The project described was supported by the National Center for Research Resources, Grant UL1 RR024975-01, and is now at the National Center for Advancing Translational Sciences, Grant 2 UL1 TR000445-06. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

1. Assessment of Response to Light Touch
<ol>
	<li>Place the electrode net (e.g.&#160;128-channels geodesic sensor net) on child or infant&#39;s head. Adjust sensors for full contact using warm saline solution. If on a child, ensure child is sitting comfortably in parent or caregiver lap. If on an infant, ensure that infant is lightly swaddled and either held in caregiver&#39;s arms or in a supine position in an open crib.</li>
	<li>Position a 1 mm nozzle 0.5 cm below the tip of the index finger of the tested hand. Place finger for a young child or palm for an infant in a mold holder and secure with Velcro tape proximal and distal to joint to ensure consistent distance from nozzle to the finger or hand. It is absolutely essential that the child maintains the proper finger position throughout the testing session. Ensure this by periodically assessing finger and hand placement and having child with caregiver if young. If testing an infant, stop protocol if infant cries and provide comfort before restarting. If testing young child, ask caregiver to provide comfort and reassurance throughout the short testing period.</li>
	<li>Start air compressor at 40 psi through regulator to supply valve inputs for tactile stimuli.</li>
	<li>Run stimulus delivery program.
	<ol>
		<li>For the tested hand, present 60 puff stimuli randomly interspersed with 60 sham trials (an air puff delivered via a separate nozzle pointed away from the finger).</li>
		<li>Do not present more than two repetitions of a puff or sham in a row. Vary the inter-trial intervals randomly between 2,000-2,500 msec. The purpose of this is to reduce habituation, where a stimulus is no longer perceived. The total time for a sequence of 120 trials should be 4.5-5 min.</li>
		<li>Run the identical protocol again for the other hand if studying asymmetrical somatosensory disorders.</li>
	</ol>
	</li>
	<li>For protocols not requiring attention to stimulus no further set up is needed. This applies to infant testing. For enhancement of attention in young children (which results in larger specific ERP peaks in recording), provide a task.
	<ol>
		<li>Task example for 5-year-olds: Describe air puffs as &#34;bubbles&#34; blown by &#34;fish&#34; in a &#34;fish tank&#34; (a decorated box concealing the puffer apparatus). Ask children to guess whether each &#34;bubble&#34; is delivered by a blue or a red &#34;fish&#34;. Tell the child that they do not need to and should not say anything while they are performing this task (see set up with mock aquarium in Figure 1).</li>
	</ol>
	</li>
</ol>
2. Assessment of Response to Multisensory Protocol (Auditory-tactile Simultaneous vs. Summed Individual Responses)
<ol>
	<li>Run through steps 1.1-1.3 as described above. Stimuli are described in Table 1.</li>
	<li>Run the stimulus delivery program (e.g.&#160;in E-Prime software). For the tested hand, an auditory-tactile paradigm can present the following 4 stimuli randomly, with 60 trials/ stimulus: puff , puff-/ga/, /ga/-sham, sham. Again, to limit the possibility of habituation, do not present more than two repetitions of a puff or sham in a row in any condition, and vary the inter-trial intervals randomly between 2,000-2,500 msec. Each sequence of 240 trials should take between 9-10 min.</li>
	<li>Run identical protocol over for the other hand.</li>
	<li>Provide a soundless age-appropriate cartoon at initiation of protocol and continue it throughout the procedure to prevent increase in motor artifacts from restlessness, and to decrease the background from large patient-generated delta waves when they are bored. For example, in 5-year olds, we used a loop of 20 min&#160;of a purchased video, played on mute and restarted before each subject was tested. No attention to stimulus is needed, therefore the looped cartoon provides a visual background disconnected from the stimuli.</li>
</ol>
3. Software and Equipment Set Up
<ol>
	<li>To program the software, set up two serial commands sent by the stimulus control application. One identifies the puff, the other the sham. Have the stimulus control application send the commands to a microcontroller.</li>
	<li>Have the microcontroller generate a TTL pulse (e.g. 20 msec duration) to the corresponding digital output channel. This output must be split into two lines, one for the digital input to the EEG recording system and one to the solenoid-gated air valves. Mark the opening of both valves in the EEG data stream.</li>
	<li>Measure the pulse to puff latency for both real and sham conditions with an oscilloscope and a microphone. These should be uniform, and in the order of 10-15 msec. Adjust for the latency post-recording.</li>
	<li>Calculate the force exerted at the nozzle in PSI using a manometer and by measuring the nozzle diameter. Use the formula F(N) = Pressure*Area. For example, the force exerted from a 1 mm radius nozzle at 6 psi yields F(N) = 0.03 lbs.</li>
	<li>To modify the control application for the multisensory protocol, send two serial commands identifying a real puff or sham to the microcontroller as well as a recorded speech sound or silence. Note: In our paradigm we have used the computer generated, accent-neutral /ga/ sound, among others such as /da/, /du/, /bu/, etc.</li>
	<li>Present auditory stimuli through a speaker placed at midline, 2 ft in front of the subject.</li>
	<li>Align the sound onset timing to be simultaneous with the onset of the puff or with the delay measured in step 3.3, depending on which condition is desirable to the tester.</li>
</ol>
4. Data Acquisition and Preparation
<ol>
	<li>Choose filters and references settings to sample data based on standard ERP methodologies. Here, use a 1,000 Hz with filters set to 0.1-400 Hz. During data collection, refer all electrodes to Cz and rereferenced them offline to an average reference.</li>
	<li>To segment the data, filter the recorded data with desired filters and segmenting. For this study use a 0.3-40 Hz bandpass filter and segment the ongoing EEG based on the stimulus onset to include a 200 msec prestimulus baseline and a 500 msec post-stimulus interval.</li>
	<li>Perform quality control of the data. Screen each segment for motor and ocular artifacts such as high frequency muscle activity, using computer algorithms included in the ERP software. Follow this screen by a manual review.</li>
	<li>The automated screening criteria are set as follows in this protocol but can be modified: for eye channels, voltage &#62;140 &#181;V = eye blink and voltage &#62;55 &#181;V = eye movements.</li>
	<li>Correct data from contaminated trials using an ocular artifact correction tool. Note: Any channel with voltage &#62;200 &#181;V is considered of poor quality. If &#62;15 channels are of poor quality, we chose to discard the entire trial for reproducibility reasons.</li>
	<li>Average ERPs. Rereference them to an average reference and then perform baseline-correction based on criteria chosen in step 4.2. Extract mean amplitude and peak latencies for various peaks, extrapolated from grand average waveforms of predefined populations. Note: In our case, we based the following on established literature of older children&#39;s response to median nerve stimulation10-14. We used P50 (30-80 msec), N70 (50-100 msec), P100 (80-150 msec), N140 (130-230 msec), and P2 (250-350 msec) peaks.</li>
	<li>Include only data from electrodes overlapping preset locations (Figure 2). Derive data for individual electrodes and average within each cluster.</li>
</ol>

<ol>
	<li>Nelson, C. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neural+plasticity+and+human+development:+the+role+of+early+experience+in+sculpting+memory+systems.">Neural plasticity and human development: the role of early experience in sculpting memory systems.</a> Dev. Sci. 3 (2), 115-136 (2000).</li><li>Wallace, M. T., Stein, B. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Early+experience+determines+how+the+senses+will+interact.">Early experience determines how the senses will interact.</a> J. Neurophysiol. 97 (1), 921-926 (2007).</li><li>Greenough, W. T., Black, J. E., Wallace, C. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Experience+and+brain+development..">Experience and brain development..</a> Child Dev. 58 (3), 539-559 (1987).</li><li>Lickliter, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Role+of+Sensory+Stimulation+in+Perinatal+Development:+insights+from+comparative+research+for+care+of+the+high-risk+infant.">The Role of Sensory Stimulation in Perinatal Development: insights from comparative research for care of the high-risk infant.</a> J. Dev. Behav. Pediatr. 21 (6), 437-447 (2000).</li><li>Lickliter, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+integrated+development+of+sensory+organization.">The integrated development of sensory organization.</a> Clin. Perinatol. 38 (4), 591-603 (2011).</li><li>Pleger, B., Villringer, 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+human+somatosensory+system:+From+perception+to+decision+making.">The human somatosensory system: From perception to decision making.</a> Prog. Neurobiol. 103, 76-97 (2013).</li><li>Allison, T., McCarthy, G., Wood, C. C., Jones, S. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Potentials+evoked+in+human+and+monkey+cerebral+cortex+by+stimulation+of+the+median+nerve:+a+review+of+scalp+and+intracranial+recordings.">Potentials evoked in human and monkey cerebral cortex by stimulation of the median nerve: a review of scalp and intracranial recordings.</a> Brain. 114 (6), 2465-2503 (1991).</li><li>Majnemer, A., Rosenblatt, B., Riley, P., Laureau, E., O'Gorman, A. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Somatosensory+evoked+response+abnormalities+in+high-risk+newborns.">Somatosensory evoked response abnormalities in high-risk newborns.</a> Pediatr. Neurol. 3 (6), 350-355 (1987).</li><li>Auld, M. L., Ware, R. S., Boyd, R. N., Moseley, G. L., Johnston, L. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reproducibility+of+tactile+assessments+for+children+with+unilateral+cerebral+palsy.">Reproducibility of tactile assessments for children with unilateral cerebral palsy.</a> Phys. Occup. Ther. Pediatr. 32 (2), 151-166 (2012).</li><li>Nakanishi, T., Shimada, Y., Toyokura, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Somatosensory+evoked+responses+to+mechanical+stimulation+in+normal+subjects+and+in+patients+with+neurological+disorders.">Somatosensory evoked responses to mechanical stimulation in normal subjects and in patients with neurological disorders.</a> J. Neuro. Sci. 21 (3), 289-298 (1974).</li><li>Schubert, R., Blankenburg, F., Lemm, S., Villringer, A., Curio, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Now+you+feel+it-now+you+don't:+ERP+correlates+of+somatosensory+awareness.">Now you feel it-now you don't: ERP correlates of somatosensory awareness.</a> Psychophysiology. 43 (1), 31-40 (2006).</li><li>Hamalainen, H., Kekoni, J., Sams, M., Reinikainen, K., Naatanen, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Human+somatosensory+evoked+potentials+to+mechanical+pulses+and+vibration:+contributions+of+SI+and+SII+somatosensory+cortices+to+P50+and+P100+components.">Human somatosensory evoked potentials to mechanical pulses and vibration: contributions of SI and SII somatosensory cortices to P50 and P100 components.</a> Electroencephal. Clin. Neurophysiol. 75 (2), 13-21 (1990).</li><li>Eimer, M., Forster, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Modulations+of+early+somatosensory+ERP+components+by+transient+and+sustained+spatial+attention.">Modulations of early somatosensory ERP components by transient and sustained spatial attention.</a> Exp. Brain Res. 151 (1), 24-31 (2003).</li><li>Forster, B., Eimer, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Covert+attention+in+touch:+Behavioral+and+ERP+evidence+for+costs+and+benefits.">Covert attention in touch: Behavioral and ERP evidence for costs and benefits.</a> Psychophysiology. 42 (2), 171-179 (2005).</li><li>Tamura, Y., 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=Cognitive+processes+in+two-point+discrimination:+an+ERP+study.">Cognitive processes in two-point discrimination: an ERP study.</a> Clin. Neurophysiol. 115 (8), 1875-1884 (2004).</li><li>Fabrizi, 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=A+shift+in+sensory+processing+that+enables+the+developing+human+brain+to+discriminate+touch+from.">A shift in sensory processing that enables the developing human brain to discriminate touch from.</a> 21 (18), 1552-1558 (2011).</li><li>Putnam, L. E., Vanman, E. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Startle+Modification:+Implications+for+Neuroscience,+Cognitive+Science.+Google+Books.">Startle Modification: Implications for Neuroscience, Cognitive Science. Google Books.</a> Startle Modification: Implications for. , (1999).</li><li>Maitre, N. L., Barnett, Z. P., Key, A. P. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Novel+assessment+of+cortical+response+to+somatosensory+stimuli+in+children+with+hemiparetic+cerebral+palsy.">Novel assessment of cortical response to somatosensory stimuli in children with hemiparetic cerebral palsy.</a> J. Child Neurol. 27 (10), 1276-1283 (2012).</li><li>Molholm, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Audio-Visual+Multisensory+Integration+in+Superior+Parietal+Lobule+Revealed+by+Human+Intracranial+Recordings.">Audio-Visual Multisensory Integration in Superior Parietal Lobule Revealed by Human Intracranial Recordings.</a> J. Neurophysiol. 96 (2), 721-729 (2006).</li><li>Molholm, S., Ritter, W., Murray, M. M., Javitt, D. C., Schroeder, C. E., Foxe, J. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Multisensory+auditory-visual+interactions+during+early+sensory+processing+in+humans:+a+high-density+electrical+mapping+study.">Multisensory auditory-visual interactions during early sensory processing in humans: a high-density electrical mapping study.</a> Brain Res. 14 (1), 115-128 (2002).</li><li>Foxe, J. J., Morocz, I. A., Murray, M. M., Higgins, B. A., Javitt, D. C., Schroeder, C. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Multisensory+auditory-somatosensory+interactions+in+early+cortical+processing+revealed+by+high-density+electrical+mapping.">Multisensory auditory-somatosensory interactions in early cortical processing revealed by high-density electrical mapping.</a> Brain Res.. 10 (1-2), 77-83 (2000).</li><li>Gick, B., Derrick, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Aero-tactile+integration+in+speech+perception.">Aero-tactile integration in speech perception.</a> Nature. 462 (7272), 502-504 (2009).</li><li>Stevens, K. N., Blumstein, S. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Invariant+cues+for+place+of+articulation+in+stop+consonants.">Invariant cues for place of articulation in stop consonants.</a> J. Acoust. Soc. Am. 64 (5), 1358-1368 (1978).</li><li>Hari, R., Parkkonen, L., Nangini, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+brain+in+time:+insights+from+neuromagnetic+recordings.">The brain in time: insights from neuromagnetic recordings.</a> Ann. NY Acad. Sci. 1191, 89-109 (2010).</li><li>Key, A. P. F., Dove, G. O., Maguire, M. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Linking+Brainwaves+to+the+Brain:+An+ERP.">Linking Brainwaves to the Brain: An ERP.</a> Dev. Neuropsychol. 27 (2), 183-215 (2005).</li></ol>

The authors declare that they have no competing financial interests.

This novel combination of air puff and ERP (referred to as the &#34;Puffer system&#34;) to measure cortical processing of light touch and tactile-auditory responses is well tolerated by young children with disabilities and by infants. This holds true for unisensory and multisensory versions, and whether the attentional component is added or not in the case of young children. The reasons for the success of this methodology in assessing a young and vulnerable population are due to both the use of an innocuous tactile stimu...

The study of developing cortical sensory processes is essential to understanding the basis for most higher order functions. Sensory experiences are responsible for much of the brain&#39;s organization through infancy and childhood, laying the foundation for complex processes such as cognition, communication, and motor development1-3. Most pediatric studies of sensory processes focus on auditory and visual domains, mainly because these stimuli are easiest to develop, standardize, and test. However, tactile processing is of particular interest in infants and children as it is the first sense to develop in the fetus4,5, and somatosensory information is integral to the function of other cortical systems (e.g. motor, memory, associative learning, limbic)6. Current methods assessing somatosensory processing are limited by the choice of tactile stimulus. A common choice is direct electrical median nerve stimulation7,8, with the potential for discomfort. Other effective methods use active tasks such as discrimination, recognition, and localization of stimuli, requiring both attention and high levels of comprehension9. All of these methods are therefore limited in their use in young children and infants.
Therefore, our goal was to develop a tactile paradigm that addresses these limitations by being noninvasive and reducing the need for a subject&#39;s active participation. Additionally, it needed to have a standardized level of stimulation and a sham-control. For this we developed the &#34;puffer&#34; system, a dual-channel, timed, and calibrated air-puff delivery system, allowing us to measure the effects of light touch in infants and other vulnerable populations.
Functional MRI studies showed that stimulation by puffs of air activates sensory cortices, although the length and challenges of such studies, such as immobilization, lengthy sessions, and anxiety-provoking settings make them difficult to perform in young children. Therefore, we combined our novel delivery system with Event-Related Potential (ERP) methodology in order to provide temporal resolution of sensory processing of light touch in a brief, child-friendly testing session.
This new paradigm offers the needed flexibility to study sensory processing in diverse populations, ages and clinical settings. It also has the advantage of being compatible with auditory stimuli, allowing for multisensory assessments. Until now, accurate and reliable tactile assessment has not been possible in infants or in children who are unable to reliably respond due to intellectual/language disorders. This methodology aims to fill this gap&#160;in order to aid in early identification of sensory processing deficits and intervention during a period of maximal brain plasticity. Improvements in sensory processing in infancy may influence the cascade of neurodevelopmental
The following procedures are all included in Vanderbilt Institutional Review Board approved protocols.

<table border="0" cellpadding="0" cellspacing="0" width="703">
	<colgroup>
		<col />
		<col />
		<col />
		<col />
	</colgroup>
	<tbody>
		<tr height="22">
			<td height="22" style="height:22px;width:249px;">Geodesic sensor net</td>
			<td style="width:168px;">EGI, Inc., Eugene, OR</td>
			<td style="width:119px;">depends on size</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:249px;">Net Station EEG software v. 4.2</td>
			<td style="width:168px;">EGI, Inc., Eugene, OR</td>
			<td style="width:119px;">NA</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:249px;">E-Prime stimulus control application</td>
			<td style="width:168px;">PST, Inc. Pittsburgh, PA</td>
			<td style="width:119px;">NA</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:249px;">Manometer (model 6&#8221; 0-60PSI)</td>
			<td style="width:168px;">H. O. Trerice Co, Oak Park, MI</td>
			<td style="width:119px;"></td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:249px;">Custom Puffer setup</td>
			<td style="width:168px;">Nathalie Maitre</td>
			<td style="width:119px;"></td>
			<td style="width:167px;"></td>
		</tr>
	</tbody>
</table>

quantitative assessment of cortical auditory-tactile processing in children with disabilities

Objective and easy measurement of sensory processing is extremely difficult in nonverbal or vulnerable pediatric patients. We developed a new methodology to quantitatively assess children&#39;s cortical processing of light touch, speech sounds and the multisensory processing of the 2 stimuli, without requiring active subject participation or causing children discomfort. To accomplish this we developed a dual channel, time and strength calibrated air puff stimulator that allows both tactile stimulation and sham control. We combined this with the use of event-related potential methodology to allow for high temporal resolution of signals from the primary and secondary somatosensory cortices as well as higher order processing. This methodology also allowed us to measure a multisensory response to auditory-tactile stimulation.

Assessment of light touch (Figure 3): 
Characteristics of the cortical response to tactile stimulation using the Puffer system: The patterns of peaks in response to the puff are very similar to the cortical responses obtained using median nerve stimulation in normal adults10,11. The early response (P50, N70, P100 peaks) primarily reflects activity in the primary sensory cortex12 and does not require awareness of stimulation....

Watch this Scientific Journal Video about Quantitative Assessment of Cortical Auditory-tactile Processing in Children with Disabilities at JoVE.com

Quantitative Assessment of Cortical Auditory-tactile Processing in Children with Disabilities

Objective and easy measurement of sensory processing is extremely difficult in nonverbal or vulnerable pediatric patients. We developed a new methodology to quantitatively assess infants and children&#39;s cortical processing of light touch, speech sounds, and the multisensory processing of the 2 stimuli, without requiring active subject participation or causing discomfort in vulnerable patients.

Objective and easy measurement of sensory processing is extremely difficult in nonverbal or vulnerable pediatric patients. We developed a new methodology ...

quantitative-assessment-cortical-auditory-tactile-processing-children

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10.7K 조회수.  Vanderbilt University.  감각 처리의 목적과 쉽게 측정 비언어적 또는 취약한 소아 환자에서 매우 어렵습니다. 우리는 활동 주체의 참여를 요구하거나 취약한 환자의 불편을 초래하지 않고, 정량적으로 유아와 가벼운 터치의 아이들의 대뇌 피질의 처리, 음성 소리를 평가하는 새로운 방법, 및 2 자극의 감각적 처리를 개발했다. 

비디오: Quantitative Assessment of Cortical Auditory-tactile Processing in Children with Disabilities

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 ...

Measurement of Fronto-limbic Activity Using an Emotional Oddball Task in Children with Familial High Risk for Schizophrenia

Adolescence is a critical developmental period where the early symptoms of schizophrenia frequently emerge. First-degree relatives of people with schizophrenia who are at familial high risk (FHR) may show similar cognitive and emotional changes. However, the neurological changes underlying the emergence of these symptoms remain unclear. This study sought to identify differences in frontal, striatal, and limbic regions in children and adolescents with FHR using functional magnetic resonance imaging. Groups of 21 children and adolescents at FHR and 21 healthy controls completed an emotional oddball task that relied on selective attention and the suppression of task-irrelevant emotional information. The standard oddball task was modified to include aversive and neutral distractors in order to examine potential group differences in both emotional and executive processing. This task was designed specifically to allow for children and adolescents to complete by keeping the difficulty and emotional image content age-appropriate. Furthermore, we demonstrate a technique for suitable fMRI registration for children and adolescent participants. This paradigm may also be applied in future studies to measure changes in neural activity in other populations with hypothesized developmental changes in executive and emotional processing.

This paper describes how to use the emotional oddball task and fMRI to measure brain activation in children and adolescents at familial high risk for schizophrenia (FHR).&#160;FMRI was used to measure differences in fronto-striato-limbic regions during an emotional oddball task. Children with FHR exhibited abnormal functional activation during adolescence.

Adolescence is a critical developmental period where the early symptoms of schizophrenia frequently emerge. First-degree relatives of people with ...

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 ...

Experimental Assessment of Mouse Sociability Using an Automated Image Processing Approach

Mouse is the preferred model organism for testing drugs designed to increase sociability. We present a method to quantify mouse sociability in which the test mouse is placed in a standardized apparatus and relevant behaviors are assessed in three different sessions (called session I, II, and III).
The apparatus has three compartments (see Figure 1), the left and right compartments contain an inverted cup which can house a mouse (called &#34;stimulus mouse&#34;).
In session I, the test mouse is placed in the cage and its mobility is characterized by the number of transitions made between compartments. In session II, a stimulus mouse is placed under one of the inverted cups and the sociability of the test mouse is quantified by the amounts of time it spends near the cup containing the enclosed stimulus mouse vs. the empty inverted cup. In session III, the inverted cups are removed and both mice interact freely. The sociability of the test mouse in session III is quantified by the number of social approaches it makes toward the stimulus mouse and by the number of times it avoids a social approach by the stimulus mouse.
The automated evaluation of the movie detects the nose of the test mouse, which allows the determination of all described sociability measures in session I and II (in session III, approaches are identified automatically but classified manually). To find the nose, the image of an empty cage is digitally subtracted from each frame of the movie and the resulting image is binarized to identify the mouse pixels. The mouse tail is automatically removed and the two most distant points of the remaining mouse are determined; these are close to nose and base of tail. By analyzing the motion of the mouse and using continuity arguments, the nose is identified.
<img alt="Figure 1" src="/files/ftp_upload/52508/52508fig1.jpg" /> 
Figure 1. Assessment of Sociability During 3 sessions. Session I (top): Acclimation of test mouse to the cage. Session II (middle): Test mouse moving freely in the cage while the stimulus mouse is enclosed in an inverted cup. Session III (bottom): Both test mouse and stimulus mouse are allowed to move freely and interact with each other.

This protocol describes a method to quantify mouse sociability. Mice are videotaped as they move and interact in a special cage. Movie processing allows for the automated quantification of sociability with excellent accuracy and reliability.

Mouse is the preferred model organism for testing drugs designed to increase sociability. We present a method to quantify mouse sociability in which the ...

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 ...

A Method to Quantify Visual Information Processing in Children Using Eye Tracking

Visual problems that occur early in life can have major impact on a child's development. Without verbal communication and only based on observational methods, it is difficult to make a quantitative assessment of a child's visual problems. This limits accurate diagnostics in children under the age of 4 years and in children with intellectual disabilities. Here we describe a quantitative method that overcomes these problems. The method uses a remote eye tracker and a four choice preferential looking paradigm to measure eye movement responses to different visual stimuli. The child sits without head support in front of a monitor with integrated infrared cameras. In one of four monitor quadrants a visual stimulus is presented. Each stimulus has a specific visual modality with respect to the background, e.g., form, motion, contrast or color. From the reflexive eye movement responses to these specific visual modalities, output parameters such as reaction times, fixation accuracy and fixation duration are calculated to quantify a child's viewing behavior. With this approach, the quality of visual information processing can be assessed without the use of communication. By comparing results with reference values obtained in typically developing children from 0-12 years, the method provides a characterization of visual information processing in visually impaired children. The quantitative information provided by this method can be advantageous for the field of clinical visual assessment and rehabilitation in multiple ways. The parameter values provide a good basis to: (i) characterize early visual capacities and consequently to enable early interventions; (ii) compare risk groups and follow visual development over time; and (iii), construct an individual visual profile for each child.

A method is described to quantify the quality of visual information processing based on reflexive eye movements in response to specific visual modalities. Reaction times and fixation output parameters are used to characterize visual performance in children with and without visual impairments from 6 months of age.

Visual problems that occur early in life can have major impact on a child's development. Without verbal communication and only based on observational ...

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.

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

Assessing Working Memory in Children: The Comprehensive Assessment Battery for Children &#8211; Working Memory (CABC-WM)

The Comprehensive Assessment Battery for Children - Working Memory (CABC-WM) is a computer-based battery designed to assess different components of working memory in young school-age children. Working memory deficits have been identified in children with language-based learning disabilities, including dyslexia1,2 and language impairment3,4, but it is not clear whether these children exhibit deficits in subcomponents of working memory, such as visuospatial or phonological working memory. The CABC-WM is administered on a desktop computer with a touchscreen interface and was specifically developed to be engaging and motivating for children. Although the long-term goal of the CABC-WM is to provide individualized working memory profiles in children, the present study focuses on the initial success and utility of the CABC-WM for measuring central executive, visuospatial, phonological loop, and binding constructs in children with typical development. Immediate next steps are to administer the CABC-WM to children with specific language impairment, dyslexia, and comorbid specific language impairment and dyslexia.

Assessing Working Memory in Children: The Comprehensive Assessment Battery for Children &amp;#8211; Working Memory (CABC-WM)

Working memory predicts a significant amount of variance for a variety of cognitive tasks, including speaking, reading, and writing. However, few tools are available to assess working memory in children. We present an innovative, computer-based battery that comprehensively assesses different components of working memory in school-age children.

The Comprehensive Assessment Battery for Children - Working Memory (CABC-WM) is a computer-based battery designed to assess different components of ...

Multi-layer Cortical Ca2+ Imaging in Freely Moving Mice with Prism Probes and Miniaturized Fluorescence Microscopy

In vivo circuit and cellular level functional imaging is a critical tool for understanding the brain in action. High resolution imaging of mouse cortical neurons with two-photon microscopy has provided unique insights into cortical structure, function and plasticity. However, these studies are limited to head fixed animals, greatly reducing the behavioral complexity available for study. In this paper, we describe a procedure for performing chronic fluorescence microscopy with cellular-resolution across multiple cortical layers in freely behaving mice. We used an integrated miniaturized fluorescence microscope paired with an implanted prism probe to simultaneously visualize and record the calcium dynamics of hundreds of neurons across multiple layers of the somatosensory cortex as the mouse engaged in a novel object exploration task, over several days. This technique can be adapted to other brain regions in different animal species for other behavioral paradigms.

Multi-layer Cortical Ca2+ Imaging in Freely Moving Mice with Prism Probes and Miniaturized Fluorescence Microscopy

Here, we present a procedure for performing large-scale Ca2+ imaging with cellular-resolution across multiple cortical layers in freely moving mice. Hundreds of active cells can be observed simultaneously using a miniature, head-mounted microscope coupled with an implanted prism probe.

In vivo circuit and cellular level functional imaging is a critical tool for understanding the brain in action. High resolution imaging of mouse cortical ...

An Electrophysiology Protocol to Measure Reward Anticipation and Processing in Children

We present a protocol designed to measure the neural correlates of reward in children. The protocol allows researchers to measure both reward anticipation and processing. Its purpose is to create a reward task that is appropriate for young children with and without autism while controlling reward properties between two conditions: social and nonsocial. The current protocol allows for comparisons of brain activity between social and nonsocial reward conditions while keeping the reward itself identical between conditions. Using this protocol, we found evidence that neurotypical children demonstrate enhanced anticipatory brain activity during the social condition. Furthermore, we found that neurotypical children anticipate social reward more robustly than children with autism diagnoses. As the task uses snacks as a reward, it is most appropriate for young children. However, the protocol may be adapted for use with adolescent or adult populations if snacks are replaced by monetary incentives. The protocol is designed to measure electrophysiological events (event-related potentials), but it may be customized for use with eye-tracking or fMRI.

This protocol is designed to measure reward anticipation and processing in young children with and without autism. Specifically, the protocol is designed to study the neural correlates of reward during social and nonsocial conditions while controlling for reward between conditions.

We present a protocol designed to measure the neural correlates of reward in children. The protocol allows researchers to measure both reward anticipation ...