Biology subjects

Razi, A.

Publications and source records attributed to Razi, A..

6 recordsLinked to original sources

bioRxiv2018

Stability and sensitivity of structural connectomes: effect of thresholding and filtering and demonstration in neurodegeneration

Structural connectomes derived using diffusion tractography are increasingly used to investigate white matter connectivity in neurological diseases. However inherent biases in diffusion tractography algorithms may lead to both false negatives and false positives in connectome construction. A range of graph thresholding approaches and more recently several streamline filtering algorithms have been developed to address these issues. However there is no consensus in the literature regarding the best available approach. Using a cohort of Huntingtons disease patients and healthy controls we compared the effect of several graph thresholding strategies: proportional, absolute, consensus and consistency thresholding, with and without streamline filtering, using Spherical Deconvolution Informed Filtering of tractograms (SIFT2) algorithm. We examined the effect of thresholding strategies on the stability of graph theory metrics and the sensitivity of these measures in neurodegeneration. We show that while a number of graph thresholding procedures result in stable metrics across thresholds, the detection of group differences is highly variable. We also showed that the application of streamline filtering using SIFT2 resultes in better detection of group differences and stronger clinical correlations. We therefore conclude that the application of SIFT2 streamline filtering without graph thresholding may be sufficient for structural connectome construction.

neuroscience↗

bioRxiv2018

Transdiagnostic variations in impulsivity and compulsivity in obsessive-compulsive disorder and gambling disorder correlate with effective connectivity in cortical-striatal-thalamic-cortical circuits.

BackgroundIndividual differences in impulsivity and compulsivity is thought to underlie vulnerability to a broad range of disorders and are closely tied to cortical-striatal-thalamic-cortical (CSTC) function. However, whether impulsivity and compulsivity in clinical disorders is continuous with the healthy population and explains CSTC dysfunction across different disorders remains unclear.\n\nMethodsWe characterized the relationship between CSTC effective connectivity, estimated using dynamic causal modelling of functional magnetic resonance imaging data, and dimensional phenotypes of impulsivity and compulsivity in two symptomatically distinct but phenotypically related disorders, obsessive-compulsive disorder (OCD) and gambling disorder (GD). 487 online participants provided data for modelling of dimensional phenotypes. These data were combined with 34 OCD patients, 22 GD patients, and 39 healthy controls, who underwent functional magnetic resonance imaging.\n\nResultsThree core dimensions were identified: disinhibition, impulsivity, and compulsivity. Patients scores on these dimensions were continuously distributed with the healthy participants, supporting a continuum model of psychopathology. Across all participants, higher disinhibition correlated with lower bottom-up connectivity in the dorsal circuit and increased bottom-up connectivity in the ventral circuit, and higher compulsivity correlated with reduced bottom-up connectivity in the dorsal circuit. Similar changes in effective connectivity were observed with increasing clinical severity that were not accounted for by phenotypic variation, demonstrating convergence towards behaviourally and clinically relevant changes in brain dynamics. Effective connectivity did not differ as a function of traditional diagnostic labels.\n\nConclusionsCSTC dysfunction across OCD and GD is better characterized by dimensional phenotypes than diagnostic comparisons, supporting investigation of quantitative liability phenotypes.

neuroscience↗

bioRxiv2018

Assessment of Functional Connectome Construction Strategies in Neurodegeneration

Connectomics can be used to investigate functional brain networks in neurodegenerative diseases including Huntingtons disease (HD). In this developing field, different connectome construction strategies have emerged in parallel. However, there is a need to understand the influences of different strategies on subsequent analyses when constructing a connectome. This study systematically compares connectome construction strategies based on their biological relevance to functional networks in neurodegeneration.\n\nWe asked which functional connectome construction strategy was best able to discriminate HD gene carriers from healthy controls, and how such a strategy affected modular organization of the network. The major factors compared were principal component-based correction versus wavelet decomposition for physiological noise correction, the type of parcellation atlas (functional, structural and multi-modal), weighted versus binarized networks, and unthresholded versus proportionally thresholded networks. We found that principal component-based correction generated the most discriminatory connectomes, while binarization and proportional thresholding did not increase discrimination between HD gene carriers and healthy controls. When a functional parcellation atlas was used, the highest discrimination rates were obtained. We observed that the group differences in modular organization of the functional connectome were greatly affected by binarization and thresholding, showing no consistent pattern of modularity.\n\nThis study suggests that functional connectome construction strategies using principal component-based correction and weighted unthresholded connectivity matrices may outperform other strategies.

neuroscience↗

bioRxiv2018

Dynamic causal modelling of fluctuating connectivity in resting-state EEG

Functional and effective connectivity are known to change systematically over time. These changes might be explained by several factors, including intrinsic fluctuations in activity-dependent neuronal coupling and contextual factors, like experimental condition and time. Furthermore, contextual effects may be subject-specific or conserved over subjects. To characterize fluctuations in effective connectivity, we used dynamic causal modelling (DCM) of cross spectral responses over 1 min of electroencephalogram (EEG) recordings during rest, divided into 1-sec windows. We focused on two intrinsic networks: the default mode and the saliency network. DCM was applied to estimate connectivity in each time-window for both networks. Fluctuations in DCM connectivity parameters were assessed using hierarchical parametric empirical Bayes (PEB). Within-subject, between-window effects were modelled with a second-level linear model with temporal basis functions as regressors. This procedure was conducted for every subject separately. Bayesian model reduction was then used to assess which (combination of) temporal basis functions best explain dynamic connectivity over windows. A third (between-subject) level model was used to infer which dynamic connectivity parameters are conserved over subjects. Our results indicate that connectivity fluctuations in the saliency network comprised both subject-specific components and a common component. For the default mode network, connectivity trajectories only showed a common component. For both networks, connections to higher order regions appear to monotonically increase during the one minute period. These results not only establish the predictive validity of dynamic connectivity estimates - in virtue of detecting systematic changes over subjects - they also suggest a network-specific dissociation in the relative contribution of fluctuations in connectivity that depend upon experimental context. We envisage these procedures could be useful for characterizing brain state transitions that may be explained by their cognitive or neuropathological underpinnings.

neuroscience↗

bioRxiv2018

Variability and reliability of effective connectivity within the core default mode network: A longitudinal spectral DCM study

Dynamic causal modelling (DCM) for resting state fMRI - namely spectral DCM - is a recently developed and widely adopted method for inferring effective connectivity in intrinsic brain networks. Most research applying spectral DCM has focused on group-averaged connectivity within large-scale intrinsic brain networks; however, the consistency of subject- and session-specific estimates of effective connectivity has not been evaluated. Establishing reliability (within subjects) is crucial for its clinical use; e.g., as a neurophysiological phenotype of disease progression. Effective connectivity during rest is likely to vary due to changes in cognitive, behavioural, and physical states. Determining the sources of fluctuations in effective connectivity may yield greater understanding of brain processes and inform clinical applications about potential confounds. In the present study, we investigated the consistency of effective connectivity within and between subjects, as well as potential sources of variability (e.g., hemispheric asymmetry). We further investigated how standard procedures for data processing and signal extraction affect this consistency. DCM analyses were applied to four longitudinal resting state fMRI datasets. Our sample consisted of 20 subjects with 653 resting state fMRI sessions in total. These data allowed to quantify the robustness of connectivity estimates for each subject, and to draw conclusions beyond specific data features. We found that subjects contributing to all datasets showed systematic and reliable patterns of hemispheric asymmetry. When asymmetry was taken into account, subjects showed very similar connectivity patterns. We also found that various processing procedures (e.g. global signal regression and ROI size) had little effect on inference and reliability of connectivity for the majority of subjects. Bayesian model reduction increased reliability (within-subjects) and stability (between-subjects) of connectivity patterns.

neuroscience↗

bioRxiv2017

Biological Self-organisation and Markov blankets

Biological self-organisation is a process of spontaneous pattern formation; namely the emergence of coherent and stable systemic configurations that distinguish themselves from their environment. This process can occur at various spatial scales: from the microscopic (giving rise to cells) to the macroscopic (the emergence of organisms). Self-organisation at each level is essential to account for the hierarchical organisation of living organisms (organelles within cells, within tissues, within organs, etc.). In this paper, we pursue the idea that Markov blankets - statistical boundaries separating states that are external to a system from its internal states - emerge at every possible level of the description of the (living) system. Through simulations, we show that the concept of a Markov blanket is fundamental in defining biological systems and underwrites the nature and form of interactions between successive levels of hierarchical structure. We demonstrate the validity of our argument using simulations, based on the normative principle of variational free energy minimisation. Specifically, we adopt a top-down approach to provide a proof of concept for the claim that the self-organisation of Markov blankets (and blankets of blankets) underwrites the self-evidencing, autopoietic behaviour of living systems.

systems biology↗