strong baseline cognitive performance, there was concern for post-operative declines in language and verbal memory were this patient to undergo open resection. She was evaluated pre- and post-ablation with clinical and experimental neuropsychological measures including semantic memory, category-specific object/face recognition and naming, spatial learning, and socio-emotional processing. The patient became seizure-free following SLAH and experienced significant improvements in school performance and social engagement. She experienced improvement in recognition and naming of multiple object categories, memory functions, and verbal fluency. In contrast, the patient declined significantly in her ability to recognize emotional tone from facial expressions, a socio-emotional process that had been normal prior to surgery. We believe this decline was related to surgical disruption of the limbic system, an area highly involved in emotional processing, and suspect such deficits are an under-assessed and unrecognized risk for all surgeries involving the amygdalohippocampal complex and broader limbic system regions. We hope this positive SLAH outcome will serve as impetus for group level research to establish its safety and efficacy in the pediatric setting.

Downregulation of hyperpolarization-activated cyclic nucleotide-gated channels (HCN) in the hippocampus of patients with medial temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS).

Changes in the expression of HCN ion channels leading to changes in Ih function and neuronal excitability are considered to be possible mechanisms involved in epileptogenesis in kinds of human epilepsy. In previous animal studies of febrile seizures and temporal lobe epilepsy, changes in the expression of HCN1 and HCN2 channels at different time points and in different parts of the brain were not consistent, suggesting that transcriptional disorders involving HCNs play a crucial role in the epileptogenic process. Therefore, we aimed to assess the transcriptional regulation of HCN channels in Medial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) patients. This study included eight nonhippocampal sclerosis patients and 40 MTLE-HS patients. The mRNA expression of HCN channels was evaluated by qRT-PCR, while the protein expression was quantitatively analyzed by Western blotting. The subcellular localization of HCN channels in the hippocampus was explored by immunofluorescence. We demonstrated that the mRNA and protein expression of HCN1 and HCN2 are downregulated in controls compared to that in MTLE-HS patients. In the hippocampal CA1/CA4 subregion and GCL, in addition to a large decrease in neurons, the expression of HCN1 and HCN2 on neuronal cell membranes was also downregulated in MTLE-HS patients. These findings suggest that the expression of HCN channels are downregulated in MTLE-HS, which indicates that the decline in HCN channels in the hippocampus during chronic epilepsy in MTLE-HS patients leads to the downregulation of Ih current density and function, thereby reducing the inhibitory effect and increasing neuronal excitability and eventually causing disturbances in the electrical activity of neurons.

Rhinal and hippocampal contributions to spontaneous inter-item binding and verbal memory recall: Evidence from temporal lobe epilepsy.

The medial temporal lobes (MTL) play a prominent role in associative memory processing. Still, it is unclear to what extent specific structures within the MTL sub-serve distinct aspects of associative memory. Here, the role of the MTL in forming spontaneous associations in a "naturalistic" setting is investigated applying a word-list memory test not presenting items in an associative fashion. This allows for the differential investigation of item recall and associative binding. Participants included patients with medial temporal lobe epilepsy (mTLE, n = 79) and healthy controls (n = 58). Memory performance in a verbal list-learning paradigm was analyzed by (1) inter-trial repetitions ("binding", i.e., number of word-pairs consistently recalled over two consecutive trials), and (2) single item recall. In patients, behavioral results were correlated with rhinal cortex and hippocampal volumetric data. Results showed that binding was specifically diminished for patients with mTLE during learning and delayed recall. Moreover, binding predicted behavioral differences in item recall. Notably, hippocampal volumes were correlated with item recall during delayed recall, whereas rhinal cortex volumes were correlated with binding during learning. Our results provide evidence that diminished verbal memory in patients with mTLE at least partly can be attributed to functional reductions in spontaneous inter-trial stimulus binding. Moreover, they demonstrate a process-dependent functional dissociation between rhinal cortex and hippocampus for verbal encoding and recall: While the rhinal cortex is mainly engaged in detecting novel associations, the hippocampus primarily subserves consolidation and recall of associations between stimuli. Our study thus advances current models of the sub-specialization of MTL structures and offers novel evidence that memory formation in the MTL is mediated by associative item-processing, even when stimuli are not presented in an associative fashion per se. Thus, our results provide valuable qualitative insights into mechanisms of memory formation and memory failures in patients with MTL dysfunctions.

Automatic labeling of the fanning and curving shape of Meyer's loop for epilepsy surgery: an atlas extracted from high-definition fiber tractography.

BACKGROUND: Visual field defects caused by injury to Meyer's loop (ML) are common in patients undergoing anterior temporal lobectomy during epilepsy surgery. Evaluation of the anatomical shapes of the curving, fanning and sharp angles of ML to guide surgeries is important but still challenging for diffusion tensor imaging. We present an advanced diffusion data-based ML atlas and labeling protocol to reproduce anatomical features in individuals within a short time. METHODS: Thirty Massachusetts General Hospital-Human Connectome Project (MGH-HCP) diffusion datasets (ultra-high magnetic gradient & 512 directions) were warped to standard space. The resulting fibers were projected together to create an atlas. The anatomical features and the tractography correspondence rates were evaluated in 30 MGH-HCP individuals and local diffusion spectrum imaging data (eight healthy subjects and six hippocampal sclerosis patients). RESULTS: In the atlas, features of curves, sharp angles and fanning shapes were adequately reproduced. The distances from the anterior tip of the temporal lobe to the anterior ridge of Meyer's loop were 23.1 mm and 26.41 mm on the left and right sides, respectively. The upper and lower divisions of the ML were revealed to be twisting. Eighty-eight labeled sides were achieved, and the correspondence rates were 87.44% ± 6.92, 80.81 ± 10.62 and 72.83% ± 14.03% for MGH-HCP individuals, DSI-healthy individuals and DSI-patients, respectively. CONCLUSION: Atlas-labeled ML is comparable to high angular resolution tractography in healthy or hippocampal sclerosis patients. Therefore, rapid identification of the ML location with a single modality of T1 is practical. This protocol would facilitate functional studies and visual field protection during neurosurgery.

[Newer studies on the strong link between sleep and epilepsy: Epilepsy as an epileptic transformation of sleep plastic functions]. / Az alvás és az epilepszia szoros kapcsolatának újabb vizsgálatai: az epilepszia mint az alvási plaszticitásfunkció epilepsziás transzformációja.

Aims - Overview of the new data about the strong link of sleep and epilepsy and conjoining cognitive impairment. Methods - Search for relevant references and summary of our own research activity on the topic. Results - Strong interrealtionship exists between epilepsy and plastic brain functions (memory processing and synaptic homeostasis) and the working modes of NREM sleep. In the most frequent childhood and adult epilepsy networks responsible for plastic functions can be derailed to an epileptic level of excitability, and suffer a transitory or permanent epileptic transformation. Exampling on the three big epilepsies: absence epilepsy; medial temporal lobe epilepsy; and childhood idiopathic focal age dependent epilepsy spectrum we demonstrate the most important features of this epileptic transformation. The association of cognitive impairment to certain sleep dependent epilepsies gains explanation by the epilepsy caused interference with slow wave decline (ICFE) and memory consolidation (MTLE) during NREM sleep. This paper serves also to introduce the concept of sleep dependent system epilepsies. Conclusions - We provide evidences about shared mechanisms among sleep related epilepsies being the derailment of sleep plastic funcions toward exaggerated excitability determined by the inherent possibilities of the signal transduction properties.

Hippocampal neuron loss and astrogliosis in medial temporal lobe epileptic patients with mental disorders.

Hippocampal neuron loss and reactive astrogliosis are pathological features of medial temporal lobe epilepsy. Here, the expression of hippocampal astrogliosis-associated genes are studied in subjects with medial temporal lobe epilepsy and mental disorders (such as depression, anxiety and psychiatric comorbidities). The relationship between functional changes in hippocampus astrocytes and concurrent mental disorders are discussed. Nissl staining identified medial temporal lobe epilepsy-induced neuronal loss in the CA1 region of hippocampus. Quantitative real-time polymerase chain reaction and immunofluorescence technology were used to detect hippocampus glial fibrillary acidic protein, metallothionein, and aquaporin-4. The hippocampus area of subjects with medial temporal lobe epilepsy (with or without mental disorders) were smaller than the control group. Hippocampal neuronal loss and astrogliosis were more obvious in groups of medial temporal lobe epileptic patients with mental disorders. Relative protein levels of glial fibrillary acidic protein, metallothionein-I/II, and aquaporin-4 were significantly higher in subjects with medial temporal lobe epilepsy than seen in controls. Medial temporal lobe epileptic patients with mental disorder or depression had elevated metallothionein-I/II protein level when compared to controls and medial temporal lobe epileptic patients without mental disorder. Protein levels of glial fibrillary acidic protein and aquaporin-4 in medial temporal lobe epileptic patients with mental disorders were significantly lower than that in medial temporal lobe epileptic patients with no mental disorder. It is concluded that functional changes in hippocampus astrocytes are associated with mental disorders in medial temporal lobe epileptic patients and the astrogliosis-related genes of glial fibrillary acidic protein, metallothionein-I/II and aquaporin-4, are involved in this process.