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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.

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.

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.