Application of graph theoretical methods to the functional connectome of human brain.

During the past decade, there has been a great interest in creating mathematical models to describe the properties of connectivity in the human brain. One of the established tools to describe these interactions among regions of the brain is graph theory. However, graph theoretical methods were mainly designed for the analysis of single network which is problematic for neuroscientists wishing to study groups of subjects. Specifically, studies using the Rich Club (RC) graph measure require cumbersome methods to make statistical inferences. In the first part of this work, we propose a framework to analyse the inter-subject variability in Rich Club organisation. The proposed framework is used to identify the changes in RC coefficient and RC organisation in patients with schizophrenia relative to healthy control. We follow this work by proposing a novel method, named Rich Block (RB), which is a combination of the tradition Rich Club and Stochastic Block Models (SBM). We show that using RBs can not only facilitate an inter-subject statistical inference, it can also account for differences in profile of connectivity, and control for subject-level covariates. We validate the Rich Block approach by simulating networks of different size and structure. We find that RB accurately estimates RC coefficients and RC organisations, specifically, in network with large number of nodes and blocks. With real data we use RB to identify changes in coefficient and organisation of highly connected sub-graphs of hub blocks in schizophrenia. In the final portion of this work, we examine the methods used to define each edge in networks formed from resting-state functional magnetic resonance imaging (rs-fMRI). The standard approach in rs-fMRI is to divide the brain into regions, extract time series, and compute the temporal correlation between each region. These correlations are assumed to follow standard results, when in fact serial autocorrelation in the time series can corrupt these results. While some authors have proposed corrections to account for autocorrelation, they are poorly documented and always assume homogeneity of autocorrelation over brain regions. Thus we propose a method to account for bias in interregion correlation estimates due to autocorrelation. We develop an exact method and an approximate, more computationally efficient method that adjusts for the sampling variability in the correlation coefficient. We use inter-subject scrambled real-data to validate the proposed methods under a null setting, and intact real-data to examine the impact of our method on graph theoretical measures. We find that the standard methods fail to practically correct the sensitivity and specificity level due to over-simplifying the temporal structure of BOLD time series, while even our approximate method is substantially more accurate

Confound modelling in UK Biobank brain imaging

© 2020 Dealing with confounds is an essential step in large cohort studies to address problems such as unexplained variance and spurious correlations. UK Biobank is a powerful resource for studying associations between imaging and non-imaging measures such as lifestyle factors and health outcomes, in part because of the large subject numbers. However, the resulting high statistical power also raises the sensitivity to confound effects, which therefore have to be carefully considered. In this work we describe a set of possible confounds (including non-linear effects and interactions that researchers may wish to consider for their studies using such data). We include descriptions of how we can estimate the confounds, and study the extent to which each of these confounds affects the data, and the spurious correlations that may arise if they are not controlled. Finally, we discuss several issues that future studies should consider when dealing with confounds

asoroosh/DVARS: OctaveCompatible

So Octave/DSEvars_octave.m and Octave/DVARSCalc_octave.m were added to this version. They are Octave compatible and were tested with white noises

Heritability of Global Architectural Features of the Functional Connectome of the Human Brain

Poster submitted to the 2016 Organization for Human Brain Mapping (OHBM) in Geneva, 26-30 June

Functional Connectivity Alterations of the Temporal Lobe and Hippocampus in Semantic Dementia and Alzheimer’s Disease

Background: Semantic memory impairments in semantic dementia are attributed to atrophy and functional disruption of the anterior temporal lobes. In contrast, the posterior medial temporal neurodegeneration found in Alzheimer’s disease is associated with episodic memory disturbance. The two dementia subtypes share hippocampal deterioration, despite a relatively spared episodic memory in semantic dementia. Objective: To unravel mutual and divergent functional alterations in Alzheimer’s disease and semantic dementia, we assessed functional connectivity between temporal lobe regions in Alzheimer’s disease (n = 16), semantic dementia (n = 23), and healthy controls (n = 17). Methods: In an exploratory study, we used a functional parcellation of the temporal cortex to extract time series from 66 regions for correlation analysis. Results: Apart from differing connections between Alzheimer’s disease and semantic dementia that yielded reduced functional connectivity, we identified a common pathway between the right anterior temporal lobe and the right orbitofrontal cortex in both dementia subtypes. This disconnectivity might be related to social knowledge deficits as part of semantic memory decline. However, such interpretations are preferably made in a holistic context of disease-specific semantic impairments and functional connectivity changes. Conclusion: Despite a major limitation owed to unbalanced databases between study groups, this study provides a preliminary picture of the brain’s functional disconnectivity in Alzheimer’s disease and semantic dementia. Future studies are needed to replicate findings of a common pathway with consistent diagnostic criteria and neuropsychological evaluation, balanced designs, and matched data MRI acquisition procedures

Directed functional connectivity using dynamic graphical models

There are a growing number of neuroimaging methods that model spatio-temporal patterns of brain activity to allow more meaningful characterizations of brain networks. This paper proposes dynamic graphical models (DGMs) for dynamic, directed functional connectivity. DGMs are a multivariate graphical model with time-varying coefficients that describe instantaneous directed relationships between nodes. A further benefit of DGMs is that networks may contain loops and that large networks can be estimated. We use network simulations, human resting-state fMRI (N = 500) to investigate the validity and reliability of the estimated networks. We simulate systematic lags of the hemodynamic response at different brain regions to investigate how these lags potentially bias directionality estimates. In the presence of such lag confounds (0.4-0.8 s offset between connected nodes), our method has a sensitivity of 72%-77% to detect the true direction. Stronger lag confounds have reduced sensitivity, but do not increase false positives (i.e., directionality estimates of the opposite direction). In human resting-state fMRI, we find the DMN has consistent influence on the cerebellar, the limbic and the auditory/temporal network, as well a consistent reciprocal relationship between the visual medial and visual lateral network. Finally, we apply the method in a small mouse fMRI sample and discover a highly plausible relationship between areas in the hippocampus feeding into the cingulate cortex. We provide a computationally efficient implementation of DGM as a free software package for R. [Abstract copyright: Copyright © 2018. Published by Elsevier Inc.

Understanding Rich Club with a Stochastic Block Model

Poster submitted to the 2016 Organization for Human Brain Mapping (OHBM) in Geneva, 26-30 June

Rich Block: Rich Club Analysis with the Erdos-Renyi Mixture Model

Poster submitted to the 2015 Organization for Human Brain Mapping (OHBM) in Hawaii, 14-18 June

Multi-subject Stochastic Blockmodels for adaptive analysis of individual differences in human brain network cluster structure

There is considerable interest in elucidating the cluster structure of brain networks in terms of modules, blocks or clusters of similar nodes. However, it is currently challenging to handle data on multiple subjects since most of the existing methods are applicable only on a subject-by-subject basis or for analysis of an average group network. The main limitation of per-subject models is that there is no obvious way to combine the results for group comparisons, and of group-averaged models that they do not reflect the variability between subjects. Here, we propose two new extensions of the classical Stochastic Blockmodel (SBM) that use a mixture model to estimate blocks or clusters of connected nodes, combined with a regression model to capture the effects of subject-level covariates on individual differences in cluster structure. The proposed Multi-Subject Stochastic Blockmodels (MS-SBMs) can flexibly account for between-subject variability in terms of homogeneous or heterogeneous covariate effects on connectivity using subject demographics such as age or diagnostic status. Using synthetic data, representing a range of block sizes and cluster structures, we investigate the accuracy of the estimated MS-SBM parameters as well as the validity of inference procedures based on the Wald, likelihood ratio and permutation tests. We show that the proposed multi-subject SBMs recover the true cluster structure of synthetic networks more accurately and adaptively than standard methods for modular decomposition (i.e. the Fast Louvain and Newman Spectral algorithms). Permutation tests of MS-SBM parameters were more robustly valid for statistical inference and Type I error control than tests based on standard asymptotic assumptions. Applied to analysis of multi-subject resting-state fMRI networks (13 healthy volunteers; 12 people with schizophrenia; n=268 brain regions), we show that Heterogeneous Stochastic Blockmodel (Het-SBM) identifies a range of network topologies simultaneously, including modular and core structures