Vibrotactile Sensitivity of the Glabrous Hand and Perioral Face in Neurotypical Children and Adults Vibrotactile Sensitivity of the Glabrous Hand and Perioral Face in Neurotypical Children and Adults.

Purpose: Experimental findings are limited concerning tactile sensitivity of the glabrous hand and perioral face in neurotypical children. Additional research examining vibrotactile detection thresholds (VDT) in neurotypical children would further understanding of tactile perception in children and add to our understanding of somatosensory development across the lifespan. Method: A microprocessor-controlled, automated single-interval up/down (SIUD) adaptive tracking system, including stimulus control and perceptual response logging, was used to estimate vibrotactile detection thresholds (VDT) bilaterally for the glabrous index finger and perioral hairy skin at the oral angle in two neurotypical cohorts, including 37 children (age 10-13 years) and 45 adults (age 19-35 years) in response to sinusoidal mechanical stimuli presented at 5, 10, 50, 150, 250, and 300 Hz. Results: Linear mixed modeling (LMM) analysis revealed that the effects of skin site (F = 115.74, p < 0.0001) and stimulus frequency (F = 146.42, p < 0.0001) were significant, whereas the effects of sex (F = 0.83, p = 0.363) and age group (F = 2.11, p = 0.1507) were not significant. The increased sensitivity (classic U-function) at 250 Hz, attributable to the presence of the rapidly adapting Pacinian corpuscles in the glabrous hand, was not apparent in the perioral vibrogram. The absolute threshold values for perioral skin were higher and the magnitude of VDT differences was greater across stimulation frequency compared to glabrous finger VDTs. No significant differences in VDT were apparent between left and right skin sites regardless of sex and age group. Conclusion: The somatosensory hand and perioral face show similar tactile acuity in response to sinusoidal mechanical stimuli ranging from 5 to 300 Hz in preadolescent children and adults. The automated SIUD adaptive VDT tracking algorithm provides clinicians with a reliable tool for rapid assessment of the cutaneous somatosensory system across the lifespan. MS.ID.005768.


Introduction
Neural encoding of tactile features by the somatosensory system serves many important perceptual roles, including texture and object discrimination, feedback for precision grip and manipulation, and orofacial motor control for speech, gesture, and eating. Tactile feature encoding also plays a central role in haptics and motor development, and maintenance of perceptual skills and fine motor control as the somatic body plan grows from infancy into adulthood. These rapidly conducting somatosensory channels also play a key role in activity-and experience-dependent cortical neuroplasticity and recovery of motor function following injury to the brain (e.g., cerebrovascular stroke). While vibrotactile threshold testing has been used for nearly 100 years [1], data are

A Comparison of VDTs of the Hand and Orofacial Structures
Recent studies have compared VDTs between orofacial structures and the hand over a range of vibratory frequencies [2,3]. In a seminal study on orofacial somatic sensation [4], an ascending method of limits was used to estimate VDTs sampled from 12 neurotypical adult participants (mean age 19.25 years) for five areas on the face including the chin, lower lip (hairy skin), lip vermilion, oral angle, and the cheek, and a single site on the glabrous hand (right D2 digit). A linear motor equipped with a nylon center probe (0.5 cm2 area) and annular surround (1 mm gap) was used to deliver ramped mechanical sinusoidal stimuli (1 second ON, 1 second OFF) at discrete test frequencies [5,10,50,150,250, 300, 400, 600 Hz]. Mean VDTs for all facial skin sites were significantly higher than thresholds for the index finger. Pacinian-type sensitivity with the classic U-function, characteristic of the glabrous finger [5], was absent in the face. Pacinian corpuscles are notably absent in the orofacial structures of non-human primates, except for the ventral tongue surface [6]. The PC dip for the glabrous finger occurred at 250Hz and is consistent with previous psychophysical work [5].
Compared to the glabrous finger, VDTs in the lower face were significantly elevated and flattened from 150 to 600 Hz [4]. A subsequent study of VDT sensitivity of the upper and lower lip using an adaptive threshold tracking algorithm found significant main effects for test frequency and stimulation site [7]. Lip vermilion skin sites near midline yielded lower VDTs compared to lateral sites on the lips. The best frequency yielding the lowest VDTs for all test sites was 50 Hz. The effects of age and sex on VDTs have been explored in two cohorts of adults using the same instrumentation [3]. Vibrotactile thresholds were measured at six test frequencies [5,10,50,150,250,300 Hz] in the face and hand of eighteen young adults (age 23.8 years) and eighteen older adults (age 62.2 years).
VDTs were measured for the right lower lip vermilion, right nonglabrous oral angle, and glabrous right D2 using a single interval up/down (SIUD) adaptive threshold tracking procedure [8].
VDTs were significantly dependent on stimulus frequency, skin site, and sex. As expected, the glabrous index finger yielded the lowest threshold and manifest the classic U-function with acute sensitivity at 250 Hz. Diminished sensitivity to vibrotactile stimulation was apparent in the older cohort for the glabrous finger (D2) between 5 and 300 Hz. Since the hands are used often to manipulate objects and perform work, they are at increased risk use or work-related damage to the glabrous skin, including primary mechanoreceptive afferents and the surrounding integument [3]. The current study will provide new information about VDTs in male and female children across a broad range of discrete test frequencies spanning 5 to 300 Hz, for comparison to similar measures obtained in adults using the automated SIUD adaptive VDT algorithm [2,8,9]. The SIUD tracking method as described in the present report generates estimates of tactile thresholds at 6 test frequencies in ~ 3 minutes 45 seconds per skin site.
An efficient psychophysical tracking algorithm is advantageous for VDT estimation in challenging pediatric and other clinical populations where vigilance may be an issue. These data will add to our understanding of somatosensory vibrotactile sensitivity from childhood through age 35 years. Moreover, expanded application of VDT measures has clear clinical applications in children and adults with neurological issues, including peripheral mechanosensory neuropathy, and central somatosensory processing disorders [9][10][11][12][13][14].

Hypotheses
Independent variables in this study included vibratory stimulation frequency, age group, sex, and stimulus site. The dependent variable was vibrotactile detection threshold. Significant main effects were predicted for stimulus frequency with adults manifesting significantly lower thresholds compared to children [15]. As for sex, it was hypothesized that there would be significant sex differences for VDTs among children and adults, inspired by our previous findings in young adult subjects [3]. For stimulus site, it was hypothesized that the glabrous index finger would yield a clear advantage with lower VDTs compared to the commissural (hairy) skin at the oral angle of the lower face, consistent with observations in young adults [2][3][4].

Adaptive Psychophysical Threshold Tracking Procedure
A single interval up/down (SIUD) adaptive procedure based on eight trials to estimate VDT [8] was used for VDT estimation. The SIUD procedure begins with a suprathreshold stimulus to orient the participant and elicit a positive button press response. Initial step size was 10dB, and subsequent step sizes were ± 5 dB relative to the amplitude of the first trial. Following a negative response, step size was reduced to 2 dB for the remaining trials. The starting point for the 8 trials was the trial before the first negative response. The algorithm incorporated false positive trials as foils. For example, if a false positive was detected (e.g., participant responded when in fact no stimulus was presented), the data were discarded, and a new trial was initiated [3].

Statistical Analysis
Linear mixed modeling (LMM) was conducted to compare vibrotactile threshold between frequency (5, 10, 50, 150, 250, 300Hz), skin surface (left-and right-index finger, left and right oral angle), sex (male, female), and age group (children, adults), and examine potential interactions of those conditions. The models accounted for nesting of repeated measurements within participants (i.e., intraclass correlation), thereby providing unbiased estimates for condition differences. When an overall difference was significant across conditions, marginal means were pairwise compared at a Bonferroni-corrected alpha level while controlling for Type I error at the nominal level. A proper error covariance structure was determined based on model fit (i.e., adjusted Akaike Information Criterion, Bayesian Information Criterion). All statistical analyses were conducted using SAS 9.4 [16].

Discussion
The efficacy of an automatic SIUD adaptive procedure to estimate with results from a previous study using the same instrumentation which included a larger cohort of 89 neurotypical adults (mean age 24.33 years) [2].
Collectively, these studies provide strong evidence that VDTs are dependent on stimulus site and frequency of vibrotactile stimulation [17] with no discernable difference between men and women, and no measurable difference in VDTs between left and

VDTs and Vibration Exposure
Prolonged exposure of the hand to mechanical vibration at test frequencies ranging from 31.5 to 250 Hz has been shown to significantly elevate VDTs in the digits of the glabrous hand among young adult males [20,21]. Upper limb and whole-body vibration in adults (e.g., 4, 20, 31.5, 100 and 125 Hz) also elevated VDTs [22].
Elevated VDTs were greatest after simultaneous exposure to wholebody and hand-arm vibration. The increase in VDTs following exposure to both types of vibration was greater than that following either type of vibration separately for all frequencies [22]. Elevated VDTs resulting from prolonged exposure to vibration may reflect changes in the dynamics of blood flow to the cutaneous sensory surface. For example, [23]. examined the potential association algorithm. This study found that blood flow was reduced in the fingers of the hand that received 125Hz vibration and the contralateral hand which was not exposed to this vibration. Thus, the Pacinian corpuscles might contribute to vibration-induced vasoconstriction. Sex was a significant factor, with women manifesting greater reductions in blood flow in the fingers attributed to vibration exposure [23]. The vibratory contactor size (3 vs 6 mm diameter) was also positively related to the magnitude of VDT elevation following vibration exposure to the hand [24]. VDT assessment shows promise as a tool to evaluate the onset and progression of diabetic neuropathy in adults and children [15].

VDTs in Normal and Atypical Development
There is growing interest in understanding somatosensory function in children. For example, tactilometry based on the method of limits was used to assess VDTs for two digits of the hand (glabrous D5, D2) at 8, 16, 64, 125, 250, and 500 Hz in 269 neurotypical children (age 8 to 20 years) using a VibroSense Meter® device in which the sinusoidal threshold stimulus amplitude is expressed as acceleration in dB relative to 0.00001 m/s 2 [15]. Digit VDTs referenced to acceleration increased as frequency increased (with the exception of 125 and 64 Hz). Older participants manifest lower thresholds than younger participants. Elevated VDTs and changes in tactile adaptation have been reported in schoolage children (age 8-12 years) with autism spectrum disorder (ASD) [14,25]. Psychophysical detection of the rate of amplitude modulation of tactile stimuli discriminates ASD from neurotypical control children [26]. Children (ages 7-18 years) with obsessive compulsive disorder showed impaired amplitude discrimination adaptation and elevated just noticeable differences (JNDs) to tactile stimuli (25Hz vibration) delivered to the fingertips on the nondominant hand [13].
Males showed a disproportionately greater impairment in these tactile processing measures. One limitation of the present study is the relatively small number of participants in the child cohorts, with substantially fewer female children compared to their male counterparts. We plan to extend VDT studies to include clinical populations at risk for peripheral neuropathy and central somatosensory dysfunction, and younger children, perhaps as young as 6 years of age. We anticipate that younger children will be able to complete the SIUD psychophysical sensory tactile tracking paradigm which is similar in many respects to pure tone audiometry which children can complete beginning around the age of 6 years.

Conclusion
The present study examined vibrotactile detection thresholds in cohorts of neurotypical children and adults. LMM revealed significant main effects for stimulus frequency, skin site, but not for age group, and sex. Overall, VDTs were higher at the oral angle compared to the glabrous hand, and the classic 250 Hz PC dip was absent at the oral angle in children and adults. As frequency increased, the differences in mean VDT between the oral angles and index fingers decreased. The automated SIUD VDT tracking protocol and mechanical stimulus control system provides clinical investigators with a reliable tool for rapid assessment of somatosensory system on both glabrous and hairy skin in humans across the lifespan.

Funding
This research received no external funding.