Patients with acute alteration in mental status from encephalopathy due to underlying metabolic-toxic or endocrine abnormalities are frequently seen in the acute hospital setting. A rapid diagnosis and correction of the underlying cause is essential as a prolonged state of encephalopathy portends a poor outcome. Correct diagnosis and management remain challenging because several encephalopathies may present similarly, and further laboratory, imaging or other testing may not always reveal the underlying cause. Electroencephalography (EEG) provides rapid additional information on the encephalopathic patient. It may help establish the diagnosis, and is indispensable for identifying non-convulsive status epilepticus – an important possible complication in this context. The EEG may assist the clinician in gauging the severity of brain dysfunction, and may aid in predicting outcome.
This review summarizes the current knowledge on EEG findings in selected metabolic and endocrine causes of encephalopathy, and highlights distinct EEG features associated with particular etiologies.
EEG; encephalopathy; altered mental status; delirium; endocrine disorders
In organotypic hippocampal slice cultures, principal neurons form aberrant excitatory connections with other principal cells in response to slicing-induced deafferentation, similar to mechanisms underlying epileptogenesis in post-traumatic epilepsy. To investigate the consequences of this synaptogenesis, we recorded field potential activity from area CA3 during perfusion with the complete growth medium used during incubation. At 7 days in vitro (DIV), slice cultures only displayed multi-unit activity. At 14 DIV the majority displayed population bursts reminiscent of interictal-like spikes, but sustained synchronous activity was rare. Bandpass filtering of interictal discharges revealed fast ripple-like complexes, similar to in vivo recordings. Spontaneous ictal-like activity became progressively more prevalent with age: at 21 DIV 50% of organotypic hippocampal slice cultures displayed long lasting, ictal-like discharges that could be suppressed by phenytoin, whereas interictal-activity was not suppressed. The fraction of cultures displaying ictal events continually increased with incubation time. Quantification of population spike activity throughout epileptogenesis using automatic detection and clustering algorithms confirmed the appearance of interictal-like activity before ictal-like discharges, and also revealed high frequency pathological multi-unit activity in slice cultures at 14–17 DIV. These experiments indicate that interictal-like spikes precede the appearance of ictal-like activity in a reduced in vitro preparation. Epileptiform activity in cultures resembled in vivo epilepsy, including sensitivity to anticonvulsants and steadily increasing seizure incidence over time, although seizure frequency and rate of epileptogenesis were higher in vitro. Organotypic hippocampal slice cultures comprise a useful model system for investigating mechanisms of epileptogenesis as well as developing anti-epileptic and anti-epileptogenic drugs.
Epileptogenesis; growth medium; interictal spikes; ictal discharges; organotypic hippocampal slices; phenytoin
We evaluated the validity and inter-rater reliability of encephalographer interpretation of color density spectral array (CDSA) EEG for seizure identification in critically ill children and explored predictors of accurate seizure identification.
Conventional EEG tracings from 21 consecutive critically ill children were scored for electrographic seizures. Four two-hour long segments from each patient were converted to 8 channel CDSA displays, yielding 84 images. Eight encephalographers received CDSA training and circled elements thought to represent seizures. Images were reviewed in random order (Group A) or with information regarding seizure presence in the initial 30 minutes and with patient images in order (Group B). Sensitivity, specificity, and inter-rater reliability were calculated. Factors associated with CDSA seizure identification were assessed.
Seizure prevalence was 43% on conventional EEG. Specificity was significantly higher for Group A (92.3% versus 78.2%, p<0.00). Sensitivity was not significantly different between Groups A and B (64.8% versus 75%, p=0.22). Inter-rater reliability was moderate in both groups. Ten percent of images were falsely classified as containing a seizure. Seizure duration ≥2 minutes predicted identification (p<0.001).
CDSA may be a useful screening tool for seizure identification by encephalographers, but it does not identify all seizures and false positives occur.
Critical Care; EEG; Pediatric; Seizure; EEG monitoring
The precision of navigated transcranial magnetic stimulation (TMS) to map the human primary motor cortex may be effected the direction of TMS-induced current in the brain as determined by the orientation of the stimulation coil. In this study, we investigated the effect of current directionality on motor output mapping using navigated brain stimulation (NBS). Our goal was to determine the optimal coil orientation (and, thus, induced brain current) to activate hand musculature representations relative to each subject’s unique neuroanatomical landmarks. We studied motor output maps for the first dorsal interosseous (FDI), abductor pollicis brevis (APB), and abductor digiti minimi (ADM) muscles in 10 normal volunteers. Monopolar current pulses were delivered through a figure-of-eight shaped TMS coil and motor evoked potentials (MEPs) were recorded using electromyography (EMG). At each targeted brain region, we systematically rotated the TMS coil to determine the direction of induced current in the brain for induction of the largest MEPs. These optimal current directions were expressed as an angle relative to each subject’s central sulcus. Consistency of the optimal current direction was assessed by repeating the entire mapping procedure on two different occasions across subjects. We demonstrate that systematic optimization of current direction as guided by MRI based neuronavigation improves the resolution of cortical output motor mapping with TMS.
Transcranial Magnetic Stimulation; Navigated Brain Stimulation; Cortical Excitability; Current Direction; Physiology; Electromyography (EMG)
Both electroencephalography (EEG) and magnetoencephalography (MEG) localize epileptiform activity but may yield different results. This discordance may arise from different detection capabilities or from different data collection and interpretation techniques. Comparisons of MEG and EEG have focused on detection of individual spikes. However, side-by-side comparisons of results as used in the clinical setting is lacking. In this report, we present our empirical comparison. We reviewed 58 simultaneous MEG-EEG recordings (35 paired-sensors, 23 whole-head) from a diverse epilepsy population, comparing previous clinical MEG interpretations with new blinded EEG interpretations, noting lobar concordance of readers’ judgments of regional abnormalities. A second-pass unblinded analysis, using all available clinical data, assessed the relative contribution and plausibility of the results of each technique. Concordance was high (85%) overall. Discordance was sometimes caused by constraints imposed by MEG dipole fitting techniques. Even when results of the techniques did not match, MEG often disambiguated the clinical scenario, especially when combined with imaging information. Thoughtful analysis of combined MEG-EEG datasets, beyond algorithm-based interictal spike detection, can help guide clinical decision-making even when concordance between techniques is imperfect. In some cases, EEG and MEG are synergistic and provide complementary information.
Magnetoencephalography; Electroencephalography; Epilepsy; Concordance
Power changes in the beta frequency range (17–25 Hz) in the human motor and premotor areas during action observation have been associated with the mirror neuron system (MNS) and have been studied extensively. These changes mimic motor activity during actual motion execution, albeit reduced in strength. Recent non-invasive (EEG/MEG) and invasive studies (ECoG) have shown that during actual motion, beta power changes are accompanied by highly localized changes in the high gamma (HG) band (70–100 Hz). In this study we investigate, using 27 channel EEG in combination with a generic head model and a cortical mapping algorithm, whether such high gamma changes are also present during motion observation. Subjects were presented with a 2.7 s video of a moving hand, contrasted with a video of moving scenery of equal length. Our results show non-lateralized beta band decrease in power in response to the moving hand vs. the response to the moving scenery. We also find significant increase in high gamma power. However, unlike the beta band response, increases in this band are lateralized, with a preference for the hemisphere of the dominant hand.
EEG; high gamma; motor system; motion observation
In contrast to EEG, which has guidelines for interpretation and a plethora of textbooks, the full range of activity seen in Magnetoencephalography (MEG) has not been fleshed out. Currently, magnetoencephalographers apply criteria for EEG waveforms to MEG signals based on an assumption that MEG activity should have morphology that is similar to EEG. The purpose of this paper is to show the characteristic MEG profile of Positive Occipital Sharp Transients of Sleep (POSTS)
Simultaneous MEG-EEG recordings of two cases are shown.
In the both cases, the morphological features of POSTS in MEG vary, and sometimes mimic epileptic spikes.
This report raises a caution that a normal variant may have an even more epileptic appearance on MEG than on EEG. Employing the simultaneously recorded EEG to avoid misinterpretation of spikey-looking POSTS in MEG is a natural and prudent practice.
EEG; Magnetoencephalography; Positive Occipital Sharp Transients of Sleep; Epileptic Spikes
To describe current continuous EEG (cEEG) utilization in critically ill children.
An online survey of pediatric neurologists from 50 United States (U.S.) and 11 Canadian institutions was conducted in August 2011.
Responses were received from 58 of 61 (95%) surveyed institutions. Common cEEG indications are altered mental status after a seizure or status epilepticus (97%), altered mental status of unknown etiology (88%), or altered mental status with an acute primary neurological condition (88%). The median number of patients undergoing cEEG per month per center increased from August 2010 to August 2011 (6 to 10 per month in U.S., 2 to 3 per month in Canada). Few institutions have clinical pathways addressing cEEG use (31%). Physicians most commonly review cEEG twice per day (37%). There is variability regarding which services can order cEEG, the degree of neurology involvement, technologist availability, and whether technologists perform cEEG screening.
Among the surveyed institutions, which included primarily large academic centers, cEEG use in pediatric intensive care units is increasing and is often considered indicated for children with altered mental status at risk for non-convulsive seizures. However, there remains substantial variability in cEEG access and utilization among institutions.
Critical Care; EEG; Pediatric; Survey; EEG monitoring
Routine EEGs remain a cornerstone test in caring for people with epilepsy. Although rare, a self-limited seizure (clinical or electrographic only) may be observed during such brief EEGs. The implications of observing a seizure in this situation, especially with respect to inferring the underlying seizure frequency, are unclear. The issue is complicated by the inaccuracy of patient-reported estimations of seizure frequency. The treating clinician is often left to wonder whether the single seizure indicates very frequent seizures, or if it is of lesser significance. We applied standard concepts of probabilistic inference to a simple model of seizure incidence to provide some guidance for clinicians facing this situation. Our analysis establishes upper and lower bounds on the seizure rate implied by observing a single seizure during routine EEG. Not surprisingly, with additional information regarding the expected seizure rate, these bounds can be further constrained. This framework should aid the clinician in applying a more principled approach toward decision making in the setting of a single seizure on a routine EEG.
Bayes’rule; seizure frequency; statistical inference; EEG
EEG monitoring; seizure; pediatric; hypoxia-ischemia; stroke; ECMO; cardiac arrest; congenital heart disease; status epilepticus
Neonatal seizures are common, often require electroencephalographic (EEG) monitoring for diagnosis and management, may be associated with worse neurodevelopmental outcome, and can often be treated with existing anticonvulsants. A neonatal electrographic seizure is defined as a sudden, repetitive, evolving and stereotyped event of abnormal electrographic pattern with amplitude of at least two microvolts and a minimum duration of ten seconds. The diagnosis of neonatal seizures relies heavily on the neurophysiologist’s interpretation of EEG. Consideration of specific criteria for the definition of a neonatal seizure, including seizure duration, location, morphology, evolution, semiology, and overall seizure burden, have utility for both the clinician and researcher. We review the importance of EEG in the diagnosis and management of neonatal seizures, the electrographic characteristics of neonatal seizures, the impact of neonatal seizures on outcome, and tools to aid in the identification of neonatal seizures.
seizures; neonate; electroencephalography; status epilepticus
Dorsolateral frontal lobe seizures often present as a diagnostic challenge. The diverse semiologies may not produce lateralizing or localizing signs, and can appear bizarre and suggest psychogenic events. Unfortunately, scalp EEG and MRI are often unsatisfactory. It is not uncommon that these traditional diagnostic studies are either unhelpful or even misleading. In some cases SPECT and PET imaging can be an effective tool to identify the origin of seizures. However, these techniques and other emerging techniques all have limitations, and new approaches are needed to improve source localization.
Frontal lobe epilepsy; EEG
Infraslow Activity (ISA), Direct Coupled (DC), or Direct Current (DC) are the terms used to describe brain activity that occurs in frequencies below 0.1Hz. ISA amplitude increase is also associated with epilepsy, traumatic brain injuries, strokes, tumors and migraines and has been studied since the early 90’s at the Henry Ford Hospital MEG Laboratory. We have used a DC based MEG system to validate and characterize the ISA from animal models of cortical spreading depression (CSD) thought to be the underlying mechanism of migraine as well as other CSD-like events seen during ischemia, anoxia, and epilepsy. MEG characterizes these slow shifts easier than EEG as there is no attenuation of these signals by the skull. In the current study we report on ISA MEG signals of 12 patients with epilepsy in the pre- and postictal state. In the minutes just prior to the onset of a seizure, large amplitude, ISA MEG waveforms were detected, signaling the onset of the seizure. It is suggested that MEG assessment of ISA, in addition to activity in the conventional frequency band, can at times be useful in the lateralization of epileptic seizures.
Magnetoencephalography (MEG); Electroencephalography (EEG); Ictal activity; Infra Slow Activity (ISA); Direct Coupled (DC); cortical spreading depression (CSD)
In neocortical epilepsy, we showed that the seizure onset defined by ictal high frequency oscillations (HFO: ≥70 Hz) with subsequent evolution into slower frequency activity (i.e., HFOs+) was smaller in spatial distribution than that defined by conventional frequency activity (CFA: 1–70 Hz), and that resection of HFO+ areas resulted in favorable seizure outcome (Modur et al., Epilepsia 2011; 52:1792–1801). This study further investigates ictal broadband EEG in the same cohort of patients by examining the infraslow activity (ISA) including ictal baseline (“DC”) shifts (IBS) and peri-ictal infraslow activity (PISA: 0.02–0.2 Hz). The seizure onset zone (SOZ) had been defined and resected based on HFO+ by a prospectively-defined protocol. We reviewed 11 representative seizures from 6 patients by visual and spectral analyses using appropriate filters and time scales. The HFO seizure onset, in the high gamma or ripple frequency, preceded or followed the IBS closely (<300-ms). The IBS were negative or positive, ~1 mV in amplitude and 2–3 s long. While the HFO+ were always ipsilateral to the surgical hemisphere, the IBS could be ipsilateral or contralateral. Compared to CFA, the HFO+ and IBS were significantly smaller in spatial distribution and likely to be concordant. The PISA consisted of distinct periodic or rhythmic (0.12–0.16 Hz) patterns, poorly concordant with IBS or HFO+. Although not statistically significant, better seizure outcome tended to correlate with smaller SOZs and more complete resection of the HFO+ and IBS contacts. We conclude that IBS, like HFO+, define a smaller SOZ and probably a more accurate epileptogenic zone in neocortical epilepsy.
Seizure; Epilepsy; Surgery; Intracranial; High frequency oscillations; HFO; Infraslow; DC shift; Broadband; EEG
The differential dysfunction of chromatic and achromatic visual pathways in early Parkinson’s disease (PD) was evaluated by means of visual-evoked potentials (VEPs) recorded in 12 patients (mean age 60.1 ± 8.3 years; range 46 to 74 years) in the early stages of PD and not yet undergoing treatment with L-dopa, and in 12 age-matched controls. Visual stimuli were full-field (14 deg) equiluminant red-green (R-G), blue-yellow (B-Y), and black-white (B-W) sinusoidal gratings of two cycles per degree, presented in onset (300 milliseconds) – offset (700 milliseconds) mode, at two contrast (K) levels (90% and 25%). The VEP mean latencies were significantly more delayed in PD patients than in controls for chromatic than for luminance stimuli, in particular for B-Y stimuli of low contrast (K90%: B-W =6.6 milliseconds, R-G =3.34 milliseconds, B-Y =15.48 milliseconds; K25%: B-W =7.8 milliseconds, R-G =14.8 milliseconds, B-Y =28.9). Latencies of chromatic VEPs were more variable that achromatic VEP latencies in both normal subjects and PD patients. Therefore, the frequency of latency abnormalities (within 30%) was not significantly different for the three visual stimuli. Our results show that, in addition to achromatic VEPs, chromatic VEPs are impaired in early PD patients not yet undergoing L-dopa therapy, indicating an acquired color deficiency in these patients. The greater delay for the B-Y VEPs suggests a higher vulnerability of visual blue-cone pathway in the early stages of the disease. However, the overall sensitivity of chromatic VEPs in detecting early visual impairment in PD is comparable with that of achromatic VEPs.
Chromatic contrast; VEPs; Parkinson’s disease; Parvocellular; Koniocellular; Magnocellular system
Magnetoencephalography (MEG) non-invasively measures the magnetic fields produced by the brain. Pertinent research articles from 1993 to 2009 that measured spontaneous, whole-head MEG activity in schizophrenic patients were reviewed. Data on localization of oscillatory activity and correlation of these findings with psychotic symptoms are summarized. While the variety of measures used by different research groups makes a quantitative meta-analysis difficult, it appears that MEG activity in patients may exhibit identifiable patterns, defined by topographic organization and frequency band. Specifically, 11 of the 12 studies showed increased theta (4–8 Hz) and delta (1–4 Hz) band oscillations in the temporal lobes of patients; of the 10 studies that examined the relationship between oscillatory activity and symptomatology, 8 found a positive correlation between temporal lobe theta activity and positive schizophrenic symptoms. Abnormally high frontal delta activity was not seen. These findings are analyzed in comparison to the EEG literature on schizophrenics, and possible confounds (e.g., medication effects) are discussed. In the future, MEG might be used to assist in diagnosis, or might be fruitfully used in conjunction with new neuroscience research approaches such as computational modeling, which may be able to link oscillatory activity and cellular-level pathology.
magnetoencephalography; schizophrenia; resting state networks; oscillations; positive symptoms; antipsychotic agents
Periodic limb movements (PLMs) and obstructive sleep apnea (OSA) may present as overlapping conditions. This study investigated the occurrence of PLM during continuous positive airway pressure (CPAP) titration, with the hypothesis that the presence of PLM during CPAP represented “unmasking” of a coexisting sleep disorder.
A total of 78 polysomnographic recordings in 39 OSA subjects with an hourly PLM index ≥5 during CPAP application were evaluated.
Application of CPAP significantly improved sleep architecture without change in the PLM index when compared with baseline. The PLM indices and PLM arousal indices were linearly correlated during both nights (r = 0.553, P < 0.01; r = 0.548, P < 0.01, respectively). Eleven subjects with low PLM indices at baseline had greater changes in the PLM index as compared with the sample remainder (P = 0.004). Sixteen subjects with significantly lower PLM indices at baseline required optimal CPAP levels higher than the sample average of 8.2 cm H2O (P = 0.032). These subjects also showed significantly higher median apnea–hypopnea index (AHI) at baseline than the sample remainder (74.4 events per hour [range: 24.2–124.4 events per hour] vs. 22.7 events per hour [range: 8.6–77.4 events per hour], respectively, P < 0.001).
These findings suggest that PLM seen during CPAP titration may be related to a concurrent sleep disorder because of “unmasking” in patients with treated OSA.
Periodic limb movements (PLM); Obstructive sleep apnea (OSA); Continuous positive airway pressure (CPAP); Sleep disorders; Polysomnography
Recent research aims at developing a biomarker to predict antidepressant treatment outcomes in Major Depressive Disorder (MDD). The Antidepressant Treatment Response index (ATRindex) has been correlated with response to antidepressant medication (Leuchter et al., 2009a, 2009b) but has not been assessed in a placebo-controlled trial. EEGs were used to calculate ATR-index for 23 randomized MDD subjects to eight weeks of fluoxetine treatment (FLX) 20 mg (n=12) or placebo (n=11). The 17-item Hamilton Depression Rating Scale (HamD17) assessed symptom severity, while a percent change in HamD17 score, endpoint response (≥ 50% improvement) and remission (HamD17 score ≤ 7) were used to assess ATR-index as a predictor. ATR-index was significantly associated with improvement on FLX (r = .64, p = .01), with a higher mean ATR-index for FLX responders than non-responders (t(10)= −2.07, p=0.03). Receiver Operating Characteristic analysis found a .83 area under the curve (p = .03), for ATR-index as a predictor for FLX, while an optimized ATR-index cutoff of 47.3 yielded 100% sensitivity, 66.7% specificity, 75% PPV and 100% NPV. Importantly, ATR-index did not correlate significantly with placebo outcomes. Results extend ATR-index findings to include predictive validity with fluoxetine, suggesting that this biomarker has specificity for drug effects.
antidepressant medication; placebo response; biomarker; EEG
To compare three methods of localizing the source of epileptiform activity recorded with magnetoencephalography (MEG): equivalent current dipole (ECD), minimum current estimate (MCE), and dynamic statistical parametric mapping (dSPM), and to evaluate the solutions by comparison with clinical symptoms and other electrophysiological and neuroradiological findings.
Fourteen children of 3 to 15 years old were studied. MEG was collected with a whole-head 204-channel helmet-shaped sensor array. We calculated ECDs and made MCE and dSPM movies to estimate the cortical distribution of interictal epileptic discharges (IED) in these patients.
The results for 4 patients with localization related epilepsy (LRE) and 1 patient with Landau-Kleffner Syndrome were consistent among all 3 analysis methods. In the rest of the patients MCE and dSPM suggested multifocal or widespread activity; in these patients the ECD results were so scattered that interpretation of the results was not possible. For 9 patients with LRE and generalized epilepsy, the epileptiform discharges were wide-spread or only slow waves, but dSPM suggested a possible propagation path of the IED.
MCE and dSPM could identify the propagation of epileptiform activity with high temporal resolution. The results of dSPM were more stable because the solutions were less sensitive to background brain activity.
MEG; epilepsy; dynamic statistical parametric mapping; minimum current estimate; minimum norm estimate; equivalent current dipole
The following are “minimum standards” for the routine clinical recording of magnetic evoked fields (MEFs) in all age-groups.
Practicing at minimum standards should not be the goal of a magnetoencephalography (MEG) center but rather a starting level for continued improvement. Minimum standards meet only the most basic responsibilities to the patient and the referring physician.
These minimum standards have been put forth to improve standardization of procedures, to facilitate interchange of recordings and reports among laboratories in the United States, and to confirm the expectations of referring physicians.
Recommendations regarding Laboratory (Center) Environment and Preparation for MEG Recordings are detailed in the American Clinical Magnetoencephalography Society Clinical Practice Guideline (CPG) 1 : Recording and Analysis of Spontaneous Cerebral Activity, except for its EEG aspect that is not considered necessary (although may be helpful in trained hands) for MEFs (presurgical functional brain mapping).
Correct outcome prediction after cardiac arrest in children may improve clinical decision making and family counseling. Various investigators have used EEG to predict outcome with varying success, but one limiting issue is the potential lack of reproducibility of EEG interpretation. Therefore, we aimed to evaluate interobserver agreement using standardized terminology in the interpretation of EEG tracings obtained from critically ill children following cardiac arrest.
3 pediatric neurophysiologists scored 74 EEG samples using standardized categories, terminology, and interpretation rules. Interobserver agreement was evaluated using kappa and intra-class correlation coefficients.
Agreement was substantial for the categories of continuity, burst suppression, sleep architecture, and overall rating. Agreement was moderate for seizure occurrence and inter-ictal epileptiform discharge type. Agreement was fair for inter-ictal epileptiform discharge presence, beta activity, predominant frequency, and fastest frequency. Agreement was slight for maximum voltage and focal slowing presence.
The variability of inter-rater agreement suggests that some EEG features are superior to others for use in a predictive algorithm. Using only reproducible EEG features is needed to ensure the most accurate and consistent predictions. Since even seizure identification had only moderate agreement, studies of non-convulsive seizures in critically ill patients must be conducted and interpreted cautiously.
Electroencephalogram; Interobserver variability; Seizure; Pediatric; Hypoxic Ischemic Encephalopathy; Cardiac Arrest
Theta Burst Stimulation (TBS) protocols have recently emerged as a method to transiently alter cortical excitability in the human brain through repetitive transcranial magnetic stimulation (rTMS). TBS involves applying short trains of stimuli at high frequency repeated at intervals of 200ms. Because rTMS is known to carry a risk of seizures, safety guidelines have been established. TBS has the theoretical potential of conferring an even higher risk of seizure than other rTMS protocols because it delivers high frequency bursts. In light of the recent report of a seizure induced by TBS, the safety of this new protocol deserves consideration. We performed an English language literature search, and reviewed all studies published from May 2004-December 2009 in which TBS was applied. The adverse events were documented and crude risk was calculated. The majority of adverse events attributed to TBS were mild and occurred in 5% of subjects. Based on this review, TBS appears to be a safe and efficacious technique. However, given its novelty, it should be applied with caution. Additionally, this review highlights the need for rigorous documentation of adverse events associated with TBS, as well as intensity dosing studies to assess the seizure risk associated with various stimulation parameters (e.g. frequency, intensity, location).
Theta Burst Stimulation; Safety; Transcranial Magnetic Stimulation; Adverse Events; Risks; Meta-analysis
Microseizures are highly focal low-frequency epileptiform-appearing events recorded from the neocortex of epilepsy patients. Because of their tiny, often submillimeter distribution they may be regarded as a high resolution window into the epileptic process, providing an excellent opportunity to study the fine temporal structure of their origin and spread. A 16 mm2 96 microelectrode array with 400 micron interelectrode spacing was implanted in seven patients undergoing invasive EEG monitoring for medically refractory epilepsy. Seven microdischarge populations were tested for a substantial contribution by volume conduction to the observed waveform amplitudes. Single unit activity was examined for specific evidence of neural activity at multiple sites within the microdischarge fields. We found that microdischarges appear to originate at a highly focal source location, likely within a single cortical macrocolumn, and spread to local and more distant sites via neural propagation.
multichannel extracellular recording; epilepsy; intracranial EEG; epileptiform discharges; microseizures
In the neocortex, neurons participate in epochs of elevated activity, or Up states, during periods of quiescent wakefulness, slow-wave sleep, and general anesthesia. The regulation of firing during and between Up states is of great interest because it can reflect the underlying connectivity and excitability of neurons within the network. Automated analysis of the onset and characteristics of Up state firing across different experiments and conditions requires a robust and accurate method for Up state detection. Using measurements of membrane potential mean and variance calculated from whole-cell recordings of neurons from control and postseizure tissue, the authors have developed such a method. This quantitative and automated method is independent of cell- or condition-dependent variability in underlying noise or tonic firing activity. Using this approach, the authors show that Up state frequency and firing rates are significantly increased in layer 2/3 neocortical neurons 24 hours after chemo-convulsant-induced seizure. Down states in postseizure tissue show greater membrane-potential variance characterized by increased synaptic activity. Previously, the authors have found that postseizure increase in excitability is linked to a gain-of-function in BK channels, and blocking BK channels in vitro and in vivo can decrease excitability and eliminate seizures. Thus, the authors also assessed the effect of BK-channel antagonists on Up state properties in control and postseizure neurons. These data establish a robust and broadly applicable algorithm for Up state detection and analysis, provide a quantitative description of how prior seizures increase spontaneous firing activity in cortical networks, and show how BK-channel antagonists reduce this abnormal activity.
epilepsy; seizure; Up state; BK channels; classification