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

Abstract

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.

Keywords: brainstem response; infants; newborns; speech ABR; speech encoding.

Figure 1

Morphology and characteristics of the frequency-following response (FFR). The FFR is a periodic auditory evoked potential that can be recorded in response to both simple stimuli (i.e., pure tones) and complex stimuli. In the top panel, a consonant–vowel syllable /da/ is represented in gray and the corresponding FFR recorded at the Fpz electrode in a newborn is represented in red. As can be observed, the FFR mimics the incoming stimulus by synchronizing with its temporal features, thus capturing with high fidelity and accuracy the periodic characteristics of sound in the ascending auditory system. Additionally, the FFR also encodes the spectral features of the incoming stimulus, as demonstrated in the frequency spectrum, tone tracking, and spectrogram in the bottom panels. The frequency spectrum illustrates the amplitude of the spectral decomposition of the FFR, which reveals a clear peak corresponding to the fundamental frequency of the stimulus (113 Hz in this recording). In addition, the pitch tracking provides a measure of the precision with which the FFR encodes changes in the fundamental frequency over the duration of the stimulus (stimulus frequency in black; FFR pitch tracking in red). The spectrogram provides combined information on both the frequency and amplitude at which the FFR synchronizes with the different components of the incoming stimulus. Overall, the figure illustrates how the FFR synchronizes with the stimulus that elicits it even in a single individual, providing a very useful tool in the fields of audiology and auditory cognitive neuroscience and in the study of auditory abilities at the individual level. For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article. (Modified with permission from Ribas-Prats T, Almeida L, Costa-Faidella J, et al. The frequency-following response (FFR) to speech stimuli: a normative dataset in healthy newborns. Hear Res 2019;371:28–39. 19 )

Figure 2

Recording setup. The recommended recording setup to obtain a neonatal FFR is with a minimum of three disposable snap Ag/AgCl electrodes placed in a vertical montage: the active electrode was located at Fpz (white electrode), reference at the mastoid behind the ear, and ground electrode at the forehead (black electrode). In this example, two reference electrodes are positioned in the mastoid bones behind the right and left ears (red and blue electrodes, respectively). Although possible, neonatal FFR is not typically recorded with EEG caps as newborns can still have vernix caseosa or blood residuals from birth on the head. The reproduction of the participant's picture is with the written consent of her mother. (The photograph has been published with consent.)

Figure 3

FFR fundamental frequency and temporal fine structure to the /oa/ diphthong. ( A ) Temporal (top) and spectral (bottom) representations of the /oa/ syllable, with a schematic overlay of its formant structure trajectory. The fundamental frequency is stable at 113 Hz from 0 to 160 milliseconds, with a linear increase to 154 Hz from 160 to 250 milliseconds. The section of the vowel /o/ (F1 = 452 Hz, F2 = 791 Hz) spans from 0 to 80 milliseconds and the section of vowel /a/ (F1 = 678 Hz, F2 = 1,017 Hz) from 90 to 250 milliseconds (F ₀ and F ₁ in solid lines; F ₂ in dotted line). ( B ) and ( C ) Grand averaged time-domain FFR and its spectral decomposition, recorded to the /oa/ stimulus in a sample of 34 newborns. As demonstrated in the spectral decomposition, when averaging the responses to alternating polarities ( B ) only the fundamental frequency of the stimulus (113 Hz) can be observed. On the other hand, when subtracting the neural responses to the two stimulus polarities ( C ), the stimulus fine-structure (the first formant for the /o/ and the /a/ region is observable). Note that the amplitude of the scale in ( B ) is twice that of ( C ). (Modified with permission from Arenillas-Alcón S, Costa-Faidella J, Ribas-Prats T, Gómez-Roig MD, Escera C. Neural encoding of voice pitch and formant structure at birth as revealed by frequency-following responses. Sci Rep 2021;11(1):1–16. 48 )