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Articles by Sampsa Vanhatalo in JoVE

 

Preterm EEG: A Multimodal Neurophysiological Protocol


JoVE 3774 2/18/2012

1Department of Children's Clinical Neurophysiology, Helsinki University Hospital, University of Helsinki , 2Department of Biosciences, University of Helsinki , 3Department of Pediatrics, Helsinki University Hospital, University of Helsinki , 4Neuroscience Center, University of Helsinki

This video explains the background theory of the neonatal EEG activity and the sensory responses, followed by a live demonstration of their recording in neonatal intensive care unit.

Other articles by Sampsa Vanhatalo on PubMed

Visual Field Constriction in 91 Finnish Children Treated with Vigabatrin

To study the prevalence and features of visual field constrictions (VFCs) associated with vigabatrin (VGB) in children.

DC-EEG Discloses Prominent, Very Slow Activity Patterns During Sleep in Preterm Infants

The objective of this study is to test the hypothesis that the immature human brain exhibits slow electrical activity that is not detected by conventional (i.e. high-pass filtered) electroencephalography (EEG).

Bioelectrical Behaviour of Hypoxic Human Neocortical Tissue Under the Influence of Nimodipine and Dimethyl Sulfoxide

Nimodipine and dimethyl sulfoxide (DMSO) have been shown to affect electrophysiological responses in rodent brain tissue in an vitro model of hypoxia. In the present study, the same agents were now examined for their effects on human neocortical brain slices under repeated hypoxic conditions. DMSO (0.4%), with and without addition of nimodipine (40 micromol/l), did not increase the latency of anoxic depolarization (AD). This finding is not in line with our previous observations of DMSO effects, with and without nimodipine, on brain slices of guinea pigs. AD latency was significantly longer in human neocortical brain slices compared with hippocampal slices of rodents even without any pharmacological influence. A possible acute effect of DMSO-nimodipine may therefore be masked by an interspecies difference of hypoxia resistance.

Millivolt-scale DC Shifts in the Human Scalp EEG: Evidence for a Nonneuronal Generator

Slow shifts in the human scalp-recorded EEG, including those related to changes in brain CO(2) levels, have been generally assumed to result from changes in the level of tonic excitation of apical dendrites of cortical pyramidal neurons. We readdressed this issue using DC-EEG shifts elicited in healthy adult subjects by hypo- or hypercapnia. A 3-min period of hyperventilation resulted in a prompt negative shift with a rate of up to 10 microV/s at the vertex (Cz) and an extremely steep dependence (up to 100 microV/mmHg) on the end-tidal Pco(2). This shift had a maximum of up to -2 mV at Cz versus the temporal derivations (T3/T4). Hyperventilation-like breathing of 5% CO(2)-95% O(2), which does not lead to a significant hypocapnia, resulted in a near-complete block of the negative DC shift at Cz. Hypoventilation, or breathing 5% CO(2) in air at normal respiratory rate, induced a positive shift. The high amplitude of the voltage gradients on the scalp induced by hyperventilation is not consistent with a neuronal origin. Instead, the present data suggest that they are generated by extracortical volume currents driven by a Pco(2)-dependent potential difference across epithelia separating the cerebrospinal fluid and blood. Since changes in respiratory patterns and, hence, in the level of brain Pco(2), are likely to occur under a number of experimental conditions in which slow EEG responses have been reported (e.g., attention shifts, preparatory states, epileptic seizures, and hypoxic episodes), the present results call for a thorough reexamination of the mechanisms underlying scalp-recorded DC-EEG responses.

Spatial Spectra of Scalp EEG and EMG from Awake Humans

Evaluate spectral scaling properties of scalp electroencephalogram (EEG) and electromyogram (EMG), optimal spacing of electrodes, and strategies for mitigating EMG.

Vertebral Artery Insufficiency As a Possible Mechanism for Sudden Infant Death--in Vivo Evidence Does Not Support Findings from Postmortem Studies

Recent postmortem studies have suggested that sudden infant death syndrome (SIDS) might involve an underlying, gradual brain stem injury caused by repeated episodes of transiently compromised brain stem circulation. Autopsy studies have also reported that vertebral artery occlusion due to head rotations, such as occurs, e.g. during prone sleeping, would be a physiological phenomenon of infant atlantooccipital junction. The present study was undertaken to examine whether vertebral artery insufficiency does truly occur in live infants during such head rotations. We studied by transcranial doppler sonography the blood flow velocity of the basilar artery (BA) in 27 infants during head rotation from straight position to maximal rotation in three directions (left, right, dorsiflexion). No significant change in BA blood flow was seen between any head positions. Weight and gestational age, but not arterial pressure or hematocrit, of the infants were correlated with blood flow velocity. Our results suggest that brain stem circulation in live infants may not be compromised due to changing the head position, which is inconsistent with the postmortem findings showing insufficiency of brain stem circulation in both controls and those succumbed to SIDS. We hence propose that the brain stem pathology observed with SIDS is likely caused by other factors (e.g. systemic disturbance) rather than by mechanical obstruction of brain stem circulation.

Vagal Nerve Stimulation Induces Intermittent Hypocapnia

To study whether respiratory alteration caused by vagal nerve stimulation (VNS) can change end-tidal carbon dioxide (EtCO2) levels.

Nonneuronal Origin of CO2-related DC EEG Shifts: an in Vivo Study in the Cat

We studied the mechanisms underlying CO(2)-dependent DC potential shifts, using epicranial, epidural, epicortical, intraventricular, and intraparenchymal (intraneuronal, intraglial, and field) recordings in ketamine-xylazine-anesthetized cats. DC shifts were elicited by changes in artificial ventilation, causing end-tidal CO(2) variations within a 2-5% range. Hypercapnia was consistently associated with negative scalp DC shifts (average shift -284.4 microV/CO(2)%, range -216 to -324 microV/CO(2)%), whereas hypocapnia induced positive scalp DC shifts (average shift 307.8 microV/CO(2)%, range 234 to 342 microV/CO(2)%) in all electrodes referenced versus the nasium bone. The former condition markedly increased intracranial pressure (ICP), whereas the latter only slightly reduced ICP. Breakdown of the blood-brain barrier (BBB) resulted in a positive DC shift and drastically reduced subsequent DC responses to hypo-/hypercapnia. Thiopental and isoflurane also elicited a dose-dependent positive DC shift and, at higher doses, hypo-/hypercapnia responses displayed reverted polarity. As to the possible implication of neurons in the production of DC shifts, no polarity reversal was recorded between scalp, various intracortical layers, and deep brain structures. Moreover, the membrane potential of neurons and glia did not show either significant or systematic variations in association with the scalp-recorded CO(2)-dependent DC shifts. Pathological activities of neurons during spike-wave seizures produced DC shifts of significantly smaller amplitude than those generated by hyper-/hypocapnia. DC shifts were still elicited when neuronal circuits were silent during anesthesia-induced burst-suppression patterns. We suggest that potentials generated by the BBB are the major source of epicortical/cranial DC shifts recorded under conditions affecting brain pH and/or cerebral blood flow.

Does Hyperventilation Elicit Epileptic Seizures?

Voluntary hyperventilation has been advocated for many decades as an "activating" procedure to provoke clinical seizures and epileptiform discharges in subjects with suspected epilepsy who undergo standard EEG recordings. This study was undertaken to determine the effects of hyperventilation in patients with proven epilepsy.

Degeneration and Regeneration of Perivascular Innervation in Arterial Grafts

Because the understanding of postoperative changes in arterial graft innervation is limited, this study was performed to characterize neuronal degeneration and regeneration events immunohistochemically in femoral arterial grafts transplanted to carotid arteries in rats. Specimens taken 1 day, 3 days, 7 days, 1 month, 3 months, and 5 months after surgery were assessed for vasoactive intestinal peptide, neurofilaments, growth-associated protein 43, tyrosine hydroxylase, and nitric oxide synthase isoenzymes. During neuronal degeneration, vasoactive intestinal peptide disappeared within 1 day, transmitter-synthesizing enzymes (nitric oxide synthase and tyrosine hydroxylase) had vanished by day 7, and neurofilaments (cytoskeletal markers) had essentially disappeared after 1 week. In the regeneration phase, the most robust axonal growth, as visualized by growth-associated protein 43, was observed at 1 month, followed by a gradual increase in neurotransmitter markers at 1 and 3 months, whereas the neurofilaments increased gradually up to the end of the 5-month observation period. Reinnervation proceeded from the proximal carotid (host) trunk distally to the graft. Axonal re-growth occurred mainly in arterial adventitia. Innervation density, as visually assessed, was denser in the graft than in the host. These findings suggest that 1) the main sequence of degeneration and regeneration follows that reported in other models of neuronal degeneration; 2) reinnervation of the arterial grafts comes mainly from the host arteries; and 3) the innervation density in the graft may differ from that in the host, which may suggest target-derived regulation of innervation. The latter finding may have clinical implications. It suggests that for a good outcome it would be beneficial to choose a sparsely innervated graft rather than a densely innervated one.

Full-band EEG (FbEEG): an Emerging Standard in Electroencephalography

While enormous resources have been recently invested into the development of a variety of neuroimaging techniques, the bandwidth of the clinical EEG, originally set by trivial technical limitations, has remained practically unaltered for over 50 years. An increasing amount of evidence shows that salient EEG signals are observed beyond the bandwidth of the routine clinical EEG, which is typically around 0.5-50 Hz. Physiological and pathological EEG activity ranges at least from 0.01 Hz to several hundred Hz, as demonstrated in recordings of spontaneous activity in the immature human brain, as well as during epileptic seizures, or various kinds of cognitive tasks and states in the adult brain. In the present paper, we will review several arguments leading to the conclusion that elimination of the lower (infraslow) or higher (ultrafast) bands of the EEG frequency spectrum in routine EEG leads to situations where salient and physiologically meaningful features of brain activity are ignored. Recording the full, physiologically relevant range of frequencies is readily attained with commercially available direct-current (DC) coupled amplifiers, which have a wide dynamic range and a high sampling rate. Such amplifiers, combined with appropriate DC-stable electrode-skin interface, provide a genuine full-band EEG (FbEEG). FbEEG is mandatory for a faithful, non-distorted and non-attenuated recording, and it does not have trade-offs that would favor any frequency band at the expense of another. With the currently available electrode, amplifier and data acquisition technology, FbEEG is likely to become the standard approach for a wide range of applications in both basic science and in the clinic.

Full-band EEG (fbEEG): a New Standard for Clinical Electroencephalography

A variety of neuroimaging techniques, such as functional magnetic resonance imaging (fMRI), positron emission tomography (PET) and magnetoencephalography (MEG), have been established during the last few decades, with progressive improvements continuously taking place in the underlying technologies. In contrast to this, the recording bandwidth of the routine clinical EEG (typically around 0.5-50 Hz) that was originally set by trivial technical limitations has remained practically unaltered for over half a decade. An increasing amount of evidence shows that salient EEG signals take place and can be recorded beyond the conventional clinical EEG bandwidth. These physiological and pathological EEG activities range from 0.01 Hz to several hundred Hz, and they have been demonstrated in recordings of spontaneous activity in the preterm human brain, and during epileptic seizures, sleep, as well as in various kinds of cognitive tasks and states in the adult brain. In the present paper, we will describe the practical aspects of recording the full physiological frequency band of the EEG (Full-band EEG; FbEEG), and we review the currently available data on the clinical applications of FbEEG. Recording the FbEEG is readily attained with commercially available direct-current (DC) coupled amplifiers if the recording setup includes electrodes providing a DC-stable electrode-skin interface. FbEEG does not have trade-offs that would favor any frequency band at the expense of another. We present several arguments showing that elimination of the lower (infraslow) or higher (ultrafast) bands of the EEG frequency spectrum in routine EEG has led, and will lead, to situations where salient and physiologically meaningful features of brain activity remain undetected or become seriously attenuated and distorted. With the currently available electrode, amplifier and data acquisition technology, it is to be expected that FbEEG will become the standard approach in both clinical and basic science.

Slow Endogenous Activity Transients and Developmental Expression of K+-Cl- Cotransporter 2 in the Immature Human Cortex

Spontaneous transients of correlated activity are a characteristic feature of immature brain structures, where they are thought to be crucial for the establishment of precise neuronal connectivity. Studies on experimental animals have shown that this kind of early activity in cortical structures is composed of long-lasting, intermittent network events, which undergo a developmental decline that is closely paralleled by the maturation of GABAergic inhibition. In order to examine whether similar events occur in the immature human cortex, we performed direct current-coupled electroencephalography (EEG) recordings from sleeping preterm babies. We show now that much of the preterm EEG activity is confined to spontaneous, slow activity transients. These transients are characterized by a large voltage deflection that nests prominent oscillatory activity in several frequency bands covering the whole frequency spectrum of the preterm EEG (<0.1-30 Hz). The slow voltage deflections had an amplitude of up to 800 microV. Most of these 'giant' events originated in the temporo-occipital areas, with a maximum rate of about 8/min, and their occurrence as well as amplitude showed a decline by the time of normal birth. In age-matched fetal brain tissue, this decrease in the spontaneous activity transients was associated with a developmental up-regulation of the neuronal chloride extruder K+-Cl- cotransporter 2, a crucial molecule for the generation of inhibitory GABAergic Cl- currents. Our work indicates that slow endogenous activity transients in the immature human neocortex are mostly confined to the prenatal stage and appear to be terminated in parallel with the maturation of functional GABAergic inhibition.

Fine Spatiotemporal Structure of Phase in Human Intracranial EEG

To transfer to the clinic for humans the technology and theory for high-resolution EEG analysis that have been developed in the laboratory with animals.

Experimental Febrile Seizures Are Precipitated by a Hyperthermia-induced Respiratory Alkalosis

Febrile seizures are frequent during early childhood, and prolonged (complex) febrile seizures are associated with an increased susceptibility to temporal lobe epilepsy. The pathophysiological consequences of febrile seizures have been extensively studied in rat pups exposed to hyperthermia. The mechanisms that trigger these seizures are unknown, however. A rise in brain pH is known to enhance neuronal excitability. Here we show that hyperthermia causes respiratory alkalosis in the immature brain, with a threshold of 0.2-0.3 pH units for seizure induction. Suppressing alkalosis with 5% ambient CO2 abolished seizures within 20 s. CO2 also prevented two long-term effects of hyperthermic seizures in the hippocampus: the upregulation of the I(h) current and the upregulation of CB1 receptor expression. The effects of hyperthermia were closely mimicked by intraperitoneal injection of bicarbonate. Our work indicates a mechanism for triggering hyperthermic seizures and suggests new strategies in the research and therapy of fever-related epileptic syndromes.

Neonatal SEP - Back to Bedside with Basic Science

Scalp-recorded somatosensory evoked potentials (SEPs) have been successfully used in neonatal assessment for several decades. The current routine SEP paradigm is markedly predictive for future cerebral palsy (CP) or other neurocognitive sequelae in brain-injured babies. Recent advances in basic science have dramatically increased our knowledge about structural-functional development of SEP-related brain mechanisms. It has thereby become apparent that preterm SEP differs from that in more mature counterparts in that it also comprises responses from transient brain structures, and hence being unique to the preterm period. It is now obvious also that several aspects in the current SEP paradigm, ranging from the type of stimulation to the methods of recording and analysis, are suboptimal for preterm babies. Recent progress in recording and analysis techniques have made it possible to combine SEP studies with EEG recordings, as well as to implement advanced analyses (e.g. time-frequency analysis) into routine practice. This review summarizes literature from relevant areas in basic science, and proposes a novel, integrated approach in neonatal SEP studies in order to significantly increase the fidelity of testing somatosensory system.

Development of Neonatal EEG Activity: from Phenomenology to Physiology

After having been in routine use for about half a century, neonatal EEG is currently facing unprecedented challenges in assessing and monitoring brain function during intensive care of preterm babies. It has therefore become increasingly important to understand the neurophysiological processes underlying EEG activity, as well as to identify those features of brain activity that are essential for brain development. By integrating the existing literature from basic neuroscience to neonatal EEG, the present review proposes a simple, neurophysiologically and neuroanatomically based framework for neonatal EEG interpretation. This is composed of two developmental trajectories: one related to discrete spontaneous activity transients (SAT) and the other to the ongoing, apparently oscillatory EEG activity. This framework can readily be applied to clinical use. It may open novel avenues to automated analysis in EEG monitoring and, moreover, it may facilitate genuine translational research.

Ictal Localization by Source Analysis of Infraslow Activity in DC-coupled Scalp EEG Recordings

New bedside long-term DC-coupled EEG techniques have demonstrated that infraslow (<0.5 Hz) activity lateralizes temporal lobe seizures (Vanhatalo, S., Holmes, M.D., Tallgren, P., Voipio, J., Kaila, K., Miller, J.W., 2003a. Very slow EEG responses indicate the laterality of temporal lobe seizures: a DC-EEG study. Neurology 60, 1098-1104). However, even high amplitude infraslow activity is difficult to localize by simple visual inspection if there is overlying faster EEG activity or slow artifact. In this study, we address this with improved DC-coupled EEG recording and analysis techniques and also extend observation to both temporal and extratemporal seizures. Recordings were performed during presurgical evaluation of medically intractable epilepsy, with 20 seizures in 11 patients analyzed. A commercial DC-coupled recording device was used, with sintered Ag/AgCl electrodes in a standard 10-10 system array, with additional anterior temporal and subtemporal electrodes. Seizures were localized with a software package by means of source montage analysis. Infraslow signals occurred with all seizures, often with amplitude orders of magnitude higher than conventional frequencies (0.5 to 70 Hz). The most reliable method to localize these signals and distinguish them from artifacts used a source montage after low-pass filtering below 0.5 Hz. Five of the eight patients who received epilepsy surgery had follow-up documenting significant seizure reduction, and infraslow signal analysis correctly localized the region of seizure onset in all five, while conventional noninvasive EEG recording and analysis localized only three of the five. Several seizures were also analyzed using principle component analysis source localization methods, with the results less consistently localizing than source montage analysis. DC-coupled EEG recordings give clinically useful information to noninvasively localize the seizure focus. The value of this method is increased by source analysis tools that reveal localized changes more clearly than direct visual inspection.

Neonatal Seizures in the EEG: to See or Not to See?

Epileptogenic Neocortical Networks Are Revealed by Abnormal Temporal Dynamics in Seizure-free Subdural EEG

Long-term video electroencephalographic (EEG) recording is currently a routine procedure in the presurgical evaluation of localization-related epilepsies. Cortical epileptogenic zone is usually localized from ictal recordings with intracranial electrodes, causing a significant burden to patients and health care. Growing literature suggests that epileptogenic networks exhibit aberrant dynamics also during seizure-free periods. We examined if neocortical epileptogenic regions can be circumscribed by quantifying local long-range temporal (auto-)correlations (LRTC) with detrended fluctuation analysis of seizure-free ongoing subdural EEG activity in 4 frequency bands in 5 patients. We show here with subdural EEG recordings that the LRTC are abnormally strong near the seizure onset area. This effect was most salient in neocortical oscillations in the beta frequency band (14-30 Hz). Moreover, lorazepam, a widely used antiepileptic drug, exerted contrasting effects on LRTC (n = 2): lorazepam attenuated beta-band LRTC near the epileptic focus, whereas it strengthened LRTC in other cortical areas. Our findings demonstrate that interictal neuronal network activity near the focus of seizure onset has pathologically strong intrinsic temporal correlations. The observed effect by lorazepam on beta-band activity suggests that the antiepileptic mechanism of benzodiazepines may be related to the normalization of LRTC within the epileptic focus. We propose that this method may become a promising candidate for routine invasive and noninvasive presurgical localization of epileptic foci.

High-fidelity Recording of Brain Activity in the Extremely Preterm Babies: Feasibility Study in the Incubator

To develop an electrode cap with high number of electrodes for recording very small preterm babies, to assess the physiological stress imposed by the application of this cap on babies, and to estimate what added information could be potentially obtained with more electrodes in this age group.

Pronounced Increase in Breathing Rate in the "hair Dryer Model" of Experimental Febrile Seizures

In a study using a heated chamber for induction of experimental febrile seizures (eFS) in rat pups, ictal activity was shown to be precipitated by a respiratory alkalosis (Schuchmann et al., 2006). In sharp contrast to this, in a recent review Dubé et al., (2007) suggest that the respiratory alkalosis is model specific, and that no increase in respiratory rate is observed in the widely used "hair dryer model" of eFS. The data in the present work, based on well-established techniques for measuring respiratory rates in rat pups, show a pronounced increase in the "hair dryer model" with values that are slightly higher than those recorded in the heated chamber model. Hence, a temperature-evoked increase in respiration is a common feature of these two models of eFS.

Generation of 'positive Slow Waves' in the Preterm EEG: by the Brain or by the EEG Setup?

Electroencephalographic Response to Procedural Pain in Healthy Term Newborn Infants

The current study aimed to characterize changes in EEG-related measures after noxious stimuli in neonates and to assess their potential utility as measures of pain and/or discomfort during neonatal intensive care. Seventy-two healthy term infants were investigated: Twenty-eight had a non-skin-breaking pin-prick on the heel, randomized to receive either oral glucose (n = 16) or water (n = 12) before the stimulus. Twenty-one infants were studied during a venous blood sample from the dorsum of the hand, 23 infants during a capillary heel stick. Behavioral pain responses were assessed with the Premature Infant Pain Profile Scale. The stimulus evoked a significant increase in higher frequency components (10-30 Hz) which also correlated to behavioral measures. The frontotemporal localization of the increased activity with frequency bands similar to electromuscular artifacts and the relation to behavioral measures confirmed that this activity corresponds to an increase in muscle tone. There was no change in frontal EEG asymmetry in any of the groups. The present results indicate that responses in cortical activity recorded by EEG are not useful for clinical assessment of infants' responses to noxious stimuli.

Neurobiological and Physiological Mechanisms of Fever-related Epileptiform Syndromes

Febrile seizures (FS) are the most common type of convulsive events in children. FS have been extensively studied using animal models, where rat and mice pups are placed in a hyperthermic environment. Such work has largely focused on the consequences rather than on the mechanisms of experimental febrile seizures (eFS). We have recently shown that eFS are preceded by a dramatic rise in the rate of respiration. The consequent respiratory alkalosis affecting the brain and increasing neuronal excitability is a direct cause of the eFS [1]. If a similar mechanism contributes to human FS and other fever-related epileptiform syndromes, a number of factors operating at the molecular, cellular and systems level that have not been previously thought to be involved in their etiology must be considered. These include physiological and pathophysiological factors affecting CO(2) chemosensitivity as well as cellular and systemic mechanisms of acid-base regulation. Furthermore, a critical role for brain pH in FS points to novel types of susceptibility genes, which include genes coding pH-sensitive target proteins (e.g. neuronal ion channels) and pH-regulatory proteins. We will discuss these novel ideas and putative therapies based on them.

Top of the Basilar Artery Embolic Stroke and Neonatal Myoclonus

Cerebellar stroke has been virtually unreported in the living newborn infant. A term newborn male weighing 3380g at birth suffered myoclonic seizures within 24 hours of birth by spontaneous vaginal delivery. Apgar scores were 3 and 4 at 1 and 5 minutes. Myoclonus persisted for 9 days, responding poorly to step-up anticonvulsant treatment including lidocaine, midazolam, and clonazepam. Imaging documented arterial ischaemic stroke within the left posterior cerebral and both superior cerebellar arteries, compatible with top of the basilar artery stroke. There was no electrographic correlate for the seizures. Disturbed oscillation within the dentato-rubro-olivary circuitry was the likely mechanism. The probable cause was embolism from an in-utero-onset inferior caval vein thrombosis. At 22 months the child was sitting unsupported. Scores on the Bayley Scales of Infant Development II were equivalent to those of a 12-month/year-old. He showed ataxic motor behaviour. Embolism can cause neonatal top of the basilar artery stroke, which may present with myoclonus due to cerebellar injury.

Bumetanide for Neonatal Seizures: Based on Evidence or Enthusiasm?

An Easy and Practical Method for Routine, Bedside Testing of Somatosensory Systems in Extremely Low Birth Weight Infants

This study was set out to develop and describe a novel, simple, and safe method for routine bedside testing of somatosensory system in very early preterm infants. We recorded electroencephalogram (EEG) activity after tactile stimulation of hand (palm) and foot (sole) by a soft hairbrush stimulator in extremely low birth weight infants (n = 10; GA, 24-28, recording at conceptional age 30-32 wk) and compared with the raw EEG responses to those seen by one- or two-channel brain monitors. In every subject, single tactile stimuli produced prominent (100-350 microV) somatosensory evoked responses (SERs) that were readily identified in the ongoing EEG signal. The maximal SER was in the contralateral hemisphere at around the corresponding somatosensory representation areas. Conventional EEG filtering did significantly reduce the SERs, but they could still be identified in the routine brain monitor setting widely available in NICUs. The method described here is directly applicable to assessment of integrity of somatosensory system in the early preterm period. It needs minimal training and requires an EEG system or a brain monitor device that is available in most units. Thus, the technique is likely to open a novel window to neurologic assessment of these babies.

Detection of 'EEG Bursts' in the Early Preterm EEG: Visual Vs. Automated Detection

To describe the characteristics of activity bursts in the early preterm EEG, to assess inter-rater agreement of burst detection by visual inspection, and to determine the performance of an automated burst detector that uses non-linear energy operator (NLEO).

Evaluation of an Easy, Standardized and Clinically Practical Method (SurePrep) for the Preparation of Electrode-skin Contact in Neurophysiological Recordings

The aim of this study was to assess the practicality, reliability and safety of a recently introduced method of skin preparation for EEG recordings. We compared the traditional skin abrasion (SA) method to a method called SurePrep (SP), which creates tiny incisions through the upper epithelial layers. The study comprised three parts. In part 1, forearm recordings (n = 400; ten healthy volunteers) were conducted to examine acute and late (24 h) impedances, skin reactions, as well as the effects on electrode movement artefacts. In part 2, the effect of repeated (up to nine) SP sticks on impedances was examined on the forearm skin in two subjects (n = 99). In part 3, preparation speed and skin impedances were measured from preparation of a standard EEG cap in four subjects (n = 74). Immediately after preparation, skin impedances were a little lower (n.s.) after SA, but the variability in impedances was significantly less after SP (p < 0.01). After one day, there was no mean impedance difference but a greater proportion of SP sites were >10 kOmega. The frequency of immediate skin irritations (93.5%) was much higher after SA compared to 42.5% after SP, but there was no clinically significant difference observed after one day. The SP method exposed interstitial fluid in 5% of cases, while SA caused a wound-like lesion in 4.5% of the sites. No macroscopic blood was observed in any case (n = 400). Three sticks with the SP device produced clinically sufficient (<10 kOmega) impedances in 85% of the cases, and a total of five to six sticks secured a sufficient skin contact in all skin sites examined (n = 99). Preparation of skin contacts in the EEG cap was faster by SP compared to SA in all four study subjects. Our results demonstrate that skin contacts of sufficient quality can be reliably, easily and quickly prepared by the SP method. SP is a useful alternative for EEG recordings in general, although SA may provide the slightly better preserved skin contacts needed for long-term recordings. Notably, SP could facilitate emergency care units, peripheral hospitals and after-hours EEG acquisition by people without special EEG training.

Optimization of an NLEO-based Algorithm for Automated Detection of Spontaneous Activity Transients in Early Preterm EEG

We propose here a simple algorithm for automated detection of spontaneous activity transients (SATs) in early preterm electroencephalography (EEG). The parameters of the algorithm were optimized by supervised learning using a gold standard created from visual classification data obtained from three human raters. The generalization performance of the algorithm was estimated by leave-one-out cross-validation. The mean sensitivity of the optimized algorithm was 97% (range 91-100%) and specificity 95% (76-100%). The optimized algorithm makes it possible to systematically study brain state fluctuations of preterm infants.

Phase Brings a New Phase to the Exploration of the Elusive Neonatal EEG

Oral Sucrose for Procedural Pain in Infants

Brain Alkalosis Causes Birth Asphyxia Seizures, Suggesting Therapeutic Strategy

The mechanisms whereby birth asphyxia leads to generation of seizures remain unidentified. To study the possible role of brain pH changes, we used a rodent model that mimics the alterations in systemic CO(2) and O(2) levels during and after intrapartum birth asphyxia.

Respiratory Alkalosis in Children with Febrile Seizures

Febrile seizures (FS) are the most common type of convulsive events in children. FS are suggested to result from a combination of genetic and environmental factors. However, the pathophysiologic mechanisms underlying FS remain unclear. Using an animal model of experimental FS, it was demonstrated that hyperthermia causes respiratory alkalosis with consequent brain alkalosis and seizures. Here we examine the acid-base status of children who were admitted to the hospital for FS. Children who were admitted because of gastroenteritis (GE), a condition known to promote acidosis, were examined to investigate a possible protective effect of acidosis against FS.

Development of Neonatal Seizure Detectors: an Elusive Target and Stretching Measuring Tapes

Five Percent CO₂ is a Potent, Fast-acting Inhalation Anticonvulsant

CO₂ has been long recognized for its anticonvulsant properties. We aimed to determine whether inhaling 5% CO₂ can be used to suppress seizures in epilepsy patients. The effect of CO₂ on cortical epileptic activity accompanying behavioral seizures was studied in rats and nonhuman primates, and based on these data, preliminary tests were carried out in humans. Methods:  In freely moving rats, cortical afterdischarges paralleled by myoclonic convulsions were evoked by sensorimotor cortex stimulation. Five percent CO₂ was applied for 5 min, 3 min before stimulation. In macaque monkeys, hypercarbia was induced by hypoventilation while seizure activity was electrically or chemically evoked in the sensorimotor cortex. Seven patients with drug-resistant partial epilepsy were examined with video-EEG (electroencephalography) and received 5% CO₂ in medical carbogen shortly after electrographic seizure onset.

Phase Synchrony in the Early Preterm EEG: Development of Methods for Estimating Synchrony in Both Oscillations and Events

Development of neuronal connections relies on proper neuronal activity, and it starts during the time when early preterm babies are treated in the neonatal intensive care units. While synchrony has been a key element in visual estimation of neonatal EEG signals, there has been no unambiguous definitions for synchrony, and no objective measures available for neonatal signals. Assessment of phase locking value (PLV) has been an established paradigm in adults, but many unique characteristics of the neonatal EEG have precluded its applicability in them. In the present paper, we developed the existing PLV-based methods further to be applicable for neonatal signals at two different temporal scales, oscillations and events, where the latter refers technically to quantitating phase synchrony (PS) between band-specific amplitude envelopes (bafPS). In addition, we present a measure for quantitation based on assessing cumulative proportion of time with statistically significant synchrony between the given signal pair. The paper uses real EEG examples and the prior neurobiological knowledge in the process of defining optimal parameters in each step of the procedure. Finally, we apply the method to a set of dense array EEG recordings from very early preterm babies, recorded at conceptional age of less than 30weeks. By comparing PS and bafPS from healthy babies to those with major cerebrovascular lesion, we show that the effects of brain lesions may be selective both in space and in frequency. These findings do by nature escape visual detection in the conventional EEG reading, however they have intriguing correlates in the current concept of how somatosensory networks are thought to develop and/or become disorganized in the early preterm babies.

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