Developmental Trajectory of the Frequency-Following Response During the First 6 Months of Life.

PURPOSE: The aim of the present study is to characterize the maturational changes during the first 6 months of life in the neural encoding of two speech sound features relevant for early language acquisition: the stimulus fundamental frequency (fo), related to stimulus pitch, and the vowel formant composition, particularly F1. The frequency-following response (FFR) was used as a snapshot into the neural encoding of these two stimulus attributes. METHOD: FFRs to a consonant-vowel stimulus /da/ were retrieved from electroencephalographic recordings in a sample of 80 healthy infants (45 at birth and 35 at the age of 1 month). Thirty-two infants (16 recorded at birth and 16 recorded at 1 month) returned for a second recording at 6 months of age. RESULTS: Stimulus fo and F1 encoding showed improvements from birth to 6 months of age. Most remarkably, a significant improvement in the F1 neural encoding was observed during the first month of life. CONCLUSION: Our results highlight the rapid and sustained maturation of the basic neural machinery necessary for the phoneme discrimination ability during the first 6 months of age.

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

OBJECTIVES: The present envelope frequency-following response (FFR ENV ) study aimed at characterizing the neural encoding of the fundamental frequency of speech sounds in neonates born at the higher end of the birth weight continuum (>90th percentile), known as large-for-gestational age (LGA). DESIGN: Twenty-five LGA newborns were recruited from the maternity unit of Sant Joan de Déu Barcelona Children's Hospital and paired by age and sex with 25 babies born adequate-for-gestational age (AGA), all from healthy mothers and normal pregnancies. FFR ENV s were elicited to the/da/ syllable and recorded while the baby was sleeping in its cradle after a successful universal hearing screening. Neural encoding of the stimulus' envelope of the fundamental frequency (F 0ENV ) was characterized through the FFR ENV spectral amplitude. Relationships between electrophysiological parameters and maternal/neonatal variables that may condition neonatal neurodevelopment were assessed, including pregestational body mass index (BMI), maternal gestational weight gain and neonatal BMI. RESULTS: LGA newborns showed smaller spectral amplitudes at the F 0ENV compared to the AGA group. Significant negative correlations were found between neonatal BMI and the spectral amplitude at the F 0ENV . CONCLUSIONS: Our results indicate that in spite of having a healthy pregnancy, LGA neonates' central auditory system is impaired in encoding a fundamental aspect of the speech sounds, namely their fundamental frequency. The negative correlation between the neonates' BMI and FFR ENV indicates that this impaired encoding is independent of the pregnant woman BMI and weight gain during pregnancy, supporting the role of the neonatal BMI. We suggest that the higher adipose tissue observed in the LGA group may impair, via proinflammatory products, the fine-grained central auditory system microstructure required for the neural encoding of the fundamental frequency of speech sounds.

Prenatal daily musical exposure is associated with enhanced neural representation of speech fundamental frequency: Evidence from neonatal frequency-following responses.

Fetal hearing experiences shape the linguistic and musical preferences of neonates. From the very first moment after birth, newborns prefer their native language, recognize their mother's voice, and show a greater responsiveness to lullabies presented during pregnancy. Yet, the neural underpinnings of this experience inducing plasticity have remained elusive. Here we recorded the frequency-following response (FFR), an auditory evoked potential elicited to periodic complex sounds, to show that prenatal music exposure is associated to enhanced neural encoding of speech stimuli periodicity, which relates to the perceptual experience of pitch. FFRs were recorded in a sample of 60 healthy neonates born at term and aged 12-72 hours. The sample was divided into two groups according to their prenatal musical exposure (29 daily musically exposed; 31 not-daily musically exposed). Prenatal exposure was assessed retrospectively by a questionnaire in which mothers reported how often they sang or listened to music through loudspeakers during the last trimester of pregnancy. The FFR was recorded to either a /da/ or an /oa/ speech-syllable stimulus. Analyses were centered on stimuli sections of identical duration (113 ms) and fundamental frequency (F0  = 113 Hz). Neural encoding of stimuli periodicity was quantified as the FFR spectral amplitude at the stimulus F0 . Data revealed that newborns exposed daily to music exhibit larger spectral amplitudes at F0 as compared to not-daily musically-exposed newborns, regardless of the eliciting stimulus. Our results suggest that prenatal music exposure facilitates the tuning to human speech fundamental frequency, which may support early language processing and acquisition. RESEARCH HIGHLIGHTS: Frequency-following responses to speech were collected from a sample of neonates prenatally exposed to music daily and compared to neonates not-daily exposed to music. Neonates who experienced daily prenatal music exposure exhibit enhanced frequency-following responses to the periodicity of speech sounds. Prenatal music exposure is associated with a fine-tuned encoding of human speech fundamental frequency, which may facilitate early language processing and acquisition.

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

The frequency-following response (FFR) to periodic complex sounds is a noninvasive scalp-recorded auditory evoked potential that reflects synchronous phase-locked neural activity to the spectrotemporal components of the acoustic signal along the ascending auditory hierarchy. The FFR has gained recent interest in the fields of audiology and auditory cognitive neuroscience, as it has great potential to answer both basic and applied questions about processes involved in sound encoding, language development, and communication. Specifically, it has become a promising tool in neonates, as its study may allow both early identification of future language disorders and the opportunity to leverage brain plasticity during the first 2 years of life, as well as enable early interventions to prevent and/or ameliorate sound and language encoding disorders. Throughout the present review, we summarize the state of the art of the neonatal FFR and, based on our own extensive experience, present methodological approaches to record it in a clinical environment. Overall, the present review is the first one that comprehensively focuses on the neonatal FFRs applications, thus supporting the feasibility to record the FFR during the first days of life and the predictive potential of the neonatal FFR on detecting short- and long-term language abilities and disruptions.

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

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.

Neural encoding of voice pitch and formant structure at birth as revealed by frequency-following responses.

Detailed neural encoding of voice pitch and formant structure plays a crucial role in speech perception, and is of key importance for an appropriate acquisition of the phonetic repertoire in infants since birth. However, the extent to what newborns are capable of extracting pitch and formant structure information from the temporal envelope and the temporal fine structure of speech sounds, respectively, remains unclear. Here, we recorded the frequency-following response (FFR) elicited by a novel two-vowel, rising-pitch-ending stimulus to simultaneously characterize voice pitch and formant structure encoding accuracy in a sample of neonates and adults. Data revealed that newborns tracked changes in voice pitch reliably and no differently than adults, but exhibited weaker signatures of formant structure encoding, particularly at higher formant frequency ranges. Thus, our results indicate a well-developed encoding of voice pitch at birth, while formant structure representation is maturing in a frequency-dependent manner. Furthermore, we demonstrate the feasibility to assess voice pitch and formant structure encoding within clinical evaluation times in a hospital setting, and suggest the possibility to use this novel stimulus as a tool for longitudinal developmental studies of the auditory system.

Emergence of prediction error along the human auditory hierarchy.

Auditory prediction errors have been extensively associated with the mismatch negativity (MMN), a cortical auditory evoked potential that denotes deviance detection. Yet, many studies lacked the appropriate controls to disentangle sensory adaptation from prediction error. Furthermore, subcortical deviance detection has been shown in humans through recordings of the frequency-following response (FFR), an early auditory evoked potential that reflects the neural tracking of the periodic characteristics of a sound, suggesting the possibility that prediction errors emerge subcortically in the auditory pathway. The present study aimed at investigating the emergence of prediction error along the auditory hierarchy in humans through combined recordings of the FFR and the MMN, tapping at subcortical and cortical levels, respectively, while disentangling prediction error from sensory adaptation with the use of appropriate controls. "Oddball" sequences of pure tones featuring repeated "standard" stimuli (269 Hz; p = 0.8) and rare "deviant" stimuli (p = 0.2; of 289, 329 and 409 Hz delivered in separated blocks to test "frequency separation" effects) were presented to nineteen healthy young participants. "Reversed" oddball sequences (where standard and deviant tones swapped their roles) were presented allowing comparison of responses to same physical stimuli as a function of functional role (i.e., standard, deviant). Critically, control sequences featuring five equiprobable tones (p = 0.2) allowed to dissociate sensory adaptation from prediction error. Results revealed that the MMN amplitude increased as a function of frequency separation yet displayed the same amplitude when retrieved against the control sequences, confirming previous results. FFRs showed repetition enhancement effects across all frequency separations, as supported by larger spectral amplitude to standard than to deviant and control stimuli. This pattern of results provides insights into the hierarchy of the human prediction error system in audition, suggesting that prediction errors in humans emerge at cortical level.

Effects of cTBS on the Frequency-Following Response and Other Auditory Evoked Potentials.

The frequency-following response (FFR) is an auditory evoked potential (AEP) that follows the periodic characteristics of a sound. Despite being a widely studied biosignal in auditory neuroscience, the neural underpinnings of the FFR are still unclear. Traditionally, FFR was associated with subcortical activity, but recent evidence suggested cortical contributions which may be dependent on the stimulus frequency. We combined electroencephalography (EEG) with an inhibitory transcranial magnetic stimulation protocol, the continuous theta burst stimulation (cTBS), to disentangle the cortical contribution to the FFR elicited to stimuli of high and low frequency. We recorded FFR to the syllable /ba/ at two fundamental frequencies (Low: 113 Hz; High: 317 Hz) in healthy participants. FFR, cortical potentials, and auditory brainstem response (ABR) were recorded before and after real and sham cTBS in the right primary auditory cortex. Results showed that cTBS did not produce a significant change in the FFR recorded, in any of the frequencies. No effect was observed in the ABR and cortical potentials, despite the latter known contributions from the auditory cortex. Possible reasons behind the negative results include compensatory mechanisms from the non-targeted areas, intraindividual variability of the cTBS effectiveness, and the particular location of our target area, the primary auditory cortex.

The frequency-following response (FFR) to speech stimuli: A normative dataset in healthy newborns.

The Frequency-Following Response (FFR) is a neurophonic auditory evoked potential that reflects the efficient encoding of speech sounds and is disrupted in a range of speech and language disorders. This raises the possibility to use it as a potential biomarker for literacy impairment. However, reference values for comparison with the normal population are not yet established. The present study pursues the collection of a normative database depicting the standard variability of the newborn FFR. FFRs were recorded to /da/ and /ga/ syllables in 46 neonates born at term. Seven parameters were retrieved in the time and frequency domains, and analyzed for normality and differences between stimuli. A comprehensive normative database of the newborn FFR is offered, with most parameters showing normal distributions and similar robust responses for /da/ and /ga/ stimuli. This is the first normative database of the FFR to characterize normal speech sound processing during the immediate postnatal days, and corroborates the possibility to record the FFRs in neonates at the maternity hospital room. This normative database constitutes the first step towards the detection of early FFR abnormalities in newborns that would announce later language impairment, allowing early preventive measures from the first days of life.