Frustrated hierarchical synchronization and emergent complexity in the human connectome network

The spontaneous emergence of coherent behavior through synchronization plays a key role in neural function, and its anomalies often lie at the basis of pathologies. Here we employ a parsimonious (mesoscopic) approach to study analytically and computationally the synchronization (Kuramoto) dynamics on the actual human-brain connectome network. We elucidate the existence of a so-far-uncovered intermediate phase, placed between the standard synchronous and asynchronous phases, i.e. between order and disorder. This novel phase stems from the hierarchical modular organization of the connectome. Where one would expect a hierarchical synchronization process, we show that the interplay between structural bottlenecks and quenched intrinsic frequency heterogeneities at many different scales, gives rise to frustrated synchronization, metastability, and chimera-like states, resulting in a very rich and complex phenomenology. We uncover the origin of the dynamic freezing behind these features by using spectral graph theory and discuss how the emerging complex synchronization patterns relate to the need for the brain to access –in a robust though flexible way– a large variety of functional attractors and dynamical repertoires without ad hoc fine-tuning to a critical pointWe acknowledge financial support from J. de Andalucía, grant P09-FQM-4682 and we thank O. Sporns for providing us access to the human connectome data

Self-Organized Criticality in Developing Neuronal Networks

Recently evidence has accumulated that many neural networks exhibit self-organized criticality. In this state, activity is similar across temporal scales and this is beneficial with respect to information flow. If subcritical, activity can die out, if supercritical epileptiform patterns may occur. Little is known about how developing networks will reach and stabilize criticality. Here we monitor the development between 13 and 95 days in vitro (DIV) of cortical cell cultures (n = 20) and find four different phases, related to their morphological maturation: An initial low-activity state (≈19 DIV) is followed by a supercritical (≈20 DIV) and then a subcritical one (≈36 DIV) until the network finally reaches stable criticality (≈58 DIV). Using network modeling and mathematical analysis we describe the dynamics of the emergent connectivity in such developing systems. Based on physiological observations, the synaptic development in the model is determined by the drive of the neurons to adjust their connectivity for reaching on average firing rate homeostasis. We predict a specific time course for the maturation of inhibition, with strong onset and delayed pruning, and that total synaptic connectivity should be strongly linked to the relative levels of excitation and inhibition. These results demonstrate that the interplay between activity and connectivity guides developing networks into criticality suggesting that this may be a generic and stable state of many networks in vivo and in vitro

Pre-invasive cervical disease and uterine cervical cancer in Brazilian adolescents: prevalence and related factors Doença cervical pré-invasiva e câncer cérvico-uterino em adolescentes brasileiras: prevalência e fatores associados

The objective was to describe the prevalence and factors associated with uterine cervical cancer (CA) and high-grade squamous intraepithelial lesions (HSIL) in adolescents. A cross-sectional study was carried out with 702 sexually active adolescents treated at a general hospital in Rio de Janeiro, Brazil, from 1993 to 2002. Screening was performed by cytopathology and colposcopy and confirmation by biopsy. Exposure variables were socio-demographic characteristics and those related to reproductive health, habits, and sexual behavior. Adjusted odds ratios were estimated using multivariate logistic regression analysis. Based on histopathology, the prevalence of HSIL/CA was 3% (95%CI: 1.8-4.6). There was one case of invasive cancer. With each additional pregnancy, the odds of HSIL/CA increased by 2.2 (95%CI: 1.1-4.4). Age was also associated with this outcome, doubling the odds of acquiring this degree of disease with each year of age (OR = 2.0; 95%CI: 1.2-3.4). The prevalence of lesions suggests the importance of including sexually active adolescent females in cervical cancer screening programs aimed at early detection and treatment of these lesions.<br>O objetivo foi descrever a freqüência e os fatores associados ao câncer cervical (CA) e lesões escamosas intra-epiteliais de alto grau (HSIL) entre adolescentes. Realizou-se estudo transversal com 702 adolescentes sexualmente ativas, assistidas em um hospital geral no Rio de Janeiro, Brasil, entre 1993 e 2002. A investigação foi realizada através de citopatologia e colposcopia, e a confirmação por biópsia cervical. As variáveis de exposição foram características sociais e demográficas, e aquelas relacionadas à saúde reprodutiva, hábitos e comportamento sexual. Baseado nos achados histopatológicos, a freqüência de HSIL/CA foi 3% (IC95%: 1,8-4,6). Houve um caso de câncer invasivo. A cada nova gestação, a chance de HSIL/CA aumentava 2,2 vezes (IC95%: 1,1-4,4). A idade também esteve associada com este resultado (OR = 2,0; IC95%: 1,2-3,4), dobrando a cada ano de idade a chance de adquirir este nível da doença. A freqüência de lesões cervicais intra-epiteliais sugere a importância de incluir adolescentes sexualmente ativas nos programas de prevenção do câncer cervical, com o objetivo de detectar e assegurar o tratamento precoce destas lesões