Every year, a committee of experts sits down with a tough job to do: from among all ICREA publications, they must find a handful that stand out from all the others. This is indeed a challenge. The debates are sometimes heated and always difficult but, in the end, a shortlist of 24 publications is produced. No prize is awarded, and the only additional acknowledge is the honour of being chosen and highlighted by ICREA. Each piece has something unique about it, whether it be a particularly elegant solution, the huge impact it has in the media or the sheer fascination it generates as a truly new idea. For whatever the reason, these are the best of the best and, as such, we are proud to share them here.


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  • Large scale brain activations predict reasoning profiles (2012)

    Bonatti, Luca (UPF)

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    Large scale brain activations predict reasoning profiles

    For many centuries, philosophers and scientists have been fascinated by a form of reasoning that allows us to draw necessary conclusions from some premises. For example, if we hear that All men are mortals, and that Socrates is a man, we know that Socrates is mortal, by simply reasoning from these premises. This way to draw novel knowledge by means of necessary inferences is so ubiquitous in human reasoning that we often do not even realize that we are making logical inferences. However its neural bases are poorly understood. Furthermore, notoriously, different individuals follow different strategies to find solutions. In our study, we propose a new approach to understand the neural basis of deductive reasoning and explore in detail the inter-individual variability.

    In general, when studying the neural basis of behavior, researchers start from a certain behavior and try to identify the underlying patterns of brain activity. We reverse this strategy and show that specific patterns of brain activity can predict what strategy an individual will use when reasoning about elementary deductive problems. We also show that the predictive power of the activity profiles is distributed in a non-uniform way across the areas activated during the corresponding cognitive operation. Thus, the activation of left ventro-lateral and occipital cortex (BA47 and BA9) predicts if participants will draw logically valid solutions. By contrast, the activations of the left lateral and superior frontal cortex ((BA44/45 and BA6/8) predict if participants will be consistent in their responses, even when they make mistakes.

    We conclude that deductive reasoning can best be described as a cascade of cognitive processes that require the concerted operation of several, functionally different brain areas. In general, the activation of some areas of the left brain are essential to reason logically. Potentially, this discovery may allow future research to better characterize some cognitive deficits that attain patients with brain injuries, and set up better rehabilitation therapies. This research may also help creating novel and more efficient educational tools inspired by how the brain actually processes problems.

    The work, realized in collaboration with Carlo Reverberi, Paolo Cherubini and Eraldo Paulesu (University of Milano-Bicocca), Richard Frackowiak (Centre Hospitalier Universitaire Vaudois, Lausanne) and Emiliano Macaluso (Fondazione Santa Lucia, Rome), won the Editor's Choice Award at the 18th World Congress of the Human Brain Mappin

  • The smallest typewriter in the world (2012)

    Catalán Bernabé, Gustau (ICN2)

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    The smallest typewriter in the world

    The search for more compact ways to store information is a running theme in nanotechnology. The basic concept is simple: one needs materials that can be in two different states (that become the 1's and 0's in binary code), and an efficient way to change between them so as to write the information. A good example is magnetic memories, which are based on tiny magnets that can be oriented with their north pole up or down. An alternative are ferroelectric memories based on the property of some materials to have a reorientable electric dipole, i.e. a molecular structure where the centers' positive charge and negative charge are separated and can be inverted by an electric field. Like magnets, ferroelectrics also have a north pole and a south pole that define a 1 and a 0. Unlike magnets, however, ferroelectrics are written with voltage rather than current, and are therefore more energy-efficient in theory. In practice, however, although in thin films the writing voltage can be only a couple of volts, the electric field (voltage divided by thickness) is still huge, and this causes problems: materials may fatigue or degrade over time, or even have dielectric breakdown. It is therefore desirable to find an alternative writing method. In a collaboration involving groups in Catalonia and the US, we have just discovered a simple alternative: pushing.

    Although mechanical pressure (stress) cannot in theory invert polarization, stress differences can, thanks to a phenomenon known as flexoelectricity, which is the ability of all materials to polarize when subject to a deformation gradient. Although it is a universal property, it is small at the macroscale. At the nanoscale, however, gradients can be huge and so is therefore flexoelectricity. Big enough, in fact, to invert the polarization of a ferroelectric memory. We have demonstrated this by using the sharp tip of an atomic force microscope (a needle with a radius of only 30nm) and pushing gently (a millionth of a Newton of force) onto the surface of a ferroelectric thin film. Because of the sharpness of the tip, the force is concentrated, leading to large but very localized deformation gradients. In the places where the tip pushes, therefore, large flexoelectricity is realized, which inverts the ferroelectric dipole from the up state to the down state -between 1 and 0 in information terms. Thus, by converting mechanical pressure into nanoscopic information, flexoelectricity brings up to date a very old memory storage device: the typewriter.

  • Understanding how malaria parasites adapt to changes in their environment: the role of epigenetic variation (2012)

    Cortés Closas, Alfred (ISGlobal)

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    Understanding how malaria parasites adapt to changes in their environment: the role of epigenetic variation

    Asexual blood stages of malaria parasites live inside red blood cells, a relatively stable environment. However, there are still exogenous changes to which they need to adapt. The majority of organisms respond to environmental fluctuations by sensing the environment and activating distinct transcriptional programs that allow survival under the different conditions, but malaria parasites are largely unable to do this. We predicted that this limited capacity is compensated by the ability of the parasite to use alternative strategies for rapid adaptation. To test this hypothesis, we took "transcriptional snapshots" of clonal populations of parasites, where all parasites have the same genes, and found that individual parasites within the populations have different combinations of expressed and repressed genes. Genes that can be found in different transcriptional states represent about 10% of the genes in the parasite's genome, and their expression patterns are clonally transmitted by epigenetic mechanisms. The majority of these genes (clonally variant genes) are involved in host-parasite interactions. They include genes involved in immune evasion but also genes involved in many other processes for which alternative conditions exist. The characteristics of these genes indicate that changes in their expression result not only in antigenic variation but also in functional variation.

    Spontaneous transcriptional and phenotypic heterogeneity within isogenic parasite populations has a clear adaptive potential. When an environmental challenge occurs, heterogeneity allows selection of pre-existing parasites with transcriptional patterns that confer fitness under the new conditions. We demonstrated experimentally that malaria parasites use this bet-hedging (risk spreading) strategy for adaptation to periodical heat-shock mimicking cyclical malaria fevers. We also found that the mechanism that mediates repression of clonally variant genes is similar for all gene families, involving formation of a conserved type of heterochromatin that can be transmitted from one generation to the next by epigenetic mechanism. The active or repressed states are heritable but spontaneously reversible, to confer the necessary flexibility to the process.

    Malaria parasites have a remarkable ability to adapt to any challenge, including adaptation to human interventions such as drugs or vaccines. Our findings bring light into the adaptive mechanisms used by malaria parasites and open the way to identify the specific genes that mediate adaptation

  • Bilingualism tunes executive control brain areas (2012)

    Costa Martínez, Albert (UPF)

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    Bilingualism tunes executive control brain areas

    Everyday life requires us to monitor cognitive conflicts induced by distracting information from either perceptual sources (e.g., competing traffic signs when driving) or internal sources (e.g., thoughts about matters irrelevant to the current goal). The anterior cingulate cortex (ACC) is an important component in
    the neural circuit mediating cognitive control and one intimately tied to monitoring conflicting information. Language use also requires cognitive control and plausibly recruits a similar circuit. The demand for such control is most evident in bilinguals, and such speakers provide an opportunity to test the generality of the neural mechanisms involved in cognitive control.

    In order to directly examine the link between the regions involved in control of language conflict and those involved in cognitive control, more generally, we need to examine the regions involved within the same study. Accordingly, we asked bilinguals to perform a language control task (i.e., language switching) and a nonverbal conflict task (a flanker task) during the same event-related functional magnetic resonance imaging (er-fMRI) session.

    The results revealed that the dorsal anterior cingulate cortex (ACC), a structure tightly bound to domain-general executive control functions, is a common locus for language control and resolving nonverbal conflict. We also show an experience-dependent effect in the same region: Bilinguals use this structure more efficiently than monolinguals to monitor nonlinguistic cognitive conflicts. They adapted better to conflicting situations showing less ACC activity while outperforming monolinguals. Importantly, for bilinguals, brain activity in the ACC, as well as behavioral measures, also correlated positively with local gray matter volume. These results suggest that early learning and lifelong practice of 2 languages exert a strong impact upon human neocortical development.

    In conclusion, from our combined findings, we suggest that practicing lifelong bilingualism has neurocognitive benefits. The fact that bilinguals learn early in life to resolve language conflicts and to avoid speaking in the nontarget language leads to beneficial plastic changes in the dorsal ACC. Bilinguals not only resolve cognitive conflicts with less neural resource but their brain also adapts better to conflicting situations as shown in our sessions effects analysis of the flanker task. The ACC conflict effect region is more tuned for conflict monitoring in

  • Theory and Simulation in Neuroscience. (2012)

    Deco, Gustavo (UPF)

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    Theory and Simulation in Neuroscience.

    Modeling work in neuroscience can be classified using two different criteria. The first one is the complexity of the model, ranging from simplified conceptual models that are amenable to mathematical analysis to detailed models that require simulations in order to understand their properties. The second criterion is that of direction of workflow, which can be from microscopic to macroscopic scales (bottom-up) or from behavioral target functions to properties of components (top-down). We reviewed in this Science article the interaction of theory and simulation using examples of top-down and bottom-up studies and point to some current developments in the fields of computational and theoretical neuroscience.

  • Structure and function of Polycomb complex in embryonic stem cells (2012)

    Di Croce, Luciano (CRG)

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    Structure and function of Polycomb complex in embryonic stem cells

    In 2012, two papers from Di Croce's lab have been highlighted on the cover of top-impacting journals.

    Embryonic stem (ES) cells are key for embryonic development. ES cells can divide extensively before they differentiate into the somatic cells that form the adult tissue. The Polycomb complex regulates the proliferation, and the subsequent differentiation into somatic cells, of ES cells, but the exact role of the different Polycomb proteins in this complex has been a long-standing puzzle. In January 2012, we elucidated the role that several specific Polycomb proteins play during cell development through their incorporation into the complex. This discovery represents a breakthrough in understanding both how stem cells proliferate and which specific functions the Cbx proteins and the Polycomb complex play during tumor development. Identifying new proteins that are essential for maintaining ES cell pluripotency is a key step in elucidating tumor formation processes and in advancing regenerative medicine.

    In parallel, we have also investigated how Polycomb complexes are recruited to DNA. We identified the protein PHF19 as a key player in directing Polycomb binding to genomic loci. Active transcribed genes are marked by the presence of a specific histone modification, which is the presence of a methyl group on the lysine 36 of histone H3 (H3K36me). The Tudor domain of Phf19 directly recognizes this histone modification and recruits the all Polycomb complex, which leads to gene silencing. These findings describe how active genes are silenced during cellular differentiation.