Evaluating the prevalence and risk factors for depression in patients with temporal lobe epilepsy with hippocampal sclerosis: A cross-sectional multicenter study.

BACKGROUND: Epilepsy frequently accompanies Major Depressive Disorder (MDD). Notably, people with temporal lobe epilepsy and hippocampal sclerosis may face an increased susceptibility to MDD, as evidence indicates the involvement of the limbic system in the development of emotional symptoms. OBJECTIVES: To determine the prevalence and predictors of depression in temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) and compare them to those of other epilepsy types. METHODS: A sample of 293 epilepsy patients, including 159 non-TLE-HS and 134 TLE-HS, were recruited from three hospitals. Of these, 215 completed a two-section electronic survey. The first section collected demographic and epilepsy data, while the second used the Arabic version of the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E). RESULTS: Of 215 patients, 104 (48%) had TLE-HS-38 with right TLE-HS (37%), 56 with left TLE-HS (54%), and 10 with bilateral TLE-HS (10%). The prevalence and severity of depression was assessed with an NDDI-E score of 15 or higher identified 35 patients (16%) with MDD. Valproic acid and lamotrigine were associated with higher NDDI-E scores. No such associations were found for levetiracetam or carbamazepine. Polytherapy in TLE-HS showed a significant correlation with daily poor concentration. CONCLUSION: We explored the differences in depression prevalence between TLE-HS and other epilepsy types and concluded they are minimal but slightly higher in TLE-HS. Predictors of depression such as seizure frequency and disease duration influenced MDD prevalence in TLE-HS. Lamotrigine and valproate were linked to higher NDDI-E scores.

Association between serum apolipoprotein E and cognitive function in Chinese patients with temporal lobe epilepsy.

OBJECTIVE: To investigate the effect of serum apolipoprotein E (APOE) levels on cognitive function in patients with temporal lobe epilepsy (TLE). METHODS: Clinical data were collected from 190 subjects including 110 TLE patients and 80 healthy people. Cognitive function was assessed using the Addenbrooke's Cognitive Examination Revised (ACE-R) scale. Serum levels of APOE were measured using ELISA kits. Genotyping of APOE in peripheral blood was detected by microarray hybridization. RESULTS: Patients with TLE had significantly lower ACE-R total score, memory and verbal fluency scores compared to the healthy group. Serum levels of APOE were significantly higher in TLE patients than in the healthy subjects. Serum APOE levels were significantly negatively correlated with ACE-R total score, memory and verbal fluency scores. The cognitive function score of TLE with APOE ε4 allele was lower than that of TLE without APOE ε4 allele. SIGNIFICANCE: Our study showed that serum APOE levels were higher in TLE patients than in the healthy population. And serum APOE levels were associated with cognitive dysfunction in TLE patients. APOE ε4 allele carriers have poor cognitive function in TLE patients.

Dynamic facial emotion recognition and affective prosody recognition are associated in patients with temporal lobe epilepsy.

Deficits in facial emotion recognition have frequently been established in temporal lobe epilepsy (TLE). However, static, rather than dynamic emotion recognition paradigms have been applied. Affective prosody has been insufficiently studied in TLE, and there is a lack of studies investigating associations between auditory and visual emotion recognition. We wished to investigate potential deficits in a dynamic morph task of facial emotion recognition and in an affective prosody recognition task, as well as associations between both tasks. 25 patients with TLE and 24 healthy controls (CG) performed a morph task with faces continuously changing in their emotional intensity. They had to press a button, as soon as they were able to recognize the emotion expressed, and label it accordingly. In the auditory task, subjects listened to neutral sentences spoken in varying emotional tones, and labeled the emotions. Correlation analyses were conducted across both tasks. TLE patients showed significantly reduced prosody recognition compared to CG, and in the morph task, there was a statistical trend towards significantly reduced performance for TLE. Recognition rates in both tasks were significantly associated. TLE patients show deficits in affective prosody recognition, and they may also be impaired in a morph task with dynamically changing facial expressions. Impairments in basic social-cognitive tasks in TLE seem to be modality-independent.

Reduced eye gaze fixation during emotion recognition among patients with temporal lobe epilepsy.

OBJECTIVES: To investigate the facial scan patterns during emotion recognition (ER) through the dynamic facial expression task and the awareness of social interference test (TASIT) using eye tracking (ET) technology, and to find some ET indicators that can accurately depict the ER process, which is a beneficial supplement to existing ER assessment tools. METHOD: Ninety-six patients with TLE and 88 healthy controls (HCs) were recruited. All participants watched the dynamic facial expression task and TASIT including a synchronized eye movement recording and recognized the emotion (anger, disgust, happiness, or sadness). The accuracy of ER was recorded. The first fixation time, first fixation duration, dwell time, and fixation count were selected and analyzed. RESULTS: TLE patients exhibited ER impairment especially for disgust (Z = - 3.391; p = 0.001) and sadness (Z = - 3.145; p = 0.002). TLE patients fixated less on the face, as evidenced by the reduced fixation count (Z = - 2.549; p = 0.011) of the face and a significant decrease in the fixation count rate (Z = - 1.993; p = 0.046). During the dynamic facial expression task, TLE patients focused less on the eyes, as evidenced by the decreased first fixation duration (Z = - 4.322; p = 0.000), dwell time (Z = - 4.083; p = 0.000), and fixation count (Z = - 3.699; p = 0.000) of the eyes. CONCLUSION: TLE patients had ER impairment, especially regarding negative emotions, which may be attributable to their reduced fixation on the eyes during ER, and the increased fixation on the mouth could be a compensatory effect to improve ER performance. Eye-tracking technology could provide the process indicators of ER, and is a valuable supplement to traditional ER assessment tasks.

Influence of psychological factors on the relationship between subjective and objective memory in adults with pharmacoresistant temporal lobe epilepsy.

PURPOSE: Many adults with temporal lobe epilepsy (TLE) report subjective cognitive impairment; however, prior studies have shown a discrepancy between these subjective complaints and objective cognitive deficits on neuropsychological measures. Mood disorders/symptoms are also common in TLE and have been linked to greater subjective cognitive difficulties. To further understand these relationships, this retrospective study sought to determine if symptoms of depression and anxiety moderate or mediate the relationship between subjective cognitive impairment and objective cognitive performance in adults with TLE. METHOD: Participants were 345 adults (mean age = 40.7; 55 % female) with pharmacoresistant TLE who completed self-report screening measures of depression, anxiety, and subjective cognitive function along with objective memory measures as part of a pre-surgical clinical neuropsychological evaluation. A series of linear regression analyses was conducted to examine the potential moderating and mediating effects of mood on the relationship between subjective and objective memory function after adjusting for relevant covariates. RESULTS: Consistent with existing literature, self-reported depression and anxiety symptoms were significantly correlated with subjective memory difficulties across all scales (all p < .001). Subjective memory impairment was also significantly correlated with objective memory performance on neuropsychological measures, albeit with small effect sizes (estimate range 0.04-0.20). Contrary to our hypothesis, depression and anxiety did not moderate or mediate the relationship between subjective memory complaints and objective memory performance. CONCLUSIONS: While symptoms of depression and anxiety were associated with subjective memory ability in this cohort of adults with TLE, this study suggests that mood symptoms do not fully explain the relationship between subjective and objective memory function, likely reflecting the complex and multifactorial relationships among these variables. Nevertheless, our results highlight the importance of screening for depression and anxiety symptoms and assessing patients' subjective memory complaints as part of a neuropsychological evaluation as each of these factors tap into a different aspect of the patient functioning.

Application of the International Classification of Cognitive Disorders in Epilepsy (IC-CoDE) to frontal lobe epilepsy using multicenter data.

RATIONALE: The International Classification of Cognitive Disorders in Epilepsy (IC-CoDE) was recently introduced as a consensus-based, empirically-driven taxonomy of cognitive disorders in epilepsy and has been effectively applied to patients with temporal lobe epilepsy (TLE). The purpose of this study was to apply the IC-CoDE to patients with frontal lobe epilepsy (FLE) using national multicenter data. METHODS: Neuropsychological data of 455 patients with FLE aged 16 years or older were available across four US-based sites. First, we examined test-specific impairment rates across sites using two impairment thresholds (1.0 and 1.5 standard deviations below the normative mean). Following the proposed IC-CoDE guidelines, patterns of domain impairment were determined based on commonly used tests within five cognitive domains (language, memory, executive functioning, attention/processing speed, and visuospatial ability) to construct phenotypes. Impairment rates and distributions across phenotypes were then compared with those found in patients with TLE for which the IC-CoDE classification was initially validated. RESULTS: The highest rates of impairment were found among tests of naming, verbal fluency, speeded sequencing and set-shifting, and complex figure copy. The following IC-CoDE phenotype distributions were observed using the two different threshold cutoffs: 23-40% cognitively intact, 24-29% single domain impairment, 13-20% bi-domain impairment, and 18-33% generalized impairment. Language was the most common single domain impairment (68% for both thresholds) followed by attention and processing speed (15-18%). Overall, patients with FLE reported higher rates of cognitive impairment compared with patients with TLE. CONCLUSIONS: These results demonstrate the applicability of the IC-CoDE to epilepsy syndromes outside of TLE. Findings indicated generally stable and reproducible phenotypes across multiple epilepsy centers in the U.S. with diverse sample characteristics and varied neuropsychological test batteries. Findings also highlight opportunities for further refinement of the IC-CoDE guidelines as the application expands.

Psychiatric changes after stereotactic laser amygdalohippocampotomy for medial temporal lobe epilepsy.

PURPOSE: Stereotactic laser amygdalohippocampotomy (SLAH) is a minimally invasive surgical treatment for drug-resistant temporal lobe epilepsy (TLE) that has comparable rates of seizure freedom to traditional open resective TLE surgery. The objective of this study was to determine psychiatric outcome (i.e., depression and anxiety changes, psychosis) after SLAH, to explore possible contributory factors to these changes, and to determine the prevalence of de novo psychopathology. METHODS: We explored mood and anxiety in 37 adult patients with TLE undergoing SLAH using the Beck psychiatric symptoms scales (i.e., Beck Depression Inventory-II [BDI-II] and Beck Anxiety Inventory [BAI]) preoperatively and 6 months following surgery. Multivariable regression analysis was conducted to identify predictors of worse depression or anxiety symptoms following SLAH. The prevalence of de novo psychopathology following SLAH was also determined. RESULTS: We found a significant decrease in BDI-II (mean decline from 16.3 to 10.9, p = 0.004) and BAI (mean decline from 13.3 to 9.0, p = 0.045) scores following SLAH at the group level. While the rate of resolution of depression (from 62% to 49%) did not achieve statistical significance (p = 0.13, McNemar's), the rate of resolution of anxiety (from 57% to 35%) was statistically significant (p = 0.03, McNemar's). The de novo rate of psychopathology (i.e., new onset depression or anxiety) following SLAH was 1 of 7 (14%). Using a metric of meaningful change rather than complete symptom resolution, 16 of 37 (43%) patients experienced improvement in depression and 6 of 37 (16%) experienced worsening. For anxiety, 14 of 37 (38%) experienced meaningful improvement and 8 of 37 (22%) experienced worsening. Baseline performance on the Beck Scales was the only factor contributing to outcome status. DISCUSSION: In one of the first studies to evaluate psychiatric outcomes after SLAH, we found promising overall trends toward stability or significant improvement in symptom burden at the group level for both depression and anxiety. There was also a significant improvement in clinical anxiety, though the decrease in clinical depression was not significant, likely owing to the limitations of sample size. SLAH may improve overall psychiatric symptoms, similarly to traditional resective TLE surgery, but de novo psychopathology and postoperative psychiatric morbidity remain significant issues, and larger samples are necessary to determine causal contributory factors.

Chemogenetic inhibition of subicular seizure-activated neurons alleviates cognitive deficit in male mouse epilepsy model.

Cognitive deficit is a common comorbidity in temporal lobe epilepsy (TLE) and is not well controlled by current therapeutics. How epileptic seizure affects cognitive performance remains largely unclear. In this study we investigated the role of subicular seizure-activated neurons in cognitive impairment in TLE. A bipolar electrode was implanted into hippocampal CA3 in male mice for kindling stimulation and EEG recording; a special promoter with enhanced synaptic activity-responsive element (E-SARE) was used to label seizure-activated neurons in the subiculum; the activity of subicular seizure-activated neurons was manipulated using chemogenetic approach; cognitive function was assessed in object location memory (OLM) and novel object recognition (NOR) tasks. We showed that chemogenetic inhibition of subicular seizure-activated neurons (mainly CaMKIIα+ glutamatergic neurons) alleviated seizure generalization and improved cognitive performance, but inhibition of seizure-activated GABAergic interneurons had no effect on seizure and cognition. For comparison, inhibition of the whole subicular CaMKIIα+ neuron impaired cognitive function in naïve mice in basal condition. Notably, chemogenetic inhibition of subicular seizure-activated neurons enhanced the recruitment of cognition-responsive c-fos+ neurons via increasing neural excitability during cognition tasks. Our results demonstrate that subicular seizure-activated neurons contribute to cognitive impairment in TLE, suggesting seizure-activated neurons as the potential therapeutic target to alleviate cognitive impairment in TLE.

Dissociation in patients with epilepsy and functional seizures: A narrative review of the literature.

Dissociation is a "disruption of the usually integrated functions of consciousness, memory, identity or perception of the environment" according to DSM-5.  It is commonly seen in psychiatric disorders including primary dissociative disorders, post-traumatic stress disorder, depression, and panic disorder. Dissociative phenomena are also described in the context of substance intoxication, sleep deprivation and medical illnesses including traumatic brain injury, migraines, and epilepsy. Patients with epilepsy have higher rates of dissociative experiences as measured on the Dissociative Experiences Scale compared to healthy controls. Ictal symptoms, especially in focal epilepsy of temporal lobe origin, may include dissociative-like experiences such as déjà vu/jamais vu, depersonalization, derealization and what has been described as a "dreamy state".  These descriptions are common in the setting of seizures that originate from mesial temporal lobe epilepsy and may involve the amygdala and hippocampus. Other ictal dissociative phenomena include autoscopy and out of body experiences, which are thought to be due to disruptions in networks responsible for the integration of one's own body and extra-personal space and involve the temporoparietal junction and posterior insula. In this narrative review, we will summarize the updated literature on dissociative experiences in epilepsy, as well as dissociative experiences in functional seizures. Using a case example, we will review the differential diagnosis of dissociative symptoms. We will also review neurobiological underpinnings of dissociative symptoms across different diagnostic entities and discuss how ictal symptoms may shed light on the neurobiology of complex mental processes including the subjective nature of consciousness and self-identity.

Multifocal hypometabolic correlates to deficits of verbal memory in mesial temporal lobe epilepsy.

BACKGROUND AND OBJECTIVES: Neuropsychological research on mesial temporal lobe epilepsy (MTLE) often highlights material-specific memory deficits, but a lesion-focused model may not accurately reflect the underlying networks that support episodic memory in these patients. Our study evaluated the pathophysiology behind verbal learning/memory deficits as revealed by hypometabolism quantified through 18-fluorodeoxyglucose positron emission tomography (FDG-PET). METHODS: This retrospective study included thirty presurgical patients with intractable unilateral MTLE who underwent interictal FDG-PET and verbal memory assessment (12 females, mean age: 38.73 years). Fluorodeoxyglucose-positron emission tomography mapping was performed with voxel-based mapping of glucose utilization to a database of age-matched controls to derive regional Z-scores. Neuropsychological outcome variables included scores on learning and recall trials of two distinct verbal memory measures validated for use in epilepsy research. Pearson's correlations evaluated relationships between clinical variables and verbal memory. Linear regression was used to relate regional hypometabolism and verbal memory assessment. Post hoc analyses assessed areas of FDG-PET hypometabolism (threshold Z ≤ -1.645 below mean) where verbal memory was impaired. RESULTS: Verbal memory deficits correlated with hypometabolism in limbic structures ipsilateral to language dominance but also correlated with hypometabolism in networks involving the ipsilateral perisylvian cortex and contralateral limbic and nonlimbic structures. DISCUSSION: We conclude that traditional models of verbal memory may not adequately capture cognitive deficits in a broader sample of patients with MTLE. This study has important implications for epilepsy surgery protocols that use neuropsychological data and FDG-PET to draw conclusions about surgical risks.

Rhinal and hippocampal event-related potentials as epileptogenic zone markers in the pre-surgical evaluation of temporal epilepsies: a systematic review.

BACKGROUND: Cognitive event-related potentials (ERPs) allow for lateralization of the epileptogenic zone (EZ) to estimate the reserve of memory in the contralateral non-epileptogenic hemisphere, and to investigate the prognosis of temporal lobe seizure control in unilateral temporal lobe epilepsy (TLE). OBJECTIVE: To define the accuracy of cognitive evoked anterior mesial temporal lobe (AMTL-N400) and P600 potentials in detecting the epileptogenic zone in temporal lobe epilepsy (TLE), and second, to evaluate the possibility of using them as markers of cognitive outcome. METHODS: The systematic review using Medline/PubMed, Embase, and Lilacs database was conducted in September 2021. Only articles published in English from 1985 to June 2021 were included. We searched for studies with: (1) depth intracranial electroencephalography (iEEG) recordings analysis of rhinal and hippocampal activity (2) correlations between ERP results obtained in the mesial temporal regions (AMTL-N400 and P600) and the epileptogenic zone. RESULTS: Six out of the seven studies included in this review defined the laterality of the epileptogenic zone (EZ) during presurgical investigation using ERPs. One study showed that the contralateral AMTL-N400 predicts seizure control. Another study found correlation between the amplitudes of the right AMTL-N400 and postoperative memory performance. CONCLUSIONS: There is evidence that the reduced amplitude of the AMTL-N400 has high accuracy in identifying the epileptogenic zone, as it does in estimating the extent of seizure control and memory impairment in postoperative patients.

ANTECEDENTES: Potenciais relacionados a eventos (PREs) cognitivos permitem a lateralização da zona epileptogênica (ZE), estimar a reserva de memória no hemisfério contralateral não-epileptogênico, e estimar o prognóstico pós-operatório em pacientes com epilepsia do lobo temporal (ELT) unilateral quanto ao controle de crises. OBJETIVO: Definir a acurácia dos potenciais evocados cognitivos do lobo temporal mesial anterior (LTMA-N400) e P600 na detecção da zona epileptogênica na epilepsia do lobo temporal (ELT), além de avaliar a possibilidade de usá-los como marcadores de desfecho cognitivo. MéTODOS: A revisão sistemática foi realizada em setembro de 2021 usando as bases de dados Medline/PubMed, Embase e Lilacs. Apenas artigos publicados em inglês no período entre 1985 e junho de 2021 foram incluídos. Buscamos estudos com: (1) análises dos registros de electroencefalografia intracraniana (EEGi) da atividade rinal e hipocampal (2) correlações entre os resultados de PREs obtidos nas regiões temporais mesiais (AMTL-N400 e P600) e a zona epileptogênica. RESULTADOS: Seis dos sete estudos incluídos nesta revisão definiram a lateralidade da zona epileptogênica (ZE) durante a investigação pré-cirúrgica usando PREs. Um estudo mostrou que o AMTL-N400 contralateral prediz o controle das crises. Outro estudo encontrou correlação entre as amplitudes do AMTL-N400 direito e o desempenho da memória pós-operatória. CONCLUSõES: Há evidências de que a amplitude reduzida do AMTL-N400 tem alta precisão na identificação da zona epileptogênica, assim como na estimativa do prognóstico quanto ao controle de crises a longo prazo e prejuízo da memória em pacientes submetidos à cirurgia ressectiva.

A comparative study of social cognition in epilepsy, brain injury, and Parkinson's disease.

The brain regions involved in social cognition and the regulation of social behavior form a widely distributed cortico-subcortical network. Therefore, many neurological disorders could affect social cognition and behavior. A persistent lack of valid tests and a rigid neuropsychological focus on language, attention, executive function, and memory have contributed to a long-standing neglect of social cognition in clinical diagnostics, although the DSM-5 recognizes it as one of the six core dimensions in neurocognitive disorders. To assess for the first time the diagnostic yield of a comprehensive social cognition battery (Networks of Emotion Processing [NEmo]), we administered several emotion recognition and theory of mind tests to three incidental clinical samples with different neurological conditions: temporal lobe epilepsy (n = 30), acquired brain injury (n = 24), Parkinson's disease (n = 19), and a healthy control group (n = 67). A multivariate analysis of covariance was performed to test the effect of group on subscales of the NEmo test battery, controlling for age and performance IQ. The results showed statistically significant differences between clinical groups and healthy controls. No differences were found for gender and lateralization of the predominant lesion side. In our incidental samples, 86% of individuals with temporal lobe epilepsy, 57% of individuals with acquired brain lesion, and 14% of individuals with Parkinson's disease underperformed on tests of social cognition compared with controls. These findings suggest a differential impact of neurological disorders on the risk of impaired social cognition and highlight the need to consider social cognition in diagnostics, counselling, therapy, and rehabilitation.

Association of Neighborhood Deprivation With Cognitive and Mood Outcomes in Adults With Pharmacoresistant Temporal Lobe Epilepsy.

BACKGROUND AND OBJECTIVES: Temporal lobe epilepsy (TLE) is the most common adult form of epilepsy and is associated with a high risk of cognitive deficits and depressed mood. However, little is known about the role of environmental factors on cognition and mood in TLE. This cross-sectional study examined the relationship between neighborhood deprivation and neuropsychological function in adults with TLE. METHODS: Neuropsychological data were obtained from a clinical registry of patients with TLE and included measures of intelligence, attention, processing speed, language, executive function, visuospatial skills, verbal/visual memory, depression, and anxiety. Home addresses were used to calculate the Area Deprivation Index (ADI) for each individual, which were separated into quintiles (i.e., quintile 1 = least disadvantaged and quintile 5 = most disadvantaged). Kruskal-Wallis tests compared quintile groups on cognitive domain scores and mood and anxiety scores. Multivariable regression models, with and without ADI, were estimated for overall cognitive phenotype and for mood and anxiety scores. RESULTS: A total of 800 patients (median age 38 years; 58% female) met all inclusion criteria. Effects of disadvantage (increasing ADI) were observed across nearly all measured cognitive domains and with significant increases in symptoms of depression and anxiety. Furthermore, patients in more disadvantaged ADI quintiles had increased odds of a worse cognitive phenotype (p = 0.013). Patients who self-identified as members of minoritized groups were overrepresented in the most disadvantaged ADI quintiles and were 2.91 (95% CI 1.87-4.54) times more likely to be in a severe cognitive phenotype than non-Hispanic White individuals (p < 0.001). However, accounting for ADI attenuated this relationship, suggesting neighborhood deprivation may account for some of the relationship between race/ethnicity and cognitive phenotype (ADI-adjusted proportional odds ratio 1.82, 95% CI 1.37-2.42). DISCUSSION: These findings highlight the importance of environmental factors and regional characteristics in neuropsychological studies of epilepsy. There are many potential mechanisms by which neighborhood disadvantage can adversely affect cognition (e.g., fewer educational opportunities, limited access to health care, food insecurity/poor nutrition, and greater medical comorbidities). Future research will seek to investigate these potential mechanisms and determine whether structural and functional alterations in the brain moderate the relationship between ADI and cognition.

Memory characteristics in mesial temporal lobe epilepsy: Insights from an eye tracking memory game and neuropsychological assessments.

AIMS: To compare different patterns of memory impairment in patients with two subtypes of mesial temporal lobe epilepsy (MTLE) and healthy controls. METHODS: Thirty-five healthy controls and 41 patients with MTLE were recruited, of which 25 patients were diagnosed as hippocampal sclerosis (HS-MTLE), and the rest 16 patients were lesion-negative (MRI-neg MTLE). Participants completed the Wechsler memory assessment and a short-term memory game on an automated computer-based memory assessment platform with an eye tracker. RESULTS: Both the MRI-neg MTLE and HS-MTLE groups took longer time to complete the short-term memory game than healthy controls (p < 0.001, Cohen's d = 1.087; p = 0.047, Cohen's d = 0.787). During the memory encoding phase, the MRI-neg MTLE group spent significantly shorter time than healthy controls on the difficult levels with three (p = 0.004, Cohen's d = 0.993) and four targets (p = 0.016, Cohen's d = 0.858). During the memory decoding phase, the HS-MTLE group spent less time looking on the targets compared to controls when recalling and finding four targets (p = 0.004, Cohen's d = -0.793), while the MRI-neg MTLE group spent significantly longer time on the distractors and shorter time on the region of interests (ROIs) for all difficulty levels (all p < 0.05) than controls. Furthermore, the eye tracking data were correlated with the scores of the Wechsler Memory Scale after Bonferroni correction (p < 0.05). CONCLUSION: Patients with MRI-neg MTLE demonstrate impaired memory mostly due to attention deficits, while those with HS-MTLE show memory impairment with relative sparing of attention. Eye tracking technology has the potential of facilitating the investigation of the mechanism of memory defect in MTLE and can serve as a supplementary neuropsychological tool for clinical diagnosis and long-term monitoring.

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.

Processing speed in temporal lobe epilepsy. A scoping review.

BACKGROUND: Impaired processing speed (PS) can affect patients with temporal lobe epilepsy (TLE). However, it is usually considered a nonspecific clinical feature and is not measured, but this raises lexical and methodological problems. This review aims to evaluate the existing terminology and assessment methods of PS in patients with TLE. METHODS: A scoping review was conducted based on the extended guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. The electronic literature search was conducted on Medline-PubMed, American Psychological Association-PsycINFO, Elton Bryson Stephens Company, and Google Scholar, using the keywords "temporal lobe epilepsy" and "speed" or "slowing" plus "processing," "cognitive," "psychomotor," or "mental." Peer-reviewed articles published before December 2022 were analyzed if they were in English, including patients older than 14 years and at least one neuropsychological measure, reported original research focused on PS and had the selected keywords in the title, keywords, and abstract. RESULTS: Seven articles published between December 2004 and September 2021 were selected. The terms "processing speed," "psychomotor speed," and "information processing speed," based on similar theoretical constructs, were the most frequently used. Assessment methods included non-computerized or paper-and-pencil tests (WAIS-III Digit Symbol and Symbol Search subtests, Purdue Pegboard and Grooved Pegboard Tests, Trail Making Test and Stroop Color-Word Test) and computerized tests (Sternberg Memory Scanning Test, Pattern Comparison Processing Speed, Computerized Visual Searching). In some studies, impairment was associated with white and gray matter damage in the brain, independent of clinical and treatment variables. CONCLUSION: Clinical research on TLE has focused inconsistently on PS. Different evaluation terms and methods have been used while referring to similar theoretical constructs. These findings highlight a gap between the clinical importance of PS and its assessment. Studies are needed to share terms and tools among clinical centers and clarify the position of PS in the TLE phenotype.

Amygdala lesions are associated with improved mood after epilepsy surgery.

Neuroimaging studies in healthy and clinical populations strongly associate the amygdala with emotion, especially negative emotions. The consequences of surgical resection of the amygdala on mood are not well characterized. We tested the hypothesis that amygdala resection would result in mood improvement. In this study, we evaluated a cohort of 52 individuals with medial temporal lobectomy for intractable epilepsy who had resections variably involving the amygdala. All individuals achieved good post-surgical seizure control and had pre- and post-surgery mood assessment with the Beck Depression Inventory (BDI) ratings. We manually segmented the surgical resection cavities and performed multivariate lesion-symptom mapping of change in BDI. Our results showed a significant improvement in average mood ratings from pre- to post-surgery across all patients. In partial support of our hypothesis, resection of the right amygdala was significantly associated with mood improvement (r = 0.5, p = 0.008). The lesion-symptom map also showed that resection of the right hippocampus and para-hippocampal gyrus was associated with worsened post-surgical mood. Future studies could evaluate this finding prospectively in larger samples while including other neuropsychological outcome measures.

Epilepsy and the "dark" literature of the Greek novelist Demosthenes Voutyras: an outstanding epileptic personality.

BACKGROUND: The role of temporal lobe epilepsy (TLE) in determining personality traits and neurobehavioral symptoms, collectively known as the interictal behavioral syndrome (also known as Geschwind syndrome or "Gastaut-Geschwind syndrome"), as well as the syndrome's association with the particular artistic expression of many epileptic litterateurs are well known in neurology and psychiatry. A deepening of emotionality along with a serious, highly ethical, and spiritual behavior have been described as positive personality changes among patients with chronic mesial-TLE. OBJECTIVES: Our narrative-based clinical hypothesis aims at contributing to the ongoing debate on the association between TLE and artistic expression, as well as the latter's supposed implication for epileptology in general and the neuropsychology of epilepsy in particular. METHODS: Through an analysis of the biography, language, and literary work of Greek novelist Demosthenes Voutyras, we hypothesize that his mystical and dark writing style could be attributed to medial temporal interictal dynamics. CONCLUSIONS: We suggest that the psycholiterary profile of Voutyras is consistent with the idiosyncratic characteristics of the temporal lobe personality, while a non-dominant temporal lobe contribution has been proposed.

ANTECEDENTES: O papel da epilepsia do lobo temporal (ELT) na determinação de traços de personalidade e sintomas neurocomportamentais, coletivamente conhecidos como síndrome comportamental interictal (também conhecida como síndrome de Geschwind ou "síndrome de Gastaut-Geschwind"), bem como a associação da síndrome com o expressão de muitos literatos epilépticos são bem conhecidos em neurologia e psiquiatria. Um aprofundamento da emotividade juntamente com um comportamento sério, altamente ético e espiritual tem sido descrito como mudanças positivas de personalidade em pacientes com ELT mesial crônica. OBJETIVOS: A nossa hipótese clínica narrativa visa contribuir para o debate em curso sobre a associação entre ELT e a expressão artística, bem como a suposta implicação desta última para a epilepsia em geral e a neuropsicologia da epilepsia em particular. MéTODOS: Através de uma análise da biografia, linguagem e obra literária do romancista grego Demóstenes Voutyras, levantamos a hipótese de que seu estilo de escrita místico e sombrio poderia ser atribuído à dinâmica interictal temporal medial. CONCLUSõES: Sugerimos que o perfil psicoliterário de Voutyras é consistente com as características idiossincráticas da personalidade do lobo temporal, enquanto uma contribuição do lobo temporal não dominante foi proposta.

Does Alzheimer's disease with mesial temporal lobe epilepsy represent a distinct disease subtype?

Alzheimer's disease (AD) patients have a high risk of developing mesial temporal lobe epilepsy (MTLE) and subclinical epileptiform activity. MTLE in AD worsens outcomes. Therefore, we need to understand the overlap between these disease processes. We hypothesize that AD with MTLE represents a distinct subtype of AD, with the interplay between tau and epileptiform activity at its core. We discuss shared pathological features including histopathology, an initial mesial temporal lobe (MTL) hyperexcitability followed by MTL dysfunction and involvement of same networks in memory (AD) and seizures (MTLE). We provide evidence that tau accumulation linearly increases neuronal hyperexcitability, neuronal hyper-excitability increases tau secretion, tau can provoke seizures, and tau reduction protects against seizures. We speculate that AD genetic mutations increase tau, which causes proportionate neuronal loss and/or hyperexcitability, leading to seizures. We discuss that tau burden in MTLE predicts cognitive deficits among (1) AD and (2) MTLE without AD. Finally, we explore the possibility that anti-seizure medications improve cognition by reducing neuronal hyper-excitability, which reduces seizures and tau accumulation and spread. HIGHLIGHTS: We hypothesize that patients with Alzheimer's disease (AD) and mesial temporal lobe epilepsy (MTLE) represents a distinct subtype of AD. AD and MTLE share histopathological features and involve overlapping neuronal and cortical networks. Hyper-phosphorylated tau (pTau) increases neuronal excitability and provoke seizures, neuronal excitability increases pTau, and pTau reduction reduces neuronal excitability and protects against seizures. The pTau burden in MTL predicts cognitive deficits among (1) AD and (2) MTLE without AD. We speculate that anti-seizure medications improve cognition by reducing neuronal excitability, which reduces seizures and pTau.