Vibration-based mitigation of noxious-evoked responses to skin puncture in neonates and infants: a randomised controlled trial.

OBJECTIVE: To assess the effect of a non-noxious vibratory stimulus on noxious-evoked cortical responses to skin puncture and to determine whether the presence of certain behavioural components may be used to predict such cortical responses. DESIGN: Randomised controlled trial. SETTING: Level IV neonatal intensive care unit at a stand-alone children's hospital. PATIENTS: 134 hospitalised infants between 36 and 52 weeks' postmenstrual age and ordered to receive a clinically required laboratory draw. INTERVENTIONS: Infants randomised to receive the intervention, a vibratory stimulus at the site of skin puncture beginning 10 s prior to a heel stick, or the control, no vibration. MAIN OUTCOME MEASURES: Electroencephalography and video recording time-locked to the deployment of the lancet for the skin puncture. Noxious-evoked cortical responses were measured by the area under the curve in the somatosensory region contralateral to the skin puncture. Behavioural responses were coded through video analysis. RESULTS: Noxious-evoked cortical responses were significantly reduced in participants receiving the vibratory stimulus compared with the control (frontal, p<0.0001; central, p=0.0088; central-parietal, p=0.0111). There were no significant differences in behavioural responses between groups (all p>0.05). CONCLUSIONS: A non-noxious vibratory stimulus presented prior to and continuing simultaneously with skin puncture significantly mitigates nociception in hospitalised infants. The presence or absence of facial expression components is inadequate to reliably predict pain signalling in the brain. TRIAL REGISTRATION NUMBER: NCT04050384.

Behavioral and neural measures of infant responsivity increase with maternal multisensory input in non-irritable infants.

INTRODUCTION: Parents often use sensory stimulation during early-life interactions with infants. These interactions, including gazing, rocking, or singing, scaffold child development. Previous studies have examined infant neural processing during highly controlled sensory stimulus presentation paradigms. OBJECTIVE: In this study, we investigated infant behavioral and neural responsiveness during a mother-child social interaction during which the mother provided infant stimulation with a progressive increase in the number of sensory modalities. METHODS: We prospectively collected and analyzed video-coded behavioral interactions and electroencephalogram (EEG) frontal asymmetry (FAS) from infants (n = 60) at 2-4 months born at ≥ 34 weeks gestation. As the number of sensory modalities progressively increased during the interaction, infant behaviors of emotional connection in facial expressiveness, sensitivity to mother, and vocal communication increased significantly. Conversely, infant FAS for the entire cohort did not change significantly. However, when we accounted for infant irritability, both video-coded behaviors and EEG FAS markers of infant responsiveness increased across the interaction in the non-irritable infants. The non-irritable infants (49%) demonstrated positive FAS, indicating readiness to engage with, rather than to withdraw from, multisensory but not unisensory interactions with their mothers. RESULTS: These results suggest that multisensory input from mothers is associated with greater infant neural approach state and highlight the importance of infant behavioral state during neural measures of infant responsiveness.

Randomized Trial to Increase Speech Sound Differentiation in Infants Born Preterm.

OBJECTIVE: To test whether infant-directed foreign language active learning would specifically increase speech sound differentiation to the intervention language while not decreasing differentiation in response to English. STUDY DESIGN: Pilot randomized controlled trial of stable infants born preterm in the newborn intensive care unit with normal auditory brainstem responses, whose parents spoke only English and had no musical training or familial hearing abnormality. Assignment was to 1 of 3 groups: passive exposure to English infant-directed lullabies and readings (English-enrichment, control group) and contingent exposure by active sucking on a sensor-equipped pacifier to either infant-directed French lullabies and readings (English environment, French-contingent learning group) or infant-directed Mandarin lullabies and readings (English environment, Chinese-contingent learning group). The main outcome measures were preintervention and postintervention event-related potentials (ERPs) in response to standardized speech syllables in each language. RESULTS: Forty-one subjects completed the study, including 15 in the English-enrichment control group and 13 each in the French-contingent and Chinese-contingent groups. The median gestational age at birth was 34 weeks (IQR, 8.75 weeks); postmenstrual age at intervention ranged from 36 to 46 weeks and was similar across the 3 groups. Postintervention mean ERP amplitude to pairs of English speech sounds did not differ across the 3 groups; however, ERP amplitude in French sound differentiation was greater in the French-contingent group than in the Chinese-contingent or English-enrichment groups, and ERP amplitude greater in Chinese sound differentiation was greater in the Chinese-contingent group compared with the other 2 groups. CONCLUSION: Contingent infant-directed foreign language exposure increased speech sound differentiation specific to the intervention language and did not decrease differentiation in response to English. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03232931.

Kinematic and Somatosensory Gains in Infants with Cerebral Palsy After a Multi-Component Upper-Extremity Intervention: A Randomized Controlled Trial.

Upper extremity (UE) impairments in infants with cerebral palsy (CP) result from reduced quality of motor experiences and "noisy" sensory inputs. We hypothesized that a neuroscience-based multi-component intervention would improve somatosensory processing and motor measures of more-affected (UEs) in infants with CP and asymmetric UE neurologic impairments, while remaining safe for less-affected UEs. Our randomized controlled trial compared infants (6-24 months) with CP receiving intervention (N = 37) versus a waitlisted group (N = 36). Treatment effects tested a direct measurement of reach smoothness (3D-kinematics), a measure of unimanual fine motor function (Bayley unimanual fine motor raw scores), and EEG measures of cortical somatosensory processing. The four-week therapist-directed, parent-administered intervention included daily (1) bimanual play; (2) less-affected UE wearing soft-constraint (6 h/day, electronically-monitored); (3) reach training on more-affected UE; (4) graduated motor-sensory training; and (5) parent education. Waitlist infants received only bimanual play. Effectiveness and safety were tested; z-scores from 54 posttest-matched typically-developing infants provided benchmarks for treatment effects. Intervention and waitlist infants had no pretest differences. Median weekly constraint wear was 38 h; parent-treatment fidelity averaged > 92%. On the more affected side, the intervention significantly increased smoothness of reach (Cohen's d = - 0.90; p < .001) and unimanual fine motor skill (d = 0.35; p = .004). Using unadjusted p values, intervention improved somatosensory processing (d = 0.53; p = .04). All intervention effects referenced well to typically developing children. Safety of the intervention was demonstrated through positive- or non-effects on measurements involving the constrained, less-affected UE and gross motor function; unexpected treatment effects on reach smoothness occurred in less-affected UEs (d = - 0.85; p = .01). This large clinical trial demonstrated intervention effectiveness and safety for developing sensory and motor systems with improvements in reach smoothness, and developmental abilities.Clinical Trail Registration: ClinicalTrials.gov NCT02567630, registered October 5, 2015.

Characteristics of the Frequency-Following Response to Speech in Neonates and Potential Applicability in Clinical Practice: A Systematic Review.

Purpose We sought to critically analyze and evaluate published evidence regarding feasibility and clinical potential for predicting neurodevelopmental outcomes of the frequency-following responses (FFRs) to speech recordings in neonates (birth to 28 days). Method A systematic search of MeSH terms in the Cumulative Index to Nursing and Allied HealthLiterature, Embase, Google Scholar, Ovid Medline (R) and E-Pub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Web of Science, SCOPUS, COCHRANE Library, and ClinicalTrials.gov was performed. Manual review of all items identified in the search was performed by two independent reviewers. Articles were evaluated based on the level of methodological quality and evidence according to the RTI item bank. Results Seven articles met inclusion criteria. None of the included studies reported neurodevelopmental outcomes past 3 months of age. Quality of the evidence ranged from moderate to high. Protocol variations were frequent. Conclusions Based on this systematic review, the FFR to speech can capture both temporal and spectral acoustic features in neonates. It can accurately be recorded in a fast and easy manner at the infant's bedside. However, at this time, further studies are needed to identify and validate which FFR features could be incorporated as an addition to standard evaluation of infant sound processing evaluation in subcortico-cortical networks. This review identifies the need for further research focused on identifying specific features of the neonatal FFRs, those with predictive value for early childhood outcomes to help guide targeted early speech and hearing interventions.

Topographic recordings of auditory evoked potentials to speech: subcortical and cortical responses.

Topographies of speech auditory brainstem response (speech ABR), a fine electrophysiological marker of speech encoding, have never been described. Yet, they could provide useful information to assess speech ABR generators and better characterize populations of interest (e.g., musicians, dyslexics). We present here a novel methodology of topographic speech ABR recording, using a 32-channel low sampling rate (5 kHz) EEG system. Quality of speech ABRs obtained with this conventional multichannel EEG system were compared to that of signals simultaneously recorded with a high sampling rate (13.3 kHz) EEG system. Correlations between speech ABRs recorded with the two systems revealed highly similar signals, without any significant difference between their signal-to-noise ratios (SNRs). Moreover, an advanced denoising method for multichannel data (denoising source separation) significantly improved SNR and allowed topography of speech ABR to be recovered.

Speech auditory brainstem response (speech ABR) characteristics depending on recording conditions, and hearing status: an experimental parametric study.

Speech elicited auditory brainstem responses (Speech ABR) have been shown to be an objective measurement of speech processing in the brainstem. Given the simultaneous stimulation and recording, and the similarities between the recording and the speech stimulus envelope, there is a great risk of artefactual recordings. This study sought to systematically investigate the source of artefactual contamination in Speech ABR response. In a first part, we measured the sound level thresholds over which artefactual responses were obtained, for different types of transducers and experimental setup parameters. A watermelon model was used to model the human head susceptibility to electromagnetic artefact. It was found that impedances between the electrodes had a great effect on electromagnetic susceptibility and that the most prominent artefact is due to the transducer's electromagnetic leakage. The only artefact-free condition was obtained with insert-earphones shielded in a Faraday cage linked to common ground. In a second part of the study, using the previously defined artefact-free condition, we recorded speech ABR in unilateral deaf subjects and bilateral normal hearing subjects. In an additional control condition, Speech ABR was recorded with the insert-earphones used to deliver the stimulation, unplugged from the ears, so that the subjects did not perceive the stimulus. No responses were obtained from the deaf ear of unilaterally hearing impaired subjects, nor in the insert-out-of-the-ear condition in all the subjects, showing that Speech ABR reflects the functioning of the auditory pathways.