Detection of regularities in auditory sequences before and at term-age in human neonates.

During the last trimester of gestation, fetuses and preterm neonates begin to respond to sensory stimulation and to discover the structure of their environment. Yet, neuronal migration is still ongoing. This late migration notably concerns the supra-granular layers neurons, which are believed to play a critical role in encoding predictions and detecting regularities. In order to gain a deeper understanding of how the brain processes and perceives regularities during this stage of development, we conducted a study in which we recorded event-related potentials (ERP) in 31-wGA preterm and full-term neonates exposed to alternating auditory sequences (e.g. "ba ga ba ga ba"), when the regularity of these sequences was violated by a repetition (e.g., ``ba ga ba ga ga''). We compared the ERPs in this case to those obtained when violating a simple repetition pattern ("ga ga ga ga ga" vs. "ga ga ga ga ba"). Our results indicated that both preterm and full-term neonates were able to detect violations of regularity in both types of sequences, indicating that as early as 31 weeks gestational age, human neonates are sensitive to the conditional statistics between successive auditory elements. Full-term neonates showed an early and similar mismatch response (MMR) in the repetition and alternating sequences. In contrast, 31-wGA neonates exhibited a two-component MMR. The first component which was only observed for simple sequences with repetition, corresponded to sensory adaptation. It was followed much later by a deviance-detection component that was observed for both alternation and repetition sequences. This pattern confirms that MMRs detected at the scalp may correspond to a dual cortical process and shows that deviance detection computed by higher-level regions accelerates dramatically with brain maturation during the last weeks of gestation to become indistinguishable from bottom-up sensory adaptation at term.

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.