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Treballs Finals de Grau d'Enginyeria Biomèdica. Facultat de Medicina i Ciències de la Salut. Universitat de Barcelona. Curs: 2022-2023. Tutor/Director: Rodríguez Allué, Manuel José, Neurodegenerative movement-related disorders are characterized by a progressive degeneration and loss of neurons, which lead to motor control impairment. Although the precise mechanisms underlying these conditions are still unknown, an increasing number of studies point towards the analysis of neural networks and functional connectivity to unravel novel insights. The main objective of this work is to understand cellular mechanisms related to dysregulated motor control symptoms in movement disorders, such as Chorea-Acanthocytosis (ChAc), by employing multielectrode arrays to analyze the electrical activity of neuronal networks in mouse models. We found no notable differences in cell viability between neurons with and without VPS13A knockdown, that is the only gene known to be implicated in the disease, suggesting that the absence of VPS13A in neurons may be partially compensated by other proteins. The MEA setup used to capture the electrical activity from neuron primary cultures is described in detail, pointing out its specific characteristics. At last, we present the alternative backup approach implemented to overcome the challenges faced during the research process and to explore the advanced algorithms for signal processing and analysis. In this report, we present a thorough account of the conception and implementation of our research, outlining the multiple limitations that have been encountered all along the course of the project. We provide a detailed analysis on the project’s economical and technical feasibility, as well as a comprehensive overview of the ethical and legal aspects considered during the execution.

Objective: This study aims to characterize electrical signals to establish a diagnosis of cognitive-emotional dysfunction and guide a successful therapeutic intervention. Therefore, the present study aimed to observe these frequency bands in a sample of dysfunctional neurological behaviors to establish a neural marker of neural dysfunction that helps diagnose and monitor treatment. Methods: A descriptive retrospective (extracted from the database) observational study design based on real-world historical data from routine clinical practice. According to DSM-5, low academic achievement (n =70), disruptive behavior (externalizing behavior problems) (n=70), and somatic syndrome disorder (n=70) were the subjects. The mean age of the sample was 14.13 (SD = 1.46; range 12-18), 31.5% women. The measuring instrument was the NeXus-10, which is suitable for acquiring a wide range of physiological signals. Brain electrical activity was recorded by using the quantitative electroencephalograph (qEEG) in accordance with the 10-20 International Electrode Placement System. In particular, the specific form of miniQ (mini-qEEG) was used. Results: A pattern record present in all cases were identified. The record refers to (a) activity along the midline, namely, Fz-Cz-Pz, (b) activity from the center (Cz) to back, namely, Pz-O1 and O2, (c) activity from the center (Cz) forward (Fz), and (d) comparison between hemispheres. The characteristics of theta, alpha, and beta waves define the characteristic pattern of neurological dysfunction. The reversal of the dysfunctional pattern coincided with the remission of the clinical symptoms after treatment, which occurred in 87,6% of the subjects. We define remission as not meeting DSM-5 criteria. Conclusion: This study suggests that miniQ register could be considered a simple and objective tool for studying neurological dysfunction. This dysfunction is explained according to current neurological knowledge of interactive cognition-emotion processing. MiniQ may be a cheap and reliable method and a promising tool for the investigation in the field.

31p.-7 fig. 1 graph. abst., Frontotemporal dementia is the second most prevalent type of early-onset dementia and up to 40% of cases are familial forms. One of the genes mutated in patients is CHMP2B, which encodes a protein found in a complex important for maturation of late endosomes, an essential process for recycling membrane proteins through the endolysosomal system. Here, we have generated a CHMP2B-mutated human embryonic stem cell line using genome editing with the purpose to create a human in vitro Frontotemporal dementia disease model. To date, most studies have focused on neuronal alterations; however, we present a new co-culture system in which neurons and astrocytes are independently generated from human embryonic stem cells and combined in co-cultures. With this approach, we have identified alterations in the endolysosomal system of Frontotemporal dementia astrocytes, a higher capacity of astrocytes to uptake and respond to glutamate, and a neuronal network hyperactivity as well as excessive synchronization. Overall, our data indicates that astrocyte alterations precede neuronal impairments and could potentially trigger neuronal network changes, indicating the important and specific role of astrocytes in disease development., This study was supported by funding from the Swedish Society for Medical Research (SSMF, S20-0003), Kockska, Segerfalk and Hardebo foundations to IC; the Swedish Research Council (VR:2018-02695), Swedish Alzheimer and Åhlen foundations to HA; the Swedish Research Council (VR:2016-01789) to AH; and the Agencia Estatal de Investigación, Ministerio de Ciencia e Innovación (RTI2018-097624-BI00) and European Regional Development Fund to DPS.

Introduction and objectives: There are scarce data on left atrial (LA) enlargement and electrophysiological features in athletes. Methods: Multicenter observational study in competitive athletes and controls. LA enlargement was defined as LA volume indexed to body surface area ≥ 34mL/m2. We analyzed its relationship with atrial electrocardiography parameters. Results: We included 356 participants, 308 athletes (mean age: 36.4±11.6 years) and 48 controls (mean age: 49.3±16.1 years). Compared with controls, athletes had a higher mean LA volume index (29.8±8.6 vs 25.6±8.0mL/m2, P=.006) and a higher prevalence of LA enlargement (113 [36.7%] vs 5 [10.4%], P

L'envelliment és un procés natural que es caracteritza per l'acumulació progressiva de canvis fisiològics i per enlentir alguns dominis cognitius. Tot i això, alguns aspectes d'aquests canvis cognitius també s'associen a estats patològics, com la malaltia d'Alzheimer (MA). La MA és un trastorn neurodegeneratiu progressiu, resultat d'una interacció complexa entre la genètica i els factors ambientals experimentats al llarg de la vida. Una aproximació per definir el patró del mecanisme biològic subjacent a l'aparició i el desenvolupament de la MA és l'ús d'eines no invasives que permetin caracteritzar i seguir el desenvolupament de la patologia de la MA des d'estadis preclínics. En aquest sentit, l'electroencefalografia (EEG) i la magnetoencefalografia (MEG) són eines útils ja que permeten estudiar l'evolució dels marcadors electrofisiològics al cervell de manera totalment no invasiva. L'objectiu principal d'aquesta Tesi Doctoral és identificar marcadors electrofisiològics i cognitius robusts que permetin distingir els subjectes sans dels pacients amb deteriorament cognitiu lleu (DCL), considerant com a fonts d'informació les dades sociodemogràfiques, l'avaluació neuropsicològica, els biomarcadors del líquid cefaloraquidi (LCR) i les mesures EEG/MEG extretes de l'activitat en repòs de mostres multiculturals. Per això, la tesi s'organitza en dues parts. Pel que fa a l'envelliment saludable, els dos primers estudis inclouen (i) l'anàlisi de l'impacte de les característiques sociodemogràfiques i d'estil de vida sobre el rendiment cognitiu en adults peruans i (ii) una revisió sistemàtica de les troballes prèvies sobre l'associació entre els perfils electrofisiològics en estat de repòs i el rendiment cognitiu. Pel que fa a l'envelliment patològic, la tesi inclou (iii) l'exploració de l'associació entre el record retardat i la connectivitat funcional en estat de repòs en subjectes cognitivament intactes i DCL; (iv) un estudi multicèntric dels marcadors del LCR i la seva associació amb el deteriorament de la memòria episòdica i les funcions executives en DCL; i (v) la relació dels patrons electrofisiològics del DCL amb els biomarcadors del LCR segons el sexe. Els nostres resultats corroboren la rellevància dels factors no modificables i modificables relacionats amb el deteriorament cognitiu en l'envelliment saludable. A més, des del punt de vista electrofisiològic, la mesura de la freqüència del pic alfa s'associa amb el rendiment cognitiu i es podria considerar com un marcador de l'envelliment saludable. D'altra banda, pel que fa al DCL, (i) els valors més alts a la connectivitat funcional de la banda beta a la regió occipital dreta es van associar amb puntuacions més baixes de record retardat en subjectes cognitivament intactes i amb DCL. El cervell sembla perdre progressivament la capacitat de desincronitzar les oscil·lacions beta, i aquest procés comença a ser significatiu a les etapes preclíniques, almenys en els participants amb vulnerabilitat a la MA, com la presència de l'al·lel APOE ε4; (ii) un deteriorament primerenc del funcionament executiu, que podria afectar en última instància el seu rendiment a la prova de memòria episòdica, podria ajudar a discriminar entre dos patrons diferents de DCL; i (iii) hi ha una possible associació diferencial entre els perfils EEG i els marcadors del LCR en els homes i les dones. Aquesta troballa podria ser la base per donar suport a la implementació d'iniciatives que fomentin un estil de vida saludable i promoguin activitats de salut cerebral que afavoreixin la reducció del deteriorament cognitiu a l'envelliment i reforcen la necessitat de realitzar assajos clínics més personalitzats per millorar la detecció primerenca de la MA fent ús de les tècniques de neuroimatge. El envejecimiento es un proceso natural que se caracteriza por la acumulación progresiva de cambios fisiológicos y la ralentización de algunos dominios cognitivos. Sin embargo, algunos aspectos de estos cambios cognitivos también se asocian a estados patológicos, como la enfermedad de Alzheimer (EA). La EA es un trastorno neurodegenerativo progresivo, resultado de una compleja interacción entre la genética y los factores ambientales experimentados a lo largo de la vida. Una aproximación para definir el patrón del mecanismo biológico que subyace a la aparición y desarrollo de la EA es el uso de herramientas no invasivas que permitan caracterizar y seguir el desarrollo de la patología de la EA desde estadios preclínicos. En este sentido, la electroencefalografía (EEG), y la magnetoencefalografía (MEG) son herramientas útiles ya que permiten estudiar la evolución de los marcadores electrofisiológicos en el cerebro de forma totalmente no invasiva. El objetivo principal de esta Tesis Doctoral es identificar marcadores electrofisiológicos y cognitivos robustos que permitan distinguir a los sujetos sanos de los pacientes con deterioro cognitivo leve (DCL), considerando como fuentes de información los datos sociodemográficos, la evaluación neuropsicológica, los biomarcadores del líquido cefalorraquídeo (LCR) y las medidas EEG/MEG extraídas de la actividad en reposo de muestras multiculturales. Para ello, la tesis se organiza en dos partes. En cuanto al envejecimiento saludable, los dos primeros estudios incluyen (i) el análisis del impacto de las características sociodemográficas y de estilo de vida sobre el rendimiento cognitivo en adultos peruanos y (ii) una revisión sistemática de los hallazgos previos sobre la asociación entre los perfiles electrofisiológicos en estado de reposo y el rendimiento cognitivo. En relación con el envejecimiento patológico, la tesis incluye (iii) la exploración de la asociación entre el recuerdo retardado y la conectividad funcional en estado de reposo en sujetos cognitivamente intactos y DCL; (iv) un estudio multicéntrico de los marcadores del LCR y su asociación con el deterioro de la memoria episódica y las funciones ejecutivas en DCL; y (v) la relación de los patrones electrofisiológicos del DCL con los biomarcadores del LCR según el sexo. Nuestros resultados corroboran la relevancia de los factores no modificables y modificables relacionados con el deterioro cognitivo en el envejecimiento saludable. Además, desde el punto de vista electrofisiológico, la medida de la frecuencia del pico alfa se asocia con el rendimiento cognitivo y podría considerarse como un marcador del envejecimiento saludable. Por otro lado, en lo que respecta al DCL, (i) los valores más altos en la conectividad funcional de la banda beta en la región occipital derecha se asociaron con puntuaciones más bajas de recuerdo retardado en sujetos cognitivamente intactos y con DCL. El cerebro parece perder progresivamente la capacidad de desincronizar las oscilaciones beta, y este proceso empieza a ser significativo en las etapas preclínicas, al menos en los participantes con vulnerabilidad a la EA, como la presencia del alelo APOE ε4; (ii) un deterioro temprano del funcionamiento ejecutivo, que podría afectar en última instancia a su rendimiento en la prueba de memoria episódica, podría ayudar a discriminar entre dos patrones diferentes de DCL; y (iii) existe una posible asociación diferencial entre los perfiles EEG y los marcadores del LCR en los hombres y mujeres. Este hallazgo podría ser la base para apoyar la implementación de iniciativas que fomenten un estilo de vida saludable y promuevan actividades de salud cerebral que favorezcan la reducción del deterioro cognitivo en el envejecimiento y refuerzan la necesidad de realizar ensayos clínicos más personalizados para mejorar la detección temprana de la EA haciendo uso de las técnicas de neuroimagen. Aging is a natural process characterized by the progressive accumulation of physiological changes and a slowdown of some cognitive domains. However, some aspects of these cognitive changes are also associated with pathological states, such as the Alzheimer's disease (AD). AD is a progressive neurodegenerative disorder, results of a complex interaction between genetics and environmental factors experienced throughout life. One approach to defining the pattern of the biological mechanism underlying the onset and development of AD is the use of non-invasive tools able to detect changes in the structure and function of the nervous system in humans, which allows characterizing and following the development of AD pathology from preclinical stages. In this sense, electroencephalography (EEG), and magnetoencephalography (MEG) are useful tools since they allow studying the evolution of electrophysiological markers in the brain in a completely non-invasive way. The combined use of these techniques, evaluation brain activity in resting-state, with neuropathological markers of AD and cognitive performance, could help to improve the distinguish pattern of early AD. The main objective of this Doctoral Thesis is to identify robust electrophysiological and cognitive markers that allow to distinguish healthy subjects from patients with mild cognitive impairment (MCI), considering as sources of information sociodemographic data, neuropsychological assessment, cerebrospinal fluid (CSF) biomarkers, and EEG/MEG measures extracted from resting activity of multicultural samples. For this purpose, the thesis is organized into two parts focusing on the study of healthy and pathological aging. Regarding healthy aging, the first two studies include (i) the analysis of the impact of sociodemographic and lifestyle characteristics on cognitive performance in Peruvian adults and (ii) a systematic review of previous findings on the association between resting-state electrophysiological profiles and cognitive performance in healthy aging. Concerning pathological aging, the thesis includes (iii) the exploration of the potential association between delayed recall performance and resting-state functional connectivity in cognitively intact subjects and MCI patients; (iv) a multicenter study of CSF markers and their association with episodic memory impairment and executive functions in patients with MCI; and (v) the relationship of electrophysiological signs of MCI with CSF biomarkers and the assessment of this relationship according to sex. Our findings corroborate the relevance of non-modifiable and modifiable factors related with cognitive decline in healthy aging. Although nonmodifiable factors impact older adults' cognition, their influence is mediated by other factors that are indeed modifiable (i.e., time spend reading, engagement in physical activity). Furthermore, since electrophysiological point of view, the measure of alpha peak frequency is associated with the cognitive performance and could be considered as an electrophysiological marker of healthy aging. On the other hand, regarding the electrophysiological profile of MCI, (i) higher values in functional connectivity of the beta band in the right occipital region were associated with lower delayed recall scores in cognitively intact and MCI subjects. The brain seems to progressively lose the ability to desynchronize beta oscillations, and this process starts to become significant in preclinical stages, at least in participants with AD vulnerability such as the presence of the APOE ε4 allele; (ii) an early executive functioning impairment, which could ultimately affect their performance on episodic memory test could help to discriminate between two different patterns of MCI; and (iii) there is a potential differential association between EEG profiles and CSF markers in male and female participants. This finding could be the base to support the implementation of initiatives encouraging a healthy lifestyle and promoting brain health activities which could favor reducing cognitive decline in aging and reinforce the need for clinical trials focused on a more personalized approach to improve the early detection of AD taking account the neuroimaging techniques.

Includes supplementary materials for the online appendix. The aim of this work was to analyze the influence of sex hormones and anatomical details (trabeculations and false tendons) on the electrophysiology of healthy human hearts. Additionally, sex- and anatomy-dependent effects of ventricular tachycardia (VT) inducibility are presented. To this end, four anatomically normal, human, biventricular geometries (two male, two female), with identifiable trabeculations, were obtained from high-resolution, ex-vivo MRI and represented by detailed and smoothed geometrical models (with and without the trabeculations). Additionally one model was augmented by a scar. The electrophysiology finite element model (FEM) simulations were carried out, using O’Hara-Rudy human myocyte model with sex phenotypes of Yang and Clancy. A systematic comparison between detailed vs smooth anatomies, male vs female normal hearts was carried out. The heart with a myocardial infarction was subjected to a programmed stimulus protocol to identify the effects of sex and anatomical detail on ventricular tachycardia inducibility. All female hearts presented QT-interval prolongation however the prolongation interval in comparison to the male phenotypes was anatomy-dependent and was not correlated to the size of the heart. Detailed geometries showed QRS fractionation and increased T-wave magnitude in comparison to the corresponding smoothed geometries. A variety of sustained VTs were obtained in the detailed and smoothed male geometries at different pacing locations, which provide evidence of the geometry-dependent differences regarding the prediction of the locations of reentry channels. In the female phenotype, sustained VTs were induced in both detailed and smooth geometries with RV apex pacing, however no consistent reentry channels were identified. Anatomical and physiological cardiac features play an important role defining risk in cardiac disease. These are often excluded from cardiac electrophysiology simulations. The assumption that the cardiac endocardium is smooth may produce inaccurate predictions towards the location of reentry channels in in-silico tachycardia inducibility studies. JA-S, FS, GH and MV are supported by the European Union’s Horizon 2020 research and innovation programme under grant agreements No 675451 (Compbiomed project phase 1) and No 823712 (CompBioMed project, phase 2) and project No 777204 (SilicoFCM project). Part of the simulation computing hours were provided by the CompBioMed project phase 1. JA-S was awarded computation time from Red Espanola de Supercomputacion (RES). (Activity IDs: FI-2018-2-0049 and BCV-2019-2-0014) JA-S is funded by a Ramon y Cajal fellowship (RYC-2017-22532), Ministerio de Ciencia e Innovacion, Spain; and by Plan Estatal de Investigacion Cientifica y Tecnica y de Innovacion 2017-2020 from the Ministerio de Ciencia e Innovacion y Universidades (PID2019-104356RBC41/AEI/10.13039/501100011033): meHeart ME PID2019-104356RB-C44. CB is funded by the Torres Quevedo Program (PTQ2018-010290), Ministerio de Ciencia e Innovacion, Spain. MV, GH and CB are funded by the Spanish Neotec project EXP - 00123159/SNEO-20191113 Generador de corazones virtuales. LKGM was funded by Fundacion Carolina-BBVA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. There was no additional external funding received for this study.

INTRODUCTION AND OBJECTIVES: This article reports the results of the 2020 Spanish Catheter Ablation Registry, a year marked by the SARS-CoV-2 pandemic. METHODS: Data were collected retrospectively through completion and return of a specific form by the participating centers. RESULTS: Data from 97 centers (67 public, 30 private) were analyzed. A total of 15 169 ablation procedures were reported with a mean of 155 ± 117 and a median [interquartile range] of 115 [62-227]. Because of the SARS-CoV-2 pandemic, both procedures and participating centers markedly decreased (-3380 procedures, -18%) and there were 5 centers less than in 2019. The most common procedure continued to be atrial fibrillation ablation (4513; 30%), well ahead of the remaining substrates, followed by ablation of the cavotricuspid isthmus (3188; 21%), and intranodal re-entry tachycardia (2808; 18%). Ablation of these 3 substrates continued to form the bulk of the procedures. The total success rate was slightly lower than in previous years (88%) with a similar complication rate (n = 309; 2%) and mortality (n = 7; 0.04%). A total of 243 procedures were performed in pediatric patients (1.6%). CONCLUSIONS: The Spanish Catheter Ablation Registry systematically and continuously reflects the national trajectory, which, in 2020, was markedly affected by the SARS-CoV-2 pandemic. Although slightly lower than in previous years, the success rate remained high, with a low complication rate.

Introduction and objectives: This article reports the results of the 2020 Spanish Catheter Ablation Registry, a year marked by the SARS-CoV-2 pandemic. Methods: Data were collected retrospectively through completion and return of a specific form by the participating centers. Results: Data from 97 centers (67 public, 30 private) were analyzed. A total of 15 169 ablation procedures were reported with a mean of 155 117 and a median [interquartile range] of 115 [62-227]. Because of the SARS-CoV-2 pandemic, both procedures and participating centers markedly decreased ( 3380 procedures, 18%) and there were 5 centers less than in 2019. The most common procedure continued to be atrial fibrillation ablation (4513; 30%), well ahead of the remaining substrates, followed by ablation of the cavotricuspid isthmus (3188; 21%), and intranodal re-entry tachycardia (2808; 18%). Ablation of these 3 substrates continued to form the bulk of the procedures. The total success rate was slightly lower than in previous years (88%) with a similar complication rate (n = 309; 2%) and mortality (n = 7; 0.04%). A total of 243 procedures were performed in pediatric patients (1.6%).Conclusions: The Spanish Catheter Ablation Registry systematically and continuously reflects the national trajectory, which, in 2020, was markedly affected by the SARS-CoV-2 pandemic. Although slightly lower than in previous years, the success rate remained high, with a low complication rate. C 2021 Sociedad Espan ̃ola de Cardiologı ́a. Published by Elsevier Espan ̃a, S.L.U. All rights reserved. Introducción y objetivos Se describen los resultados del Registro Español de Ablación con Catéter de 2020, año marcado por la pandemia por SARS-CoV-2. Métodos La recogida de datos fue restrospectiva mediante la cumplimentación y envío de un formulario específico por los centros participantes. Resultados Se analizaron los datos de 97 centros (67 públicos, 30 privados). Se comunicaron 15.169 procedimientos de ablación (media, 155 ± 117; mediana, 115 [62-227]). La pandemia de SARS-CoV-2 ha condicionado una disminución notable tanto de los procedimientos (–3.380 casos, –18%) como de los centros participantes (5 menos que en 2019). La ablación de FA sigue siendo el procedimiento más frecuente (4.513; 30%), a distancia de los demás sustratos; junto con la ablación del ICT (3.188; 21%) y la taquicardia por reentrada intranodular (2.808; 18%), son los 3 sustratos más abordados. La tasa total de éxito reportada es discretamente inferior a las de años previos (88%), con similares tasas de complicaciones (309; 2%) y mortalidad (7; 0,04%). Se realizaron 243 procedimientos en pacientes pediátricos (1,6%). Conclusiones El Registro Español de Ablación con Catéter recoge de manera sistemática e ininterrumpida la trayectoria nacional, que este año se ha visto notablemente marcada por la pandemia por SARS-CoV-2. Aunque discretamente inferior a las años previos, la tasa de éxito sigue siendo alta, con una baja tasa de complicaciones.

Human beings continuously make use of learned associations to generate predictions about future occurrences in the environment. Such memory-related predictive processes provide a scaffold for learning in that mental rep-resentations of foreseeable events can be adjusted or strengthened based on a specific outcome. Learning the meaning of novel words through picture-word associations constitutes a prime example of associative learning because pictures preceding words can trigger word prediction through the pre-activation of the related mne-monic representations. In the present electroencephalography (EEG) study, we used event-related potentials (ERPs) to compare neural indices of word pre-activation between a word learning condition with maximal prediction likelihood and a non-learning control condition with low prediction. Results revealed that prediction -related N400 amplitudes in response to pictures decreased over time at central electrodes as a function of word learning, whereas late positive component (LPC) amplitudes increased. Notably, N400 but not LPC changes were also predictive of word learning performance, suggesting that the N400 component constitutes a sensitive marker of word pre-activation during associative word learning.

[ES] Las enfermedades cardiovasculares comprenden la gran mayoría de afecciones a los seres humanos, siendo así la principal causa de defunción a nivel global. Dentro de las enfermedades que más afectan a la población se encuentra la fibrilación auricular, la cual, es una arritmia que desarrolla en el paciente la remodelación de la aurícula con tejido fibrótico, afectando así la fisiología eléctrica y anatómica del órgano. Por esta razón, las simulaciones de la fisiología eléctrica empleando modelos cardiacos están cada vez en demanda para el estudio de las afecciones del corazón. En consecuencia, este trabajo pretende estudiar el comportamiento de la actividad eléctrica a través de estímulos en tejidos fibróticos generados a partir imágenes reales de fibrosis. Inicialmente, se cuenta con nueve imágenes de tejido fibrótico y se desarrolla un código de programación que genere las mallas de tejido a partir de ellas. En segundo lugar, las mallas generadas se emplean para realizar simulaciones eléctricas, para posteriormente medir registros de electrogramas en diferentes puntos de los tejidos, los cuales se comparan con registros obtenidos en otras investigaciones con el objetivo de explicarlos. Finalmente, se concluye que las mallas de tejido generadas poseen similaridad con las imágenes reales y, los registros muestran la influencia de la fibrosis en la conducción del potencial a través de las mallas de tejido generadas, pudiendo ser comparados con registros patológicos., [EN] Cardiovascular diseases comprise the vast majority of diseases affecting human beings, being the leading cause of death worldwide. Among the diseases that most affect the population is atrial fibrillation, which is an arrhythmia that develops in the patient the remodeling of the atrium with fibrotic tissue, thus affecting the electrical and anatomical physiology of the organ. For this reason, simulations of electrical physiology using cardiac models are increasingly in demand for the study of heart conditions. Consequently, this work aims to study the behavior of electrical activity through stimuli in fibrotic tissues generated from real images. Initially, nine images of fibrotic tissue are presented, and a programming code is developed to generate the tissue meshes from them. Secondly, the generated meshes are used to perform electrical simulations, to subsequently measure electrogram records at different points of the tissues, which are compared with records obtained in other investigations in order to explain them. Finally, it is concluded that the generated tissue meshes have similarity with real images and, the recordings show the influence of fibrosis in the conduction of the potential through the generated tissue meshes, being able to be compared with pathological recordings.

[ES] La irrupción de los navegadores electroanatómicos cardiacos en la electrofisiología ha supuesto un desarrollo tecnológico sustancial en los últimos años. Aún así, el conocimiento sobre los mecanismos desencadenantes y de perpetuación de arritmias complejas sigue siendo un reto sin resolver. Los últimos avances indican la necesidad de mejorar la exploración local de las propiedades electrofisiológicas a partir del procesado adecuado de las señales registradas por la nueva generación de catéters basado en multielectrodos de alta densidad (HD). En ese sentido, el presente TFM pretende desarrollar una nueva metodología basada en conceptos vectoriales que permita un mejor aprovechamiento de la información proporcionada por los catéteres de nueva generación para la determinación de biomarcadores relevantes como los LATs (tiempos de activación local) y la velocidad de conducción. Los algoritmos implementados se validarán sobre un modelo de propagación de señales intracavitarias y se realizarán test sobre un conjunto de registros clínicos. Todo ello con el objetivo de mejorar la identificación de regiones de tejido con fibrosis susceptibles de ser ablacionadas.. El TFM se desarrolla en el marco de un proyecto de I+D+i competitiva. En concreto el proyecto Q-Substrate de referencia PID2019-109547RB-I00., [EN] The irruption of cardiac electroanatomic navigators in electrophysiology has led to substantial technological developments in recent years. Even so, knowledge of the triggering and perpetuating mechanisms of complex arrhythmias remains an unresolved challenge. Recent advances indicate the need to improve the local exploration of electrophysiological properties based on the appropriate processing of the signals recorded by the new generation of catheters based on high-density (HD) multielectrodes. In this sense, the present TFM aims to develop a new methodology based on vector concepts that allows a better use of the information provided by the new generation catheters for the determination of relevant biomarkers such as LATs (local activation times) and conduction velocity. The implemented algorithms will be validated on an intracavitary signal propagation model and tested on a set of clinical records. All this with the aim of improving the identification of tissue regions with fibrosis susceptible to ablation. The TFM will be developed within the framework of a competitive R+D+i project. Specifically the Q-Substrate project reference PID2019-109547RB-I00.

En els darrers anys, a través de diferents estudis s'ha demostrat que l'electrofisiologia de les plantes proporciona informació significativa sobre l'estat d'una planta, però encara queden coneixements substancials per obtenir que es traduiran en pràctiques agrícoles millorades. En aquest Treball de Fi de Grau, que forma part d'un projecte realitzat en col·laboració amb un soci industrial, s'ha utilitzat un conjunt de dades de senyals elèctrics de plantes sota estrès, recopilades amb un biosensor d'electrofisiologia vegetal multicanal. En enfocaments anteriors, es van aplicar tècniques de processament de senyals en aquests conjunts de dades per extreure característiques i després fer servir algoritmes d'anàlisi de dades intel·ligents en aquestes característiques per predir si les plantes estan estressades. L'objectiu principal d'aquest treball és fer la mateixa tasca fent servir tècniques d'aprenentatge profund d'última generació per avaluar l'ús de plantes com a dispositius de detecció d'estímuls biològics. In the recent years it has been shown through different studies that plant electrophysiology provides meaningful information about the state of a plant, but there are still substantial insights to be gained which will flow through to improved agriculture practices. In this Bachelor's Thesis, being part of a project realized in collaboration with an industrial partner, it has been used a dataset of under-stress plants' electrical signals, collected with a multi-channel plant electrophysiology biosensor. In previous approaches, signal-processing techniques were applied on these datasets to extract features, and then use intelligent data analysis algorithms on these features in order to predict if the plants are stressed. The main objective of this work is to realize the same task by employing state-of-the-art Deep Learning techniques, in order to evaluate the use of plants as biological stimuli-sensing devices.

Cardiac amyloidosis (CA) is a form of cardiomyopathy characterized by the extracellular deposit of protein fibers in the myocardium, leading to the development of heart failure, arrhythmias, and electrical conduction system alterations. It is known that most cardiomyopathies have a close relationship with heart rhythm abnormalities, however, CA is specially related to different kinds of arrhythmias even in pre-diagnosis stages. Arrhythmias like atrial fibrillation are present in up to 70% of patients with CA associated with a high risk of cardioembolic complications independent of the risk stratification. Ventricular arrhythmias are frequent, but the use of implantable cardioverter defibrillator has not been demonstrated to improve survival. The Atrial-Ventricular node disease is also common, and is frequently associated with the implantation of a pacemaker, even in asymptomatic patients. In this review, we clarify the recommendations of the most current guidelines, summarize historical and contemporaneous data and describe evidence-based strategies for the management of arrhythmias and their complications in CA. La amiloidosis cardíaca (AC) es una forma de cardiomiopatía caracterizada por el depósito extracelular de fibrillas de proteínas en el miocardio, lo que produce insuficiencia cardíaca, arritmias y alteraciones en el sistema de conducción eléctrica. La mayoría de las cardiomiopatías tienen una estrecha relación con las alteraciones del ritmo cardiaco, en especial la AC que está asociada a diferentes formas de arritmias, incluso en fases previas al diagnóstico. Arritmias como la fibrilación auricular se observan hasta en el 70% de los pacientes con AC asociadas a un especial riesgo de complicaciones cardioembólicas independiente de la estratificación de riesgo. Las arritmias ventriculares son frecuentes; sin embargo, la colocación del cardiodesfibrilador implantable no ha demostrado mejorar la sobrevida. La enfermedad del sistema de conducción eléctrica también es común, y con frecuencia es necesario implantar un marcapaso definitivo, incluso en pacientes asintomáticos. En esta revisión delimitamos las recomendaciones de las guías más recientes, resumimos datos históricos y contemporáneos, y describimos estrategias basadas en evidencia para el manejo de arritmias y sus secuelas en la AC.

Neuroactivació transcutània (NaT); Electrofisiologia; Avaluació Neuroactivación transcutánea (NaT); Electrofisiología; Evaluación Transcutaneous neuroactivation (NaT); Electrophysiology; Evaluation L’objectiu d’aquest informe és descriure l’evidència científica respecte al tractament NaT, tot incloent la base científica en què es basa i la seguretat, eficàcia i efectivitat.

Understanding the dopaminergic system is a priority in neurobiology and neuropharmacology. Dopamine receptors are involved in the modulation of fundamental physiological functions, and dysregulation of dopaminergic transmission is associated with major neurological disorders. However, the available tools to dissect the endogenous dopaminergic circuits have limited specificity, reversibility, resolution, or require genetic manipulation. Here, we introduce azodopa, a novel photoswitchable ligand that enables reversible spatiotemporal control of dopaminergic transmission. We demonstrate that azodopa activates D1-like receptors in vitro in a light-dependent manner. Moreover, it enables reversibly photocontrolling zebrafish motility on a timescale of seconds and allows separating the retinal component of dopaminergic neurotransmission. Azodopa increases the overall neural activity in the cortex of anesthetized mice and displays illumination-dependent activity in individual cells. Azodopa is the first photoswitchable dopamine agonist with demonstrated efficacy in wild-type animals and opens the way to remotely controlling dopaminergic neurotransmission for fundamental and therapeutic purposes. This research was funded by EU Horizon 2020 Framework Programme for Research and Innovation: Human Brain Project WaveScalES, Specific Grant Agreement 2 No. 785907 and Specific Grant Agreement 3 No. 945539; NEUROPA project, Grant Agreement No. 863214; DEEPER project ICT-36-2020-101016787; European Union Regional Development Fund within the framework of the ERDF Operational Program of Catalonia 2014-2020: CECH project; Ministry of Science and Innovation DEEP RED grant PID2019-111493RB-I00 funded by MCIN/AEI/10.13039/501100011033; Ministerio de Economía y Competitividad and European Regional Development Funds: Grant no. SAF2017-87629-R to V.C., SAF2016-80726-R to M.V.P., SAF2017-88076-R to M.M.; AGAUR/Generalitat de Catalunya: CERCA Programme; Generalitat de Catalunya: Grant no. 2017-SGR-1442 to P.G., 2017-SGR-1497 to V.C., 2017-SGR-210 to M.V.P., and 2017-SGR-00465 to J.H.; Fundaluce and “la Caixa” foundations: ID 100010434, grant agreement LCF/PR/HR19/52160010.

[ES] Las arritmias cardíacas son un problema importante para los sistemas de salud en el mundo desarrollado debido a su alta incidencia y prevalencia a medida que la población envejece. La fibrilación auricular (FA) y la fibrilación ventricular (FV) se encuentran entre las arritmias más complejas observadas en la práctica clínica. Las consecuencias clínicas de tales alteraciones arrítmicas incluyen el desarrollo de eventos cardioembólicos complejos en la FA, y repercusiones dramáticas debido a procesos fibrilatorios sostenidos que amenazan la vida infringiendo daño neurológico tras paro cardíaco por FV, y que pueden provocar la muerte súbita cardíaca (MSC). Sin embargo, a pesar de los avances tecnológicos de las últimas décadas, sus mecanismos intrínsecos se comprenden de forma incompleta y, hasta la fecha, las estrategias terapéuticas carecen de una base mecanicista suficiente y poseen bajas tasas de éxito. Entre los mecanismos implicados en la inducción y perpetuación de arritmias cardíacas, como la FA, se cree que las dinámicas de las fuentes focales y reentrantes de alta frecuencia, en sus diferentes modalidades, son las fuentes primarias que mantienen la arritmia. Sin embargo, se sabe poco sobre los atractores, así como, de la dinámica espacio-temporal de tales fuentes fibrilatorias primarias, específicamente, las fuentes focales o rotacionales dominantes que mantienen la arritmia. Por ello, se ha desarrollado una plataforma computacional, para comprender los factores (activos, pasivos y estructurales) determinantes, y moduladores de dicha dinámica. Esto ha permitido establecer un marco para comprender la compleja dinámica de los rotores con énfasis en sus propiedades deterministas para desarrollar herramientas basadas en los mecanismos para ayuda diagnóstica y terapéutica. Comprender los procesos fibrilatorios es clave para desarrollar marcadores y herramientas fisiológica- y clínicamente relevantes para la ayuda de diagnóstico temprano. Específicamente, las propiedades espectrales y de tiempo-frecuencia de los procesos fibrilatorios han demostrado resaltar el comportamiento determinista principal de los mecanismos intrínsecos subyacentes a las arritmias y el impacto de tales eventos arrítmicos. Esto es especialmente relevante para determinar el pronóstico temprano de los supervivientes comatosos después de un paro cardíaco debido a fibrilación ventricular (FV). Las técnicas de mapeo electrofisiológico, el mapeo eléctrico y óptico cardíaco, han demostrado ser recursos muy valiosos para dar forma a nuevas hipótesis y desarrollar nuevos enfoques mecanicistas y estrategias terapéuticas mejoradas. Esta tecnología permite además el trabajo multidisciplinar entre clínicos y bioingenieros, para el desarrollo y validación de dispositivos y metodologías para identificar biomarcadores multi-dominio que permitan rastrear con precisión la dinámica de las arritmias identificando fuentes dominantes y atractores con alta precisión para ser dianas de estrategias terapeúticas innovadoras. Es por ello que uno de los objetivos fundamentales ha sido la implantación y validación de nuevos sistemas de mapeo en distintas configuraciones que sirvan de plataforma de desarrollo de nuevas estrategias terapeúticas. Aunque el mapeo panorámico es el método principal y más completo para rastrear simultáneamente biomarcadores electrofisiológicos, su adopción por la comunidad científica es limitada principalmente debido al coste elevado de la tecnología. Aprovechando los avances tecnológicos recientes, nos hemos enfocado en desarrollar, y validar, sistemas de mapeo óptico de alta resolución para registro panorámico cardíaco, utilizando modelos clínicamente relevantes para la investigación básica y la bioingeniería., [CA] Les arítmies cardíaques són un problema important per als sistemes de salut del món desenvolupat a causa de la seva alta incidència i prevalença a mesura que la població envelleix. La fibril·lació auricular (FA) i la fibril·lació ventricular (FV), es troben entre les arítmies més complexes observades a la pràctica clínica. Les conseqüències clíniques d'aquests trastorns arítmics inclouen el desenvolupament d'esdeveniments cardioembòlics complexos en FA i repercussions dramàtiques a causa de processos fibril·latoris sostinguts que posen en perill la vida amb danys neurològics posteriors a la FV, que condueixen a una aturada cardíaca i a la mort cardíaca sobtada (SCD). Tanmateix, malgrat els avanços tecnològics de les darreres dècades, els seus mecanismes intrínsecs s'entenen de forma incompleta i, fins a la data, les estratègies terapèutiques no tenen una base mecanicista suficient i tenen baixes taxes d'èxit. La majoria dels avenços en el desenvolupament de biomarcadors òptims i noves estratègies terapèutiques en aquest camp provenen de tècniques valuoses en la investigació de mecanismes d'arítmia. Entre els mecanismes implicats en la inducció i perpetuació de les arítmies cardíaques, es creu que les fonts primàries subjacents a l'arítmia són les fonts focals reingressants d'alta freqüència dinàmica i AF, en les seves diferents modalitats. Tot i això, se sap poc sobre els atractors i la dinàmica espaciotemporal d'aquestes fonts primàries fibril·ladores, específicament les fonts rotacionals o focals dominants que mantenen l'arítmia. Per tant, s'ha desenvolupat una plataforma computacional per entendre determinants actius, passius, estructurals i moduladors d'aquestes dinàmiques. Això va permetre establir un marc per entendre la complexa dinàmica multidomini dels rotors amb ènfasi en les seves propietats deterministes per desenvolupar enfocaments mecanicistes per a l'ajuda i la teràpia diagnòstiques. La comprensió dels processos fibril·latoris és clau per desenvolupar puntuacions i eines rellevants fisiològicament i clínicament per ajudar al diagnòstic precoç. Concretament, les propietats espectrals i de temps-freqüència dels processos fibril·latoris han demostrat destacar un comportament determinista important dels mecanismes intrínsecs subjacents a les arítmies i l'impacte d'aquests esdeveniments arítmics. Mitjançant coneixements previs, processament de senyals, tècniques d'aprenentatge automàtic i anàlisi de dades, es va desenvolupar una puntuació de risc mecanicista a la aturada cardíaca per FV. Les tècniques de cartografia òptica cardíaca i electrofisiològica han demostrat ser recursos inestimables per donar forma a noves hipòtesis i desenvolupar nous enfocaments mecanicistes i estratègies terapèutiques. Aquesta tecnologia ha permès durant molts anys provar noves estratègies terapèutiques farmacològiques o ablatives i desenvolupar mètodes multidominis per fer un seguiment precís de la dinàmica d'arrímies que identifica fonts i atractors dominants. Tot i que el mapatge panoràmic és el mètode principal per al seguiment simultani de paràmetres electrofisiològics, la seva adopció per part de la comunitat multidisciplinària d'investigació cardiovascular està limitada principalment pel cost de la tecnologia. Aprofitant els avenços tecnològics recents, ens centrem en el desenvolupament i la validació de sistemes de mapes òptics de baix cost per a imatges panoràmiques mitjançant models clínicament rellevants per a la investigació bàsica i la bioenginyeria., [EN] Cardiac arrhythmias are a major problem for health systems in the developed world due to their high incidence and prevalence as the population ages. Atrial fibrillation (AF) and ventricular fibrillation (VF), are amongst the most complex arrhythmias seen in the clinical practice. Clinical consequences of such arrhythmic disturbances include developing complex cardio-embolic events in AF, and dramatic repercussions due to sustained life-threatening fibrillatory processes with subsequent neurological damage under VF, leading to cardiac arrest and sudden cardiac death (SCD). However, despite the technological advances in the last decades, their intrinsic mechanisms are incompletely understood, and, to date, therapeutic strategies lack of sufficient mechanistic basis and have low success rates. Most of the progress for developing optimal biomarkers and novel therapeutic strategies in this field has come from valuable techniques in the research of arrhythmia mechanisms. Amongst the mechanisms involved in the induction and perpetuation of cardiac arrhythmias such AF, dynamic high-frequency re-entrant and focal sources, in its different modalities, are thought to be the primary sources underlying the arrhythmia. However, little is known about the attractors and spatiotemporal dynamics of such fibrillatory primary sources, specifically dominant rotational or focal sources maintaining the arrhythmia. Therefore, a computational platform for understanding active, passive and structural determinants, and modulators of such dynamics was developed. This allowed stablishing a framework for understanding the complex multidomain dynamics of rotors with enphasis in their deterministic properties to develop mechanistic approaches for diagnostic aid and therapy. Understanding fibrillatory processes is key to develop physiologically and clinically relevant scores and tools for early diagnostic aid. Specifically, spectral and time-frequency properties of fibrillatory processes have shown to highlight major deterministic behaviour of intrinsic mechanisms underlying the arrhythmias and the impact of such arrhythmic events. Using prior knowledge, signal processing, machine learning techniques and data analytics, we aimed at developing a reliable mechanistic risk-score for comatose survivors of cardiac arrest due to VF. Cardiac optical mapping and electrophysiological mapping techniques have shown to be unvaluable resources to shape new hypotheses and develop novel mechanistic approaches and therapeutic strategies. This technology has allowed for many years testing new pharmacological or ablative therapeutic strategies, and developing multidomain methods to accurately track arrhymia dynamics identigying dominant sources and attractors. Even though, panoramic mapping is the primary method for simultaneously tracking electrophysiological parameters, its adoption by the multidisciplinary cardiovascular research community is limited mainly due to the cost of the technology. Taking advantage of recent technological advances, we focus on developing and validating low-cost optical mapping systems for panoramic imaging using clinically relevant models for basic research and bioengineering.