A Thalamic-Fronto-Parietal Structural Covariance Network Emerging in the Course of Recovery from Hand Paresis after Ischemic Stroke.

AIM To describe structural covariance networks of gray matter volume (GMV) change in 28 patients with first-ever stroke to the primary sensorimotor cortices, and to investigate their relationship to hand function recovery and local GMV change. METHODS Tensor-based morphometry maps derived from high-resolution structural images were subject to principal component analyses to identify the networks. We calculated correlations between network expression and local GMV change, sensorimotor hand function and lesion volume. To verify which of the structural covariance networks of GMV change have a significant relationship to hand function, we performed an additional multivariate regression approach. RESULTS Expression of the second network, explaining 9.1% of variance, correlated with GMV increase in the medio-dorsal (md) thalamus and hand motor skill. Patients with positive expression coefficients were distinguished by significantly higher GMV increase of this structure during stroke recovery. Significant nodes of this network were located in md thalamus, dorsolateral prefrontal cortex, and higher order sensorimotor cortices. Parameter of hand function had a unique relationship to the network and depended on an interaction between network expression and lesion volume. Inversely, network expression is limited in patients with large lesion volumes. CONCLUSION Chronic phase of sensorimotor cortical stroke has been characterized by a large scale co-varying structural network in the ipsilesional hemisphere associated specifically with sensorimotor hand skill. Its expression is related to GMV increase of md thalamus, one constituent of the network, and correlated with the cortico-striato-thalamic loop involved in control of motor execution and higher order sensorimotor cortices. A close relation between expression of this network with degree of recovery might indicate reduced compensatory resources in the impaired subgroup.

Brain network analysis of patients with Temporal Lobe Epilepsy

Patients with Temporal Lobe Epilepsy (TLE) suffer from widespread subtle white matter abnormalities and abnormal functional connectivity extending beyond the affected lobe, as revealed by Diffusion Tensor MR Imaging, volumetric and functional MRI studies. Diffusion Spectrum Imaging (DSI) is a diffusion imaging technique with high angular resolution for improving the mapping of white matter pathways. In this study, we used DSI, connectivity matrices and topological measures to investigate how the alteration in structural connectivity influences whole brain structural networks. Eleven patients with right-sided TLE and hippocampal sclerosis and 18 controls underwent our DSI protocol at 3T. The cortical and subcortical grey matters were parcellated into 86 regions of interest and the connectivity between every region pair was estimated using global tractography and a connectivity matrix (the adjacency matrix of the structural network). We then compared the networks of patients and controls using topological measures. In patients, we found a higher characteristic path length and a lower clustering coefficient compared to controls. Local measures at node level of the clustering and efficiency showed a significant difference after a multiple comparison correction (Bonferroni). These significant nodes were located within as well outside the temporal lobe, and the localisation of most of them was consistent with regions known to be part of epileptic networks in TLE. Our results show altered connectivity patterns that are concordant with the mapping of functional epileptic networks in patients with TLE. Further studies are needed to establish the relevance of these findings for the propagation of epileptic activity, cognitive deficits in medial TLE and outcome of epilepsy surgery in individual patients.

The structural substrate of brain function: analysis of brain structural networks based on diffusion-weighted imaging

The brain is a complex neural network with a hierarchical organization and the mapping of its elements and connections is an important step towards the understanding of its function. Recent developments in diffusion-weighted imaging have provided the opportunity to reconstruct the whole-brain structural network in-vivo at a large scale level and to study the brain structural substrate in a framework that is close to the current understanding of brain function. However, methods to construct the connectome are still under development and they should be carefully evaluated. To this end, the first two studies included in my thesis aimed at improving the analytical tools specific to the methodology of brain structural networks. The first of these papers assessed the repeatability of the most common global and local network metrics used in literature to characterize the connectome, while in the second paper the validity of further metrics based on the concept of communicability was evaluated. Communicability is a broader measure of connectivity which accounts also for parallel and indirect connections. These additional paths may be important for reorganizational mechanisms in the presence of lesions as well as to enhance integration in the network. These studies showed good to excellent repeatability of global network metrics when the same methodological pipeline was applied, but more variability was detected when considering local network metrics or when using different thresholding strategies. In addition, communicability metrics have been found to add some insight into the integration properties of the network by detecting subsets of nodes that were highly interconnected or vulnerable to lesions. The other two studies used methods based on diffusion-weighted imaging to obtain knowledge concerning the relationship between functional and structural connectivity and about the etiology of schizophrenia. The third study integrated functional oscillations measured using electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) as well as diffusion-weighted imaging data. The multimodal approach that was applied revealed a positive relationship between individual fluctuations of the EEG alpha-frequency and diffusion properties of specific connections of two resting-state networks. Finally, in the fourth study diffusion-weighted imaging was used to probe for a relationship between the underlying white matter tissue structure and season of birth in schizophrenia patients. The results are in line with the neurodevelopmental hypothesis of early pathological mechanisms as the origin of schizophrenia. The different analytical approaches selected in these studies also provide arguments for discussion of the current limitations in the analysis of brain structural networks. To sum up, the first studies presented in this thesis illustrated the potential of brain structural network analysis to provide useful information on features of brain functional segregation and integration using reliable network metrics. In the other two studies alternative approaches were presented. The common discussion of the four studies enabled us to highlight the benefits and possibilities for the analysis of the connectome as well as some current limitations.

Conectividade estrutural do cérebro

Mestrado em Radiações Aplicadas às Tecnologias da Saúde. Área de especialização: Ressonância Magnética

Conectividade estrutural do cérebro: diferenças entre um cérebro normal e um cérebro com patologia

Perceber a rede estrutural formada pelos neurónios no cérebro a nível da macro escala é um desafio atual na área das neurociências. Neste estudo analisou-se a conectividade estrutural do cérebro em 22 indivíduos saudáveis e em dois doentes com epilepsia pós-traumática. Avaliaram-se as diferenças entre estes dois grupos. Também se pesquisaram diferenças a nível do género e idade no grupo de indivíduos saudáveis e os que têm valores médios mais elevados nas métricas de caracterização da rede. Para tal, desenvolveu-se um protocolo de análise recorrendo a diversos softwares especializados e usaram-se métricas da Teoria dos Grafos para a caracterização da conectividade estrutural entre 118 regiões encefálicas distintas. Dentro do grupo dos indivíduos saudáveis concluiu-se que os homens, no geral, são os que têm média mais alta para as métricas de caracterização da rede estrutural. Contudo, não se observaram diferenças significativas em relação ao género nas métricas de caracterização global do cérebro. Relativamente à idade, esta correlaciona-se negativamente, no geral, com as métricas de caracterização da rede estrutural. As regiões onde se observaram as diferenças mais importantes entre indivíduos saudáveis e doentes são: o sulco rolândico, o hipocampo, o pré-cuneus, o tálamo e o cerebelo bilateralmente. Estas diferenças são consistentes com as imagens radiológicas dos doentes e com a literatura estudada sobre a epilepsia pós-traumática. Preveem-se desenvolvimentos para o estudo da conectividade estrutural do cérebro humano, uma vez que a sua potencialidade pode ser combinada com outros métodos de modo a caracterizar as alterações dos circuitos cerebrais.

Modeling the impact of lesions in the human brain.

Lesions of anatomical brain networks result in functional disturbances of brain systems and behavior which depend sensitively, often unpredictably, on the lesion site. The availability of whole-brain maps of structural connections within the human cerebrum and our increased understanding of the physiology and large-scale dynamics of cortical networks allow us to investigate the functional consequences of focal brain lesions in a computational model. We simulate the dynamic effects of lesions placed in different regions of the cerebral cortex by recording changes in the pattern of endogenous ("resting-state") neural activity. We find that lesions produce specific patterns of altered functional connectivity among distant regions of cortex, often affecting both cortical hemispheres. The magnitude of these dynamic effects depends on the lesion location and is partly predicted by structural network properties of the lesion site. In the model, lesions along the cortical midline and in the vicinity of the temporo-parietal junction result in large and widely distributed changes in functional connectivity, while lesions of primary sensory or motor regions remain more localized. The model suggests that dynamic lesion effects can be predicted on the basis of specific network measures of structural brain networks and that these effects may be related to known behavioral and cognitive consequences of brain lesions.

Mapping the development of the human connectome

From birth to early adulthood the brain undergoes dramatic modifications resulting in network development and optimization. In the present study we investigate the development of the human connectome but measuring myelination trajectories of individual connections over the entire brain structural network using high b-value diffusion imaging and tractography. We found significant changes in several network measures that support increased integration and efficiency. We also observe that the network doesn't myelinate at a uniform rate but with different myelination speeds dependant on the type of cortex.

Transfer entropy reconstruction and labeling of neuronal connections from simulated calcium imaging

Neuronal dynamics are fundamentally constrained by the underlying structural network architecture, yet much of the details of this synaptic connectivity are still unknown even in neuronal cultures in vitro. Here we extend a previous approach based on information theory, the Generalized Transfer Entropy, to the reconstruction of connectivity of simulated neuronal networks of both excitatory and inhibitory neurons. We show that, due to the model-free nature of the developed measure, both kinds of connections can be reliably inferred if the average firing rate between synchronous burst events exceeds a small minimum frequency. Furthermore, we suggest, based on systematic simulations, that even lower spontaneous inter-burst rates could be raised to meet the requirements of our reconstruction algorithm by applying a weak spatially homogeneous stimulation to the entire network. By combining multiple recordings of the same in silico network before and after pharmacologically blocking inhibitory synaptic transmission, we show then how it becomes possible to infer with high confidence the excitatory or inhibitory nature of each individual neuron.

Oppivan organisaation edellytysten selvittäminen Mikkelin puhelin Oyj:ssä

Yritysten kilpailukyky ei perustu nykypäivän pelkästään aineellisiin resursseihin. Yritysten on pyrittävä luomaan kyvykkyyksiä, joilla yritys pystyy sopeutumaan nopeasti muuttuviin olosuhteisiin toimintaympäristössään. Aineettoman pääoman, kuten rakenne-, suhde- ja ihmispääoman kehittäminen mahdollistaa edellä mainittujen kyvykkyyksien luomisen ja hallitsemisen organisaatiossa. Pääoman kehittäminen sekä hallinta vaativat organisaatiolta kulttuurisia ominaisuuksia, jotka mahdollistavat jatkuvan oppimisen ja toiminnan parantamisen. Tässä työssä on pyritty selvittämään, mitä nämä oppivan organisaation edellytykset ovat ja miten niiden nykytilaa voidaan mitata. Työn teoreettisen viitekehyksen avulla muodostettiin teemoittain kysymyksiä, joilla organisaation tilaa suhteessa oppivan organisaation tavoitteisiin pystytään tuomaan läpinäkyväksi. Kyselyn tuloksista huomattiin, että tällä mittaristolla saatiin esiin monia oppivan organisaation toimintaan vaikuttavia elementtejä ja niiden vaatimia kehityskohteita.

Estimating complex cortical networks via surface recordings-A critical note

We discuss potential caveats when estimating topologies of 3D brain networks from surface recordings. It is virtually impossible to record activity from all single neurons in the brain and one has to rely on techniques that measure average activity at sparsely located (non-invasive) recording sites Effects of this spatial sampling in relation to structural network measures like centrality and assortativity were analyzed using multivariate classifiers A simplified model of 3D brain connectivity incorporating both short- and long-range connections served for testing. To mimic M/EEG recordings we sampled this model via non-overlapping regions and weighted nodes and connections according to their proximity to the recording sites We used various complex network models for reference and tried to classify sampled versions of the ""brain-like"" network as one of these archetypes It was found that sampled networks may substantially deviate in topology from the respective original networks for small sample sizes For experimental studies this may imply that surface recordings can yield network structures that might not agree with its generating 3D network. (C) 2010 Elsevier Inc All rights reserved

Preparation and Characterization of Novel Micro- and Nanocomposite Hydrogels Containing Cellulosic Fibrils

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Neuroimaging in specific phobia disorder: a systematic review of the literature

OBJECTIVE: Specific phobia (SP) is characterized by irrational fear associated with avoidance of specific stimuli. In recent years, neuroimaging techniques have been used in an attempt to better understand the neurobiology of anxiety disorders. The objective of this study was to perform a systematic review of articles that used neuroimaging techniques to study SP. METHOD:A literature search was conducted through electronic databases, using the keywords: imaging, neuroimaging, PET, spectroscopy, functional magnetic resonance, structural magnetic resonance, SPECT, MRI, DTI, and tractography, combined with simple phobia and specific phobia. One-hundred fifteen articles were found, of which 38 were selected for the present review. From these, 24 used fMRI, 11 used PET, 1 used SPECT, 2 used structural MRI, and none used spectroscopy. RESULT: The search showed that studies in this area were published recently and that the neuroanatomic substrate of SP has not yet been consolidated. CONCLUSION: In spite of methodological differences among studies, results converge to a greater activation in the insula, anterior cingulate cortex, amygdala, and prefrontal and orbitofrontal cortex of patients exposed to phobia-related situations compared to controls. These findings support the hypotheses of the hyperactivation of a neuroanatomic structural network involved in SP.

A Comparative Study of Central and Eastern European Social Policy Concernig Mental Disability

The main goal of this project was to identity whether an imported system of social policy can be suitable for a host country, and if not why not. Romanian social policy concerning the mentally disabled represents a paradoxical situation in that while social policy is designed to ensure both an institutional structure and a juridical environment, in practice it is far from successful. The central question which Ms. Ciumageanu asked therefore was whether this failure was due to systemic factors, or whether the problem lay in reworking an imported social policy system to meet local needs. She took a comparative approach, also considering both the Scandinavian model of social policy, particularly the Danish model which has been adopted in Romania, and the Hungarian system, which has inherited a similar universal welfare system and perpetuated it to some extent. In order to verify her hypothesis, she also studied the transformation of the welfare system in Great Britain, which meant a shift from state responsibility towards community care. In all these she concentrated on two major aspects: the structural design within the different countries and, at a micro level, the societal response. Following her analyses of the various in the other countries concerned, Ms. Ciumageanu concluded that the major differences lie first in the difference between the stages of policy design. Here Denmark is the most advanced and Romania the most backwards. Denmark has a fairly elaborate infrastructure, Britain a system with may gaps to bridge, and Hungary and Romania are struggling with severe difficulties owing both to the inherited structure and the limits imposed by an inadequate GDP. While in Denmark and Britain, mental patients are integrated into an elaborate system of care, designed and administered by the state (in Denmark) or communities (in Britain), in Hungary and Romania, the state designs and fails to implement the policy and community support is minimal, partly due to the lack of a fully developed civil society. At the micro level the differences are similar. While in Denmark and Britain there is a consensus about the roles of the state and of civil societies (although at different levels in the two countries, with the state being more supportive in Denmark), in Romania and to a considerable extent in Hungary, civil society tends to expect too much from the state, which in its turn is withdrawing faster from its social roles than from its economic ones, generating a gap between the welfare state and the market economy and disadvantaging the expected transition from a welfare state to a welfare society and, implicitly, the societal response towards those mentally disabled persons in it. On an intermediate level, the factors influencing social policy as a whole were much the same for Hungary and Romania. Economic factors include the accumulated economic resources of both state and citizens, and the inherited pattern of redistribution, as well as the infrastructure; institutional resources include the role of the state and the efficiency of the state bureaucracy, the strength and efficiency of the state apparatus, political stability and the complexity of political democratisation, the introduction of market institutions, the strength of civil society and civic sector institutions. From the standpoint of the societal response, some factors were common to all countries, particularly the historical context, the collective and institutional memories and established patterns of behaviour. In the specific case of Romania, general structural and environmental factors - industrialisation and forced urbanisation - have had a definite influence on family structure, values and behavioural patterns. The analysis of Romanian social policy revealed several causes for failure to date. The first was the instability of the policy and the failure to consider the structural network involved in developing it, rather than just the results obtained. The second was the failure to take into account the relationship between the individual and the group in all its aspects, followed by the lack of active assistance for prevention, re-socialisation or professional integration of persons with mental disabilities. Finally, the state fails to recognise its inability to support an expensive psychiatric enterprise and does not provide any incentive to the private sector. This creates tremendous social costs for both the state and the individual. NGOs working in the field in Romania have been somewhat more successful but are still limited by their lack of funding and personnel and the idea of a combined system is as yet utopian in the circumstances in the country.

(N)um lugar ao sol: contributos do turismo para as dinâmicas criativas e para a atração da classe criativa no Algarve

Tese de Doutoramento, Turismo, Faculdade de Economia, Universidade do Algarve, 2016