scholarly journals Optimising network modelling methods for fMRI

2019 ◽  
Author(s):  
Usama Pervaiz ◽  
Diego Vidaurre ◽  
Mark W. Woolrich ◽  
Stephen M. Smith

AbstractA major goal of neuroimaging studies is to develop predictive models to analyse the relationship between whole brain functional connectivity patterns and behavioural traits. However, there is no single widely-accepted standard pipeline for analyzing functional connectivity. The common procedure for designing functional connectivity based predictive models entails three main steps: parcellating the brain, estimating the interaction between defined parcels, and lastly, using these integrated associations between brain parcels as features fed to a classifier for predicting non-imaging variables e.g., behavioural traits, demographics, emotional measures, etc. There are also additional considerations when using correlation-based measures of functional connectivity, resulting in three supplementary steps: utilising Riemannian geometry tangent space parameterization to preserve the geometry of functional connectivity; penalizing the connectivity estimates with shrinkage approaches to handle challenges related to short time-series (and noisy) data; and removing confounding variables from brain-behaviour data. These six steps are contingent on each-other, and to optimise a general framework one should ideally examine these various methods simultaneously. In this paper, we investigated strengths and short-comings, both independently and jointly, of the following measures: parcellation techniques of four kinds (categorized further depending upon number of parcels), five measures of functional connectivity, the decision of staying in the ambient space of connectivity matrices or in tangent space, the choice of applying shrinkage estimators, six alternative techniques for handling confounds and finally four novel classifiers/predictors. For performance evaluation, we have selected two of the largest datasets, UK Biobank and the Human Connectome Project resting state fMRI data, and have run more than 9000 different pipeline variants on a total of ∼14000 individuals to determine the optimum pipeline. For independent performance validation, we have run some best-performing pipeline variants on ABIDE and ACPI datasets (∼1000 subjects) to evaluate the generalisability of proposed network modelling methods.

2020 ◽  
Author(s):  
Arun S. Mahadevan ◽  
Ursula A. Tooley ◽  
Maxwell A. Bertolero ◽  
Allyson P. Mackey ◽  
Danielle S. Bassett

AbstractFunctional connectivity (FC) networks are typically inferred from resting-state fMRI data using the Pearson correlation between BOLD time series from pairs of brain regions. However, alternative methods of estimating functional connectivity have not been systematically tested for their sensitivity or robustness to head motion artifact. Here, we evaluate the sensitivity of six different functional connectivity measures to motion artifact using resting-state data from the Human Connectome Project. We report that FC estimated using full correlation has a relatively high residual distance-dependent relationship with motion compared to partial correlation, coherence and information theory-based measures, even after implementing rigorous methods for motion artifact mitigation. This disadvantage of full correlation, however, may be offset by higher test-retest reliability and system identifiability. FC estimated by partial correlation offers the best of both worlds, with low sensitivity to motion artifact and intermediate system identifiability, with the caveat of low test-retest reliability. We highlight spatial differences in the sub-networks affected by motion with different FC metrics. Further, we report that intra-network edges in the default mode and retrosplenial temporal sub-networks are highly correlated with motion in all FC methods. Our findings indicate that the method of estimating functional connectivity is an important consideration in resting-state fMRI studies and must be chosen carefully based on the parameters of the study.


2020 ◽  
Author(s):  
Jakub Kopal ◽  
Anna Pidnebesna ◽  
David Tomeček ◽  
Jaroslav Tintěra ◽  
Jaroslav Hlinka

AbstractFunctional connectivity analysis of resting state fMRI data has recently become one of the most common approaches to characterizing individual brain function. It has been widely suggested that the functional connectivity matrix, calculated by correlating signals from regions of interest, is a useful approximate representation of the brain’s connectivity, potentially providing behaviorally or clinically relevant markers. However, functional connectivity estimates are known to be detrimentally affected by various artifacts, including those due to in-scanner head motion. Treatment of such artifacts poses a standing challenge because of their high variability. Moreover, as individual functional connections generally covary only very weakly with head motion estimates, motion influence is difficult to quantify robustly, and prone to be neglected in practice. Although the use of individual estimates of head motion, or group-level correlation of motion and functional connectivity has been suggested, a sufficiently sensitive measure of individual functional connectivity quality has not yet been established. We propose a new intuitive summary index, the Typicality of Functional Connectivity, to capture deviations from normal brain functional connectivity pattern. Based on results of resting state fMRI for 245 healthy subjects we show that this measure is significantly correlated with individual head motion metrics. The results were further robustly reproduced across atlas granularity and preprocessing options, as well as other datasets including 1081 subjects from the Human Connectome Project. The Typicality of Functional Connectivity provides individual proxy measure of motion effect on functional connectivity and is more sensitive to inter-individual variation of motion than individual functional connections. In principle it should be sensitive also to other types of artifacts, processing errors and possibly also brain pathology, allowing wide use in data quality screening and quantification in functional connectivity studies as well as methodological investigations.


2020 ◽  
Author(s):  
Yi Zhao ◽  
Brian S. Caffo ◽  
Bingkai Wang ◽  
Chiang-shan R. Li ◽  
Xi Luo

AbstractResting-state functional connectivity is an important and widely used measure of individual and group differences. These differences are typically attributed to various demographic and/or clinical factors. Yet, extant statistical methods are limited to linking covariates with variations in functional connectivity across subjects, especially at the voxel-wise level of the whole brain. This paper introduces a generalized linear model method that regresses whole-brain functional connectivity on covariates. Our approach builds on two methodological components. We first employ whole-brain group ICA to reduce the dimensionality of functional connectivity matrices, and then search for matrix variations associated with covariates using covariate assisted principal regression, a recently introduced covariance matrix regression method. We demonstrate the efficacy of this approach using a resting-state fMRI dataset of a medium-sized cohort of subjects obtained from the Human Connectome Project. The results show that the approach enjoys improved statistical power in detecting interaction effects of sex and alcohol on whole-brain functional connectivity, and in identifying the brain areas contributing significantly to the covariate-related differences in functional connectivity.


2021 ◽  
Author(s):  
Javier Gonzalez-Castillo ◽  
Isabel Fernandez ◽  
Daniel A Handwerker ◽  
Peter A Bandettini

Vigilance and wakefulness modulate estimates of functional connectivity, and, if unaccounted for, they can become a substantial confound in resting-state fMRI. Unfortunately, wakefulness is rarely monitored due to the need for additional concurrent recordings (e.g., eye tracking, EEG). Recent work has shown that strong fluctuations around 0.05Hz, hypothesized to be CSF inflow, appear in the fourth ventricle (FV) when subjects fall asleep. The analysis of these fluctuations could provide an easy way to evaluate wakefulness in fMRI-only data. Here we evaluate this possibility using the 7T resting-state sample from the Human Connectome Project. Our results confirm the presence of those fluctuations in the HCP sample despite this data having relatively small inflow weighting. Moreover, we show that fluctuations of a similar frequency appear in large portions of grey matter with different temporal delays, and that they can substantially influence estimates of functional connectivity. Finally, we demonstrate that the temporal evolution of this signal cannot only help us reproduce previously reported overall sleep patterns in resting-state data, but also predict individual periods of eye closure with 70% accuracy, matching predictions attainable using the amplitude of the global signal (a common fMRI marker of arousal). In summary, our results demonstrate the ubiquitous presence of this signal in a large, publicly available, fMRI sample, its value as a marker of arousal in absence of a better metric, its relationship to the global signal, and its potential nuisance effects on functional connectivity estimates when ignored.


2021 ◽  
pp. 135245852110302
Author(s):  
Einar August Høgestøl ◽  
Samuele Ghezzo ◽  
Gro Owren Nygaard ◽  
Thomas Espeseth ◽  
Piotr Sowa ◽  
...  

Background: Brain functional connectivity (FC) in multiple sclerosis (MS) is abnormal compared to healthy controls (HCs). More longitudinal studies in MS are needed to evaluate whether FC stability is clinically relevant. Objective: To compare functional magnetic resonance imaging (fMRI)-based FC between MS and HC, and to determine the relationship between longitudinal FC changes and structural brain damage, cognitive performance and physical disability. Methods: T1-weighted MPRAGE and resting-state fMRI (1.5T) were acquired from 70 relapsing-remitting MS patients and 94 matched HC at baseline (mean months since diagnosis 14.0 ± 11) and from 60 MS patients after 5 years. Independent component analysis and network modelling were used to measure longitudinal FC stability and cross-sectional comparisons with HC. Linear mixed models, adjusted for age and sex, were used to calculate correlations. Results: At baseline, patients with MS showed FC abnormalities both within networks and in single connections compared to HC. Longitudinal analyses revealed functional stability and no significant relationships with clinical disability, cognitive performance, lesion or brain volume. Conclusion: FC abnormalities occur already at the first decade of MS, yet we found no relevant clinical correlations for these network deviations. Future large-scale longitudinal fMRI studies across a range of MS subtypes and outcomes are required.


2021 ◽  
Author(s):  
Shachar Gal ◽  
Yael Coldham ◽  
Michal Bernstein-Eliav ◽  
Ido Tavor

The search for an 'ideal' approach to investigate the functional connections in the human brain is an ongoing challenge for the neuroscience community. While resting-state functional magnetic resonance imaging (fMRI) has been widely used to study individual functional connectivity patterns, recent work has highlighted the benefits of collecting functional connectivity data while participants are exposed to naturalistic stimuli, such as watching a movie or listening to a story. For example, functional connectivity data collected during movie-watching were shown to predict cognitive and emotional scores more accurately than resting-state-derived functional connectivity. We have previously reported a tight link between resting-state functional connectivity and task-derived neural activity, such that the former successfully predicts the latter. In the current work we use data from the Human Connectome Project to demonstrate that naturalistic-stimulus-derived functional connectivity predicts task-induced brain activation maps more accurately than resting-state-derived functional connectivity. We then show that activation maps predicted using naturalistic stimuli are better predictors of individual intelligence scores than activation maps predicted using resting-state. We additionally examine the influence of naturalistic-stimulus type on prediction accuracy. Our findings emphasize the potential of naturalistic stimuli as a promising alternative to resting-state fMRI for connectome-based predictive modelling of individual brain activity and cognitive traits.


2019 ◽  
Author(s):  
Heather Shappell ◽  
Brian S. Caffo ◽  
James J. Pekar ◽  
Martin A. Lindquist

AbstractThe study of functional brain networks has grown rapidly over the past decade. While most functional connectivity (FC) analyses estimate one static network structure for the entire length of the functional magnetic resonance imaging (fMRI) time series, recently there has been increased interest in studying time-varying changes in FC. Hidden Markov models (HMMs) have proven to be a useful modeling approach for discovering repeating graphs of interacting brain regions (brain states). However, a limitation lies in HMMs assuming that the sojourn time, the number of consecutive time points in a state, is geometrically distributed. This may encourage inaccurate estimation of the time spent in a state before switching to another state. We propose a hidden semi-Markov model (HSMM) approach for inferring time-varying brain networks from fMRI data, which explicitly models the sojourn distribution. Specifically, we propose using HSMMs to find each subject’s most probable series of network states and the graphs associated with each state, while properly estimating and modeling the sojourn distribution for each state. We perform a simulation study, as well as an analysis on both task-based fMRI data from an anxiety-inducing experiment and resting-state fMRI data from the Human Connectome Project. Our results demonstrate the importance of model choice when estimating sojourn times and reveal their potential for understanding healthy and diseased brain mechanisms.


2020 ◽  
Author(s):  
Einar August Høgestøl ◽  
Samuele Ghezzo ◽  
Gro Owren Nygaard ◽  
Thomas Espeseth ◽  
Piotr Sowa ◽  
...  

ABSTRACTObjective1) To assess fMRI-based functional connectivity (FC) anomalies in early multiple sclerosis (MS), 2) To determine the relation between FC changes and structural brain damage due to disease progression 3) To study the association between FC changes and cognitive and physical disability.MethodsStructural MRI and resting-state fMRI were acquired from 76 early relapsing-remitting MS patients at baseline (average disease duration 71.7 months ± 63) and after five years. Ninety-four healthy controls (HCs) matched for age and sex were included at baseline. Independent component analysis (ICA) and network modelling were used to measure FC. FC variation was related to expanded disability status scale and neuropsychological outcomes. Brain and lesion volumes were quantified using standard methods. We used the 25 independent components obtained from ICA to estimate the longitudinal stability of the brain connectome as a proxy for functional reorganization over time.ResultsThe MS subjects were clinically and cognitively stable. Compared to HCs, FC abnormalities were detected within networks and in single connections in patients with early MS at baseline. Over time, FC was relatively invariable, but changes in FC were associated with progression of brain atrophy (ρ = 0.39, p = .06). No significant relationship with clinical and cognitive measures or lesion load was detected.ConclusionPatients with MS showed evidence of altered FC in the early stages of the disease. Over time, changes in FC seem to be related to a progression of brain atrophy, which are known to precede changes in clinical and cognitive functioning.


2017 ◽  
Author(s):  
Christof Seiler ◽  
Susan Holmes

ABSTRACTFunctional brain connectivity is the co-occurrence of brain activity in different areas during resting and while doing tasks. The data of interest are multivariate timeseries measured simultaneously across brain parcels using resting-state fMRI (rfMRI). We analyze functional connectivity using two heteroscedasticity models. Our first model is low-dimensional and scales linearly in the number of brain parcels. Our second model scales quadratically. We apply both models to data from the Human Connectome Project (HCP) comparing connectivity between short and conventional sleepers. We find stronger functional connectivity in short than conventional sleepers in brain areas consistent with previous findings. This might be due to subjects falling asleep in the scanner. Consequently, we recommend the inclusion of average sleep duration as a covariate to remove unwanted variation in rfMRI studies. A power analysis using the HCP data shows that a sample size of 40 detects 50% of the connectivity at a false discovery rate of 20%. We provide implementations using R and the probabilistic programming language Stan.


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