Effect of interictal epileptiform discharges on EEG-based functional connectivity networks

ObjectiveFunctional connectivity networks (FCNs) based on interictal electroencephalography (EEG) can identify pathological brain networks associated with epilepsy. FCNs are altered by interictal epileptiform discharges (IEDs), but it is unknown whether this is due to the morphology of the IED or the underlying pathological activity. Therefore, we characterized the impact of IEDs on the FCN through simulations and EEG analysis.MethodsWe introduced simulated IEDs to sleep EEG recordings of eight healthy controls and analyzed the effect of IED amplitude and rate on the FCN. We then generated FCNs based on epochs with and without IEDs and compared them to the analogous FCNs from eight subjects with infantile spasms (IS), based on 1340 visually marked IEDs. Differences in network structure and strength were assessed.ResultsIEDs in IS subjects caused increased connectivity strength but no change in network structure. In controls, simulated IEDs with physiological amplitudes and rates did not alter network strength or structure.ConclusionsIncreases in connectivity strength in IS subjects are not artifacts caused by the interictal spike waveform and may be related to the underlying pathophysiology of IS.SignificanceDynamic changes in EEG-based FCNs during IEDs may be valuable for identification of pathological networks associated with epilepsy.     

Can single pulse electrical stimulation provoke responses similar to spontaneous interictal epileptiform discharges?

ObjectiveTo estimate the proportion of patients where EEG responses to single pulse electrical stimulation (SPES) are similar to spontaneous interictal epileptiform discharges (IEDs) in the same patient, and whether such resemblance is related to seizure onset.MethodsWe have visually compared the morphology, topography and distribution of IEDs and of SPES responses in 36 patients with intracranial EEG recordings during presurgical evaluation.ResultsEach patient showed between 3 and 17 different IED patterns, located at seizure onset zone and elsewhere. Only 13 patients showed the highest incidence and amplitude of IEDs at the site of focal seizure onset. Twenty-eight patients showed early responses which were similar to at least one IED pattern. Thirty patients showed delayed responses which were always similar to at least one IED pattern and were always located at seizure onset or in its vicinity.ConclusionsEarly SPES responses often, and delayed responses always, were similar to at least one IED pattern in the same patient. The IEDs resembling delayed responses were those associated with seizure onset.SignificanceThe similarities between IEDs and SPES responses suggest that SPES can trigger the mechanisms responsible for generating IEDs, which may become a tool to study the pathophysiology of IEDs.     

EEG–fMRI in focal epilepsy: Local activation and regional networks

ObjectiveTo identify features of BOLD signal change associated with interictal epileptiform discharges (IEDs) in a heterogeneous group of focal epilepsy patients.MethodsEEG/fMRI studies in 27 focal epilepsy patients were reviewed with attention given to the extent and location of the IED and the resulting pattern of BOLD signal change. Second order group analysis was used to identify common features.ResultsfMRI results provided novel clinical information for individual patients. We identified a significant common node within the ipsilateral piriform cortex as well as patterns involving distant cortical or subcortical areas.ConclusionDespite the heterogeneity of IEDs in focal epilepsy, there are important common features underpining IEDs with a highly significant fMRI node in the ipsilateral piriform cortex.SignificanceThere are important common features in the networks involved in IEDs in patients with a heterogeneous range of epileptogenic foci. We confirm that the piriform cortex is a common node underlying IEDs in patients with focal epilepsy and so provides a target for further study and potential therapy. We describe important features of BOLD signal change that accompany focal and diffuse IEDs that will help researchers and clinicians navigate the sometimes complex findings revealed by these studies.     

Towards fast and reliable simultaneous EEG-fMRI analysis of epilepsy with automatic spike detection

ObjectiveThe process of manually marking up epileptic spikes for simultaneous electroencephalogram (EEG) and resting state functional MRI (rsfMRI) analysis in epilepsy studies is a tedious and subjective task for a human expert. The aim of this study was to evaluate whether automatic EEG spike detection can facilitate EEG-rsfMRI analysis, and to assess its potential as a clinical tool in epilepsy.MethodsWe implemented a fast algorithm for detection of uniform interictal epileptiform discharges (IEDs) in one-hour scalp EEG recordings of 19 refractory focal epilepsy datasets (from 16 patients) who underwent a simultaneous EEG-rsfMRI recording. Our method was based on matched filtering of an IED template (derived from human markup) used to automatically detect other ‘similar’ EEG events. We compared simultaneous EEG-rsfMRI results between automatic IED detection and standard analysis with human EEG markup only.ResultsIn contrast to human markup, automatic IED detection takes a much shorter time to detect IEDs and export an output text file containing spike timings. In 13/19 focal epilepsy datasets, statistical EEG-rsfMRI maps based on automatic spike detection method were comparable with human markup, and in 6/19 focal epilepsy cases automatic spike detection revealed additional brain regions not seen with human EEG markup. Additional events detected by our automated method independently revealed similar patterns of activation to a human markup. Overall, automatic IED detection provides greater statistical power in EEG-rsfMRI analysis compared to human markup in a short timeframe.ConclusionsAutomatic spike detection is a simple and fast method that can reproduce comparable and, in some cases, even superior results compared to the common practice of manual EEG markup in EEG-rsfMRI analysis of epilepsy.SignificanceOur study shows that IED detection algorithms can be effectively used in epilepsy clinical settings. This work further helps in translating EEG-rsfMRI research into a fast, reliable and easy-to-use clinical tool for epileptologists.     

Lateralization of interictal EEG findings.

Several reports indicate that interictal epileptiform discharges (IED) may be more likely to occur over the left cerebral hemisphere than over the right. The objective of our study was to determine the frequency and type of IED on routine and multihour EEGs in a tertiary epilepsy center to estimate the frequency of left-sided versus right-sided IED and to determine interictal spike distribution pattern differences between adult and pediatric epilepsy patients. The current study retrospectively reviewed 31,207 EEGs (25,793 routine EEGs and 5414 multihour EEGs) recorded on 24,003 patients during the period from 1993 to 2003. All EEGs were read according to a systematic EEG classification system. Every patient was considered only once by including the first abnormal EEG. Regional unilateral or bilateral IEDs were recorded in 1707 patients (7%). Regional unilateral or bilateral slow was recorded in 2297 patients (9.6%). Left-sided regional IED were seen in 828 patients and accounted for 58% of all unilateral IED. Left-sided slow was seen in 1389 patients and accounted for 65% of all unilateral slow. Lateralization of slow was due to intermittent slow, whereas continuous slow involved both hemispheres equally. There was no lateralization difference in benign focal epileptiform discharges of childhood. Lateralization shows a tendency toward greater left-sided lateralization of interictal findings with aging. Benign focal epileptiform discharges were only seen under the age of 20 years old. Regional IEDs were seen in approximately 7% of patients and slowing occurs in 10% of patients. Both abnormalities were seen more frequently in the left hemisphere. Age adjusted analysis of the data revealed that this left-sided predominance was mildly increased in adults as compared with pediatric patients.     

Interictal activity is an important contributor to abnormal intrinsic network connectivity in paediatric focal epilepsy

Patients with focal epilepsy have been shown to have reduced functional connectivity in intrinsic connectivity networks (ICNs), which has been related to neurocognitive development and outcome. However, the relationship between interictal epileptiform discharges (IEDs) and changes in ICNs remains unclear, with evidence both for and against their influence. EEG‐fMRI data was obtained in 27 children with focal epilepsy (mixed localisation and aetiologies) and 17 controls. A natural stimulus task (cartoon blocks verses blocks where the subject was told “please wait”) was used to enhance the connectivity within networks corresponding to ICNs while reducing potential confounds of vigilance and motion. Our primary hypothesis was that the functional connectivity within visual and attention networks would be reduced in patients with epilepsy. We further hypothesized that controlling for the effects of IEDs would increase the connectivity in the patient group. The key findings were: (1) Patients with mixed epileptic foci showed a common connectivity reduction in lateral visual and attentional networks compared with controls. (2) Having controlled for the effects of IEDs there were no connectivity differences between patients and controls. (3) A comparison within patients revealed reduced connectivity between the attentional network and basal ganglia associated with interictal epileptiform discharges. We also found that the task activations were reduced in epilepsy patients but that this was unrelated to IED occurrence. Unexpectedly, connectivity changes in ICNs were strongly associated with the transient effects of interictal epileptiform discharges. Interictal epileptiform discharges were shown to have a pervasive transient influence on the brain's functional organisation. Hum Brain Mapp 38:221–236, 2017. © 2016 Wiley Periodicals, Inc.     

The influence of the abundance and morphology of epileptiform discharges on diagnostic accuracy: How many spikes you need to spot in an EEG

ObjectiveThe operational definition of interictal epileptiform discharges (IEDs) of the International Federation of Clinical Neurophysiology (IFCN) described six morphological criteria. Our objective was to assess the impact of pattern-repetition in the EEG-recording, on the diagnostic accuracy of using the IFCN criteria. For clinical implementation, specificity over 95% was set as target.MethodsInterictal EEG-recordings of 20-minutes, containing sharp-transients, from 60 patients (30 with epilepsy and 30 with non-epileptic paroxysmal events) were evaluated by three experts, who first marked IEDs solely based on expert opinion, and then, independently from the first session evaluated the presence of the IFCN criteria for each sharp-transient. The gold standard was derived from long-term video-EEG recordings of the patientś habitual paroxysmal episodes.ResultsPresence of at least one discharge fulfilling five criteria provided a specificity of 100% (sensitivity: 70%). For discharges fulfilling fewer criteria, a higher number of discharges was needed to keep the specificity over 95% (5 discharges, when only 3 criteria were fulfilled). A sequential combination of these sets of criteria and thresholds provided a specificity of 97% and sensitivity of 80%.ConclusionsPattern-repetition and IED morphology influence diagnostic accuracy.SignificanceSystematic application of these criteria will improve quality of clinical EEG interpretation.     

EEG‐fMRI in atypical benign partial epilepsy

Atypical benign partial epilepsy (ABPE) is a subgroup among the idiopathic focal epilepsies of childhood. Aim of this study was to investigate neuronal networks underlying ABPE and compare the results with previous electroencephalography (EEG)–functional magnetic resonance imaging (fMRI) studies of related epilepsy syndromes. Ten patients with ABPE underwent simultaneous EEG‐fMRI recording. In all 10 patients several types of interictal epileptiform discharges (IEDs) were recorded. Individual IED‐associated blood oxygen level–dependent (BOLD) signal changes were analyzed in a single subject analysis for each IED type (33 studies). A group analysis was also performed to determine common BOLD signal changes across the patients. IED‐associated BOLD signal changes were found in 31 studies. Focal BOLD signal changes concordant with the spike field (21 studies) and distant cortical and subcortical BOLD signal changes (31 studies) were detected. The group analysis revealed a thalamic activation. This study demonstrated that ABPE is characterized by patterns similar to studies in rolandic epilepsy (focal BOLD signal changes in the spike field) as well as patterns observed in continuous spikes and waves during slow sleep (CSWS) (distant BOLD signal changes in cortical and subcortical structures), thereby underscoring that idiopathic focal epilepsies of childhood form a spectrum of overlapping syndromes.     

Latency to first interictal epileptiform discharge in epilepsy with outpatient ambulatory EEG

ObjectiveThe diagnosis and classification of epilepsy often relies upon the demonstration of interictal epileptiform discharges (IEDs). Routine 20-min EEG recording has low sensitivity, with multiple EEGs increasing sensitivity to a maximum of 77% (Doppelbauer et al., 1993). An alternate strategy is the use of prolonged continuous EEG; however, there are no data on the average latency to first IED with ambulatory monitoring.MethodsIn this retrospective study we reviewed 180 consecutive patients with epilepsy referred to a Specialist Epilepsy Unit who had undergone 96 h outpatient ambulatory EEGs, without medication withdrawal, where IEDs were recorded. Latency to, and factors affecting first IED were analysed.ResultsMedian latency to first IED was 316 min, (interquartile range 70–772 min, n = 180). IEDs were recorded in 44% of patients within 4 h, 58% within 8 h, 85% within 24 h and 95% within 48 h. Recording for the full 96 h period revealed only 5% further IEDs. Multivariate analysis showed the latencies to IEDs with generalised epilepsies were shorter than with focal epilepsies (p < 0.0001).ConclusionsIn 95% of patients showing scalp IEDs a 48 h recording was sufficient for electro-clinical classification in this study.SignificanceOur data are the first to show the latency to recording interictal epileptiform discharges with prolonged outpatient EEG monitoring. These data are important in guiding diagnostic practice in Specialist Epilepsy Services.     

Focal interictal epileptiform discharges in idiopathic generalized epilepsy

Are idiopathic generalized epilepsies (IGEs) truly generalized? Do IGEs represent a continuum or rather distinct syndromes? Focal changes in the electroencephalography (EEG) have been reported in IGEs. The aim of this work is to investigate focal interictal epileptiform discharges (IEDs) in IGEs, and their relation to clinical variables. Forty-one IGE patients (classified according to ILAE, 2001) were recruited from a tertiary center (age 23 ± 10.938 years). Their files were reviewed and they were subjected to clinical examination and interictal EEG. Patients with focal IEDs were compared to those without focal IEDs. Nine patients had juvenile myoclonic epilepsy (JME) and 32 had idiopathic epilepsy with generalized tonic–clonic seizures only (EGTCSA). Focal IEDs were found in 20 patients, mostly in the frontal (45.5 %) and temporal (31.8 %) distribution. Patients with focal IEDs were treated with a larger number of combined antiepileptic drugs (AEDs) (p value = 0.022). No significant difference was found between the two groups regarding age, sex, age at onset, epilepsy syndrome, seizure frequency, family history, AEDs used (sodium valproate and carbamazepine) and their doses. Seventeen EGTCSA patients had focal IEDs. They were treated with larger number of combined AEDs (p value = 0.0142). No significant difference was found between the EGTCSA patients with and those without focal IEDs regarding age, sex, age at onset, seizure frequency, family history and AEDs doses. Caution must be applied in the interpretation of interictal focal IEDs. These focal changes may be related to prognosis, however this needs further investigation.     

Optimized set of criteria for defining interictal epileptiform EEG discharges

ObjectiveTo find and validate the optimal combination of criteria that define interictal epileptiform EEG discharges (IEDs). Our target was a specificity over 95%, to avoid over-reading in clinical EEG.MethodsWe constructed 63 combinations of the six criteria from the operational definition of IEDs, recently issued in the EEG-glossary of the International Federation of Clinical Neurophysiology (IFCN). The diagnostic gold standard was derived from video-EEG recordings. In a testing EEG dataset from 100 patients, we selected the best performing combinations of criteria and then we validated them in an independent dataset from 70 patients. We compared their performance with subjective, expert-scorings and we determined inter-rater agreement (IRA).ResultsWithout using criteria, the specificity of expert-scorings was lower than the pre-defined threshold (86%). The best performing combination of criteria was the following: waves with spiky morphology, followed by a slow-afterwave and voltage map suggesting a source in the brain. In the validation dataset this achieved a specificity of 97% and a sensitivity of 89%. IRA was substantial.ConclusionsThe optimized set of criteria for defining IEDs has high accuracy and IRA.SignificanceUsing these criteria will contribute to decreasing over-reading of EEG and avoid misdiagnosis of epilepsy.     

The seizure onset zone drives state-dependent epileptiform activity in susceptible brain regions

ObjectiveDue to variability in the patterns of propagation of interictal epileptiform discharges (IEDs), qualitative definition of the irritative zone has been challenging. Here, we introduce a quantitative approach toward exploration of the dynamics of IED propagation within the irritative zone.MethodsWe examined intracranial EEG (iEEG) in nine participants undergoing invasive monitoring for seizure localization. We used an automated IED detector and a community detection algorithm to identify populations of electrodes exhibiting IED activity that co-occur in time, and to group these electrodes into communities.ResultsWithin our algorithmically-identified communities, IED activity in the seizure onset zone (SOZ) tended to lead IED activity in other functionally coupled brain regions. The tendency of pathological activity to arise in the SOZ, and to spread to non-SOZ tissues, was greater in the asleep state.ConclusionsIED activity, and, by extension, the variability observed between the asleep and awake states, is propagated from a core seizure focus to nearby less pathological brain regions.SignificanceUsing an unsupervised, computational approach, we show that the spread of IED activity through the epilepsy network varies with physiologic state.     

Interictal epileptiform discharges in sleep and the role of the thalamus in Encephalopathy related to Status Epilepticus during slow Sleep

EEG activation of interictal epileptiform discharges (IEDs) during NREM sleep is a well‐described phenomenon that occurs in the majority of epileptic syndromes. In drug‐resistant focal epilepsy, IED activation seems to be related to slow wave activity (SWA), especially during arousal fluctuations, namely phase A of the cyclic alternating pattern (CAP). Conversely, in childhood focal epileptic syndromes, including Encephalopathy related to Status Epilepticus during slow Sleep (ESES), IED activation seems primarily modulated by sleep‐inducing and maintaining mechanisms as reflected by the dynamics of spindle frequency activity (SFA) rather than SWA. In this article, we will review the effect of sleep on IEDs with a particular attention on the activation and modulation of IEDs in ESES. Finally, we will discuss the role of the thalamus and cortico‐thalamic circuitry in this syndrome.     

A novel method for extracting interictal epileptiform discharges in multi-channel MEG: Use of fractional type of blind source separation

ObjectiveVisual inspection of interictal epileptiform discharges (IEDs) in multi-channel MEG requires a time-consuming evaluation process and often leads to inconsistent results due to variability of IED waveforms. Here, we propose a novel extraction method for IEDs using a T/k type of blind source separation (BSS_T/k).MethodsWe applied BSS_T/k with seven patients with focal epilepsy to test the accuracy of identification of IEDs. We conducted comparisons of the results of BSS components with those obtained by visual inspection in sensor-space analysis.ResultsBSS_T/k provided better signal estimation of IEDs compared with sensor-space analysis. Importantly, BSS_T/k was able to uncover IEDs that could not be detected by visual inspection. Furthermore, IED components were clearly extracted while preserving spike and wave morphology. Variable IED waveforms were decomposed into one dominant component.ConclusionsBSS_T/k was able to visualize the spreading signals over multiple channels into a single component from a single epileptogenic zone. BSS_T/k can be applied to focal epilepsy with a simple parameter setting.SignificanceOur novel method was able to highlight IEDs with increased accuracy for identification of IEDs from multi-channel MEG data.     

Diagnostic yield of high-density versus low-density EEG: The effect of spatial sampling,timing and duration of recording

ObjectiveTo investigate the effect of spatial sampling and of recording duration on the diagnostic yield of EEG for identification of interictal epileptiform discharges (IEDs). Previous studies demonstrated that high-density (HD) recordings increased accuracy of localization compared to low-density (LD) recordings.MethodsWe have prospectively evaluated the effect of spatial sampling and of recording duration in patients who had short-term (ST) recordings with a HD array of 256 electrodes following long-term (LT) recordings with a LD array consisting of the standard IFCN array of 25 electrodes. IED clusters were identified in four datasets: LT-LD, ST-LD (spatially down-sampled to the standard IFCN array), ST-HD and a shortened (90 minutes) epoch of LT-LD.ResultsSixty consecutive patients were recruited. We identified 89 IED clusters totally. Two clusters were found by increasing spatial sampling from 25 to 256 electrodes. This modest increase was not statistically significant. Eight clusters were missed by reducing the recording duration to 90 minutes, as compared with the LT recordings (p = 0.003).ConclusionsRecording duration is more important for the diagnostic yield of EEGs than increasing spatial sampling beyond the standard IFCN electrode array.SignificanceThe standard IFCN electrode array provides sufficient spatial sampling for identification of the IEDs.     

The network integration of epileptic activity in relation to surgical outcome

ObjectiveEpilepsy is a network disease with epileptic activity and cognitive impairment involving large-scale brain networks. A complex network is involved in the seizure and in the interictal epileptiform discharges (IEDs). Directed connectivity analysis, describing the information transfer between brain regions, and graph analysis are applied to high-density EEG to characterise networks.MethodsWe analysed 19 patients with focal epilepsy who had high-density EEG containing IED and underwent surgery. We estimated cortical activity during IED using electric source analysis in 72 atlas-based cortical regions of the individual brain MRI. We applied directed connectivity analysis (information Partial Directed Coherence) and graph analysis on these sources and compared patients with good vs poor post-operative outcome at global, hemispheric and lobar level.ResultsWe found lower network integration reflected by global, hemispheric, lobar efficiency during the IED (p < 0.05) in patients with good post-surgical outcome, compared to patients with poor outcome. Prediction was better than using the IED field or the localisation obtained by electric source imaging.ConclusionsAbnormal network patterns in epilepsy are related to seizure outcome after surgery.SignificanceOur finding may help understand networks related to a more “isolated” epileptic activity, limiting the extent of the epileptic network in patients with subsequent good post-operative outcome.     

Electrical cortical stimulations modulate spike and post-spike slow-related high-frequency activities in human epileptic foci

ObjectiveUsing interictal epileptiform discharges (IEDs), consisting of spikes and post-spike slow waves (PSSs), and IED-related high-frequency activities (HFAs), we elucidated inhibitory effects of electrical cortical stimulation (ECS) on human epileptic foci.MethodsWe recruited 8 patients with intractable focal epilepsy, and 50-Hz ECS was applied to the seizure-onset zone (SOZ) and non-SOZ. Before (5-min) and after (20-min) ECS, we evaluated the number of IED, the amplitudes of spikes and PSSs, spike-related HFA power, and PSS-related low gamma (30–50 Hz) activities.ResultsSOZ stimulation significantly decreased the number of IEDs and amplitude of spikes. Spike-related HFA power values in fast ripple (200–300 Hz) and ripple (80–150 Hz) bands were significantly suppressed only by SOZ stimulation in 4 and 3 patients, respectively. Among 4 patients with discrete PSSs, the amplitude ratio of spike/PSS decreased and the PSS-related low gamma activity power increased significantly in 2 patients and marginally in 1 patient.ConclusionsECS potentially modulates cortical excitability by reducing excitation and increasing inhibition, and monitoring IED-related HFAs may help achieve the optimal effects of ECS.SignificanceIED and IED-related HFAs are dynamic, potential surrogate markers for epileptic excitability during the interictal period.     

Magnetoencephalography to confirm epileptiform discharges mimicking small sharp spikes in temporal lobe epilepsy

ObjectiveTo determine whether magnetoencephalography (MEG) can identify epileptiform discharges mimicking small sharp spikes (SSSs) on scalp electroencephalography (EEG) in patients with temporal lobe epilepsy (TLE).MethodsWe retrospectively reviewed simultaneous scalp EEG and MEG recordings of 83 consecutive patients with TLE and 49 with extra-TLE (ETLE).ResultsSSSs in scalp EEG were detected in 15 (18.1%) of 83 TLE patients compared to only two (4.1%) of 49 ETLE patients (p = 0.029). Five of the 15 TLE patients had MEG spikes with concurrent SSSs in EEG, but neither of the 2 ETLE patients. Three of these 5 TLE patients had additional interictal epileptiform discharges (IEDs) in EEG and MEG. Equivalent current dipoles (ECDs) of MEG spikes with concurrent SSSs and IEDs showed no difference in temporal lobe localization and horizontal orientation, whereas ECD moments were smaller in MEG spikes with concurrent SSSs than those with IEDs.ConclusionsSSSs were more common in TLE than in ETLE. At least some morphologically diagnosed SSSs are true but low-amplitude epileptiform discharges in TLE which can be identified with simultaneous MEG.SignificanceSimultaneous MEG is useful to identify epileptiform discharges mimicking SSSs in patients with TLE.     

Different seizure-onset patterns in mesiotemporal lobe epilepsy have a distinct interictal signature

Objective

Experimental research demonstrated that distinct underlying mechanisms go along with different seizure-onset patterns on EEG. These different mechanisms may reflect different tissue abnormalities which, we hypothesize, could also be reflected in morphological differences in the interictal epileptic and background EEG activity.

Interictal Spiking Increases with Sleep Depth in Temporal Lobe Epilepsy

Summary: Purpose : To test the hypothesis that deepening sleep activates focal interictal epileptiform discharges (IEDs), we performed EEG-polysomnography in 21 subjects with medically refractory temporal lobe epilepsy.
Methods: At the time of study, subjects were seizure-free for 224 h and were taking stable doses of antiepileptic medications (AEDs). Sleep depth was measured by log delta power (LDP). Visual sleep scoring and visual detection of IEDs also were performed. Logistic-regression analyses of IED occurrence in relation to LDP were carried out for two groups of subjects, nine with frequent IEDs (group 1) and 12 with rare IEDs (group 2).
Results: The LDP differentiated visually scored non-rapid eye movement (NREM) sleep stages (p = 0.0001). The IEDs were most frequent in NREM stages 3/4 and least frequent in REM sleep. Within NREM sleep, in both groups, IEDs were more frequent at higher levels of LDP (p < 0.05). In group 1, after accounting for the level of LDP, IEDs were more frequent (a) on the ascending limb of LDP and with more rapid increases in LDP (p = 0.007), (b) in NREM than in REM sleep (p = 0.002), and (c) closer to sleep onset (p < 0.0001). Fewer than 1% of IEDs occurred within 10 s of an EEG arousal.
Conclusions: Processes underlying the deepening of NREM sleep, including progressive hyperpolarization in thalamocortical projection neurons, may contribute to IED activation in partial epilepsy. Time from sleep onset and NREM versus REM sleep also influence IED occurrence.