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

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

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 in 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 sung 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

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

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

Detection of abnormal neural enconding of speech sounds at birth using the frequency-following response

[eng] In humans, auditory system is functional at the end of the second trimester of pregnancy and its correct development is crucial to receive auditory inputs from our acoustic environment, exposure which, in turn, is essential far the language acquisition. Although the auditory system formation is influenced by genetic factors that program anatomic and physiologic changes, is also susceptible to environmental agents and the intrauterine period is the most vulnerable stage. Previous studies described that an unfavorable intrauterine environment could conditionate structurally and functionally the auditory system. Taking into account that birth weight represents the fetus growth during pregnancy and is a correlate of the intrauterine environment state, the present thesis aims to explore if an altered fetal growth is associated which abnormal neural encoding of speech sounds at birth. Neonates born with an unexpected birth weight far their gestational age are at high risk of short­ and long-term complications. According to the Gaussian distribution of birth weight, there are two groups of babies located at each end that require special attention: neonates born small­ far-gestational age (SGA) are affected by fetal growth restriction (FGR) and neonates born large­ far-gestational age (LGA). Since the prevalence is approximately 9% far each group (SGA/FGR and LGA), reaching a combined incidence of 18% of total births in developed countries and being even higher in developing countries, the clinical and societal impact of an altered fetal growth cannot be ruled out. lnternational health organizations claim the need to improve SGA/FGR and LGA detection techniques and objective tooIs that enable the early identification of those cases at greatest health risk. Therefare, to contribute to this goal, we would like to explore whether essential language skills such as voice perception at birth could be affected by altered fetal growth through an auditory evoked potential called frequency-fallowing response (FFR). FFR reproduces with great fidelity the spectro-temporal features of the complex auditory stimulus such as music or speech. Due to the small number of studies in which the neonatal FFR has been recorded, the first objective of the present doctoral thesis was to describe in depth the neonatal FFR and to corroborate the possibility of recording this electrophysiological response as part of the clinical routine. In the first study, we achieved this specific goal and a normative database describing neonatal FFR standards was published. Once the possibility of recording neonatal FFR was confirmed, we explored whether newborns affected by fetal growth restriction - a population traditionally associated with a high risk of communication disorders - were more likely to exhibit alterations in the encoding of voice-pitch through the FFR that their healthy peers. The second study revealed that FGR neonates hadan altered perception of voice-pitch in the vowel region, an alteration that was consistent with the effects of white matter reported by radiological and animal studies. Finally, in the third study, we investigated whether those newborns located at the opposite end of the birth weight continuum, the so-called large-for­ gestational age (LGA), have an altered voice-pitch encoding. The results showed that being born LGA was associated with altered voice-pitch perception, and it was suggested that elevated adipose tissue could functionally limit, through proinflammatory agents, the brain structures involved in encoding complex sounds. Therefore, in the present thesis we have observed that being born with altered fetal growth is associated with altered coding of voice-pitch. However, more studies are needed with larger cohorts and longitudinal approaches that make it possible to corroborate the FFR's predictive power on language skills assessed by neurobehavioral test s.[cat] En humans, el sistema auditiu és funcional al final del segon trimestre de l'embaràs i el seu correcte desenvolupament és crucial per rebre aportacions auditives del nostre entorn acústic, exposició que, al seu torn, és essencial pera l'adquisició del llenguatge. Tot i que la formació del sistema auditiu està influenciada per factors genètics els quals programen canvis anatòmics i fisiològics, també és susceptible als agents ambientals, i el període intrauterí és l'etapa més vulnerable. Estudis previs han descrit que un entorn intrauterí desfavorable podria condicionar estructuralment i funcionalment el sistema auditiu. Tenint en compte que el pes al naixement representa el creixement del fetus durant l'embaràs i és un correlat de l'estat del medi intrauterí, la present tesi té com a objectiu explorar si un creixement fetal alterat s'associa a una codificació neuronal anòmala de la parla en néixer. Els nounats nascuts amb un pes al naixement no esperat per a la seva edat gestacional tenen un risc elevat de complicacions a curt i a llarg termini. Segons la distribució gaussiana del pes al naixement, es distingeixen dos grups de nadons situats un a cada extrem de la distribució que reclamen especial atenció: els nounats nascuts petits per la seva edat gestacional (PEG) o afectats per una restricció del creixement fetal (FGR) i els nounats nascuts grans per la seva edat gestacional (GEG). Atès que la prevalença és del 9% aproximadament per a cada grup (PEG / FGR i GEG), arribant a una incidència conjunta del 18% del total de naixements als països desenvolupats i sent, fins i tot, superior als països en desenvolupament, l'impacte clínic i social d'un creixement fetal alterat no es pot descartar. Les organitzacions internacionals de salut reclamen la necessitat de millorar les tècniques de detecció de PEG / FGR i GEG i eines objectives que possibilitin la identificació precoç d'aquells casos en major risc de salut. Per tant, per contribuir a aquesta finalitat, ens proposem explorar si les habilitats lingüístiques essencials com la percepció del to de veu en néixer podrien veure's afectades per un creixement fetal alterat mitjançant un potencial evocat auditiu anomenat resposta de seguiment de freqüencia (RSF). La RSF reprodueix amb una gran fidelitat els trets espectro-temporals de l'estímul auditiu complex que l'ha evocat. Per tant, recentment es suggereix aquesta resposta electrofisiològica com un correlat neuronal de la codificació de sons com la música o la parla. Degut al nombre reduït d'estudis en que s'ha registrat la RSF en nadons, el primer objectiu de la present tesi doctoral va ser descriure amb profunditat la RSF neonatal i corroborar la possibilitat de registrar aquesta resposta electrofisiològica com a part de la rutina clínica de l'hospital. En el primer estudi, vam assolir aquest objectiu específic i es va publicar una base de dades normativa que descrivia els estàndards de la RSF neonatal. Un cop confirmada la possibilitat de registrar el RSF neonatal, vam explorar si els nounats afectats per restricció de creixement fetal -una població tradicionalment associada a un alt risc de trastorns de la comunicació- tenien una probabilitat major de presentar alteracions en la codificació del to de veu per mitjà de la RSF que els seus companys sans. El segon estudi va revelar que els nounats FGR tenien una percepció del to alterada a la regió vocal, alteració que era compatible ambles afectacions de la substancia blanca reportades per estudis radiologics i animaIs. Finalment, al tercer estudi vam investigar si aquells nounats situats a l'extrem oposat del continu de pes al naixement, els anomenats nounats grans per la seva edat gestacional (GEG), presenten una codificació del to de veu alterada. Els resultats van mostrar que el fet de néixer GEG es va associar amb una percepció de to alterada i es va suggerir que el teixit adipós elevat podria limitar funcionalment, per mitjà d'agents proinflamatoris, les estructures cerebrals implicades en la codificació de sons complexos. Per tant, en la present tesi hem observat que néixer amb un creixement fetal alterat s'associa amb una codificació alterada del to de veu. No obstant això, es necessiten més estudis amb cohorts més grans i enfocaments longitudinals que facin possible corroborar el poder predictiu del FFR sobre les destreses lingüístiques avaluades per proves neuroconductuals