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Detailed neural encoding of voice pitch and formant structure plays a crucial role in speech perception, and is of key importance for an appropriate acquisition of the phonetic repertoire in infants since birth. However, the extent to what newborns are capable of extracting pitch and formant structure information from the temporal envelope and the temporal fine structure of speech sounds, respectively, remains unclear. Here, we recorded the frequency-following response (FFR) elicited by a novel two-vowel, rising-pitch-ending stimulus to simultaneously characterize voice pitch and formant structure encoding accuracy in a sample of neonates and adults. Data revealed that newborns tracked changes in voice pitch reliably and no differently than adults, but exhibited weaker signatures of formant structure encoding, particularly at higher formant frequency ranges. Thus, our results indicate a well-developed encoding of voice pitch at birth, while formant structure representation is maturing in a frequency-dependent manner. Furthermore, we demonstrate the feasibility to assess voice pitch and formant structure encoding within clinical evaluation times in a hospital setting, and suggest the possibility to use this novel stimulus as a tool for longitudinal developmental studies of the auditory system.

17 páginas, 7 figuras., Although previous studies suggest that neural stem cells (NSCs) exist in the adult olfactory bulb (OB), their location, identity, and capacity to generate mature neurons in vivo has been little explored. Here, we injected enhanced green fluorescent protein (EGFP)-expressing retroviral particles into the OB core of adult mice to label dividing cells and to track the differentiation/maturation of any neurons they might generate. EGFP-labeled cells initially expressed adult NSC markers on days 1 to 3 postinjection (dpi), including Nestin, GLAST, Sox2, Prominin-1, and GFAP. EGFP+ -doublecortin (DCX) cells with a migratory morphology were also detected and their abundance increased over a 7-day period. Furthermore, EGFP-labeled cells progressively became NeuN+ neurons, they acquired neuronal morphologies, and they became immunoreactive for OB neuron subtype markers, the most abundant representing calretinin expressing interneurons. OB-NSCs also generated glial cells, suggesting they could be multipotent in vivo. Significantly, the newly generated neurons established and received synaptic contacts, and they expressed presynaptic proteins and the transcription factor pCREB. By contrast, when the retroviral particles were injected into the subventricular zone (SVZ), nearly all (98%) EGFP+ -cells were postmitotic when they reached the OB core, implying that the vast majority of proliferating cells present in the OB are not derived from the SVZ. Furthermore, we detected slowly dividing label-retaining cells in this region that could correspond to the population of resident NSCs. This is the first time NSCs located in the adult OB core have been shown to generate neurons that incorporate into OB circuits in vivo., This work was funded by grants from the Spanish “Ministerio de Economía y Competitividad and Ministerio de Ciencia, Innovacion y Universidades ” (MINECO and MICIU: SAF2013-4759R and SAF2016-80419-R, PID2019-109059RB-I00 to C.V., SAF2015-70433-R to H.M., BFU2016-80870-P to A.C., and CIBERNED CB06/05/0065 to C.V.), from the “Comunidad de Madrid” (S2011/BMD-2336) to C.V. and H.M., from the “Generalitat Valenciana” (PROMETEO/2018/055) to H.M., and from the CSIC Intramural program (Refs. 201220E098 and 201320E054) to C.V. Additional support was provided by the European Research Council (ERC) 2012-StG (311736-PD-HUMMODEL), the Instituto de Salud Carlos III - ISCIII/FEDER (Red de Terapia Celular - TerCel RD16/0011/0024 and PIE14/00061) to A.C. Ç.D. received a short-term fellowship from the Red Olfativa Española (ROE). M.M.-E, M.D.-M., A.H.-C., and V.N.-E. were supported by FPI Fellowships from the MICINN and MINECO.

Intraventricular hemorrhage is a common cause of morbidity and mortality in premature infants. The rupture of the germinal zone into the ventricles entails loss of neural stem cells and disturbs the normal cytoarchitecture of the region, compromising late neurogliogenesis. Here we demonstrate that neural stem cells can be easily and robustly isolated from the hemorrhagic cerebrospinal fluid obtained during therapeutic neuroendoscopic lavage in preterm infants with severe intraventricular hemorrhage. Our analyses demonstrate that these neural stem cells, although similar to human fetal cell lines, display distinctive hallmarks related to their regional and developmental origin in the germinal zone of the ventral forebrain, the ganglionic eminences that give rise to interneurons and oligodendrocytes. These cells can be expanded, cryopreserved, and differentiated in vitro and in vivo in the brain of nude mice and show no sign of tumoral transformation 6 months after transplantation. This novel class of neural stem cells poses no ethical concerns, as the fluid is usually discarded, and could be useful for the development of an autologous therapy for preterm infants, aiming to restore late neurogliogenesis and attenuate neurocognitive deficits. Furthermore, these cells represent a valuable tool for the study of the final stages of human brain development and germinal zone biology., Germinal zone neural stem cells (Gz‐NSC) are isolated from the hemorrhagic cerebrospinal fluid of preterm infants with severe intraventricular hemorrhage. These cells express ventral and posterior forebrain markers, can be differentiated and do not cause tumors. Gz‐NSC represent a valuable tool for the development of new cell therapies and the study of human Gz biology.

The aim of this study was to develop a rabbit neurosphere culture to characterize differences in basic processes of neurogenesis induced by intrauterine growth restriction (IUGR). A novel in vitro neurosphere culture has been established using fresh or frozen neural progenitor cells from newborn (PND0) rabbit brains. After surgical IUGR induction in pregnant rabbits and cesarean section 5 days later, neural progenitor cells from both control and IUGR groups were isolated and directly cultured or frozen at −80°C. These neural progenitor cells spontaneously formed neurospheres after 7 days in culture. The ability of control and IUGR neurospheres to migrate, proliferate, differentiate to neurons, astrocytes, or oligodendrocytes was compared and the possibility to modulate their responses was tested by exposure to several positive and negative controls. Neurospheres obtained from IUGR brains have a significant impairment in oligodendrocyte differentiation, whereas no significant differences are observed in other basic processes of neurogenesis. This impairment can be reverted by in vitro exposure of IUGR neurospheres to thyroid hormone, which is known to play an essential role in white matter maturation in vivo. Our new rabbit neurosphere model and the results of this study open the possibility to test several substances in vitro as neuroprotective candidates against IUGR induced neurodevelopmental damage while decreasing the number of animals and resources and allowing a more mechanistic approach at a cellular functional level., Rabbit “Neurosphere Assay.” PND0 rabbit brains are dissected and either frozen or directly cultured until neurosphere formation. “Neurosphere Assay” starts when neurospheres are plated in 8‐chamber slides and maintained under differentiating conditions to evaluate migration and differentiation into neurons, into astrocytes or into oligodendrocytes. Neurospheres were also plated in 96‐well plates under proliferating conditions and evaluated for diameter increase.

IntroductionThe Tousled-like kinases 1 and 2 (TLK1 and TLK2) are involved in many fundamental processes, including DNA replication, cell cycle checkpoint recovery and chromatin remodelling. Mutations in TLK2 were recently associated with ‘Mental Retardation Autosomal Dominant 57’ (MRD57, MIM# 618050), a neurodevelopmental disorder characterised by a highly variable phenotype, including mild-to-moderate intellectual disability, behavioural abnormalities, facial dysmorphisms, microcephaly, epilepsy and skeletal anomalies.MethodsWe re-evaluate whole exome sequencing and array-CGH data from a large cohort of patients affected by neurodevelopmental disorders. Using spatial proteomics (BioID) and single-cell gel electrophoresis, we investigated the proximity interaction landscape of TLK2 and analysed the effects of p.(Asp551Gly) and a previously reported missense variant (c.1850C>T; p.(Ser617Leu)) on TLK2 interactions, localisation and activity.ResultsWe identified three new unrelated MRD57 families. Two were sporadic and caused by a missense change (c.1652A>G; p.(Asp551Gly)) or a 39 kb deletion encompassing TLK2, and one was familial with three affected siblings who inherited a nonsense change from an affected mother (c.1423G>T; p.(Glu475Ter)). The clinical phenotypes were consistent with those of previously reported cases. The tested mutations strongly impaired TLK2 kinase activity. Proximal interactions between TLK2 and other factors implicated in neurological disorders, including CHD7, CHD8, BRD4 and NACC1, were identified. Finally, we demonstrated a more relaxed chromatin state in lymphoblastoid cells harbouring the p.(Asp551Gly) variant compared with control cells, conferring susceptibility to DNA damage.ConclusionOur study identified novel TLK2 pathogenic variants, confirming and further expanding the MRD57-related phenotype. The molecular characterisation of missense variants increases our knowledge about TLK2 function and provides new insights into its role in neurodevelopmental disorders.

Contains fulltext : 207577.pdf (Publisher’s version ) (Open Access) Brain imaging methods have contributed to shed light on the mechanisms of recovery after early brain insult. The assumption that the unaffected right hemisphere can take over language functions after left perinatal stroke is still under debate. Here, we report how patterns of brain structural and functional reorganization were associated with language outcomes in a group of four-year-old children with left perinatal arterial ischemic stroke (PAIS). Specifically, we gathered specific fine-grained developmental measures of receptive and productive aspects of language as well as standardized measures of cognitive development. We also collected structural neuroimaging data as well as functional activations during a passive listening story-telling fMRI task and a resting state session (rs-fMRI). Children with a left perinatal stroke showed larger lateralization indices of both structural and functional connectivity of the dorsal language pathway towards the right hemisphere that, in turn, were associated with better language outcomes. Importantly, the pattern of structural asymmetry was significantly more right-lateralized in children with a left perinatal brain insult than in a group of matched healthy controls. These results strongly suggest that early lesions of the left dorsal pathway and the associated perisylvian regions can induce the interhemispheric transfer of language functions to right homolog regions. This study provides combined evidence of structural and functional brain reorganization of language networks after early stroke with strong implications for neurobiological models of language development. 18 p.

Objectives To perform a comprehensive assessment of cortical development in fetuses with isolated nonsevere ventriculomegaly (INSVM) by neurosonography. Methods We prospectively included 40 fetuses with INSVM and 40 controls. INSVM was defined as atrial width between 10.0 and 14.9 mm without associated malformation, infection, or chromosomal abnormality. Cortical development was assessed by neurosonography at 26 and 30 weeks of gestation measuring depth of selected sulci and applying a maturation scale from 0 (no appearance) to 5 (maximally developed) of main sulci and areas. Results INSVM showed underdeveloped calcarine and parieto-occipital sulci. In addition, significant delayed maturation pattern was also observed in regions distant to ventricular system including Insula depth (controls 30.8 mm [SD 1.7] vs INSVM 31.7 mm [1.8]; P = .04), Sylvian fissure grading (>2 at 26 weeks: controls 87.5% vs INSVM 50%, P = .01), mesial area grading (>2 at 30 weeks: controls 95% vs INSVM 62.5%; P = .03), and cingulate sulcus grading (>2 at 30 weeks: controls 100% vs INSVM 80.5%; P = .01). Conclusions Fetuses with INSVM showed underdeveloped cortical maturation including also regions, where effect of ventricular dilatation is unlikely. These results suggest that in a proportion of fetuses with INSVM, ventricular dilation might be related with altered cortical architecture.

The study of psychiatric disorders usually focuses on emotional symptoms assessment. However, cognitive deficiencies frequently constitute the core symptoms, are often poorly controlled and handicap individual's quality of life. Adenosine receptors, through the control of both dopamine and glutamate systems, have been implicated in the pathophysiology of several psychiatric disorders such as schizophrenia and attention deficit/hyperactivity disorder. Indeed, clinical data indicate that poorly responsive schizophrenia patients treated with adenosine adjuvants show improved treatment outcomes. The A2A adenosine receptor subtype (A2AR) is highly expressed in brain areas controlling cognition and motivational responses including the striatum, hippocampus and cerebral cortex. Accordingly, we study the role of A2AR in the regulation of cognitive processes based on a complete cognitive behavioural analysis coupled with the assessment of neurogenesis and sub-synaptic protein expression in adult and middle-aged A2AR constitutional knockout mice and wild-type littermates. Our results show overall cognitive impairments in A2AR knockout mice associated with a decrease in new-born hippocampal neuron proliferation and concomitant changes in synaptic protein expression, in both the prefrontal cortex and the hippocampus. These results suggest a deficient adenosine signalling in cognitive processes, thus providing new opportunities for the therapeutic management of cognitive deficits associated with psychiatric disorders. This study was supported by MINECO (SAF 2013-41761-RFEDER, SAF 2014-55700-P, SAF 2016-75966-R, FEDER, PCIN-2013-019-C03-03), Ministry of Health (ReticeISCIIIeRD/12/0028/0024-FEDER; RD16/017/010-FEDER, PIE14/00034), Plan Nacional sobre Drogas (2014/020), IWT (SBO-140028), Fundacio la Marato de TV3 (Grant 20152031), UE Medbioinformatic project (grant number 634143) and Generalitat de Catalunya (2014 SGR 34, 2014 SGR 1251). IG-R was funded by an FPI fellowship, BES-2011-046655, associated with SAF 2010-15793.

DOI: 10.1007/s00204-016-1709-8 URL: http://link.springer.com/article/10.1007%2Fs00204-016-1709-8 Filiació URV: SI Memòria Food supplements based on herbal products are widely used during pregnancy as part of a self-care approach. The idea that such supplements are safe and healthy is deeply seated in the general population, although they do not underlie the same strict safety regulations than medical drugs. We aimed to characterize the neurodevelopmental effects of the green tea catechin epigallocatechin gallate (EGCG), which is now commercialized as high-dose food supplement. We used the “Neurosphere Assay” to study the effects and unravel underlying molecular mechanisms of EGCG treatment on human and rat neural progenitor cells (NPCs) development in vitro. EGCG alters human and rat NPC development in vitro. It disturbs migration distance, migration pattern, and nuclear density of NPCs growing as neurospheres. These functional impairments are initiated by EGCG binding to the extracellular matrix glycoprotein laminin, preventing its binding to β1-integrin subunits, thereby prohibiting cell adhesion and resulting in altered glia alignment and decreased number of migrating young neurons. Our data raise a concern on the intake of high-dose EGCG food supplements during pregnancy and highlight the need of an in vivo characterization of the effects of high-dose EGCG exposure during neurodevelopment.

Adverse conditions during fetal life have been associated to both structural and functional changes in neurodevelopment from the neonatal period to adolescence. In this study, connectomics was used to assess the evolution of brain networks from infancy to early adolescence. Brain network reorganization over time in subjects who had suffered adverse perinatal conditions is characterized and related to neurodevelopment and cognition. Three cohorts of prematurely born infants and children (between 28 and 35 weeks of gestational age), including individuals with a birth weight appropriated for gestational age and with intrauterine growth restriction (IUGR), were evaluated at 1, 6, and 10 years of age, respectively. A common developmental trajectory of brain networks was identified in both control and IUGR groups: network efficiencies of the fractional anisotropy (FA)-weighted and normalized connectomes increase with age, which can be related to maturation and myelination of fiber connections while the number of connections decreases, which can be associated to an axonal pruning process and reorganization. Comparing subjects with or without IUGR, a similar pattern of network differences between groups was observed in the three developmental stages, mainly characterized by IUGR group having reduced brain network efficiencies in binary and FA-weighted connectomes and increased efficiencies in the connectome normalized by its total connection strength (FA). Associations between brain networks and neurobehavioral impairments were also evaluated showing a relationship between different network metrics and specific social cognition-related scores, as well as a higher risk of inattention/hyperactivity and/or executive functional disorders in IUGR children.

Endocannabinoids participate in the control of neurogenesis, neural cell death and gliosis. The pharmacological effect of the fatty acid amide hydrolase (FAAH) inhibitor URB597, which limits the endocannabinoid degradation, was investigated in the present study. Cell proliferation (phospho-H3(+) or BrdU(+) cells) of the main adult neurogenic zones as well as apoptosis (cleaved caspase-3(+)), astroglia (GFAP(+)), and microglia (Iba1(+) cells) were analyzed in the hippocampus, hypothalamus and striatum of rats intraperitoneally treated with URB597 (0.3 mg/kg/day) at one dose/4-days resting or 5 doses (1 dose/day). Repeated URB597 treatment increased the plasma levels of the N-acylethanolamines oleoylethanolamide, palmitoylethanolamide and arachidonoylethanolamine, reduced the plasma levels of glucose, triglycerides and cholesterol, and induced a transitory body weight decrease. The hippocampi of repeated URB597-treated rats showed a reduced number of phospho-H3(+) and BrdU(+) subgranular cells as well as GFAP(+), Iba1(+) and cleaved caspase-3(+) cells, which was accompanied with decreased hippocampal expression of the cannabinoid CB1 receptor gene Cnr1 and Faah. In the hypothalami of these rats, the number of phospho-H3(+), GFAP(+) and 3-weeks-old BrdU(+) cells was specifically decreased. The reduced striatal expression of CB1 receptor in repeated URB597-treated rats was only associated with a reduced apoptosis. In contrast, the striatum of acute URB597-treated rats showed an increased number of subventricular proliferative, astroglial and apoptotic cells, which was accompanied with increased Faah expression. Main results indicated that FAAH inhibitor URB597 decreased neural proliferation, glia and apoptosis in a brain region-dependent manner, which were coupled to local changes in Faah and/or Cnr1 expression and a negative energy context. Grant sponsor: 7th Framework Programme of European Union; Grant number: HEALTH-F2-2008-223713, REPROBESITY to FR and BL; Grant sponsor: Ministerio de Ciencia e Innovación; Grant numbers: SAF2010-19087, SAF 2010-20521; Grant sponsor: Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, UE-ERDF; Grant number: CP12/03109; Grant sponsor: Red de Trastornos Adictivos; Grant numbers: RD12/0028/0001, RD12/0028/0009; Grant sponsor: CIBERobn; Grant sponsor: Plan Nacional Sobre Drogas, Ministerio de Sanidad y Consumo; Grant number: PNSD2010/143; Grant sponsor: Consejería de Economía, Innovación y Ciencia, Junta de Andalucía, UE/ERDF; Grant numbers: CTS-433, P-11-CVI-07637; Grant sponsor: Consejería de Salud, Junta de Andalucía; Grant numbers: PI0232/2008, PI0029/2008, SAS111224; Grant sponsor: Fundació La Marató de TV3; Grant number: 386/C/2011; Grant sponsor: German Research Foundation DFG; Grant number: FOR629, project CP2 to BL. JS, FP, and AS hold “Miguel Servet” research contracts from the National System of Health, ISCIII (Grant numbers: CP12/03109, CP14/00212, CP14/00173 respectively).

Alternative splicing (AS) generates extensive transcriptomic and proteomic complexity. However, the functions of species- and lineage-specific splice variants are largely unknown. Here we show that mammalian-specific skipping of polypyrimidine tract-binding protein 1 (PTBP1) exon 9 alters the splicing regulatory activities of PTBP1 and affects the inclusion levels of numerous exons. During neurogenesis, skipping of exon 9 reduces PTBP1 repressive activity so as to facilitate activation of a brain-specific AS program. Engineered skipping of the orthologous exon in chicken cells induces a large number of mammalian-like AS changes in PTBP1 target exons. These results thus reveal that a single exon-skipping event in an RNA binding regulator directs numerous AS changes between species. Our results further suggest that these changes contributed to evolutionary differences in the formation of vertebrate nervous systems SG is supported by an NSERC Alexander Graham Bell Studentship, TGP is supported by fellowships from EMBO and OSCI, and MI was supported by a LTF from the Human Frontiers Science Program Organization. This research was supported by grants from the CIHR to BJB and A-C.G. BJB holds the Banbury Chair of Medical Research at the University of Toronto. Data presented in this manuscript is archived in the gene Gene Expression Omnibus (GEO) under accession number GSE69656.

Santiago Ramón y Cajal developed a great body of scientific research during the last decade of 19th century, mainly between 1888 and 1892, when he published more than 30 manuscripts. The neuronal theory, the structure of dendrites and spines, and fine microscopic descriptions of numerous neural circuits are among these studies. In addition, numerous cell types (neuronal and glial) were described by Ramón y Cajal during this time using this “reazione nera” or Golgi method. Among these neurons were the special cells of the molecular layer of the neocortex. These cells were also termed Cajal cells or Retzius cells by other colleagues. Today these cells are known as Cajal–Retzius cells. From the earliest description, several biological aspects of these fascinating cells have been analyzed (e.g., cell morphology, physiological properties, origin and cellular fate, putative function during cortical development, etc). In this review we will summarize in a temporal basis the emerging knowledge concerning this cell population with specific attention the pioneer studies of Santiago Ramón y Cajal.

22 páginas, 16 figuras.-- et al., [Background]: Nolz1 is a zinc finger transcription factor whose expression is enriched in the lateral ganglionic eminence (LGE), although its function is still unknown. [Results]: Here we analyze the role of Nolz1 during LGE development. We show that Nolz1 expression is high in proliferating neural progenitor cells (NPCs) of the LGE subventricular zone. In addition, low levels of Nolz1 are detected in the mantle zone, as well as in the adult striatum. Similarly, Nolz1 is highly expressed in proliferating LGE-derived NPC cultures, but its levels rapidly decrease upon cell differentiation, pointing to a role of Nolz1 in the control of NPC proliferation and/or differentiation. In agreement with this hypothesis, we find that Nolz1 over-expression promotes cell cycle exit of NPCs in neurosphere cultures and negatively regulates proliferation in telencephalic organotypic cultures. Within LGE primary cultures, Nolz1 over-expression promotes the acquisition of a neuronal phenotype, since it increases the number of β-III tubulin (Tuj1)- and microtubule-associated protein (MAP)2-positive neurons, and inhibits astrocyte generation and/or differentiation. Retinoic acid (RA) is one of the most important morphogens involved in striatal neurogenesis, and regulates Nolz1 expression in different systems. Here we show that Nolz1 also responds to this morphogen in E12.5 LGE-derived cell cultures. However, Nolz1 expression is not regulated by RA in E14.5 LGE-derived cell cultures, nor is it affected during LGE development in mouse models that present decreased RA levels. Interestingly, we find that Gsx2, which is necessary for normal RA signaling during LGE development, is also required for Nolz1 expression, which is lost in Gsx2 knockout mice. These findings suggest that Nolz1 might act downstream of Gsx2 to regulate RA-induced neurogenesis. Keeping with this hypothesis, we show that Nolz1 induces the selective expression of the RA receptor (RAR)β without altering RARα or RARγ. In addition, Nozl1 over-expression increases RA signaling since it stimulates the RA response element. This RA signaling is essential for Nolz1-induced neurogenesis, which is impaired in a RA-free environment or in the presence of a RAR inverse agonist. It has been proposed that Drosophila Gsx2 and Nolz1 homologues could cooperate with the transcriptional co-repressors Groucho-TLE to regulate cell proliferation. In agreement with this view, we show that Nolz1 could act in collaboration with TLE-4, as they are expressed at the same time in NPC cultures and during mouse development. [Conclusions]: Nolz1 promotes RA signaling in the LGE, contributing to the striatal neurogenesis during development., This study was supported by grants from the Ministerio de Ciencia e Innovación (SAF2008-04360, to JA; SAF2009-07774 and PLE2009-0089, to JMC; SAF2004- 05798, to CV-A), Spain; Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (CIBERNED, to JA and CV-A; and RETICS (RD06/0010/0006; Red de Terapia Celular), to JMC), Spain; the Fundació La Marató de TV3 (to JA), Spain; Generalitat de Catalunya (2009SGR-00326 to JA), Spain; and the National Institutes of Health (EY013969, to GD). The Cell Therapy Program is supported by the Centre of Regenerative Medicine in Barcelona (CMRB; Promt-0901, to JMC; Generalitat de Catalunya), Spain.

BACKGROUND: Neuropsychological instruments to assess cognitive trajectories during childhood in epidemiological studies are needed. This would improve neurodevelopment characterization in order to identify its potential determinants. We aimed to study whether repeated measures of n-back, a working memory task, detect developmental trajectories in schoolchildren during a 1-year follow-up. METHODS: We administered the n-back task to 2897 healthy children aged 7-11 years old from 39 schools in Barcelona (Spain). The task consisted of 2 levels of complexity or loads (2- and 3-back) and 2 different stimuli (numbers and words). Participants performed the task four times from January 2012 to March 2013. To study the trajectories during the follow-up, we performed linear mixed-effects models including school, individual and age as random effects. RESULTS: We observed improvements related to age in n-back outcomes d', HRT and accuracy, as well as reduced cognitive growth at older ages in d' and HRT. Greater improvements in performance were observed at younger ages, in 2-back, in verbal rather than numerical stimuli and in girls compared to boys. Boys responded faster at baseline, while girls showed increased growth in 2-back numbers. Children with ADHD (Attention Deficit and Hyperactivity Disorder) symptoms (15% of boys and 6% of girls) had a lower working memory at baseline, but they showed similar cognitive growth trajectories in numbers variants of the task, as compared to children without ADHD symptoms. However, the age-related improvement in response speed was not observed in children with ADHD symptoms. CONCLUSIONS: Changes in n-back outcomes reflected developmental trajectories in 1-year follow-up. The present results suggest that the repeated administration of this task can be used to study the factors that may alter the cognitive development during childhood.

Neuroimaging of brain diseases plays a crucial role in understanding brain abnormalities and early diagnosis. Of great importance is the study of brain abnormalities in utero and the assessment of deviations in case of maldevelopment. In this work, brain magnetic resonance images from 23 isolated non-severe ventriculomegaly (INSVM) fetuses and 25 healthy controls between 26 and 29 gestational weeks were used to identify INSVM-related cortical folding deviations from normative development. Since these alterations may reflect abnormal neurodevelopment, our working hypothesis is that markers of cortical folding can provide cues to improve the prediction of later neurodevelopmental problems in INSVM subjects. We analyzed the relationship of ventricular enlargement with cortical folding alterations in a regional basis using several curvature-based measures describing the folding of each cortical region. Statistical analysis (global and hemispheric) and sparse linear regression approaches were then used to find the cortical regions whose folding is associated with ventricular dilation. Results from both approaches were in great accordance, showing a significant cortical folding decrease in the insula, posterior part of the temporal lobe and occipital lobe. Moreover, compared to the global analysis, stronger ipsilateral associations of ventricular enlargement with reduced cortical folding were encountered by the hemispheric analysis. Our findings confirm and extend previous studies by identifying various cortical regions and emphasizing ipsilateral effects of ventricular enlargement in altered folding. This suggests that INSVM is an indicator of altered cortical development, and moreover, cortical regions with reduced folding constitute potential prognostic biomarkers to be used in follow-up studies to decipher the outcome of INSVM fetuses., Highlights • Studies showed high risk of neurodevelopmental impairment in fetuses with ventriculomegaly. • Fetal ventriculomegaly may be related to other neurodevelopmental processes. • We studied the relationship of isolated non-severe ventriculomegaly with cortical folding. • Reduced cortical folding is observed in fetuses with ventriculomegaly. • Cortical regions with altered folding may constitute potential prognostic biomarkers.

The development and maturation of cortical circuits relies on the coordinated actions of long and short range axonal guidance cues. In this regard, the class 3 semaphorins and their receptors have been seen to be involved in the development and maturation of the hippocampal connections. However, although the role of most of their family members have been described, very few data about the participation of Semaphorin 3E (Sema3E) and its receptor PlexinD1 during the development and maturation of the entorhino-hippocampal (EH) connection are available. In the present study, we focused on determining their roles both during development and in adulthood. We determined a relevant role for Sema3E/PlexinD1 in the layer-specific development of the EH connection. Indeed, mice lacking Sema3E/PlexinD1 signalling showed aberrant layering of entorhinal axons in the hippocampus during embryonic and perinatal stages. In addition, absence of Sema3E/PlexinD1 signalling results in further changes in postnatal and adult hippocampal formation, such as numerous misrouted ectopic mossy fibers. More relevantly, we describe how subgranular cells express PlexinD1 and how the absence of Sema3E induces a dysregulation of the proliferation of dentate gyrus progenitors leading to the presence of ectopic cells in the molecular layer. Lastly, Sema3E mutant mice displayed increased network excitability both in the dentate gyrus and the hippocampus proper.