Advanced morphometric techniques applied to the study of human brain anatomy

El desarrollo de las t��cnicas de im��genes por resonancia magn��tica han permitido el estudio y cuantificaci��n, in vivo, de los cambios que ocurren en la morfolog��a cerebral ligados a procesos tales como el neurodesarrollo, el envejecimiento, el aprendizaje o la enfermedad. Un gran n��mero de m��todos de morfometr��a han sido desarrollados con el fin de extraer la informaci��n contenida en estas im��genes y traducirla en indicadores de forma o tama��o, tales como el volumen o el grosor cortical; marcadores que son posteriormente empleados para encontrar diferencias estad��sticas entre poblaciones de sujetos o realizar correlaciones entre la morfolog��a cerebral y, por ejemplo, la edad o la severidad de determinada enfermedad. A pesar de la amplia variedad de biomarcadores y metodolog��as de morfometr��a, muchos estudios sesgan sus hip��tesis, y con ello los resultados experimentales, al empleo de un n��mero reducido de biomarcadores o a al uso de una ��nica metodolog��a de procesamiento. Con el presente trabajo se pretende demostrar la importancia del empleo de diversos m��todos de morfometr��a para lograr una mejor caracterizaci��n del proceso que se desea estudiar. En el mismo se emplea el an��lisis de forma para detectar diferencias, tanto globales como locales, en la morfolog��a del t��lamo entre pacientes adolescentes con episodios tempranos de psicosis y adolescentes sanos. Los resultados obtenidos demuestran que la diferencia de volumen tal��mico entre ambas poblaciones de sujetos, previamente descrita en la literatura, se debe a una reducci��n del volumen de la regi��n anterior-mediodorsal y del n��cleo pulvinar del t��lamo de los pacientes respecto a los sujetos sanos. Adem��s, se describe el desarrollo de un estudio longitudinal, en sujetos sanos, que emplea simult��neamente distintos biomarcadores para la caracterizaci��n y cuantificaci��n de los cambios que ocurren en la morfolog��a de la corteza cerebral durante la adolescencia. A trav��s de este estudio se revela que el proceso de ���alisado��� que experimenta la corteza cerebral durante la adolescencia es consecuencia de una disminuci��n de la profundidad, ligada a un incremento en el ancho, de los surcos corticales. Finalmente, esta metodolog��a es aplicada, en un dise��o transversal, para el estudio de las causas que provocan el decrecimiento tanto del grosor cortical como del ��ndice de girificaci��n en adolescentes con episodios tempranos de psicosis. ABSTRACT The ever evolving sophistication of magnetic resonance image techniques continue to provide new tools to characterize and quantify, in vivo, brain morphologic changes related to neurodevelopment, senescence, learning or disease. The majority of morphometric methods extract shape or size descriptors such as volume, surface area, and cortical thickness from the MRI image. These morphological measurements are commonly entered in statistical analytic approaches for testing between-group differences or for correlations between the morphological measurement and other variables such as age, sex, or disease severity. A wide variety of morphological biomarkers are reported in the literature. Despite this wide range of potentially useful biomarkers and available morphometric methods, the hypotheses and findings of the grand majority of morphological studies are biased because reports assess only one morphometric feature and usually use only one image processing method. Throughout this dissertation biomarkers and image processing strategies are combined to provide innovative and useful morphometric tools for examining brain changes during neurodevelopment. Specifically, a shape analysis technique allowing for a fine-grained assessment of regional thalamic volume in early-onset psychosis patients and healthy comparison subjects is implemented. Results show that disease-related reductions in global thalamic volume, as previously described by other authors, could be particularly driven by a deficit in the anterior-mediodorsal and pulvinar thalamic regions in patients relative to healthy subjects. Furthermore, in healthy adolescents different cortical features are extracted and combined and their interdependency is assessed over time. This study attempts to extend current knowledge of normal brain development, specifically the largely unexplored relationship between changes of distinct cortical morphological measurements during adolescence. This study demonstrates that cortical flattening, present during adolescence, is produced by a combination of age-related increase in sulcal width and decrease in sulcal depth. Finally, this methodology is applied to a cross-sectional study, investigating the mechanisms underlying the decrease in cortical thickness and gyrification observed in psychotic patients with a disease onset during adolescence.

The anatomy of urban social networks and its implications in the searchability problem

The appearance of large geolocated communication datasets has recently increased our understanding of how social networks relate to their physical space. However, many recurrently reported properties, such as the spatial clustering of network communities, have not yet been systematically tested at different scales. In this work we analyze the social network structure of over 25���million phone users from three countries at three different scales: country, provinces and cities. We consistently find that this last urban scenario presents significant differences to common knowledge about social networks. First, the emergence of a giant component in the network seems to be controlled by whether or not the network spans over the entire urban border, almost independently of the population or geographic extension of the city. Second, urban communities are much less geographically clustered than expected. These two findings shed new light on the widely-studied searchability in self-organized networks. By exhaustive simulation of decentralized search strategies we conclude that urban networks are searchable not through geographical proximity as their country-wide counterparts, but through an homophily-driven community structure.