Publications

Published on December 2, 2025

Premature birth impacts the development of superior temporal brain regions, including the superior temporal sulcus (STS), a key cortical area for language, voice recognition, and music processing. Using three distinct newborn imaging datasets, we examined the impact of premature birth on STS morphology at term-equivalent age.

In the large cohort of the Developing Human Connectome Project (dHCP), we observed a linear relationship between gestational age at birth and STS depth, with earlier birth associated with a shallower STS. We hypothesized that this effect may have resulted from reduced structured auditory stimulation during a critical period of perisylvian network development. To test this hypothesis, we analyzed two additional published cohorts in which preterm neonates were exposed to contrasting auditory environments: either enhanced with structured music or minimized in quiet private rooms. We found that music exposure was associated with deeper STS, while a quieter environment was linked to further STS shallowing.

Although the cross-sectional design limits causal inference, our findings suggest that early auditory experience—both in and ex utero—may influence the structural development of temporal brain regions. These results highlight the need to deepen our understanding of environmental influences in order to optimize postnatal settings that support the harmonious development of auditory and language networks.

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Published onDecember 7, 2025

Preventing gender disparities in mathematics is a worldwide concern. In infancy and early childhood, boys and girls exhibit similar core knowledge of numbers and space. Gender disparities in maths are, therefore, thought to primarily reflect an internalization of the sociocultural stereotype that ‘girls are bad at maths’. However, where, when, and how widely this stereotype becomes entrenched remains uncertain.

Here, we report the results of a 4-year longitudinal assessment of language and mathematical performance of all French first and second graders (2,653,082 children). Boys and girls exhibited very similar maths scores upon school entry, but a gender gap in favor of boys became highly significant after 4 months of schooling and reached an effect size of about 0.20 after 1 year.

These findings were repeated each year and varied only slightly across family, class or school type and socioeconomic level. Although schooling correlated with age, exploiting the near-orthogonal variations indicated that the gender gap increased with schooling rather than with age. These findings point to the first year of school as the time and place where a maths gender gap emerges in favor of boys, thus helping to focus the search for solutions and interventions.

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Published on December 9, 2025

Connectome harmonic analysis has been proposed as a multimodal approach for studying brain dynamics by decomposing functional MRI signals in a Fourier basis informed by the structural connectome derived from diffusion MRI. In this work, we pose the following question: is the propensity of the connectomic Fourier basis to reconstruct resting state fMRI signals truly contingent upon anatomical priors?

We present evidence that it is not, by demonstrating that when fewer than n = 100 modes are considered, the connectomic eigenbasis obtained through state-of-the-art methodology performs similarly to geometrically transformed versions of that same basis. The main theoretical contribution of this paper is the construction of a regular planar embedding of the left hemisphere’s cortical surface, which we use to compute a smoothly parametrized family of cortical transformations that form the basis for an improved Spin Test.

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Raphaël Vock, Antoine Grigis, Benoit Dufumier, Edouard Duchesnay

• HAL ID: hal-05302478, version 1
• DOI: 10.1007/978-3-032-05162-2_27

Published on December 12, 2025

Objectives To assess the effects of and related evidence certainty of interventions for attention deficit/hyperactivity disorder (ADHD) across an individual’s lifespan, and to develop a continuously updated web platform for people with lived experience of ADHD as a method to disseminate living evidence synthesis for shared decision making.

Design Umbrella review and platform for shared decision making. Data sources Six databases from inception to January 19, 2025. Study authors were contacted for additional information when necessary. Eligibility criteria for selecting studies Systematic reviews that used meta-analyses of randomized controlled trials were eligible if they compared a drug or non-drug intervention with a passive control in individuals with a diagnosis of ADHD.

Primary outcomes were severity of ADHD symptoms, analyzed by rater type (clinician-rated, parent-rated, teacher-rated, or self-rated) and time point (short term (12 weeks, or study endpoint), medium term (26 weeks), and long term (52 weeks)), acceptability (participants dropping out for any reason), and tolerability (participants dropping out owing to any side effects). Secondary outcomes included daily functioning, quality of life, comorbid symptoms, and key side effects (decreased sleep and appetite). Data synthesis Eligible meta-analyses were re-estimated with a standardized statistical approach. Methodological quality was assessed using AMSTAR-2. Evidence certainty was evaluated using an algorithmic version of the GRADE framework, adapted for drug and non-drug interventions. Results 115 of 414 full text articles were deemed eligible and 299 were excluded; the eligible articles comprised 221 unique combinations of participants, interventions, comparators, and outcomes.

For each combination, the most recent and methodologically robust meta-analysis was selected for re-estimation, which gave 221 re-estimated meta-analyses in total, derived from 47 meta-analytic reports. In the short term, alpha-2 agonists, amphetamines, atomoxetine, methylphenidate, and viloxazine showed medium to large effect sizes in reducing the severity of ADHD symptoms in children and adolescents, with moderate to high certainty evidence. Methylphenidate showed consistent benefits across raters (standardized mean difference >0.75, 95% confidence interval (CI) 0.56 to 1.03; moderate or high certainty evidence). These interventions showed lower tolerability than the placebo, but this effect was not significant for methylphenidate and atomoxetine. In adults, atomoxetine, cognitive behavioral therapy, methylphenidate (and, when restricting analyses to high quality trials, amphetamines) showed at least moderate certainty evidence of efficacy on ADHD symptoms, with medium effect sizes. Methylphenidate, amphetamines, and atomoxetine had worse tolerability than placebo (methylphenidate, risk ratio 0.50, 95% CI 0.36 to 0.69; amphetamines, 0.40, 0.22 to 0.72; atomoxetine, 0.45, 0.35 to 0.58). Some non-drug interventions (acupuncture and cognitive behavioral therapy in children and adolescents, and mindfulness in adults) showed large effect sizes for ADHD symptoms, but with low certainty evidence. No high certainty, long-term evidence was found for any intervention.

An online platform showing effects and evidence certainty of each intervention across age groups, time points, and outcomes (https://ebiadhd-database.org/) was developed. Conclusions This review provides updated evidence to inform patients, practitioners, and guideline developers how best to manage ADHD symptoms. The online platform should facilitate the implementation of shared decision making in daily practice.

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Published on 04-11-2025

The sensorimotor system develops early in utero and supports the emergence of body representations critical for perception, action, and interaction with the environment. While somatotopic protomaps are already developed in the primary somatosensory and motor cortices in late pregnancy, little is known about the anatomical substrates of this functional specialization. In this study, we aimed to decipher the microstructural properties of these regions in the developing brain.

Using advanced diffusion MRI and post-processing tools, we parcellated the pre- and post-central gyri into microstructurally distinct clusters along the lateral-to-medial axis in 25 full-term neonates, confirming the early differentiation within sensorimotor regions. These clusters were further analyzed in 59 preterm infants scanned at term-equivalent age (TEA, PT TEA), of which 45 were also scanned near birth (PT Birth), and compared with another group of 59 full-term neonates. Applying a multivariate Mahalanobis distance approach, we quantified deviations in preterm cortical microstructure relative to the full-term reference.

Preterm infants showed significant region-and position-specific deviations at both ages, though these were smaller at TEA (repeated-measures ANCOVA: PT Birth : region effect F=25.48, position effect F=16.06; PT TEA : region effect F=14.87, all p < 0.001), consistently with ongoing maturation during the pre-term period. Differences between the pre-and post-central gyri, and along the somatotopic axis, suggested differential vulnerability to prematurity. In particular, compared with somatosensory regions, the motor regions appeared to be at a more advanced stage of maturation close to birth (paired t-test, T = -4.388, p < 0.001) and less vulnerable at TEA (paired t-test, T = -4.169, p < 0.001), suggesting lesser impact of prematurity. An opposite pattern was observed, particularly close to birth, for lateral positions related to mouth representation compared with intermediary (paired t-test: T = 5.933, p < 0.001) and medial (paired t-test: T = 4.712, p < 0.001) positions.

These findings support the notion that early sensorimotor cortical specialization is microstructurally emergent during gestation and sensitive to the atypical developmental context of preterm birth.

Alexandra Brandstaetter, Andrea Gondová, Laurie Devisscher, Denis Rivière, Guillaume Auzias, Yann Leprince, Jessica Dubois

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• • PMID : 40907278
  • PMCID : PMC12446505
  • DOI : 10.1016/j.dcn.2025.101610

Published on October 14, 2025

At the physical level, the experience of pitch has a single determinant: the repetition rate of a waveform in the acoustic signal. Yet, psychologists describe pitch as composed of two perceptual dimensions, height and chroma. Chroma accounts for octave equivalence, whereby sounds with fundamental frequencies at a 1:2 ratio are perceived as sharing the same pitch. A current controversy debates whether chroma is a basic perceptual property dependent on biological constraints or a higher-order cognitive construct shaped by culture.

Here, we used high-density electroencephalography (EEG) and time-resolved multivariate pattern analyses to characterize pitch processing in humans at 3 months of age. We found that, when exposed to repetitive sequences of orchestral tones, infants encode two separate pitch-related dimensions automatically and with divergent dynamics. Namely, our classifiers isolated height-specific information from the neural signal rapidly after the onset of the auditory sequences. Beyond approximately 600 ms, the performance of pitch height decoders fell to chance level and did not recover.

In contrast, neural patterns displaying octave equivalence were retrieved later in the trial, over multiple time windows throughout the unfolding of the auditory sequence, and after sequence offset.

Overall, this study reveals that very early in human development, the pitch of naturally rich tones is processed over two distinct encoding stages, capturing not only their absolute height but also their relative position in the octave. We speculate that separate encoding mechanisms reflect distinct functional roles carried by the two dimensions.

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Giulia Gennari, Ghislaine Dehaene-Lambertz

• HAL ID: hal-05314723, version 1
• DOI: 10.1111/desc.70037

Published on September 23, 2025

Non-shivering thermogenesis in brown adipose tissue (BAT) is linked to metabolic health. Yet, how its activity states impact on systemic metabolism and in particular on lactate, a highly abundant metabolite increasingly recognized as a critical player in energy metabolism, remains unresolved.

The goal of this study was to investigate the impact of BAT activity on lactate metabolism at the whole organism level. To activate or inactivate non-shivering thermogenesis in BAT, we housed C57Bl6/J male mice at 4, 21, and 30°C and then conducted lactate tolerance tests. In mice exposed to cold exposure (4°C), systemic lactate clearance was elevated. In contrast, clearance of systemic lactate was poor in mice housed under thermoneutral conditions (30°C) that inactivate BAT thermogenesis, as well as in mice deficient for the mitochondrial uncoupling protein-1. To better understand lactate metabolic fate during the clearance phase, in vivo stable isotope tracing experiments with labeled 13C-lactate and analyses by mass spectrometry were performed.

These experiments revealed that lactate contribution to gluconeogenesis was increased under cold exposure while its contribution to the tricarboxylic acid cycle was reduced in BAT under thermoneutrality. Remarkably, we also identified that lactate entered a pyruvate cycling process that was highly active in BAT, and repressed at thermoneutrality.

Our study shows that inactivation of non-shivering thermogenesis decreased systemic lactate clearance, concomitantly with changes in the metabolic fate of lactate in BAT and in gluconeogenic organs, in male mice.

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Published on September 4, 2025

The superior temporal sulcus (STS) plays a central role in auditory and linguistic processing and undergoes rapid development during the last trimester of gestation. Yet, the extent to which its development is shaped by early sensory experience remains unclear. Premature birth offers a unique opportunity to address this question, as it exposes the brain to an extra-uterine auditory environment at a critical stage of network maturation. We analyzed resting-state fMRI data in 116 neonates (63 males), scanned at term-equivalent age but born at varying gestational ages (24.3 to 41.7 weeks gestational age) using the developing Human Connectome Project (dHCP) database.

Functional connectivity was computed in native space using regions of interest based on each infant’s sulcal anatomy to assess the respective contributions of STS subregions. Our analyses reveal a functional division between the inferior and superior banks of the STS, with the inferior bank showing stronger connectivity to distant parietal and frontal areas along the dorsal language pathway. The left posterior STS emerged as a functional hub, displaying broad inter-area connectivity. Longer gestations correlated with increased local connectivity, notably in the right temporal region, despite equal age at scan. Additionally, female neonates exhibited stronger connectivity from the left posterior STS compared to males. These findings highlight the early emergence of adult-like auditory-linguistic networks and their sensitivity to the in-utero environment.

Further research is needed to investigate the consequences of these early differences and to determine which postnatal interventions might help compensate, if necessary.

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Published on August 28, 2025

Early-onset restrictive eating disorders (rEO-ED) encompass a heterogeneous group of conditions, including early-onset anorexia nervosa (EO-AN) and avoidant/restrictive food intake disorders (ARFID).

However, the impact of rEO-ED on brain morphometry remains largely unknown. Here we performed the largest magnetic resonance imaging-derived brain features comparison of children and early adolescents (<13 years) with EO-AN (n = 124) or ARFID (n = 50) versus typically developing individuals (TD, n = 116). EO-AN was associated with widespread cortex thinning, while underweight patients with ARFID exhibited reduced surface area and volumes compared with TD.

Despite similar body mass index distributions, EO-AN and ARFID showed distinct structural patterns, suggesting independent brain mechanisms. Finally, we identified overlapping patterns of brain thickness differences between EO-AN and obsessive-compulsive disorder and between ARFID and autism spectrum disorder.

Future studies are required to partition the contribution of body mass index versus rEO-ED mechanisms, as well as to identify shared mechanisms with other neurodevelopmental conditions toward a multidimensional approach to eating disorders.

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• HAL Id : pasteur-05228359, version 1
• DOI : 10.1038/s44220-025-00447-x
• PUBMED : 40655158
• PUBMEDCENTRAL : PMC12240815

Published on June 2, 2025

Down syndrome (DS) is a genetic disorder caused by an extra copy of chromosome 21, leading to various physical features, developmental and cognitive delays, and intellectual disability. Obstructive sleep apnea (OSA) is highly prevalent in children with DS, with severity reported to be inversely related to age and peaking in newborns. OSA causes intermittent hypoxia and hypercapnia, which may have detrimental effects on health and development.

Consequently, there are concerns about the impact of OSA on neurodevelopmental disorders associated with DS, particularly in newborns. Dp(16)1Yey mice, a genetically engineered model of DS, exhibit cognitive impairments and characteristics typically associated with OSA, including craniofacial hypoplasia and reduced upper airway volume in adulthood.

To investigate the contribution of respiratory-related disorders to DS pathophysiology, we examined the cardio-respiratory phenotype of Dp(16)1Yey mice at birth, with special attention to OSA, using a pneumotachograph and a facemask combined with a laser abdominal profilometer to distinguish obstructive, central, and mixed apneas. Dp(16)1Yey mouse pups exhibited lower weight and heart rates compared to their wild-type counterparts. Baseline breathing variables and responses to hypercapnia were similar between the two groups. Obstructive apneas were observed in both Dp(16)1Yey and wild-type mice, but the total time spent in obstructive apneas was longer in Dp(16)1Yey mice, due to their longer mean duration.

These findings highlight the relevance of the Dp(16)1Yey model for studying OSA in DS during the neonatal period and for investigating the contribution of early respiratory disorders to DS pathology.

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• HAL Id : hal-05093100 , version 1
• DOI : 10.1152/jn.00001.2025

Published on March 5, 2025

Semaine du Cerveau 2024 - Welcome to the world of brain imaging! What can different brain imaging techniques contribute to our understanding of the typical and atypical brain? Come and discover the techniques used by our team and their relevance to our research themes. Are you ready for adventure?

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Lucas Arcamone, Ombline Delassus, Alexia Gerard, Eliot Kerdreux, Aurélie Lebrun, Julia Micaux

• HAL Id : hal-04978716, version 1

Published on February 13, 2025

GRASP65 is a Golgi-associated peripheral protein encoded by the GORASP1 gene and required for Golgi cisternal stacking in vitro. A key role of GRASP65 in the regulation of cell division has also been suggested. However, depletion of GRASP65 in mice has little effect on the Golgi structure and the gene has not been associated with any human phenotype to date.

Here, we report the identification of the first human pathogenic variant of GORASP1 (c.1170_1171del; p.Asp390Glufs*18) in a patient combining a neurodevelopmental disorder with neurosensory, neuromuscular, and skeletal abnormalities. Functional analysis revealed that the variant leads to a total absence of GRASP65. The structure of the Golgi apparatus did not show fragmentation, but glycosylation anomalies such as hyposialylation were detected. Mitosis analyses revealed an excess of prometaphases and metaphases with polar chromosomes, suggesting a delay in the cell cycle.

These phenotypes were recapitulated in RPE cells in which a similar mutation was introduced by CRISPR/Cas9. These results indicate that loss of GRASP65 in humans causes a novel Golgipathy associated with defects in glycosylation and mitotic progression.

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Published on April 16, 2024

Perceptual awareness in infants during the first year of life is understudied, despite the philosophical, scientific, and clinical importance of understanding how and when consciousness emerges during human brain development. Although parents are undoubtedly convinced that their infant is conscious, the lack of adequate experimental paradigms to address this question in preverbal infants has been a hindrance to research on this topic.

However, recent behavioral and brain imaging studies have shown that infants are engaged in complex learning from an early age and that their brains are more structured than traditionally thought. I will present a rapid overview of these results, which might provide indirect evidence of early perceptual awareness and then describe how a more systematic approach to this question could stand within the framework of global workspace theory, which identifies specific signatures of conscious perception in adults. Relying on these brain signatures as a benchmark for conscious perception, we can deduce that it exists in the second half of the first year, whereas the evidence before the age of 5 months is less solid, mainly because of the paucity of studies.

The question of conscious perception before term remains open, with the possibility of short periods of conscious perception, which would facilitate early learning. Advances in brain imaging and growing interest in this subject should enable us to gain a better understanding of this important issue in the years to come.

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Ghislaine Dehaene-Lambertz

• HAL Id : hal-04548117 , version 1
• DOI: 10.1162/jocn_a_02149