This work was funded, at least in part, by the National Institutes of Health (NIH grant numbers MH086383, MH056539 and MH015442) and by the Institute for Children&#8217;s Mental Disorders.

1. Institutional Review and Oversight
<ol>
	<li>All work with human subjects requires Institutional Review Board approval and oversight. Methods reported here, when used in research, have been reviewed and approved by the Colorado Multiple Institutional Review Board (COMIRB).</li>
</ol>
2. Preparation and Recording
<ol>
	<li>Schedule the baby for 90 min at the infant&#39;s regular nap time. Have clean electrodes, conductive EEG paste, and a dark quite room available. Feed, burp, and diaper the infant before beginning.</li>
	<li>Wipe the head to minimize impedance. CZ has the largest amplitude P5011. Place an electrodes at CZ, on the forehead, above and below one eye, on the chin, and on the right mastoid.</li>
	<li>Present 50 msec broad-spectrum stimuli (clicks) as pairs with a 500 msec interstimulus interval. Pairs of clicks should be presented 10 sec apart.</li>
	<li>Record until there are 15 min of continuous active sleep (the infant equivalent of REM sleep). Allow the infant to complete their natural sleep period. This may take &#62;90 min to achieve. Record baby&#39;s status (e.g. eyes open or closed, movement, etc.) during the entire sleep period.</li>
</ol>
3. Data Analysis
<ol>
	<li>Identify 15 min of continuous, active sleep. This period will have high frequency, low voltage brain waves, low muscle tone, large eye movements, and will be noted for having eyes closed.</li>
	<li>Filter data to remove 60 Hz interference and low frequency (&#60;1 Hz drift)12.</li>
	<li>Identify epochs by the presentation of the first sound in each pair. Average at least 60 epochs. The greater the number of epochs used, the greater signal to noise ratio possible.</li>
	<li>Filter the averaged tracing using a bandpass filter between 10-50 Hz. This allows the component to be identified more easily. Using the filtered averaged tracing, measure P50 amplitude in response to the first and second stimulus independently. P50 waves are identified as the first wave between 40 and 100 msec after stimulus presentation; amplitude is measured from the preceding trough to the peak.</li>
	<li>Divide the amplitude of the P50 wave in response to the second sound by the amplitude of the P50 wave in response to the first sound to obtain a P50 sensory gating ratio.</li>
</ol>

<ol>
	<li>Braff, D. L., Light, G. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Preattentional+and+attentional+cognitive+deficits+as+targets+for+treating+schizophrenia.">Preattentional and attentional cognitive deficits as targets for treating schizophrenia.</a> Psychopharmacology. 174 (1), 75-85 (2004).</li><li>Boutros, N. N., Belger, A., Campbell, D., DG&#199;&#214;Souza, C., Krystal, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comparison+of+four+components+of+sensory+gating+in+schizophrenia+and+normal+subjects:+a+preliminary+report.">Comparison of four components of sensory gating in schizophrenia and normal subjects: a preliminary report.</a> Psychiat. Res. 88 (2), 119-130 (1999).</li><li>Cullum, C. M., Harris, J. 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C., Griffith, J., Freedman, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Gating+of+auditory+response+in+schizophrenics+and+normal+controls:+Effects+of+recording+site+and+stimulation+interval+on+the+P50+wave.">Gating of auditory response in schizophrenics and normal controls: Effects of recording site and stimulation interval on the P50 wave.</a> Schizo. Res. 4 (1), 31-40 (1991).</li><li>Hunter, S. K., Kisley, M. A., McCarthy, L., Freedman, R., Ross, R. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Diminished+cerebral+inhibition+in+neonates+associated+with+risk+factors+for+schizophrenia:+Parental+psychosis,+maternal+depression,+and+nicotine.">Diminished cerebral inhibition in neonates associated with risk factors for schizophrenia: Parental psychosis, maternal depression, and nicotine.</a> 37 (6), 1200-1208 (2011).</li><li>Siegel, C., Waldo, M., Mizner, G., Adler, L. E., Freedman, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Deficits+in+sensory+gating+in+schizophrenic+patients+and+their+relatives:+Evidence+obtained+with+auditory+evoked+responses.">Deficits in sensory gating in schizophrenic patients and their relatives: Evidence obtained with auditory evoked responses.</a> Arch. Gen. Psychiat. 41, 607-612 (1984).</li><li>Ross, R. G., Hunter, S. K., 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=Perinatal+choline+effects+on+neonatal+pathophysiology+related+to+later+schizophrenia+risk.">Perinatal choline effects on neonatal pathophysiology related to later schizophrenia risk.</a> Am. J. Psychiat. 170 (3), 290-298 (2013).</li><li>Tregellas, J. R., Davalos, D. B., 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=Increased+hemodynamic+response+in+the+hippocampus,+thalamus,+and+prefrontal+cortex+during+abnormal+sensory+gating+in+schizophrenia.">Increased hemodynamic response in the hippocampus, thalamus, and prefrontal cortex during abnormal sensory gating in schizophrenia.</a> Schizo. Res. 92 (1-3), 262-272 (2007).</li><li>Ross, R. G., Stevens, K. E., 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=Cholinergic+mechanisms,+early+brain+development,+and+risk+for+schizophrenia.">Cholinergic mechanisms, early brain development, and risk for schizophrenia.</a> J. Child Psychol. Psychiat. 51 (5), 535-549 (2010).</li><li>Leonard, S., Gault, J., 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=Association+of+promoter+variants+in+the+alpha7+nicotinic+acetylcholine+receptor+subunit+gene+with+an+inhibitory+deficit+found+in+schizophrenia.">Association of promoter variants in the alpha7 nicotinic acetylcholine receptor subunit gene with an inhibitory deficit found in schizophrenia.</a> Arch. Gen. Psychiat. 59 (12), 1085-1096 (2002).</li><li>Stevens, K. E., Kem, W. R., Freedman, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Selective+alphay+7+nicotinic+receptor+stimulation+normalizes+chronic+cocaine-induced+loss+of+hippocampal+sensory+inhibition+in+C3H+mice.">Selective alphay 7 nicotinic receptor stimulation normalizes chronic cocaine-induced loss of hippocampal sensory inhibition in C3H mice.</a> Biol. Psychiat. 46 (10), 1443-1450 (1999).</li><li>Adler, L. E., Hoffer, L. J., Griffith, J., Waldo, M. C., Freedman, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Normalization+by+nicotine+of+deficient+auditory+sensory+gating+in+the+relatives+of+schizophrenics.">Normalization by nicotine of deficient auditory sensory gating in the relatives of schizophrenics.</a> Biol. Psychiatr. 32 (7), 607-616 (1992).</li><li>Griffith, J. M., O'Neill, J. E., 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=Nicotinic+receptor+desensitization+and+sensory+gating+deficits+in+schizophrenia.">Nicotinic receptor desensitization and sensory gating deficits in schizophrenia.</a> Biol. Psychiat. 44, 98-106 (1998).</li><li>Giniatullin, R., Nistri, A., Yakel, J. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Desensitization+of+nicotinic+ACh+receptors:+shaping+cholinergic+signaling.">Desensitization of nicotinic ACh receptors: shaping cholinergic signaling.</a> Trends Neurosci. 28 (7), 371-378 (2005).</li><li>Kisley, M. A., Polk, S. D., Ross, R. G., Levisohn, P. M., Freedman, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Early+postnatal+development+of+sensory+gating.">Early postnatal development of sensory gating.</a> Neurophysiol. Basic Clin. 14, 693-697 (2003).</li><li>Hunter, S. K., Corral, N., Ponicsan, H., Ross, R. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reliability+of+P50+auditory+sensory+gating+measures+in+infants+during+active+sleep.">Reliability of P50 auditory sensory gating measures in infants during active sleep.</a> Neuroreport. 19 (1), 79-82 (2008).</li><li>Gillow, S., Hunter, S., Ross, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Stability+of+P50+sensory+gating+in+preschoolers.">Stability of P50 sensory gating in preschoolers.</a> J. Invest. Med. 58 (1), 154-155 (2010).</li><li>Hunter, S. K., Mendoza, J. H., 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=Antidepressants+may+mitigate+the+effects+of+prenatal+maternal+anxiety+on+infant+auditory+sensory+gating.">Antidepressants may mitigate the effects of prenatal maternal anxiety on infant auditory sensory gating.</a> Am. J. Psychiatr. 169 (6), 616-624 (2012).</li><li>Hutchison, A. K., Hunter, S. K., 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=Diminished+infant+P50+sensory+gting+predicts+increased+40-month-old+attention,+anxiety/depression+and+externalizing.">Diminished infant P50 sensory gting predicts increased 40-month-old attention, anxiety/depression and externalizing.</a> J. Atten. Disord.. , (2013).</li></ol>

Drs. Ross and Hunter receive salary support from NIH-funded grants. All other authors have no conflicts to disclose.

P50 sensory gating is thought to reflect a complex interaction of inhibitory neurocircuits located primarily in the hippocampus, dorsolateral prefrontal cortex, and thalamus16. Thus, alterations in P50 sensory gating in infants may suggest altered development in these regions of the brain.
In these brain regions, GABAergic interneuron inhibition of glutaminergic pyramidal cells likely accounts for the gating process, with the inhibition provided by GABAergic cells. The GABAergic interneurons are themselves modulated by adrenergic and cholinergic input. The adrenergic input is intermittent and inhibits the interneurons which decreases their ability to inhibit pyramidal cells and thus blocks sensory gating. One of the difficulties in recording awake infants is that even very mild stressors, such as applying electrodes, can increase adrenergic tone an interfere with the ability to measure functional gating abilities.
In contrast to the impact of intermittent adrenergic input, cholinergic stimulation of interneurons is tonic and results in enhanced interneuron firing, thus improving sensory gating17. Factors which decrease cholinergic input, such as genetic phenotypes related to decreased cholinergic receptor expression, lead to chronic problems in sensory gating18. Similarly, decreased neuronal release of choline, as occurs during non-REM sleep, also decreases interneuron activity and sensory gating. Nicotine is an interesting compound as acute use stimulates nicotinic cholinergic receptors and improves sensory gating19,20, while repeated or chronic nicotine use has no effect when used alone but blocks the effects of other agonists21, presumably because chronic stimulation leads to receptor desensitization22. Infants who are exposed to prenatally exposed to nicotine through maternal cigarette use have impaired P50 sensory gating12.
This awareness of the fundamental biology of sensory gating was the rationale for a randomized trial of supplementation during pregnancy with the dietary component choline, an agonist at the cholinergic receptor on interneurons. Supplementation occurred in from early in the second trimester through approximately 3 months post birth. Infants who had received choline supplementation had accelerated development of sensory gating15.
Infant P50 sensory gating ratio assessment is feasible23, reliable24, and stable between infancy and four years of age25. Impairments in infant P50 sensory gating are associated with prenatal risk factors for later psychiatric illness12,26 and with increased risk for developing psychiatric symptoms at 4 years of age27. However, infants with impaired P50 sensory gating have never been followed beyond 4 years of age; thus it remains unclear if infant P50 sensory gating is predictive of later psychopathology or if efforts to alter infant P50 sensory gating will be useful as primary prevention strategies.
The adaptation of auditory P50 sensory gating paradigm for infant study allows exploration of questions related to when during development cerebral inhibition develops and when that development goes awry for individuals vulnerable to later attention-associated neuropsychiatric illnesses. Similar efforts with other physiological tasks, such as mismatch negativity, eye tracking, and prepulse inhibition may offer other windows into early development. It is hoped that the adaptation of tasks for use in early infancy may increase understanding of the developmental time course of these disorders as well as suggest novel primary prevention strategies17.

Many neuropsychiatric illnesses- including attention deficit-hyperactivity disorder (ADHD), bipolar mood disorder, and schizophrenia- are considered neurodevelopmental disorders, meaning that the onset of symptoms is at least partially due to very early aberrations in brain development. The early brain developmental aberrations may be silent or only associated with nonspecific symptoms for years or even decades prior to onset of the full disorder. This model suggests that a full understanding of the disorder may require methods to measure very subtle changes in brain function very early in brain development.
P50 sensory gating reflects an early step in the attentional process1,2. P50 sensory gating refers to a specific task, an auditory evoked potential task, which correlates with behavioral and neurocognitive tests of attention and reflects cerebral inhibitory mechanisms3,4. In this task, subjects are presented with two identical broad spectrum auditory stimuli (&#34;clicks&#34;) while an EEG response is recorded. An auditory stimulus elicits a consistent EEG-measured brain response; the response includes a wave which, in adults, occurs approximately 50 msec after the stimulus. Since the wave is in the positive direction, this wave is described as the P50 wave. Most individuals demonstrate a significantly reduced response to the second stimulus of a pair relative to the first, reflective of the brain&#39;s ability to automatically inhibit response to irrelevant repetitive information (to &#34;gate&#34; sensory information). Many psychiatric illnesses with attentional symptoms-including attention deficit-hyperactivity disorder (ADHD), bipolar mood disorder, and schizophrenia-are associated with impairment in sensory gating5-7.
Auditory P50 sensory gating results can be confounded by a subject&#39;s adrenergic tone8. During REM sleep, adrenergic tone is diminished making REM sleep an optimal time for task administration9,10. Because P50 sensory gating is a passive task and because infants spend much of their day in active sleep (the infant version of REM sleep), P50 sensory gating can be measured even in very young infants.

<table><tbody><tr><td>E-Prime Version 2.0 Professional</td><td>Psychology Software Tools</td><td>EPR-225142</td><td>Stimulus presentation software</td></tr><tr><td>Alcohol Prep Pads with Pumice</td><td>Compumedics</td><td>95000016</td><td>Cleans skin in preparation for electrode placement</td></tr><tr><td>Ten20 Paste</td><td>Compumedics</td><td>92100032</td><td>EEG conductive paste that has adhesive qualities to hold electrodes in place</td></tr><tr><td>Grass Ag/AgCl Surface Electrodes (10mm)</td><td>Grass Technologies</td><td>FS E5SHC-48</td><td>10 mm electrodes are used to record EEG signals from the surface of the scalp and serve as reference and ground electrodes</td></tr><tr><td>Grass Ag/AgCl Surface Electrodes (6 mm)</td><td>Grass Technologies</td><td>F E6SHC-48</td><td>6mm electrodes are used to record eye movements (EOG) and muscle tension (EMG) from the surface of the skin</td></tr><tr><td>Paper Surgical Tape</td><td>Micropore</td><td>1530-0</td><td>low adhesive tape used to keep electrodes in place</td></tr><tr><td>NuAmps Amplifier</td><td>Neuroscan</td><td>N/A</td><td>40-channel monopolar digital amplifier for recording EEG</td></tr><tr><td>Harmon/Kardon computer Speakers</td><td>Harman/Kardon</td><td>HK206</td><td>Used to present auditory &quot;clicks&quot;</td></tr></tbody></table>

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.

P50 sensory gating ratios should generally range from 0 to slightly greater than 1.0. Values above 2 generally only occur in the case of P50 amplitudes below 1.0 &#956;V, may represent poor signal to noise ratio and should either be discarded or truncated to a value of 2.0&#160;11. Mean values from infants drawn from the general population should average about 0.4&#160;13. Figure 1 provides two sample tracings: one from an infant with typical sensory gating; one from an infant with poor sensory gating.
P50 sensory gating can be computed by subtraction: amplitude of response to the first sound minus amplitude of response to the second sound. However, there is wide variability in attenuation of signal from its source through the scalp to the measuring electrode. Things which can effect attenuation include thickness of the skull, debris (e.g. dirt) on the scalp, and moisture content on the surface of the scalp. This variation in attenuation of signal across individuals and across the same individual over time decreases reliability of results from a subtraction method. Thus, P50 sensory gating is generally reported as a ratio: amplitude of response to the second sound divided by amplitude of response to the second sound.
P50 sensory gating ratios can be utilized as a continuous measure. However, the creation of a ratio introduces additional variability. An alternative is to dichotomize results into &#8220;normal&#8221; versus &#8220;impaired&#8221; P50 sensory gating. In adults, ratios &#60; 0.40 are considered normal and &#62;0.50 are considered impaired14. Ratios between 0.40-0.50 are considered indeterminate and can either be added to either group or excluded from further analysis. Appropriate cutoff points for infants have not been firmly established; however, preliminary work suggests similar cutoff points as used in adults are appropriate15.
<img alt="Figure 1" fo:content-width="6in" fo:src="/files/ftp_upload/50065/50065fig1highres.jpg" src="/files/ftp_upload/50065/50065fig1.jpg" width="500px" /> 
Figure 1. Sample Tracings.&#160;&#160;<a href="https://www.jove.com/files/ftp_upload/50065/50065fig1highres.jpg" target="_blank">Click here to view larger image</a>.

Watch this Scientific Journal Video about P50 Sensory Gating in Infants at JoVE.com

P50 Sensory Gating in Infants

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 ...

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9.1K vistas.  University of Colorado School of Medicine. Methods to record auditory P50 sensory gating, a physiological marker of cerebral inhibition which reflects early stages of attention, are described.

Video: P50 Sensory Gating in Infants

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

Behavioral Assessment of Hearing in 2 to 4 Year-old Children: A Two-interval, Observer-based Procedure Using Conditioned Play-based Responses

Collecting reliable behavioral data from toddlers and preschoolers is challenging. As a result, there are significant gaps in our understanding of human auditory development for these age groups. This paper describes an observer-based procedure for measuring hearing sensitivity with a two-interval, two-alternative forced-choice paradigm. Young children are trained to perform a play-based, motor response (e.g., putting a block in a bucket) whenever they hear a target signal. An experimenter observes the child&#39;s behavior and makes a judgment about whether the signal was presented during the first or second observation interval; the experimenter is blinded to the true signal interval, so this judgment is based solely on the child&#39;s behavior. These procedures were used to test 2 to 4 year-olds (n = 33) with no known hearing problems. The signal was a 1,000 Hz warble tone presented in quiet, and the signal level was adjusted to estimate a threshold corresponding to 71%-correct detection. A valid threshold was obtained for 82% of children. These results indicate that the two-interval procedure is both feasible and reliable for use with toddlers and preschoolers. The two-interval, observer-based procedure described in this paper is a powerful tool for evaluating hearing in young children because it guards against response bias on the part of the experimenter.

This paper describes a procedure for measuring hearing sensitivity in 2 to 4 year-old children. Children are trained to perform play-based responses when they hear a target signal. Thresholds are then estimated in a two-interval, two-alternative forced-choice paradigm, based on observations of the child&#39;s behaviors.

Evaluación del Comportamiento de la audición en 2 a 4 años de edad, los niños: un procedimiento en dos intervalos, a base de Observador El uso de respuestas condicionadas en base a juegos

Collecting reliable behavioral data from toddlers and preschoolers is challenging. As a result, there are significant gaps in our understanding of human ...

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.

Las mediciones electrofisiológicas y Análisis de la nocicepción en los bebés humanos

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

Neurociencias

Experience is Instrumental in Tuning a Link Between Language and Cognition: Evidence from 6-  to 7- Month-Old Infants' Object Categorization

At birth, infants not only prefer listening to human vocalizations, but also have begun to link these vocalizations to cognition: For infants as young as three months of age, listening to human language supports object categorization, a core cognitive capacity. This precocious link is initially broad: At 3 and 4 months, vocalizations of both humans and nonhuman primates support categorization. But by 6 months, infants have narrowed the link: Only human vocalizations support object categorization. Here we ask what guides infants as they tune their initially broad link to a more precise one, engaged only by the vocalizations of our species. Across three studies, we use a novel exposure paradigm to examine the effects of experience. We document that merely exposing infants to nonhuman primate vocalizations enables infants to preserve the early-established link between this signal and categorization. In contrast, exposing infants to backward speech &#8212; a signal that fails to support categorization at any age &#8212; offers no such advantage. Our findings reveal the power of early experience as infants specify which signals, from an initially broad set, they will continue to link to cognition.

At 3-4 months, listening to human and nonhuman primate vocalizations boosts infants&#39; cognition; by 6 months, only human vocalizations exert this cognitive advantage. We describe an exposure manipulation that reveals the powerful shaping role of experience as infants specify which sounds to link to cognition and which to tune out.

La experiencia es instrumental en el ajuste de un vínculo entre el lenguaje y la cognición: Evidencia de 6 a 7 meses de edad, la categorización de objetos bebés

At birth, infants not only prefer listening to human vocalizations, but also have begun to link these vocalizations to cognition: For infants as young as ...

Habituation and Prepulse Inhibition of Acoustic Startle in Rodents

The acoustic startle response is a protective response, elicited by a sudden and intense acoustic stimulus. Facial and skeletal muscles are activated within a few milliseconds, leading to a whole body flinch in rodents1. Although startle responses are reflexive responses that can be reliably elicited, they are not stereotypic. They can be modulated by emotions such as fear (fear potentiated startle) and joy (joy attenuated startle), by non-associative learning processes such as habituation and sensitization, and by other sensory stimuli through sensory gating processes (prepulse inhibition), turning startle responses into an excellent tool for assessing emotions, learning, and sensory gating, for review see 2, 3. The primary pathway mediating startle responses is very short and well described, qualifying startle also as an excellent model for studying the underlying mechanisms for behavioural plasticity on a cellular/molecular level3.
We here describe a method for assessing short-term habituation, long-term habituation and prepulse inhibition of acoustic startle responses in rodents. Habituation describes the decrease of the startle response magnitude upon repeated presentation of the same stimulus. Habituation within a testing session is called short-term habituation (STH) and is reversible upon a period of several minutes without stimulation. Habituation between testing sessions is called long-term habituation (LTH)4. Habituation is stimulus specific5. Prepulse inhibition is the attenuation of a startle response by a preceding non-startling sensory stimulus6. The interval between prepulse and startle stimulus can vary from 6 to up to 2000 ms. The prepulse can be any modality, however, acoustic prepulses are the most commonly used.
Habituation is a form of non-associative learning. It can also be viewed as a form of sensory filtering, since it reduces the organisms' response to a non-threatening stimulus. Prepulse inhibition (PPI) was originally developed in human neuropsychiatric research as an operational measure for sensory gating7. PPI deficits may represent the interface of "psychosis and cognition" as they seem to predict cognitive impairment8-10. Both habituation and PPI are disrupted in patients suffering from schizophrenia11, and PPI disruptions have shown to be, at least in some cases, amenable to treatment with mostly atypical antipsychotics12, 13. However, other mental and neurodegenerative diseases are also accompanied by disruption in habituation and/or PPI, such as autism spectrum disorders (slower habituation), obsessive compulsive disorder, Tourette's syndrome, Huntington's disease, Parkinson's disease, and Alzheimer's Disease (PPI)11, 14, 15 Dopamine induced PPI deficits are a commonly used animal model for the screening of antipsychotic drugs16, but PPI deficits can also be induced by many other psychomimetic drugs, environmental modifications and surgical procedures.

Habituation and prepulse inhibition of startle are operational measures of sensory gating. Sensory gating is disrupted in schizophrenia, and some other mental disorders and neurodegenerative diseases. We here describe a standard protocol to assess short-term and long-term habituation as well as prepulse inhibition of acoustic startle responses in rats and mice.

Habituación y la inhibición prepulso de sobresalto acústico en roedores

The acoustic startle response is a protective response, elicited by a sudden and intense acoustic stimulus. Facial and skeletal muscles are activated ...

Classical Short-Delay Eyeblink Conditioning in One-Year-Old Children

Classical eyeblink conditioning (EBC) refers to the learned association between a conditioned stimulus (an auditory tone) and an unconditioned stimulus (a puff of air to the cornea). Eyeblink conditioning is often used experimentally to detect abnormalities in cerebellar-dependent learning and memory that underlies this type of associative learning. While experiments in adults and older children are relatively simple to administer using commercial equipment, eyeblink conditioning in infants is more challenging due to their poor compliance, which makes correct positioning of the equipment difficult. To achieve conditioning in one-year-old infants, a custom-made or an adapted commercial system can be used to deliver the air puff to the infant's cornea. The main challenge lies in successfully detecting and classifying the behavioral responses. We report that automated blink detection methods are unreliable in this population, and that conditioning experiments should be analyzed using frame-by-frame analysis of supplementary video camera recordings. This method can be applied to study developmental changes in eyeblink conditioning and to examine whether this paradigm can detect children with neurological disorders.

This protocol describes an eyeblink conditioning paradigm appropriate for experiments with one-year-old infants. Commercial or custom-made equipment can be used to deliver the stimuli, and data collection and analysis should be performed on the video recordings.

Clásico corto retardo Eyeblink acondicionado en niños menores de un año

Classical eyeblink conditioning (EBC) refers to the learned association between a conditioned stimulus (an auditory tone) and an unconditioned stimulus (a ...

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.

Explorar la sensibilidad infantil al lenguaje visual mediante el seguimiento ocular y el paradigma de aspecto preferencial

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 ...

The Power of Interstimulus Interval for the Assessment of Temporal Processing in Rodents

Temporal processing deficits have been implicated as a potential elemental dimension of higher-level cognitive processes, commonly observed in neurocognitive disorders. Despite the popularization of prepulse inhibition (PPI) in recent years, many current protocols promote using a percent of control measure, thereby precluding the assessment of temporal processing. The present study used cross-modal PPI and gap prepulse inhibition (gap-PPI) to demonstrate the benefits of employing a range of interstimulus intervals (ISIs) to delineate effects of sensory modality, psychostimulant exposure, and age. Assessment of sensory modality, psychostimulant exposure, and age reveals the utility of an approach varying the interstimulus interval (ISI) to establish the shape of the ISI function, including increases (sharper curve inflections) or decreases (flattening of the response amplitude curve) in startle amplitude. Additionally, shifts in peak response inhibition, suggestive of a differential sensitivity to the manipulation of ISI, are often revealed. Thus, the systematic manipulation of ISI affords a critical opportunity to evaluate temporal processing, which may reveal the underlying neural mechanisms involved in neurocognitive disorders.

Temporal processing, a preattentive process, may underlie deficits in higher-level cognitive processes, including attention, commonly observed in neurocognitive disorders. Using prepulse inhibition as an exemplar paradigm, we present a protocol for manipulating interstimulus interval (ISI) to establish the shape of the ISI function to provide an assessment of temporal processing.

El poder del Interstimulus intervalo para la evaluación de proceso Temporal en roedores

Temporal processing deficits have been implicated as a potential elemental dimension of higher-level cognitive processes, commonly observed in ...

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.

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.