Модифицированная q-нарная модель Поттса с бинаризованными синаптическими коэффициентами

Практическое применение q-нарных моделей Поттса осложняется высокими требованиями к оперативной памяти (необходимо 32N^2q^2 бит, где N – число нейронов, q – число состояний нейрона). В работе исследуется модифицированная модель Поттса с бинаризованными синаптическими коэффициентами. Процедура бинаризации позволяет в 32 раза уменьшить размер требуемой оперативной памяти (N^2q^2 бит) и более чем в q раз ускорить алгоритм. Ожидалось, что бинаризация приведет к ухудшению распознающих характеристик. Однако анализ показал неожиданные результаты: процедура бинаризации приводит к увеличению объема нейросетевой памяти в 2 раза. Полученные результаты согласуются с проведенными экспериментами.Практичне застосування q-нарних моделей Поттса ускладнюється високими вимогами до оперативної пам’яті (необхідно 32N^2q^2 біт, де N – число нейронів, q – число станів нейрона). У роботі досліджується модифікована модель Поттса з бінаризованими синаптичними коефіцієнтами. Процедура бінаризації дозволяє в 32 рази зменшити розмір необхідної оперативної пам’яті (N^2q^2 біт) і більш ніж в q разів прискорити алгоритм. Очікувалося, що бінаризація призведе до погіршення розпізнавальних характеристик. Проте аналіз показав несподівані результати: процедура бінаризації приводить до збільшення об’єму нейромережної пам’яті в 2 рази. Отримані результати узгоджуються з проведеними експериментами.Practical applications of q-state Potts models are complicated, as they require very large RAM (32N^2q^2 bits, where N is the number of neurons and q is the number of the states of a neuron). In this work we examine a modified Potts model with binarized synaptic coefficients. The procedure of binarization allows one to make the required RAM 32 times smaller (N^2q^2 bits), and the algorithm more than q times faster. One would expect that the binarization worsens the recognizing properties. However, our analysis shows an unexpected result: the binarization procedure leads to the increase of the storage capacity by a factor of 2. The obtained results are in a good agreement with the results of computer simulations

Statistical physics of neural systems

The ability of processing and storing information is considered a characteristic trait of intelligent systems. In biological neural networks, learning is strongly believed to take place at the synaptic level, in terms of modulation of synaptic efficacy. It can be thus interpreted as the expression of a collective phenomena, emerging when neurons connect each other in constituting a complex network of interactions. In this work, we represent learning as an optimization problem, actually implementing a local search, in the synaptic space, of specific configurations, known as solutions and making a neural network able to accomplish a series of different tasks. For instance, we would like the network to adapt the strength of its synaptic connections, in order to be capable of classifying a series of objects, by assigning to each object its corresponding class-label. Supported by a series of experiments, it has been suggested that synapses may exploit a very few number of synaptic states for encoding information. It is known that this feature makes learning in neural networks a challenging task. Extending the large deviation analysis performed in the extreme case of binary synaptic couplings, in this work, we prove the existence of regions of the phase space, where solutions are organized in extremely dense clusters. This picture turns out to be invariant to the tuning of all the parameters of the model. Solutions within the clusters are more robust to noise, thus enhancing the learning performances. This has inspired the design of new learning algorithms, as well as it has clarified the effectiveness of the previously proposed ones. We further provide quantitative evidence that the gain achievable when considering a greater number of available synaptic states for encoding information, is consistent only up to a very few number of bits. This is in line with the above mentioned experimental results. Besides the challenging aspect of low precision synaptic connections, it is also known that the neuronal environment is extremely noisy. Whether stochasticity can enhance or worsen the learning performances is currently matter of debate. In this work, we consider a neural network model where the synaptic connections are random variables, sampled according to a parametrized probability distribution. We prove that, this source of stochasticity naturally drives towards regions of the phase space at high densities of solutions. These regions are directly accessible by means of gradient descent strategies, over the parameters of the synaptic couplings distribution. We further set up a statistical physics analysis, through which we show that solutions in the dense regions are characterized by robustness and good generalization performances. Stochastic neural networks are also capable of building abstract representations of input stimuli and then generating new input samples, according to the inferred statistics of the input signal. In this regard, we propose a new learning rule, called Delayed Correlation Matching (DCM), that relying on the matching between time-delayed activity correlations, makes a neural network able to store patterns of neuronal activity. When considering hidden neuronal states, the DCM learning rule is also able to train Restricted Boltzmann Machines as generative models. In this work, we further require the DCM learning rule to fulfil some biological constraints, such as locality, sparseness of the neural coding and the Dale’s principle. While retaining all these biological requirements, the DCM learning rule has shown to be effective for different network topologies, and in both on-line learning regimes and presence of correlated patterns. We further show that it is also able to prevent the creation of spurious attractor states

The Role of Social Context in Modulating Gene Expression, Neural Activity, and Neuroendocrine Response in Individuals of Varying Social Status

Social context, which includes both the direct social experience of individuals as well as the characteristics of their social network as a whole, has been shown to be an important modulator of behavior across species. However, relatively little is known about the role of social context in regulating the complex relationships between neurobiology, neuroendocrine response, and behavior in mammals. Historically, the neurobiology of social behavior has been studied at the dyadic level, looking at brief social interactions between pairs of individuals. Given that all social species live in groups, rather than pairs, it is essential that we begin to understand the role social context at the group level plays in regulating physiology. Throughout this thesis, I use a novel behavioral housing system to study how the characteristics of stable social groups and how instances of social opportunity, when individuals are ascending up a social hierarchy, are associated with differential brain gene expression, neuroendocrine output, and behavior. I first extensively analyze the social dynamics of male dominance hierarchies, showing that they are both consistent, in that males reliably form significantly linear dominance hierarchies, and unique, in that the characteristics of these hierarchies vary from group to group. I further prove that mice living in these social hierarchies are extremely socially competent, displaying the ability to respond appropriately to individuals of varying social status. I demonstrate that females are capable of forming dominance hierarchies as well, but that their hierarchies differ from those of males. I then use this foundational knowledge to investigate how these different hierarchy characteristics can lead to differences in physiology, how one’s social status is associated with brain gene expression and neuroendocrine response, and how disruption of a hierarchy through removal of the alpha male leads to robust behavioral as well as physiological consequences. Finally, I use the insights gained from this immediate early gene work to demonstrate the crucial role of the infralimbic/prelimbic region of the medial prefrontal cortex in regulating socially competent response to changing social contexts. Taken together, this work establishes the broad role social context plays in regulating the complex relationships between behavior, brain gene expression, neural activation, and neuroendocrine output

Doctor of Philosophy

dissertationFunctional magnetic resonance imaging (fMRI) measures the change of oxygen consumption level in the blood vessels of the human brain, hence indirectly detecting the neuronal activity. Resting-state fMRI (rs-fMRI) is used to identify the intrinsic functional patterns of the brain when there is no external stimulus. Accurate estimation of intrinsic activity is important for understanding the functional organization and dynamics of the brain, as well as differences in the functional networks of patients with mental disorders. This dissertation aims to robustly estimate the functional connectivities and networks of the human brain using rs-fMRI data of multiple subjects. We use Markov random field (MRF), an undirected graphical model to represent the statistical dependency among the functional network variables. Graphical models describe multivariate probability distributions that can be factorized and represented by a graph. By defining the nodes and the edges along with their weights according to our assumptions, we build soft constraints into the graph structure as prior information. We explore various approximate optimization methods including variational Bayesian, graph cuts, and Markov chain Monte Carlo sampling (MCMC). We develop the random field models to solve three related problems. In the first problem, the goal is to detect the pairwise connectivity between gray matter voxels in a rs-fMRI dataset of the single subject. We define a six-dimensional graph to represent our prior information that two voxels are more likely to be connected if their spatial neighbors are connected. The posterior mean of the connectivity variables are estimated by variational inference, also known as mean field theory in statistical physics. The proposed method proves to outperform the standard spatial smoothing and is able to detect finer patterns of brain activity. Our second work aims to identify multiple functional systems. We define a Potts model, a special case of MRF, on the network label variables, and define von Mises-Fisher distribution on the normalized fMRI signal. The inference is significantly more difficult than the binary classification in the previous problem. We use MCMC to draw samples from the posterior distribution of network labels. In the third application, we extend the graphical model to the multiple subject scenario. By building a graph including the network labels of both a group map and the subject label maps, we define a hierarchical model that has richer structure than the flat single-subject model, and captures the shared patterns as well as the variation among the subjects. All three solutions are data-driven Bayesian methods, which estimate model parameters from the data. The experiments show that by the regularization of MRF, the functional network maps we estimate are more accurate and more consistent across multiple sessions

The modular structure of brain functional connectivity networks: a graph theoretical approach

Complex networks theory offers a framework for the analysis of brain functional connectivity as measured by magnetic resonance imaging. Within this approach the brain is represented as a graph comprising nodes connected by links, with nodes corresponding to brain regions and the links to measures of inter-regional interaction. A number of graph theoretical methods have been proposed to analyze the modular structure of these networks. The most widely used metric is Newman's Modularity, which identifies modules within which links are more abundant than expected on the basis of a random network. However, Modularity is limited in its ability to detect relatively small communities, a problem known as ``resolution limit''. As a consequence, unambiguously identifiable modules, like complete sub-graphs, may be unduly merged into larger communities when they are too small compared to the size of the network. This limit, first demonstrated for Newman's Modularity, is quite general and affects, to a different extent, all methods that seek to identify the community structure of a network through the optimization of a global quality function. Hence, the resolution limit may represent a critical shortcoming for the study of brain networks, and is likely to have affected many of the studies reported in the literature. This work pioneers the use of Surprise and Asymptotical Surprise, two quality functions rooted in probability theory that aims at overcoming the resolution limit for both binary and weighted networks. Hereby, heuristics for their optimization are developed and tested, showing that the resulting optimal partitioning can highlight anatomically and functionally plausible modules from brain connectivity datasets, on binary and weighted networks. This novel approach is applied to the partitioning of two different human brain networks that have been extensively characterized in the literature, to address the resolution-limit issue in the study of the brain modular structure. Surprise maximization in human resting state networks revealed the presence of a rich structure of modules with heterogeneous size distribution undetectable by current methods. Moreover, Surprise led to different, more accurate classification of the network's connector hubs, the elements that integrate the brain modules into a cohesive structure. In synthetic networks, Asymptotical Surprise showed high sensitivity and specificity in the detection of ground-truth structures, particularly in the presence of noise and variability such as those observed in experimental functional MRI data. Finally, the methodological advances hereby introduced are shown to be a helpful tool to better discern differences between the modular organization of functional connectivity of healthy subjects and schizophrenic patients. Importantly, these differences may point to new clinical hypotheses on the etiology of schizophrenia, and they would have gone unnoticed with resolution-limited methods. This may call for a revisitation of some of the current models of the modular organization of the healthy and diseased brain

Partial‐volume modeling reveals reduced gray matter in specific thalamic nuclei early in the time course of psychosis and chronic schizophrenia

The structural complexity of the thalamus, due to its mixed composition of gray and white matter, make it challenging to disjoint and quantify each tissue contribution to the thalamic anatomy. This work promotes the use of partial-volume-based over probabilistic-based tissue segmentation approaches to better capture thalamic gray matter differences between patients at different stages of psychosis (early and chronic) and healthy controls. The study was performed on a cohort of 23 patients with schizophrenia, 41 with early psychosis and 69 age and sex-matched healthy subjects. Six tissue segmentation approaches were employed to obtain the gray matter concentration/probability images. The statistical tests were applied at three different anatomical scales: whole thalamus, thalamic subregions and voxel-wise. The results suggest that the partial volume model estimation of gray matter is more sensitive to detect atrophies within the thalamus of patients with psychosis. However all the methods detected gray matter deficit in the pulvinar, particularly in early stages of psychosis. This study demonstrates also that the gray matter decrease varies nonlinearly with age and between nuclei. While a gray matter loss was found in the pulvinar of patients in both stages of psychosis, reduced gray matter in the mediodorsal was only observed in early psychosis subjects. Finally, our analyses point to alterations in a sub-region comprising the lateral posterior and ventral posterior nuclei. The obtained results reinforce the hypothesis that thalamic gray matter assessment is more reliable when the tissues segmentation method takes into account the partial volume effect

From Dynamics to Structure of Complex Networks: Exploiting Heterogeneity in the Sakaguchi-Kuramoto Model

[eng] Most of the real-world complex systems are best described as complex networks and can be mathematically described as oscillatory systems, coupled with the neighbours through the connections of the network. The flashing of fireflies, the neuronal brain signals or the energy flow through the power grid are some examples. Yoshiki Kuramoto came up with a tractable mathematical model that could capture the phenomenology of collective synchronization by suggesting that oscillators were coupled by a sinusoidal function of their phase differences. Later, Yoshiki Kuramoto together with Hidetsugu Sakaguchi presented a generalization of the previous limit-cycle set of oscillators Kuramoto’s model which incorporated a constant phase lag between oscillators. Subsequent studies of the model included the network structure within the model together with the global shift. For a wide range of the phase lag values, the system becomes synchronized to a resulting frequency, i.e., the dynamics reaches a stationary state. In the original work of Kuramoto and Sakaguchi and in most of the consequent later studies, a uniform distribution of phase lag parameters is customarily assumed. However, the intrinsic properties of nodes – that assuredly represent the constituents of real systems – do not need be identical but distributed non-homogeneously among the population. This thesis contributes to the understanding of the Kuramoto-Sakaguchi model with a generalization for nonhomogeneous phase lag parameter distribution. Considering different scenarios concerning the distribution of the frustration parameter among the oscillators represents a major step towards the extension of the original model and provides significant novel insights into the structure and function of the considered network. The first setting that the present thesis considers consists in perturbing the stationary state of the system by introducing a non-zero phase lag shift into the dynamics of a single node. The aim of this work is to sort the nodes by their potential effect on the whole network when a change on their individual dynamics spreads over the entire oscillatory system by disrupting the otherwise synchronized state. In particular, we define functionability, a novel centrality measure that addresses the question of which are the nodes that, when individually perturbed, are best able to move the system away from the fully synchronized state. This issue may be relevant for the identification of critical nodes that are either beneficial – by enabling access to a broader spectrum of states – or harmful – by destroying the overall synchronization. The second scenario that the present thesis addresses considers a more general configuration in which the phase lag parameter is an intrinsic property of each node, not necessarily zero, and hence exploring the potential heterogeneity of the frustration among oscillators. We obtain the analytical solution of frustration parameters so as to achieve any phase configuration, by linearizing the most general model. We also address the fact that the question ’among all the possible solutions, which is the one that makes the system achieve a particular phase configuration with the minimum required cost?’ is of particular relevance when we consider the plausible real nature of the system. Finally, the homogenous distribution of phase lag parameters is revisited in the last scenario. As studied in the literature, a certain degree of symmetry is an attribute of real-world networks. Nevertheless, beyond structural or topological symmetry, one should consider the fact that real- world networks are exposed to fluctuations or errors, as well as mistaken insertions or removals. In the present thesis, we provide an alternative notion to approximate symmetries, which we call ‘Quasi-Symmetries’ and are defined such that they remain free to impose any invariance of a particular network property and are obtained from the stationary state of the Kuramoto-Sakaguchi model with a homogeneous phase lag distribution. A first contribution is exploring the distributions of structural similarity among all pairs of nodes. Secondly, we define the ‘dual network’, a weighted network –and its corresponding binarized counterpart– that effectively encloses all the information of quasi-symmetries in the original one.[cat] La major part dels sistemes complexos presents en la natura i la societat es poden descriure com a xarxes complexes. Molts d’aquests sistemes es poden modelitzar matemàticament com un sistema oscil·latori, on les unitats queden acoblades amb els components veïns a través de les connexions de la xarxa. Yoshiki Kuramoto i Hidetsugu Sakaguchi van presentar la generalització del ben conegut model d’oscil·ladors de Kuramoto, on s’incorporava un terme de desfasament entre parelles d’oscil·ladors. Aquesta tesi contribueix en la comprensió d’aquest model, tot considerant una distribució no homogènia d’aquest paràmetre de desfasament o frustració. S’han considerat tres escenaris diferents, tots ells donant lloc a resultats que permeten una millor descripció de l’estructura i funció de la xarxa que s’està considerant. Una primera configuració consisteix en pertorbar l’estat estacionari tot introduint un desfasament en la dinàmica d’un node de manera aïllada. Seguidament, definim la funcionabilitat, una mesura de centralitat única que respon a la pregunta de, quins nodes, quan són pertorbats individualment, són més capaços d’allunyar el sistema de l’estat sincronitzat. Aquest fet podria suposar un comportament beneficiós o perjudicial per sistemes reals. El segon escenari considera la configuració més flexible, explorant la potencial heterogeneïtat dels paràmetres de frustració dels diferents nodes. Obtenim la solució analítica d’aquesta distribució per tal d’assolir qualsevol configuració de les fases dels oscil·ladors, a través de la linearització del model. També contestem a la pregunta: “de totes les possibles solucions, quina és la que implica un menor cost per tal d’assolir una configuració en particular?”. Finalment, en l’últim escenari, proporcionem una definició alternativa al concepte de simetria aproximada d’una xarxa, i que anomenem “Quasi simetries”. Aquestes són definides sense imposar invariàncies en les propietats del sistema, sinó que s’obtenen de l’estat estacionari del model de Kuramoto-Sakaguchi model, tot considerant una distribució homogènia dels paràmetres de frustració

Restauration d'images en IRM anatomique pour l'étude préclinique des marqueurs du vieillissement cérébral

Les maladies neurovasculaires et neurodégénératives liées à l'âge sont en forte augmentation. Alors que ces changements pathologiques montrent des effets sur le cerveau avant l'apparition de symptômes cliniques, une meilleure compréhension du processus de vieillissement normal du cerveau aidera à distinguer l'impact des pathologies connues sur la structure régionale du cerveau. En outre, la connaissance des schémas de rétrécissement du cerveau dans le vieillissement normal pourrait conduire à une meilleure compréhension de ses causes et peut-être à des interventions réduisant la perte de fonctions cérébrales associée à l'atrophie cérébrale. Par conséquent, ce projet de thèse vise à détecter les biomarqueurs du vieillissement normal et pathologique du cerveau dans un modèle de primate non humain, le singe marmouset (Callithrix Jacchus), qui possède des caractéristiques anatomiques plus proches de celles des humains que de celles des rongeurs. Cependant, les changements structurels (par exemple, de volumes, d'épaisseur corticale) qui peuvent se produire au cours de leur vie adulte peuvent être minimes à l'échelle de l'observation. Dans ce contexte, il est essentiel de disposer de techniques d'observation offrant un contraste et une résolution spatiale suffisamment élevés et permettant des évaluations détaillées des changements morphométriques du cerveau associé au vieillissement. Cependant, l'imagerie de petits cerveaux dans une plateforme IRM 3T dédiée à l'homme est une tâche difficile car la résolution spatiale et le contraste obtenus sont insuffisants par rapport à la taille des structures anatomiques observées et à l'échelle des modifications attendues. Cette thèse vise à développer des méthodes de restauration d'image pour les images IRM précliniques qui amélioreront la robustesse des algorithmes de segmentation. L'amélioration de la résolution spatiale des images à un rapport signal/bruit constant limitera les effets de volume partiel dans les voxels situés à la frontière entre deux structures et permettra une meilleure segmentation tout en augmentant la reproductibilité des résultats. Cette étape d'imagerie computationnelle est cruciale pour une analyse morphométrique longitudinale fiable basée sur les voxels et l'identification de marqueurs anatomiques du vieillissement cérébral en suivant les changements de volume dans la matière grise, la matière blanche et le liquide cérébral.Age-related neurovascular and neurodegenerative diseases are increasing significantly. While such pathological changes show effects on the brain before clinical symptoms appear, a better understanding of the normal aging brain process will help distinguish known pathologies' impact on regional brain structure. Furthermore, knowledge of the patterns of brain shrinkage in normal aging could lead to a better understanding of its causes and perhaps to interventions reducing the loss of brain functions. Therefore, this thesis project aims to detect normal and pathological brain aging biomarkers in a non-human primate model, the marmoset monkey (Callithrix Jacchus) which possesses anatomical characteristics more similar to humans than rodents. However, structural changes (e.g., volumes, cortical thickness) that may occur during their adult life may be minimal with respect to the scale of observation. In this context, it is essential to have observation techniques that offer sufficiently high contrast and spatial resolution and allow detailed assessments of the morphometric brain changes associated with aging. However, imaging small brains in a 3T MRI platform dedicated to humans is a challenging task because the spatial resolution and the contrast obtained are insufficient compared to the size of the anatomical structures observed and the scale of the xpected changes with age. This thesis aims to develop image restoration methods for preclinical MR images that will improve the robustness of the segmentation algorithms. Improving the resolution of the images at a constant signal-to-noise ratio will limit the effects of partial volume in voxels located at the border between two structures and allow a better segmentation while increasing the results' reproducibility. This computational imaging step is crucial for a reliable longitudinal voxel-based morphometric analysis and for the identification of anatomical markers of brain aging by following the volume changes in gray matter, white matter and cerebrospinal fluid

Augmentation of Brain Function: Facts, Fiction and Controversy. Volume III: From Clinical Applications to Ethical Issues and Futuristic Ideas

The final volume in this tripartite series on Brain Augmentation is entitled “From Clinical Applications to Ethical Issues and Futuristic Ideas”. Many of the articles within this volume deal with translational efforts taking the results of experiments on laboratory animals and applying them to humans. In many cases, these interventions are intended to help people with disabilities in such a way so as to either restore or extend brain function. Traditionally, therapies in brain augmentation have included electrical and pharmacological techniques. In contrast, some of the techniques discussed in this volume add specificity by targeting select neural populations. This approach opens the door to where and how to promote the best interventions. Along the way, results have empowered the medical profession by expanding their understanding of brain function. Articles in this volume relate novel clinical solutions for a host of neurological and psychiatric conditions such as stroke, Parkinson’s disease, Huntington’s disease, epilepsy, dementia, Alzheimer’s disease, autism spectrum disorders (ASD), traumatic brain injury, and disorders of consciousness. In disease, symptoms and signs denote a departure from normal function. Brain augmentation has now been used to target both the core symptoms that provide specificity in the diagnosis of a disease, as well as other constitutional symptoms that may greatly handicap the individual. The volume provides a report on the use of repetitive transcranial magnetic stimulation (rTMS) in ASD with reported improvements of core deficits (i.e., executive functions). TMS in this regard departs from the present-day trend towards symptomatic treatment that leaves unaltered the root cause of the condition. In diseases, such as schizophrenia, brain augmentation approaches hold promise to avoid lengthy pharmacological interventions that are usually riddled with side effects or those with limiting returns as in the case of Parkinson’s disease. Brain stimulation can also be used to treat auditory verbal hallucination, visuospatial (hemispatial) neglect, and pain in patients suffering from multiple sclerosis. The brain acts as a telecommunication transceiver wherein different bandwidth of frequencies (brainwave oscillations) transmit information. Their baseline levels correlate with certain behavioral states. The proper integration of brain oscillations provides for the phenomenon of binding and central coherence. Brain augmentation may foster the normalization of brain oscillations in nervous system disorders. These techniques hold the promise of being applied remotely (under the supervision of medical personnel), thus overcoming the obstacle of travel in order to obtain healthcare. At present, traditional thinking would argue the possibility of synergism among different modalities of brain augmentation as a way of increasing their overall effectiveness and improving therapeutic selectivity. Thinking outside of the box would also provide for the implementation of brain-to-brain interfaces where techniques, proper to artificial intelligence, could allow us to surpass the limits of natural selection or enable communications between several individual brains sharing memories, or even a global brain capable of self-organization. Not all brains are created equal. Brain stimulation studies suggest large individual variability in response that may affect overall recovery/treatment, or modify desired effects of a given intervention. The subject’s age, gender, hormonal levels may affect an individual’s cortical excitability. In addition, this volume discusses the role of social interactions in the operations of augmenting technologies. Finally, augmenting methods could be applied to modulate consciousness, even though its neural mechanisms are poorly understood. Finally, this volume should be taken as a debate on social, moral and ethical issues on neurotechnologies. Brain enhancement may transform the individual into someone or something else. These techniques bypass the usual routes of accommodation to environmental exigencies that exalted our personal fortitude: learning, exercising, and diet. This will allow humans to preselect desired characteristics and realize consequent rewards without having to overcome adversity through more laborious means. The concern is that humans may be playing God, and the possibility of an expanding gap in social equity where brain enhancements may be selectively available to the wealthier individuals. These issues are discussed by a number of articles in this volume. Also discussed are the relationship between the diminishment and enhancement following the application of brain-augmenting technologies, the problem of “mind control” with BMI technologies, free will the duty to use cognitive enhancers in high-responsibility professions, determining the population of people in need of brain enhancement, informed public policy, cognitive biases, and the hype caused by the development of brain- augmenting approaches