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1Department of Pediatrics, Monroe Carell Jr. Children's Hospital at Vanderbilt, Vanderbilt University, 2Vanderbilt Kennedy Center, Vanderbilt University, 3Department of Hearing and Speech Sciences, Vanderbilt University
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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'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.
Maitre, N. L., Key, A. P. Quantitative Assessment of Cortical Auditory-tactile Processing in Children with Disabilities. J. Vis. Exp. (83), e51054, doi:10.3791/51054 (2014).
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'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.
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'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's active participation. Additionally, it needed to have a standardized level of stimulation and a sham-control. For this we developed the "puffer" 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 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.
1. Assessment of Response to Light Touch
2. Assessment of Response to Multisensory Protocol (Auditory-tactile Simultaneous vs. Summed Individual Responses)
3. Software and Equipment Set Up
4. Data Acquisition and Preparation
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. The secondary response (N140 peak) primarily reflects activity in the secondary sensory cortex and awareness of a somatosensory stimulus as has been documented in published studies13,14. This peak in our paradigm reflects processes in the secondary sensory cortex, modulated by attention to touch (the 'fish blowing bubbles task'). The late response (P2 peak) primarily reflects the beginning of cognitive neural activity related to sensory stimulation. This peak may reflect subjective attention to touch and involuntary orientation15,16.
Puff vs. sham: Even though the sham presents a nonspecific tone-like sound at less than 35 dB, it cannot be considered completely inaudible17, and therefore constituted an appropriate sham control. The sham is the sound of the air puff without the sensation of the puff, and therefore cortical responses for such trials are small at left and right central locations optimal for detection of tactile SEPs. Sham trials produced early low amplitude responses under all conditions, different from the tactile stimulation and consistent with tone-like auditory stimuli. Specifically, analysis of peak amplitudes showed a measurable difference between sham and air puff for P50 (mean amplitude difference (D = -2.8 mV 2.7, p = 0.04), N70 (D = -3.9 mV 4.0, p = 0.04) and N140 (D = -4.1 mV 3.5, p = 0.02).
Differences between affected vs. unaffected hand puffer responses in children with hemiparetic cerebral palsy (see Table 2, modified from J. Child Neurology18). As a proof of concept for the Puffer system, statistical analysis was performed on peak amplitudes and latencies to characterize differences upon stimulation of the affected hand compared to the unaffected hand. While the subject population was small (N = 8), significant differences were observed between the two hands.
Assessment of response to multisensory protocol: auditory-tactile simultaneous vs. summed individual responses (Figure 4)
To determine the effects of multisensory interactions associated with the simultaneous tactile (puff) and auditory (speech sound) presentation it is essential to compare the observed brain response to the algebraic sum of the responses to auditory and tactile stimulation presented separately. This analysis principle has been well documented in audio-visual studies19-21. In this case, the sham-sound condition and the puff alone condition are added, as a coupled sham - speech-sound allows us to account for low amplitude nonspecific auditory responses demonstrated in Figure 1. Because auditory-tactile multisensory effects are typically evident in the early phases of cortical responses21, we focused our observation on the 0-140 msec time window. Two positive calculated peaks are observed, corresponding to the P50 (30-80 msec) and P100 (80-150 msec). Immediately after this, a large negative deflection can be observed, most likely corresponding to the N140 (130-230 msec).
In a second study of 10 children (ages 5-8) (Figure 4), the true multisensory response to auditory-tactile condition can be observed to have differences in all three deflections. The difference between the amplitude of the summed and multisensory mean amplitudes represents the contributions of multisensory neural processes to individual sensory responses. The existence of a multisensory auditory-tactile response to a speech sound-air puff stimulus had been suggested in adults by using neurobehavioral measures22 and this ERP methodology appears to confirm its existence in children as well, but at the level of cortical processing.
|ERP Peaks||Characteristics of response||P for affected vs unaffected|
|P50 and N70||No statistical difference between affected and unaffected hand stimulation||NS|
|N140||↑ amplitude in affected||0.036|
|compared to unaffected hand stimulation|
|P2||↓ amplitude ipsilateral and ↑ contralateral in affected||0.046|
|compared to unaffected hand stimulation|
|↑ latency ipsilateral in affected hand only||0.005|
|compared to contralateral|
Table 1. Selection of stimuli for multisensory paradigm.
|Sensory modality||Stimulus type||Specific example|
|auditory||Speech sound||computer generated /ga/sound|
|Nonspecific sound||tone-like sound generated by air puff|
|tactile||Light touch||calibrated air puff|
|auditory-tactile = multisensory||Simultaneous speech sound with touch||simultaneous /ga/and puff|
Table 2. Comparison of puffer results for affected and unaffected hand in children with cerebral palsy (N =8).
Figure 1. Electrode cluster representation on ERP net:
C : centroparietal
F : frontal
Odd numbers correspond to left-sided locations
Even numbers correspond to right-sided locations
Figure 2. Child undergoing Multisensory Testing. Compressed air flows through yellow flexible nozzles through cardboard "aquarium box" and out into clay mold in which finger is secured. For sham puffs, compressed air flows through nozzle aimed in back of box. ERP net is in place and child can visualize his arm, surroundings, and the box.
Figure 3. Comparison of responses to puff and sham control in the contralateral cortical side to stimulation of an affected hand. Tracings represent averages of N = 8 children (ages 5-8), centroparietal locations only. Black line represents puff, grey line represents sham response.
Figure 4. Responses recorded in somatosensory area of hemisphere contralateral to tactile stimulus, binaural auditory stimulus. Tracings represent averages of N = 10 children (ages 5-8)*, centroparietal locations only. Grey line represents calculated summed response of /ga/-sham + puff, black line represents true multisensory response of simultaneous /ga/-puff.
* This was a separate study from the one described in Figure 3, performed in 2012, also with Vanderbilt IRB-approved protocols.
This novel combination of air puff and ERP (referred to as the "Puffer system") 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 stimulus as well as to the use of ERP methods and equipment. The tactile paradigm can be performed in a total of 5 min, while the multisensory paradigm takes 10 min. This is especially useful for assessment of toddlers or subjects with behavioral challenges. The stimulus itself can be calibrated to never exceed light touch or pressure, making tolerance a nonissue, in contrast to electrical nerve stimulation. Finally, the openness and flexibility of the measurement device, the commonplace surroundings and the lack of physical restraint create a reassuring and child-friendly setting for experiments. This holds true especially in infants who can be comforted by light swaddling and being held by a caregiver. Therefore this methodology has applications for patient populations throughout the spectrum of health and disease, as well as through the lifespan from infancy to older adulthood.
While these characteristics make the "Puffer system" easier to administer in young children than functional MRI, ERP does not provide the same degree of spatial resolution24. Caution should be used in attributing ERP signal sources to underlying structures, even in the case of well-studied somatosensory potentials25. This is especially relevant for children with large space-occupying brain lesions. However, the temporal resolution offered by the Puffer system equals that of direct median nerve stimulation in adults, in whom the cortical origins of various ERP peaks have been well characterized.
A critical step in this paradigm is the positioning of the nozzle in proximity to more densely innervated areas in order to achieve optimal ERP signal. Hands, feet and face are obvious choices due to their dense innervation and large sensory representations in the somatosensory cortex. The force of the compressed air may also be optimized, either through the compressor or through the modification of the nozzle diameter. Use of a manometer to calibrate the force at the level of the nozzle itself is recommended to ensure accuracy. Ensuring the proper positioning of the hand with a mold or armboard with Velcro straps will further ensure that the distance between the nozzle and the skin surface remains constant.
Caution should also be used in trying to further decrease the time for paradigm administration or increase the number of stimulus trials. Sixty trials are sufficient to generate a clear ERP signal and allow for some data loss due to artifacts but fewer trials may not produce reliable, reproducible data. Conversely, more trials per condition may improve the ERP signal strength but could also result in habituation to stimulations, or increased motor/ocular artifacts due to boredom.
Possible modifications built into the methodology are the study of attentional effects on stimuli. The stimulus is light enough not to require attention but this can easily be enhanced, resulting in increases in ERP amplitudes especially in the early peaks from P50 to N140. Also built-into the multisensory system are the addition of varied speech sounds and tones. The timing of auditory and tactile signals can also be modified to from simultaneous to staggered, to study the effects of one modality on another.
Applications being realized in the near future include wider extension of the paradigm to infants and newborns with brain injury or abnormal sensory experiences in the neonatal period such as intensive care hospitalization as well as adolescents with disabilities. The value of such testing can be both predictive of future sensory-motor limb function. It may also be indicative of the ability of children to process multiple sensory streams as connected inputs and be a measure of efficacy for therapies aimed at sensory integration. For adults, the force of the tactile stimulus may need to be increased to provide similar results. Finally, additions of visual stimuli to the multisensory model are in conceptual stages and will provide an invaluable objective tool for the measurement of sensory processing functions and disorders.
The authors declare that they have no competing financial interests.
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.
|Geodesic sensor net||EGI, Inc., Eugene, OR||depends on size|
|Net Station EEG software v. 4.2||EGI, Inc., Eugene, OR||NA|
|E-Prime stimulus control application||PST, Inc. Pittsburgh, PA||NA|
|Manometer (model 6 in, 0-60 psi)||H. O. Trerice Co, Oak Park, MI|
|Custom Puffer setup||Nathalie Maitre|
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