Generation of Urine-Derived Induced Pluripotent Stem Cells and Cerebral Organoids for Modeling Down Syndrome.

Down syndrome (DS, or trisomy 21, T21), is the most common genetic cause of intellectual disability. Alterations in the complex process of cerebral cortex development contribute to the neurological deficits in DS, although the underlying molecular and cellular mechanisms are not completely understood. Human cerebral organoids (COs) derived from three-dimensional (3D) cultures of induced pluripotent stem cells (iPSCs) provide a new avenue for gaining a better understanding of DS neuropathology. In this study, we aimed to generate iPSCs from individuals with DS (T21-iPSCs) and euploid controls using urine-derived cells, which can be easily and noninvasively obtained from most individuals, and examine their ability to differentiate into neurons and astrocytes grown in monolayer cultures, as well as into 3D COs. We employed nonintegrating episomal vectors to generate urine-derived iPSC lines, and a simple-to-use system to produce COs with forebrain identity. We observed that both T21 and control urine-derived iPSC lines successfully differentiate into neurons and astrocytes in monolayer, as well as into COs that recapitulate early features of human cortical development, including organization of neural progenitor zones, programmed differentiation of excitatory and inhibitory neurons, and upper-and deep-layer cortical neurons as well as astrocytes. Our findings demonstrate for the first time the suitability of using urine-derived iPSC lines to produce COs for modeling DS.

An atlas of gene regulatory elements in adult mouse cerebrum.

The mammalian cerebrum performs high-level sensory perception, motor control and cognitive functions through highly specialized cortical and subcortical structures1. Recent surveys of mouse and human brains with single-cell transcriptomics2-6 and high-throughput imaging technologies7,8 have uncovered hundreds of neural cell types distributed in different brain regions, but the transcriptional regulatory programs that are responsible for the unique identity and function of each cell type remain unknown. Here we probe the accessible chromatin in more than 800,000 individual nuclei from 45 regions that span the adult mouse isocortex, olfactory bulb, hippocampus and cerebral nuclei, and use the resulting data to map the state of 491,818 candidate cis-regulatory DNA elements in 160 distinct cell types. We find high specificity of spatial distribution for not only excitatory neurons, but also most classes of inhibitory neurons and a subset of glial cell types. We characterize the gene regulatory sequences associated with the regional specificity within these cell types. We further link a considerable fraction of the cis-regulatory elements to putative target genes expressed in diverse cerebral cell types and predict transcriptional regulators that are involved in a broad spectrum of molecular and cellular pathways in different neuronal and glial cell populations. Our results provide a foundation for comprehensive analysis of gene regulatory programs of the mammalian brain and assist in the interpretation of noncoding risk variants associated with various neurological diseases and traits in humans.

Electrophysiological Maturation of Cerebral Organoids Correlates with Dynamic Morphological and Cellular Development.

Cerebral organoids (COs) are rapidly accelerating the rate of translational neuroscience based on their potential to model complex features of the developing human brain. Several studies have examined the electrophysiological and neural network features of COs; however, no study has comprehensively investigated the developmental trajectory of electrophysiological properties in whole-brain COs and correlated these properties with developmentally linked morphological and cellular features. Here, we profiled the neuroelectrical activities of COs over the span of 5 months with a multi-electrode array platform and observed the emergence and maturation of several electrophysiologic properties, including rapid firing rates and network bursting events. To complement these analyses, we characterized the complex molecular and cellular development that gives rise to these mature neuroelectrical properties with immunohistochemical and single-cell transcriptomic analyses. This integrated approach highlights the value of COs as an emerging model system of human brain development and neurological disease.

Robust Hi-C Maps of Enhancer-Promoter Interactions Reveal the Function of Non-coding Genome in Neural Development and Diseases.

Genome-wide mapping of chromatin interactions at high resolution remains experimentally and computationally challenging. Here we used a low-input "easy Hi-C" protocol to map the 3D genome architecture in human neurogenesis and brain tissues and also demonstrated that a rigorous Hi-C bias-correction pipeline (HiCorr) can significantly improve the sensitivity and robustness of Hi-C loop identification at sub-TAD level, especially the enhancer-promoter (E-P) interactions. We used HiCorr to compare the high-resolution maps of chromatin interactions from 10 tissue or cell types with a focus on neurogenesis and brain tissues. We found that dynamic chromatin loops are better hallmarks for cellular differentiation than compartment switching. HiCorr allowed direct observation of cell-type- and differentiation-specific E-P aggregates spanning large neighborhoods, suggesting a mechanism that stabilizes enhancer contacts during development. Interestingly, we concluded that Hi-C loop outperforms eQTL in explaining neurological GWAS results, revealing a unique value of high-resolution 3D genome maps in elucidating the disease etiology.

Altered Features of Vimentin-containing Cells in Cerebrum of Tg(SOD1*G93A)1Gur Mice: A Preliminary Study on Cerebrum Endogenous Neural Precursor Cells in Amyotrophic Lateral Sclerosis.

Vimentin-containing cells (VCCs) are potential neural precursor cells in central nervous systems, Thus, we studied the alteration of VCCs proliferation, differentiation and migration in the cerebrum during different stages of Tg(SOD1*G93A)1Gur mice. It aims to search potential ways regulating the proliferation, differentiation and migration of endogenous VCCs, to enhance their neural repair function and to cure or prevent from the development of ALS. We observed and analyzed the proliferation, differentiation and migration of VCCs in different anatomic regions and cell types of cerebrum at different stages including the pre-onset (60-70 days), onset (90-100 days) and progression (120-130 days) of wild-type (WT) and Tg(SOD1*G93A)1Gur mice using the fluorescent immunohistochemical technology. Results showed that VCCs in the cerebrum were mostly distributed in the ventricular system, periventricular structures, the hippocampus and the cerebral cortex in WT mice. VCCs significantly reduced in the motor cortex and the cingulate cortex in Tg(SOD1*G93A)1Gur mice. All vimentin expressed in the extranuclear and almost all VCCs were astrocytes in WT mice and Tg(SOD1*G93A)1Gur mice. There were no significant difference in the number of Brdu and nestin positive cells in left and right brains of WT mice and Tg(SOD1*G93A)1Gur mice in the period of 60-130 days. Our data suggested that there existed extensively NPCs in the cerebrum of adult mice. In ALS-like Tg(SOD1*G93A)1Gur mice, VCCs in the motor cortex, the olfactory cortex and the cingulate cortex showed that no any proliferation and redistribution in neural cells of VCCs in the cerebrum occurred in all stages of ALS, might migrate to damaged regions.

Mechanisms of hyperexcitability in Alzheimer's disease hiPSC-derived neurons and cerebral organoids vs isogenic controls.

Human Alzheimer's disease (AD) brains and transgenic AD mouse models manifest hyperexcitability. This aberrant electrical activity is caused by synaptic dysfunction that represents the major pathophysiological correlate of cognitive decline. However, the underlying mechanism for this excessive excitability remains incompletely understood. To investigate the basis for the hyperactivity, we performed electrophysiological and immunofluorescence studies on hiPSC-derived cerebrocortical neuronal cultures and cerebral organoids bearing AD-related mutations in presenilin-1 or amyloid precursor protein vs. isogenic gene corrected controls. In the AD hiPSC-derived neurons/organoids, we found increased excitatory bursting activity, which could be explained in part by a decrease in neurite length. AD hiPSC-derived neurons also displayed increased sodium current density and increased excitatory and decreased inhibitory synaptic activity. Our findings establish hiPSC-derived AD neuronal cultures and organoids as a relevant model of early AD pathophysiology and provide mechanistic insight into the observed hyperexcitability.

Lzts1 controls both neuronal delamination and outer radial glial-like cell generation during mammalian cerebral development.

In the developing central nervous system, cell departure from the apical surface is the initial and fundamental step to form the 3D, organized architecture. Both delamination of differentiating cells and repositioning of progenitors to generate outer radial glial cells (oRGs) contribute to mammalian neocortical expansion; however, a comprehensive understanding of their mechanisms is lacking. Here, we demonstrate that Lzts1, a molecule associated with microtubule components, promotes both cell departure events. In neuronally committed cells, Lzts1 functions in apical delamination by altering apical junctional organization. In apical RGs (aRGs), Lzts1 expression is variable, depending on Hes1 expression levels. According to its differential levels, Lzts1 induces diverse RG behaviors: planar division, oblique divisions of aRGs that generate oRGs, and their mitotic somal translocation. Loss-of-function of lzts1 impairs all these cell departure processes. Thus, Lzts1 functions as a master modulator of cellular dynamics, contributing to increasing complexity of the cerebral architecture during evolution.

Gliogenesis in the outer subventricular zone promotes enlargement and gyrification of the primate cerebrum.

The primate cerebrum is characterized by a large expansion of cortical surface area, the formation of convolutions, and extraordinarily voluminous subcortical white matter. It was recently proposed that this expansion is primarily driven by increased production of superficial neurons in the dramatically enlarged outer subventricular zone (oSVZ). Here, we examined the development of the parietal cerebrum in macaque monkey and found that, indeed, the oSVZ initially adds neurons to the superficial layers II and III, increasing their thickness. However, as the oSVZ grows in size, its output changes to production of astrocytes and oligodendrocytes, which in primates outnumber cerebral neurons by a factor of three. After the completion of neurogenesis around embryonic day (E) 90, when the cerebrum is still lissencephalic, the oSVZ enlarges and contains Pax6+/Hopx+ outer (basal) radial glial cells producing astrocytes and oligodendrocytes until after E125. Our data indicate that oSVZ gliogenesis, rather than neurogenesis, correlates with rapid enlargement of the cerebrum and development of convolutions, which occur concomitantly with the formation of cortical connections via the underlying white matter, in addition to neuronal growth, elaboration of dendrites, and amplification of neuropil in the cortex, which are primary factors in the formation of cerebral convolutions in primates.

Developmental profiles of SUMOylation pathway proteins in rat cerebrum and cerebellum.

Protein SUMOylation regulates multiple processes involved in the differentiation and maturation of cells and tissues during development. Despite this, relatively little is known about the spatial and temporal regulation of proteins that mediate SUMOylation and deSUMOylation in the CNS. Here we monitor the expression of key SUMO pathway proteins and levels of substrate protein SUMOylation in the forebrain and cerebellum of Wistar rats during development. Overall, the SUMOylation machinery is more highly-expressed at E18 and decreases thereafter, as previously described. All of the proteins investigated are less abundant in adult than in embryonic brain. Furthermore, we show for first time that the profiles differ between cerebellum and cerebrum, indicating differential regional regulation of some of the proteins analysed. These data provide further basic observation that may open a new perspective of research about the role of SUMOylation in the development of different brain regions.

Brain-selective mild hypothermia promotes long-term white matter integrity after ischemic stroke in mice.

INTRODUCTION: The neuroprotective effects of hypothermia in acute ischemic stroke are well documented. However, the mechanisms involved in the effects remain to be clearly elucidated and the role of hypothermia on long-term white matter integrity after acute ischemic stroke has yet to be investigated. AIMS: To investigate the role of mild focal hypothermia on long-term white matter (WM) integrity after transient cerebral ischemia. RESULTS: Mild focal hypothermia treatment immediately after ischemic stroke significantly promotes WM integrity 28 days after the occlusion of the middle cerebral artery (MCAO) in mice. Higher integrity of white matter, lower activation of total microglia, less infarct volume, and better neurobehavioral function were detected in hypothermia-treated mice compared to normothermia-treated mice. Furthermore, we found that hypothermia could decrease detrimental M1 phenotype microglia and promote healthy M2 phenotype microglia. In vitro, results also indicated that hypothermia promoted oligodendrocytes differentiation and maturation after oxygen glucose deprivation. CONCLUSION: Hypothermia promotes long-term WM integrity and inhibits neuroinflammation in a mouse model of ischemic brain injury.

Comparative Action of Cardiotonic Steroids on Intracellular Processes in Rat Cortical Neurons.

Binding to Na+,K+-ATPase, cardiotonic steroids (CTS) activate intracellular signaling cascades that affect gene expression and regulation of proliferation and apoptosis in cells. Ouabain is the main CTS used for studying these processes. The effects of other CTS on nervous tissue are practically uncharacterized. Previously, we have shown that ouabain affects the activation of mitogen-activated protein kinases (MAP kinases) ERK1/2, p38, and JNK. In this study, we compared the effects of digoxin and bufalin, which belong to different subclasses of CTS, on primary culture of rat cortical cells. We found that CTS toxicity is not directly related to the degree of Na+,K+-ATPase inhibition, and that bufalin and digoxin, like ouabain, are capable of activating ERK1/2 and p38, but with different concentration and time profiles. Unlike bufalin and ouabain, digoxin did not decrease JNK activation after long-term incubation. We concluded that the toxic effect of CTS in concentrations that inhibit less than 80% of Na+,K+-ATPase activity is related to ERK1/2 activation as well as the complex profile of MAP kinase activation. A direct correlation between Na+,K+-ATPase inhibition and the degree of MAP kinase activation is only observed for ERK1/2. The different action of the three CTS on JNK and p38 activation may indicate that it is associated with intracellular signaling cascades triggered by protein-protein interactions between Na+,K+-ATPase and various partner proteins. Activation of MAP kinase pathways by these CTS occurs at concentrations that inhibit Na+,K+-ATPase containing the α1 subunit, suggesting that these signaling cascades are realized via α1. The results show that the signaling processes in neurons caused by CTS can differ not only because of different inhibitory constants for Na+,K+-ATPase.

Tracking Effects of SIL1 Increase: Taking a Closer Look Beyond the Consequences of Elevated Expression Level.

SIL1 acts as a co-chaperone for the major ER-resident chaperone BiP and thus plays a role in many BiP-dependent cellular functions such as protein-folding control and unfolded protein response. Whereas the increase of BiP upon cellular stress conditions is a well-known phenomenon, elevation of SIL1 under stress conditions was thus far solely studied in yeast, and different studies indicated an adverse effect of SIL1 increase. This is seemingly in contrast with the beneficial effect of SIL1 increase in surviving neurons in neurodegenerative disorders such as amyotrophic lateral sclerosis and Alzheimer's disease. Here, we addressed these controversial findings. Applying cell biological, morphological and biochemical methods, we demonstrated that SIL1 increases in various mammalian cells and neuronal tissues upon cellular stress. Investigation of heterozygous SIL1 mutant cells and tissues supported this finding. Moreover, SIL1 protein was found to be stabilized during ER stress. Increased SIL1 initiates ER stress in a concentration-dependent manner which agrees with the described adverse SIL1 effect. However, our results also suggest that protective levels are achieved by the secretion of excessive SIL1 and GRP170 and that moderately increased SIL1 also ameliorates cellular fitness under stress conditions. Our immunoprecipitation results indicate that SIL1 might act in a BiP-independent manner. Proteomic studies showed that SIL1 elevation alters the expression of proteins including crucial players in neurodegeneration, especially in Alzheimer's disease. This finding agrees with our observation of increased SIL1 immunoreactivity in surviving neurons of Alzheimer's disease autopsy cases and supports the assumption that SIL1 plays a protective role in neurodegenerative disorders.

Temporal relation between neural activity and neurite pruning on a numerical model and a microchannel device with micro electrode array.

Synapse elimination and neurite pruning are essential processes for the formation of neuronal circuits. These regressive events depend on neural activity and occur in the early postnatal days known as the critical period, but what makes this temporal specificity is not well understood. One possibility is that the neural activities during the developmentally regulated shift of action of GABA inhibitory transmission lead to the critical period. Moreover, it has been reported that the shifting action of the inhibitory transmission on immature neurons overlaps with synapse elimination and neurite pruning and that increased inhibitory transmission by drug treatment could induce temporal shift of the critical period. However, the relationship among these phenomena remains unclear because it is difficult to experimentally show how the developmental shift of inhibitory transmission influences neural activities and whether the activities promote synapse elimination and neurite pruning. In this study, we modeled synapse elimination in neuronal circuits using the modified Izhikevich's model with functional shifting of GABAergic transmission. The simulation results show that synaptic pruning within a specified period like the critical period is spontaneously generated as a function of the developmentally shifting inhibitory transmission and that the specific firing rate and increasing synchronization of neural circuits are seen at the initial stage of the critical period. This temporal relationship was experimentally supported by an in vitro primary culture of rat cortical neurons in a microchannel on a multi-electrode array (MEA). The firing rate decreased remarkably between the 18-25 days in vitro (DIV), and following these changes in the firing rate, the neurite density was slightly reduced. Our simulation and experimental results suggest that decreasing neural activity due to developing inhibitory synaptic transmission could induce synapse elimination and neurite pruning at particular time such as the critical period. Additionally, these findings indicate that we can estimate the maturity level of inhibitory transmission and the critical period by measuring the firing rate and the degree of synchronization in engineered neural networks.

Retinoblastoma protein controls growth, survival and neuronal migration in human cerebral organoids.

The tumor suppressor retinoblastoma protein (RB) regulates S-phase cell cycle entry via E2F transcription factors. Knockout (KO) mice have shown that RB plays roles in cell migration, differentiation and apoptosis, in developing and adult brain. In addition, the RB family is required for self-renewal and survival of human embryonic stem cells (hESCs). Since little is known about the role of RB in human brain development, we investigated its function in cerebral organoids differentiated from gene-edited hESCs lacking RB. We show that RB is abundantly expressed in neural stem and progenitor cells in organoids at 15 and 28 days of culture. RB loss promoted S-phase entry in DCX+ cells and increased apoptosis in Sox2+ neural stem and progenitor cells, and in DCX+ and Tuj1+ neurons. Associated with these cell cycle and pro-apoptotic effects, we observed increased CCNA2 and BAX gene expression, respectively. Moreover, we observed aberrant Tuj1+ neuronal migration in RB-KO organoids and upregulation of the gene encoding VLDLR, a receptor important in reelin signaling. Corroborating the results in RB-KO organoids in vitro, we observed ectopically localized Tuj1+ cells in RB-KO teratomas grown in vivo Taken together, these results identify crucial functions for RB in the cerebral organoid model of human brain development.

Induction of Expansion and Folding in Human Cerebral Organoids.

An expansion of the cerebral neocortex is thought to be the foundation for the unique intellectual abilities of humans. It has been suggested that an increase in the proliferative potential of neural progenitors (NPs) underlies the expansion of the cortex and its convoluted appearance. Here we show that increasing NP proliferation induces expansion and folding in an in vitro model of human corticogenesis. Deletion of PTEN stimulates proliferation and generates significantly larger and substantially folded cerebral organoids. This genetic modification allows sustained cell cycle re-entry, expansion of the progenitor population, and delayed neuronal differentiation, all key features of the developing human cortex. In contrast, Pten deletion in mouse organoids does not lead to folding. Finally, we utilized the expanded cerebral organoids to show that infection with Zika virus impairs cortical growth and folding. Our study provides new insights into the mechanisms regulating the structure and organization of the human cortex.

Pertussis Toxin Exploits Host Cell Signaling Pathways Induced by Meningitis-Causing E. coli K1-RS218 and Enhances Adherence of Monocytic THP-1 Cells to Human Cerebral Endothelial Cells.

Pertussis toxin (PTx), the major virulence factor of the whooping cough-causing bacterial pathogen Bordetella pertussis, permeabilizes the blood-brain barrier (BBB) in vitro and in vivo. Breaking barriers might promote translocation of meningitis-causing bacteria across the BBB, thereby facilitating infection. PTx activates several host cell signaling pathways exploited by the neonatal meningitis-causing Escherichia coli K1-RS218 for invasion and translocation across the BBB. Here, we investigated whether PTx and E. coli K1-RS218 exert similar effects on MAPK p38, NF-κB activation and transcription of downstream targets in human cerebral endothelial TY10 cells using qRT-PCR, Western blotting, and ELISA in combination with specific inhibitors. PTx and E. coli K1-RS218 activate MAPK p38, but only E. coli K1-RS218 activates the NF-κB pathway. mRNA and protein levels of p38 and NF-κB downstream targets including IL-6, IL-8, CxCL-1, CxCL-2 and ICAM-1 were increased. The p38 specific inhibitor SB203590 blocked PTx-enhanced activity, whereas E. coli K1-RS218's effects were inhibited by the NF-κB inhibitor Bay 11-7082. Further, we found that PTx enhances the adherence of human monocytic THP-1 cells to human cerebral endothelial TY10 cells, thereby contributing to enhanced translocation. These modulations of host cell signaling pathways by PTx and meningitis-causing E. coli support their contributions to pathogen and monocytic THP-1 cells translocation across the BBB.

[RATIO OF PREFRONTAL CORTEX NEURAL ACTIVITY BOTH HEMISPHERES DURING TASK OF CHOICE IN THE TWO-RING MAZE].

Neural activity in two symmetrical areas of the prefrontal cortex left and right hemispheres of the rat brain (55 and 47 neurons, respectively) were recorded during the execution of behavioral tasks in the two-ring maze. Experiments were carried out in two different conditions - task with the key, when only appropriate side to signal was reinforced, and without a key, when any choice was reinforced. Differential neural activity was estimated - the level of difference in firing on the right and left choice. When the animal did not guided by external keys (two behavioral situations: trails in a behavior block without any keys or error trails in behavior block with key presentation) there was observed prevalence of differential activity in the left hemisphere. The prevalence in the right hemisphere was observed in the correct trials in behavior block with key presentation. Apparently this is evidence of the dynamics in the hemispheric balance, depending on the external and internal conditions and the special role of the right hemisphere in the mechanisms of learning and inclusion of external determinants of the adaptive behavior response.

Neuroscience and education: We already reached the tipping point / Neurociencia y educación: ya hemos alcanzado el punto crítico

The aim of this contribution is to introduce the present Special Issue on Neuroscience and Education of the Revista de Psicología Educativa/Educational Psychology. After a brief introduction to current advances in general cognitive neuroscience that are being possible by means of brain imaging techniques available only during the most recent decades, we will discuss some aspects that have been contributing to hamper a true integration between both disciplines (neuroscience and education). The articles included in the present monograph provide empirical evidence that neuroscience has already reached a sufficient body of knowledge as to substantially improve education and political decisions in this respect. Neuroscience reveals that brain maturation extends at least until the second decade of life and that the exposition to different developmental experiences and opportunities is crucial along this extensive life period, so that none of its phases should be downplayed

Esta contribución pretende introducir y contextualizar el presente monográfico de la Revista de Psicología Educativa/Educational Psychology sobre neurociencia y educación. Tras introducir brevemente los avances que en neurociencia cognitiva, en general, se están alcanzando gracias a las técnicas de imagen cerebral disponibles sólo en las últimas décadas, se discuten algunos aspectos que han hecho difícil la verdadera integración entre ambas disciplinas (la neurociencia y la educación). Los artículos incluidos en este monográfico demostrarán que la neurociencia ofrece una cantidad más que suficiente de conocimiento acumulado como para aportar sustancialmente a la educación y a las políticas educativas. La neurociencia revela que la maduración cerebral no se alcanza hasta la segunda década de vida de la persona y que la exposición a diferentes experiencias y oportunidades de desarrollo es crucial a lo largo de toda esta extensa etapa vital, sin que debamos descuidar unos momentos más que otros

The emerging role of educational neuroscience in education reform / El papel emergente de la neurociencia educativa en la reforma de la educación

In the early 90s a movement began in education called "brain-based learning" that attempted to link neuroscience and education. However, many in both science and education felt it was untenable to make this leap. While early attempts to bridge the fields sparked controversy, it can now be argued that neuroscience does have a role to play in education reform. This paper explores suggestions for the appropriate training of the Educational Neuroscientist, broad interventions based on Educational Neuroscience that could reform curriculum, and emerging ways the Educational Neuroscientist can inform professional development of educators

A principios de los años 90 surgió un movimiento en educación llamado "aprendizaje basado en el cerebro" que trataba de unir neurociencia y educación. No obstante, muchas personas tanto en ciencia como en educación, pensaban que no era viable dar tal salto. Mientras que los primeros intentos por tender puentes entre estos campos suscitó controversia, puede decirse ahora que la neurociencia sí tiene un papel que jugar en la reforma de la educación. Este artículo explora propuestas para el adecuado entrenamiento del neurocientífico educativo, intervenciones amplias sustentadas en la neurociencia educativa que podrían reformar el currículum y de qué nuevas maneras podría contribuir neurocientífico educativo al desarrollo profesional de los educadores

Development of the social brain during adolescence / Desarrollo del cerebro social durante la adolescencia

This article describes recent research which informs our understanding of changes in social cognition during adolescence. The focus will be on mentalising, the ability to attribute and manipulate mental states in the self and others. Mentalising is supported by the medial prefrontal cortex (MPFC) and both anterior and posterior regions of the temporal lobes. In the past decade, studies have demonstrated development during adolescence of white and grey matter brain structure, with most protracted changes observed in frontal and temporal lobes, including those regions supporting mentalising. This article presents evidence that certain aspects of social cognition continue to change during adolescence, highlighting results from recent research investigating the use of theory of mind information in a communicative context. The findings highlight how adolescence, and not only childhood, is a time of continued maturation of brain and behaviour, when education and the environment can have an impact on cognitive development

Este artículo describe resultados de investigaciones recientes sobre cambios en la cognición social durante la adolescencia. Se centra en la mentalización, la capacidad de atribuir y manipular estados mentales en uno mismo y en los demás. La mentalización está asociada con la corteza prefrontal media (MPFC) y las regiones anterior y posterior de los lóbulos temporales. En el último decenio hay estudios que demuestran que a lo largo de la adolescencia se desarrolla la estructura cerebral tanto de la sustancia blanca como de la gris, observándose los cambios más notables en los lóbulos frontal y temporal, que incluyen regiones en las que se asienta la mentalización. Este artículo demuestra que determinados aspectos de la cognición social siguen desarrollándose durante la adolescencia, presentando los resultados de estudios recientes que investigan la utilización de la teoría de la mente en un contexto comunicativo. Los resultados subrayan cómo la adolescencia, y no sólo la niñez, es una etapa de maduración continua del cerebro y del comportamiento, cuando la educación y el entorno pueden influir en el desarrollo cognitivo