1,238 research outputs found

    Phase synchronization during the processing of taxonomic and thematic relations

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    Semantic relations include “taxonomic” relations based on shared features and “thematic” relations based on co-occurrence in events. The “dual-hub” account proposes that the anterior temporal lobe (ATL) is functionally specialized for taxonomic relations and the inferior parietal lobule (IPL) for thematic relations. This study examined this claim by analyzing the intra- and inter-region phase synchronization of intracranial EEG data from electrodes in the ATL, IPL, and two subregions of the semantic control network: left inferior frontal gyrus (IFG) and posterior middle temporal gyrus (pMTG). Ten participants with epilepsy completed a semantic relatedness judgment task during intracranial EEG recording and had electrodes in at least one hub and at least one semantic control region. Theta band phase synchronization was partially consistent with the dual-hub account: synchronization between the ATL and IFG/pMTG increased when processing taxonomic relations, and synchronization within the IPL and between IPL and pMTG increased when processing thematic relations

    Exploring missing heritability in neurodevelopmental disorders:Learning from regulatory elements

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    In this thesis, I aimed to solve part of the missing heritability in neurodevelopmental disorders, using computational approaches. Next to the investigations of a novel epilepsy syndrome and investigations aiming to elucidate the regulation of the gene involved, I investigated and prioritized genomic sequences that have implications in gene regulation during the developmental stages of human brain, with the goal to create an atlas of high confidence non-coding regulatory elements that future studies can assess for genetic variants in genetically unexplained individuals suffering from neurodevelopmental disorders that are of suspected genetic origin

    Exploring missing heritability in neurodevelopmental disorders:Learning from regulatory elements

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    Introduction to Psychology

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    Introduction to Psychology is a modified version of Psychology 2e - OpenStax

    Brain organoids as innovative tool for regenerative medicine

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    The introduction of the tridimensional (3D) organoids technology is revolutionizing the fields of developmental and stem cell biology and it is emerging as the latest frontier in regenerative medicine for the treatment of neurodegenerative disorders, such as epilepsy. The overall objective of my PhD thesis was to set the stage to develop functional hippocampal brain organoid that can be used for regenerative medicine to cure the Temporal Lobe epilepsy (TLE)

    The influence of morphometric changes of gray and white matter on brain functional connectivity in schizophrenia

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    Více než století po vymezení konceptu schizofrenie (SZ) zůstává její etiologie, neuropatologie a patofyziologie do značné míry neobjasněná. Teoretická část práce přináší přehled současných znalostí o klasifikaci a patofyziologii SZ se zvláštním zřetelem věnovaným strukturálním a funkčně zobrazovácím metodám. Zobrazovací nálezy se shodují na tom, že u SZ dochází k redukci šedé hmoty, poruše integrity bílé hmoty a snížení inter-regionální funkční konektivity (FC). Otevřenou otázkou zůstává, zda jsou změny FC od počátku spojené se strukturálními změnami mozku (které jsou jednoznačně potvrzené již před propuknutím nemoci), nebo zda se vyvíjí až s chronifikací SZ. Současně není jasná souvislost mezi narušením FC a prožitkem "jáství", jako možnou jádrovou symptomatikou SZ. Rovněž je nebytné vyvíjet efektivní metody prevence relapsu s cílem zabránit progresi neurobiologických změn mozku. V návaznosti na uvedené otázky zahrnovala praktická část práce celkem tři cíle, v rámci kterých jsme studovali tři odlišné skupiny nemocných. V první skupině pacientů po první epizodě schizofrenie (FES) jsme hodnotili souvislost mezi morfologickými změnami šedé a bílé hmoty mozku a funkční konektivitou. V téže populaci jsme pak studovali změny regionální mozkové konektivity v kontextu narušeného prožitkem "jáství". Druhá...More than a century has passed since a clear definition for schizophrenia was established, yet, the etiology, neuropathological and pathophysiological mechanisms of this psychiatric disorder still, to a large extent, remain to be elucidated. In the theoretical part of this dissertation, we review current classification and pathophysiology of schizophrenia, paying a particular attention to the findings from structural and functional imaging techniques. These techniques demonstrate that patients with schizophrenia tend to have reduced volume of grey matter, reduced integrity of white matter and a disrupted inter-regional functional connectivity (FC). The temporal association between structural changes, already detectable on imaging before symptoms appear, and development of disrupted FC remains to be uncovered. At the same time, current knowledge does not fully explain the link between disrupted FC and disturbed experience of self-awareness, a core symptom of schizophrenia. In addition, it is necessary to develop novel effective methods to prevent relapse and prevent the progression of neurobiological changes in the brain. In the practical part of this dissertation, we designed a study with three different groups of subjects aiming to fulfil three key aims that would help us to fill the gaps in...Klinika psychiatrie a lékařské psychologie 3. LF UK a NÚDZDepartment of Psychiatry and Medical Psychology 3FM CU and NIMH3. lékařská fakultaThird Faculty of Medicin

    Advancing the Study of Functional Connectome Development

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    A better understanding of functional changes in the brain across childhood offers the potential to better support neurodevelopmental and learning challenges. However, neuroimaging tools such as functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) are vulnerable to head motion and other artifacts, and studies have had limited reproducibility. To accomplish research goals, we need to understand the reliability and validity of data collection, processing, and analysis strategies. Neuroimaging datasets contain individually unique information, but identifiability is reduced by noise or lack of signal, suggesting it can be a measure of validity. The goal of this thesis was to use identifiability to benchmark different methodologies, and describe how identifiability associates with age across early childhood. I first compared several different fMRI preprocessing pipelines for data collected from young children. Preprocessing techniques are often controversial due to specific drawbacks and have typically been assessed with adult datasets, which have much less head motion. I found benefits to the use of global signal regression and temporal censoring, but overly strict censoring can impact identifiability, suggesting noise removed must be balanced against signal retained. I also compared several different EEG measures of functional connectivity (FC). EEG can be vulnerable to volume conduction artifacts that can be mitigated by only considering shared information with a time delay between signals. However, I found that mitigation strategies result in lower identifiability, suggesting that while removing confounding noise they also discard substantial signal of interest. Individual experiences may shape development in an individually unique way, which is supported by evidence that adults have more individually identifiable patterns of FC than children. I found that across 4 to 8 years of age, identifiability increased via increased self-stability, but without changes in similarity-to-others. In the absence of ground truth, it is difficult to argue for or against analysis decisions based solely on a theoretical framework and need to also be validated. My work highlights the importance of not thinking about techniques in a valid-invalid dichotomy; certain methods may be sub-optimal while still being preferable to alternatives if they better manage the trade off between noise removed and signal retained

    Structural basis of envelope and phase intrinsic coupling modes in the cerebral cortex

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    Intrinsic coupling modes (ICMs) can be observed in ongoing brain activity at multiple spatial and temporal scales. Two families of ICMs can be distinguished: phase and envelope ICMs. The principles that shape these ICMs remain partly elusive, in particular their relation to the underlying brain structure. Here we explored structure-function relationships in the ferret brain between ICMs quantified from ongoing brain activity recorded with chronically implanted micro-ECoG arrays and structural connectivity (SC) obtained from high-resolution diffusion MRI tractography. Large-scale computational models were used to explore the ability to predict both types of ICMs. Importantly, all investigations were conducted with ICM measures that are sensitive or insensitive to volume conduction effects. The results show that both types of ICMs are significantly related to SC, except for phase ICMs when using measures removing zero-lag coupling. The correlation between SC and ICMs increases with increasing frequency which is accompanied by reduced delays. Computational models produced results that were highly dependent on the specific parameter settings. The most consistent predictions were derived from measures solely based on SC. Overall, the results demonstrate that patterns of cortical functional coupling as reflected in both phase and envelope ICMs are both related, albeit to different degrees, to the underlying structural connectivity in the cerebral cortex.This work was supported by funding from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - SFB 936 - 178316478 - A1 (C.C.H.), A2 (A.K.E.), and Z3 (C.C.H. and A.M.), SPP1665 - 220176618 - EN533/13-1 (A.K.E.), SPP2041 - 313856816 - HI1286/6-1 (C.C.H.) and EN533/15-1 (A.K.E.), from the European Unions Horizon 2020 Framework Programme for Research and Innovation under Specific Grant Agreements 785907 and 945539 (Human Brain Project SGA2 and SGA3, C.C.H.), and from the 2015 FLAG-ERA Joint Transnational Call for project FIIND - ANR-15-HBPR-0005 (R.T.).Peer reviewe

    When smaller is more – investigating the interplay between continuous sensory cues and numerical information

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    Research on numerical cognition is not limited to symbolic numbers and mathematics but it also includes discrete and continuous magnitudes. Continuous magnitudes are ubiquitous in nature and serve as important cues in everyday life situations. When one tries to choose the plate with more cookies in the cafeteria, they usually do not count the cookies but rather arrive at a fair estimate by comparing such continuous magnitudes. For example, nine cookies on a plate will occupy a larger area and have to be placed denser to each other than five cookies. Recent research has shown that, as opposed to the classical view, the processing of symbolic numbers and non-symbolic numerosities is not independent from such sensory cues. The present dissertation consists of two studies that investigate what psychological processes underlie the interaction between sensory cues and numerical information. Study 1 aimed to replicate and extend the findings of Gebuis & Reynvoet who systematically manipulated the relationship between continuous and discrete magnitudes in a non-symbolic numerical comparison task. The main goal was to assess the stability and the robustness of the influence of sensory cues on numerical comparisons as the originally reported patterns suggest a complex interaction between these two kinds of information that are difficult to reconcile with the classic views on numerical processing. Indeed, the results confirmed that continuous magnitudes have a complex effect on numerical judgements and that their interaction can be either due to incomplete inhibition or due to integration of continuous magnitudes during numerical tasks. Study 2 turned to symbolic numbers and investigated whether inhibition underlies the interaction of continuous sensory properties and numerical information. To this end a novel paradigm was introduced that allowed to investigate well-established electrophysiological correlates of inhibition with numerical stimuli. The results provide evidence that inhibition underlies the interaction between sensory cues and numerical information. Additionally, they show that the paradigm introduced in Study 2 may suitable to investigate these processes across different developmental stages and numeracy levels

    Characterizing of Robo downstream signalling to promote direct neurogenesis

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    The size and degree of folding of the mammalian cortex are pivotal factors that affect species’ cognitive abilities and sensorimotor skills. The cerebral cortex is the main region in the mammalian brain that governs complex cognitive behaviors. The development of the cortex depends on the amplification of neural stem cells (NSCs), neural progenitors (NPs) and the generation and differentiation of postmitotic neurons. There are two main types of NPs in the mouse neocortex (NCx): apical radial glia (aRGCs) and intermediate progenitor cells (IPCs). Robo receptors play an important role in regulating the amplification of cortical progenitors. The absence of Robo receptor signalling plus the alteration of the Notch signalling pathway in the mouse NCx leads to an overproduction of poorly functional IPCs. Ancient amniotic cortices exhibit a predominance of direct neurogenesis during development, where aRGCs produce neurons directly. Intriguingly, Robo receptors as well as Notch signalling play a major role in attenuating the mode of neurogenesis. This hypothesis was validated in several brain structures with phyletic antiquity, confirming that Robo receptors are essential in the shift towards indirect neurogenesis during the evolution and expansion of the cerebral cortex. However, little is known about the precise signalling cascade or interactors employed by Robo to initiate direct neurogenesis. In this thesis, we demonstrated the transcriptomic differences between the developing mouse NCx and OB (where direct neurogenesis is predominant in the OB vs NCx) using single cell RNA sequencing (scRNA). We showed aRGCs populations that are differently enriched between these regions. We traced lineage trajectories of indirect and direct neurogenesis, as well as validating the expression of several differentially expressed genes between the two regions. We used Robo intracellular domain (ICD)—this region is considered a constitutively active form of Robo receptor—and demonstrated the protein interactors that bind it. Following that, we demonstrated Robo ICD localization to the nucleus. We discovered that Robo conserved cytoplasmic domains play an important role in Robo ICD nucleocytoplasmic localization and direct neurogenesis induction in the mouse NCx. Next, we showed that Robo ICD localizes to chromatin, and causes transcriptional changes that occur upon the experimental gain of function of Robo ICD in the NCx and in vitro. Additionally, we showed that loss of function of Nup107, a nuclear pore complex (NPC) protein and one of Robo ICD protein interactors, induces direct neurogenesis in mouse NCx and chick lateral pallium. Taken together, our findings suggest the transcriptional role Robo ICD exerts by binding DNA and, consequently, its conserved role in moderating direct neurogenesis. El tamaño y el grado de plegamiento de la corteza cerebral son factores fundamentales que afectan a las capacidades cognitivas y habilidades sensoriomotoras de los mamíferos. La corteza cerebral es la principal región del cerebro que gobierna conductas cognitivas complejas. El desarrollo de la corteza depende de la amplificación de células madre neurales (CMN), progenitores neurales (PN) y de la generación y diferenciación de neuronas postmitóticas. Hay dos tipos principales de PN en la neocorteza o neocórtex (NCx) del ratón: las células de glía radial apical (CGRa) y las células progenitoras intermedias (CPI). Los receptores Robo juegan un papel importante en la regulación de la amplificación de los progenitores corticales. La ausencia de señalización del receptor Robo sumada a la alteración de la vía de señalización de Notch en el NCx de ratón conduce a una sobreproducción de CPI poco funcionales. La corteza de especies amniotas anteriores en la evolución a los mamíferos (como los reptiles y las aves) exhiben un predominio de neurogénesis directa durante el desarrollo, por el cual las CGRa producen neuronas directamente. Curiosamente, los receptores Robo, así como la señalización de Notch, desempeñan un papel importante en la atenuación de esta modalidad de neurogénesis a lo largo de la evolución. Esta hipótesis ha sido validada en varias estructuras cerebrales con antigüedad filética, confirmando que los receptores Robo son esenciales en el cambio hacia la neurogénesis indirecta durante la evolución y la consecuente expansión de la corteza cerebral. Sin embargo, se sabe poco sobre la cascada de señalización de Robo, así como de los mensajeros secundarios empleados por este receptor para iniciar el proceso de neurogénesis directa. En esta tesis, demostramos las diferencias transcriptómicas que existen entre el NCx y el bulbo olfatorio (BO) de ratón en desarrollo (sabiendo que la neurogénesis directa es predominante en BO frente al NCx). Para ello usamos la técnica de secuenciación de ARN de células individuales (single-cell RNA sequencing (scRNAseq) en inglés). Mostramos que hay poblaciones de RGCa que están diferentemente enriquecidas entre estas regiones. Trazamos trayectorias de linaje de neurogénesis indirecta y directa y validamos la expresión de varios genes expresados diferencialmente entre las dos regiones. Utilizamos el dominio intracelular (DIC) de Robo (esta región se considera una forma constitutivamente activa del receptor) y demostramos los mensajeros secundarios que se unen. Después, demostramos la localización del DIC de Robo en el núcleo. Descubrimos que sus dominios citoplasmáticos, muy conservados a lo largo de la evolución, tienen un papel importante en la localización núcleo-citoplasmática del DIC y la inducción directa de neurogénesis en el NCx de ratón. A continuación, mostramos que una vez en el núcleo, el DIC se une a la cromatina y provoca cambios transcripcionales que tienen como resultado una la ganancia de función de Robo tanto en el NCx como in vitro. Además, demostramos que la pérdida de función de Nup107, una proteína que forma parte del complejo del poro nuclear (CPN) además de ser una proteína de interacción del DIC de Robo, induce neurogénesis directa en el NCx de ratón y en el palio lateral de pollo. En conjunto, nuestros resultados sugieren el papel de modulación transcripcional que ejerce el DIC de Robo al unirse al ADN y, en consecuencia, su rol conservado a lo largo de la evolución en la disminución de la neurogénesis directa
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