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The current diagnostic criteria for autoimmune limbic encephalitis (LE) stress bilaterality of temporal MRI and EEG findings. This retrospective cohort study aimed to determine whether bilaterality is indeed more common in LE than in other mesiotemporal epilepsies.We compared EEG findings mostly from long-term EEG monitoring in patients with LE (n=59), hippocampal sclerosis (HS, n=44), and mesiotemporal tumors (n=24).Bilateral temporal EEG findings including temporal slowing, interictal epileptiform discharges (IED), and seizures were equally frequent with 37% in LE, 32% in HS, and 17% in tumor patients. Bilateral independent temporal seizures were infrequent with 3%, 9%, and 0%, respectively. Patients with seropositive LE more often showed an EEG without IED or seizure patterns than patients with seronegative LE (n=37) with a higher proportion of unilateral temporal findings. Patients with immunotherapy naïve LE (n=40) showed a higher proportion of bilateral temporal IED or slowing in comparison with tumor patients.We conclude that unilateral or absent temporal EEG findings are common in LE and should not discourage this differential diagnosis.

Background To mitigate the potential consequences of the coronavirus disease 2019 (COVID-19) pandemic on public life, the German Federal Government and Ministry of Health enacted a strict lockdown protocol on March 16, 2020. This study aimed to evaluate the impact of the COVID-19 pandemic on physical and mental health status and the supply of medical care and medications for people with epilepsy (PWE) in Germany. Methods The Epi2020 study was a large, multicenter study focused on different healthcare aspects of adults with epilepsy. In addition to clinical and demographic characteristics, patients were asked to answer a questionnaire on the impact of the first wave of the COVID-19 pandemic between March and May 2020. Furthermore, the population-based number of epilepsy-related admissions in Hessen was evaluated for the January-June periods of 2017–2020 to detect pandemic-related changes. Results During the first wave of the pandemic, 41.6% of PWE reported a negative impact on their mental health, while only a minority reported worsening of their seizure situation. Mental and physical health were significantly more negatively affected in women than men with epilepsy and in PWE without regular employment. Moreover, difficulties in ensuring the supply of sanitary products (25.8%) and antiseizure medications (ASMs; 19.9%) affected PWE during the first lockdown; no significant difference regarding these impacts between men and women or between people with and without employment was observed. The number of epilepsy-related admissions decreased significantly during the first wave. Conclusions This analysis provides an overview of the general and medical care of epilepsy patients during the COVID-19 pandemic. PWE in our cohort frequently reported psychosocial distress during the first wave of the pandemic, with significant adverse effects on mental and physical health. Women and people without permanent jobs especially reported distress due to the pandemic. The COVID‐19 pandemic has added to the mental health burden and barriers to accessing medication and medical services, as self-reported by patients and verified in population-based data on hospital admissions. Trial registration German Clinical Trials Register (DRKS), DRKS00022024. Registered October 2, 2020, http://www.drks.de/DRKS00022024

Spinal and bulbar muscular atrophy (SBMA) is a progressive, X-linked lower motor neuron disorder exclusively affecting men. Since knowledge on sleep disorders in SBMA is scarce compared to other motoneuron diseases, this retrospective case-control study aimed to investigate sleep and sleep-related breathing in patients with SBMA. In 23 non-ventilated patients with SBMA (median age 52 years), clinical disease characteristics, forced vital capacity and diagnostic polysomnographies were retrospectively evaluated. In 16 patients, overnight transcutaneous capnometry was available. Twenty-three male control subjects with chronic insomnia were matched for age and body mass index. In patients with SBMA obstructive sleep apnoea (OSA, apnoea-hypopnoea index/AHI > 5/h) was more frequent than in control subjects (14/23 or 61% vs. 6/23 or 26%, p = 0.02), and median AHI was significantly higher in patients (9.0/h vs. 3.4/h, p 15/h) were frequent in SBMA patients but rarely disrupted sleep. In patients with SBMA, sleep-disordered breathing may comprise both OSA and nocturnal hypoventilation. REM sleep without atonia may also be found, but its clinical significance remains unclear. In patients complaining of sleep-related symptoms, cardiorespiratory polysomnography and transcutaneous capnometry are recommended.

ZusammenfassungDie genaue Beobachtung und Testung der unterschiedlichen Symptome epileptischer Anfälle trägt entscheidend zur Identifikation der symptomatogenen Zone bei. Diese Informationen sind insbesondere für die prächirurgische Epilepsiediagnostik relevant. Um Anfallssymptome möglichst detailliert zu erfassen, ist eine Testung während der Anfallsaufzeichnung in der EEG-Monitoring-Einheit erforderlich. Eine adäquate Anfallstestung setzt wiederum die Kenntnis der neurobiologischen Grundlagen der unterschiedlichen Anfallssymptome voraus. Der vorliegende Artikel soll eine Übersicht über typische Anfallssemiologien, die Entstehung ihrer Symptome und ihre Testung geben und als Leitfaden insbesondere für Mitarbeiter dienen, die neu in einer EEG-Monitoring-Einheit eingearbeitet werden.

Ein Status epilepticus kann Komplikation oder Erstmanifestation einer autoimmunen Enzephalitis sein. Zum Ausschluss von Differenzialdiagnosen sind eine breite labor- und insbesondere liquorchemische Diagnostik erforderlich, bei Erstmanifestation auch eine Tumorsuche. Haufig ist der autoimmune Status therapierefraktar, bei Erstmanifestation einer Epilepsie als „new onset refractory status epilepticus“ (NORSE). Zusatzlich zur antikonvulsiven Therapie ist eine Immuntherapie erforderlich, wobei sowohl Erst- als auch Zweitlinienimmuntherapeutika eingesetzt werden. Der autoimmune Status epilepticus geht mit einer Mortalitat von 10–20 % einher, etwa ein Drittel der Patienten uberlebt mit schweren neurologischen Defiziten. Daher sind eine rasche Diagnostik und konsequente Therapie erforderlich.

Background: Reference values derived from existing diaphragm ultrasound protocols are inconsistent, and the association between sonographic measures of diaphragm function and volitional tests of respiratory muscle strength is still ambiguous. Objective: To propose a standardized and comprehensive protocol for diaphragm ultrasound in order to determine lower limits of normal (LLN) for both diaphragm excursion and thickness in healthy subjects and to explore the association between volitional tests of respiratory muscle strength and diaphragm ultrasound parameters. Methods: Seventy healthy adult subjects (25 men, 45 women; age 34 ± 13 years) underwent spirometric lung function testing, determination of maximal inspiratory and expiratory pressure along with ultrasound evaluation of diaphragm excursion and thickness during tidal breathing, deep breathing, and maximum voluntary sniff. Excursion data were collected for amplitude and velocity of diaphragm displacement. Diaphragm thickness was measured in the zone of apposition at total lung capacity (TLC) and functional residual capacity (FRC). All participants underwent invasive measurement of transdiaphragmatic pressure (Pdi) during different voluntary breathing maneuvers. Results: Ultrasound data were successfully obtained in all participants (procedure duration 12 ± 3 min). LLNs (defined as the 5th percentile) for diaphragm excursion were as follows: (a) during tidal breathing: 1.2 cm (males; M) and 1.2 cm (females; F) for amplitude, and 0.8 cm/s (M) and 0.8 cm/s (F) for velocity, (b) during maximum voluntary sniff: 2.0 cm (M) and 1.5 cm (F) for amplitude, and 6.7 (M) cm/s and 5.2 cm/s (F) for velocity, and (c) at TLC: 7.9 cm (M) and 6.4 cm (F) for amplitude. LLN for diaphragm thickness was 0.17 cm (M) and 0.15 cm (F) at FRC, and 0.46 cm (M) and 0.35 cm (F) at TLC. Values for males were consistently higher than for females, independent of age. LLN for diaphragmatic thickening ratio was 2.2 with no difference between genders. LLN for invasively measured Pdi during different breathing maneuvers are presented. Voluntary Pdi showed only weak correlation with both diaphragm excursion velocity and amplitude during forced inspiration. Conclusions: Diaphragm ultrasound is an easy-to-perform and reproducible diagnostic tool for noninvasive assessment of diaphragm excursion and thickness. It supplements but does not replace respiratory muscle strength testing.

Objective Autoimmune limbic encephalitis (ALE) is characterized by memory impairment, psychiatric symptoms, and epileptic seizures. Though, the neuropsychological profile of ALE is not yet well defined. However, there is some evidence that neuropsychological impairments might exceed those related to the limbic system and that different autoantibodies (AABs) are associated with distinguishable pattern of neuropsychological impairments. We provide a comprehensive presentation of neuropsychological performance of ALE in an immune therapy-naïve sample. Methods We retrospectively analyzed 69 immunotherapy-naïve ALE-patients (26 seropositive—[8 LGI1-, 4 CASPR2-, 2 GABAB-R-, 3 Hu-, 4 GAD65-, 2 Ma2-, 2 unknown antigen, and 1 Yo-AABs] and 43 seronegative patients, mean age 56.0 years [21.9–78.2], mean disease duration 88 weeks [0–572]). Neuropsychological evaluations comprised of the domains memory, attention, praxis, executive functions, language, social cognition, and psychological symptoms. We compared these functions between seronegative −, seropositive patients with AABs against intracellular neural antigens and seropositive patients with AABs against surface membrane neural antigens. Results No effect of AAB group on neuropsychological performance could be detected. Overall, ALE predominantly presents with deficits in long-term memory and memory recognition, autobiographical-episodic memory loss, impairment of emotion recognition, and depressed mood. Furthermore, deficits in praxis of pantomimes and imitations, visuo-construction, and flexibility may occur. Conclusion ALE shows a wide spectrum of neuropsychological impairments, which might exceed the limbic system, with no evidence of differences between AAB groups. Neuropsychological assessment for diagnosing ALE should include long-term memory, memory recognition, autobiographical-episodic memory, emotion recognition, and a detailed investigation of depression.

This study was undertaken to quantify epilepsy-related costs of illness (COI) in Germany and identify cost-driving factors.COI were calculated among adults with epilepsy of different etiologies and severities. Multiple regression analysis was applied to determine any epilepsy-related and sociodemographic factors that serve as cost-driving factors.In total, 486 patients were included, with a mean age of 40.5 ± 15.5 years (range = 18-83 years, 58.2% women). Mean 3-month COI were estimated at €4911, €2782, and €2598 for focal, genetic generalized, and unclassified epilepsy, respectively. The mean COI for patients with drug-refractory epilepsy (DRE; €7850) were higher than those for patients with non-DRE (€4720), patients with occasional seizures (€3596), or patients with seizures in remission for1 year (€2409). Identified cost-driving factors for total COI included relevant disability (unstandardized regression coefficient b = €2218), poorer education (b = €2114), living alone (b = €2612), DRE (b = €1831), and frequent seizures (b = €2385). Younger age groups of 18-24 years (b = -€2945) and 25-34 years (b = -€1418) were found to have lower overall expenditures. A relevant disability (b = €441), DRE (b = €1253), frequent seizures (b = €735), and the need for specialized daycare (b = €749) were associated with higher direct COI, and poorer education (b = €1969), living alone (b = €2612), the presence of a relevant disability (b = €1809), DRE (b = €1831), and frequent seizures (b = €2385) were associated with higher indirect COI.This analysis provides up-to-date COI data for use in further health economics analyses, highlighting the high economic impacts associated with disease severity, disability, and disease-related loss of productivity among adult patients with epilepsy. The identified cost drivers could be used as therapeutic and socioeconomic targets for future cost-containment strategies.

Objective This study was undertaken to evaluate the long-term efficacy, retention, and tolerability of add-on brivaracetam (BRV) in clinical practice. Methods A multicenter, retrospective cohort study recruited all patients who initiated BRV between February and November 2016, with observation until February 2021. Results Long-term data for 262 patients (mean age = 40 years, range = 5-81 years, 129 men) were analyzed, including 227 (87%) diagnosed with focal epilepsy, 19 (7%) with genetic generalized epilepsy, and 16 (6%) with other or unclassified epilepsy syndromes. Only 26 (10%) patients had never received levetiracetam (LEV), whereas 133 (50.8%) were switched from LEV. The length of BRV exposure ranged from 1 day to 5 years, with a median retention time of 1.6 years, resulting in a total BRV exposure time of 6829 months (569 years). The retention rate was 61.1% at 12 months, with a reported efficacy of 33.1% (79/239; 50% responder rate, 23 patients lost-to-follow-up), including 10.9% reported as seizure-free. The retention rate for the entire study period was 50.8%, and at last follow-up, 133 patients were receiving BRV at a mean dose of 222 ± 104 mg (median = 200, range = 25-400), including 52 (39.1%) who exceeded the recommended upper dose of 200 mg. Fewer concomitant antiseizure medications and switching from LEV to BRV correlated with better short-term responses, but no investigated parameters correlated with positive long-term outcomes. BRV was discontinued in 63 (24%) patients due to insufficient efficacy, in 29 (11%) for psychobehavioral adverse events, in 25 (10%) for other adverse events, and in 24 (9%) for other reasons. Significance BRV showed a clinically useful 50% responder rate of 33% at 12 months and overall retention of >50%, despite 90% of included patients having previous LEV exposure. BRV was well tolerated; however, psychobehavioral adverse events occurred in one out of 10 patients. Although we identified short-term response and retention predictors, we could not identify significant predictors for long-term outcomes.

Purpose We aimed to identify clinical characteristics of patients with shoulder dislocations caused by an epileptic seizure. Methods In our retrospective analysis, we identified 15 patients, recorded over an 8-year period, who were diagnosed with shoulder dislocations in the setting of a bilateral tonic-clonic seizure. Results Patients were almost exclusively male (13/15) and drug-naive patients suffering their first or second seizure (14/15). Epilepsy was diagnosed in five of these 14 patients after further diagnostic tests, four patients were diagnosed with a provoked or acute symptomatic seizure and five patients with an unprovoked seizure. Treatment with anticonvulsant drugs (AED) was initiated in 10/15 patients after the first seizure, without recommendation for tapering, although long-term treatment was retrospectively judged to be appropriate for only four of those cases. Posterior dislocations – usually rare – were seen in 12/15 patients and often required complex orthopedic interventions. Conclusions We conclude that in particular posterior shoulder dislocations are often caused by a first seizure and should always raise the suspicion of an epileptic seizure even in the absence of a clear history. AED treatment likely has a protective effect against this type of injury, even if seizure-freedom is not achieved.

Patients with seizures and epilepsy routinely undergo multiple diagnostic tests, which may include cerebrospinal fluid (CSF) analysis. This review aims to outline different CSF parameters and their alterations in seizures or epilepsy. We then discuss the utility of CSF analysis in seizure patients in different clinical settings in depth. Some routine CSF parameters are frequently altered after seizures, but are not specific such as CSF protein and lactate. Pleocytosis and CSF specific oligoclonal bands are rare and should be considered as signs of infectious or immune mediated seizures and epilepsy. Markers of neuronal damage show conflicting results, and are as yet not established in clinical practice. Parameters of neuronal degeneration and more specific immune parameters are less well studied, and are areas of further research. CSF analysis in new-onset seizures or status epilepticus serves well in the differential diagnosis of seizure etiology. Here, considerations should include autoimmune-associated seizures. CSF findings in these disorders are a special focus of this review and are summarized in a comprehensive overview. Until now, CSF analysis has not yielded clinically helpful biomarkers for refractory epilepsy or for assessment of neuronal damage which is a subject of further studies.

The prescription patterns of antiseizure medication (ASM) are subject to new scientific evidence and sociodemographic and practical aspects. This study analyzed trends in ASM prescription patterns among all adults with epilepsy, with special consideration for women of childbearing potential (WOCBP) and older adult (≥65 years old) patients.Data from four questionnaire-based cohort studies, conducted in 2008, 2013, 2016, and 2020, were analyzed for ASM prescription frequencies and common mono- and dual therapy regimens. Statistical comparisons were performed with the Chi-square test and one-way analysis of variance.Overall, the individual prescription patterns among 1,642 adult patients with epilepsy were analyzed. A significant increase in the prescription frequency of third-generation ASMs, from 59.3% to 84.2% (p = 0.004), was accompanied by a decrease in the frequency of first- and second-generation ASMs (5.4% to 2.1% and 34.9% to 12.6%, respectively). This trend was accompanied by a significant decrease in the use of enzyme-inducing ASMs, from 23.9% to 4.6% (p = 0.004). Among frequently prescribed ASMs, prescriptions of carbamazepine (18.6% to 3.1%, p = 0.004) and valproate (15.4% to 8.7%, p = 0.004) decreased, whereas prescriptions of levetiracetam (18.0% up to 32.4%, p = 0.004) increased significantly. The prescription frequency of lamotrigine remained largely constant at approximately 20% (p = 0.859). Among WOCBP, the prescription frequencies of carbamazepine (11.4% to 2.0%, p = 0.004) and valproate (16.1% to 6.1%, p = 0.004) decreased significantly. Levetiracetam monotherapy prescriptions increased significantly (6.6% to 30.4%, p = 0.004) for WOCBP, whereas lamotrigine prescriptions remained consistent (37.7% to 44.9%, p = 0.911). Among older adult patients, a significant decrease in carbamazepine prescriptions (30.1% to 7.8%, p = 0.025) was the only relevant change in ASM regimens between 2008 and 2020. In patients with genetic generalized epilepsies, levetiracetam was frequently used as an off-label monotherapy (25.0% to 35.3%).These results show a clear trend toward the use of newer and less interacting third-generation ASMs, with lamotrigine, levetiracetam, and lacosamide representing the current ASMs of choice, displacing valproate and carbamazepine over the last decade. In WOCBP, prescription patterns shifted to minimize teratogenic effects, whereas, among older adults, the decrease in carbamazepine use may reflect the avoidance of hyponatremia risks and attempts to reduce the interaction potential with other drugs and ASMs. Levetiracetam is frequently used off-label as a monotherapy in patients with genetic generalized epilepsy.

To analyze the concerns and worries about planning to have children and being a parent as a person with epilepsy and investigate gender differences in these perceptions.The Epi2020 study was a large multicenter study focusing on different healthcare aspects of adult patients with epilepsy in Germany. In addition to basic clinical and demographic characteristics, patients were asked to answer a questionnaire regarding their plan to have children, if they had children, and concerns about their children's health. Data were analyzed to detect differences between men and women with epilepsy according to age group.In total, 477 patients with epilepsy with a mean age of 40.5 years (SD = 15.5, range: 18-83 years) participated in this study; 280 (58.7%) were female and 197 (41.3%) were male. Both women and men frequently reported concerns and worries about having children: In the age group below 45 years of age, 72.5% of women and 58.2% of men described being worried to some extent that their children may also suffer from epilepsy (p = .006). Furthermore, 67.3% of women and 54.2% of men below the age of 45 years reported being worried that their children may be disabled (p = .003). Women were more likely to have family members who are reluctant to support their desire to have children (p = .048).Women with epilepsy of childbearing age are significantly more likely to report major concerns that their children might be disabled or also have epilepsy than men with epilepsy and, therefore, express more concerns about choosing to have a child. However, men also report frequent concerns and worries, and this should be addressed not only on request but should be included in the provision of general information on epilepsy.

Spinal and bulbar muscular atrophy (SBMA) is a progressive, X-linked lower motor neuron disorder exclusively affecting men. Since knowledge on sleep disorders in SBMA is scarce compared to other motoneuron diseases, this retrospective case-control study aimed to investigate sleep and sleep-related breathing in patients with SBMA.In 23 non-ventilated patients with SBMA (median age 52 years), clinical disease characteristics, forced vital capacity and diagnostic polysomnographies were retrospectively evaluated. In 16 patients, overnight transcutaneous capnometry was available. Twenty-three male control subjects with chronic insomnia were matched for age and body mass index.In patients with SBMA obstructive sleep apnoea (OSA, apnoea-hypopnoea index/AHI5/h) was more frequent than in control subjects (14/23 or 61% vs. 6/23 or 26%, p = 0.02), and median AHI was significantly higher in patients (9.0/h vs. 3.4/h, p0.01). Among SBMA patients, the AHI was not related to age or body mass index. Alveolar hypoventilation as reflected by nocturnal hypercapnia was found in 3/16 patients. Rapid eye movement (REM) sleep without atonia was present in 44% of SBMA patients but only in 4% of controls (p0.01). During REM and non-REM sleep, no behavioural abnormalities were observed in either group. Periodic limb movements in sleep (index15/h) were frequent in SBMA patients but rarely disrupted sleep.In patients with SBMA, sleep-disordered breathing may comprise both OSA and nocturnal hypoventilation. REM sleep without atonia may also be found, but its clinical significance remains unclear. In patients complaining of sleep-related symptoms, cardiorespiratory polysomnography and transcutaneous capnometry are recommended.

Sleep-related hypermotor epilepsy, or nocturnal frontal lobe epilepsy, as it was formerly called, is a focal epilepsy with mostly sleep-related seizures of hypermotor, tonic or dystonic semiology. Sleep-related hypermotor epilepsy may be attributed to a monogenetic cause with autosomal dominant inheritance. Mutations are described in different genes, including the genes for three subunits of the nicotinic acetylcholine receptor. We present a family with members over four generations exhibiting sleep-related hypermotor epilepsy. Genetic testing was available for three members from three generations, and revealed two variants in the alpha-4 subunit of the nicotinic acetylcholine receptor (one of them being novel) which are likely to be disease-causing. As these mutations were identified in cis configuration (on the same allele), we do not know whether one of the variants alone or a combination of the two is responsible for the pathogenicity.

Objective The objective of this study was to evaluate effectiveness, retention, and tolerability of brivaracetam (BRV) in genetic generalized epilepsies (GGE) in clinical practice. Methods A multicenter, retrospective cohort study recruiting all patients that started BRV in 2016 and 2017. Results A total of 61 patients (mean age = 29.8, range = 9-90 years, 41 female [67%]) were treated with BRV. They were difficult to control, with 2.4 failed antiepileptic drugs (AEDs) in the past, taking 1.9 AEDs on average at baseline. The length of exposure to BRV ranged from 7 days to 24 months, with a mean retention time of 7.9 months, resulting in a total exposure time to BRV of 483 months. The retention rate was 82% at 3 months and 69% at 6 months. Efficacy at 3 months was 36% (50% responder rate), with 25% seizure-free for 3 months. Patients with juvenile myoclonic epilepsy showed a responder rate of 60%, with 40% being free of any seizures. Long-term 50% responder rate was present in 17 patients (28%; 11 seizure-free [18%]) for >6 months and in 14 patients (23%; 10 seizure-free [16%]) for >12 months. Treatment-emergent adverse events were observed in 26% of the patients, with the most common being somnolence, ataxia, and psychobehavioral adverse events. Use of intravenous BRV with bolus injection of 200-300 mg in two females with absence status epilepticus was well tolerated, but did not result in cessation of status epilepticus. Significance Use of BRV in GGE is well tolerated, and 50% responder rates are similar to those observed in the regulatory trials for focal epilepsies. An immediate switch from levetiracetam (LEV) to BRV at a ratio of 15:1 is feasible. The occurrence of psychobehavioral adverse events seems less prominent than under LEV, and a switch to BRV can be considered in patients with LEV-induced adverse events.

ObjectivesBrivaracetam (BRV) is the latest approved antiepileptic drug and acts as a synaptic vesicle protein 2A ligand. The aim of the present study was to evaluate the efficacy and tolerability of BRV in the clinical setting.DesignRetrospective, observational multicentre study.SettingWe retrospectively collected clinical data of patients who received BRV in 10 epilepsy centres using a questionnaire that was answered by the reporting neurologist.ParticipantsData of 615 epilepsy patients treated with BRV were included in the study.Primary and secondary outcome measuresEfficacy regarding seizure frequency and tolerability of BRV were evaluated. Descriptive statistics complemented by X2 contingency tests and effect sizes were performed.ResultsOverall, 44% of the patients had a decreased, 38% a stable and 18% an increased seizure frequency. 17% of patients achieved seizure freedom after initiation of BRV. The seizure frequency decreased in 63% of 19 patients with BRV monotherapy. 27% reported adverse effects, but only 10% of patients with monotherapy. Brivaracetam was significantly more often associated with decreased seizure frequency in levetiracetam (LEV) naïve patients (p=0.012), but BRV also led to a decreased seizure frequency in 42% of patients who had been treated with LEV before, including 17% of patients who were completely seizure free. Adverse effects under LEV improved in 62% and deteriorated in 2% of patients after the switch to BRV. At latest follow-up (mean±SD = 26.3±6.5 months), 68% were still on BRV.ConclusionsThe present study shows that results of the phase III studies on BRV match data from real life clinical settings. Brivaracetam seems to be a useful alternative in patients who have suffered adverse effects while taking LEV.

Increasing evidence from neuroimaging studies points towards a hippocampal role in resolving approach-avoidance goal conflicts. Furthermore, previous neuroimaging findings suggest that the hippocampus (HC) contributes to successful conflict resolution as it is measured, for example, in a Stroop paradigm. However, it is still an open question whether the hippocampus is indeed causally relevant for resolving cognitive conflicts. Here, we investigated whether conflict resolution performance is affected by hippocampal pathology. N = 30 patients with mesial temporal lobe epilepsy (MTLE), almost exclusively showing MRI signs of hippocampal sclerosis, and an equal number of age-matched healthy controls performed an auditory Stroop paradigm. Participants listened to the words 'high' and 'low', spoken in either a high or a low pitch. Subjects' response time and accuracy to the phonetic information in the presence of incongruent (conflict trials) or congruent (non-conflict trials) semantic information were assessed. In addition, patients' regional grey matter (GM) brain volumes were analysed. We observed an increased effect of conflict on accuracy in patients with MTLE compared to healthy controls. This effect was negatively correlated with right HC volume. The results suggest that the impairment in the resolution of a response conflict is related to hippocampal structural integrity and thus add further support to the notion that the HC is not only involved but even causally relevant for successful cognitive conflict processing.

Recent evidence suggests that the human hippocampus (HC) is not only involved in the processing of motivationally relevant approach-avoidance conflicts but is also engaged in the resolution of more general response conflicts as measured in the Stroop paradigm. Here we investigated whether neural activity in the HC is necessary for successful response conflict resolution. We compared hippocampal recruitment during an auditory Stroop paradigm in 20 patients with mesial temporal lobe epilepsy (MTLE) due to hippocampal sclerosis and 20 age-matched healthy controls using functional magnetic resonance imaging (fMRI). We analyzed hippocampal activation and behavioral performance in conflict trials relative to non-conflict trials. Moreover, functional connectivity (FC) analyses with left and right HCs as seeds were performed. Subjects’ regional gray matter volumes were analyzed based on high-resolution T2-weighted MRI scans. The current study replicated previous results showing increased activation in left HC during the processing of conflict trials in healthy subjects. By contrast, MTLE patients showed higher behavioral costs of response conflict resolution and reduced conflict-related HC activation. In patients with left MTLE, left HC activation was predictive of faster conflict-related response times (RTs). By contrast, right HC activation was related to RT slowing, suggestive of a maladaptive compensation attempt in MTLE patients. Our results provide evidence that left hippocampal activation is required for the successful resolution of response conflicts.