Development of new methods in biomedical engineering for brain connectivity biomarkers in epilepsy and other pathological conditions

243 p.The aim of this thesis is to humbly explore the application of diverse methodologies and theories comingfrom Computer Sciences, Mathematics and Physics in the field of neurosciences, with an special focus onneurodegenerative diseases.In this thesis brain network analysis was used to unveil functional and structural patterns in bothpathological and healthy brains. We explore in a different manner various aspects related with theepilepsy, AD and healthy aging

Development of new methods in biomedical engineering for brain connectivity biomarkers in epilepsy and other pathological conditions

243 p.The aim of this thesis is to humbly explore the application of diverse methodologies and theories comingfrom Computer Sciences, Mathematics and Physics in the field of neurosciences, with an special focus onneurodegenerative diseases.In this thesis brain network analysis was used to unveil functional and structural patterns in bothpathological and healthy brains. We explore in a different manner various aspects related with theepilepsy, AD and healthy aging

guifi.net : Red Abierta, Libre y Neutral en Txulapain

En este proyecto fin de carrera se estudia, analiza y redacta la implantación de la primera red libre guifi.net de la Comunidad Foral. En este trabajo, además, se resuelve la necesidad concreta del acceso a Internet en las zonas rurales del municipio de Xulapain (formado por 13 concejos) a 12 kms de Iruñea. guifi.net es un proyecto libre que cumple los requisitos de red libre, abierta y neutral.Ingeniería en InformáticaInformatika Ingeniaritz

Identification of redundant and synergetic circuits in triplets of electrophysiological data

Neural systems are comprised of interacting units, and relevant information regarding their function or malfunction can be inferred by analyzing the statistical dependencies between the activity of each unit. Whilst correlations and mutual information are commonly used to characterize these dependencies, our objective here is to extend interactions to triplets of variables to better detect and characterize dynamic information transfer. Our approach relies on the measure of interaction information (II). The sign of II provides information as to the extent to which the interaction of variables in triplets is redundant (R) or synergetic (S). Here, based on this approach, we calculated the R and S status for triplets of electrophysiological data recorded from drug-resistant patients with mesial temporal lobe epilepsy in order to study the spatial organization and dynamics of R and S close to the epileptogenic zone (the area responsible for seizure propagation). In terms of spatial organization, our results show that R matched the epileptogenic zone while S was distributed more in the surrounding area. In relation to dynamics, R made the largest contribution to high frequency bands (14-100Hz), whilst S was expressed more strongly at lower frequencies (1-7Hz). Thus, applying interaction information to such clinical data reveals new aspects of epileptogenic structure in terms of the nature (redundancy vs. synergy) and dynamics (fast vs. slow rhythms) of the interactions. We expect this methodology, robust and simple, can reveal new aspects beyond pair-interactions in networks of interacting units in other setups with multi-recording data sets (and thus, not necessarily in epilepsy, the pathology we have approached here).Comment: 31 pages, 6 figures, 3 supplementary figures. To appear in the Journal of Neural Engineering in its current for

Information flow between resting state networks

The resting brain dynamics self-organizes into a finite number of correlated patterns known as resting state networks (RSNs). It is well known that techniques like independent component analysis can separate the brain activity at rest to provide such RSNs, but the specific pattern of interaction between RSNs is not yet fully understood. To this aim, we propose here a novel method to compute the information flow (IF) between different RSNs from resting state magnetic resonance imaging. After haemodynamic response function blind deconvolution of all voxel signals, and under the hypothesis that RSNs define regions of interest, our method first uses principal component analysis to reduce dimensionality in each RSN to next compute IF (estimated here in terms of Transfer Entropy) between the different RSNs by systematically increasing k (the number of principal components used in the calculation). When k = 1, this method is equivalent to computing IF using the average of all voxel activities in each RSN. For k greater than one our method calculates the k-multivariate IF between the different RSNs. We find that the average IF among RSNs is dimension-dependent, increasing from k =1 (i.e., the average voxels activity) up to a maximum occurring at k =5 to finally decay to zero for k greater than 10. This suggests that a small number of components (close to 5) is sufficient to describe the IF pattern between RSNs. Our method - addressing differences in IF between RSNs for any generic data - can be used for group comparison in health or disease. To illustrate this, we have calculated the interRSNs IF in a dataset of Alzheimer's Disease (AD) to find that the most significant differences between AD and controls occurred for k =2, in addition to AD showing increased IF w.r.t. controls.Comment: 47 pages, 5 figures, 4 tables, 3 supplementary figures. Accepted for publication in Brain Connectivity in its current for

Spatial characterization of the effect of age and sex on macular layer thicknesses and foveal pit morphology

Characterizing the effect of age and sex on macular retinal layer thicknesses and foveal pit morphology is crucial to differentiating between natural and disease-related changes. We applied advanced image analysis techniques to optical coherence tomography (OCT) to: 1) enhance the spatial description of age and sex effects, and 2) create a detailed open database of normative retinal layer thickness maps and foveal pit shapes. The maculae of 444 healthy subjects (age range 21–88) were imaged with OCT. Using computational spatial data analysis, thickness maps were obtained for retinal layers and averaged into 400 (20 x 20) sectors. Additionally, the geometry of the foveal pit was radially analyzed by computing the central foveal thickness, rim height, rim radius, and mean slope. The effect of age and sex on these parameters was analyzed with multiple regression mixed-effects models. We observed that the overall age-related decrease of the total retinal thickness (TRT) (-1.1% per 10 years) was mainly driven by the ganglion cell-inner plexiform layer (GCIPL) (-2.4% per 10 years). Both TRT and GCIPL thinning patterns were homogeneous across the macula when using percentual measurements. Although the male retina was 4.1 μm thicker on average, the greatest differences were mainly present for the inner retinal layers in the inner macular ring (up to 4% higher TRT than in the central macula). There was an age-related decrease in the rim height (1.0% per 10 years) and males had a higher rim height, shorter rim radius, and steeper mean slope. Importantly, the radial analysis revealed that these changes are present and relatively uniform across angular directions. These findings demonstrate the capacity of advanced analysis of OCT images to enhance the description of the macula. This, together with the created dataset, could aid the development of more accurate diagnosis models for macular pathologies.This study was partially co-funded by the Instituto de Salud Carlos III (https://www.isciii.es) through the projects PI14/00679 (IG) and PI16/00005 (IG), by the Basque Foundation for Health Innovation and Research (https://www.bioef.org) through the project BIO17/ND/010 (IG), and by the Department of Health of the Basque Government (https://www.euskadi.eus/gobierno-vasco/departamento-salud) through the projects 2019111100 (IG), 2020333033(IG). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Foveal remodeling of retinal microvasculature in Parkinson’s disease

[EN] Background: Retinal microvascular alterations have been previously described in Parkinson’s disease (PD) patients using optical coherence tomography angiography (OCT-A). However, an extensive description of retinal vascular morphological features, their association with PD-related clinical variables and their potential use as diagnostic biomarkers has not been explored. Methods: We performed a cross-sectional study including 49 PD patients (87 eyes) and 40 controls (73 eyes). Retinal microvasculature was evaluated with Spectralis OCT-A and cognitive status with Montreal Cognitive Assessment. Unified PD Rating Scale and disease duration were recorded in patients. We extracted microvascular parameters from superficial and deep vascular plexuses of the macula, including the area and circularity of foveal avascular zone (FAZ), skeleton density, perfusion density, vessel perimeter index, vessel mean diameter, fractal dimension (FD) and lacunarity using Python and MATLAB. We compared the microvascular parameters between groups and explored their association with thickness of macular layers and clinical outcomes. Data were analyzed with General Estimating Equations (GEE) and adjusted for age, sex, and hypertension. Logistic regression GEE models were fitted to predict diagnosis of PD versus controls from microvascular, demographic, and clinical data. The discrimination ability of models was tested with receiver operating characteristic curves. Results: FAZ area was significantly smaller in patients compared to controls in superficial and deep plexuses, whereas perfusion density, skeleton density, FD and lacunarity of capillaries were increased in the foveal zone of PD. In the parafovea, microvascular parameters of superficial plexus were associated with ganglion cellinner plexiform layer thickness, but this was mainly driven by PD with mild cognitive impairment. No such associations were observed in controls. FAZ area was negatively associated with cognition in PD (non-adjusted models). Foveal lacunarity, combined with demographic and clinical confounding factors, yielded an outstanding diagnostic accuracy for discriminating PD patients from controls. Conclusion: Parkinson’s disease patients displayed foveal microvascular alterations causing an enlargement of the vascular bed surrounding FAZ. Parafoveal microvascular alterations were less pronounced but were related to inner retinal layer thinning. Retinal microvascular abnormalities helped discriminating PD from controls. All this supports OCT-A as a potential non-invasive biomarker to reveal vascular pathophysiology and improve diagnostic accuracy in PD.This study was partially co-funded by the Instituto de Salud Carlos III through the projects PI14/00679 and PI16/00005 (co-funded by European Regional Development Fund/European Social Fund “A way to make Europe”/“Investing in your future”), and by the Department of Health of the Basque Government through the projects “2019111100” and “2020333033”

Heart-brain synchronization breakdown in Parkinson's disease

Heart rate variability (HRV) abnormalities are potential early biomarkers in Parkinson's disease (PD) but their relationship with central autonomic network (CAN) activity is not fully understood. We analyzed the synchronization between HRV and brain activity in 31 PD patients and 21 age-matched healthy controls using blood-oxygen-level-dependent (BOLD) signals from resting-state functional brain MRI and HRV metrics from finger plethysmography recorded for 7.40 min. We additionally quantified autonomic symptoms (SCOPA-AUT) and objective autonomic cardiovascular parameters (blood pressure and heart rate) during deep breathing, Valsalva, and head-up tilt, which were used to classify the clinical severity of dysautonomia. We evaluated HRV and BOLD signals synchronization (HRV-BOLD-sync) with Pearson lagged cross-correlations and Fisher's statistics for combining window-length-dependent HRV-BOLD-Sync Maps and assessed their association with clinical dysautonomia. HRV-BOLD-sync was lower significantly in PD than in controls in various brain regions within CAN or in networks involved in autonomic modulation. Moreover, heart-brain synchronization index (HBSI), which quantifies heart-brain synchronization at a single-subject level, showed an inverse exposure-response relationship with dysautonomia severity, finding the lowest HBSI in patients with severe dysautonomia, followed by moderate, mild, and, lastly, controls. Importantly, HBSI was associated in PD, but not in controls, with Valsalva pressure recovery time (sympathetic), deep breathing E/I ratio (cardiovagal), and SCOPA-AUT. Our findings support the existence of heart-brain de-synchronization in PD with an impact on clinically relevant autonomic outcomes.We want to thank all the patients and participants involved in the study. This study was partially co-funded by Michael J. Fox Foundation [RRIA 2014 (Rapid Response Innovation Awards) Program (Grant ID: 10189)], by the Carlos III Health Institute, and the European Union (ERDF/ESF, "A Way to Make Europe"/"Investing in Your Future") through the projects PI14/00679 and PI16/00005, the Juan Rodes grant "JR15/00008" (I.G.), and by the Department of Health of the Basque Government through the project "2016111009" and "2020333033". A.J.M. was supported by a predoctoral grant from the Basque Government (PRE_2019_1_0070). M.I. acknowledges financial support from"La Caixa" Foundation (ID 100010434, fellowship LCF/BQ/EU20/11810065). The Edmond and Lily Safra Center for Brain Sciences and the Basque Government (POS_2019_2_0020) to A.E. J.M.C. is funded by Ikerbasque: The Basque Foundation for Science and from the Ministerial de Economia, Industria y Competitividad (Spain) and FEDER (grant DPI2016-79874-R), and from the Department of Economic and Infrastructure Development of the Basque Country (Elkartek Program, KK-2018/00032, KK-2018/00090, and KK-2021/00009/BCB)

Gestión académica de un centro escolar mediante un CMS: el caso de Iturrama BHI

Actualmente el centro de enseñanza secundaria Iturrama BHI cuenta con 80 docentes y más de 600 alumnos. El Departamento de Tecnología ha desarrollado un plan para implantar nuevas tecnologías en el centro. El proyecto fin de carrera se enmarca dentro de este plan y consiste en instalar y configurar un servidor para el centro y dotarlo de los servicios requeridos por el departamento. Se desean cumplir los siguientes objetivos: −Gestión de la Intranet. Diversos programas de la Intranet actual funcionan bajo Apache y están programados en PHP + MySQL. Adicionalmente habrá que implementar un sistema de gestión de contenidos (CMS) para poder actualizar y mantener más fácilmente el contenido de la misma. El profesorado necesita un espacio donde guardar sus documentos e información y un sistema de copias de seguridad de estos. −Mejorar la gestión (en base a perfiles de usuario) de todos los documentos del centro agrupándolos en un servidor. Estos son en su mayoría documentos de texto, hojas de cálculo y alguna presentación. −Centralizar el máximo de recursos didácticos posibles para que sean accesibles desde cualquier punto del centro. Asimismo, se desea acceder a estos recursos desde fuera del centro, lo cual ahora no es posible