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Consisting of distributed and interconnected structures that interact through cortico-cortical connections and cortico-subcortical loops, the sensorimotor (SM) network undergoes rapid maturation during the perinatal period and is thus particularly vulnerable to preterm birth. However, the impact of prematurity on the development and integrity of the emerging SM connections and their relationship to later motor and global impairments are still poorly understood. In this study we aimed to explore to which extent the early microstructural maturation of SM white matter (WM) connections at term-equivalent age (TEA) is modulated by prematurity and related with neurodevelopmental outcome at 18 months corrected age. We analyzed 118 diffusion MRI datasets from the developing Human Connectome Project (dHCP) database: 59 preterm (PT) low-risk infants scanned near TEA and a control group of full-term (FT) neonates paired for age at MRI and sex. We delineated WM connections between the primary SM cortices (S1, M1 and paracentral region) and subcortical structures using probabilistic tractography, and evaluated their microstructure with diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) models. To go beyond tract-specific univariate analyses, we computed a maturational distance related to prematurity based on the multi-parametric Mahalanobis distance of each PT infant relative to the FT group. Our results confirmed the presence of microstructural differences in SM tracts between PT and FT infants, with effects increasing with lower gestational age at birth. Maturational distance analyses highlighted that prematurity has a differential effect on SM tracts with higher distances and thus impact on (i) cortico-cortical than cortico-subcortical connections; (ii) projections involving S1 than M1 and paracentral region; and (iii) the most rostral cortico-subcortical tracts, involving the lenticular nucleus. These different alterations at TEA suggested that vulnerability follows a specific pattern coherent with the established WM caudo-rostral progression of maturation. Finally, we highlighted some relationships between NODDI-derived maturational distances of specific tracts and fine motor and cognitive outcomes at 18 months. As a whole, our results expand understanding of the significant impact of premature birth and early alterations on the emerging SM network even in low-risk infants, with possible relationship with neurodevelopmental outcomes. This encourages further exploration of these potential neuroimaging markers for prediction of neurodevelopmental disorders, with special interest for subtle neuromotor impairments frequently observed in preterm-born children.

In carefully designed experiments, cognitive scientists interpret the mean event-related potentials (ERP) in terms of cognitive operations. However, the huge signal variability from one trial to the next, questions the representability of such mean events. We explored here whether this variability is an unwanted noise, or an informative part of the neural response. We took advantage of the rapid changes in the visual system during human infancy and analyzed the variability of visual responses to central and lateralized faces in 2-to 6-month-old infants and adults using high-density electroencephalography (EEG). We observed that neural trajectories of individual trials always remain very far from ERP components, only moderately bending their direction with a substantial temporal jitter across trials. However, single trial trajectories displayed characteristic patterns of acceleration and deceleration when approaching ERP components, as if they were under the active influence of steering forces causing transient attraction and stabilization. These dynamic events could only partly be accounted for by induced microstate transitions or phase reset phenomena. Furthermore, these structured modulations of response variability, both between and within trials, had a rich sequential organization, which, in infants, was modulated by the task difficulty. Our approaches to characterize Event Related Variability (ERV) expand and reinterpret classic ERP analyses, making them compliant with pervasive neural variability and providing a more faithful description of neural events following stimulus presentation.

International audience; In the human brain, the appearance of cortical sulci is a complex process that takes place mostly during the second half of pregnancy, with a relatively stable temporal sequence across individuals. Since deviant gyrification patterns have been observed in many neurodevelopmental disorders, mapping cortical development in vivo from the early stages on is an essential step to uncover new markers for diagnosis or prognosis. Recently this has been made possible by MRI combined with post-processing tools, but the reported results are still fragmented. Here we aimed to characterize the typical folding progression ex utero from the pre- to the post-term period, by considering 58 healthy preterm and full-term newborns and infants imaged between 27 and 62 weeks of post-menstrual age. Using a method of spectral analysis of gyrification (SPANGY), we detailed the spatial-frequency structure of cortical patterns in a quantitative way. The modeling of developmental trajectories revealed three successive waves that might correspond to primary, secondary and tertiary folding. Some deviations were further detected in 10 premature infants without apparent neurological impairment and imaged at term equivalent age, suggesting that our approach is sensitive enough to highlight the subtle impact of preterm birth and extra-uterine life on folding.

Exploring the developing brain is a major issue in understanding what enables children to acquire amazing abilities, and how early disruptions can lead to a wide range of neurodevelopmental disorders. MRI plays a key role here by providing a noninvasive way to link brain and behavioral changes. Several modalities are used in newborns and infants to characterize the properties of the developing brain, from growth, morphology to microstructure and functional specialization. Recent multimodal studies have sought to couple complementary MRI markers to provide a more integrated view of brain development. In this chapter, we describe successively how these approaches have made it possible to assess the early maturation of brain tissues, to link different aspects of structural development, and to compare structural and functional brain development.

Brain development incorporates several intermingled mechanisms throughout infancy leading to intense and asynchronous maturation across cerebral networks and functional modalities. Combining electroencephalography (EEG) and diffusion magnetic resonance imaging (MRI), previous studies in the visual modality showed that the functional maturation of the event-related potentials (ERP) during the first postnatal semester relates to structural changes in the corresponding white matter pathways. Here we aimed to investigate similar issues in the auditory modality. We measured ERPs to syllables in 1-to 6-month-old infants and analyzed them in relation with the maturational properties of underlying neural substrates measured with diffusion tensor imaging (DTI). We first observed a decrease in the latency of the auditory P2, and a decrease of diffusivities in the auditory tracts and perisylvian regions with age. Secondly, we highlighted some of the early functional and structural substrates of lateralization. Contralateral responses to monoaural syllables were stronger and faster than ipsilateral responses, particularly in the left hemisphere. Besides, the acoustic radiations, arcuate fasciculus, middle temporal and angular gyri showed DTI asymmetries with a more complex and advanced microstructure in the left hemisphere, whereas the reverse was observed for the inferior frontal and superior temporal gyri. Finally, after accounting for the age-related variance, we correlated the inter-individual variability in P2 responses and in the microstructural properties of callosal fibers and inferior frontal regions. This study combining dedicated EEG and MRI approaches in infants highlights the complex relation between the functional responses to auditory stimuli and the maturational properties of the corresponding neural network.

International audience; Already during the last trimester of gestation, functional responses are recorded in foetuses and preterm newborns, attesting an already complex cerebral architecture. Then throughout childhood, anatomical connections are further refined but at different rates and over asynchronous periods across functional networks. Concurrently, infants gradually achieve new psychomotor and cognitive skills. Only the recent use of non-invasive techniques such as magnetic resonance imaging (MRI) and magneto-and electroencephalography (M/EEG) has opened the possibility to understand the relationships between brain maturation and skills development in vivo. In this review, we describe how these techniques have been applied to study the white matter maturation. At the structural level, the early architecture and myelination of bundles have been assessed with diffusion and relaxometry MRI, recently integrated in multi-compartment models and multi-parametric approaches. Nevertheless, technical limitations prevent us to map major developmental mechanisms such as fibers growth and pruning, and the progressive maturation at the bundle scale in case of mixing trajectories. At the functional level, M/EEG have been used to record different visual, somatosensory and auditory evoked responses. Because the conduction velocity of neural impulses increases with the myelination of connections, major changes in the components latency are observed throughout development. But so far, only a few studies have related structural and functional markers of white matter myelination. Such multi-modal approaches will be a major challenge in future research, not only to understand normal development, but also to characterize early mechanisms of pathologies and the influence of fetal and perinatal interventions on later outcome.

The development of the human brain is a complex process that starts during early pregnancy and extends until the end of adolescence. In parallel to morphological changes in brain size and gyrification, several microstructural changes occur in the cortex, such as the development of dendritic arborization, synaptogenesis and pruning, and fiber myelination. Magnetic Resonance Imaging (MRI) can provide indirect markers of these mechanisms through the mapping of quantitative parameters. Here, we used a dedicated methodological framework to perform reliable voxel-wise analyses over the infant cortex. The examination of hemispheric asymmetries in microstructure required careful alignment of morphological asymmetries through registration of native and flipped brains using a 2-step matching strategy of sulci (DISCO approach) and cortical ribbon (DARTEL approach). We tested the potential of this approach in 1-to-5-month-old infants, with a focus on cortical longitudinal diffusivity from Diffusion Tensor Imaging (DTI). This enabled us to unravel different microstructural evolution patterns of specific sensorimotor and language regions in the left and right hemispheres.

Cortical folding in humans is different for every individual, and is associated with functional specificities. It forms mainly during the last trimester of pregnancy, hence its development lacks description, especially in a longitudinal way. To cope with this issue, this study focused on the evolution of the central sulcus’ variability of 71 preterm infants studied longitudinally with MRI at 30 and 40 weeks (w) postmenstrual age (PMA). Our aim was to investigate the main shape characteristics and whether they are encoded early on or appear closer to term birth. We captured shape dissimilarity between the sulci using a distance matrix after pairwise co-registration using an Iterative Closest Point algorithm. We applied non-linear dimensionality reduction to this matrix using the Isomap algorithm in order to capture the most discriminative shape features among the central sulci. We characterized the three most discriminative features over the group, and found that the sulci evolved consistently from a given feature at 30w PMA to the 40w PMA equivalent feature. We incidentally captured a feature that could coincide with the most discriminative adult feature, both visually and by its asymmetry in left and right sulcal distribution. These results captured the main shape features of the central sulcus in preterm infants and suggest that they are already encoded at 30w PMA.

International audience; Shortly after reading instruction, a region in the ventral occipital temporal cortex (vOTC) of the left hemisphere, the Visual Word Form Area (VWFA), becomes specialized for written words. Its reproducible location across scripts suggests important anatomical constraints, such as specific patterns of connectivity, notably to spoken language areas. Here, we explored the structural connectivity of the emerging VWFA in terms of its specificity relative to other ventral visual regions and its stability throughout the process of reading instruction in 10 children studied longitudinally over 2 years. Category-specific regions for words, houses, faces, and tools were identified in the left vOTC of each subject with functional MRI. With diffusion MRI and tractography, we reconstructed the connections of these regions at two time points (mean age ± standard deviation: 6.2±0.3, 7.2±0.4 years). We first showed that the regions for each visual category harbor their own specific connectivity, all of which precede reading instruction and remain stable throughout development. The most specific connections of the VWFA were to the dorsal posterior parietal cortex. We then showed that microstructural changes in these connections correlated with improvements in reading scores over the first year of instruction but not one year later in a subsample of 8 children (age: 8.4±0.3 years). These results suggest that the VWFA location depends on its connectivity to distant regions, in particular the left inferior parietal region which may play a crucial role in visual field maps and eye movement dynamics in addition to attentional control in letter-by-letter reading and disambiguation of mirror letters during the first stages of learning to read.

International audience; Dynamic macrostructural and microstructural changes take place from the mid-fetal stage to 2 years after birth. Delineating structural changes of the brain during early development provides new insights into the complicated processes of both typical development and the pathological mechanisms underlying various psychiatric and neurological disorders including autism, attention deficit hyperactivity disorder and schizophrenia. Decades of histological studies have identified strong spatial and functional maturation gradients in human gray and white matter. The recent improvements in magnetic resonance imaging (MRI) techniques, especially diffusion MRI (dMRI), relaxometry imaging, and magnetization transfer imaging (MTI) have provided unprecedented opportunities to non-invasively quantify and map the early developmental changes at whole brain and regional levels. Here, we review the recent advances in understanding early brain structural development during the second half of gestation and the first two postnatal years using modern MR techniques. Specifically, we review studies that delineate the emergence and microstructural maturation of white matter tracts, as well as dynamic mapping of inhomogeneous cortical microstructural organization unique to fetuses and infants. These imaging studies converge into maturational curves of MRI measurements that are distinctive across different white matter tracts and cortical regions. Furthermore, contemporary models offering biophysical interpretations of the dMRI-derived measurements are illustrated to infer the underlying microstructural changes. Collectively, this review summarizes findings that contribute to charting spatiotemporally heterogeneous gray and white matter structural development, offering MRI-based biomarkers of typical brain development and setting the stage for understanding aberrant brain development in neurodevelopmental disorders.

International audience; Characteristic preterm EEG patterns of "Delta-brushes" (DBs) have been reported in the temporal cortex following auditory stimuli, but their spatio-temporal dynamics remains elusive. Using 32-electrode EEG recordings and co-registration of electrodes' position to 3D-MRI of age-matched neonates, we explored the cortical auditory-evoked responses (AERs) after 'click' stimuli in 30 healthy neonates aged 30-38 post-menstrual weeks (PMW). (1) We visually identified auditory-evoked DBs within AERs in all the babies between 30 and 33 PMW and a decreasing response rate afterwards. (2) The AERs showed an increase in EEG power from delta to gamma frequency bands over the middle and posterior temporal regions with higher values in quiet sleep and on the right. (3) Time-frequency and averaging analyses showed that the delta component of DBs, which negatively peaked around 550 and 750 ms over the middle and posterior temporal regions, respectively, was superimposed with fast (alpha-gamma) oscillations and corresponded to the late part of the cortical auditory-evoked potential (CAEP), a feature missed when using classical CAEP processing. As evoked DBs rate and AERs delta to alpha frequency power decreased until full term, auditory-evoked DBs are thus associated with the prenatal development of auditory processing and may suggest an early emerging hemispheric specialization.

International audience; The left hemisphere specialization for language is a well-established asymmetry in the human brain. Structural and functional asymmetries are observed as early as the prenatal period suggesting genetically determined differences between both hemispheres. The corpus callosum is a large tract connecting mostly homologous areas; some have proposed that it might participate in an enhancement of the left-hemispheric advantage to process speech. To investigate its role in early development, we compared 13 3-4-month-old infants with an agenesis of the corpus callosum ("AgCC") with 18 typical infants using high-density electroencephalography (EEG) in an auditory task. We recorded event-related potentials (ERP) for speech stimuli (syllables and babbling noise), presented binaurally (same syllable in both ears), monaurally (babbling noise in one ear) and dichotically (syllable in one ear and babbling noise in the other ear). In response to these stimuli, both groups developed an anterior positivity synchronous with a posterior negativity, yet the topography significantly differed between groups likely due to the atypical gyration of the medial surface in AgCC. In particular, the anterior positivity was lateral in AgCC infants while it covered the midline in typical infants. We then measured the latencies of the main auditory response (P2 at this age) for the different conditions on the symmetrical left and right clusters. The main difference between groups was a ~60 ms delay in typical infants relative to AgCC, for the ipsilateral response (i.e. left hemisphere) to babbling noise presented in the left ear, whereas no difference was observed in the case of right-ear stimulation. We suggest that our results highlight an asymmetrical callosal connectivity favoring the right-to-left hemisphere direction in typical infants. This asymmetry, similar to recent descriptions in adults, might contribute to an enhancement of left lateralization for language processing beyond the initial cortical left-hemisphere advantage.

The ontogeny of the functional asymmetries of the human brain is poorly understood. Are they a consequence of differential development based on competition mechanisms, or are they constitutive of the human brain architecture from the start? Using structural magnetic resonance imaging and a face-discrimination electroencephalography paradigm with lateralized presentation of faces, we studied face perception in infants over the first postnatal semester. We showed that the corpus callosum is sufficiently mature to transfer visual information across hemispheres, but the inter-hemispheric transfer time of early visual responses is modulated by callosal fibre myelination. We also revealed that only the right hemisphere shows evidence of face discrimination when presented in the left visual hemifield. This capability improved throughout the first semester with no evidence of discrimination in the left hemisphere. Face-processing lateralization is thus a characteristic of the infant's extra-striate visual cortex, highlighting the differential left-right organization of the human brain already established in infanthood.

Identifying potentially unique features of the human cerebral cortex is a first step to understanding how evolution has shaped the brain in our species. By analyzing MR images obtained from 177 humans and 73 chimpanzees, we observed a human-specific asymmetry in the superior temporal sulcus at the heart of the communication regions and which we have named the "superior temporal asymmetrical pit" (STAP). This 45-mm-long segment ventral to Heschl's gyrus is deeper in the right hemisphere than in the left in 95% of typical human subjects, from infanthood till adulthood, and is present, irrespective of handedness, language lateralization, and sex although it is greater in males than in females. The STAP also is seen in several groups of atypical subjects including persons with situs inversus, autistic spectrum disorder, Turner syndrome, and corpus callosum agenesis. It is explained in part by the larger number of sulcal interruptions in the left than in the right hemisphere. Its early presence in the infants of this study as well as in fetuses and premature infants suggests a strong genetic influence. Because this asymmetry is barely visible in chimpanzees, we recommend the STAP region during midgestation as an important phenotype to investigate asymmetrical variations of gene expression among the primate lineage. This genetic target may provide important insights regarding the evolution of the crucial cognitive abilities sustained by this sulcus in our species, namely communication and social cognition.

International audience; While the main neural networks are in place at term birth, intense changes in cortical microstructure occur during early infancy with the development of dendritic arborization, synaptogenesis and fiber myelination. These maturational processes are thought to relate to behavioral acquisitions and the development of cognitive abilities. Nevertheless, in vivo investigations of such relationships are still lacking in healthy infants. To bridge this gap, we aimed to study the cortical maturation using non-invasive Magnetic Resonance Imaging, over a largely unexplored period (1-5 post-natal months). In a first univariate step, we focused on different quantitative parameters: longitudinal relaxation time (T1), transverse relaxation time (T2), and axial diffusivity from diffusion tensor imaging (λ//) These individual maps, acquired with echo-planar imaging to limit the acquisition time, showed spatial distortions that were first corrected to reliably match the thin cortical ribbon identified on high-resolution T2-weighted images. Averaged maps were also computed over the infants group to summarize the parameter characteristics during early infancy. In a second step, we considered a multi-parametric approach that leverages parameters complementarity, avoids reliance on pre-defined regions of interest, and does not require spatial constraints. Our clustering strategy allowed us to group cortical voxels over all infants in 5 clusters with distinct microstructural T1 and λ// properties The cluster maps over individual cortical surfaces and over the group were in sound agreement with benchmark post mortem studies of sub-cortical white matter myelination, showing a progressive maturation of 1) primary sensori-motor areas, 2) adjacent unimodal associative cortices, and 3) higher-order associative regions. This study thus opens a consistent approach to study cortical maturation in vivo.

Developmental research, as well as paediatric clinical activity crucially depends on non-invasive and painless brain recording techniques, such as electroencephalography (EEG), and near infrared spectroscopy (NIRS). However, both of these techniques measure cortical activity from the scalp without precise knowledge of the recorded cerebral structures. An accurate and reliable mapping between external anatomical landmarks and internal cerebral structures is therefore fundamental to localise brain sources in a non-invasive way. Here, using MRI, we examined the relations between the 10-20 sensor placement system and cerebral structures in 16 infants (3-17 weeks post-term). We provided an infant template parcelled in 94 regions on which we reported the variability of sensors locations, concurrently with the anatomical variability of six main cortical sulci (superior and inferior frontal sulcus, central sulcus, sylvian fissure, superior temporal sulcus, and intraparietal sulcus) and of the distances between the sensors and important cortical landmarks across these infants. The main difference between infants and adults was observed for the channels O1-O2, T5-T6, which projected over lower structures than in adults. We did not find any asymmetry in the distances between the scalp and the brain envelope. However, because of the Yakovlean torque pushing dorsally and frontally the right sylvian fissure, P3-P4 were not at the same distance from the posterior end of this structure. This study should help to refine hypotheses on functional cognitive development by providing an accurate description of the localization of standardised channels relative to infants' brain structures. Template and atlas are publicly available on our Web site (http://www.unicog.org/pm/pmwiki.php/Site/InfantTemplate).

Studying how the healthy human brain develops is important to understand early pathological mechanisms and to assess the influence of fetal or perinatal events on later life. Brain development relies on complex and intermingled mechanisms especially during gestation and first post-natal months, with intense interactions between genetic, epigenetic and environmental factors. Although the baby's brain is organized early on, it is not a miniature adult brain: regional brain changes are asynchronous and protracted, i.e. sensory-motor regions develop early and quickly, whereas associative regions develop later and slowly over decades. Concurrently, the infant/child gradually achieves new performances, but how brain maturation relates to changes in behavior is poorly understood, requiring non-invasive in vivo imaging studies such as magnetic resonance imaging (MRI). Two main processes of early white matter development are reviewed: (1) establishment of connections between brain regions within functional networks, leading to adult-like organization during the last trimester of gestation, (2) maturation (myelination) of these connections during infancy to provide efficient transfers of information. Current knowledge from post-mortem descriptions and in vivo MRI studies is summed up, focusing on T1- and T2-weighted imaging, diffusion tensor imaging, and quantitative mapping of T1/T2 relaxation times, myelin water fraction and magnetization transfer ratio.

The ontogeny of linguistic functions in the human brain remains elusive. Although some auditory capacities are described before term, whether and how such immature cortical circuits might process speech are unknown. Here we used functional optical imaging to evaluate the cerebral responses to syllables at the earliest age at which cortical responses to external stimuli can be recorded in humans (28- to 32-wk gestational age). At this age, the cortical organization in layers is not completed. Many neurons are still located in the subplate and in the process of migrating to their final location. Nevertheless, we observed several points of similarity with the adult linguistic network. First, whereas syllables elicited larger right than left responses, the posterior temporal region escaped this general pattern, showing faster and more sustained responses over the left than over the right hemisphere. Second, discrimination responses to a change of phoneme (ba vs. ga) and a change of human voice (male vs. female) were already present and involved inferior frontal areas, even in the youngest infants (29-wk gestational age). Third, whereas both types of changes elicited responses in the right frontal region, the left frontal region only reacted to a change of phoneme. These results demonstrate a sophisticated organization of perisylvian areas at the very onset of cortical circuitry, 3 mo before term. They emphasize the influence of innate factors on regions involved in linguistic processing and social communication in humans.

International audience; The volume fraction of water related to myelin (f my) is a promising MRI index for in vivo assessment of brain myelination, that can be derived from multi-component analysis of T1 and T2 relaxometry signals. However, existing quantification methods require rather long acquisition and/or post-processing times, making implementation difficult both in research studies on healthy unsedated children and in clinical examinations. The goal of this work was to propose a novel strategy for f my quantification within acceptable acquisition and post-processing times. Our approach is based on a 3-compartment model (myelin-related water, intra/extra-cellular water and unrestricted water), and uses calibrated values of inherent relaxation times (T1 c and T2 c) for each compartment c. Calibration was first performed on adult relaxometry datasets (N = 3) acquired with large numbers of inversion times (TI) and echo times (TE), using an original combination of a region contraction approach and a non-negative least-square (NNLS) algorithm. This strategy was compared with voxel-wise fitting, and showed robust estimation of T1 c and T2 c. The accuracy of f my calculations depending on multiple factors was investigated using simulated data. In the testing stage, our strategy enabled fast f my mapping, based on relaxometry datasets acquired with reduced TI and TE numbers (acquisition

International audience; In the developing human brain, gyrification is a complex process going through the successive appearance of primary folds (from 20 weeks of gestational age GA), secondary folds (from 32w GA) and tertiary folds (around term age). While this sequence is finely described in fetuses and preterm newborns of different ages using MRI and folding indices, there is still no fully objective assessment of the folding stage at the individual level. We examined the potential of a new method of spectral analysis of gyrification (SPANGY) that was applied to cortical surfaces of 26 preterm newborns, 9 full-term newborns and 17 infants to quantify the spatial-frequency structure of folding. Based on modelling approaches, we unraveled 4 periods along the developmental sequence from 27 to 62w GA, with relevant timepoints around 31w, 36-38w, and 44-47w GA. These periods showed specific folding features, with spatial patterns of increasing frequencies.

International audience; Linguistic processing is based on a close collaboration between temporal and frontal regions connected by two pathways: the "dorsal" and "ventral pathways" (assumed to support phonological and semantic processing respectively in adults). We investigated here the development of these pathways at the onset of language acquisition, during the first post-natal weeks, using cross-sectional diffusion imaging in 21 healthy infants (6 to 22 weeks of age) and 17 young adults. We compared the bundle organization and microstructure at these two ages using tractography and original clustering analyses of DTI parameters. We observed structural similarities between both groups, especially concerning the dorsal/ventral pathway segregation and the arcuate fasciculus asymmetry. We further highlighted the developmental tempos of the linguistic bundles: the ventral pathway maturation was more advanced than the dorsal pathway maturation, but the latter catches up during the first post-natal months. Its fast development during this period might relate to the learning of speech cross-modal representations and to the first combinatorial analyses of the speech input.

The deformable atlas paradigm has been at the core of computational anatomy during the last two decades. Spatial normalization is the variant endowing the atlas with a coordinate system used for voxel-based aggregation of images across subjects and studies. This framework has largely contributed to the success of brain mapping. Brain spatial normalization, however, is still ill-posed because of the complexity of the human brain architecture and the lack of architectural landmarks in standard morphological MRI. Multi-atlas strategies have been developed during the last decade to overcome some difficulties in the context of segmentation. A new generation of registration algorithms embedding architectural features inferred for instance from diffusion or functional MRI is on the verge to improve the architectural value of spatial normalization. A better understanding of the architectural meaning of the cortical folding pattern will lead to use some sulci as complementary constraints. Improving the architectural compliance of spatial normalization may impose to relax the diffeomorphic constraint usually underlying atlas warping. A two-level strategy could be designed: in each region, a dictionary of templates of incompatible folding patterns would be collected and matched in a way or another using rare architectural information, while individual subjects would be aligned using diffeomorphisms to the closest template. Manifold learning could help to aggregate subjects according to their morphology. Connectivity-based strategies could emerge as an alternative to deformation-based alignment leading to match the connectomes of the subjects rather than images.

The description of cortical folding pattern (CFP) is challenging because of geometric complexity and inter-subject variability. On a cortical surface mesh, curvature estimation provides a good scalar proxy of CFP. The oscillations of this function can be studied using a Fourier-like analysis to produce a power spectrum representative of the spatial frequency composition of CFP. First, we introduce an original method for the SPectral ANalysis of GYrication (Spangy), which performs a spectral decomposition of the mean curvature of the grey/white interface mesh based on the Laplace-Beltrami operator eigenfunctions. Spangy produces an ordered 7 bands power spectrum of curvature (B0-B6) and provides an anatomically relevant segmentation of CFP based on local spectral composition. A spatial frequency being associated with each eigenfunction, the bandwidth design assumes frequency doubling between consecutive spectral bands. Next, we observed that the last 3 spectral bands (B4, 5 and 6) accounted for 93% of the analyzed spectral power and were associated with fold-related variations of curvature, whereas the lower frequency bands were related to global brain shape. The spectral segmentation of CFP revealed 1st, 2nd and 3rd order elements associated with B4, B5 and B6 respectively. These elements could be related to developmentally-defined primary, secondary and tertiary folds. Finally, we used allometric scaling of frequency bands power and segmentation to analyze the relationship between the spectral composition of CFP and brain size in a large adult dataset. Total folding power followed a positive allometric scaling which did not divide up proportionally between the bands: B4 contribution was constant, B5 increased like total folding power and B6 much faster. Besides, apparition of new elements of pattern with increasing size only concerned the 3rd order. Hence, we demonstrate that large brains are twistier than smaller ones because of an increased number of high spatial frequency folds, ramifications and kinks that accommodate the allometric increase of cortical surface.

Studying how the brain develops and becomes functional is important to understand how the man has been able to develop specific cognitive abilities, and to comprehend the complexity of some developmental pathologies. Thanks to magnetic resonance imaging (MRI), it is now possible to image the baby's immature brain and to consider subtle correlations between the brain anatomical development and the early acquisition of cognitive functions. Dedicated methodologies for image acquisition and post-treatment must then be used because the size of cerebral structures and the image contrast are very different in comparison with the adult brain, and because the examination length is a major constraint. Two recent studies have evaluated the developing brain under an original perspective. The first one has focused on cortical folding in preterm newborns, from 6 to 8 months of gestational age, assessed with T2-weighted conventional MRI. The second study has mapped the organization and maturation of white matter fiber bundles in 1- to 4-month-old healthy infants with diffusion tensor imaging (DTI). Both studies have enabled to highlight spatio-temporal differences in the brain regions' maturation, as well as early anatomical asymmetries between cerebral hemispheres. These studies emphasize the potential of MRI to evaluate brain development compared with the infant's psychomotor acquisitions after birth.

Pendant le developpement prenatal et postnatal precoce, les activites electriques synchrones peuvent etre generees au sein des cortex sensoriels eux-memes, des structures sous-corticales ou etre evoquees par l’activite des organes sensoriels, elle-meme spontanee ou provoquee par les stimuli sensoriels. L’un des patterns EEG typique du premature, le « Delta-brush » (DB), qui associe une onde lente et des oscillations rapides, peut etre genere de facon spontanee ou etre evoque dans les cortex sensorimoteur, visuel et auditif par les mouvements et par les stimuli sensoriels correspondants. L’objectif de la presente etude, dediee aux reponses corticales aux stimuli auditifs (click), etait de preciser les caracteristiques spatio-temporelles des DBs evoques ainsi que leur rapport avec des potentiels evoques auditifs corticaux du premature tel que decrits anterieurement. Pour cela, les enregistrements EEG ont ete realises en haute resolution (32 electrodes) chez 30 nouveau-nes prematures de 30 a 38 semaines d’âge gestationnel sans risque neurologique et la position des electrodes a ete recalee sur des IRM 3D acquis chez d’autres prematures representatifs des âges etudies. L’analyse spectrale des reponses au click a montre une augmentation significative de la puissance spectrale dans une large bande des frequences, situee au niveau de la partie moyenne et posterieure du lobe temporal. Ces reponses du cortex temporal avaient une predominance droite, etaient plus amples dans le sommeil calme et diminuaient en puissance avec l’âge. Le moyennage des reponses a revele que la composante lente du DB etait une onde lente negative de grande amplitude qui culminait dans les regions temporales moyenne et posterieure successivement a 550 et 700 ms et correspondait au pole negatif d’un dipole s’inversant dans la region temporo-peri-sylvienne. Le DB evoque par les stimuli auditifs reflete probablement l’activite du cortex auditif et represente un biomarqueur potentiel du fonctionnement normal du cortex auditif chez le premature.