Interictal epileptiform discharges affect memory in an Alzheimer's disease mouse model.

Interictal epileptiform discharges (IEDs) are transient abnormal electrophysiological events commonly observed in epilepsy patients but are also present in other neurological diseases, such as Alzheimer's disease (AD). Understanding the role IEDs have on the hippocampal circuit is important for our understanding of the cognitive deficits seen in epilepsy and AD. We characterize and compare the IEDs of human epilepsy patients from microwire hippocampal recording with those of AD transgenic mice with implanted multilayer hippocampal silicon probes. Both the local field potential features and firing patterns of pyramidal cells and interneurons were similar in the mouse and human. We found that as IEDs emerged from the CA3-1 circuits, they recruited pyramidal cells and silenced interneurons, followed by post-IED suppression. IEDs suppressed the incidence and altered the properties of physiological sharp-wave ripples, altered their physiological properties, and interfered with the replay of place field sequences in a maze. In addition, IEDs in AD mice inversely correlated with daily memory performance. Together, our work implies that IEDs may present a common and epilepsy-independent phenomenon in neurodegenerative diseases that perturbs hippocampal-cortical communication and interferes with memory.

Identifying sources of human interictal discharges with travelling wave and white matter propagation.

Interictal epileptiform discharges have been shown to propagate from focal epileptogenic sources as travelling waves or through more rapid white matter conduction. We hypothesize that both modes of propagation are necessary to explain interictal discharge timing delays. We propose a method that, for the first time, incorporates both propagation modes to identify unique potential sources of interictal activity. We retrospectively analysed 38 focal epilepsy patients who underwent intracranial EEG recordings and diffusion-weighted imaging for epilepsy surgery evaluation. Interictal discharges were detected and localized to the most likely source based on relative delays in time of arrival across electrodes, incorporating travelling waves and white matter propagation. We assessed the influence of white matter propagation on distance of spread, timing and clinical interpretation of interictal activity. To evaluate accuracy, we compared our source localization results to earliest spiking regions to predict seizure outcomes. White matter propagation helps to explain the timing delays observed in interictal discharge sequences, underlying rapid and distant propagation. Sources identified based on differences in time of receipt of interictal discharges are often distinct from the leading electrode location. Receipt of activity propagating rapidly via white matter can occur earlier than more local activity propagating via slower cortical travelling waves. In our cohort, our source localization approach was more accurate in predicting seizure outcomes than the leading electrode location. Inclusion of white matter in addition to travelling wave propagation in our model of discharge spread did not improve overall accuracy but allowed for identification of unique and at times distant potential sources of activity, particularly in patients with persistent postoperative seizures. Since distant white matter propagation can occur more rapidly than local travelling wave propagation, combined modes of propagation within an interictal discharge sequence can decouple the commonly assumed relationship between spike timing and distance from the source. Our findings thus highlight the clinical importance of recognizing the presence of dual modes of propagation during interictal discharges, as this may be a cause of clinical mislocalization.

Visualization of the Spatiotemporal Propagation of Interictal Spikes in Temporal Lobe Epilepsy: A MEG Pilot Study.

Magnetoencephalography (MEG) is clinically used to localize interictal spikes in discrete brain areas of epilepsy patients through the equivalent current dipole (ECD) method, but does not account for the temporal dynamics of spike activity. Recent studies found that interictal spike propagation beyond the temporal lobe may be associated with worse postsurgical outcomes, but studies using whole-brain data such as in MEG remain limited. In this pilot study, we developed a tool that visualizes the spatiotemporal dynamics of interictal MEG spikes normalized to spike-free sleep activity to assess their onset and propagation patterns in patients with temporal lobe epilepsy (TLE). We extracted interictal source data containing focal epileptiform activity in awake and asleep states from seven patients whose MEG ECD clusters localized to the temporal lobe and normalized the data against spike-free sleep recordings. We calculated the normalized activity over time per cortical label, confirmed maximal activity at onset, and mapped the activity over a 10 ms interval onto each patient's brain using a custom-built Multi-Modal Visualization Tool. The onset of activity in all patients appeared near the clinically determined epileptogenic zone. By 10 ms, four of the patients had propagated source activity restricted to within the temporal lobe, and three had propagated source activity spread to extratemporal regions. Using this tool, we show that noninvasively identifying the onset and propagation of interictal spike activity in MEG can be achieved, which may help provide further insight into epileptic networks and guide surgical planning and interventions in patients with TLE.

Detection of subclinical epileptiform discharges in Alzheimer's disease using long-term outpatient EEG monitoring.

BACKGROUND: In patients with Alzheimer's disease (AD) without clinical seizures, up to half have epileptiform discharges on long-term in-patient electroencephalography (EEG) recordings. Long-term in-patient monitoring is obtrusive, and expensive as compared to outpatient monitoring. No studies have so far investigated if long-term outpatient EEG monitoring is able to identify epileptiform discharges in AD. Our aim is to investigate if epileptiform discharges as measured with ear-EEG are more common in patients with AD compared to healthy elderly controls (HC). METHODS: In this longitudinal observational study, 24 patients with mild to moderate AD and 15 age-matched HC were included in the analysis. Patients with AD underwent up to three ear-EEG recordings, each lasting up to two days, within 6 months. RESULTS: The first recording was defined as the baseline recording. At baseline, epileptiform discharges were detected in 75.0% of patients with AD and in 46.7% of HC (p-value = 0.073). The spike frequency (spikes or sharp waves/24 h) was significantly higher in patients with AD as compared to HC with a risk ratio of 2.90 (CI: 1.77-5.01, p < 0.001). Most patients with AD (91.7%) showed epileptiform discharges when combining all ear-EEG recordings. CONCLUSIONS: Long-term ear-EEG monitoring detects epileptiform discharges in most patients with AD with a three-fold increased spike frequency compared to HC, which most likely originates from the temporal lobes. Since most patients showed epileptiform discharges with multiple recordings, elevated spike frequency should be considered a marker of hyperexcitability in AD.

Effect of high-frequency stimulation on the complexity of low-Mg2+-induced epileptiform discharge rhythm waves in the CA3 region of rat hippocampal slices.

High-frequency stimulation (HFS) is a crucial therapeutic approach for neurodegenerative conditions, such as epilepsy. However, its underlying mechanism of inhibition remains unclear. In this study, a rat model of epileptiform discharges (EDs) was constructed by perfusing brain slices with magnesium-free artificial cerebrospinal fluid (aCSF), where after HFS was used to stimulate the CA3 area of the hippocampus. The EDs signals of each sub-region of hippocampal slices before and after HFS were recorded based on a multi-electrode Array (MEA). Secondly, the changes of approximate entropy (ApEn) complexity of rhythms in different regions of hippocampal slices before and after HFS were deeply analyzed The results showed that different rhythm characteristics of EDs signals exhibited significant differences before and after HFS. Here HFS significantly inhibited the delta rhythm of field potential and enhanced the beta rhythm. Finally, the changing rhythm of the EDs signal in the propagation path before and after HFS was analyzed, and it was found that the inhibitory target of HFS on EDs signal was in the CA3b sub-region. The rhythm would gradually decline with the propagation of EDs signal in the hippocampal neural pathway. This study shows that HFS can modulate the local field potential, thus inhibiting the pathological rhythm caused by epilepsy, which provides a novel research incentive for HFS to inhibit EDs.

Subclinical Epileptiform Activity in Dementia with Lewy Bodies.

BACKGROUND: Patients with dementia with Lewy bodies (DLB) have a higher probability of seizures than in normal aging and in other types of neurodegenerative disorders. Depositions of α-synuclein, a pathological hallmark of DLB, can induce network excitability, which can escalate into seizure activity. Indicator of seizures are epileptiform discharges as observed using electroencephalography (EEG). However, no studies have so far investigated the occurrence of interictal epileptiform discharges (IED) in patients with DLB. OBJECTIVES: To investigate if IED as measured with ear-EEG occurs with a higher frequency in patients with DLB compared to healthy controls (HC). METHODS: In this longitudinal observational exploratory study, 10 patients with DLB and 15 HC were included in the analysis. Patients with DLB underwent up to three ear-EEG recordings, each lasting up to 2 days, over a period of 6 months. RESULTS: At baseline, IED were detected in 80% of patients with DLB and in 46.7% of HC. The spike frequency (spikes or sharp waves/24 hours) was significantly higher in patients with DLB as compared to HC with a risk ratio of 2.52 (CI, 1.42-4.61; P-value = 0.001). Most IED occurred at night. CONCLUSIONS: Long-term outpatient ear-EEG monitoring detects IED in most patients with DLB with an increased spike frequency compared to HC. This study extends the spectrum of neurodegenerative disorders in which epileptiform discharges occurs at an elevated frequency. It is possible that epileptiform discharges are, therefore, a consequence of neurodegeneration. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Design and fabrication of a microelectrode array for studying epileptiform discharges from rodents.

Local field potentials, the extracellular electrical activities from brain regions, provide clinically relevant information about the status of neurophysiological conditions, including epilepsy. In this study, a 13-channel silicon-based single-shank microelectrode array (MEA) was designed and fabricated to record local field potentials (LFPs) from the different depths of a rat's brain. A titanium/gold layer was patterned as electrodes on an oxidized silicon substrate, and silicon dioxide was deposited as a passivation layer. The fabricated array was implanted in the somatosensory cortex of the right hemisphere of an anesthetized rat. The developed MEA was interfaced with an OpenBCI Cyton Daisy Biosensing Board to acquire the local field potentials. The LFPs were acquired at three different neurophysiological conditions, including baseline signals, chemically-induced epileptiform discharges, and recovered baseline signals after anti-epileptic drug (AED) administration. Further, time-frequency analyses were performed on the acquired biopotentials to study the difference in spatiotemporal features. The processed signals and time-frequency analyses clearly distinguish between pre-convulsant and post-AED baselines and evoked epileptiform discharges.

Transcranial direct current stimulation for focal status epilepticus or lateralized periodic discharges in four patients in a critical care setting.

OBJECTIVE: Transcranial direct current stimulation (tDCS) has been advocated for various neurological conditions, including epilepsy. A 1-4-mA cathodal current applied to the scalp over a seizure focus can reduce spikes and seizures. This series of four patients with focal status epilepticus is among the first case series to demonstrate benefit of tDCS in the critical care setting. METHODS: Patients in the intensive care unit were referred for tDCS treatment when focal status epilepticus or clinically relevant lateralized periodic discharges did not resolve with conventional antiseizure medications and anesthetics. Battery-powered direct cathodal current at 2 mA was delivered by an ActivaDose (Caputron) tDCS device via a saline-soaked sponge on the scalp over the seizure focus. Anode was on the contralateral forehead or shoulder. Treatment was for 30 min, repeated twice in a day, then again 1-4 times more over the next few days. RESULTS: Three females and one male, aged 34-68 years, were treated. Etiologies of status epilepticus were posterior reversible encephalopathy syndrome in association with immunosuppressants for a liver transplant, perinatal hypoxic-ischemic injury, a prior cardioembolic parietal stroke, and central nervous system lupus. tDCS led to significant reduction of interictal spikes (.78 to .38/s, p < .0001) in three cases and electrographic seizures (3.83/h to 0/h, p < .001) in two cases. Medication reductions were enabled in all cases subsequent to tDCS. The only side effect of tDCS was transient erythema under the sponge in one case. Two patients died of causes unrelated to tDCS, one was discharged to a nursing home, and one became fully responsive as seizures were controlled with tDCS. SIGNIFICANCE: Spikes and electrographic seizure frequency significantly improved within 1 day of tDCS. Results are potentially confounded by multiple ongoing changes in medications and treatments. These results might encourage further investigation of tDCS in the critical care setting, but verification by controlled studies will be required.

Effect of the revised definition of epilepsy on treatment decisions and seizure recurrence after a first epileptic seizure.

BACKGROUND: Studies on risk factors for epilepsy and seizure recurrence after a first seizure are usually based on the old definition of epilepsy with the need for two unprovoked seizures. The current definition of epilepsy allows diagnosis and treatment of epilepsy after a first seizure if the recurrence risk is >60%. We evaluate treatment decisions, seizure recurrence and risk factors for epilepsy related to the application of the new definition of epilepsy. METHODS: Data of 629 patients with a first seizure were analyzed to investigate changes of treatment decisions and seizure recurrence after the revised definition of epilepsy. We used binary logistic regression to investigate the impact of multiple factors influencing seizure recurrence like electroencephalogram (EEG) and magnetic resonance imaging (MRI) results and administration of antiseizure medication (ASM). RESULTS: The proportion of patients receiving ASM significantly increased from 70.4% to 80.5% (p = 0.015) following the new epilepsy definition, without any significant changes in the recurrence rate (40.8% vs. 45.5% after 2 years, p > 0.05). The presence of interictal epileptiform discharges (IED) in the EEG increased (OR = 1.98) and administration of ASM decreased (OR = 0.43) recurrence rates significantly. CONCLUSIONS: The new definition of epilepsy was associated with increased application of ASM, but not with reduced recurrence rates. The study confirms the presence of IED as a strong risk factor for seizure recurrence and the protective effect of ASM. The influence of imaging findings, which have a strong impact on the new definition of epilepsy, could not be confirmed.

Cognitive dysfunction in drug-naïve late-onset temporal lobe epilepsy.

OBJECTIVES: To evaluate cognitive functions including memory in middle-aged and elderly patients with antiseizure drug-naïve late-onset temporal lobe epilepsy (TLE). METHODS: We performed assessments with the Wechsler Adult Intelligence Scale-III (WAIS-III) and Wechsler Memory Scale-Revised (WMS-R) in 26 antiseizure drug-naïve patients with late-onset TLE, in comparison to 30 healthy subjects. We investigated the relationships between these cognitive function scores and clinical characteristics, seizure frequency, and frequency of interictal epileptic discharges (IEDs). RESULTS: Patients with epilepsy had a significantly lower score than healthy controls in the verbal intelligence quotient (IQ), the performance IQ, and full-scale IQ in intelligence testing. Patients showed significantly decrease in the verbal memory scores, visual memory scores, general memory scores, and delayed recall scores compared with those in the control subjects. Delayed recall scores were significantly negatively correlated with recent seizure frequency and the total IEDs count per minute, but not with age of onset or duration of illness. SIGNIFICANCE: Patients with antiseizure drug-naïve late-onset TLE displayed cognitive deficits including the domains of memory by using standard clinical neuropsychological test. Patients with late-onset epilepsy need to be considered for cognitive dysfunction at the time of diagnosis of TLE because they may have their daily life and work affected not only by epileptic seizures but also by cognitive deficits. Appearance of seizures and EEG abnormalities may affect the memory function in patients with late-onset TLE.

AsHC 360 Exposure Influence on Epileptiform Discharges in Hippocampus of Infantile Male Rats In Vitro.

Arsenic-containing hydrocarbons (AsHCs) are typical arsenolipids found in various marine organisms. They can penetrate the blood-brain barrier, specifically affecting synaptic plasticity and the learning and memory ability of hippocampal neurons. Temporal lobe epilepsy often occurs in the hippocampus. Thus, the possible influence of AsHCs exposure to temporal lobe epilepsy garnered attention. The present study investigated the effects of epileptiform discharges (EDs) signals introduced by low-magnesium ACSF in the hippocampus of infantile male rats in vitro, using electrophysiological techniques with multi-electrode arrays under AsHC 360 exposure. In our study of the effects of AsHC 360 on EDs signals, we found that inter-ictal discharges (IIDs) were not significantly impacted. When AsHC 360 was removed, any minor effects observed were reversed. However, when we examined the impact of AsHC 360 on ictal discharges (IDs), distinct patterns emerged based on the concentration levels. For low-concentration groups (5, 20, 60 µg As L-1), both the frequency and duration effects on IDs returned to normal post-elimination of AsHC 360. However, this recovery was not evident for concentrations of 100 µg As L-1 or higher. IDs were only observed in EDs signals during exposures to AsHC 360 concentrations up to 60 µg As L-1. In these conditions, ID frequencies significantly enhanced with the increased of AsHC 360 concentration. At high concentrations of AsHC 360 (≥100 µg As L-1), the transition from IIDs or pre-ictal discharges (PIDs) to IDs was notably inhibited. Additional study on co-exposure of AsHC 360 (100 µg As L-1) and agonist (10 nM (S)-(-)-Bay-K-8644) indicated that the regulation of EDs signals under AsHC 360 exposure could be due to directly interference with the α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) expression which influences the binding of excitatory glutamate neurotransmitter to AMPAR. The results suggest that EDs activities in the hippocampus of infantile Sprague Dawley rats are concentration-dependent on AsHC 360 exposure. Thus, it provides a basis for the seafood intake with AsHCs for epileptic patients and those with potential seizures.

Modulation of in vitro epileptiform activity by optogenetic stimulation of parvalbumin-positive interneurons.

GABAA signaling is surprisingly involved in the initiation of epileptiform activity since increased interneuron firing, presumably leading to excessive GABA release, often precedes ictal discharges. Field potential theta (4-12 Hz) oscillations, which are thought to mirror the synchronization of interneuron networks, also lead to ictogenesis. However, the exact role of parvalbumin-positive (PV) interneurons in generating theta oscillations linked to epileptiform discharges remains unexplored. We analyzed here the field responses recorded in the CA3, entorhinal cortex (EC), and dentate gyrus (DG) during 8-Hz optogenetic stimulation of PV-positive interneurons in brain slices obtained from PV-ChR2 mice during 4-aminopyridine (4AP) application. This optogenetic protocol triggered similar field oscillations in both control conditions and during 4AP application. However, in the presence of 4AP, optogenetic stimuli also induced: 1) interictal discharges that were associated in all regions with 8-Hz field oscillations and 2) low-voltage fast onset ictal discharges. Interictal and ictal events occurred more frequently during optogenetic activation than during periods of no stimulation. 4AP also increased synchronicity during PV-interneuron activation in all three regions. In opsin-negative mice, optogenetic stimulation did not change the rate of both types of epileptiform activity. Our findings suggest that PV-interneuron recruitment at theta (8 Hz) frequency contributes to epileptiform synchronization in limbic structures in the in vitro 4AP model.NEW & NOTEWORTHY Previous studies have identified contradictory roles of PV-interneurons in ictogenesis and the link between theta oscillations and epileptiform activity remains unexplored. Here, we investigated in vitro the effect of PV-interneuron optogenetic stimulation under 4AP in temporal lobe regions obtained from PV-ChR2 transgenic mice. Under theta (8 Hz) optogenetic stimulation and 4AP application, interictal spikes and low-voltage fast onset ictal discharges were triggered, suggesting that the activation of PV-interneurons favors synchronization and ictogenesis.

Prolongation of cortical sleep spindles during hippocampal interictal epileptiform discharges in epilepsy patients.

OBJECTIVE: Memory deficits are frequent among patients with epilepsies affecting the temporal lobe. Hippocampal interictal epileptic discharges (hIEDs), the presumed epileptic exaggeration of sharp wave-ripples (SWRs), are known to contribute to memory dysfunction, but the potential underlying mechanism is unknown. The precise temporal coordination between hippocampal SWRs and corticothalamic spindles during sleep is critical for memory consolidation. Moreover, previous investigation indicated that hIEDs induce neocortical spindlelike oscillation. In the present study, we aimed to assess the influence of hIEDs on neocortical spindles. METHODS: We analyzed the spindle characteristics (duration, amplitude, frequency) of 21 epilepsy patients implanted with foramen ovale (FO) electrodes during a whole night sleep. Scalp sleep spindles were categorized based on their temporal relationship to hIEDs detected on the FO electrodes. Three groups were created: (1) spindles coinciding with hIEDs, (2) spindles "induced" by hIEDs, and (3) spindles without hIED co-occurrence. RESULTS: We found that spindles co-occurring with hIEDs had altered characteristics in all measured properties, lasted longer by 126 ± 48 ms (mean ± SD), and had higher amplitude by 3.4 ± 3.2 µV, and their frequency range shifted toward the higher frequencies within the 13-15-Hz range. Also, hIED-induced spindles had identical oscillatory properties to spindles without any temporal relationships with hIEDs. In more than half of our subjects, clear temporal coherence was revealed between hIEDs and spindles, but the direction of the coupling was patient-specific. SIGNIFICANCE: We investigated the effect of hippocampal IEDs on neocortical spindle activity and found spindle alterations in cases of spindle-hIED co-occurrence, but not in cases of hIED-initiated spindles. We propose that this is a marker of a pathologic process, where IEDs may have direct effect on spindle generation. It could mark a potential mechanism whereby IEDs disrupt memory processes, and also provide a potential therapeutic target to treat memory disturbances in epilepsy.

Detection of interictal epileptiform discharges in an extended scalp EEG array and high-density EEG-A prospective multicenter study.

OBJECTIVES: High counts of averaged interictal epileptiform discharges (IEDs) are key components of accurate interictal electric source imaging (ESI) in patients with focal epilepsy. Automated detections may be time-efficient, but they need to identify the correct IED types. Thus we compared semiautomated and automated detection of IED types in long-term video-EEG (electroencephalography) monitoring (LTM) using an extended scalp EEG array and short-term high-density EEG (hdEEG) with visual detection of IED types and the seizure-onset zone (SOZ). METHODS: We prospectively recruited consecutive patients from four epilepsy centers who underwent both LTM with 40-electrode scalp EEG and short-term hdEEG with 256 electrodes. Only patients with a single circumscribed SOZ in LTM were included. In LTM and hdEEG, IED types were identified visually, semiautomatically and automatically. Concordances of semiautomated and automated detections in LTM and hdEEG, as well as visual detections in hdEEG, were compared against visually detected IED types and the SOZ in LTM. RESULTS: Fifty-two of 62 patients with LTM and hdEEG were included. The most frequent IED types per patient, detected semiautomatically and automatically in LTM and visually in hdEEG, were significantly concordant with the most frequently visually identified IED type in LTM and the SOZ. Semiautomated and automated detections of IED types in hdEEG were significantly concordant with visually identified IED types in LTM, only when IED types with more than 50 detected single IEDs were selected. The threshold of 50 detected IED in hdEEG was reached in half of the patients. For all IED types per patient, agreement between visual and semiautomated detections in LTM was high. SIGNIFICANCE: Semiautomated and automated detections of IED types in LTM show significant agreement with visually detected IED types and the SOZ. In short-term hdEEG, semiautomated detections of IED types are concordant with visually detected IED types and the SOZ in LTM if high IED counts were detected.

Temporal lobe interictal spikes disrupt encoding and retrieval of verbal memory: A subregion analysis.

OBJECTIVE: The medial temporal lobe (MTL) encodes and recalls memories and can be a predominant site for interictal spikes (IS) in patients with focal epilepsy. It is unclear whether memory deficits are due to IS in the MTL producing a transient decline. Here, we investigated whether IS in the MTL subregions and lateral temporal cortex impact episodic memory encoding and recall. METHODS: Seventy-eight participants undergoing presurgical evaluation for medically refractory focal epilepsy with depth electrodes placed in the temporal lobe participated in a verbal free recall task. IS were manually annotated during the pre-encoding, encoding, and recall epochs. We examined the effect of IS on word recall using mixed-effects logistic regression. RESULTS: IS in the left hippocampus (odds ratio [OR] = .73, 95% confidence interval [CI] = .63-.84, p < .001) and left middle temporal gyrus (OR = .46, 95% CI = .27-.78, p < .05) during word encoding decreased subsequent recall performance. Within the left hippocampus, this effect was specific for area CA1 (OR = .76, 95% CI = .66-.88, p < .01) and dentate gyrus (OR = .74, 95% CI = .62-.89, p < .05). IS in other MTL subregions or inferior and superior temporal gyrus and IS occurring during the prestimulus window did not affect word encoding (p > .05). IS during retrieval in right hippocampal (OR = .22, 95% CI = .08-.63, p = .01) and parahippocampal regions (OR = .24, 95% CI = .07-.8, p < .05) reduced the probability of recalling a word. SIGNIFICANCE: IS in medial and lateral temporal cortex contribute to transient memory decline during verbal episodic memory.

Spatiotemporal dynamics between interictal epileptiform discharges and ripples during associative memory processing.

We describe the spatiotemporal course of cortical high-gamma activity, hippocampal ripple activity and interictal epileptiform discharges during an associative memory task in 15 epilepsy patients undergoing invasive EEG. Successful encoding trials manifested significantly greater high-gamma activity in hippocampus and frontal regions. Successful cued recall trials manifested sustained high-gamma activity in hippocampus compared to failed responses. Hippocampal ripple rates were greater during successful encoding and retrieval trials. Interictal epileptiform discharges during encoding were associated with 15% decreased odds of remembering in hippocampus (95% confidence interval 6-23%). Hippocampal interictal epileptiform discharges during retrieval predicted 25% decreased odds of remembering (15-33%). Odds of remembering were reduced by 25-52% if interictal epileptiform discharges occurred during the 500-2000 ms window of encoding or by 41% during retrieval. During encoding and retrieval, hippocampal interictal epileptiform discharges were followed by a transient decrease in ripple rate. We hypothesize that interictal epileptiform discharges impair associative memory in a regionally and temporally specific manner by decreasing physiological hippocampal ripples necessary for effective encoding and recall. Because dynamic memory impairment arises from pathological interictal epileptiform discharge events competing with physiological ripples, interictal epileptiform discharges represent a promising therapeutic target for memory remediation in patients with epilepsy.

Isolated epileptiform activity in children and adolescents: prevalence, relevance, and implications for treatment.

In the field of psychiatry diagnoses are primarily based on the report of symptoms from either the patient, parents, or both, and a psychiatrist's observations. A psychiatric diagnosis is currently the most widely used basis for medication selection and the brain is seldom investigated directly as a source of those symptoms. This study addresses the request from the National Institute of Mental Health (NIMH) Research Domain Criteria Project (RDoC) for scientific research into neurological abnormalities that can be linked to psychiatric symptoms for the purpose of predicting medication response. One such neurological abnormality that has been the focus of many studies over the last three decades is isolated epileptiform discharges (IEDs) in children and adolescents without seizures. We conducted a systematic review of the literature to determine prevalence rates of IEDs within diagnostic categories. We then compared the prevalence of IEDs in the selected literature to our IRB-approved data archive. Our study found a consistent high prevalence of IEDs specifically for ADHD (majority > 25%) and ASD (majority > 59%), and consistent low prevalence rates were found for Depression (3%). If children and adolescents have failed multiple medication attempts, and more than one-third of them have IEDs, then an EEG would be justified within the RDoC paradigm.

[Inferior temporal electrodes in 24-h EEG]. / Subtemporale Elektroden im 24­Stunden-EEG.

BACKGROUND: To improve the sensitivity of the EEG in the diagnosis and classification of seizures or epilepsy, long-term recording with inferior temporal electrodes are recommended. MATERIAL AND METHODS: The spatial distribution of epileptiform discharges from 24­h EEG with 25 electrodes (10-20, extended by F9/F10, T9/T10, P9/P10) was retrospectively analyzed in 25 cases. RESULTS: Maximum negativity was located below the 10-20 electrodes in 84%. Epileptiform discharges were more clearly detected on inferior temporal electrodes in 64%. In the intention-to-test population of 77 patients the number needed to test with extra electrodes was estimated as 5. CONCLUSION: Recording EEG with 25 electrodes for 24 h improves the detection and localization of temporal epileptiform discharges also in geriatric patients with suspected nonlesional epilepsy.

[How our view of epileptogenesis and mechanism of epilepsy changes? The system epilepsies' concept]. / Nézetváltozások az epilepszia keletkezésérol és mechanizmusáról. Rendszeralapú megközelítés.

Background and purpose: To examine the ways of epileptogenesis closely linked to the system epilepsies' concept. Methods: We follow the ways of epileptic transformation in the declarative memory-system, in the sleep/arousal twin-systems, in the perisylvian neuronal network and in postinjury epilepsy, which we consider a general model of the epileptic transformation. Results: In the presented systems, epileptogenesis shares a similar mechanism in the form of augmentation and derailment of plasticity and sleep-related synaptic homeo-stasis. This highlights the central role of NREM sleep in those epilepsies. Conclusion: We try to characterize the concept of system epilepsies and suggest a shared mechanism of epileptogenesis.

How cerebral cortex protects itself from interictal spikes: The alpha/beta inhibition mechanism.

Interactions between interictal epileptiform discharges (IEDs) and distant cortical regions subserve potential effects on cognition of patients with focal epilepsy. We hypothesize that "healthy" brain areas at a distance from the epileptic focus may respond to the interference of IEDs by generating inhibitory alpha and beta oscillations. We predict that more prominent alpha-beta oscillations can be found in patients with less impaired neurocognitive profile. We performed a source imaging magnetoencephalography study, including 41 focal epilepsy patients: 21 with frontal lobe epilepsy (FLE) and 20 with mesial temporal lobe epilepsy. We investigated the effect of anterior (i.e., frontal and temporal) IEDs on the oscillatory pattern over posterior head regions. We compared cortical oscillations (5-80 Hz) temporally linked to 3,749 IEDs (1,945 frontal and 1,803 temporal) versus an equal number of IED-free segments. We correlated results from IED triggered oscillations to global neurocognitive performance. Only frontal IEDs triggered alpha-beta oscillations over posterior head regions. IEDs with higher amplitude triggered alpha-beta oscillations of higher magnitude. The intensity of posterior head region alpha-beta oscillations significantly correlated with a better neuropsychological profile. Our study demonstrated that cerebral cortex protects itself from IEDs with generation of inhibitory alpha-beta oscillations at distant cortical regions. The association of more prominent oscillations with a better cognitive status suggests that this mechanism might play a role in determining the cognitive resilience in patients with FLE.