Abnormal synchrony and effective connectivity in patients with schizophrenia and auditory hallucinations

[EN] Auditory hallucinations (AH) are the most frequent positive symptoms in patients with schizophrenia. Hallucinations have been related to emotional processing disturbances, altered functional connectivity and effective connectivity deficits. Previously, we observed that, compared to healthy controls, the limbic network responses of patients with auditory hallucinations differed when the subjects were listening to emotionally charged words. We aimed to compare the synchrony patterns and effective connectivity of task-related networks between schizophrenia patients with and without AH and healthy controls. Schizophrenia patients with AH (n = 27) and without AH (n = 14) were compared with healthy participants (n = 31). We examined functional connectivity by analyzing correlations and cross-correlations among previously detected independent component analysis time courses. Granger causality was used to infer the information flow direction in the brain regions. The results demonstrate that the patterns of cortico-cortical functional synchrony differentiated the patients with AH from the patients without AH and from the healthy participants. Additionally, Granger-causal relationships between the networks clearly differentiated the groups. In the patients with AH, the principal causal source was an occipital¿cerebellar component, versus a temporal component in the patients without AH and the healthy controls. These data indicate that an anomalous process of neural connectivity exists when patients with AH process emotional auditory stimuli. Additionally, a central role is suggested for the cerebellum in processing emotional stimuli in patients with persistent AH.Funding for this study was provided by Spanish grants from Ministry of Science and Innovation (ISCIII: FIS P.I.02/0018, P.I.05/2332.), Spanish Mental Health Network: CIBERSAM and Combiomed Network.De La Iglesia-Vaya, M.; Escartí Fabra, MJ.; Molina-Mateo, J.; Marti-Bonmati, L.; Gadea, M.; Castellanos, FX.; Aguilar Garcia-Iturrospe, EJ.... (2014). Abnormal synchrony and effective connectivity in patients with schizophrenia and auditory hallucinations. NeuroImage Clinical. 6:171-179. https://doi.org/10.1016/j.nicl.2014.08.027S171179

A Novel Synergistic Model Fusing Electroencephalography and Functional Magnetic Resonance Imaging for Modeling Brain Activities

Study of the human brain is an important and very active area of research. Unraveling the way the human brain works would allow us to better understand, predict and prevent brain related diseases that affect a significant part of the population. Studying the brain response to certain input stimuli can help us determine the involved brain areas and understand the mechanisms that characterize behavioral and psychological traits. In this research work two methods used for the monitoring of brain activities, Electroencephalography (EEG) and functional Magnetic Resonance (fMRI) have been studied for their fusion, in an attempt to bridge together the advantages of each one. In particular, this work has focused in the analysis of a specific type of EEG and fMRI recordings that are related to certain events and capture the brain response under specific experimental conditions. Using spatial features of the EEG we can describe the temporal evolution of the electrical field recorded in the scalp of the head. This work introduces the use of Hidden Markov Models (HMM) for modeling the EEG dynamics. This novel approach is applied for the discrimination of normal and progressive Mild Cognitive Impairment patients with significant results. EEG alone is not able to provide the spatial localization needed to uncover and understand the neural mechanisms and processes of the human brain. Functional Magnetic Resonance imaging (fMRI) provides the means of localizing functional activity, without though, providing the timing details of these activations. Although, at first glance it is apparent that the strengths of these two modalities, EEG and fMRI, complement each other, the fusion of information provided from each one is a challenging task. A novel methodology for fusing EEG spatiotemporal features and fMRI features, based on Canonical Partial Least Squares (CPLS) is presented in this work. A HMM modeling approach is used in order to derive a novel feature-based representation of the EEG signal that characterizes the topographic information of the EEG. We use the HMM model in order to project the EEG data in the Fisher score space and use the Fisher score to describe the dynamics of the EEG topography sequence. The correspondence between this new feature and the fMRI is studied using CPLS. This methodology is applied for extracting features for the classification of a visual task. The results indicate that the proposed methodology is able to capture task related activations that can be used for the classification of mental tasks. Extensions on the proposed models are examined along with future research directions and applications

Disentangling causal webs in the brain using functional Magnetic Resonance Imaging: A review of current approaches

In the past two decades, functional Magnetic Resonance Imaging has been used to relate neuronal network activity to cognitive processing and behaviour. Recently this approach has been augmented by algorithms that allow us to infer causal links between component populations of neuronal networks. Multiple inference procedures have been proposed to approach this research question but so far, each method has limitations when it comes to establishing whole-brain connectivity patterns. In this work, we discuss eight ways to infer causality in fMRI research: Bayesian Nets, Dynamical Causal Modelling, Granger Causality, Likelihood Ratios, LiNGAM, Patel's Tau, Structural Equation Modelling, and Transfer Entropy. We finish with formulating some recommendations for the future directions in this area

Disrupted Functional Brain Connectivity in Partial Epilepsy: A Resting-State fMRI Study

Examining the spontaneous activity to understand the neural mechanism of brain disorder is a focus in recent resting-state fMRI. In the current study, to investigate the alteration of brain functional connectivity in partial epilepsy in a systematical way, two levels of analyses (functional connectivity analysis within resting state networks (RSNs) and functional network connectivity (FNC) analysis) were carried out on resting-state fMRI data acquired from the 30 participants including 14 healthy controls(HC) and 16 partial epilepsy patients. According to the etiology, all patients are subdivided into temporal lobe epilepsy group (TLE, included 7 patients) and mixed partial epilepsy group (MPE, 9 patients). Using group independent component analysis, eight RSNs were identified, and selected to evaluate functional connectivity and FNC between groups. Compared with the controls, decreased functional connectivity within all RSNs was found in both TLE and MPE. However, dissociating patterns were observed within the 8 RSNs between two patient groups, i.e, compared with TLE, we found decreased functional connectivity in 5 RSNs increased functional connectivity in 1 RSN, and no difference in the other 2 RSNs in MPE. Furthermore, the hierarchical disconnections of FNC was found in two patient groups, in which the intra-system connections were preserved for all three subsystems while the lost connections were confined to intersystem connections in patients with partial epilepsy. These findings may suggest that decreased resting state functional connectivity and disconnection of FNC are two remarkable characteristics of partial epilepsy. The selective impairment of FNC implicated that it is unsuitable to understand the partial epilepsy only from global or local perspective. We presumed that studying epilepsy in the multi-perspective based on RSNs may be a valuable means to assess the functional changes corresponding to specific RSN and may contribute to the understanding of the neuro-pathophysiological mechanism of epilepsy

Tensor Analysis and Fusion of Multimodal Brain Images

Current high-throughput data acquisition technologies probe dynamical systems with different imaging modalities, generating massive data sets at different spatial and temporal resolutions posing challenging problems in multimodal data fusion. A case in point is the attempt to parse out the brain structures and networks that underpin human cognitive processes by analysis of different neuroimaging modalities (functional MRI, EEG, NIRS etc.). We emphasize that the multimodal, multi-scale nature of neuroimaging data is well reflected by a multi-way (tensor) structure where the underlying processes can be summarized by a relatively small number of components or "atoms". We introduce Markov-Penrose diagrams - an integration of Bayesian DAG and tensor network notation in order to analyze these models. These diagrams not only clarify matrix and tensor EEG and fMRI time/frequency analysis and inverse problems, but also help understand multimodal fusion via Multiway Partial Least Squares and Coupled Matrix-Tensor Factorization. We show here, for the first time, that Granger causal analysis of brain networks is a tensor regression problem, thus allowing the atomic decomposition of brain networks. Analysis of EEG and fMRI recordings shows the potential of the methods and suggests their use in other scientific domains.Comment: 23 pages, 15 figures, submitted to Proceedings of the IEE

Towards Deeper Understanding in Neuroimaging

Neuroimaging is a growing domain of research, with advances in machine learning having tremendous potential to expand understanding in neuroscience and improve public health. Deep neural networks have recently and rapidly achieved historic success in numerous domains, and as a consequence have completely redefined the landscape of automated learners, giving promise of significant advances in numerous domains of research. Despite recent advances and advantages over traditional machine learning methods, deep neural networks have yet to have permeated significantly into neuroscience studies, particularly as a tool for discovery. This dissertation presents well-established and novel tools for unsupervised learning which aid in feature discovery, with relevant applications to neuroimaging. Through our works within, this dissertation presents strong evidence that deep learning is a viable and important tool for neuroimaging studies

SEARCHING NEUROIMAGING BIOMARKERS IN MENTAL DISORDERS WITH GRAPH AND MULTIMODAL FUSION ANALYSIS OF FUNCTIONAL CONNECTIVITY

Mental disorders such as schizophrenia (SZ), bipolar (BD), and major depression disorders (MDD) can cause severe symptoms and life disruption. They share some symptoms, which can pose a major clinical challenge to their differentiation. Objective biomarkers based on neuroimaging may help to improve diagnostic accuracy and facilitate optimal treatment for patients. Over the last decades, non-invasive in-vivo neuroimaging techniques such as magnetic resonance imaging (MRI) have been increasingly applied to measure structure and function in human brains. With functional MRI (fMRI) or structural MRI (sMRI), studies have identified neurophysiological deficits in patients’ brain from different perspective. Functional connectivity (FC) analysis is an approach that measures functional integration in brains. By assessing the temporal coherence of the hemodynamic activity among brain regions, FC is considered capable of characterizing the large-scale integrity of neural activity. In this work, we present two data analysis frameworks for biomarker detection on brain imaging with FC, 1) graph analysis of FC and 2) multimodal fusion analysis, to better understand the human brain. Graph analysis reveals the interaction among brain regions based on graph theory, while the multimodal fusion framework enables us to utilize the strength of different imaging modalities through joint analysis. Four applications related to FC using these frameworks were developed. First, FC was estimated using a model-based approach, and revealed altered the small-world network structure in SZ. Secondly, we applied graph analysis on functional network connectivity (FNC) to differentiate BD and MDD during resting-state. Thirdly, two functional measures, FNC and fractional amplitude of low frequency fluctuations (fALFF), were spatially overlaid to compare the FC and spatial alterations in SZ. And finally, we utilized a multimodal fusion analysis framework, multi-set canonical correlation analysis + joint independent component analysis (mCCA+jICA) to link functional and structural abnormalities in BD and MDD. We also evaluated the accuracy of predictive diagnosis through classifiers generated on the selected features. In summary, via the two frameworks, our work has made several contributions to advance FC analysis, which improves our understanding of underlying brain function and structure, and our findings may be ultimately useful for the development of biomarkers of mental disease

Characterization of groups using composite kernels and multi-source fMRI analysis data: application to schizophrenia

Pattern classification of brain imaging data can enable the automatic detection of differences in cognitive processes of specific groups of interest. Furthermore, it can also give neuroanatomical information related to the regions of the brain that are most relevant to detect these differences by means of feature selection procedures, which are also well-suited to deal with the high dimensionality of brain imaging data. This work proposes the application of recursive feature elimination using a machine learning algorithm based on composite kernels to the classification of healthy controls and patients with schizophrenia. This framework, which evaluates nonlinear relationships between voxels, analyzes whole-brain fMRI data from an auditory task experiment that is segmented into anatomical regions and recursively eliminates the uninformative ones based on their relevance estimates, thus yielding the set of most discriminative brain areas for group classification. The collected data was processed using two analysis methods: the general linear model (GLM) and independent component analysis (ICA). GLM spatial maps as well as ICA temporal lobe and default mode component maps were then input to the classifier. A mean classification accuracy of up to 95% estimated with a leave-two-out cross-validation procedure was achieved by doing multi-source data classification. In addition, it is shown that the classification accuracy rate obtained by using multi-source data surpasses that reached by using single-source data, hence showing that this algorithm takes advantage of the complimentary nature of GLM and ICAPublicad