Engineer H&#233;ctor Belmont, Dr. M&#243;nica Carlier, Dr. Yuria Cruz and Dr. Mar&#237;a Elena Ju&#225;rez collaborated in data collection. The authors thank Paul Kersey for revising English language use. The project was partially funded by PAPIIT grant IN2009/7 and CONACYT (National Council for Science and Technology, Mexico) grant 4971.

1. Preparation of the Newborns
NOTE: The procedure followed is innocuous and painless, so there are no counter-indications for evaluating full-term and preterm newborns, once they are clinically stable.
<ol>
	<li>Ensure two and half hour fasting and wakefulness before beginning the study, in neonates older than 40 weeks of postconceptional age.</li>
	<li>Make sure that the baby&#39;s head be washed with neutral soap the day before the study. Thus, his/her hair will be clean and dry. Do not apply conditioners.</li>
	<li>Allow the mother to start feeding the newborn 30 min before beginning the study. Allow him/her to burp and start the sleep wrapped in sheets. This will ensure that he/she sleeps easily and spontaneously.</li>
	<li>Wash hands carefully before handling the neonate.</li>
	<li>Use sanitary masks.</li>
	<li>Gently wipe the scalp of the newborn with a cotton ball or gauze soaked in alcohol to remove residual dirt and superficial grease, before the neonate falls asleep.</li>
	<li>Measure the distance between nasion and inion, and between both pre-auricular pits. Calculate 10% and 20% to ensure proper placement of the cranial electrodes according to the international 10-20 system of electrode placement.</li>
	<li>Cover the newborn&#39;s entire head with a tubular elastic mesh for the correct attachment of the electroencephalography (EEG) and VEP electrodes. Leave the face fully free and exposed, as shown in Figure 1.</li>
	<li>Mark on the mesh the location of the surface electrodes.</li>
	<li>Use a swab to perfectly separate the newborn&#39;s hair at the sites where each electrode will be placed, and lightly rub the skin with abrasive gel for neurophysiological studies. 
	NOTE: Reschedule the study if the neonate takes more than 2 h to fall asleep.</li>
</ol>
2. Placement of the Surface Electrodes for EEG and VEP Sleep Recording
NOTE: Before beginning, set the values of the instrument&#39;s frequency filters using the specifications in Table 1. It is advisable to connect all electrodes to the EEG and VEP instruments before placing them on the newborn.
<ol>
	<li>Place the elastic band sensor on the baby&#39;s chest to record thoracic respiratory expansion.</li>
	<li>Place the individual surface disc electrodes (standard silver-silver chloride, or gold disc electrodes) with conductive paste through the mesh to fix them in the cranial locations established by the international 10-20 EEG system, adapted for newborns.</li>
	<li>Locate the cranial electrodes for EEG at leads F3, F4, C3, C4, O1 and O2, or at least C3 and C4, referred to linked earlobes, to identify the stages of neonatal sleep.</li>
	<li>Fix the surface disc electrodes to the skin with medical adhesive tape. To record ocular movements (EOG), place one electrode 1 cm above the external canthus of the left eye and place another 1 cm below the external canthus of the right eye, also referred to linked earlobes.</li>
	<li>Similarly, attach the electrodes for surface electromyogram recording (EMG) on both sides of the chin, referenced against each other.</li>
	<li>Use two channels of the VEP equipment with the following leads: Oz (-) vs. Fz (+), and Oz (-) vs. A1 (+); the ground electrode is to be placed on the right mastoid.</li>
	<li>Set the analysis time for VEP registration in 600 ms. 
	NOTE: Table 1 shows the filter settings used for recording sleep EEGs and VEPs.</li>
	<li>Do not begin VEP recording until impedance values are below 5 k&#937;.</li>
</ol>
3. Sleep Recording
NOTE: VEPs are obtained while the newborn sleeps in hospital crib; the sleep stages are monitored simultaneously by polysomnography17,18.
<ol>
	<li>Prolong the EEG recording for 60&#8722;90 min or until AS is identified, to evaluate active (AS) and quiet sleep (QS) in newborns.</li>
	<li>Begin EEG recording while carefully observing the characteristics of neonatal sleep, to identify the active sleep stage, during which VEPs will be recorded.</li>
	<li>Identify neonatal sleep stages according to the criteria summarized in Table 2.</li>
</ol>
4. VEP Recording
NOTE: VEPs are registered according to established standards19,20.
<ol>
	<li>Allow one minute of EEG recording without visual stimulation when the neonate begins well-defined active sleep.</li>
	<li>Apply monocular light stimulation through handheld goggles with a LED matrix held manually 2 cm directly above each newborn&#39;s eyes.</li>
	<li>Observe if the infant has his eyes closed during VEP registration in AS and note if this does not occur.</li>
	<li>Begin the averaging of the VEPs in the equipment, presenting 20 to 40 luminous stimuli whose corresponding recordings are averaged to obtain an average curve or evoked response.</li>
	<li>Observe the reproducibility of the recorded averages. At least two reproducible evoked potentials are recommended.</li>
	<li>Visually recognize PII component of the VEPs during recording, since this peak is considered typical of neonatal VEPs. Identify the PII component as the maximal positive peak between 120 and 300 ms, preceded by a negative wave (NII) and followed by a maximal negativity between 200 and 400 ms, also called NIII.</li>
	<li>Stop the averaging of the VEPs if the newborn moves excessively, wakes up, or changes to another sleep stage, distinct from AS. Renew recording once the AS stage reestablishes. 
	NOTE: This point is critical, because VEPs obtained during QS or transitional sleep are less reliable than in AS.</li>
	<li>Finish registration after 2 averages with reproducible VEP are attained, or when 6 averages occur without a recognizable VEP. In the latter case, consider the result an absence of a replicable response.</li>
</ol>
5. Review and analysis of VEPs
NOTE: Figure 2 shows the main components of neonatal VEPs and their measurements.
<ol>
	<li>Evaluate the reproducibility of the VEPs by similar appearance and measurements between the two averaged curves. 
	NOTE: Some VEP recording systems offer a correlation measure between two averages.</li>
	<li>Measure the absolute latencies of the NII, PII and NIII waves using the device&#39;s cursors. Absolute latency is the time in ms elapsed from the onset of stimulation to the maximal or minimal peak of each component.</li>
	<li>Calculate the interpeak latencies in ms, including the differences between the absolute PII-NII, NII-NIII and PII-NIII latencies.</li>
	<li>Measure peak-to-peak amplitudes in &#181;V, for the NII-PII and PII-NIII components.</li>
	<li>Compare the latency and amplitude values obtained to the normal, or expected, values estimated for a population of healthy, similar-age newborns.</li>
</ol>

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	<li>Harmony, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Longitudinal+study+of+children+with+perinatal+brain+damage+in+whom+early+neurohabilitation+was+applied:+Preliminary+report.">Longitudinal study of children with perinatal brain damage in whom early neurohabilitation was applied: Preliminary report.</a> Neuroscience Letter. 12 (611), 59-67 (2016).</li><li>Spittle, A., Orton, J., Anderson, P. J., Boyd, R., Doyle, L. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Early+developmental+intervention+programs+provided+post+hospital+discharge+to+prevent+motor+and+cognitive+impairment+in+preterm+infants.">Early developmental intervention programs provided post hospital discharge to prevent motor and cognitive impairment in preterm infants.</a> Cochrane Database System Review. 24 (11), CD005495 (2015).</li><li>Huang, X., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Volume+Changes+and+Correlation+with+Visual+Evoked+Potential+in+Patients+with+Optic+Neuritis:+A+Voxel-Based+Morphometry+Study.">Volume Changes and Correlation with Visual Evoked Potential in Patients with Optic Neuritis: A Voxel-Based Morphometry Study.</a> Medical Science Monitor. 22, 1115-1123 (2016).</li><li>McGlone, L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neonatal+Visual+Evoked+Potentials+in+Infants+Born+to+Mothers+Prescribed+Methadone.">Neonatal Visual Evoked Potentials in Infants Born to Mothers Prescribed Methadone.</a> Pediatrics. 131 (3), 857-863 (2013).</li><li>Cruz, S., Crego, A., Ribeiro, E., Goncalves, O., Sampaio, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+VEP+study+in+sleeping+and+awake+one-month-old+infants+and+its+relation+with+social+behavior.">A VEP study in sleeping and awake one-month-old infants and its relation with social behavior.</a> International Journal of Developmental Neuroscience. 41, 37-43 (2015).</li><li>Kato, T., Watanabe, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Visual+evoked+potential+in+the+newborn:+Does+it+have+predictive+value?.">Visual evoked potential in the newborn: Does it have predictive value?.</a> Seminars in Fetal &amp; Neonatal Medicine. 11, 459-463 (2006).</li><li>Shepherd, A., Saunders, K., McCulloch, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effect+of+sleep+state+on+the+&#64258;ash+visual+evoked+potential.+A+case+study.">Effect of sleep state on the &#64258;ash visual evoked potential. 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M., Hirano, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Establishment+of+normal+values+for+flash+visual+evoked+potentials+(VEPs)+in+preterm+infants:+a+longitudinal+study+with+special+reference+to+two+components+of+the+N1+wave.">Establishment of normal values for flash visual evoked potentials (VEPs) in preterm infants: a longitudinal study with special reference to two components of the N1 wave.</a> Electroencephalography and Clinical Neurophysiology. 96, 291-299 (1995).</li><li>Roy, M. S., Gosselin, J., Hanna, N., Orquin, J., Chemtob, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=In&#64258;uence+of+the+state+of+alertness+on+the+pattern+visual+evoked+potentials+(PVEP)+in+very+young+infant.">In&#64258;uence of the state of alertness on the pattern visual evoked potentials (PVEP) in very young infant.</a> Brain &amp; Development. 26, 197-202 (2004).</li><li>Kraemer, M., Abrahamsson, M., Sjostrom, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+neonatal+development+of+the+light+&#64258;ash+visual+evoked+potential.">The neonatal development of the light &#64258;ash visual evoked potential.</a> Documenta Ophthalmologica. 99, 21-39 (1999).</li><li>Apkarian, P., Mirmiran, M., Tijssen, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+Behavioral+State+on+Visual+Processing+in+Neonates.">Effects of Behavioral State on Visual Processing in Neonates.</a> Neuropediatrics. 22, 85-91 (1991).</li><li>Cubero-Rego, L., Corsi-Cabrera, M., Ricardo-Garcell, J., Cruz-Mart&#237;nez, R., Harmony, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Visual+evoked+potentials+are+similar+in+polysomnographically+de&#64257;ned+quiet+and+active+sleep+in+healthy+newborns.">Visual evoked potentials are similar in polysomnographically de&#64257;ned quiet and active sleep in healthy newborns.</a> International Journal of Developmental Neuroscience. 68, 26-34 (2018).</li><li>Mizrahi, E. M., Mosh&#233;, S. L., Hrachovy, R. A., Niedermeyer, E., Lopes da Silva, F. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Normal+EEG+and+Sleep:+Preterm+and+Term+Neonates.">Normal EEG and Sleep: Preterm and Term Neonates.</a> Niedermeyer's Electroencephalography: Basic Principles, Clinical Applications, and Related. , 154-163 (2011).</li><li>Grigg-Damberger, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Visual+Scoring+of+Sleep+in+Infants+0+to+2+Months+of+Age.">The Visual Scoring of Sleep in Infants 0 to 2 Months of Age.</a> Journal of Clinical Sleep Medicine. 12 (3), 429-445 (2016).</li><li>Husain, A. M., Niedermeyer, E., Lopes da Silva, F. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Evoked+Potentials+in+Children+and+Infants.">Evoked Potentials in Children and Infants.</a> In Niedermeyer's Electroencephalography: Basic Principles, Clinical Applications, and Related Fields. , 1057-1082 (2011).</li><li>Odom, J. V., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=ISCEV+standard+for+clinical+visual+evoked+potentials:+2016+update.">ISCEV standard for clinical visual evoked potentials: 2016 update.</a> Documenta Ophthalmologica. 133 (1), 1-11 (2016).</li><li>Pojda-Wilczek, D., Maruszczyk, W., Sirek, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Flash+visual+evoked+potentials+(FVEP)+in+various+stimulation+conditions.">Flash visual evoked potentials (FVEP) in various stimulation conditions.</a> Documenta Ophthalmologica. 138, 35-42 (2019).</li><li>Tsuneishi, S., Casaer, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Stepwise+decrease+in+VEP+latencies+and+the+process+of+myelination+in+the+human+visual+pathway.">Stepwise decrease in VEP latencies and the process of myelination in the human visual pathway.</a> Brain &amp; Development. 19, 547-551 (1997).</li></ol>

The authors have nothing to disclose.

Three components of visual-evoked responses (NII, PII and NIII) were characterized in healthy, full-term newborns while doing stimulation with LED googles, and recorded during polygraphically-identified sleep states. The VEP morphology observed is consistent with previous results reported for fewer neonates11,15. The characterization of VEP responses was achieved by recording 20 healthy, full-term newborns at similar post-conceptional age16</sup...

Early detection of abnormal development of the central nervous system in at-risk newborns is crucial for successful early interventions1,2. Visual event-related potentials (VEPs) provide a useful means of evaluating visual cortical status because they do not require patient cooperation, which is not possible in the first month of life, are objective, and are sensitive to structural and functional brain damage3,4.
Though, some studies of newborns have shown that normal visual-evoked responses indicate adequate neural maturation of the cerebral cortex4,5, and that this has often been studied in newborns to assess neurodevelopment and identify abnormal development of the visual pathways4,5, the clinical use of VEPs has been limited by the variability observed in their morphology4,5,6,7. Therefore, it is important to obtain better, more reliable characterizations of VEPs in newborns.
One cause of the variability in VEP morphology is that earlier studies have mixed preterm and older babies (over one month)8,9,10. However, the most important source is the lack of attention paid to the infants&#39; behavioral state while recording VEPs; namely, awake, quiet (QS), active (AS), or transitional sleep. QS and AS have either not been analyzed separately5,11,12, or studies have relied exclusively on behavioral observation without using polysomnography to identify states7,8. Trac&#233; alternant, which consists in bursts of high amplitude slow activity alternating with inter-burst intervals of minimal amplitudes is present in QS, but has not been taken into account when averaging VEPs. Some studies with newborns have measured VEPs by recording during wakefulness13,14, but at this stage of development waking periods are brief and newborns are usually crying or moving, which makes it difficult to obtain high quality, reliable recordings.
Few studies have used light-emitting diodes (LEDs) googles6,9 to elicit VEPs, though this light source generates more consistent recordings than the usual strobe flashes of white light11,14,15, which are less reliable. Obtaining replicable VEPs in the same newborn is indispensable for clinical use4, but another cause of variability is the low reproducibility of VEP morphology, likely due to the lack of control of physiological states and of the stimuli used to elicit VEPs. Given these conditions, the high variability of VEP morphology is hardly surprising.
A previous study conducted with 20 healthy full-term newborns that considered several sources of variability: post-conceptional age, polysomnographically-identified sleep states, LED googles to elicit VEPs, and measures of reproducibility between two VEP averages found that a clearer, more reliable VEP morphology can be obtained during active sleep. During this sleep stage all infants generated clear VEPs with higher correlations between two averages than in QS. Also, fewer VEP averages were required to obtain reproducibility16.
Given the clinical usefulness of VEP studies to assess, as early as possible, the integrity of visual pathways, this study proposes a series of methodological steps designed to obtain reliable VEPs in preterm and older newborns, using LED goggles during AS unambiguously defined by simultaneous polysomnography.

<table><tbody><tr><td>Digital Electroencephalograph</td><td>Neuronic Mexicana, SA</td><td>Medicid 3E</td><td>Sleep electroencephalogram record</td></tr><tr><td>Evoked Potentials equipment</td><td>Neuronic Mexicana, SA</td><td>Neuronic PE (N_N-SW-2.0)</td><td>Visual evoked potentials record</td></tr><tr><td>Nuprep Gel</td><td>WEAVER and Company</td><td>Skin preparing abrasive gel (114 g)</td><td></td></tr><tr><td>Ten20 Conductive Paste</td><td>WEAVER and Company</td><td>Neurodiagnostic electrode paste (228 g)</td><td></td></tr><tr><td>Tubular elastic mesh bandage</td><td>Le Roy</td><td></td><td>Fixation of cranial surface electrodes, Size 4 or Small</td></tr></tbody></table>

how to obtain reliable visual event-related potentials in newborns

The present study discusses the characteristics of visual event-related potentials (VEPs) and outlines methodological steps for obtaining reliable measurements in newborns. Obtaining high-quality, reliable VEPs is crucial for the early detection of abnormal development of the central nervous system in at-risk newborns, and for implementing successful early interventions. Recommendations are based on a previous study which showed that when post-conceptional age, polysomnography-identified sleep stages, and light-emitting diodes (LEDs) googles as the luminous source are controlled, no more than 4 repetitions of VEP averages are required to obtain replicable recordings, variability decreases, and reliable VEPs can be obtained. By controlling for these sources of variability and using statistical analyses, we were able to clearly and reliably identify the amplitude and latency of three main components (NII, PII and NIII) present in 100% of newborns (n = 20) during active sleep. Recording VEPs during awake states, quiet sleep and transitional sleep is not recommended because VEP morphology may differ significantly from one average to the next, leading to the risk of misleading clinical prognoses. Moreover, it is easier to obtain VEPs during active sleep because this state can be clearly and reliably identified at this stage of development, sleep cycles are short enough to allow measurements to be taken in a reasonable time, and the method does not require new o expensive equipment.

To detect adequate maturation in the function of the visual pathway it is essential to obtain the PII component of the VEP, which can be seen in both term and preterm infants. The simultaneous recording of VEPs with polysomnography during AS makes it possible to obtain typical VEPs.
Reliable VEP studies require obtaining reproducible average waveforms that will be indispensable for clinical use. Figure 2</st...

Watch this Scientific Journal Video about How to Obtain Reliable Visual Event-related Potentials in Newborns at JoVE.com

How to Obtain Reliable Visual Event-related Potentials in Newborns

Several important points for obtaining high-quality reliable visual evoked potentials (VEPs) in newborns while minimizing variability and the risk of misleading prognoses are presented.

The present study discusses the characteristics of visual event-related potentials (VEPs) and outlines methodological steps for obtaining reliable ...

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6.3K Views.  National Autonomous University of Mexico. Het verkrijgen van visuele event-gerelateerde mogelijkheden van hoge kwaliteit is cruciaal voor de vroegtijdige opsporing van abnormale ontwikkeling binnen het centrale zenuwstelsel en is belangrijk voor een succesvolle vroegtijdige interventie-implementatie bij risicovolle pasgeborenen. VEPs zijn objectief, niet-invasief, en gevoelig voor structurele en functionele hersenschade. Opname tijdens polysomnografie-geïdentificeerde actieve slaap vermindert variabiliteit waardoor betrouwbare VEPs ...

Video: How to Obtain Reliable Visual Event-related Potentials in Newborns

P50 Sensory Gating in Infants

Attentional deficits are common in a variety of neuropsychiatric disorders including attention deficit-hyperactivity disorder, autism, bipolar mood disorder, and schizophrenia. There has been increasing interest in the neurodevelopmental components of these attentional deficits; neurodevelopmental meaning that while the deficits become clinically prominent in childhood or adulthood, the deficits are the results of problems in brain development that begin in infancy or even prenatally. Despite this interest, there are few methods for assessing attention very early in infancy. This report focuses on one method, infant auditory P50 sensory gating.
Attention has several components. One of the earliest components of attention, termed sensory gating, allows the brain to tune out repetitive, noninformative sensory information. Auditory P50 sensory gating refers to one task designed to measure sensory gating using changes in EEG. When identical auditory stimuli are presented 500 ms apart, the evoked response (change in the EEG associated with the processing of the click) to the second stimulus is generally reduced relative to the response to the first stimulus (i.e. the response is &#34;gated&#34;). When response to the second stimulus is not reduced, this is considered a poor sensory gating, is reflective of impaired cerebral inhibition, and is correlated with attentional deficits.
Because the auditory P50 sensory gating task is passive, it is of potential utility in the study of young infants and may provide a window into the developmental time course of attentional deficits in a variety of neuropsychiatric disorders. The goal of this presentation is to describe the methodology for assessing infant auditory P50 sensory gating, a methodology adapted from those used in studies of adult populations.

Methods to record auditory P50 sensory gating, a physiological marker of cerebral inhibition which reflects early stages of attention, are described.

Attentional deficits are common in a variety of neuropsychiatric disorders including attention deficit-hyperactivity disorder, autism, bipolar mood ...

Behavior

Cortical Source Analysis of High-Density EEG Recordings in Children

EEG is traditionally described as a neuroimaging technique with high temporal and low spatial resolution. Recent advances in biophysical modelling and signal processing make it possible to exploit information from other imaging modalities like structural MRI that provide high spatial resolution to overcome this constraint1. This is especially useful for investigations that require high resolution in the temporal as well as spatial domain. In addition, due to the easy application and low cost of EEG recordings, EEG is often the method of choice when working with populations, such as young children, that do not tolerate functional MRI scans well. However, in order to investigate which neural substrates are involved, anatomical information from structural MRI is still needed. Most EEG analysis packages work with standard head models that are based on adult anatomy. The accuracy of these models when used for children is limited2, because the composition and spatial configuration of head tissues changes dramatically over development3.&#160;
In the present paper, we provide an overview of our recent work in utilizing head models based on individual structural MRI scans or age specific head models to reconstruct the cortical generators of high density EEG. This article describes how&#160;EEG recordings are acquired, processed, and analyzed with pediatric populations at the London Baby Lab, including laboratory setup, task design, EEG preprocessing, MRI processing, and EEG channel level and source analysis.&#160;

In recent years, there has been increasing interest in estimating the cortical sources of scalp measured electrical activity for cognitive neuroscience experiments. This article describes how high density EEG is acquired and how recordings are processed for cortical source estimation in children from the age of 2 years at the London Baby Lab.

EEG is traditionally described as a neuroimaging technique with high temporal and low spatial resolution. Recent advances in biophysical modelling and ...

Infant Auditory Processing and Event-related Brain Oscillations

Rapid auditory processing and acoustic change detection abilities play a critical role in allowing human infants to efficiently process the fine spectral and temporal changes that are characteristic of human language. These abilities lay the foundation for effective language acquisition; allowing infants to hone in on the sounds of their native language. Invasive procedures in animals and scalp-recorded potentials from human adults suggest that simultaneous, rhythmic activity (oscillations) between and within brain regions are fundamental to sensory development; determining the resolution with which incoming stimuli are parsed. At this time, little is known about oscillatory dynamics in human infant development. However, animal neurophysiology and adult EEG data provide the basis for a strong hypothesis that rapid auditory processing in infants is mediated by oscillatory synchrony in discrete frequency bands. In order to investigate this, 128-channel, high-density EEG responses of 4-month old infants to frequency change in tone pairs, presented in two rate conditions (Rapid: 70 msec ISI and Control: 300 msec ISI) were examined. To determine the frequency band and magnitude of activity, auditory evoked response averages were first co-registered with age-appropriate brain templates. Next, the principal components of the response were identified and localized using a two-dipole model of brain activity. Single-trial analysis of oscillatory power showed a robust index of frequency change processing in bursts of Theta band (3 - 8 Hz) activity in both right and left auditory cortices, with left activation more prominent in the Rapid condition. These methods have produced data that are not only some of the first reported evoked oscillations analyses in infants, but are also, importantly, the product of a well-established method of recording and analyzing clean, meticulously collected, infant EEG and ERPs. In this article, we describe our method for infant EEG net application, recording, dynamic brain response analysis, and representative results.

High-density electroencephalography (dEEG) is being used increasingly to study brain development and plasticity in the early years of life. Here we present an application of sophisticated analysis techniques that builds on traditional EEG recording to understand the oscillatory dynamics of rapid auditory processing in the infant brain.

Rapid auditory processing and acoustic change detection abilities play a critical role in allowing human infants to efficiently process the fine spectral ...

Event-related Potentials During Target-response Tasks to Study Cognitive Processes of Upper Limb Use in Children with Unilateral Cerebral Palsy

Unilateral Cerebral Palsy (CP) is a neurodevelopmental disorder that is a very common cause of disability in childhood. It is characterized by unilateral motor impairments that are frequently dominated in the upper limb. In addition to a reduced movement capacity of the affected upper limb, several children with unilateral CP show a reduced awareness of the remaining movement capacity of that limb. This phenomenon of disregarding the preserved capacity of the affected upper limb is regularly referred to as Developmental Disregard (DD). Different theories have been postulated to explain DD, each suggesting slightly different guidelines for therapy. Still, cognitive processes that might additionally contribute to DD in children with unilateral CP have never been directly studied. The current protocol was developed to study cognitive aspects involved in upper limb control in children with unilateral CP with and without DD. This was done by recording event-related potentials (ERPs) extracted from the ongoing EEG during target-response tasks asking for a hand-movement response. ERPs consist of several components, each of them associated with a well-defined cognitive process (e.g., the N1 with early attention processes, the N2 with cognitive control and the P3 with cognitive load and mental effort). Due to its excellent temporal resolution, the ERP technique enables to study several covert cognitive processes preceding overt motor responses and thus allows insight into the cognitive processes that might contribute to the phenomenon of DD. Using this protocol adds a new level of explanation to existing behavioral studies and opens new avenues to the broader implementation of research on cognitive aspects of developmental movement restrictions in children.

Several children with unilateral Cerebral Palsy seem to disregard the preserved capacity of their affected upper limb. This Developmental Disregard is extensively described in the literature but the involved cognitive processes have not been studied. To study underlying cognitive factors of upper limb control, an event-related potential protocol was developed.

Unilateral Cerebral Palsy (CP) is a neurodevelopmental disorder that is a very common cause of disability in childhood. It is characterized by unilateral ...

Electrophysiological Measurements and Analysis of Nociception in Human Infants

Pain is an unpleasant sensory and emotional experience. Since infants cannot verbally report their experiences, current methods of pain assessment are based on behavioural and physiological body reactions, such as crying, body movements or changes in facial expression. While these measures demonstrate that infants mount a response following noxious stimulation, they are limited: they are based on activation of subcortical somatic and autonomic motor pathways that may not be reliably linked to central sensory processing in the brain. Knowledge of how the central nervous system responds to noxious events could provide an insight to how nociceptive information and pain is processed in newborns.
The heel lancing procedure used to extract blood from hospitalised infants offers a unique opportunity to study pain in infancy. In this video we describe how electroencephalography (EEG) and electromyography (EMG) time-locked to this procedure can be used to investigate nociceptive activity in the brain and spinal cord.
This integrative approach to the measurement of infant pain has the potential to pave the way for an effective and sensitive clinical measurement tool.

The assessment and treatment of pain in infants is difficult because infants cannot verbally report their experience. In this video we describe quantitative electrophysiological methods and analysis techniques that can be used to measure the response to noxious events from the infant nervous system.

Pain is an unpleasant sensory and emotional experience. Since infants cannot verbally report their experiences, current methods of pain assessment are ...

Preterm EEG: A Multimodal Neurophysiological Protocol

Since its introduction in early 1950s, electroencephalography (EEG) has been widely used in the neonatal intensive care units (NICU) for assessment and monitoring of brain function in preterm and term babies. Most common indications are the diagnosis of epileptic seizures, assessment of brain maturity, and recovery from hypoxic-ischemic events. EEG recording techniques and the understanding of neonatal EEG signals have dramatically improved, but these advances have been slow to penetrate through the clinical traditions. The aim of this presentation is to bring theory and practice of advanced EEG recording available for neonatal units. 
In the theoretical part, we will present animations to illustrate how a preterm brain gives rise to spontaneous and evoked EEG activities, both of which are unique to this developmental phase, as well as crucial for a proper brain maturation. Recent animal work has shown that the structural brain development is clearly reflected in early EEG activity. Most important structures in this regard are the growing long range connections and the transient cortical structure, subplate. Sensory stimuli in a preterm baby will generate responses that are seen at a single trial level, and they have underpinnings in the subplate-cortex interaction. This brings neonatal EEG readily into a multimodal study, where EEG is not only recording cortical function, but it also tests subplate function via different sensory modalities. Finally, introduction of clinically suitable dense array EEG caps, as well as amplifiers capable of recording low frequencies, have disclosed multitude of brain activities that have as yet been overlooked.
In the practical part of this video, we show how a multimodal, dense array EEG study is performed in neonatal intensive care unit from a preterm baby in the incubator. The video demonstrates preparation of the baby and incubator, application of the EEG cap, and performance of the sensory stimulations.

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.

Since its introduction in early 1950s, electroencephalography (EEG) has been widely used in the neonatal intensive care units (NICU) for assessment and ...

Exploring Infant Sensitivity to Visual Language using Eye Tracking and the Preferential Looking Paradigm

We discuss the use of the preferential looking paradigm in eye tracking studies in order to study how infants develop, understand, and attend to the world around them. Eye tracking is a safe and non-invasive way to collect gaze data from infants, and the preferential looking paradigm is simple to design and only requires the infant to be attending to the screen. By simultaneously showing two visual stimuli that differ in one dimension, we can assess whether infants show different looking behavior for either stimulus, thus demonstrating sensitivity to that difference. The challenges in such experimental approaches are that experiments must be kept brief (no more than 10 min) and be carefully controlled such that the two stimuli differ in only one way. The interpretation of null results must also be carefully considered. In this paper, we illustrate a successful example of an infant eye tracking study with a preferential looking paradigm to discover that 6-month-olds are sensitive to linguistic cues in a signed language despite having no prior exposure to signed language, suggesting that infants possess intrinsic or innate sensitivities to these cues.

Eye tracking studies using a preferential looking paradigm can be used to study infants&#39;&#160;emerging understanding of, and attention to, their external visual world.

We discuss the use of the preferential looking paradigm in eye tracking studies in order to study how infants develop, understand, and attend to the world ...

Application of an Amplitude-integrated EEG Monitor (Cerebral Function Monitor) to Neonates

Amplitude-integrated EEG (aEEG) is an easily accessible technique to monitor the electrocortical activity in preterm and term infants in neonatal intensive care units (NICUs). This method was first used to monitor newborns after asphyxia, providing information about future neurological outcomes. The aEEG is also helpful to select newborns who benefit from cooling. The aEEG monitoring of preterm infants is becoming more widespread, as various studies have shown that neurodevelopmental outcome is related to early aEEG tracings. Here, we demonstrate the application of the aEEG monitoring system and present typical patterns that depend upon gestational age and pathophysiological conditions. Furthermore, we mention pitfalls in the interpretation of the aEEG, as this method requires accurate fixation and localization of the electrodes. Additionally, the raw EEG can be used to detect neonatal seizures or to identify aEEG application problems. In conclusion, aEEG is a safe and generally well-tolerated method for the bedside monitoring of neonatal cerebral function; it can even provide information about long-term outcome.

Application of an Amplitude-integrated EEG Monitor Cerebral Function Monitor to Neonates

Here, we show how to apply amplitude-integrated electroencephalography to monitor cerebral function in neonates.

Amplitude-integrated EEG (aEEG) is an easily accessible technique to monitor the electrocortical activity in preterm and term infants in neonatal ...

Medicine

Electrophysiological Measurement of Noxious-evoked Brain Activity in Neonates Using a Flat-tip Probe Coupled to Electroencephalography

Pain is an unpleasant sensory and emotional experience. In non-verbal patients, it is very difficult to measure pain, even with pain assessment tools. Those tools are subjective or determine secondary physiological indicators which also have certain limitations particularly when exploring the effectiveness of analgesia. As cortical processing is essential for pain perception, brain activity measures may provide a useful approach to assess pain in infants. Here we present a method to assess nociception with electrophysiological brain activity recordings optimized for the use in newborn infants. To produce highly standardized and reproducible noxious stimuli we applied mechanical stimulation with a flat-tip probe, e.g., PinPrick, which is not skin-breaking and does not cause behavioral distress. The noxious-evoked potential allows the objective measurement of nociception in non-verbal patients. This method can be used in newborn infants as early as 34 weeks of gestational age. Moreover, it could be applied in different situations such as measuring the efficacy of analgesic or anesthetic drugs.

Measuring pain in non-verbal patients is a challenge. In this study we combine EEG recording with stimulation using a flat-tip probe to detect noxious-evoked brain activity in an objective manner.

Pain is an unpleasant sensory and emotional experience. In non-verbal patients, it is very difficult to measure pain, even with pain assessment tools. ...

Stimulus-specific Cortical Visual Evoked Potential Morphological Patterns

This paper presents a methodology for the recording and analysis of cortical visual evoked potentials (CVEPs) in response to various visual stimuli using 128-channel high-density electroencephalography (EEG). The specific aim of the described stimuli and analyses is to examine whether it is feasible to replicate previously reported CVEP morphological patterns elicited by an apparent motion stimulus, designed to simultaneously stimulate both ventral and dorsal central visual networks, using object and motion stimuli designed to separately stimulate ventral and dorsal visual cortical networks.&#160; Four visual paradigms are presented: 1. Randomized visual objects with consistent temporal presentation. 2. Randomized visual objects with inconsistent temporal presentation (or jitter).&#160; 3. Visual motion via a radial field of coherent central dot motion without jitter.&#160; 4. Visual motion via a radial field of coherent central dot motion with jitter.&#160; These four paradigms are presented in a pseudo-randomized order for each participant.&#160; Jitter is introduced in order to view how possible anticipatory-related effects may affect the morphology of the object-onset and motion-onset CVEP response.&#160; EEG data analyses are described in detail, including steps of data exportation from and importation to signal processing platforms, bad channel identification&#160;and removal, artifact rejection, averaging, and categorization of average CVEP morphological pattern type based upon latency ranges of component peaks. Representative data show that the methodological approach is indeed sensitive in eliciting differential object-onset and motion-onset CVEP morphological patterns and may, therefore, be useful in addressing the larger research aim. Given the high temporal resolution of EEG and the possible application of high-density EEG in source localization analyses, this protocol is ideal for the investigation of distinct CVEP morphological patterns and the underlying neural mechanisms which generate these differential responses.&#160; &#160; &#160;&#160;

In this paper, we present a protocol to investigate differential cortical visual evoked potential morphological patterns through stimulation of ventral and dorsal networks using high-density EEG. Visual object and motion stimulus paradigms, with and without temporal jitter, are described. Visual evoked potential morphological analyses are also outlined.&#160;&#160;

This paper presents a methodology for the recording and analysis of cortical visual evoked potentials (CVEPs) in response to various visual stimuli using ...

How to Obtain Reliable Visual Event-related Potentials in Newborns

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