New Approaches for Data-mining and Classification of Mental Disorder in Brain Imaging Data

Brain imaging data are incredibly complex and new information is being learned as approaches to mine these data are developed. In addition to studying the healthy brain, new approaches for using this information to provide information about complex mental illness such as schizophrenia are needed. Functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) are two well-known neuroimaging approaches that provide complementary information, both of which provide a huge amount of data that are not easily modelled. Currently, diagnosis of mental disorders is based on a patients self-reported experiences and observed behavior over the longitudinal course of the illness. There is great interest in identifying biologically based marker of illness, rather than relying on symptoms, which are a very indirect manifestation of the illness. The hope is that biological markers will lead to earlier diagnosis and improved treatment as well as reduced costs. Understanding mental disorders is a challenging task due to the complexity of brain structure and function, overlapping features between disorders, small numbers of data sets for training, heterogeneity within disorders, and a very large amount of high dimensional data. This doctoral work proposes machine learning and data mining based algorithms to detect abnormal functional network connectivity patterns of patients with schizophrenia and distinguish them from healthy controls using 1) independent components obtained from task related fMRI data, 2) functional network correlations based on resting-state and a hierarchy of tasks, and 3) functional network correlations in both fMRI and MEG data. The abnormal activation patterns of the functional network correlation of patients are characterized by using a statistical analysis and then used as an input to classification algorithms. The framework presented in this doctoral study is able to achieve good characterization of schizophrenia and provides an initial step towards designing an objective biological marker-based diagnostic test for schizophrenia. The methods we develop can also help us to more fully leverage available imaging technology in order to better understand the mystery of the human brain, the most complex organ in the human body

Neurovascular coupling: insights from multi-modal dynamic causal modelling of fMRI and MEG

This technical note presents a framework for investigating the underlying mechanisms of neurovascular coupling in the human brain using multi-modal magnetoencephalography (MEG) and functional magnetic resonance (fMRI) neuroimaging data. This amounts to estimating the evidence for several biologically informed models of neurovascular coupling using variational Bayesian methods and selecting the most plausible explanation using Bayesian model comparison. First, fMRI data is used to localise active neuronal sources. The coordinates of neuronal sources are then used as priors in the specification of a DCM for MEG, in order to estimate the underlying generators of the electrophysiological responses. The ensuing estimates of neuronal parameters are used to generate neuronal drive functions, which model the pre or post synaptic responses to each experimental condition in the fMRI paradigm. These functions form the input to a model of neurovascular coupling, the parameters of which are estimated from the fMRI data. This establishes a Bayesian fusion technique that characterises the BOLD response - asking, for example, whether instantaneous or delayed pre or post synaptic signals mediate haemodynamic responses. Bayesian model comparison is used to identify the most plausible hypotheses about the causes of the multimodal data. We illustrate this procedure by comparing a set of models of a single-subject auditory fMRI and MEG dataset. Our exemplar analysis suggests that the origin of the BOLD signal is mediated instantaneously by intrinsic neuronal dynamics and that neurovascular coupling mechanisms are region-specific. The code and example dataset associated with this technical note are available through the statistical parametric mapping (SPM) software package

The Human Connectome Project: A retrospective

The Human Connectome Project (HCP) was launched in 2010 as an ambitious effort to accelerate advances in human neuroimaging, particularly for measures of brain connectivity; apply these advances to study a large number of healthy young adults; and freely share the data and tools with the scientific community. NIH awarded grants to two consortia; this retrospective focuses on the WU-Minn-Ox HCP consortium centered at Washington University, the University of Minnesota, and University of Oxford. In just over 6 years, the WU-Minn-Ox consortium succeeded in its core objectives by: 1) improving MR scanner hardware, pulse sequence design, and image reconstruction methods, 2) acquiring and analyzing multimodal MRI and MEG data of unprecedented quality together with behavioral measures from more than 1100 HCP participants, and 3) freely sharing the data (via the ConnectomeDB database) and associated analysis and visualization tools. To date, more than 27 Petabytes of data have been shared, and 1538 papers acknowledging HCP data use have been published. The HCP-style neuroimaging paradigm has emerged as a set of best-practice strategies for optimizing data acquisition and analysis. This article reviews the history of the HCP, including comments on key events and decisions associated with major project components. We discuss several scientific advances using HCP data, including improved cortical parcellations, analyses of connectivity based on functional and diffusion MRI, and analyses of brain-behavior relationships. We also touch upon our efforts to develop and share a variety of associated data processing and analysis tools along with detailed documentation, tutorials, and an educational course to train the next generation of neuroimagers. We conclude with a look forward at opportunities and challenges facing the human neuroimaging field from the perspective of the HCP consortium

Investigation of neural activity in Schizophrenia during resting-state MEG : using non-linear dynamics and machine-learning to shed light on information disruption in the brain

Environ 25% de la population mondiale est atteinte de troubles psychiatriques qui sont typiquement associés à des problèmes comportementaux, fonctionnels et/ou cognitifs et dont les corrélats neurophysiologiques sont encore très mal compris. Non seulement ces dysfonctionnements réduisent la qualité de vie des individus touchés, mais ils peuvent aussi devenir un fardeau pour les proches et peser lourd dans l’économie d’une société. Cibler les mécanismes responsables du fonctionnement atypique du cerveau en identifiant des biomarqueurs plus robustes permettrait le développement de traitements plus efficaces. Ainsi, le premier objectif de cette thèse est de contribuer à une meilleure caractérisation des changements dynamiques cérébraux impliqués dans les troubles mentaux, plus précisément dans la schizophrénie et les troubles d’humeur. Pour ce faire, les premiers chapitres de cette thèse présentent, en intégral, deux revues de littératures systématiques que nous avons menées sur les altérations de connectivité cérébrale, au repos, chez les patients schizophrènes, dépressifs et bipolaires. Ces revues révèlent que, malgré des avancées scientifiques considérables dans l’étude de l’altération de la connectivité cérébrale fonctionnelle, la dimension temporelle des mécanismes cérébraux à l’origine de l’atteinte de l’intégration de l’information dans ces maladies, particulièrement de la schizophrénie, est encore mal comprise. Par conséquent, le deuxième objectif de cette thèse est de caractériser les changements cérébraux associés à la schizophrénie dans le domaine temporel. Nous présentons deux études dans lesquelles nous testons l’hypothèse que la « disconnectivité temporelle » serait un biomarqueur important en schizophrénie. Ces études explorent les déficits d’intégration temporelle en schizophrénie, en quantifiant les changements de la dynamique neuronale dite invariante d’échelle à partir des données magnétoencéphalographiques (MEG) enregistrés au repos chez des patients et des sujets contrôles. En particulier, nous utilisons (1) la LRTCs (long-range temporal correlation, ou corrélation temporelle à longue-distance) calculée à partir des oscillations neuronales et (2) des analyses multifractales pour caractériser des modifications de l’activité cérébrale arythmique. Par ailleurs, nous développons des modèles de classification (en apprentissage-machine supervisé) pour mieux cerner les attributs corticaux et sous-corticaux permettant une distinction robuste entre les patients et les sujets sains. Vu que ces études se basent sur des données MEG spontanées enregistrées au repos soit avec les yeux ouvert, ou les yeux fermées, nous nous sommes par la suite intéressés à la possibilité de trouver un marqueur qui combinerait ces enregistrements. La troisième étude originale explore donc l’utilité des modulations de l’amplitude spectrale entre yeux ouverts et fermées comme prédicteur de schizophrénie. Les résultats de ces études démontrent des changements cérébraux importants chez les patients schizophrènes au niveau de la dynamique d’invariance d’échelle. Elles suggèrent une dégradation du traitement temporel de l’information chez les patients, qui pourrait être liée à leurs symptômes cognitifs et comportementaux. L’approche multimodale de cette thèse, combinant la magétoencéphalographie, analyses non-linéaires et apprentissage machine, permet de mieux caractériser l’organisation spatio-temporelle du signal cérébrale au repos chez les patients atteints de schizophrénie et chez des individus sains. Les résultats fournissent de nouvelles preuves supportant l’hypothèse d’une « disconnectivité temporelle » en schizophrénie, et étendent les recherches antérieures, en explorant la contribution des structures cérébrales profondes et en employant des mesures non-linéaires avancées encore sous-exploitées dans ce domaine. L’ensemble des résultats de cette thèse apporte une contribution significative à la quête de nouveaux biomarqueurs de la schizophrénie et démontre l’importance d’élucider les altérations des propriétés temporelles de l’activité cérébrales intrinsèque en psychiatrie. Les études présentées offrent également un cadre méthodologique pouvant être étendu à d’autres psychopathologie, telles que la dépression.Psychiatric disorders affect nearly a quarter of the world’s population. These typically bring about debilitating behavioural, functional and/or cognitive problems, for which the underlying neural mechanisms are poorly understood. These symptoms can significantly reduce the quality of life of affected individuals, impact those close to them, and bring on an economic burden on society. Hence, targeting the baseline neurophysiology associated with psychopathologies, by identifying more robust biomarkers, would improve the development of effective treatments. The first goal of this thesis is thus to contribute to a better characterization of neural dynamic alterations in mental health illnesses, specifically in schizophrenia and mood disorders. Accordingly, the first chapter of this thesis presents two systematic literature reviews, which investigate the resting-state changes in brain connectivity in schizophrenia, depression and bipolar disorder patients. Great strides have been made in neuroimaging research in identifying alterations in functional connectivity. However, these two reviews reveal a gap in the knowledge about the temporal basis of the neural mechanisms involved in the disruption of information integration in these pathologies, particularly in schizophrenia. Therefore, the second goal of this thesis is to characterize the baseline temporal neural alterations of schizophrenia. We present two studies for which we hypothesize that the resting temporal dysconnectivity could serve as a key biomarker in schizophrenia. These studies explore temporal integration deficits in schizophrenia by quantifying neural alterations of scale-free dynamics using resting-state magnetoencephalography (MEG) data. Specifically, we use (1) long-range temporal correlation (LRTC) analysis on oscillatory activity and (2) multifractal analysis on arrhythmic brain activity. In addition, we develop classification models (based on supervised machine-learning) to detect the cortical and sub-cortical features that allow for a robust division of patients and healthy controls. Given that these studies are based on MEG spontaneous brain activity, recorded at rest with either eyes-open or eyes-closed, we then explored the possibility of finding a distinctive feature that would combine both types of resting-state recordings. Thus, the third study investigates whether alterations in spectral amplitude between eyes-open and eyes-closed conditions can be used as a possible marker for schizophrenia. Overall, the three studies show changes in the scale-free dynamics of schizophrenia patients at rest that suggest a deterioration of the temporal processing of information in patients, which might relate to their cognitive and behavioural symptoms. The multimodal approach of this thesis, combining MEG, non-linear analyses and machine-learning, improves the characterization of the resting spatiotemporal neural organization of schizophrenia patients and healthy controls. Our findings provide new evidence for the temporal dysconnectivity hypothesis in schizophrenia. The results extend on previous studies by characterizing scale-free properties of deep brain structures and applying advanced non-linear metrics that are underused in the field of psychiatry. The results of this thesis contribute significantly to the identification of novel biomarkers in schizophrenia and show the importance of clarifying the temporal properties of altered intrinsic neural dynamics. Moreover, the presented studies offer a methodological framework that can be extended to other psychopathologies, such as depression

Brain connectivity analysis: a short survey

This short survey the reviews recent literature on brain connectivity studies. It encompasses all forms of static and dynamic connectivity whether anatomical, functional, or effective. The last decade has seen an ever increasing number of studies devoted to deduce functional or effective connectivity, mostly from functional neuroimaging experiments. Resting state conditions have become a dominant experimental paradigm, and a number of resting state networks, among them the prominent default mode network, have been identified. Graphical models represent a convenient vehicle to formalize experimental findings and to closely and quantitatively characterize the various networks identified. Underlying these abstract concepts are anatomical networks, the so-called connectome, which can be investigated by functional imaging techniques as well. Future studies have to bridge the gap between anatomical neuronal connections and related functional or effective connectivities

The use of fMRI in consumer psychology

Consumer Neuroscience presents Marketers with the challenge of dealing intensively with the multitude of neuroscientific topics and methods. This area is becoming very important as consumers interests are changing. In order to be able to analyse questions of consumer behavioural research from a neuroscience perspective, knowledge about the application of functional magnetic resonance imaging (fMRI) is extremely valuable. However, methodological problems in connection with the fMRI are not sufficiently discussed in the Marketing area. Under this perspective, the central aim of the present work is to present concrete strategies for empirical investigations using the fMRI and to discuss the characteristics, advantages and disadvantages of these options, taking into account already existing research designs. On the one hand of this scientific work theoretical and conceptional reviews of the fMRI and on the other hand empirical fMRI studies are evaluated. Only publications that are marked as A + or higher Journals are considered in this research. First, the results of the literature research show a noticeable increase in the use of event-related designs. Second, it can be seen that only a fraction of the fMRI respondents have a sufficiently large sample size. Third, it is likely that the analysis of fMRI data will become more complex and therefore continue to be the main challenge in conducting an fMRI study

Serotonergic psychedelics LSD & psilocybin increase the fractal dimension of cortical brain activity in spatial and temporal domains.

Psychedelic drugs, such as psilocybin and LSD, represent unique tools for researchers investigating the neural origins of consciousness. Currently, the most compelling theories of how psychedelics exert their effects is by increasing the complexity of brain activity and moving the system towards a critical point between order and disorder, creating more dynamic and complex patterns of neural activity. While the concept of criticality is of central importance to this theory, few of the published studies on psychedelics investigate it directly, testing instead related measures such as algorithmic complexity or Shannon entropy. We propose using the fractal dimension of functional activity in the brain as a measure of complexity since findings from physics suggest that as a system organizes towards criticality, it tends to take on a fractal structure. We tested two different measures of fractal dimension, one spatial and one temporal, using fMRI data from volunteers under the influence of both LSD and psilocybin. The first was the fractal dimension of cortical functional connectivity networks and the second was the fractal dimension of BOLD time-series. In addition to the fractal measures, we used a well-established, non-fractal measure of signal complexity and show that they behave similarly. We were able to show that both psychedelic drugs significantly increased the fractal dimension of functional connectivity networks, and that LSD significantly increased the fractal dimension of BOLD signals, with psilocybin showing a non-significant trend in the same direction. With both LSD and psilocybin, we were able to localize changes in the fractal dimension of BOLD signals to brain areas assigned to the dorsal-attenion network. These results show that psychedelic drugs increase the fractal dimension of activity in the brain and we see this as an indicator that the changes in consciousness triggered by psychedelics are associated with evolution towards a critical zone.NIHR Wellcome NSF-NRT MRC Beckley Foundation Alex Mosley Charitable Trust Ad Astria Chandaria Foundation. Neuro-psychoanalysis Foundation Multidisplinary Association for Psychedelic Studies The Heffter Research Institut

Functional MRI investigations of cortical mechanisms of auditory spatial attention

In everyday settings, spatial attention helps listeners isolate and understand individual sound sources. However, the neural mechanisms of auditory spatial attention (ASpA) are only partially understood. This thesis uses within-subject analysis of functional magnetic resonance imaging (fMRI) data to address fundamental questions regarding cortical mechanisms supporting ASpA by applying novel multi-voxel pattern analysis (MVPA) and resting-state functional connectivity (rsFC) approaches. A series of fMRI studies of ASpA were conducted in which subjects performed a one-back task in which they attended to one of two spatially separated streams. Attention modulated blood oxygenation level-dependent (BOLD) activity in multiple areas in the prefrontal, temporal, and parietal cortex, including non-visuotopic intraparietal sulcus (IPS), but not the visuotopic maps in IPS. No spatial bias was detected in any cortical area using standard univariate analysis; however, MVPA revealed that activation patterns in a number of areas, including the auditory cortex, predicted the attended direction. Furthermore, we explored how cognitive task demands and the sensory modality of the inputs influenced activity with a visual one-back task and a visual multiple object tracking (MOT) task. Activity from the visual and auditory one-back tasks overlapped along the fundus of IPS and lateral prefrontal cortex (lPFC). However, there was minimal overlap of activity in the lPFC between the visual MOT task and the two one-back tasks. Finally, we endeavored to identify visual and auditory networks using rsFC. We identified a dorsal visual attention network reliably within individual subjects using visuotopic seeds. Using auditory seeds, we found a prefrontal area nested between segments of the dorsal visual attention network. These findings mark fundamental progress towards elucidating the cortical network controlling ASpA. Our results suggest that similar lPFC structures support both ASpA and its visual counterpart during a spatial one-back task, but that ASpA does not drive visuotopic IPS in the parietal cortex. Furthermore, rsFC reveals that visual and auditory seed regions are functionally connected with non-overlapping lPFC regions, possibly reflecting spatial and temporal cognitive processing biases, respectively. While we find no evidence for a spatiotopic map, the auditory cortex is sensitive to direction of attention in its patterns of activation

The promise of layer-specific neuroimaging for testing predictive coding theories of psychosis

Predictive coding potentially provides an explanatory model for understanding the neurocognitive mechanisms of psychosis. It proposes that cognitive processes, such as perception and inference, are implemented by a hierarchical system, with the influence of each level being a function of the estimated precision of beliefs at that level. However, predictive coding models of psychosis are insufficiently constrained—any phenomenon can be explained in multiple ways by postulating different changes to precision at different levels of processing. One reason for the lack of constraint in these models is that the core processes are thought to be implemented by the function of specific cortical layers, and the technology to measure layer specific neural activity in humans has until recently been lacking. As a result, our ability to constrain the models with empirical data has been limited. In this review we provide a brief overview of predictive processing models of psychosis and then describe the potential for newly developed, layer specific neuroimaging techniques to test and thus constrain these models. We conclude by discussing the most promising avenues for this research as well as the technical and conceptual challenges which may limit its application

Population neuroimaging:generation of a comprehensive data resource within the ALSPAC pregnancy and birth cohort

Neuroimaging offers a valuable insight into human brain development by allowing in vivo assessment of structure, connectivity and function. Multimodal neuroimaging data have been obtained as part of three sub-studies within the Avon Longitudinal Study of Parents and Children, a prospective multigenerational pregnancy and birth cohort based in the United Kingdom. Brain imaging data were acquired when offspring were between 18 and 24 years of age, and included acquisition of structural, functional and magnetization transfer magnetic resonance, diffusion tensor, and magnetoencephalography imaging. This resource provides a unique opportunity to combine neuroimaging data with extensive phenotypic and genotypic measures from participants, their mothers, and fathers