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Treatment with enzyme-inducing antiepileptic drugs (AEDs) such as carbamazepine (CBZ) can lead to changes in reproductive, endocrine, and lipid parameters, resulting in clinical symptoms for some patients. Previous studies indicate that these changes can be reversed by switching to a nonenzyme-inducing AED. Lacosamide is a newer-generation AED, not known to induce or strongly inhibit cytochrome P450 (CYP450) enzymes. In this phase IIIb, prospective, multicenter, open-label, single-arm trial ( NCT01375374 ), the serum concentrations of CYP-related reproductive hormones, thyroid hormones, and lipids were assessed in otherwise healthy male patients with focal seizures (N = 11), before and after a switch from CBZ (600–1200 mg/day at baseline) to lacosamide (target dose: 400 mg/day by the end of titration) as adjunctive treatment to the nonenzyme-inducing AED levetiracetam (LEV, stable dosage of > 1000 mg/day throughout). Cross titration took place over 4 weeks, followed by an 8-week maintenance period. Serum measurements were conducted at baseline and at the end of maintenance. The median serum sex-hormone-binding globulin (SHBG) concentration was towards the higher end of the normal range at baseline and decreased following the switch (61.7 to 47.5 nmol/L, N = 10, p = 0.027 by Wilcoxon signed-rank test). Free androgen index (100 × testosterone/SHBG) and free thyroxine serum concentration increased (25.4 to 36.4 and 13.0 to 14.9 pmol/L, respectively, both N = 10 and p = 0.002). At baseline, the median progesterone serum concentration was below the normal range (0.7 nmol/L), whereas median cholesterol and low-density lipoprotein concentrations were above the normal range (5.5 and 3.6 mmol/L, respectively). By the end of maintenance, all measured parameters were within the normal range. The safety and tolerability profile of lacosamide was consistent with that observed in previous studies. Furthermore, antiseizure efficacy appeared to be maintained, suggesting that deinduction of CYP enzymes following a switch from CBZ to lacosamide as adjunctive therapy to LEV is feasible within 8 weeks and is associated with normalization of serum parameters. [ABSTRACT FROM AUTHOR]

Abstract: Gray matter heterotopia are a common cause of pharmacoresistant epilepsy. Recently, several case studies have addressed the question of whether heterotopia can contribute to physiological cerebral functions. We describe two cases that demonstrate a functional role for periventricular heterotopia in higher cognitive processes. During presurgical diagnostics, two patients underwent electric stimulation of both the periventricular heterotopia and the overlying cortex. This revealed a functional role of periventricular heterotopia in higher cerebral functions such as language and complex visual and acoustic processing. Furthermore, stimulation of the overlying cortex led to unusually intense positive phenomena, including complex acoustic and gustatory hallucinations and language production. These cases illustrate that periventricular heterotopic neurons can contribute to higher cerebral functions. Interestingly, the anterior-to-posterior representation of these functions is comparable to the normal anterior-to-posterior representation in a normal neocortex (similar to a periventricular “minicortex” in early developmental stages). [Copyright &y& Elsevier]

Abstract: The epilepsies are among the most common serious brain disorders, can occur at all ages, and are characterized by a variety of presentations and causes. Diagnosis of epilepsy remains clinical, and neurophysiological investigations support the diagnosis of the syndrome. Brain imaging is able to identify many of the structural causes of the epilepsies. Current antiepileptic drugs (AEDs) block seizures without influencing the underlying tendency to generate seizures, and are effective in 60–70% of individuals. Several modern drugs are as efficacious as the older medications, but have important advantages including the absence of adverse drug interactions and hypersensitivity reactions. Epilepsy is associated with an increased prevalence of mental health disorders including anxiety, depression, and suicidal thoughts. An understanding of the psychiatric correlates of epilepsy is important to the adequate management of people with epilepsy. Anticipation of common errors in the diagnosis and management of epilepsy is important. Frequent early diagnostic errors include nonepileptic psychogenic seizures, syncope with myoclonus, restless legs syndrome, and REM behavioral disorders, the last mostly in elderly men. Overtreatment with too rapid titration and too high doses or too many AEDs should be avoided. For people with refractory focal epilepsy, vagus nerve stimulation offers palliative treatment with possible mood improvement and neurosurgical resection offers the possibility of a life-changing cure. Potential advances in the management of epilepsy are briefly discussed. This short review summarizes the authors’ how-to-do approach to the modern management of people with epilepsy. [Copyright &y& Elsevier]

Abstract: Flexibly adapting behavior in dynamic environments relies on fronto-limbic networks that include the amygdala, orbitofrontal cortex, and striatum. Animal work demonstrates that interactions among these regions are critical for flexible feedback-guided learning, but it remains unknown to what extent such anatomical–functional interactions operate in humans. Here, we use connectivity analyses in both structural and functional MRI to further our understanding of how brain circuits work in conjunction to promote goal-directed behavior. In particular, fiber tracking based on diffusion-weighted imaging provides information about anatomical connectivity between brain structures, and functional MRI provides estimates of functional connectivity between structures. We found that, during a feedback-guided reversal learning task, the strength of estimated white matter tracts from the amygdala to the hippocampus, orbitofrontal cortex, and ventral striatum predicted both how subjects adapted their behavior following positive and negative feedback, and the functional connectivity (estimated from functional MRI time series) between the amygdala and these regions. In addition, we identified a dissociation between an amygdala-hippocampus circuit that predicted response switching, and an amygdala-orbitofrontal cortex circuit that predicted learning following rule reversals. These findings provide novel insights into how the anatomy and functioning of amygdala-related brain circuits mediate different aspects of feedback-guided learning behavior. [Copyright &y& Elsevier]

Abstract: Limbic encephalitis (LE) was described in the 1960s as a clinical–pathological syndrome in adults. Initially, the paraneoplastic form was the center of interest. An increasing number of diagnostically valuable autoantibodies in patients’ sera (and cerebrospinal fluid) have been identified. Lately, the impact of non-paraneoplastic LE cases has been acknowledged. In the serum of some of these patients, antibodies against voltage-dependent potassium channels (VGKC antibodies) have been detected. The characteristic MRI course of LE patients has recently been described in detail: hippocampal swelling and T2/FLAIR signal increase are early findings. After a few months, the swelling regresses, followed by hippocampal atrophy with continuous signal increase. A general consensus on formal diagnostic criteria for all LE subsyndromes has not yet been reached. This article proposes such diagnostic criteria and formulates suggestions for treatment. [Copyright &y& Elsevier]

Abstract: The ability to evaluate outcomes of previous decisions is critical to adaptive decision-making. The feedback-related negativity (FRN) is an event-related potential (ERP) modulation that distinguishes losses from wins, but little is known about the effects of outcome probability on these ERP responses. Further, little is known about the frequency characteristics of feedback processing, for example, event-related oscillations and phase synchronizations. Here, we report an EEG experiment designed to address these issues. Subjects engaged in a probabilistic reinforcement learning task in which we manipulated, across blocks, the probability of winning and losing to each of two possible decision options. Behaviorally, all subjects quickly adapted their decision-making to maximize rewards. ERP analyses revealed that the probability of reward modulated neural responses to wins, but not to losses. This was seen both across blocks as well as within blocks, as learning progressed. Frequency decomposition via complex wavelets revealed that EEG responses to losses, compared to wins, were associated with enhanced power and phase coherence in the theta frequency band. As in the ERP analyses, power and phase coherence values following wins but not losses were modulated by reward probability. Some findings between ERP and frequency analyses diverged, suggesting that these analytic approaches provide complementary insights into neural processing. These findings suggest that the neural mechanisms of feedback processing may differ between wins and losses. [Copyright &y& Elsevier]

Oxcarbazepine (OXC, Trileptal) is a modern antiepileptic drug (AED) used as both monotherapy and adjunctive therapy for the treatment of partial seizures with or without secondary generalization in adults and children above 4 years (USA) or 6 years (Europe) of age. Although OXC has been developed through structural variation of carbamazepine (CBZ) with the intent to avoid metabolites causing side effects, significant differences have emerged between the two drugs. The mechanism of action of OXC involves mainly blockade of sodium currents but differs from CBZ by modulating different types of calcium channels. In contrast to CBZ, which is oxidized by the cytochrome P-450 system, OXC undergoes reductive metabolism at its keto moiety to form the monohydroxy derivative (MHD), which is glucuronidated and excreted in the urine. The involvement of the hepatic cytochrome P-450-dependent enzymes in the metabolism of OXC is minimal. Although it does not prevent interaction with oral contraceptives, it explains why OXC can be more effectively combined with other AEDs such as valproate compared with CBZ. Switching from CBZ to OXC normalized CBZ-associated thyroid and sexual hormone abnormalities and pathological lipid values in small patient samples. OXC is often better tolerated than CBZ and causes fewer rashes than CBZ. Add-on or substitution treatment with OXC was effective in controlled trials even when CBZ did not achieve sufficient seizure control. This constitutes compelling clinical evidence that OXC and CBZ are distinctly different medications. From postmarketing experience in over 1,000,000 patient years, OXC had an advantageous risk–benefit balance also in comparison to other new AEDs. OXC should be preferred over CBZ and other older AEDs because of its proven efficacy and excellent side effect profile in children, adolescents, and adults with partial seizures. [Copyright &y& Elsevier]

This retrospective study was conducted to identify cognitive domains affected by topiramate (TPM), and to evaluate the role of blood serum levels of TPM and comedication in the etiology of TPM-induced cognitive impairment.Forty-two patients on AED polytherapy containing topiramate and a random sample of 42 patients with lamotrigine as the corresponding agent underwent extensive neuropsychological testing. Current blood serum levels of TPM were correlated with test scores.Patients on TPM scored significantly worse in phonematic verbal fluency, memory spans, and working memory; language and memory function were not affected per se. In few cognitive domains, serum levels of TPM and performance were correlated before correction for multiple testing. Drug load of additional medication did not account for differences between or within groups.Consistent with previous reports, patients on AED polytherapy including TPM display a cognitive pattern with specific impairment in executive functions. The severity of the cognitive side effects of TPM may be related to dosing to a certain extent, but this relationship may be disclosed only with larger sample sizes. Accordingly, TPM dosage does not appear to be a good indicator of TPM-related cognitive side effects in the individual patient. [Copyright &y& Elsevier]

The population incidence of psychogenic nonepileptic seizures (PNES) may be only 4% that of epilepsy, but many patients with PNES have a tendency to seek medical attention, and PNES make up a larger share of the workload of neurologists and emergency and general physicians. Although a great number of publications describe how PNES can be distinguished from epileptic seizures, it usually takes several years to arrive at this diagnosis, and three-quarters of patients (with no additional epilepsy) are treated with anticonvulsants initially. However, the management of PNES as epileptic seizures can lead to significant iatrogenic harm. Moreover, the failure to recognize the psychological cause of the disorder detracts from addressing associated psychopathology and enhances secondary somatization processes. This review provides an overview of studies of the diagnosis, etiology, treatment, and prognosis of PNES. Physicians should always consider PNES in the differential diagnosis of a seizure disorder. If a diagnosis of PNES is possible, or a diagnosis of epilepsy in doubt, a clear diagnostic categorization should be sought. This should involve the assessment of the patient by a physician versed in the diagnosis of seizure disorders and, in many cases, the documentation of a typical seizure by video-EEG. Outcome may be improved if the diagnosis is more actively sought, made earlier, and communicated more convincingly. [Copyright &y& Elsevier]

Abstract: There is ample evidence that side effects of antiepileptic pharmacotherapy negatively affect quality of life, adherence, and long-term retention. The study was set up to evaluate the anticipated tolerance of common side effects provided that a 50% or 100% reduction of seizure frequency would be achieved. An anonymous inquiry in 79 consecutive patients with epilepsy comprised questions regarding the severity of epilepsy/seizures and the perceived impact of seizures and drug treatment on daily functioning and a 10-tiered rating which assesses 11 common behavioral/psychiatric, cognitive, physiological, or physical side effects according to the degree to which they would be tolerated. Least acceptance was evident for psychiatric side effects followed by cognitive, physiological, and physical side effects. Weight gain and tiredness were the most tolerated side effects. The overall low acceptance of negative side effects was slightly higher in the case of a 100% vs. 50% seizure frequency reduction (28% vs. 21% of the maximum toleration score regarding all side effects). Surely, there is a trade-off between the severity of epilepsy, seizure control, and the acceptance of adverse treatment effects. However, the data disclose that psychiatric and cognitive side effects are least accepted. Thus, consideration of individual tolerance and monitoring of side effects in addition to seizures may increase adherence and therapy success. [Copyright &y& Elsevier]

Abstract: Analysis of ictal semiology is essential to presurgical evaluation of patients with epilepsy. To assess the localizing value of behavioral arrest in temporal lobe epilepsy (TLE), we analyzed 107 video/EEG monitoring-documented seizures of 107 adult patients with TLE for a set of defined seizure phenomena with respect to frequency and sequence of occurrence in relation to epileptogenic (mesial vs extramesial, left vs right) origin. Behavioral arrest was observed more frequently in left-sided temporal seizures: 25.7% of left-sided mesial seizures and 25.0% of left-sided extramesial seizures exhibited behavioral arrest, whereas only 3.4% of right-sided mesial seizures and 10.5% of right-sided extramesial seizures were associated with behavioral arrest. In addition, occurence of behavioral arrest within the sequence of seizure phenomena was remarkably consistent, being observed mainly as the first apparent feature of seizure onset. Thus, behavioral arrest is a valuable early indicator of a left-sided temporal epileptogenic focus in adult patients with TLE. [Copyright &y& Elsevier]

Objectives Postictal generalized EEG suppression (PGES) frequently occurs after generalized convulsive seizures (GCS) and may be involved in the pathophysiology of sudden unexpected death in epilepsy (SUDEP). It is usually determined using conventional scalp EEG which is likely to miss cerebral activity in deeper brain structures. Here, we examined intracranial EEG activity after GCS to unravel the pattern and extent of local brain activity during apparent PGES on scalp EEG (s-PGES). Methods We retrospectively reviewed electroencephalographic data of people with chronic epilepsy who had GCS during presurgical video-EEG monitoring using simultaneous intracranial and scalp EEG (10–20 system) electrodes. Results Twenty-five GCS (20 with s-PGES) of 15 patients with an average number of 88 ± 42 intracranial electrode contacts were included. The majority of GCS with s-PGES (18 of 20) displayed persisting or reemerging intracranial EEG activity during apparent PGES on scalp EEG. Three patterns were identified: Pattern 1 (11 GCS, 6 patients) consisted of continuous local interictal activity; Pattern 2 (5 GCS, 5 patients) displayed suppressed EEG activity at all intracranial contacts in the early phase of s-PGES, but reemerging local brain activity before s-PGES dissolved; and Pattern 3 (2 GCS, 2 patients) showed persistent local ictal activity during s-PGES. Persisting intracranial EEG activity at PGES onset on scalp EEG was present in 10 ± 14% (range: 0 to 42%) of all intracranial contacts and mostly in the temporal lobe. Conclusions Our results reveal that, during apparently generalized postictal EEG suppression, local brain activity persists or reemerges in most GCS. Possible implications of this localized neuronal activity in the context of SUDEP are discussed in the paper. [ABSTRACT FROM AUTHOR]

Abstract: The function of sensory gating is usually studied in paired-click experiments and quantified by the decrease of the event-related potential (ERP) component P50 and other ERP components from the 1st to the 2nd stimuli. The impact of attention on these gating measures is still not fully resolved. In the current study, the impact of attention on sensory gating was studied by scalp and intracranial recordings. The study sample consisted of epilepsy and tumor patients undergoing presurgical evaluation by means of implanted electrodes. In the unattend condition, patients had no overt task. In the active condition, patients had to count simultaneously trials with paired clicks, as well as interspersed trials with single clicks. The ERPs in the active condition were characterized by an underlying negativity both for scalp and neocortical recordings, reaching their maximum at the N100 latency of the 2nd stimulus. A time–frequency analysis revealed that this attention effect comprised only low frequency signals (<3 Hz). In line with that, P50 amplitude and P50 gating were unaffected by attention when data were filtered from 10 to 50 Hz. In addition, attention effects were revealed for intrahippocampal ERP components and for induced high frequency neocortical gamma band activity. Findings indicate that N100 and P200 gating measures can potentially be affected by attention and have to be interpreted carefully when studying clinical populations. [Copyright &y& Elsevier]

Abstract: Mitochondrial dysfunction has been identified as a potential cause of epileptic seizures and therapy-resistant forms of severe epilepsy. Thus, a broad variety of mutation in mitochondrial DNA or nuclear genes leading to the impairment of mitochondrial respiratory chain or of mitochondrial ATP synthesis has been associated with epileptic phenotypes. Additionally, with a variety of different methods impaired mitochondrial function has been reported for the seizure focus of patients with temporal lobe epilepsy and Ammon''s horn sclerosis and of animal models of temporal lobe epilepsy. Since mitochondrial oxidative phosphorylation provides the major source of ATP in neurons and mitochondria participate in cellular Ca2+ homeostasis, their dysfunction strongly affects neuronal excitability and synaptic transmission, which is proposed to be highly relevant for seizure generation. Additionally, mitochondrial dysfunction is known to trigger neuronal cell death, which is a prominent feature of therapy-resistant temporal lobe epilepsy. Therefore, mitochondria have to be considered as promising targets for neuroprotective strategies in epilepsy. [Copyright &y& Elsevier]

Abstract: The medial temporal lobes (MTLs) are essential for both encoding and retrieval processes in declarative memory. In addition, they are a frequent seizure focus for medically refractory epilepsy. One of the major side effects of MTL resection is a decline in memory functions. Most functional imaging paradigms have been developed to find preoperative measures that, to obtain a prognosis of postoperative memory performance, employ explicit memory encoding strategies to elicit MTL activation, and require a great amount of cognitive effort. We applied three different implicit encoding tasks, which require less effort and time, to a group of healthy subjects. We found left-lateralized activation for verbal stimuli, bilateral activation for pictures, and right-lateralized activation for faces. The present study shows that even with an implicit memory-encoding paradigm, a lateralized activation of MTL structures can be achieved. This may lead to paradigms for routine clinical application that require less cognitive effort and time on the part of patients. [Copyright &y& Elsevier]

Right temporal lobe structures are involved in face and facial expression processing and in mnestic functions. Face and facial expression memory was investigated in 15 patients with left (LTLE) and 18 patients with right (RTLE) temporal lobe epilepsy as well as 13 healthy controls. Pairs of pictures combining four faces and four emotions had to be matched according to face identity or facial expression. In the memory tasks, the two pictures of a pair were divided by a memory interval of 2000 milliseconds, whereas in the perception tasks (control condition) both pictures were presented simultaneously. RTLE patients had significantly lower scores than healthy controls in face memory. LTLE patients had significantly lower scores than healthy controls in face and facial expression memory. The data confirm impaired face memory in RTLE patients and show that LTLE patients display deficits in face as well as in facial expression memory. Results are discussed according to functional reorganization, memory strategies, perception performance, naming problems, and group characteristics. [Copyright &y& Elsevier]

The attentional blink (AB) is an impairment of attention, which occurs when subjects have to report a target stimulus (T2) following a previous target (T1) with a short delay (up to 600 ms). Theories explaining the AB assume that processing of T2 is more vulnerable to decay or substitution, as long as attention is allocated to T1. Existing models of the AB, however, do not account for the fact that T2 detection accuracy reaches the minimum when T2 is presented after about 300 ms and not immediately following T1. Therefore, a new model is suggested, which is based on chronometrical considerations together with recent neurophysiological findings concerning the relation between the P3 event-related potential and the AB, the interaction between P3 and gamma oscillations, and the significance of the early evoked gamma band response. We hypothesize that suppression of the early gamma response to T2, accompanying the P3 related to T1, causes the AB. [Copyright &y& Elsevier]

Abstract Objective Paraneoplastic limbic encephalitis (LE) occurs frequently with considerable variability according to literature reports. We thus determined the cancer frequency in mixed LE subtypes sharing the diagnosis of temporal lobe epilepsy (TLE). Methods All patients underwent magnetic resonance imaging (MRI) of the brain, electroencephalography (EEG) recordings, neuropsychological testing, immunohistochemistry, and clinical examination together with whole body 2-fluor-2-desoxy- d -glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) to detect cancer in this observatory study. Results Ninety-three patients (median: 52 years) with TLE due to autoimmune LE were investigated. Cancer was detected in the FDG-PET/CTs of 3 out of 93 (3.2%) patients with LE. Cancer was diagnosed upon, 5 years earlier and 5 years after FDG-PET/CT in 7 of 93 (7.5%) of all patients with LE. The cancer frequency in those patients was significantly lower than that reported in the largest series of patients with LE associated with and without different antibodies (7.5% vs. 23.5%, Bootstrap test, p < 0.05), but was indistinguishable from the estimated age-dependent cancer frequency in the German regional North-Rhine-Westfalian population without LE in 2014 (Chi-square test: p = 0.2). Conclusions Our findings reveal that the cancer frequency in patients with TLE with LE detected by FDG-PET/CT is low and not different from the age-dependent natural cancer occurrence in a regional population. Highlights • Cancer frequency in limbic encephalitis detected via FDG-PET/CT is low. • Low cancer frequency evidenced when compared to a large limbic encephalitis cohort. • Cancer in pooled limbic encephalitis subtypes occurs as in a regional population. [ABSTRACT FROM AUTHOR]

Abstract Objective The objective of the study was to evaluate cognitive and epilepsy-related features in 166 surgically treated patients with epilepsy with long-term epilepsy-associated tumors (LEATs) located in the temporal lobe. Method Pre- and postsurgical cognitive as well as the one-year seizure outcome of adult patients with histopathologically confirmed LEATs (28 grade-I dysembryoplastic neuroepithelial tumors (DNET), 95 grade-I gangliogliomas (GG), 24 grade-I pilocytic astrocytomas (PA), 9 grade-II pleomorphic xanthoastrocytoma (PXA), 10 grade-II diffuse astrocytoma (DA)) who underwent epilepsy surgery in Bonn/Germany between 1988 and 2012 were evaluated. Results At baseline, tumor groups differed in regard to age at epilepsy onset and location within the temporal lobe. Postoperative seizure freedom was achieved most frequently (> 77.8%) in DNET, GG, and DA, less often in PXA (62.5%) and the least in PA (56.5%). Preoperative memory was impaired in 67.1% of all patients, executive functions in 44.7%, and language in 45.5%. Patients with PA displayed the poorest cognitive performance. Individual significant memory decline that was observed in 27.1% of all patients was predicted by left-sided surgery, a mesial pathology, and extended hippocampal resection. Executive functions depended on antiepileptic drug (AED) load and remained stable (72.0%) or even improved (21.6%) after surgery. Language functions were unchanged in 89.5% of patients. Conclusion Patients with LEATs in the temporal lobe frequently show cognitive impairments. Predictors for pre- and postoperative cognition mostly correspond to what is known for temporal lobe epilepsy and resections in general. However, different tumor types appear to be associated with different cognitive and seizure outcomes with astrocytoma as the least benefitted group. Highlights • Resective surgery in long-term epilepsy associated tumors lead to an overall rate of 78% seizure free patients • The cognitive outcomes mostly mirror what is described for temporal lobe epilepsy and surgery in general • Higher baseline performance, left side, mesial location and hippocampal resection relate to postsurgical memory decline • DNT and GG showed the best cognitive and seizure outcome as compared to astrocytoma and particularly PA [ABSTRACT FROM AUTHOR]

Background There is evidence that the sudden unexpected death in epilepsy (SUDEP) risk can be reduced by good seizure control, nocturnal supervision, and by early cardiopulmonary resuscitation if cardiorespiratory arrest occurs in the aftermaths of generalized tonic–clonic seizures (GTCS). These measures, however, may critically depend on the knowledge of patients and relatives on SUDEP. Here, we assessed the basic knowledge on SUDEP of people with epilepsy at a tertiary epilepsy center in Germany. Methods Adult patients with epilepsy and relatives or caregivers of patients with epilepsy aged 16 years or older attending our outpatient clinic from January to March 2014 were given the opportunity to participate in a (assisted or unassisted) written survey. In the anonymized questionnaire, people were asked if they had already heard about SUDEP, by what means and if they wish to learn (more) about SUDEP. Furthermore, age, sex, epilepsy duration, highest degree of education, number of GTCS during the last year, and estimation of subjective impairment by their disease were assessed. Statistics were done using mixed linear or logistic regression models. Results A total of 372 patients' questionnaires were included in this survey. More than 87% of the participants had never heard of SUDEP before. Whereas about 50% of the participants wanted to learn more about SUDEP, about 40% did not. Only the age at survey was significantly associated with both being informed and the desire of learning more about SUDEP: Younger patients had more often heard (p = 0.022) and wanted to know more about SUDEP (p = 0.020). Thirty-nine patients were considered at high risk for SUDEP. Of these, only 6 patients (15%) knew about SUDEP prior to this survey, but 18 patients (46%) wanted to learn more about this fatal complication. Conclusion Our data suggest that the level of information on SUDEP among people with epilepsy is poor in Germany regardless of sex, school education, or epilepsy severity. Additionally, a considerable proportion of people with epilepsy seems to prefer not getting detailed information on SUDEP. More efforts are required to understand the potential barriers of the education of patients and relatives on sudden death with the ultimate goal of decreasing the risk of SUDEP. [ABSTRACT FROM AUTHOR]

Objective Limbic encephalitis (LE) is defined by mesiotemporal lobe structure abnormalities, seizures, memory, and psychiatric disturbances. This study aimed to identify the long-term clinical and neuropsychological outcome of selective amygdalohippocampectomy (sAH) in drug-resistant patients with temporal lobe epilepsy due to known or later diagnosed subacute LE not responding to immunotherapy associated with neuronal autoantibodies. Methods In seven patients with temporal lobe epilepsy due to antibody positive LE (glutamic acid decarboxylase (GAD65): n = 5; voltage-gated potassium channel complex (VGKC), N -methyl d -aspartate receptor (NMDAR): n = 1; Ma-2/Ta: n = 1) sAH (6 left, 1 right) was performed. Those patients underwent repeated electroencephalography (EEG) recordings, magnetic resonance imaging (MRI) volumetry of the amygdala and hippocampus, and neuropsychological examinations and were followed up for 6–7 years on average. Results Verbal memory and figural memory were affected in 57% of patients at baseline and 71% at the last follow-up. At the last follow-up, 14% of the patients had declined in verbal memory and figural memory. We observed improved memory in 43% of patients regarding figural memory, but not in a single patient regarding verbal memory. Repeated evaluations across the individual courses reveal cognitive and MRI dynamics that appear to be unrelated to surgery and drug treatment. Three of the seven patients with LE with different antibodies (NMDAR: n = 1, Ma-2/Ta: n = 1 and GAD65: n = 1) achieved persistent seizure freedom along with no accelerated memory decline after surgery. Two of the five GAD65-antibody patients positive with LE showed progressive memory decline and a long-term tendency to contralateral hippocampus atrophy. Conclusions While memory demonstrated some decline in the long run, what is most important is that a progressive decline in memory is seldom found after sAH in patients with LE. Moreover, the dynamics in performance and MRI before and after surgery reveal disease dynamics independent of surgery. Selective amygdalohippocampectomy can lead to seizure freedom, but should be considered as a last resort treatment option for drug-resistant patients with temporal lobe epilepsy due to LE. Particular caution is recommended in patients with GAD65-LE. [ABSTRACT FROM AUTHOR]

Objective To assess the safety and efficacy of once-daily (QD) adjunctive eslicarbazepine acetate (ESL). Methods This post-hoc pooled analysis of three randomized, placebo-controlled trials (2093-301, -302, -304) involved adults with refractory partial-onset seizures (POS) receiving 1–3 antiepileptic drugs (AEDs). All studies included 8-week baseline, 2-week titration, and 12-week maintenance periods. Patients were randomized equally to placebo, ESL 400 mg (studies 301, 302), 800 mg, or 1200 mg QD. The primary endpoint was standardized seizure frequency (SSF; per 4 weeks); secondary endpoints included responder rates (maintenance period), and incidence of treatment-emergent adverse events (TEAEs), TEAEs leading to discontinuation, serious AEs (SAEs), and deaths. Results The safety and efficacy analysis populations totaled 1447 and 1410 patients, respectively. SSF was significantly reduced versus placebo with ESL 800 mg (p = 0.0001) and 1200 mg (p < 0.0001) but not 400 mg (p = 0.81). There were no significant interactions between treatment effect and age, gender, race/ethnicity, geographic region, epilepsy duration, or concomitant AED use. Incidences of TEAEs and TEAEs leading to discontinuation increased with ESL dose. Incidences of the most frequent TEAEs were lower for patients who initiated dosing at 400 versus 800 mg QD, regardless of titration regimen and maintenance dose. SAE incidence was < 10%; there were 3 deaths (placebo, n = 2; ESL 800 mg, n = 1). Conclusions ESL (800 and 1200 mg QD) was effective and well tolerated as adjunctive therapy for adults with refractory POS. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are key regulators of gene expression and are involved in the pathomechanisms of epilepsy. MiRNAs may also serve as peripheral biomarkers of epilepsy. We investigated the miRNA profile in the blood serum of patients suffering from mesial temporal lobe epilepsy (mTLE) following a single focal seizure evolving to a bilateral convulsive seizure (BCS) during video-EEG monitoring. Data of 15 patients were included in the final analysis. MiRNA expression was determined using Real Time-PCR followed by thorough bioinformatical analysis of expression levels. We found that more than 200 miRNAs were differentially expressed in the serum of patients within 30 min after a single seizure. Validation of the 20 top miRNA candidates confirmed that 4 miRNAs (miR-143, miR-145, miR-532, miR-365a) were significantly deregulated. Interestingly, in a sub-group of patients with seizures occurring during sleep, we found 10 miRNAs to be deregulated up to 20–28 h after the seizure. In this group of patients, miR-663b was significantly deregulated. We conclude that single seizures are associated with detectable transient miRNA alterations in blood serum in the early postictal phase. The significant upregulation of miR-663b following BCS arising during sleep indicates potential suitability of this miRNA as a potential biomarker for seizure diagnostics. [ABSTRACT FROM AUTHOR]

Objectives Patient-reported seizure frequency is essential for therapy management and clinical research but lacks validity mainly due to seizure-induced seizure unawareness. Automated seizure detection by mobile monitoring devices promises to settle this serious methodological issue. Here, we explored attitudes and preferences towards future devices for seizure detection in adult patients with therapy-refractory epilepsies. Methods A total of 102 inpatients enrolled and underwent a newly constructed semistructured 30-minute interview on automated seizure registration. Results Most patients would generally apply and permanently use seizure registration devices. Removable devices were preferred (e.g., wristband sensors), but also patch electrodes at invisible body sites appeared acceptable. Only a minority of patients would accept implantations for seizure registration (especially of depth electrodes). Also, permanent optical or acoustical surveillance were accepted by a few patients only. Most patients were ready to care for the device (e.g., charging battery), to have doctor's appointments for device control, and even to pay for the device. Seizure prediction was evaluated as an essential additional function. Only half of the patients wanted emergency calls in case of a seizure. Significance Patients would accept automated seizure registration if the device had as little as possible negative effect on daily living. High acceptance might, therefore, be expected for hardware equipment as it is nowadays used by many healthy subjects for physiological self-monitoring and life-logging. The proper medical engineering task of the future, therefore, is to optimize sensors in those highly feasible devices and to establish reliable biomarkers and outcome measures for a diversity of diseases (including epilepsy) from data obtained by this generic hardware. [ABSTRACT FROM AUTHOR]

In daily life, responses are often facilitated by anticipatory imagery of expected targets which are announced by associated stimuli from different sensory modalities. Silent music reading represents an intriguing case of visuotonal modality transfer in working memory as it induces highly defined auditory imagery on the basis of presented visuospatial information (i.e. musical notes). Using functional MRI and a delayed sequence matching-to-sample paradigm, we compared brain activations during retention intervals (10 s) of visual (VV) or tonal (TT) unimodal maintenance versus visuospatial-to-tonal modality transfer (VT) tasks. Visual or tonal sequences were comprised of six elements, white squares or tones, which were low, middle, or high regarding vertical screen position or pitch, respectively (presentation duration: 1.5 s). For the cross-modal condition (VT, session 3), the visuospatial elements from condition VV (session 1) were re-defined as low, middle or high “notes” indicating low, middle or high tones from condition TT (session 2), respectively, and subjects had to match tonal sequences (probe) to previously presented note sequences. Tasks alternately had low or high cognitive load. To evaluate possible effects of music reading expertise, 15 singers and 15 non-musicians were included. Scanner task performance was excellent in both groups. Despite identity of applied visuospatial stimuli, visuotonal modality transfer versus visual maintenance (VT > VV) induced “inhibition” of visual brain areas and activation of primary and higher auditory brain areas which exceeded auditory activation elicited by tonal stimulation (VT > TT). This transfer-related visual-to-auditory activation shift occurred in both groups but was more pronounced in experts. Frontoparietal areas were activated by higher cognitive load but not by modality transfer. The auditory brain showed a potential to anticipate expected auditory target stimuli on the basis of non-auditory information and sensory brain activation rather mirrored expectation than stimulation. Silent music reading probably relies on these basic neurocognitive mechanisms. [ABSTRACT FROM AUTHOR]

[Display omitted] • Eigenvalues of the Laplace–Beltrami operator on 3D mesh = Shape ("BrainPrint"). • Shape is complementary to volume in limbic encephalitis classification. • In lesional temporal lobe epilepsy shape is redundant to volume. • Shape explains memory performance in limbic encephalitis. Shape-based markers have entered the field of morphometric neuroimaging analysis as a second mainstay alongside conventional volumetric approaches. We aimed to assess the added value of shape description for the analysis of lesional and autoimmune temporal lobe epilepsy (TLE) focusing on hippocampus and amygdala. We retrospectively investigated MRI and clinical data from 65 patients with lesional TLE (hippocampal sclerosis (HS) and astrogliosis) and from 62 patients with limbic encephalitis (LE) with serologically proven autoantibodies. Surface reconstruction and volumetric segmentation were performed with FreeSurfer. For the shape analysis, we used BrainPrint , a tool that utilizes eigenvalues of the Laplace–Beltrami operator on triangular meshes to calculate intra-subject asymmetry. Psychometric tests of memory performance were ascertained, to evaluate clinical relevance of the shape descriptor. The potential benefit of shape in addition to volumetric information for classification was assessed by five-fold repeated cross validation and logistic regression. For the LE group, the best performing classification model consisted of a combination of volume and shape asymmetry (mean AUC = 0.728), the logistic regression model was significantly improved considering both modalities instead of just volume asymmetry. For lesional TLE, the best model only considered volumetric information (mean AUC = 0.867). Shape asymmetry of the hippocampus was largely associated with verbal memory performance only in LE patients (OR = 1.07, p = 0.02). For lesional TLE, shape description is robust, but redundant when compared to volumetric approaches. For LE, in contrast, shape asymmetry as a complementary modality significantly improves the detection of subtle morphometric changes and is further associated with memory performance, which underscores the clinical relevance of shape asymmetry as a novel imaging biomarker. [ABSTRACT FROM AUTHOR]

Abstract: This study characterizes the spatial–temporal distribution of epileptic activity in mesial and neocortical temporal lobe epilepsy (TLE) assessed by subdural and depth electrodes during sleep. We determined in 13 patients the frequency, lateralization, and localization of interictal epileptic discharges (IEDs). As compared to the waking state, IEDs increased in light sleep (196%, p<0.05) and in deep sleep (601%, p<0.05) but did not change significantly in REM sleep (−8.33%, p=0.94). From 11 patients with unilateral TLE, in all cases, IEDs lateralized to the seizure onset side during REM sleep and the waking state. In mesial TLE, IEDs tended to shift in an anterior–posterior axis and remained always localized in the amygdalo–hippocampal complex. By contrast, in neocortical TLE, the maximal activity moved in a mesial–lateral axis between neocortical and mesial structures. Twenty-six seizures were registered in 7 patients, 22 of which occurred in light sleep and 4 in wakefulness, but none occurred in deep or REM sleep. [Copyright &y& Elsevier]

Abstract: To investigate whether alterations in RNA editing (an enzymatic base-specific change to the RNA sequence during primary transcript formation from DNA) of neurotransmitter receptor genes and of transmembrane ion channel genes play a role in human temporal lobe epilepsy (TLE), this exploratory study analyzed 14 known cerebral editing sites in RNA extracted from the brain tissue of 41 patients who underwent surgery for mesial TLE, 23 with hippocampal sclerosis (MTLE+HS). Because intraoperatively sampled RNA cannot be obtained from healthy controls and the best feasible control is identically sampled RNA from patients with a clinically shorter history of epilepsy, the primary aim of the study was to assess the correlation between epilepsy duration and RNA editing in the homogenous group of MTLE+HS. At the functionally relevant I/V site of the voltage-gated potassium channel Kv1.1, an inverse correlation of RNA editing was found with epilepsy duration (r=−0.52, p=0.01) but not with patient age at surgery, suggesting a specific association with either the epileptic process itself or its antiepileptic medication history. No significant correlations were found between RNA editing and clinical parameters at other sites within glutamate receptor or serotonin 2C receptor gene transcripts. An “all-or-none” (≥95% or ≤5%) editing pattern at most or all sites was discovered in 2 patients. As a secondary part of the study, RNA editing was also analyzed as in the previous literature where up to now, few single editing sites were compared with differently obtained RNA from inhomogenous patient groups and autopsies, and by measuring editing changes in our mouse model. The present screening study is first to identify an editing site correlating with a clinical parameter, and to also provide an estimate of the possible effect size at other sites, which is a prerequisite for power analysis needed in planning future studies. [Copyright &y& Elsevier]

Abstract: Despite general agreement on shared syntactic resources in music and language, the neuroanatomical underpinnings of this overlap remain largely unexplored. While previous studies mainly considered frontal areas as supramodal grammar processors, the domain-general syntactic role of temporal areas has been so far neglected. Here we capitalized on the excellent spatial and temporal resolution of subdural EEG recordings to co-localize low-level syntactic processes in music and language in the temporal lobe in a within-subject design. We used Brain Surface Current Density mapping to localize and compare neural generators of the early negativities evoked by violations of phrase structure grammar in both music and spoken language. The results show that the processing of syntactic violations relies in both domains on bilateral temporo-fronto-parietal neural networks. We found considerable overlap of these networks in the superior temporal lobe, but also differences in the hemispheric timing and relative weighting of their fronto-temporal constituents. While alluding to the dissimilarity in how shared neural resources may be configured depending on the musical or linguistic nature of the perceived stimulus, the combined data lend support for a co-localization of early musical and linguistic syntax processing in the temporal lobe. [Copyright &y& Elsevier]

Abstract: The neurophysiological mechanisms underlying superior cognitive performance are a research area of high interest. The majority of studies on the brain–performance relationship assessed the effects of capability-related group factors (e.g. talent, gender) on task-related brain activations while only few studies examined the effect of the inherent experimental task performance factor. In this functional MRI study, we combined both approaches and simultaneously assessed the effects of three relatively independent factors on the neurofunctional correlates of mental rotation in same-aged adolescents: math talent (gifted/controls: 17/17), gender (male/female: 16/18) and experimental task performance (median split on accuracy; high/low: 17/17). Better experimental task performance of mathematically gifted vs. control subjects and male vs. female subjects validated the selected paradigm. Activation of the inferior parietal lobule (IPL) was identified as a common effect of mathematical giftedness, gender and experimental task performance. However, multiple linear regression analyses (stepwise) indicated experimental task performance as the only predictor of parietal activations. In conclusion, increased activation of the IPL represents a positive neural correlate of mental rotation performance, irrespective of but consistent with the obtained neurocognitive and behavioral effects of math talent and gender. As experimental performance may strongly affect task-related activations this factor needs to be considered in capability-related group comparison studies on the brain–performance relationship. [Copyright &y& Elsevier]

Abstract: Germline mutations of TSC1 (harmartin) and TSC2 (tuberin) are known to cause tuberous sclerosis (TSC), an autosomal dominant disorder with severe neurological and systemic manifestations. In addition, increasing data indicate aberrant patterns of allelic variants in patients with lesion-associated epilepsy, but absence of other stigmata of TSC. Animal models of TSC suggested that mutations in the TSC2 gene, even in absence of manifest neuropathological changes, induce aberrant neuronal activity. On this basis, we have carried out a mutational analysis of TSC1 and TSC2 in patients with pharmarcoresistant focal epilepsy without evidence of epileptogenic lesions on neuroradiological and histopathological examination (n =10). SSCP analysis revealed an allelic variant of TSC2 to be significantly increased (exon 41: 50.0% vs controls 14%, P =0.0132), which previously was reported to be increased in gangliogliomas and mineralized focal cortical dysplasia as well. Our data suggest allelic imbalances of TSC2 in nonlesional focal epileptic tissue. [Copyright &y& Elsevier]

Abstract: Assessment for epilepsy surgery may require invasive measures such as implantation of intracranial electrodes or the Wada test. These investigations are commonly well tolerated. However, complications, including visual disturbances of various etiologies, have been reported. Here we describe two patients with pharmacoresistant temporal lobe epilepsy (TLE) who displayed loss of vision in the context of presurgical assessment and in whom mutations associated with Leber''s hereditary optic neuropathy (LHON) were detected. Genetic analysis revealed in one patient the frequent mitochondrial G11778A LHON mutation in ND4. In the second patient, the mitochondrial C4640A mutation in ND2 was detected. This rare LHON mutation enhanced the sensitivity of the patient''s muscle and brain tissue to amobarbital, a known blocker of the mitochondrial respiratory chain. Mitochondrial dysfunction has been reported in epilepsy. Thus, the presence of LHON mutations can be a rare cause of visual disturbances in patients with epilepsy and may have predisposed to development of epilepsy. [Copyright &y& Elsevier]

Abstract: Reward processing is a central component of learning and decision making. Functional magnetic resonance imaging (fMRI) has contributed essentially to our understanding of reward processing in humans. The strength of reward-related brain responses might prove as a valuable marker for, or correlate of, individual preferences or personality traits. An essential prerequisite for this is a sufficient reliability of individual measures of reward-related brain signals. We therefore determined test–retest reliabilities of BOLD responses to reward prediction, reward receipt and reward prediction errors in the ventral striatum and the orbitofrontal cortex in 25 subjects undergoing three different simple reward paradigms (retest interval 7–13 days). Although on a group level the paradigms consistently led to significant activations of the relevant brain areas in two sessions, across-subject retest reliabilities were only poor to fair (with intraclass correlation coefficients (ICCs) of −0.15 to 0.44). ICCs for motor activations were considerably higher (ICCs 0.32 to 0.73). Our results reveal the methodological difficulties behind across-subject correlations in fMRI research on reward processing. These results demonstrate the need for studies that address methods to optimize the retest reliability of fMRI. [Copyright &y& Elsevier]

Abstract: The aim of the present study was to investigate whether forgetting is merely a passive process or whether it can also be caused by active suppression of memory contents. We investigated effects of directed forgetting by intracranial event-related potentials (ERPs) in 12 patients with mesial temporal lobe epilepsy. In a single-item directed forgetting paradigm, the patients were presented with words either followed by the instruction that this word has to-be-remembered (TBR) or to-be-forgotten (TBF). All patients were implanted with multicontact depth electrodes along the rhinal cortex and hippocampus as part of their presurgical evaluation. Patients recognized significantly less TBF than TBR words in a subsequent recognition test. In the hippocampus, TBF cues that caused subsequent forgetting were associated with decreased negative ERPs. In the rhinal cortex, TBF cues elicited a generally prolonged positivity, as compared to TBR cues. We interpret the decreased hippocampal ERPs following the TBF cues as an indication for an active suppression of hippocampal functions. The increased rhinal activity in response to the TBF cue might indicate an active involvement of this structure in the suppression of hippocampal memory formation. [Copyright &y& Elsevier]

Abstract: NeuroCog FX, a computerized neuropsychological screening instrument for serial examinations of patients with epilepsy and other neurological diseases, was developed to fill the gap between unspecific ratings and comprehensive assessments. Eight subtests address attention, working memory, verbal and figural memory, and language. The test duration is less than 30min. In research contexts, the test can be applied at multiple sites by nonacademic personnel. Normative data were recorded from healthy subjects (N =244, age range=16–75years; retest: N =44; validation: N =40) and unselected patients from an epileptology unit (N =212; retest: N =94; validation: N =126). Psychometric analyses confirmed sufficient reliability and concurrent validity, particularly in patients. NeuroCog FX memory and overall performance scores showed “fair” to “good” diagnostic utility with respect to deficits revealed by established tests. NeuroCog FX provides reliable and valid measures of cognitive performance and may be used in clinical and research contexts as a screening instrument. [Copyright &y& Elsevier]

Abstract: Temporal lobe epilepsy with hippocampus sclerosis (HS) is the most frequent focal epilepsy and often refractory to anticonvulsant therapy. Secondary structural damage has been reported in several studies of temporal lobe epilepsy and unilateral hippocampal sclerosis. Applying diffusion tensor imaging (DTI) we investigated alterations in white matter following temporal lobe surgery in patients with medial temporal lobe epilepsy. We examined 40 patients who underwent surgery at our hospital for HS between 1996 and 2006 with diffusion tensor imaging (DTI). Images were obtained at a 3 T MRI scanner employing 60 gradient directions. Tract-based spatial statistics (TBSS), a novel voxel-based approach, was applied to analyze the data. Both patients with left- as well as right-sided surgery exhibited widespread degradation of fractional anisotropy (FA) in main fiber tracts not limited to the respective temporal lobe such as the uncinate fasciculus, the fronto-occipital fasciculus, the superior longitudinal fasciculus, the corpus callosum and the corticospinal tract on the respective hemisphere. Patients with left-hemispheric surgery showed more widespread affections ipsilaterally and also FA decrease in the contralateral inferior longitudinal fasciculus. DTI demonstrates widespread clusters of abnormal diffusivity and anisotropy in prominent white matter tracts linking mesial temporal lobe structures with other brain areas. Alterations in the ipsilateral mesial temporal lobe can be attributed to be a result of surgery, whereas extratemporal FA decrease is more likely the result of the underlying seizure disorder. [Copyright &y& Elsevier]

Abstract: For patients with schizophrenia, a deficient gating (or filtering) of sensory input has been described. One major approach to study this sensory gating is to measure event-related potentials (ERPs) in response to paired clicks. In these experiments, sensory gating is quantified as amplitude reduction of the ERP components P50 and N100 from the 1st to the 2nd stimulus. In ERP studies brain electrical signals are averaged over single trials. Alterations in phase locking might be one factor contributing to the observed deficits in sensory gating, but findings have been inconclusive as yet. In particular, the contribution of different frequency bands to the deficit required further investigation. We studied N100 gating by intracranial recordings in a sample of epilepsy patients and subdivided the group into good and poor gators of the intracranial ERP component N100. Data were evaluated by frequency specific wavelet-based phase and power analyses. Poor N100 gators had an increased phase locking in the frequency range from 6.0–15.1 Hz after the 2nd stimulus, as compared to good gators. Other group differences were apparent already before the 2nd stimulus. Poor gators had less phase locked beta band activity (20.2–30.0 Hz) than good gators 200–315 ms after the onset of the 1st stimulus. Within the group of poor gators, lower values of phase locking in this frequency range were also associated with lower gating ratios. The reduced beta band response in response to the 1st stimulus may reflect poorer memory encoding of the 1st stimulus in poor gators. This in turn might lead to increased demands to process the 2nd stimulus. [Copyright &y& Elsevier]

Abstract: Lesion and imaging studies have demonstrated that encoding of declarative memories, i.e. consciously accessible events and facts, is supported by processes within the rhinal cortex and the hippocampus, two substructures of the mediotemporal lobe (MTL). Successful memory formation has, for instance, been shown to be accompanied by the rhinal N400 component, followed by a hippocampal positivity, as well as by transient rhinal–hippocampal phase synchronization. However, it has been an open question, which mediotemporal electroencephalogram (EEG) measures predict memory formation most accurately. Therefore, we analyzed and compared the association of different mediotemporal EEG measures with successful memory formation. EEG characteristics were extracted from intracranial rhinal and hippocampal depth recordings in 31 epilepsy patients performing a continuous word recognition paradigm. Classical event-related potential measures, rhinal–hippocampal synchronization, as well as inter-trial phase-locking and power changes within rhinal cortex and hippocampus were evaluated. We found that inter-trial phase-locking is superior to other EEG measures in predicting subsequent memory. This means that memory formation is related to the precise timing of EEG phases within the MTL with respect to stimulus onset. In particular, early rhinal and hippocampal phase-locking in the alpha/beta range reaching its maximum already between 100 and 300 ms after stimulus onset appears to be a precursor of successful memory formation. Our data suggest that early mediotemporal phase adjustments constitute a relevant mechanism underlying declarative memory encoding. [Copyright &y& Elsevier]

Abstract: Neuropsychological and neuroimaging data have shown a functional lateralization of the medial temporal lobes for verbal and non-verbal memory material respectively. We hypothesized that this lateralization is related to language lateralization. Using fMRI we conducted three memory tasks with different memory material (words, faces, landscape images) alongside with a paradigm for the determination of language dominance in 44 healthy subjects. We included left as well as right-handed subjects because persons with atypical language dominance are known to be overrepresented in the group of left-handers. Lateralization indices for the BOLD activation in the medial temporal lobes from the memory tasks were correlated with those for the language task. We show that the material-specific lateralization is related to language dominance such that verbal encoding shows strong positive relation to language dominance whereas face encoding shows the opposite effect. Our data provide first fMRI evidence for a relation between language dominance and material specificity of the medial temporal lobes for memory functions. We suggest that the language-dominant hemisphere is more strongly engaged in memory processing of verbal material. These data provide grounds for the investigation of pathological changes in this relationship due to cortical dysfunctions. [Copyright &y& Elsevier]

Abstract: The mismatch negativity (MMN), a component of event-related potentials (ERPs), is assumed to reflect a preattentive auditory discrimination process. Although an involvement of hippocampal structures in deviance detection was shown in animal experiments, invasive recordings in humans have not been able to provide such an evidence so far. In the current study, ERPs were recorded from intrahippocampal and scalp electrodes in 16 epilepsy patients. Stimulation consisted of trains of six tones, with one tone deviating in duration (100 vs. 50 ms). In the rhinal cortex, ERPs elicited by deviants were larger in amplitude than those of standards (around 200 ms). The rhinal activation was succeeded by a long-lasting hippocampal ERP component (around 350 ms). However, in contrast to the rhinal activation, hippocampal activation was also elicited by the 1st stimuli of the train and might, therefore, be related more to salience detection than to deviance detection. The current study provides evidence that the MMN is part of a multistage comparison process and that the rhinal cortex is part of its underlying cortical network. [Copyright &y& Elsevier]

Abstract: Event-related functional Magnetic Resonance Imaging (fMRI) allows for the comparison of hemodynamic responses evoked by items that are remembered in a subsequent memory task vs. items that are forgotten. In this way, brain regions that assumingly contribute to successful memory encoding have been identified, including the left inferior prefrontal cortex (LIPC) and the medial temporal lobe. Although a cerebellar involvement in verbal working memory is well-established, a contribution of the cerebellum to episodic long-term encoding has only sporadically been described, and mechanisms underlying cerebellar memory effects are unclear. We conducted a typical incidental verbal memory fMRI experiment with three different encoding tasks varying the depth of semantic processing. Slice positioning allowed for the coverage of the entire cerebellum. We observed a significant subsequent memory effect within the superior and posterior right cerebellar hemisphere that was task independent. Additionally, we found a different area within the superior right cerebellum displaying a memory effect specifically for semantically processed words and a bilateral cerebellar activation specifically associated with encoding success only for a non-semantic task. Our results suggest that besides its known role in verbal working memory, the cerebellum contributes to episodic long-term encoding and should therefore be considered in future fMRI studies dealing with episodic memory. [Copyright &y& Elsevier]

Abstract: Human decision making has become one of the major research-foci in economics, marketing and in neuroscience. This study integrates perspectives from these disciplines by examining neurophysiological correlates to Reference-dependence of utility evaluations in real market contexts both before and after choice. First, by comparing buying and selling decisions, we observe an activation of the amygdala only in the latter. We interpret this as loss aversion with respect to prior possessions. This finding contributes to the settling of an ongoing fundamental dispute in economic theory by indicating the absence of loss aversion for money in routine transactions. Second, ex post satisfaction statements are accompanied by an activation of the reward processing orbitofrontal cortex, if the evaluation context is framed by a high external reference price instead of a lower internal reference price. This indicates a nonrational Reference-dependence – despite the neoclassical view of a rational Homo Economicus – of satisfaction measures and challenges a central marketing variable. [Copyright &y& Elsevier]

Abstract: Little is known about the neural mechanisms underlying top–down control of repetition priming. Here, we use functional brain imaging to investigate these mechanisms. Study and repetition tasks used a natural/man-made forced choice task. In the study phase subjects were required to respond to either pictures or words that were presented superimposed on each other. In the repetition phase only words were presented that were new, previously attended or ignored, or picture names that were derived from previously attended or ignored pictures. Relative to new words we found repetition priming for previously attended words. Previously ignored words showed a reduced priming effect, and there was no significant priming for pictures repeated as picture names. Brain imaging data showed that neural priming of words in the left prefrontal cortex (LIPFC) and left fusiform gyrus (LOTC) was affected by attention, semantic compatibility of superimposed stimuli during study and cross-modal priming. Neural priming reduced for words in the LIPFC and for words and pictures in the LOTC if stimuli were previously ignored. Previously ignored words that were semantically incompatible with a superimposed picture during study induce increased neural priming compared to semantically compatible ignored words (LIPFC) and decreased neural priming of previously attended pictures (LOTC). In summary, top–down control induces dissociable effects on neural priming by attention, cross-modal priming and semantic compatibility in a way that was not evident from behavioral results. [Copyright &y& Elsevier]

Abstract: Asymmetry is a common phenomenon in higher organisms. In humans, the cortical representation of language exhibits a high degree of asymmetry with a prevalence of about 90% of left hemispheric dominance, the underlying mechanisms of which are largely unknown. Another sign that exhibits a form of lateralization is the scalp hair-whorl direction, which is either clockwise or anti-clockwise. The scalp hair-whorl develops from the same germ layer as the nervous system, the ectoderm, between the 10th and 16th week in utero and has been shown to be associated with various neurodevelopmental disorders. Here, we use an established fMRI paradigm to examine the association of a solely biological marker of asymmetry, hair-whorl direction and language lateralization. We show that the mechanism that influences hair-whorl direction and handedness [Klar, A.J.S., 2003. Human handedness and scalp hair-whorl direction develop from a common genetic mechanism. Genetics 1651, 269–276.] also affects cerebral language dominance. [Copyright &y& Elsevier]

Abstract: Up to 50 or 60% of patients with chronic epilepsy have various mood disorders including depression and anxiety. Whereas the relationship between epilepsy and depression has received much attention, less is known about anxiety disorders. It is now recognized that anxiety can have a profound influence on the quality of life of patients with epilepsy. The relationship between anxiety disorders and epilepsy is complex. It is necessary to distinguish between different manifestations of anxiety disorder: ictal, postictal, and interictal anxiety. Preexisting vulnerability factors, neurobiological factors, iatrogenic influences (antiepileptic drugs, epilepsy surgery), and psychosocial factors are all likely to play a role, but with considerable individual differences. Despite the high prevalence of anxiety disorders in patients with epilepsy, there are no systematic treatment studies or evidence-based guidelines for best treatment practice. Nevertheless, a practical approach based on the temporal relationship between anxiety and epileptic seizures allows clinicians to consider appropriate treatment strategies to reduce the psychiatric comorbidity in patients with epilepsy. [Copyright &y& Elsevier]

Abstract: Amplitudes of the P3 recorded invasively from the medial temporal lobe (MTL-P3) have been reported to be reduced on the side of a mediotemporal epileptogenic focus. This reduction has been attributed to the massive cell loss within the hippocampus associated with hippocampal sclerosis. It has remained unclear how functional connectivity between the hippocampus and rhinal cortex, as well as within the hippocampus, is altered in hippocampal sclerosis. To investigate this issue, we analyzed to what extent stimulus-related phase-locking and power changes within the low-frequency range (2–30 Hz) and within the gamma band (32–48 Hz), as well as rhinal–hippocampal phase synchronization contribute to the averaged MTL-P3 potentials. Event-related responses were recorded via bilateral depth electrodes in epilepsy patients with unilateral hippocampal sclerosis, who performed a visual oddball experiment. On the contralateral (nonsclerotic) side, successful target detection was associated with an increase of power and phase locking of hippocampal activity in both the low-frequency range and in the gamma range. Besides, there were rhinal–hippocampal synchronization enhancements in the theta and gamma range. On the ipsilateral (sclerotic) side, the event-related power increase in the low-frequency range had almost disappeared, a finding likely to be explained by the loss of principle neurons. However, low-frequency phase-locking, rhinal–hippocampal synchronization, as well as event-related power changes in the gamma range persisted ipsilaterally, although there were differences in temporal and spectral characteristics. These findings support the hypothesis that functional connectivity between hippocampus and rhinal cortex, as well as intrahippocampal connectivity, are partially preserved in hippocampal sclerosis. [Copyright &y& Elsevier]

Memory disorders and depressed mood are prominent psychological symptoms of temporal lobe epilepsies (TLEs). We examined the interaction of depressive mood and memory as a function of focus localization.One hundred fifty-two TLE patients with right mesial (n=37, RTLE-AHS), right lateral (n=31, RTLE-LAT), left mesial (n=42, LTLE-AHS), and left lateral (n=42, LTLE-LAT) lesions and epilepsies underwent comprehensive presurgical evaluation and neuropsychological assessment of mood and memory. Univariate and multivariate analyses of covariance (ANCOVAs) and partial correlation analyses were performed to reveal interactions of depression and memory as a function of focus localization.No differences between the study groups were revealed for depression, indicating a general risk of 30% for depressed mood (BDI>12) in patients with TLE. ANCOVAs revealed significant main effects of focus side (left: verbal learning deficits; right: figural learning deficits) and site (mesial at disadvantage) on learning and memory scores. Correlation analyses revealed interactions between memory and mood only in LTLE-LAT patients.Although the data provide evidence that side and site of the epileptogenic region differentially affect material specific memory performance, there was no evidence of a specific temporal target region for depressive mood. In the majority of the patients, depressed mood and memory impairment appeared as independent rather than as related symptoms of TLE. In LTLE-LAT, however, mood was significantly related to verbal and figural memory performance. Epilepsy-driven pathological left temporofrontal circuits are discussed as a prerequisite for the coupling of mood disorders and memory impairment in this specific patient subgroup which is also known from the psychiatric major depression syndrome. [Copyright &y& Elsevier]

Major depression (MD) is underdiagnosed and undertreated in patients with temporal lobe epilepsy (TLE). Side effects of some antidepressants, like increased risk of seizures and drug–drug interactions with anticonvulsants, contribute to undertreatment of MD in patients with TLE. We analyzed post hoc the data from 2 years of treatment of inpatients with MD and TLE. Seventy-five patients received standard treatment with citalopram, mirtazapine, or reboxetine, respectively, at recommended dosage. Examinations were done with the Hamilton Rating Scale for Depression at admission and after 4 and 20–30 weeks. Plasma levels of anticonvulsants were examined at admission and discharge. Seizures were documented. The antidepressive treatment was efficacious in all antidepressant groups. No case of serious adverse event or drug interaction occurred. There was no increase in frequency or severity of seizures. At endpoint the dropout rate for mirtazapine was significantly higher than that for reboxetine or citalopram. Reboxetine showed a trend to be more efficacious than citalopram but not mirtazapine at Week 4. [Copyright &y& Elsevier]