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. G., 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=Neurophysiological+and+neuropsychological+evidence+for+attentional+dysfunction+in+schizophrenia.">Neurophysiological and neuropsychological evidence for attentional dysfunction in schizophrenia.</a> Schizo. Res. 10 (2), 131-141 (1993).</li><li>Kisley, M. A., Noecker, T. L., Guinther, P. M. <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+sensory+gating+to+mismatch+negativity+and+self-reported+perceptual+phenomena+in+healthy+adults.">Comparison of sensory gating to mismatch negativity and self-reported perceptual phenomena in healthy adults.</a> Psychophysiology. 41 (4), 604-612 (2004).</li><li>Olincy, A., Ross, R. G., Harris, J. 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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 border="0" cellpadding="0" cellspacing="0" width="846">
	<colgroup>
		<col />
		<col />
		<col />
		<col />
	</colgroup>
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:243px;">E-Prime Version 2.0 Professional</td>
			<td style="width:187px;">Psychology Software Tools</td>
			<td style="width:137px;">EPR-225142</td>
			<td style="width:280px;">Stimulus presentation software</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:243px;">Alcohol Prep Pads with Pumice</td>
			<td style="width:187px;">Compumedics</td>
			<td style="width:137px;">95000016</td>
			<td style="width:280px;">Cleans skin in preparation for electrode placement</td>
		</tr>
		<tr height="51">
			<td height="51" style="height:51px;width:243px;">Ten20 Paste</td>
			<td style="width:187px;">Compumedics</td>
			<td style="width:137px;">92100032</td>
			<td style="width:280px;">EEG conductive paste that has adhesive qualities to hold electrodes in place</td>
		</tr>
		<tr height="61">
			<td height="61" style="height:61px;width:243px;">Grass Ag/AgCl Surface Electrodes (10mm)</td>
			<td style="width:187px;">Grass Technologies</td>
			<td style="width:137px;">FS E5SHC-48</td>
			<td style="width:280px;">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 height="69">
			<td height="69" style="height:69px;width:243px;">Grass Ag/AgCl Surface Electrodes (6 mm)</td>
			<td style="width:187px;">Grass Technologies</td>
			<td style="width:137px;">F E6SHC-48</td>
			<td style="width:280px;">6mm electrodes are used to record eye movements (EOG) and muscle tension (EMG) from the surface of the skin</td>
		</tr>
		<tr height="46">
			<td height="46" style="height:46px;width:243px;">Paper Surgical Tape</td>
			<td style="width:187px;">Micropore</td>
			<td style="width:137px;">1530-0</td>
			<td style="width:280px;">low adhesive tape used to keep electrodes in place</td>
		</tr>
		<tr height="43">
			<td height="43" style="height:43px;width:243px;">NuAmps Amplifier</td>
			<td style="width:187px;">Neuroscan</td>
			<td style="width:137px;">N/A</td>
			<td style="width:280px;">40-channel monopolar digital amplifier for recording EEG</td>
		</tr>
		<tr height="25">
			<td height="25" style="height:25px;width:243px;">Harmon/Kardon computer Speakers</td>
			<td style="width:187px;">Harman/Kardon</td>
			<td style="width:137px;">HK206</td>
			<td style="width:280px;">Used to present auditory &#34;clicks&#34;</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 Views.  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

Assessment and Evaluation of the High Risk Neonate: The NICU Network Neurobehavioral Scale

There has been a long-standing interest in the assessment of the neurobehavioral integrity of the newborn infant. The NICU Network Neurobehavioral Scale (NNNS) was developed as an assessment for the at-risk infant. These are infants who are at increased risk for poor developmental outcome because of insults during prenatal development, such as substance exposure or prematurity or factors such as poverty, poor nutrition or lack of prenatal care that can have adverse effects on the intrauterine environment and affect the developing fetus. The NNNS assesses the full range of infant neurobehavioral performance including neurological integrity, behavioral functioning, and signs of stress/abstinence. The NNNS is a noninvasive neonatal assessment tool with demonstrated validity as a predictor, not only of medical outcomes such as cerebral palsy diagnosis, neurological abnormalities, and diseases with risks to the brain, but also of developmental outcomes such as mental and motor functioning, behavior problems, school readiness, and IQ. The NNNS can identify infants at high risk for abnormal developmental outcome and is an important clinical tool that enables medical researchers and health practitioners to identify these infants and develop intervention programs to optimize the development of these infants as early as possible. The video shows the NNNS procedures, shows examples of normal and abnormal performance and the various clinical populations in which the exam can be used.

The NICU Network Neurobehavioral Scale (NNNS) was developed as an assessment for the at-risk infant. The purpose of this article is to describe the NNNS, provide video examples of the NNNS procedures and discuss the ways in which the exam has been used.

There has been a long-standing interest in the assessment of the neurobehavioral integrity of the newborn infant.  The NICU Network Neurobehavioral Scale ...

A Procedure to Observe Context-induced Renewal of Pavlovian-conditioned Alcohol-seeking Behavior in Rats

Environmental contexts in which drugs of abuse are consumed can trigger craving, a subjective Pavlovian-conditioned response that can facilitate drug-seeking behavior and prompt relapse in abstinent drug users. We have developed a procedure to study the behavioral and neural processes that mediate the impact of context on alcohol-seeking behavior in rats. Following acclimation to the taste and pharmacological effects of 15% ethanol in the home cage, male Long-Evans rats receive Pavlovian discrimination training (PDT) in conditioning chambers. In each daily (Mon-Fri) PDT session, 16 trials each of two different 10 sec auditory conditioned stimuli occur. During one stimulus, the CS+, 0.2 ml of 15% ethanol is delivered into a fluid port for oral consumption. The second stimulus, the CS-, is not paired with ethanol. Across sessions, entries into the fluid port during the CS+ increase, whereas entries during the CS- stabilize at a lower level, indicating that a predictive association between the CS+ and ethanol is acquired. During PDT each chamber is equipped with a specific configuration of visual, olfactory and tactile contextual stimuli. Following PDT, extinction training is conducted in the same chamber that is now equipped with a different configuration of contextual stimuli. The CS+ and CS- are presented as before, but ethanol is withheld, which causes a gradual decline in port entries during the CS+. At test, rats are placed back into the PDT context and presented with the CS+ and CS- as before, but without ethanol. This manipulation triggers a robust and selective increase in the number of port entries made during the alcohol predictive CS+, with no change in responding during the CS-. This effect, referred to as context-induced renewal, illustrates the powerful capacity of contexts associated with alcohol consumption to stimulate alcohol-seeking behavior in response to Pavlovian alcohol cues.

A procedure to study the capacity of an alcohol associated environmental context to trigger the renewal of alcohol-seeking behavior in rats is described.

Environmental contexts in which drugs of abuse are consumed can trigger craving, a subjective Pavlovian-conditioned response that can facilitate ...

Functional Near Infrared Spectroscopy of the Sensory and Motor Brain Regions with Simultaneous Kinematic and EMG Monitoring During Motor Tasks

There are several advantages that functional near-infrared spectroscopy (fNIRS) presents in the study of the neural control of human movement. It is relatively flexible with respect to participant positioning and allows for some head movements during tasks. Additionally, it is inexpensive, light weight, and portable, with very few contraindications to its use. This presents a unique opportunity to study functional brain activity during motor tasks in individuals who are typically developing, as well as those with movement disorders, such as cerebral palsy. An additional consideration when studying movement disorders, however, is the quality of actual movements performed and the potential for additional, unintended movements. Therefore, concurrent monitoring of both blood flow changes in the brain and actual movements of the body during testing is required for appropriate interpretation of fNIRS results. Here, we show a protocol for the combination of fNIRS with muscle and kinematic monitoring during motor tasks. We explore gait, a unilateral multi-joint movement (cycling), and two unilateral single-joint movements (isolated ankle dorsiflexion, and isolated hand squeezing). The techniques presented can be useful in studying both typical and atypical motor control, and can be modified to investigate a broad range of tasks and scientific questions.

Monitoring brain activity during upright motor tasks is of great value when investigating the neural source of movement disorders. Here, we demonstrate a protocol that combines functional near infrared spectroscopy with continuous monitoring of muscle and kinematic activity during 4 types of motor tasks.

There are several advantages that functional near-infrared spectroscopy (fNIRS) presents in the study of the neural control of human movement. It is ...

Testing Sensory and Multisensory Function in Children with Autism Spectrum Disorder

In addition to impairments in social communication and the presence of restricted interests and repetitive behaviors, deficits in sensory processing are now recognized as a core symptom in autism spectrum disorder (ASD). Our ability to perceive and interact with the external world is rooted in sensory processing. For example, listening to a conversation entails processing the auditory cues coming from the speaker (speech content, prosody, syntax) as well as the associated visual information (facial expressions, gestures). Collectively, the &#8220;integration&#8221; of these multisensory (i.e., combined audiovisual) pieces of information results in better comprehension. Such multisensory integration has been shown to be strongly dependent upon the temporal relationship of the paired stimuli. Thus, stimuli that occur in close temporal proximity are highly likely to result in behavioral and perceptual benefits &#8211; gains believed to be reflective of the perceptual system&#39;s judgment of the likelihood that these two stimuli came from the same source. Changes in this temporal integration are expected to strongly alter perceptual processes, and are likely to diminish the ability to accurately perceive and interact with our world. Here, a battery of tasks designed to characterize various aspects of sensory and multisensory temporal processing in children with ASD is described. In addition to its utility in autism, this battery has great potential for characterizing changes in sensory function in other clinical populations, as well as being used to examine changes in these processes across the lifespan.

We describe how to implement a battery of behavioral tasks to examine the processing and integration of sensory stimuli in children with ASD. The goal is to characterize individual differences in temporal processing of simple auditory and visual stimuli and relate these to higher order perceptual skills like speech perception.

In addition to impairments in social communication and the presence of restricted interests and repetitive behaviors, deficits in sensory processing are ...

Quantifying Learning in Young Infants: Tracking Leg Actions During a Discovery-learning Task

Task-specific actions emerge from spontaneous movement during infancy. It has been proposed that task-specific actions emerge through a discovery-learning process. Here a method is described in which 3-4 month old infants learn a task by discovery and their leg movements are captured to quantify the learning process. This discovery-learning task uses an infant activated mobile that rotates and plays music based on specified leg action of infants. Supine infants activate the mobile by moving their feet vertically across a virtual threshold. This paradigm is unique in that as infants independently discover that their leg actions activate the mobile, the infants&#8217; leg movements are tracked using a motion capture system allowing for the quantification of the learning process. Specifically, learning is quantified in terms of the duration of mobile activation, the position variance of the end effectors (feet) that activate the mobile, changes in hip-knee coordination patterns, and changes in hip and knee muscle torque. This information describes infant exploration and exploitation at the interplay of person and environmental constraints that support task-specific action. Subsequent research using this method can investigate how specific impairments of different populations of infants at risk for movement disorders influence the discovery-learning process for task-specific action.

A method is described in which 3-4 month old infants learn a task by discovery and their leg movements are captured to quantify the learning process.

Task-specific actions emerge from spontaneous movement during infancy. It has been proposed that task-specific actions emerge through a discovery-learning ...

A Novel Experimental and Analytical Approach to the Multimodal Neural Decoding of Intent During Social Interaction in Freely-behaving Human Infants

Understanding typical and atypical development remains one of the fundamental questions in developmental human neuroscience. Traditionally, experimental paradigms and analysis tools have been limited to constrained laboratory tasks and contexts due to technical limitations imposed by the available set of measuring and analysis techniques and the age of the subjects. These limitations severely limit the study of developmental neural dynamics and associated neural networks engaged in cognition, perception and action in infants performing &#8220;in action and in context&#8221;. This protocol presents a novel approach to study infants and young children as they freely organize their own behavior, and its consequences in a complex, partly unpredictable and highly dynamic environment. The proposed methodology integrates synchronized high-density active scalp electroencephalography (EEG), inertial measurement units (IMUs), video recording and behavioral analysis to capture brain activity and movement non-invasively in freely-behaving infants. This setup allows for the study of neural network dynamics in the developing brain, in action and context, as these networks are recruited during goal-oriented, exploration and social interaction tasks.

This protocol presents a novel methodology for the neural decoding of intent from freely-behaving infants during unscripted social interaction with an actor. Neural activity is acquired using non-invasive high-density active scalp electroencephalography (EEG). Kinematic data is collected with inertial measurement units and supplemented with synchronized video recording.

Understanding typical and atypical development remains one of the fundamental questions in developmental human neuroscience. Traditionally, experimental ...

Protocol for Data Collection and Analysis Applied to Automated Facial Expression Analysis Technology and Temporal Analysis for Sensory Evaluation

We demonstrate a method for capturing emotional response to beverages and liquefied foods in a sensory evaluation laboratory using automated facial expression analysis (AFEA) software. Additionally, we demonstrate a method for extracting relevant emotional data output and plotting the emotional response of a population over a specified time frame. By time pairing each participant's treatment response to a control stimulus (baseline), the overall emotional response over time and across multiple participants can be quantified. AFEA is a prospective analytical tool for assessing unbiased response to food and beverages. At present, most research has mainly focused on beverages. Methodologies and analyses have not yet been standardized for the application of AFEA to beverages and foods; however, a consistent standard methodology is needed. Optimizing video capture procedures and resulting video quality aids in a successful collection of emotional response to foods. Furthermore, the methodology of data analysis is novel for extracting the pertinent data relevant to the emotional response. The combinations of video capture optimization and data analysis will aid in standardizing the protocol for automated facial expression analysis and interpretation of emotional response data.

A protocol for capturing and statistically analyzing emotional response of a population to beverages and liquefied foods in a sensory evaluation laboratory using automated facial expression analysis software is described.

We demonstrate a method for capturing emotional response to beverages and liquefied foods in a sensory evaluation laboratory using automated facial ...

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.

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 ...

A View of Their Own: Capturing the Egocentric View of Infants and Toddlers with Head-Mounted Cameras

Infants and toddlers view the world, at a basic sensory level, in a fundamentally different way from their parents. This is largely due to biological constraints: infants possess different body proportions than their parents and the ability to control their own head movements is less developed. Such constraints limit the visual input available. This protocol aims to provide guiding principles for researchers using head-mounted cameras to understand the changing visual input experienced by the developing infant. Successful use of this protocol will allow researchers to design and execute studies of the developing child&#39;s visual environment set in the home or laboratory. From this method, researchers can compile an aggregate view of all the possible items in a child&#39;s field of view. This method does not directly measure exactly what the child is looking at. By combining this approach with machine learning, computer vision algorithms, and hand-coding, researchers can produce a high-density dataset to illustrate the changing visual ecology of the developing infant.

Infants and toddlers view the world in a fundamentally different way from their parents. Head-mounted cameras provide a tractable mechanism to understand the infant visual environment. This protocol provides guiding principles for experiments in the home or laboratory to capture the egocentric view of toddlers and infants.

Infants and toddlers view the world, at a basic sensory level, in a fundamentally different way from their parents. This is largely due to biological ...

Defining the Role Of Language in Infants' Object Categorization with Eye-tracking Paradigms

Assessing infant category learning is a challenging but vital aspect of studying infant cognition. By employing a familiarization-test paradigm, we straightforwardly measure infants&#8217; success in learning a novel category while relying only on their looking behavior. Moreover, the paradigm can directly measure the impact of different auditory signals on the infant categorization across a range of ages. For instance, we assessed how 2-year-olds learn categories in a variety of labeling environments: in our task, 2-year-olds successfully learned categories when all exemplars were labeled&#160;or the first two exemplars were labeled, but they failed to categorize when no exemplars were labeled or only the final two exemplars were labeled. To determine infants&#8217; success in such tasks, researchers can examine both the overall preference displayed by infants in each condition and infants&#8217; pattern of looking over the course of the test phase, using an eye-tracker to provide fine-grained time-course data. Thus, we present a powerful paradigm for identifying the role of language, or any auditory signal, in infants&#8217; object category learning.

Here we present a protocol for familiarization-test paradigms which provide a direct test of infant categorization and help to define the role of language in early category learning.

Assessing infant category learning is a challenging but vital aspect of studying infant cognition. By employing a familiarization-test paradigm, we ...