Rhythm in the Premature Neonate Brain: Very Early Processing of Auditory Beat and Meter.

The ability to extract rhythmic structure is important for the development of language, music, and social communication. Although previous studies show infants' brains entrain to the periodicities of auditory rhythms and even different metrical interpretations (e.g., groups of two vs three beats) of ambiguous rhythms, whether the premature brain tracks beat and meter frequencies has not been explored previously. We used high-resolution electroencephalography while premature infants (n = 19, 5 male; mean age, 32 ± 2.59 weeks gestational age) heard two auditory rhythms in the incubators. We observed selective enhancement of the neural response at both beat- and meter-related frequencies. Further, neural oscillations at the beat and duple (groups of 2) meter were phase aligned with the envelope of the auditory rhythmic stimuli. Comparing the relative power at beat and meter frequencies across stimuli and frequency revealed evidence for selective enhancement of duple meter. This suggests that even at this early stage of development, neural mechanisms for processing auditory rhythms beyond simple sensory coding are present. Our results add to a few previous neuroimaging studies demonstrating discriminative auditory abilities of premature neural networks. Specifically, our results demonstrate the early capacities of the immature neural circuits and networks to code both simple beat and beat grouping (i.e., hierarchical meter) regularities of auditory sequences. Considering the importance of rhythm processing for acquiring language and music, our findings indicate that even before birth, the premature brain is already learning this important aspect of the auditory world in a sophisticated and abstract way.SIGNIFICANCE STATEMENT Processing auditory rhythm is of great neurodevelopmental importance. In an electroencephalography experiment in premature newborns, we found converging evidence that when presented with auditory rhythms, the premature brain encodes multiple periodicities corresponding to beat and beat grouping (meter) frequencies, and even selectively enhances the neural response to meter compared with beat, as in human adults. We also found that the phase of low-frequency neural oscillations aligns to the envelope of the auditory rhythms and that this phenomenon becomes less precise at lower frequencies. These findings demonstrate the initial capacities of the developing brain to code auditory rhythm and the importance of special care to the auditory environment of this vulnerable population during a highly dynamic period of neural development.

Preterm neonates distinguish rhythm violation through a hierarchy of cortical processing.

Rhythm is a fundamental component of the auditory world, present even during the prenatal life. While there is evidence that some auditory capacities are already present before birth, whether and how the premature neural networks process auditory rhythm is yet not known. We investigated the neural response of premature neonates at 30-34 weeks gestational age to violations from rhythmic regularities in an auditory sequence using high-resolution electroencephalography and event-related potentials. Unpredicted rhythm violations elicited a fronto-central mismatch response, indicating that the premature neonates detected the rhythmic regularities. Next, we examined the cortical effective connectivity underlying the elicited mismatch response using dynamic causal modeling. We examined the connectivity between cortical sources using a set of 16 generative models that embedded alternate hypotheses about the role of the frontal cortex as well as backward fronto-temporal connection. Our results demonstrated that the processing of rhythm violations was not limited to the primary auditory areas, and as in the case of adults, encompassed a hierarchy of temporo-frontal cortical structures. The result also emphasized the importance of top-down (backward) projections from the frontal cortex in explaining the mismatch response. Our findings demonstrate a sophisticated cortical structure underlying predictive rhythm processing at the onset of the thalamocortical and cortico-cortical circuits, two months before term.

Neurodevelopment and asymmetry of auditory-related responses to repetitive syllabic stimuli in preterm neonates based on frequency-domain analysis.

Sensory development of the human brain begins prenatally, allowing cortical auditory responses to be recorded at an early age in preterm infants. Despite several studies focusing on the temporal characteristics of preterm infants' cortical responses, few have been conducted on frequency analysis of these responses. In this study, we performed frequency and coherence analysis of preterm infants' auditory responses to series of syllables and also investigated the functional brain asymmetry of preterm infants for the detection of the regularity of auditory stimuli. Cortical auditory evoked potentials (CAEPs) were recorded in 16 preterm infants with a mean recording age of 31.48 weeks gestational age (29.57-34.14 wGA) in response to a repetitive syllabic stimulus. Peak amplitudes of the frequency response at the target frequency and the first harmonic, as well as the phase coherence (PC) at the target frequency were extracted as age-dependent variables. A functional asymmetry coefficient was defined as a lateralization index for the amplitude of the target frequency at each electrode site. While the findings revealed a significant positive correlation between the mean amplitude at the target frequency vs. age (R2 = 0.263, p = 0.042), no significant correlation was observed for age-related changes of the mean amplitude at the first harmonic. A significant correlation was also observed between the mean PC and age (R2 = 0.318, p = 0.023). A right hemisphere lateralization over many channels was also generally observed. The results demonstrate that rightward lateralization for slow rate modulation, previously observed in adults, children and newborns, appears to be in place at a very young age, even in preterm infants.

Consequence of intraventricular hemorrhage on neurovascular coupling evoked by speech syllables in preterm neonates.

Intraventricular Hemorrhage (IVH) is the leading cause of neurological and cognitive impairment in preterm neonates with an incidence that increases with increasing prematurity. In the present study, we tested how preterm neonates with IVH react to external stimulation (i.e. speech syllables). We compared their neural responses measured by electroencephalography (EEG), and hemodynamic responses measured by functional near-infrared spectroscopy (fNIRS), with those of healthy preterms. A neural response to syllables was observed in these infants, but did not induce a vascular response in contrast with healthy neonates. These results clearly demonstrate that the cerebral vascular network in IVH preterm neonates was unable to compensate for the increased metabolism resulting from neuronal activation in response to external stimulation. Optical imaging is thus a sensitive tool to identify altered cerebral hemodynamic in critically ill preterms before behavioral changes are manifested or when only minor abnormalities on other functional monitoring techniques such as EEG are visible. We propose that a multi-modal approach provides unique opportunities for early monitoring of cognitive functions and opens up new possibilities for clinical care and recommended practices by studying the difficulties of the premature brain to adapt to its environment.

Functional Maps at the Onset of Auditory Inputs in Very Early Preterm Human Neonates.

During the last trimester of human gestation, neurons reach their final destination and establish long- and short-distance connections. Due to the difficulties obtaining functional data at this age, the characteristics of the functional architecture at the onset of sensory thalamocortical connectivity in humans remain largely unknown. In particular, it is unknown to what extent responses evoked by an external stimulus are general or already sensitive to certain stimuli. In the present study, we recorded high-density event-related potentials (ERPs) in 19 neonates, tested ten weeks before term (28-32 weeks gestational age (wGA), that is, at an average age of 30 wGA) by means of a syllable discrimination task (i.e., a phonetic change: ba vs. ga; and a voice change: male vs. female voice). We first observed that the syllables elicited 4 peaks with distinct topographies implying a progression of the sensory input along a processing hierarchy; second, repetition induced a decrease in the amplitude (repetition suppression) of these peaks, but their latencies and topographies remained stable; and third, a change of stimulus generated mismatch responses, which were more precisely time-locked to event onset in the case of a phonetic change than in the case of a voice change. A hierarchical and parallel functional architecture is therefore able to process environmental sounds in a timely precise fashion, well before term birth. This elaborate functional architecture at the onset of extrinsic neural activity suggests that specialized areas weakly dependent on the environment are present in the perisylvian region as part of the genetic endowment of the human species.

Realistic head model design and 3D brain imaging of NIRS signals using audio stimuli on preterm neonates for intra-ventricular hemorrhage diagnosis.

In this paper we propose an auditory stimulation and near infra-red spectroscopy (NIRS) hemodynamic changes acquisition protocol for preterm neonates. This study is designed to assess the specific characteristics of neurovascular coupling to auditory stimuli in healthy and ill neonate brains. The method could lead to clinical application in intra-ventricular hemorrhage (IVH) diagnosis along with other techniques such as EEG. We propose a realistic head model creation with all useful head structures and brain tissues including the neonate fontanel for more accurate results from NIRS signals modeling. We also design a 3D imaging tool for dynamic mapping and analysis of brain activation onto the cortex surface. Results show significant differences in oxy-hemoglobin between healthy neonates and subjects with IVH.