Amygdala and cortical gamma-band responses to emotional faces are modulated by attention to valence.

The amygdala might support an attentional bias for emotional faces. However, whether and how selective attention toward a specific valence modulates this bias is not fully understood. Likewise, it is unclear whether amygdala and cortical signals respond to emotion and attention in a similar way. We recorded gamma-band activity (GBA, > 30 Hz) intracranially in the amygdalae of 11 patients with epilepsy and collected scalp recordings from 19 healthy participants. We presented angry, neutral, and happy faces randomly, and we denoted one valence as the target. Participants detected happy targets most quickly and accurately. In the amygdala, during attention to negative faces, low gamma-band activity (LGBA, < 90 Hz) increased for angry compared with happy faces from 160 ms. From 220 ms onward, amygdala high gamma-band activity (HGBA, > 90 Hz) was higher for angry and neutral faces than for happy ones. Monitoring neutral faces increased amygdala HGBA for emotions compared with neutral faces from 40 ms. Expressions were not differentiated in GBA while monitoring positive faces. On the scalp, only threat monitoring resulted in expression differentiation. Here, posterior LGBA was increased selectively for angry targets from 60 ms. The data show that GBA differentiation of emotional expressions is modulated by attention to valence: Top-down-controlled threat vigilance coordinates widespread GBA in favor of angry faces. Stimulus-driven emotion differentiation in amygdala GBA occurs during a neutral attentional focus. These findings align with a multi-pathway model of emotion processing and specify the role of GBA in this process.

German questionnaires assessing quality of life and psycho-social status in people with epilepsy: Reliable change and intercorrelations.

OBJECTIVES: People with epilepsy (PWE) not only suffer from seizures but also from various psycho-social issues containing facets such as social functioning, anxiety, depression or stigmatization, and consequently quality of life. (1) Assessing reliable change of these issues is crucial to evaluate their course and potential treatment effects. As most psycho-social self-report questionnaires have been validated in separate samples, their clinical-socio-demographic differences may limit the comparability and generalizability of the scales' internal consistency, which is important for the reliable change index (RCI). Using a co-normalized approach, we provide the internal consistency and RCIs for a large set of questionnaires targeting quality of life (QOLIE-31-P), depressive symptoms (NDDI-E), anxiety (GAD-7), seizure severity (LSSS), subjective antiseizure medication adverse events (LAEP), stigma, epilepsy-related fear, and restrictions in daily life (PESOS), and subjective cognition (FLei). As for some German versions of these measures, psychometric data is still missing, we also add important information for the German language area. (2) In addition, knowledge about intercorrelations of these constructs is needed to shape questionnaire usage and treatment approaches. We thus investigate associations of these scales and compare weighted and unweighted subscales of the QOLIE-31-P. METHODS: In our prospective study, 202 adult in-patients of the Epilepsy-Center Berlin-Brandenburg with a reliable diagnosis of epilepsy filled out a set of self-report questionnaires between 03/2018 and 03/2021. We calculated Cronbach's α, RCIs, and bivariate intercorrelations and compared the respective correlations of weighted and unweighted scales of the QOLIE-31-P. RESULTS: For most of the scales, good to excellent internal consistency was identified. Furthermore, we found intercorrelations in the expected directions with strong links between scales assessing similar constructs (e.g., QOLIE-31-P Cognition and FLei), but weak relationships between measures for different constructs (e.g., QOLIE-31-P Seizure worry and FLei). The QOLIE-31-P Total score was highly correlated with most of the other scales. Some differences regarding their correlational patterns for weighted and unweighted QOLIE-31-P scales were identified. CONCLUSIONS: Psycho-social constructs share a large amount of common variance, but still can be separated from each other. The QOLIE-31-P Total score represents an adequate measure of general psycho-social burden.

How patients' psycho-social profiles contribute to decision-making in epilepsy surgery: A prospective study.

OBJECTIVE: Identifying factors associated with surgical decision-making is important to understand reasons for underutilization of epilepsy surgery. Neurologists' recommendations for surgery and patients' acceptance of these recommendations depend on clinical epilepsy variables, for example, lateralization and localization of seizure onset zones. Moreover, previous research shows associations with demographic factors, for example, age and sex. Here, we investigate the relevance of patients' psycho-social profile for surgical decision-making. METHODS: We prospectively studied 296 patients from two large German epilepsy centers. Multiple logistic regression analyses were used to investigate variables linked to neurologists' recommendations for and patients' acceptance of surgery or intracranial video-electroencephalographic monitoring. Patients' psycho-social profiles were assessed via self-reports and controlled for various clinical-demographic variables. Model selection was performed using the Akaike information criterion. RESULTS: As expected, models for neurologists' surgery recommendations primarily revealed clinical factors such as lateralization and localization of the seizure onset zone, load with antiseizure medication (ASM), and site of the epilepsy-center. For this outcome, employment was the only relevant psycho-social aspect (odds ratio [OR] = .38, 95% confidence interval [CI] = .13-1.11). In contrast, three of the five relevant predictors for patients' acceptance were psycho-social. Higher odds were found for those with more subjective ASM adverse events (OR = 1.04, 95% CI = .99-1.00), more subjective seizure severity (OR = 1.12, 95% CI = 1.01-1.24), and lower subjective cognitive impairment (OR = .98, 95% CI = .96-1.00). SIGNIFICANCE: We demonstrated the relevance of the patients' psycho-social profile for decision-making in epilepsy surgery, particularly for patients' decisions. Thus, in addition to clinical-demographic variables, patients' individual psycho-social characteristics add to the understanding of surgical decision-making. From a clinical perspective, this calls for individually tailored counseling to assist patients in finding the optimal treatment option.

Differences in pediatric and adult epilepsy surgery: A comparison at one center from 1990 to 2014.

OBJECTIVE: Surgical volumes at large epilepsy centers are decreasing. Pediatric cohorts, however, show a trend toward more resections and superior outcome. Differences in pediatric and adult epilepsy surgery were investigated in our cohort. METHODS: The Bethel database between 1990 and 2014 was retrospectively analyzed. RESULTS: A total of 1916 adults and 1300 children underwent presurgical workup. The most common etiologies were medial temporal sclerosis (35.4%) in adults, and focal cortical dysplasias (21.1%) and diffuse hemispheric pathologies (14.7%) in children. Only 1.4% of the total cohort had normal histopathology. A total of 1357 adults (70.8%) and 751 children (57.8%) underwent resections. Surgery types for children were more diverse and showed a higher proportion of extratemporal resections (32.8%) and functional hemispherectomies (20.8%). Presurgical evaluations increased in both groups; surgical numbers remained stable for children, but decreased in the adult group from 2007 on. The patients' decision against surgery in the adult nonoperated cohort increased over time (total = 44.9%, 27.4% in 1995-1998 up to 53.2% in 2011-2014; for comparison, in children, total = 22.1%, stable over time). Postsurgical follow-up data were available for 1305 adults (96.2%) and 690 children (91.9%) 24 months after surgery. The seizure freedom rate was significantly higher in children than in adults (57.8% vs 47.5%, P < 0.001) and significantly improved over time (P = 0.016). SIGNIFICANCE: Pediatric epilepsy surgery has stable surgical volumes and renders more patients seizure-free than epilepsy surgery in adults. A relative decrease in hippocampal sclerosis, the traditional substrate of epilepsy surgery, changes the focus of epilepsy surgery toward other pathologies.

Pre- and postoperative verbal memory and executive functioning in frontal versus temporal lobe epilepsy.

There is accumulating evidence for considerable overlap in preoperatively affected cognitive functions in patients with temporal lobe epilepsy (TLE) and frontal lobe epilepsy (FLE). The current study investigated whether it is possible to differentiate between patients with FLE and TLE prior to surgery, based on measures of verbal memory and executive functioning. Furthermore, the postoperative cognitive development was compared. Pre- and postoperative data from 109 patients with FLE and 194 patients with TLE were retrospectively analyzed. Preoperatively, there were no differences in verbal memory, and postoperatively, no distinctive cognitive change was found between patients with FLE and TLE. However, patients with FLE performed worse on a cognitive switching task. Notably, irrespective of localization, patients with a presumed epileptogenic area in the language-dominant hemisphere performed worse than patients with seizures that originated in the nonlanguage-dominant hemisphere on measures of verbal memory, both pre- and postoperatively. In sum, the results suggest that verbal memory scores may be less valuable for differentiation between TLE and FLE, while measures of executive functioning may help identify patients with FLE. Additionally, rather than the localization, epilepsy lateralization critically impacts the evaluation of verbal memory functioning in both TLE and FLE. The results are discussed in light of the current frameworks of functional disturbances in epileptic networks.

Trends in epilepsy surgery: stable surgical numbers despite increasing presurgical volumes.

INTRODUCTION: Despite the success of epilepsy surgery, recent reports suggest a decline in surgical numbers. We tested these trends in our cohort to elucidate potential reasons. PATIENTS AND METHODS: Presurgical, surgical and postsurgical data of all patients undergoing presurgical evaluation in between 1990 and 2013 were retrospectively analysed. Patients were grouped according to the underlying pathology. RESULTS: A total of 3060 patients were presurgically studied, and resective surgery was performed in 66.8% (n=2044) of them: medial temporal sclerosis (MTS): n=675, 33.0%; benign tumour (BT): n=408, 20.0%; and focal cortical dysplasia (FCD): n=284, 13.9%. Of these, 1929 patients (94.4%) had a follow-up of 2 years, and 50.8% were completely seizure free (Engel IA). Seizure freedom rate slightly improved over time. Presurgical evaluations continuously increased, whereas surgical interventions did not. Numbers for MTS, BT and temporal lobe resections decreased since 2009. The number of non-lesional patients and the need for intracranial recordings increased. More evaluated patients did not undergo surgery (more than 50% in 2010-2013) because patients were not suitable (mainly due to missing hypothesis: 4.5% in 1990-1993 up to 21.1% in 2010-2013, total 13.4%) or declined from surgery (maximum 21.0% in 2010-2013, total 10.9%). One potential reason may be that increasingly detailed information on chances and risks were given over time. CONCLUSIONS: The increasing volume of the presurgical programme largely compensates for decreasing numbers of surgically remediable syndromes and a growing rate of informed choice against epilepsy surgery. Although comprehensive diagnostic evaluation is offered to a larger group of epilepsy patients, surgical numbers remain stable.

Disturbed spatial cognitive processing of body-related stimuli in a case of a lesion to the right fusiform gyrus.

The fusiform gyrus (FG) is well known as one of the main neural sites of human face and body processing. We report the case of a young male patient with epilepsy and a circumscribed lesion in the right FG who presented with isolated impairments in spatial cognitive processing of body-related stimuli. However, he did not show any clinical signs of prosopagnosia. In particular, handling/processing of body and face stimuli was impaired, when stimuli were presented in unconventional views and orientations, thus requiring additional spatial cognitive operations. In this case study, we discuss the patient's selective impairment from the view of current empirical and theoretical work on the segregation of functions in the FG.

The Bergen left-right discrimination test: practice effects, reliable change indices, and strategic performance in the standard and alternate form with inverted stimuli.

Several authors pointed out that left-right discrimination (LRD) tasks may be entangled with differential demands on mental rotation (MR). However, studies considering this interrelationship are rare. To differentially assess LRD of stimuli with varying additional demands on MR, we constructed and evaluated an extended version of the Bergen right-left discrimination (BRLD) test including additional subtests with inverted stickmen stimuli in 174 healthy participants (50♂, 124♀) and measured subjective reports on participants' strategies to accomplish the task. Moreover, we analyzed practice effects and reliable change indices (RCIs) on BRLD performance, as well as gender differences. Performance significantly differed between subtests with high and low demands on MR with best scores on subtests with low demands on MR. Participants' subjective strategies corroborate these results: MR was most frequently reported for subtests with highest MR demands (and lowest test performance). Pronounced practice effects were observed for all subtests. Sex differences were not observed. We conclude that our extended version of the BRLD allows for the differentiation between LRD with high and low demands on MR abilities. The type of stimulus materials is likely to be critical for the differential assessment of MR and LRD. Moreover, RCIs provide a basis for the clinical application of the BRLD.

Learning real-life cognitive abilities in a novel 360°-virtual reality supermarket: a neuropsychological study of healthy participants and patients with epilepsy.

BACKGROUND: To increase the ecological validity of neuropsychological instruments the use of virtual reality (VR) applications can be considered as an effective tool in the field of cognitive neurorehabilitation. Despite the growing use of VR programs, only few studies have considered the application of everyday activities like shopping or travelling in VR training devices. METHODS: We developed a novel 360°-VR supermarket, which is displayed on a circular arrangement of 8 touch-screens--the "OctaVis". In this setting, healthy human adults had to memorize an auditorily presented shopping list (list A) and subsequently buy all remembered products of this list in the VR supermarket. This procedure was accomplished on three consecutive days. On day four, a new shopping list (list B) was introduced and participants had to memorize and buy only products of this list. On day five, participants had to buy all remembered items of list A again, but without new presentation of list A. Additionally, we obtained measures of participants' presence, immersion and figural-spatial memory abilities. We also tested a sample of patients with focal epilepsy with an extended version of our shopping task, which consisted of eight days of training. RESULTS: We observed a comprehensive and stable effect of learning for the number of correct products, the required time for shopping, and the length of movement trajectories in the VR supermarket in the course of the training program. Task performance was significantly correlated with participants' figural-spatial memory abilities and subjective level of immersion into the VR. CONCLUSIONS: Learning effects in our paradigm extend beyond mere verbal learning of the shopping list as the data show evidence for multi-layered learning (at least visual-spatial, strategic, and verbal) on concordant measures. Importantly, learning also correlated with measures of figural-spatial memory and the degree of immersion into the VR. We propose that cognitive training with the VR supermarket program in the OctaVis will be efficient for the assessment and training of real-life cognitive abilities in healthy subjects and patients with epilepsy. It is most likely that our findings will also apply for patients with cognitive disabilities resulting from other neurological and psychiatric syndromes.

Discrepancy between subjective and objective memory change after epilepsy surgery: Relation with seizure outcome and depressive symptoms.

Complaints pertaining to memory functioning are among the most often reported cognitive symptoms in patients with epilepsy. However, research suggests a considerable mismatch between patients' perception of memory functioning and the objective performance as measured with standardized neuropsychological tests. Depressive mood might be an important factor in explaining this discrepancy, though other variables have also occasionally been reported as relevant. There are mixed results as to which role these factors play in determining the overall quality of life of patients with epilepsy. The present study aimed to quantify the mismatch between subjective and objective memory functioning by taking into account the dynamic change of these factors as well as depressive symptoms after epilepsy surgery. Moreover, the influencing factors of subjective and objective memory change were investigated as well as their effects on the overall quality of life. Pre- and postoperative data from 78 patients with focal epilepsy were retrospectively analyzed. The results showed that (1) patients with clinically relevant postoperative depressive symptoms underestimate their actual memory performance; (2) for non-seizure-free patients, a postoperative decrease in depressive symptoms was associated with a tendency to underestimate memory decline; (3) the relationship between objective memory change and quality of life is mediated by the factors subjective memory change and depressive mood. Our data demonstrate a quantitative approximation of a pronounced depression-related negative biased self-perception of memory functioning of roughly 1 to 1.5 standard deviations. Moreover, it seems that when patients are relieved of having recurrent epileptic seizures, they may be less influenced by depressive symptoms when judging their memory change. Taken together, our study demonstrates the clinical relevance of incorporating subjective measures of memory functioning and mood that go beyond objective memory performance for the interpretation of how changes in memory functioning may affect patients' quality of life after epilepsy surgery.

Emotion and attention in face processing: Complementary evidence from surface event-related potentials and intracranial amygdala recordings.

Face processing is biased by emotional and voluntarily directed attention, both of which modulate processing in distributed cortical areas. The amygdala is assumed to contribute to an attentional bias for emotional faces, although its interaction with directed attention awaits further clarification. Here, we studied the interaction of emotion and attention during face processing via scalp EEG potentials of healthy participants and intracranial EEG (iEEG) recordings of the right amygdala in one patient. Three randomized blocks consisting of angry, neutral, and happy facial expressions were presented, and one expression was denoted as the target category in each block. Happy targets were detected fastest and most accurately both in the group study and by the iEEG patient. Occipital scalp potentials revealed emotion differentiation for happy faces in the early posterior negativity (EPN) around 300 ms after stimulus onset regardless of the target condition. A similar response to happy faces occurred in the amygdala only for happy targets. On the scalp, a late positive potential (LPP, around 600 ms) enhancement for targets occurred for all target conditions alike. A simultaneous late signal in the amygdala was largest for emotional targets. No late signal enhancements were found for neutral targets in the amygdala. Cortical modulations, by contrast, showed both attention-independent effects of emotion and emotion-independent effects of attention. These results demonstrate an attention-dependence of amygdala activity during the processing of facial expressions and partly independent cortical mechanisms.

Epilepsy Surgery in Extratemporal vs Temporal Lobe Epilepsy: Changes in Surgical Volumes and Seizure Outcome Between 1990 and 2017.

BACKGROUND AND OBJECTIVES: Seizure outcome after extratemporal lobe epilepsy (exTLE) surgery has often been poorer than after temporal lobe epilepsy (TLE) surgery, but recent improvements in diagnostics and surgery may have changed this. Our aim was to analyze the changes in presurgical and surgical volumes and seizure outcome 2 years after surgery for patients with exTLE compared with those with TLE. METHODS: We performed a retrospective, single-center cohort study including patients from the Bethel presurgical-surgical-postsurgical database from 1990 to 2017. We used logistic regression to analyze factors influencing the odds for surgery and the odds for seizure freedom after surgery. RESULTS: We included 3,822 patients with presurgical evaluation, 2,404 of whom had subsequently undergone surgery. The proportion of patients with exTLE in presurgical evaluation increased from 41% between 1990 and 1993 to 64% in 2014-2017. The odds for surgery decreased over time (2003-2011: odds ratio [OR] 0.50 [95% CI 0.36-0.70]; 2012-2017: OR 0.24 [CI 0.17-0.35]; reference: 1990-2002) and patients with exTLE had lower odds for surgery than patients with TLE, but this difference diminished over time (exTLE vs TLE 1990-2002: OR 0.14 [CI 0.09-0.20]; 2003-2011: OR 0.32 [CI 0.24-0.44]; 2012-2017: OR 0.46 [CI 0.34-0.63]). Etiology, the side of the epileptogenic lesion, and invasive recordings influenced the odds for surgery. The most frequent reasons for not undergoing surgery were missing identification of a circumscribed epileptogenic zone or an unacceptable risk of postsurgical deficits in patients with exTLE and the patient's decision in patients with TLE. Compared with patients with TLE, the odds for seizure freedom after surgery started lower for patients with exTLE in earlier years, but increased (≤2 lobes 1990-2002: OR 0.47 [CI 0.33-0.68]; 2003-2011: OR 0.62 [CI 0.44-0.87]; 2012-2017: OR 0.78 [CI 0.53-1.15]; ≥3 lobes 1990-2002: OR 0.37 [CI 0.22-0.62]; 2003-2011: OR 0.73 [CI 0.43-1.23]; 2012-2017: OR 1.46 [CI 0.91-2.42]). Etiology, age at surgery, and invasive recordings were further predictors for the odds for seizure freedom. DISCUSSION: Over the past 28 years, the success of resective surgery for patients with exTLE has improved. At the same time, the number of patients with exTLE being evaluated for surgery increased, as well as their odds for undergoing surgery.

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.

Hippocampal theta phases organize the reactivation of large-scale electrophysiological representations during goal-directed navigation.

Humans are adept in simultaneously following multiple goals, but the neural mechanisms for maintaining specific goals and distinguishing them from other goals are incompletely understood. For short time scales, working memory studies suggest that multiple mental contents are maintained by theta-coupled reactivation, but evidence for similar mechanisms during complex behaviors such as goal-directed navigation is scarce. We examined intracranial electroencephalography recordings of epilepsy patients performing an object-location memory task in a virtual environment. We report that large-scale electrophysiological representations of objects that cue for specific goal locations are dynamically reactivated during goal-directed navigation. Reactivation of different cue representations occurred at stimulus-specific hippocampal theta phases. Locking to more distinct theta phases predicted better memory performance, identifying hippocampal theta phase coding as a mechanism for separating competing goals. Our findings suggest shared neural mechanisms between working memory and goal-directed navigation and provide new insights into the functions of the hippocampal theta rhythm.