Arachidonic and docosahexaenoic acid supplementation and brain maturation in preterm infants; a double blind RCT.

BACKGROUND: Arachidonic acid (ARA) and docosahexaenoic acid (DHA) are important structural components of neural cellular membranes and possess anti-inflammatory properties. Very preterm infants are deprived of the enhanced placental supply of these fatty acids, but the benefit of postnatal supplementation on brain development is uncertain. The aim of this study was to test the hypothesis that early enteral supplementation with ARA and DHA in preterm infants improves white matter (WM) microstructure assessed by diffusion-weighted MRI at term equivalent age. METHODS: In this double-blind, randomized controlled trial, infants born before 29 weeks gestational age were allocated to either 100 mg/kg ARA and 50 mg/kg DHA (ARA:DHA group) or medium chain triglycerides (control). Supplements were started on the second day of life and provided until 36 weeks postmenstrual age. The primary outcome was brain maturation assessed by diffusion tensor imaging (DTI) using Tract-Based Spatial Statistics (TBSS) analysis. RESULTS: We included 120 infants (60 per group) in the trial; mean (range) gestational age was 26+3 (22+6 - 28+6) weeks and postmenstrual age at scan was 41+3 (39+1 - 47+0) weeks. Ninety-two infants underwent MRI imaging, and of these, 90 had successful T1/T2 weighted MR images and 74 had DTI data of acceptable quality. TBSS did not show significant differences in mean or axial diffusivity between the groups, but demonstrated significantly higher fractional anisotropy in several large WM tracts in the ARA:DHA group, including corpus callosum, the anterior and posterior limb of the internal capsula, inferior occipitofrontal fasciculus, uncinate fasciculus, and the inferior longitudinal fasciculus. Radial diffusivity was also significantly lower in several of the same WM tracts in the ARA:DHA group. CONCLUSION: This study suggests that supplementation with ARA and DHA at doses matching estimated fetal accretion rates improves WM maturation compared to control treatment, but further studies are needed to ascertain any functional benefit. CLINICAL TRIAL REGISTRATION: www. CLINICALTRIALS: gov; ID:NCT03555019.

Preterm infants show an atypical processing of the mother's voice.

To understand the consequences of prematurity on language perception, it is fundamental to determine how atypical early sensory experience affects brain development. At term equivalent age, ten preterm and ten full-term newborns underwent high-density EEG during mother or stranger speech presentation, in the forward or backward order. A general group effect terms > preterms is evident in the theta frequency band, in the left temporal area, with preterms showing significant activation for strangers' and terms for the mother's voice. A significant group contrast in the low and high theta in the right temporal regions indicates higher activations for the stranger's voice in preterms. Finally, only full terms presented a late gamma band increase for the maternal voice, indicating a more mature brain response. EEG time-frequency analysis demonstrate that preterm infants are selectively responsive to stranger voices in both temporal hemispheres, and that they lack selective brain responses to their mother's forward voice.

Cortical alterations after very preterm birth and the association with socio-emotional abilities from childhood to early adolescence.

Very preterm birth (VPT; <32 weeks' gestation) leads to a situation where crucial steps of brain development occur in an abnormal ex utero environment, translating to vulnerable cortical and subcortical development. Associated with this atypical brain development, children and adolescents born VPT are at a high risk of socio-emotional difficulties. In the current study, we unravel developmental changes in cortical gray matter (GM) concentration in VPT and term-born controls aged 6-14 years, together with their associations with socio-emotional abilities. T1-weighted images were used to estimate signal intensities of brain tissue types in a single voxel (GM, white matter, and cortico-spinal fluid) and extract GM concentration disentangled from the presence of partial volume effects (PVEs). General linear model analysis was used to compare groups. Socio-emotional abilities were assessed and associations with GM concentration were explored using univariate and multivariate analyses. The effects of prematurity were far-reaching, with intricated patterns of increases and decreases of GM concentration mainly in frontal, temporal, parietal, and cingular regions. Better socio-emotional abilities were associated with increased GM concentration in regions known to be involved in such process for both groups. Our findings suggest that the trajectory of brain development following VPT birth may be fundamentally distinctive and impact socio-emotional abilities.

Music impacts brain cortical microstructural maturation in very preterm infants: A longitudinal diffusion MR imaging study.

Preterm birth disrupts important neurodevelopmental processes occurring from mid-fetal to term-age. Musicotherapy, by enriching infants' sensory input, might enhance brain maturation during this critical period of activity-dependent plasticity. To study the impact of music on preterm infants' brain structural changes, we recruited 54 very preterm infants randomized to receive or not a daily music intervention, that have undergone a longitudinal multi-shell diffusion MRI acquisition, before the intervention (at 33 weeks' gestational age) and after it (at term-equivalent-age). Using whole-brain fixel-based (FBA) and NODDI analysis (n = 40), we showed a longitudinal increase of fiber cross-section (FC) and fiber density (FD) in all major cerebral white matter fibers. Regarding cortical grey matter, FD decreased while FC and orientation dispersion index (ODI) increased, reflecting intracortical multidirectional complexification and intracortical myelination. The music intervention resulted in a significantly higher longitudinal increase of FC and ODI in cortical paralimbic regions, namely the insulo-orbito-temporopolar complex, precuneus/posterior cingulate gyrus, as well as the auditory association cortex. Our results support a longitudinal early brain macro and microstructural maturation of white and cortical grey matter in preterm infants. The music intervention led to an increased intracortical complexity in regions important for socio-emotional development, known to be impaired in preterm infants.

Behavioral outcome of very preterm children at 5 years of age: Prognostic utility of brain tissue volumes at term-equivalent-age, perinatal, and environmental factors.

OBJECTIVE: Prematurity is associated with a high risk of long-term behavioral problems. This study aimed to assess the prognostic utility of volumetric brain data at term-equivalent-age (TEA), clinical perinatal factors, and parental social economic risk in the prediction of the behavioral outcome at 5 years in a cohort of very preterm infants (VPT, <32 gestational weeks). METHODS: T2-weighted magnetic resonance brain images of 80 VPT children were acquired at TEA and automatically segmented into cortical gray matter, deep subcortical gray matter, white matter (WM), cerebellum (CB), and cerebrospinal fluid. The gray matter structure of the amygdala was manually segmented. Children were examined at 5 years of age with a behavioral assessment, using the strengths and difficulties questionnaire (SDQ). The utility of brain volumes at TEA, perinatal factors, and social economic risk for the prediction of behavioral outcome was investigated using support vector machine classifiers and permutation feature importance. RESULTS: The predictive modeling of the volumetric data showed that WM, amygdala, and CB volumes were the best predictors of the SDQ emotional symptoms score. Among the perinatal factors, sex, sepsis, and bronchopulmonary dysplasia were the best predictors of the hyperactivity/inattention score. When combining the social economic risk with volumetric and perinatal factors, we were able to accurately predict the emotional symptoms score. Finally, social economic risk was positively correlated with the scores of conduct problems and peer problems. CONCLUSIONS: This study provides information on the relation between brain structure at TEA and clinical perinatal factors with behavioral outcome at age 5 years in VPT children. Nevertheless, the overall predictive power of our models is relatively modest, and further research is needed to identify factors associated with subsequent behavioral problems in this population.

Musical memories in newborns: A resting-state functional connectivity study.

Music is known to induce emotions and activate associated memories, including musical memories. In adults, it is well known that music activates both working memory and limbic networks. We have recently discovered that as early as during the newborn period, familiar music is processed differently from unfamiliar music. The present study evaluates music listening effects at the brain level in newborns, by exploring the impact of familiar or first-time music listening on the subsequent resting-state functional connectivity in the brain. Using a connectome-based framework, we describe resting-state functional connectivity (RS-FC) modulation after music listening in three groups of newborn infants, in preterm infants exposed to music during their neonatal-intensive-care-unit (NICU) stay, in control preterm, and full-term infants. We observed modulation of the RS-FC between brain regions known to be implicated in music and emotions processing, immediately following music listening in all newborn infants. In the music exposed group, we found increased RS-FC between brain regions known to be implicated in familiar and emotionally arousing music and multisensory processing, and therefore implying memory retrieval and associative memory. We demonstrate a positive correlation between the occurrence of the prior music exposure and increased RS-FC in brain regions implicated in multisensory and emotional processing, indicating strong engagement of musical memories; and a negative correlation with the Default Mode Network, indicating disengagement due to the aforementioned cognitive processing. Our results describe the modulatory effect of music listening on brain RS-FC that can be linked to brain correlates of musical memory engrams in preterm infants.

Altered trajectory of neurodevelopment associated with fetal growth restriction.

Fetal growth restriction (FGR) is principally caused by suboptimal placental function. Poor placental function causes an under supply of nutrients and oxygen to the developing fetus, restricting development of individual organs and overall growth. Estimated fetal weight below the 10th or 3rd percentile with uteroplacental dysfunction, and knowledge regarding the onset of growth restriction (early or late), provide diagnostic criteria for fetuses at greatest risk for adverse outcome. Brain development and function is altered with FGR, with ongoing clinical and preclinical studies elucidating neuropathological etiology. During the third trimester of pregnancy, from ~28 weeks gestation, neurogenesis is complete and neuronal complexity is expanding, through axonal and dendritic outgrowth, dendritic branching and synaptogenesis, accompanied by myelin production. Fetal compromise over this period, as occurs in FGR, has detrimental effects on these processes. Total brain volume and grey matter volume is reduced in infants with FGR, first evident in utero, with cortical volume particularly vulnerable. Imaging studies show that cerebral morphology is disturbed in FGR, with altered cerebral cortex, volume and organization of brain networks, and reduced connectivity of long- and short-range circuits. Thus, FGR induces a deviation in brain development trajectory affecting both grey and white matter, however grey matter volume is preferentially reduced, contributed by cell loss, and reduced neurite outgrowth of surviving neurons. In turn, cell-to-cell local networks are adversely affected in FGR, and whole brain left and right intrahemispheric connections and interhemispheric connections are altered. Importantly, disruptions to region-specific brain networks are linked to cognitive and behavioral impairments.

Maternal Stress, Depression, and Attachment in the Neonatal Intensive Care Unit Before and During the COVID Pandemic: An Exploratory Study.

The main aim of the present study was to investigate the effects of the COVID-19 pandemic on the mothers' postnatal depression, stress, and attachment during their stay in the Neonatal Intensive Care Unit (NICU). Twenty mothers of very premature infants born before 32weeks of gestational age were recruited at the Geneva University Hospital between January 2018 and February 2020 before the COVID-19 pandemic started. Mothers were screened for postnatal depression after their preterm infant's birth (Edinburgh Postnatal Depression Scale, EPDS), then for stress (Parental Stressor Scale: Neonatal Intensive Care Unit, PSS:NICU), and attachment (Maternal Postnatal Attachment Scale, MPAS) at infant's term-equivalent age. Data were compared with 14 mothers recruited between November 2020 and June 2021 during the COVID-19 pandemic. No significant differences were found in the scores for depression, stress, and attachment between the two groups. However, a non-statistically significant trend showed a general increase of depression symptoms in mothers during the COVID-19 pandemic, which significantly correlated to the attachment and stress scores. Moreover, the PSS:NICU Sights and Sounds score was significantly positively correlated with EPDS scores and negatively with the MPAS score only in the During-COVID group. To conclude, we discussed a possible dampened effect of the several protective family-based actions that have been adopted in the Geneva University Hospital during the health crisis, and we discussed the most appropriate interventions to support parents in this traumatic period during the COVID-19 pandemic.

Altered orbitofrontal activation in preterm-born young adolescents during performance of a reality filtering task.

Preterm birth is one of the main causes for neurodevelopmental problems, and has been associated with a wide range of impairments in cognitive functions including executive functions and memory. One of the factors contributing to these adverse outcomes is the intrinsic vulnerability of the premature brain. Neuroimaging studies have highlighted structural and functional alterations in several brain regions in preterm individuals across lifetime. The orbitofrontal cortex (OFC) is crucial for a multitude of complex and adaptive behaviours, and its structure is particularly affected by premature birth. Nevertheless, studies on the functional impact of prematurity on the OFC are still missing. Orbitofrontal Reality filtering (ORFi) refers to the ability to distinguish if a thought is relevant to present reality or not. It can be tested using a continuous recognition task and is mediated by the OFC in adults and typically developing young adolescents. Therefore, the ORFi task was used to investigate whether OFC functioning is affected by prematurity. We compared the neural correlates of ORFi in 35 young adolescents born preterm (below 32 weeks of gestation) and aged 10 to 14 years with 25 full term-born controls. Our findings indicate that OFC activation was required only in the full-term group, whereas preterm young adolescents did not involve OFC in processing the ORFi task, despite being able to correctly perform it.

Shedding light on excessive crying in babies.

BACKGROUND: Excessive and inconsolable crying behavior in otherwise healthy infants (a condition called infant colic (IC)) is very distressing to parents, may lead to maternal depression, and in extreme cases, may result in shaken baby syndrome. Despite the high prevalence of this condition (20% of healthy infants), the underlying neural mechanisms of IC are still unknown. METHODS: By employing the latest magnetic resonance imaging (MRI) techniques in newborns, we prospectively investigated whether newborns' early brain responses to a sensory stimulus (smell) is associated with a subsequent crying behavior. RESULTS: In our sample population of 21 healthy breastfed newborns, those who developed IC at 6 weeks exhibited brain activation and functional connectivity in primary and secondary olfactory brain areas that were distinct from those in babies that did not develop IC. Different activation in brain regions known to be involved in sensory integration was also observed in colicky babies. These responses measured shortly after birth were highly correlated with the mean crying time at 6 weeks of age. CONCLUSIONS: Our results offer novel insights into IC pathophysiology by demonstrating that, shortly after birth, the central nervous system of babies developing IC has already greater reactivity to sensory stimuli than that of their noncolicky peers. IMPACT: Shortly after birth, the central nervous system of colicky infants has a greater sensitivity to olfactory stimuli than that of their noncolicky peers. This early sensitivity explains as much as 48% of their subsequent crying behavior at 6 weeks of life. Brain activation patterns to olfactory stimuli in colicky infants include not only primary olfactory areas but also brain regions involved in pain processing, emotional valence attribution, and self-regulation. This study links earlier findings in fields as diverse as gastroenterology and behavioral psychology and has the potential of helping healthcare professionals to define strategies to advise families.

MRI of the Neonatal Brain: A Review of Methodological Challenges and Neuroscientific Advances.

In recent years, exploration of the developing brain has become a major focus for researchers and clinicians in an attempt to understand what allows children to acquire amazing and unique abilities, as well as the impact of early disruptions (eg, prematurity, neonatal insults) that can lead to a wide range of neurodevelopmental disorders. Noninvasive neuroimaging methods such as MRI are essential to establish links between the brain and behavioral changes in newborns and infants. In this review article, we aim to highlight recent and representative studies using the various techniques available: anatomical MRI, quantitative MRI (relaxometry, diffusion MRI), multiparametric approaches, and functional MRI. Today, protocols use 1.5 or 3T MRI scanners, and specialized methodologies have been put in place for data acquisition and processing to address the methodological challenges specific to this population, such as sensitivity to motion. MR sequences must be adapted to the brains of newborns and infants to obtain relevant good soft-tissue contrast, given the small size of the cerebral structures and the incomplete maturation of tissues. The use of age-specific image postprocessing tools is also essential, as signal and contrast differ from the adult brain. Appropriate methodologies then make it possible to explore multiple neurodevelopmental mechanisms in a precise way, and assess changes with age or differences between groups of subjects, particularly through large-scale projects. Although MRI measurements only indirectly reflect the complex series of dynamic processes observed throughout development at the molecular and cellular levels, this technique can provide information on brain morphology, structural connectivity, microstructural properties of gray and white matter, and on the functional architecture. Finally, MRI measures related to clinical, behavioral, and electrophysiological markers have a key role to play from a diagnostic and prognostic perspective in the implementation of early interventions to avoid long-term disabilities in children. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY STAGE: 1.

Preterm birth leads to impaired rich-club organization and fronto-paralimbic/limbic structural connectivity in newborns.

Prematurity disrupts brain development during a critical period of brain growth and organization and is known to be associated with an increased risk of neurodevelopmental impairments. Investigating whole-brain structural connectivity alterations accompanying preterm birth may provide a better comprehension of the neurobiological mechanisms related to the later neurocognitive deficits observed in this population. Using a connectome approach, we aimed to study the impact of prematurity on neonatal whole-brain structural network organization at term-equivalent age. In this cohort study, twenty-four very preterm infants at term-equivalent age (VPT-TEA) and fourteen full-term (FT) newborns underwent a brain MRI exam at term age, comprising T2-weighted imaging and diffusion MRI, used to reconstruct brain connectomes by applying probabilistic constrained spherical deconvolution whole-brain tractography. The topological properties of brain networks were quantified through a graph-theoretical approach. Furthermore, edge-wise connectivity strength was compared between groups. Overall, VPT-TEA infants' brain networks evidenced increased segregation and decreased integration capacity, revealed by an increased clustering coefficient, increased modularity, increased characteristic path length, decreased global efficiency and diminished rich-club coefficient. Furthermore, in comparison to FT, VPT-TEA infants had decreased connectivity strength in various cortico-cortical, cortico-subcortical and intra-subcortical networks, the majority of them being intra-hemispheric fronto-paralimbic and fronto-limbic. Inter-hemispheric connectivity was also decreased in VPT-TEA infants, namely through connections linking to the left precuneus or left dorsal cingulate gyrus - two regions that were found to be hubs in FT but not in VPT-TEA infants. Moreover, posterior regions from Default-Mode-Network (DMN), namely precuneus and posterior cingulate gyrus, had decreased structural connectivity in VPT-TEA group. Our finding that VPT-TEA infants' brain networks displayed increased modularity, weakened rich-club connectivity and diminished global efficiency compared to FT infants suggests a delayed transition from a local architecture, focused on short-range connections, to a more distributed architecture with efficient long-range connections in those infants. The disruption of connectivity in fronto-paralimbic/limbic and posterior DMN regions might underlie the behavioral and social cognition difficulties previously reported in the preterm population.

Endogenous erythropoietin signaling regulates migration and laminar positioning of upper-layer neurons in the developing neocortex.

Erythropoietin (EPO), the hypoxia-inducible hematopoietic hormone, has well-established neuroprotective/neurotrophic roles in the developing central nervous system and the therapeutic potential of EPO has been widely explored in clinical studies for the treatment of perinatal hypoxic brain lesion, as well as prematurity. Here, we reveal that both EPO and Epo receptor (EPOR) are expressed in the developing rat somatosensory cortex during radial migration and laminar positioning of granular and supragranular neurons. Experimental deregulation of EPO signaling using genetic approaches results in aberrant migration, as well as permanent neuronal misplacement leading to abnormal network activity and protracted sensory behavioral deficits. We identify ERK as the downstream effector of the EPO signaling pathway for neuronal migration. These findings reveal a crucial role for endogenous EPO signaling in neuronal migration, and offer important insights for understanding how the temporary deregulation of EPO could result in migration defects that lead to abnormal behavior in the adult.

Neural Correlates of Voice Perception in Newborns and the Influence of Preterm Birth.

Maternal voice is a highly relevant stimulus for newborns. Adult voice processing occurs in specific brain regions. Voice-specific brain areas in newborns and the relevance of an early vocal exposure on these networks have not been defined. This study investigates voice perception in newborns and the impact of prematurity on the cerebral processes. Functional magnetic resonance imaging (fMRI) and high-density electroencephalography (EEG) were used to explore the brain responses to maternal and stranger female voices in full-term newborns and preterm infants at term-equivalent age (TEA). fMRI results and the EEG oddball paradigm showed enhanced processing for voices in preterms at TEA than in full-term infants. Preterm infants showed additional cortical regions involved in voice processing in fMRI and a late mismatch response for maternal voice, considered as a first trace of a recognition process based on memory representation. Full-term newborns showed increased cerebral activity to the stranger voice. Results from fMRI, oddball, and standard auditory EEG paradigms highlighted important change detection responses to novelty after birth. These findings suggest that the main components of the adult voice-processing networks emerge early in development. Moreover, an early postnatal exposure to voices in premature infants might enhance their capacity to process voices.

Transient tone anomalies in very preterm infants: Association with term-equivalent brain magnetic resonance imaging and neurodevelopment at 18 months.

BACKGROUND: Very preterm (VPT) infants are at risk for neurodevelopmental impairments and early clinical findings such as transient tone anomalies (TTA) might represent potential predictive indicators. AIMS: The aims of this study were to assess 1) the prevalence of TTA at 6 months corrected age in a population of VPT infants, 2) the association with term-equivalent age (TEA) brain MRI and 3) the neurodevelopmental outcome at 18 months corrected age. STUDY DESIGN AND SUBJECTS: A prospective case-control cohort of 103 VPT infants (<29 weeks of gestation) was followed up at 6 months and classified into TTA+ or TTA-. TTA+ was defined by the presence of ≥2 criteria among anomalies of posture, anomalies of tone and hyperreflexia. OUTCOME MEASURES: Conventional and diffusion-weighted MRIs at TEA were analyzed according to a semi-quantitative MRI scoring system and apparent diffusion coefficients (ADC) and fractional anisotropy (FA) were measured in frontal, occipital white matter and posterior limb of the internal capsule (PLIC). Neurodevelopment was assessed at 18 months using Bayley-II scales (Psychomotor Developmental Index: PDI; Mental Developmental Index: MDI). RESULTS: TTA+ infants represented 29.1% of the total population. They had: 1) significantly higher ADC values in 3 regions of interest (p < 0.001), 2) significant lower FA in the PLIC (p < 0.001), and 3) significant lower PDI score (p < 0.05). No differences were observed regarding MDI scores. Interaction of TTA by cerebellum score was related to lower MDI scores. CONCLUSIONS: In VPT infants, TTA at 6 months and/or structural brain abnormality at TEA are associated with poorer neurodevelopmental outcome at 18 months.

Time-resolved effective connectivity in task fMRI: Psychophysiological interactions of Co-Activation patterns.

Investigating context-dependent modulations of Functional Connectivity (FC) with functional magnetic resonance imaging is crucial to reveal the neurological underpinnings of cognitive processing. Most current analysis methods hypothesise sustained FC within the duration of a task, but this assumption has been shown too limiting by recent imaging studies. While several methods have been proposed to study functional dynamics during rest, task-based studies are yet to fully disentangle network modulations. Here, we propose a seed-based method to probe task-dependent modulations of brain activity by revealing Psychophysiological Interactions of Co-activation Patterns (PPI-CAPs). This point process-based approach temporally decomposes task-modulated connectivity into dynamic building blocks which cannot be captured by current methods, such as PPI or Dynamic Causal Modelling. Additionally, it identifies the occurrence of co-activation patterns at single frame resolution as opposed to window-based methods. In a naturalistic setting where participants watched a TV program, we retrieved several patterns of co-activation with a posterior cingulate cortex seed whose occurrence rates and polarity varied depending on the context; on the seed activity; or on an interaction between the two. Moreover, our method exposed the consistency in effective connectivity patterns across subjects and time, allowing us to uncover links between PPI-CAPs and specific stimuli contained in the video. Our study reveals that explicitly tracking connectivity pattern transients is paramount to advance our understanding of how different brain areas dynamically communicate when presented with a set of cues.

Early vocal contact and music in the NICU: new insights into preventive interventions.

It is now clearly established that the environment and the sensory stimuli, particularly during the perinatal period, have an impact on infant's development. During the last trimester of gestation, activity-dependent plasticity shapes the fetal brain, and prematurity has been shown to alter the typical developmental trajectories. In this delicate period, preventive interventions aiming at modulating these developmental trajectories through activity-inducing interventions are currently underway to be tested. The purpose of this review paper is to describe the potentialities of early vocal contact and music on the preterm infant's brain development, and their potential beneficial effect on early development. Scientific evidence supports a behavioral orientation of the newborn to organized sounds, such as those of voice and music, and recent neuroimaging studies further confirm full cerebral processing of music as multisensory stimuli. However, the impact of long-term effects of music exposure and early vocal contact on preterm infants' long-term neurodevelopment needs be further investigated. To conclude, it is necessary to establish the neuroscientific bases of the early perception and the long-term effects of music and early vocal contact on the premature newborns' development. Scientific projects are currently on the way to fill this gap in knowledge.

Neural functional correlates of the impact of socio-emotional stimuli on performances on a flanker task in children aged 9-11 years.

Immature cognition is susceptible to interference from competing information, and particularly in affectively charged situations. Several studies have reported activation in the anterior cingulate cortex, prefrontal cortex and amygdala associated with emotional conflict processing in adults but literature is lacking regarding children. Moreover, studies in children and adolescents still disagree regarding the functional activation of amygdala related to facial stimuli. In the purpose of investigating both the effect of socio-emotional stimuli and its interaction with interference control, we designed a flanker task associated with an event-related fMRI paradigm in 30 healthy children ages 9-11. In addition to happy, angry and neutral faces, we presented scrambled stimuli to examine a potential effect of faces. Regarding both brain and behavior results, no effect of emotional valence was observed. However, both results evidenced an emotional effect of faces compared with scrambled stimuli. This was expressed by faster RTs associated with increased amygdala activity and activation of the ventral ACC, in congruent trials only. When scrambled were inversely compared to faces, increased activity was observed within the lateral prefrontal cortex. Regarding the amygdala, the results suggest that in late school age children, activity in the amygdala seemed to underlie the socio-emotional effect induced by faces but not the emotional conflict. Studying brain regions involved in emotion regulation is important to further understand neurodevelopmental disorders and psychopathologies, particularly in late childhood and adolescence.

Music enhances structural maturation of emotional processing neural pathways in very preterm infants.

Prematurity disrupts brain maturation by exposing the developing brain to different noxious stimuli present in the neonatal intensive care unit (NICU) and depriving it from meaningful sensory inputs during a critical period of brain development, leading to later neurodevelopmental impairments. Musicotherapy in the NICU environment has been proposed to promote sensory stimulation, relevant for activity-dependent brain plasticity, but its impact on brain structural maturation is unknown. Neuroimaging studies have demonstrated that music listening triggers neural substrates implied in socio-emotional processing and, thus, it might influence networks formed early in development and known to be affected by prematurity. Using multi-modal MRI, we aimed to evaluate the impact of a specially composed music intervention during NICU stay on preterm infant's brain structure maturation. 30 preterm newborns (out of which 15 were exposed to music during NICU stay and 15 without music intervention) and 15 full-term newborns underwent an MRI examination at term-equivalent age, comprising diffusion tensor imaging (DTI), used to evaluate white matter maturation using both region-of-interest and seed-based tractography approaches, as well as a T2-weighted image, used to perform amygdala volumetric analysis. Overall, WM microstructural maturity measured through DTI metrics was reduced in preterm infants receiving the standard-of-care in comparison to full-term newborns, whereas preterm infants exposed to the music intervention demonstrated significantly improved white matter maturation in acoustic radiations, external capsule/claustrum/extreme capsule and uncinate fasciculus, as well as larger amygdala volumes, in comparison to preterm infants with standard-of-care. These results suggest a structural maturational effect of the proposed music intervention on premature infants' auditory and emotional processing neural pathways during a key period of brain development.