Deficient neural encoding of speech sounds in term neonates born after fetal growth restriction

Abstract

Infants born after fetal growth restriction (FGR)-an obstetric condition defined as the failure to achieve the genetic growth potential-are prone to neurodevelopmental delays, with language being one of the major affected areas. Yet, while verbal comprehension and expressive language impairments have been observed in FGR infants, children and even adults, specific related impairments at birth, such as in the ability to encode the sounds of speech, necessary for language acquisition, remain to be disclosed. Here, we used the frequency-following response (FFR), a brain potential correlate of the neural phase locking to complex auditory stimuli, to explore the encoding of speech sounds in FGR neonates. Fifty-three neonates born with FGR and 48 controls born with weight adequate-for-gestational age (AGA) were recruited. The FFR was recorded to the consonant-vowel stimulus (/da/) during sleep and quantified as the spectral amplitude to the fundamental frequency of the syllable and its signal-to-noise ratio (SNR). The outcome was available in 45 AGA and 51 FGR neonates, yielding no differences for spectral amplitudes. However, SNR was strongly attenuated in the FGR group compared to the AGA group at the vowel region of the stimulus. These findings suggest that FGR population present a deficit in the neural pitch tracking of speech sounds already present at birth. Our results pave the way for future research on the potential clinical use of the FFR in this population, so that if confirmed, a disrupted FFR recorded at birth may help deriving FGR neonates at risk for postnatal follow-ups.

Speech-Encoding Deficits in Neonates Born Large-for-Gestational Age as Revealed With the Envelope Frequency-Following Response

“…A sample of 27 LGA mother-neonate pairs were recruited from the SJD Barcelona Children's Hospital (Catalonia, Spain) between April 2019 and January 2020. Based on the data quality inspection criteria used in previous studies from our lab (Ribas-Prats et al 2022), two cases were excluded because the FFR ENV signal could not be identified. Thus, the final sample included 25 LGA neonates and 25 neonates born AGA, all paired by sex and GA at birth (Table 1).…”

“…Thus, the final sample included 25 LGA neonates and 25 neonates born AGA, all paired by sex and GA at birth (Table 1). AGA neonates were drawn from a larger cohort assessed in a previous study (Ribas-Prats et al 2022). In case that an LGA case could be paired with more than one AGA neonate, the AGA pair was selected randomly using MATLAB (R2019b, Mathworks).…”

“…While no group differences were observed for spectral amplitudes, results revealed that SNR was strongly attenuated in the FGR group compared to the AGA group at the vowel region. These authors interpreted that the FGR population presents, as a group, impoverished neural tracking of the stimulus' F 0ENV at birth compared to healthy neonates, and suggested that these FFRs disruptions in FGR neonates could anticipate poor neurobehavioral outcomes (Ribas-Prats et al 2022).…”

Neonatal Frequency-Following Responses: A Methodological Framework for Clinical Applications

“…Taking into account the sensitivity of the auditory system to the state of the fetal environment and the innate and essential role of pitch encoding in language acquisition, we have been studying whether abnormal intrauterine growth could negatively affect the functionality of the auditory system. To this end, the encoding of speech sounds during the first days of life was analyzed to the /da/ stimulus with the FFR in two phenotypes representing the two ends of the birth weight continuum: babies affected by FGR 59 and babies classified as large for gestational age (LGA 60 ). Altered neural encoding of the fundamental frequency was observed in both clinical groups.…”

Implementation of Machine Learning on Human Frequency-Following Responses: A Tutorial

“…7 19 For example, the FFR has been carefully characterized in neonates, 41 42 infants, 43 44 children, 27 45 adults, 46 47 and the elderly. 31 32 The FFR has also been used to examine how the temporal and spectral cues are processed in individuals with autism, 45 48 dyslexia, 28 49 learning problems, 50 51 and brain concussion, 26 52 as well as for neonates who are born with fetal growth restriction 53 or hyperbilirubinemia. 54 The importance of musical training 40 55 and language experience 22 56 on fine-tuning the auditory neural pathways has also been documented.…”