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Introduction: Critical Care Continuous EEG (CCEEG) is a common procedure to monitor brain function in patients with altered mental status in intensive care units. There is significant variability in patient populations undergoing CCEEG and in technical specifications for CCEEG performance. Methods: The Critical Care Continuous EEG Task Force of the American Clinical Neurophysiology Society developed expert consensus recommendations on the use of CCEEG in critically ill adults and children. Recommendations: The consensus panel recommends CCEEG for diagnosis of nonconvulsive seizures, nonconvulsive status epilepticus, and other paroxysmal events, and for assessment of the efficacy of therapy for seizures and status epilepticus. The consensus panel suggests CCEEG for identification of ischemia in patients at high risk for cerebral ischemia; for assessment of level of consciousness in patients receiving intravenous sedation or pharmacologically induced coma; and for prognostication in patients after cardiac arrest. For each indication, the consensus panel describes the patient populations for which CCEEG is indicated, evidence supporting use of CCEEG, utility of video and quantitative EEG trends, suggested timing and duration of CCEEG, and suggested frequency of review and interpretation. Conclusion: CCEEG has an important role in detection of secondary injuries such as seizures and ischemia in critically ill adults and children with altered mental status

Introduction: Critical Care Continuous EEG (CCEEG) is a common procedure to monitor brain function in patients with altered mental status in intensive care units. There is significant variability in patient populations undergoing CCEEG and in technical specifications for CCEEG performance. Methods: The Critical Care Continuous EEG Task Force of the American Clinical Neurophysiology Society developed expert consensus recommendations on the use of CCEEG in critically ill adults and children. Recommendations: The consensus panel describes the qualifications and responsibilities of CCEEG personnel including neurodiagnostic technologists and interpreting physicians. The panel outlines required equipment for CCEEG, including electrodes, EEG machine and amplifier specifications, equipment for polygraphic data acquisition, EEG and video review machines, central monitoring equipment, and network, remote access, and data storage equipment. The consensus panel also describes how CCEEG should be acquired, reviewed and interpreted. The panel suggests methods for patient selection and triage; initiation of CCEEG; daily maintenance of CCEEG; electrode removal and infection control; quantitative EEG techniques; EEG and behavioral monitoring by non-physician personnel; review, interpretation, and reports; and data storage protocols. Conclusion: Recommended qualifications for CCEEG personnel and CCEEG technical specifications will facilitate standardization of this emerging technology

Interictal epileptiform discharges (IEDs), also known as interictal spikes, are large intermittent electrophysiological events observed between seizures in patients with epilepsy. Although they occur far more often than seizures, IEDs are less studied, and their relationship to seizures remains unclear. To better understand this relationship, we examined multi-day recordings of microelectrode arrays implanted in human epilepsy patients, allowing us to precisely observe the spatiotemporal propagation of IEDs, spontaneous seizures, and how they relate. These recordings showed that the majority of IEDs are traveling waves, traversing the same path as ictal discharges during seizures, and with a fixed direction relative to seizure propagation. Moreover, the majority of IEDs, like ictal discharges, were bidirectional, with one predominant and a second, less frequent antipodal direction. These results reveal a fundamental spatiotemporal similarity between IEDs and ictal discharges. These results also imply that most IEDs arise in brain tissue outside the site of seizure onset and propagate toward it, indicating that the propagation of IEDs provides useful information for localizing the seizure focus., Competing Interests: ES, JL, EM, TD, KT, BG, RE, RG, CS No competing interests declared, PH is affiliated with Neurosurgical Associates, LLC. The author has no financial interests to declare, GM reports fees from Koh Young, Inc, SS consulting for Boston Scientific, Abbott, Neuropace, Zimmer Biomet, JR reports fees from Medtronic, Inc, (© 2022, Smith et al.)

Analyzing neuronal activity during human seizures is pivotal to understanding mechanisms of seizure onset and propagation. These analyses, however, invariably using extracellular recordings, are greatly hindered by various phenomena that are well established in animal studies: changes in local ionic concentration, changes in ionic conductance, and intense, hypersynchronous firing. The first two alter the action potential waveform, whereas the third increases the "noise"; all three factors confound attempts to detect and classify single neurons. To address these analytical difficulties, we developed a novel template-matching-based spike sorting method, which enabled identification of 1239 single neurons in 27 patients (13 female) with intractable focal epilepsy, that were tracked throughout multiple seizures. These new analyses showed continued neuronal firing with widespread intense activation and stereotyped action potential alterations in tissue that was invaded by the seizure: neurons displayed increased waveform duration ( p < 0.001) and reduced amplitude ( p < 0.001), consistent with prior animal studies. By contrast, neurons in "penumbral" regions (those receiving intense local synaptic drive from the seizure but without neuronal evidence of local seizure invasion) showed stable waveforms. All neurons returned to their preictal waveforms after seizure termination. We conclude that the distinction between "core" territories invaded by the seizure versus "penumbral" territories is evident at the level of single neurons. Furthermore, the increased waveform duration and decreased waveform amplitude are neuron-intrinsic hallmarks of seizure invasion that impede traditional spike sorting and could be used as defining characteristics of local recruitment. SIGNIFICANCE STATEMENT Animal studies consistently show marked changes in action potential waveform during epileptic discharges, but acquiring similar evidence in humans has proven difficult. Assessing neuronal involvement in ictal events is pivotal to understanding seizure dynamics and in defining clinical localization of epileptic pathology. Using a novel method to track neuronal firing, we analyzed microelectrode array recordings of spontaneously occurring human seizures, and here report two dichotomous activity patterns. In cortex that is recruited to the seizure, neuronal firing rates increase and waveforms become longer in duration and shorter in amplitude as the neurons are recruited to the seizure, while penumbral tissue shows stable action potentials, in keeping with the "dual territory" model of seizure dynamics., (Copyright © 2021 the authors.)

High frequency oscillations (HFOs) are bursts of neural activity in the range of 80 Hz or higher, recorded from intracranial electrodes during epileptiform discharges. HFOs are a proposed biomarker of epileptic brain tissue and may also be useful for seizure forecasting. Despite such clinical utility of HFOs, the spatial context and neuronal activity underlying these local field potential (LFP) events remains unclear. We sought to further understand the neuronal correlates of ictal high frequency LFPs using multielectrode array recordings in the human neocortex and mesial temporal lobe during rhythmic onset seizures. These multiscale recordings capture single cell, multiunit, and LFP activity from the human brain. We compare features of multiunit firing and high frequency LFP from microelectrodes and macroelectrodes during ictal discharges in both the seizure core and penumbra (spatial seizure domains defined by multiunit activity patterns). We report differences in spectral features, unit-local field potential coupling, and information theoretic characteristics of high frequency LFP before and after local seizure invasion. Furthermore, we tie these time-domain differences to spatial domains of seizures, showing that penumbral discharges are more broadly distributed and less useful for seizure localization. These results describe the neuronal and synaptic correlates of two types of pathological HFOs in humans and have important implications for clinical interpretation of rhythmic onset seizures.

Background Context: Hemodynamically significant bradycardia and cardiac arrest (CA) are rare under general anesthesia (GA) for spine surgery. Although patient risks are well defined, emerging data implicate surgical, anesthetic and neurologic factors which should be considered in the immediate management and decision to continue or terminate surgery., Purpose: To characterize causes and contributors to significant arrhythmias during spine surgery. We also provide an updated literature review to inform spine care teams and aid in the management of intraoperative bradycardia and CA., Study Design: Case series and literature review., Patient Sample: Six patients who underwent spine surgery from 03/2016 to 01/2020 at a single institution and developed unexpected hemodynamically significant arrhythmia., Outcome Measures: Our primary outcome was to identify potential risk factors of interest for significant arrhythmia during spine surgery., Methods: Medical records of patients who underwent spine surgery from 03/2016 to 01/2020 at a single institution and developed unexpected hemodynamically significant arrhythmia during spine surgery were identified from a departmental Quality Assurance Database. We evaluated the presence/absence of patient, surgical, anesthetic and neurologic risk factors and estimated the most likely etiology of the event, immediate and subsequent management, whether surgery was postponed or continued and outcomes., Results: We found a temporal relationship of bradyarrhythmia and CA after somatosensory evoked potential (SSEP) stimulation in 4/6 cases and pharmacy/polypharmacy in 2/6. Surgery was completed in 4/6 patients, and terminated in 2/6 (subsequently completed in both). We found no adverse outcomes in any patients. Our literature review predominately identified case reports for guidance to support decision making. New literaure suggests peripheral nerve blocks and opioid-sparing anesthetic agents should also be considered., Conclusions: Significant bradycardia and CA during spine surgery does not always require termination of the surgical procedure. Decision making should be undertaken in each case individually, with an updated awareness of potential causes. The study also suggests the need for large prospective studies to adequately assess incidence, risk factors and outcomes., Competing Interests: The authors have no conflict of interest directly relevant to this work., (© 2020 The Authors. Published by Elsevier Ltd on behalf of North American Spine Society.)

We developed a neural network model that can account for major elements common to human focal seizures. These include the tonic-clonic transition, slow advance of clinical semiology and corresponding seizure territory expansion, widespread EEG synchronization, and slowing of the ictal rhythm as the seizure approaches termination. These were reproduced by incorporating usage-dependent exhaustion of inhibition in an adaptive neural network that receives global feedback inhibition in addition to local recurrent projections. Our model proposes mechanisms that may underline common EEG seizure onset patterns and status epilepticus, and postulates a role for synaptic plasticity in the emergence of epileptic foci. Complex patterns of seizure activity and bi-stable seizure end-points arise when stochastic noise is included. With the rapid advancement of clinical and experimental tools, we believe that this model can provide a roadmap and potentially an in silico testbed for future explorations of seizure mechanisms and clinical therapies., Competing Interests: JL, ES, LB, SB, GM, RG, RE, CS, LA No competing interests declared, (© 2020, Liou et al.)

We analyze the role of inhibition in sustaining focal epileptic seizure activity. We review ongoing seizure activity at the mesoscopic scale that can be observed with microelectrode arrays as well as at the macroscale of standard clinical EEG. We provide clinical, experimental, and modeling data to support the hypothesis that paroxysmal depolarization (PD) is a critical component of the ictal machinery. We present dual-patch recordings in cortical cultures showing reduced synaptic transmission associated with presynaptic occurrence of PD, and we find that the PD threshold is cell size related. We further find evidence that optically evoked PD activity in parvalbumin neurons can promote propagation of neuronal excitation in neocortical networks in vitro. Spike sorting results from microelectrode array measurements around ictal wave propagation in human focal seizures demonstrate a strong increase in putative inhibitory firing with an approaching excitatory wave, followed by a sudden reduction of firing at passage. At the macroscopic level, we summarize evidence that this excitatory ictal wave activity is strongly correlated with oscillatory activity across a centimeter-sized cortical network. We summarize Wilson-Cowan-type modeling showing how inhibitory function is crucial for this behavior. Our findings motivated us to develop a network motif of neurons in silico, governed by a reduced version of the Hodgkin-Huxley formalism, to show how feedforward, feedback, PD, and local failure of inhibition contribute to observed dynamics across network scales. The presented multidisciplinary evidence suggests that the PD not only is a cellular marker or epiphenomenon but actively contributes to seizure activity. NEW & NOTEWORTHY We present mechanisms of ongoing focal seizures across meso- and macroscales of microelectrode array and standard clinical recordings, respectively. We find modeling, experimental, and clinical evidence for a dual role of inhibition across these scales: local failure of inhibition allows propagation of a mesoscopic ictal wave, whereas inhibition elsewhere remains intact and sustains macroscopic oscillatory activity. We present evidence for paroxysmal depolarization as a mechanism behind this dual role of inhibition in shaping ictal activity.

The cellular activity underlying human focal seizures, and its relationship to key signatures in the EEG recordings used for therapeutic purposes, has not been well characterized despite many years of investigation both in laboratory and clinical settings. The increasing use of microelectrodes in epilepsy surgery patients has made it possible to apply principles derived from laboratory research to the problem of mapping the spatiotemporal structure of human focal seizures, and characterizing the corresponding EEG signatures. In this review, we describe results from human microelectrode studies, discuss some data interpretation pitfalls, and explain the current understanding of the key mechanisms of ictogenesis and seizure spread., (Copyright © 2019 Elsevier Inc. All rights reserved.)

During neocortical seizures in patients with epilepsy, microelectrode array recordings from the ictal core show a strong correlation between the fast, cellular spiking activities and the low-frequency component of the potential field, reflected in the electrocorticogram (ECoG). Here, we model the relationship between the cellular spike activity and this low-frequency component as the input and output signals of a linear time invariant system. Our approach is based on the observation that this relationship can be characterized by a so-called sinc function, the unit impulse response of an ideal (brick-wall) filter. Accordingly, using a brick-wall filter, we are able to convert ictal cellular spike inputs into an output that significantly correlates with the observed seizure activity in the ECoG ( r = 0 . 4 0 - 0 . 5 6 , p < 0 . 0 1 ) , while ECoG recordings of subsequent seizures within patients also show significant, but lower, correlations ( r = 0 . 1 0 - 0 . 3 0 , p < 0 . 0 1 ) . Furthermore, we can produce seizure-like output signals using synthetic spike trains with ictal properties. We propose a possible physiological mechanism to explain the observed properties associated with an ideal filter, and discuss the potential use of our approach for the evaluation of anticonvulsant strategies.

This is a pilot study to assess the clinical safety and efficacy of recording real-time flash visual evoked potentials (VEPs) using the SightSaver TM Visual Stimulator mask during prone spine surgery. A prospective, observational pilot study. Twenty patients presenting for spine surgery (microdiscectomy, 1-2 level lumbar fusion, or > 2 levels thoraco-lumbar fusion) were enrolled. The SightSaver™ Visual Stimulator™ was used to elicit VEPs throughout surgery. Somatosensory evoked potentials (SSEPs) were simultaneously recorded. All patients underwent general anesthesia with a combination of intravenous and inhaled agents. The presence, absence, and changes in VEP were qualitatively analyzed. Reproducible VEPs were elicited in 18/20 patients (36/40 eyes). VEPs were exquisitely sensitive to changes in anesthesia and decayed with rising MAC of isoflurane and/or N 2 O. Decrements in VEPs were observed without concomitant changes in SSEPs. The mask was simple to apply and use and was not associated with adverse effects. The SightSaver™ mask represents an emerging technology for monitoring developing visual insults during surgery. The definitive applications remain to be determined, but likely include use in select patients and/or surgeries. Here, we have validated the device as safe and effective, and show that VEPs can be recorded in real time under general anesthesia in the prone position. Future studies should be directed towards understanding the ideal anesthetic regimen to facilitate stable VEP recording during prone spine surgery.

Background Context: Lidocaine has emerged as a useful adjuvant anesthetic agent for cases requiring intraoperative monitoring of motor-evoked potentials (MEPs) and somatosensory-evoked potentials (SSEPs). A previous retrospective study suggested that lidocaine could be used as a component of propofol-based intravenous anesthesia without adversely affecting MEP or SSEP monitoring, but did not address the effect of the addition of lidocaine on the MEP and SSEP signals of individual patients., Purpose: The purpose of this study was to examine the intrapatient effects of the addition of lidocaine to balanced anesthesia on MEPs and SSEPs during multilevel posterior spinal fusion., Study Design: This is a prospective, two-treatment, two-period crossover randomized controlled trial with a blinded primary outcome assessment., Patient Sample: Forty patients undergoing multilevel posterior spinal fusion were studied., Outcome Measures: The primary outcome measures were MEP voltage thresholds and SSEP amplitudes. Secondary outcome measures included isoflurane concentrations and hemodynamic parameters., Methods: Each participant received two anesthetic treatments (propofol 50 mcg/kg/h and propofol 25 mcg/kg/h+lidocaine 1 mg/kg/h) along with isoflurane, ketamine, and diazepam. In this manner, each patient served as his or her own control. The order of administration of the two treatments was determined randomly., Results: There were no significant within-patient differences between MEP threshold voltages or SSEP amplitudes during the two anesthetic treatments., Conclusions: Lidocaine may be used as a component of balanced anesthesia during multilevel spinal fusions without adversely affecting the monitoring of SSEPs or MEPs in individual patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Small-scale neuronal networks may impose widespread effects on large network dynamics. To unravel this relationship, we analyzed eight multiscale recordings of spontaneous seizures from four patients with epilepsy. During seizures, multiunit spike activity organizes into a submillimeter-sized wavefront, and this activity correlates significantly with low-frequency rhythms from electrocorticographic recordings across a 10-cm-sized neocortical network. Notably, this correlation effect is specific to the ictal wavefront and is absent interictally or from action potential activity outside the wavefront territory. To examine the multiscale interactions, we created a model using a multiscale, nonlinear system and found evidence for a dual role for feedforward inhibition in seizures: while inhibition at the wavefront fails, allowing seizure propagation, feedforward inhibition of the surrounding centimeter-scale networks is activated via long-range excitatory connections. Bifurcation analysis revealed that distinct dynamical pathways for seizure termination depend on the surrounding inhibition strength. Using our model, we found that the mesoscopic, local wavefront acts as the forcing term of the ictal process, while the macroscopic, centimeter-sized network modulates the oscillatory seizure activity., Competing Interests: The authors declare no conflict of interest.

Background: Intraoperative neurophysiologic monitoring has become a standard tool for mitigating neurologic injury during spinal deformity surgery. Significant monitoring changes during deformity correction are relatively uncommon. This study characterizes precipitating factors for neurologic injury and relates significant events and postoperative neurologic prognosis., Methods: All spinal deformity surgeries at a West African hospital over a 12-month period were reviewed. Patients were included if complete operative reports, monitoring data, and postoperative neurologic examinations were available for review. Surgical and systemic triggers of monitoring events were recorded and neurologic status was followed for 6 weeks postoperatively., Results: Eighty-eight patients met inclusion criteria. The average age was 14 years (3-28). The average kyphosis was 108° (54°-176°) and average scoliosis was 100° (48°-177°). There were 44 separate neurologic events in 34 patients (39%). The most common triggers were traction or positioning (16), posterior column osteotomies/vertebral column resections (9/1), and distraction, corrective maneuvers, or implant placement (12). On surgery completion, 100% (12/12) of events from non-osteotomy-related surgical procedures, 75% (12/16) of events from traction or positioning resolved; however, 0% (0/10) of events from osteotomies resolved completely. Eight percent (7/88) had new neurologic deficits postoperatively, all with intraoperative monitoring changes. In 6 of these 7 patients, the event was attributed to an osteotomy; in 1 patient the cause was not determined. At 6-week follow-up, all patients had some preserved motor function bilaterally with the ability to walk (ASIA D/E) or recovered completely., Conclusions: Intraoperative signal changes were most frequently from traction or positioning. However, the most common cause of persistent neurologic deterioration and the only cause of postoperative neurologic deficit was the performance of osteotomies. Unlike traction- or instrument-related correction, osteotomies produce irreversible changes, from canal intrusion or sudden localized deformity change. The incidence of postoperative neurologic deficit is very low when the inciting cause is reversed; however, osteotomy-related events are irreversible, with a high incidence of associated lasting neurologic injury., (Copyright © 2016 Scoliosis Research Society. Published by Elsevier Inc. All rights reserved.)

High-gamma (HG; 80-150 Hz) activity in macroscopic clinical records is considered a marker for critical brain regions involved in seizure initiation; it is correlated with pathological multiunit firing during neocortical seizures in the seizure core, an area identified by correlated multiunit spiking and low frequency seizure activity. However, the effects of the spatiotemporal dynamics of seizure on HG power generation are not well understood. Here, we studied HG generation and propagation, using a three-step, multiscale signal analysis and modeling approach. First, we analyzed concurrent neuronal and microscopic network HG activity in neocortical slices from seven intractable epilepsy patients. We found HG activity in these networks, especially when neurons displayed paroxysmal depolarization shifts and network activity was highly synchronized. Second, we examined HG activity acquired with microelectrode arrays recorded during human seizures (n = 8). We confirmed the presence of synchronized HG power across microelectrode records and the macroscale, both specifically associated with the core region of the seizure. Third, we used volume conduction-based modeling to relate HG activity and network synchrony at different network scales. We showed that local HG oscillations require high levels of synchrony to cross scales, and that this requirement is met at the microscopic scale, but not within macroscopic networks. Instead, we present evidence that HG power at the macroscale may result from harmonics of ongoing seizure activity. Ictal HG power marks the seizure core, but the generating mechanism can differ across spatial scales.

The extensive distribution and simultaneous termination of seizures across cortical areas has led to the hypothesis that seizures are caused by large-scale coordinated networks spanning these areas. This view, however, is difficult to reconcile with most proposed mechanisms of seizure spread and termination, which operate on a cellular scale. We hypothesize that seizures evolve into self-organized structures wherein a small seizing territory projects high-intensity electrical signals over a broad cortical area. Here we investigate human seizures on both small and large electrophysiological scales. We show that the migrating edge of the seizing territory is the source of travelling waves of synaptic activity into adjacent cortical areas. As the seizure progresses, slow dynamics in induced activity from these waves indicate a weakening and eventual failure of their source. These observations support a parsimonious theory for how large-scale evolution and termination of seizures are driven from a small, migrating cortical area.

Spike-sorting algorithms have been used to identify the firing patterns of isolated neurons ('single units') from implanted electrode recordings in patients undergoing assessment for epilepsy surgery, but we do not know their potential for providing helpful clinical information. It is important therefore to characterize both the stability of these recordings and also their context. A critical consideration is where the units are located with respect to the focus of the pathology. Recent analyses of neuronal spiking activity, recorded over extended spatial areas using microelectrode arrays, have demonstrated the importance of considering seizure activity in terms of two distinct spatial territories: the ictal core and penumbral territories. The pathological information in these two areas, however, is likely to be very different. We investigated, therefore, whether units could be followed reliably over prolonged periods of times in these two areas, including during seizure epochs. We isolated unit recordings from several hundred neurons from four patients undergoing video-telemetry monitoring for surgical evaluation of focal neocortical epilepsies. Unit stability could last in excess of 40 h, and across multiple seizures. A key finding was that in the penumbra, spike stereotypy was maintained even during the seizure. There was a net tendency towards increased penumbral firing during the seizure, although only a minority of units (10-20%) showed significant changes over the baseline period, and notably, these also included neurons showing significant reductions in firing. In contrast, within the ictal core territories, regions characterized by intense hypersynchronous multi-unit firing, our spike sorting algorithms failed as the units were incorporated into the seizure activity. No spike sorting was possible from that moment until the end of the seizure, but recovery of the spike shape was rapid following seizure termination: some units reappeared within tens of seconds of the end of the seizure, and over 80% reappeared within 3 min (τrecov = 104 ± 22 s). The recovery of the mean firing rate was close to pre-ictal levels also within this time frame, suggesting that the more protracted post-ictal state cannot be explained by persistent cellular neurophysiological dysfunction in either the penumbral or the core territories. These studies lay the foundation for future investigations of how these recordings may inform clinical practice.See Kimchi and Cash (doi:10.1093/awv264) for a scientific commentary on this article., (© The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Objective: To determine whether resection of areas with evidence of intense, synchronized neural firing during seizures is an accurate indicator of postoperative outcome., Methods: Channels meeting phase-locked high gamma (PLHG) criteria were identified retrospectively from intracranial EEG recordings (102 seizures, 46 implantations, 45 patients). Extent of removal of both the seizure onset zone (SOZ) and PLHG was correlated with seizure outcome, classified as good (Engel class I or II, n = 32) or poor (Engel class III or IV, n = 13)., Results: Patients with good outcomes had significantly greater proportions of both SOZ and the first 4 (early) PLHG sites resected. Improved outcome classification was noted with early PLHG, as measured by the area under the receiver operating characteristic curves (PLHG 0.79, SOZ 0.68) and by odds ratios for resections including at least 75% of sites identified by each measure (PLHG 9.7 [95% CI: 2.3-41.5], SOZ 5.3 [95% CI: 1.2-23.3]). Among patients with resection of at least 75% of the SOZ, 78% (n = 30) had good outcomes, increasing to 91% when the resection also included at least 75% of early PLHG sites (n = 22)., Conclusions: This study demonstrates the localizing value of early PLHG, which is comparable to that provided by the SOZ. Incorporation of PLHG into the clinical evaluation may improve surgical efficacy and help to focus resections on the most critical areas., (© 2015 American Academy of Neurology.)

Unlabelled: Measurements of neuronal signals during human seizure activity and evoked epileptic activity in experimental models suggest that, in these pathological states, the individual nerve cells experience an activity driven depolarization block, i.e. they saturate. We examined the effect of such a saturation in the Wilson-Cowan formalism by adapting the nonlinear activation function; we substituted the commonly applied sigmoid for a Gaussian function. We discuss experimental recordings during a seizure that support this substitution. Next we perform a bifurcation analysis on the Wilson-Cowan model with a Gaussian activation function. The main effect is an additional stable equilibrium with high excitatory and low inhibitory activity. Analysis of coupled local networks then shows that such high activity can stay localized or spread. Specifically, in a spatial continuum we show a wavefront with inhibition leading followed by excitatory activity. We relate our model simulations to observations of spreading activity during seizures., Electronic Supplementary Material: The online version of this article (doi:10.1186/s13408-015-0019-4) contains supplementary material 1.

It has been well established in animal models that electrical fields generated during inter-ictal and ictal discharges are strong enough in intensity to influence action potential firing threshold and synchronization. We discuss recently published data from microelectrode array recordings of human neocortical seizures and speculate about the possible role of field effects in neuronal synchronization. We have identified two distinct seizure territories that cannot be easily distinguished by traditional EEG analysis. The ictal core exhibits synchronized neuronal burst firing, while the surrounding ictal penumbra exhibits asynchronous and relatively sparse neuronal activity. In the ictal core large amplitude rhythmic ictal discharges produce large electric fields that correspond with highly synchronous neuronal firing. In the penumbra rhythmic ictal discharges are smaller in amplitude, but large enough to influence spike timing, yet neuronal synchrony is not observed. These in homine observations are in accord with decades of animal studies supporting a role of field effects in neuronal synchronization during seizures, yet also highlight how field effects may be negated in the presence of strong synaptic inhibition in the penumbra.

High frequency oscillations have been proposed as a clinically useful biomarker of seizure generating sites. We used a unique set of human microelectrode array recordings (four patients, 10 seizures), in which propagating seizure wavefronts could be readily identified, to investigate the basis of ictal high frequency activity at the cortical (subdural) surface. Sustained, repetitive transient increases in high gamma (80-150 Hz) amplitude, phase-locked to the low-frequency (1-25 Hz) ictal rhythm, correlated with strong multi-unit firing bursts synchronized across the core territory of the seizure. These repetitive high frequency oscillations were seen in recordings from subdural electrodes adjacent to the microelectrode array several seconds after seizure onset, following ictal wavefront passage. Conversely, microelectrode recordings demonstrating only low-level, heterogeneous neural firing correlated with a lack of high frequency oscillations in adjacent subdural recording sites, despite the presence of a strong low-frequency signature. Previously, we reported that this pattern indicates a failure of the seizure to invade the area, because of a feedforward inhibitory veto mechanism. Because multi-unit firing rate and high gamma amplitude are closely related, high frequency oscillations can be used as a surrogate marker to distinguish the core seizure territory from the surrounding penumbra. We developed an efficient measure to detect delayed-onset, sustained ictal high frequency oscillations based on cross-frequency coupling between high gamma amplitude and the low-frequency (1-25 Hz) ictal rhythm. When applied to the broader subdural recording, this measure consistently predicted the timing or failure of ictal invasion, and revealed a surprisingly small and slowly spreading seizure core surrounded by a far larger penumbral territory. Our findings thus establish an underlying neural mechanism for delayed-onset, sustained ictal high frequency oscillations, and provide a practical, efficient method for using them to identify the small ictal core regions. Our observations suggest that it may be possible to reduce substantially the extent of cortical resections in epilepsy surgery procedures without compromising seizure control.

The location and trajectory of seizure activity is of great importance, yet our ability to map such activity remains primitive. Recently, the development of multi-electrode arrays for use in humans has provided new levels of temporal and spatial resolution for recording seizures. Here, we show that there is a sharp delineation between areas showing intense, hypersynchronous firing indicative of recruitment to the seizure, and adjacent territories where there is only low-level, unstructured firing. Thus, there is a core territory of recruited neurons and a surrounding 'ictal penumbra'. The defining feature of the 'ictal penumbra' is the contrast between the large amplitude EEG signals and the low-level firing there. Our human recordings bear striking similarities with animal studies of an inhibitory restraint, indicating that they can be readily understood in terms of this mechanism. These findings have important implications for how we localize seizure activity and map its spread.

Previous studies raise the hypothesis that attentional bias in the phase of neocortical excitability fluctuations (oscillations) represents a fundamental mechanism for tuning the brain to the temporal dynamics of task-relevant event patterns. To evaluate this hypothesis, we recorded intracranial electrocortical activity in human epilepsy patients while they performed an audiovisual stream selection task. Consistent with our hypothesis, (1) attentional modulation of oscillatory entrainment operates in a distinct network of areas including auditory, visual, posterior parietal, inferior motor, inferior frontal and superior midline frontal cortex, (2) the degree of oscillatory entrainment depends on the predictability of the stimulus stream, and (3) the attentional phase shift of entrained oscillation cooccurs with classical attentional effects observed on phase-locked evoked activity in sensory-specific areas but seems to operate on entrained low-frequency oscillations that cannot be explained by sensory activity evoked at the rate of stimulation. Thus, attentional entrainment appears to tune a network of brain areas to the temporal dynamics of behaviorally relevant event streams, contributing to its perceptual and behavioral selection.

Background: Spinal cord monitoring is now considered standard care during surgery for spinal deformity. Combined somatosensory and motor evoked potential monitoring allows the detection of early spinal cord dysfunction in most patients. The purpose of the current study was to identify clinical factors that increase the risk of intraoperative electrophysical changes and to provide management recommendations., Methods: The records of 162 consecutive patients who underwent surgery for the treatment of spinal deformity at a tertiary referral center were reviewed. Electrophysical monitoring of these patients was considered to have been successful if reproducible signals had been obtained. Relevant electrophysical changes included a reduction, as compared with baseline, of >50% in the amplitude of the somatosensory evoked potentials; an increase, as compared with baseline, of >10% in the latency of the somatosensory evoked potentials; a loss of motor evoked potentials; and an abrupt decrease of >75% in the motor evoked potentials., Results: One hundred and fifty-one (93%) of the 162 patients were monitored successfully. Four of the eleven patients with unsuccessful monitoring had neuromuscular scoliosis. Twelve of the 151 successfully monitored patients had a true electrophysical event, and two of them were found to have new postoperative neurologic deficits that represented a change from the findings of their preoperative neurologic examination. The determined causes of these electrophysical events included curve correction in eight patients, hypotension in two, direct cord trauma in one, and malposition of a pedicle screw in one. The patients with a true electrophysical event had a significantly higher rate of neurologic events than did the patients who did not have a true electrophysical event (p < 0.001). The rate of true electrophysical events was significantly higher in the patients with cardiopulmonary comorbidities than it was in the patients with no comorbidities (p = 0.011)., Conclusions: Combined somatosensory and motor evoked potential monitoring effectively prevents neurologic injury in most children undergoing surgery for spinal deformity. Despite the potential for false-positive results, we recommend setting a low threshold for defining relevant electrophysical changes. Rapid intervention can reverse these changes and avoid potentially serious neurologic complications. Patients with cardiopulmonary comorbidities may be at a higher risk for having relevant electrophysical events.

Background: Devices that monitor the depth of anesthesia are increasingly used to titrate sedation and avoid awareness during anesthesia. Many of these monitors are based upon electroencephalography (EEG) collected from large adult reference populations and not pediatric populations (Anesthesiology, 86, 1997, 836; Journal of Anaesthesia, 92, 2004, 393; Anesthesiology, 99, 2003, 34). We hypothesized that EEG patterns in children would be different from those previously reported in adults and that they would show anesthetic-specific characteristics., Methods: This prospective observational study was approved by the Institutional Review Board, and informed written consent was obtained. Patients were randomized to receive maintenance anesthesia with isoflurane or sevoflurane. EEG data collection included at least 10 min at steady-state maintenance anesthesia. The EEG was recorded continuously through emergence until after extubation. A mixed model procedure was performed on global and regional power by pooled data analysis and by analyzing each anesthetic group separately. Statistical significance was defined as P < 0.05., Results: Thirty-seven children completed the study (ages 22 days-3.6 years). Isoflurane and sevoflurane had different effects on global and regional EEG power during emergence from anesthesia, and frontal predominance patterns were significantly different between these two anesthetic agents., Conclusions: The principal finding of the present study was that there are anesthetic-specific and concentration-dependent EEG effects in children. Depth-of-anesthesia monitors that utilize algorithms based on the EEGs of adult reference populations therefore may not be appropriate for use in children.

Interictal high frequency oscillations (HFOs), in particular those with frequency components in excess of 200 Hz, have been proposed as important biomarkers of epileptic cortex as well as the genesis of seizures. We investigated the spatial extent, classification and distribution of HFOs using a dense 4 x 4 mm(2) two dimensional microelectrode array implanted in the neocortex of four patients undergoing epilepsy surgery. The majority (97%) of oscillations detected included fast ripples and were concentrated in relatively few recording sites. While most HFOs were limited to single channels, approximately 10% occurred on a larger spatial scale with simultaneous but morphologically distinct detections in multiple channels. Eighty per cent of these large-scale events were associated with interictal epileptiform discharges. We propose that large-scale HFOs, rather than the more frequent highly focal events, are the substrates of the HFOs detected by clinical depth electrodes. This feature was prominent in three patients but rarely seen in only one patient recorded outside epileptogenic cortex. Additionally, we found that HFOs were commonly associated with widespread interictal epileptiform discharges but not with locally generated 'microdischarges'. Our observations raise the possibility that, rather than being initiators of epileptiform activity, fast ripples may be markers of a secondary local response.

Somatosensory-evoked potential (SSEP) monitoring is commonly used to detect changes in nerve conduction and prevent impending nerve injury. We present a case series of two patients who had SSEP monitoring for their surgical craniotomy procedure, and who, upon positioning supine with their head tilted 30 degrees-45 degrees, developed unilateral upper extremity SSEP changes. These SSEP changes were reversed when the patients were repositioned. These cases indicate the clinical usefulness of monitoring SSEPs while positioning the patient and adjusting position accordingly to prevent injury.

Objective: Continuous electroencephalography (EEG) is used in patients with neurological injury to detect electrographic seizures and clinically important changes in brain function. Scalp EEG has poor spatial resolution, is often contaminated by artifact, and frequently demonstrates activity that is suspicious for but not diagnostic of ictal activity. We hypothesized that bedside placement of an intracortical multicontact electrode would allow for improved monitoring of cortical potentials in critically ill neurological patients., Methods: Sixteen individuals with brain injury, requiring invasive neuromonitoring, underwent implantation of an eight-contact minidepth electrode., Results: Intracortical EEG (ICE) was successfully performed and compared with scalp EEG in 14 of these 16 individuals. ICE provided considerable improvement in signal-to-noise ratio compared with surface EEG, demonstrating clinically important findings in 12 of 14 patients (86%) including electrographic seizures (n = 10) and acute changes related to secondary neurological injury (n = 2, 1 ischemia, 1 hemorrhage). In patients with electrographic seizures detected by ICE, scalp EEG demonstrated no concurrent ictal activity in six, nonictal-appearing rhythmic delta in two, and intermittently correlated ictal activity in two. In two patients with secondary neurological complications, ICE demonstrated prominent attenuation 2 to 6 hours before changes in other neuromonitoring modalities and more than 8 hours before the onset of clinical deterioration., Interpretation: ICE can provide high-fidelity intracranial EEG in an intensive care unit setting, can detect ictal discharges not readily apparent on scalp EEG, and can identify early changes in brain activity caused by secondary neurological complications. We predict that ICE will facilitate the development of EEG-based alarm systems and lead to prevention of secondary neuronal injury.

Objective: Detailed investigations of cortical physiology require the ability to record brain electrical activity at a submillimeter scale. Standard intracranial electrodes result in significant averaging of potentials generated by large numbers of neurons. In contrast, microelectrode arrays allow for recording of local field potentials and single-unit activity. We describe our initial surgical experience with the NeuroPort microelectrode array (Cyberkinetics Neurotechnology Systems, Inc., Salt Lake City, UT) in a series of patients undergoing subdural electrode implantation for epilepsy monitoring., Methods: Seven patients were implanted with and underwent semichronic recording from the NeuroPort array during standard subdural electrode monitoring for epilepsy. The electrode was placed according to company specifications in putative noneloquent epileptogenic cortex. After the monitoring period, microelectrode arrays were removed during explantation of subdural electrodes and resection of epileptogenic tissue., Results: Successful implantation of the microelectrode array was achieved in all patients, with minor operative difficulties. Robust and durable local field potentials and single-unit recordings were obtained from all implanted individuals. Implantation times ranged from 3 to 28 days; histological analysis of implanted tissue demonstrated no significant tissue injury or inflammatory response. There were no neurological complications or infections associated with electrode implantation or prolonged monitoring. Two patients developed postresection issues with wound healing at the site of scalp egress, with 1 requiring operative wound revision., Conclusion: Our experience demonstrates that semichronic microelectroencephalographic recording can be safely and effectively achieved using the NeuroPort microarray. Although significant tissue injury, infection, or cerebrospinal fluid leak was not encountered, the large profile of the connection pedestal resulted in suboptimal wound closure and healing in several patients. We predict that this problem will be easily addressed in second-generation devices.

The authors report the use of dense two-dimensional microelectrode array recordings to characterize fine resolution electrocortical activity ("microEEG") in epileptogenic human cortex. A 16-mm(2) 96 microelectrode array with 400-mum interelectrode spacing was implanted in five patients undergoing invasive EEG monitoring for medically refractory epilepsy. High spatial resolution data from the array were analyzed in conjunction with simultaneously acquired data from standard intracranial electrode grids and strips. microEEG recorded from within the epileptogenic zone demonstrates discharges resembling both interictal epileptiform activity ("microdischarges") and electrographic seizures ("microseizures") but confined to cortical regions as small as 200 microm(2). In two patients, this activity appeared to be involved in the initiation or propagation of electrographic seizures. The authors hypothesize that microdischarges and microseizures are generated by small cortical domains that form the substrate of epileptogenic cortex and play important roles in seizure initiation and propagation.

Objectives: To determine the prevalence, predictors, and clinical significance of electrographic seizures (ESz) and other continuous electroencephalographic monitoring findings in critically ill patients with central nervous system infections., Design: Retrospective cohort study., Setting: Eighteen-bed neurocritical care unit., Patients: We identified 42 consecutive patients with primary central nervous system infection (viral, 27 patients [64%]; bacterial, 8 patients [18%]; and fungal or parasitic, 7 patients [17%]) who underwent continuous electroencephalographic monitoring between January 1, 1996, and February 28, 2007., Main Outcome Measures: Presence of ESz or periodic epileptiform discharges (PEDs)., Results: Electrographic seizures were recorded in 14 patients (33%), and PEDs were recorded in 17 patients (40%). Twenty patients (48%) had either PEDs or ESz. Of the 14 patients with ESz, only 5 (36%) had a clinical correlate. Periodic epileptiform discharges (odds ratio=13.4; P=.001) and viral cause (odds ratio=13.0; P=.02) were independently associated with ESz. Both ESz (odds ratio=5.9; P=.02) and PEDs (odds ratio=6.1; P=.01) were independently associated with poor outcome at discharge (severe disability, vegetative state, or death)., Conclusions: In patients with central nervous system infections undergoing continuous electroencephalographic monitoring, ESz and/or PEDs were frequent, occurring in 48% of our cohort. More than half of the ESz had no clinical correlate. Both ESz and PEDs were independently associated with poor outcome. Additional studies are needed to determine whether prevention or treatment of these electrographic findings improves outcome.

Purpose: We have previously demonstrated that it is common for alerting stimuli to induce electrographic seizures and other periodic or rhythmic patterns in the critically ill; however, only 1 of the first 33 patients we reported with this phenomenon had a detectable clinical correlate., Methods: Review of charts and video EEG findings in critically ill patients in a neurological ICU at a tertiary care medical center in Manhattan., Results: We identified nine patients who had focal motor seizures repeatedly induced by alerting stimuli. All patients were comatose, and 8/9 had nonconvulsive status epilepticus at some point during their acute illness. Imaging abnormalities involved bilateral thalami in three patients, upper brainstem in one, and the perirolandic region in five., Discussion: We hypothesize that in encephalopathic patients, alerting stimuli activate the arousal circuitry, and, when combined with hyperexcitable cortex, result in epileptiform activity or seizures. This activity can be focal or generalized, and is usually nonconvulsive, as is true of seizures in general in the critically ill. However, when the cortex is hyperexcitable in a specific region only, focal EEG findings arise. If the electrographic seizure activity is adequately synchronized and involves motor pathways, this can present as focal motor seizures, as seen in these nine patients. Alerting can induce seizures in encephalopathic/comatose patients. The observation of clear focal clinical seizures removes the last remaining doubt that these stimulus-induced patterns are indeed seizures by any definition, not simply abnormal arousal patterns.