An empirical Bayes normalization method for connectivity metrics in resting state fMRI.
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ABSTRACT:
SUBMITTER: Chen S
PROVIDER: S-EPMC4584951 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Low image sampling rates used in resting state functional magnetic resonance imaging (rs-fMRI) may cause aliasing of the cardiorespiratory pulsations over the very low frequency (VLF) BOLD signal fluctuations which reflects to functional connectivity (FC). In this study, we examine the effect of sampling rate on currently used rs-fMRI FC metrics. Ultra-fast fMRI magnetic resonance encephalography (MREG) data, sampled with TR 0.1 s, was downsampled to different subsampled repetition times (sTR, range 0.3-3 s) for comparisons. Echo planar k-space sampling (TR 2.15 s) and interleaved slice collection schemes were also compared against the 3D single shot trajectory at 2.2 s sTR. The quantified connectivity metrics included stationary spatial, time, and frequency domains, as well as dynamic analyses. Time domain methods included analyses of seed-based functional connectivity, regional homogeneity (ReHo), coefficient of variation, and spatial domain group level probabilistic independent component analysis (ICA). In frequency domain analyses, we examined fractional and amplitude of low frequency fluctuations. Aliasing effects were spatially and spectrally analyzed by comparing VLF (0.01-0.1 Hz), respiratory (0.12-0.35 Hz) and cardiac power (0.9-1.3 Hz) FFT maps at different sTRs. Quasi-periodic pattern (QPP) of VLF events were analyzed for effects on dynamic FC methods. The results in conventional time and spatial domain analyses remained virtually unchanged by the different sampling rates. In frequency domain, the aliasing occurred mainly in higher sTR (1-2 s) where cardiac power aliases over respiratory power. The VLF power maps suffered minimally from increasing sTRs. Interleaved data reconstruction induced lower ReHo compared to 3D sampling (p < 0.001). Gradient recalled echo-planar imaging (EPI BOLD) data produced both better and worse metrics. In QPP analyses, the repeatability of the VLF pulse detection becomes linearly reduced with increasing sTR. In conclusion, the conventional resting state metrics (e.g., FC, ICA) were not markedly affected by different TRs (0.1-3 s). However, cardiorespiratory signals showed strongest aliasing in central brain regions in sTR 1-2 s. Pulsatile QPP and other dynamic analyses benefit linearly from short TR scanning.
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Project description:The human brain at rest exhibits intrinsic dynamics transitioning among the multiple metastable states of the inter-regional functional connectivity. Accordingly, the demand for exploring the state-specific functional connectivity increases for a deeper understanding of mental diseases. Functional connectivity, however, lacks information about the directed causal influences among the brain regions, called effective connectivity. This study presents the dynamic causal modeling (DCM) framework to explore the state-dependent effective connectivity using spectral DCM for the resting-state functional MRI (rsfMRI). We established the sequence of brain states using the hidden Markov model with the multivariate autoregressive coefficients of rsfMRI, summarizing the functional connectivity. We decomposed the state-dependent effective connectivity using a parametric empirical Bayes scheme that models the effective connectivity of consecutive windows with the time course of the discrete states as regressors. We showed the plausibility of the state-dependent effective connectivity analysis in a simulation setting. To test the clinical applicability, we applied the proposed method to characterize the state- and subtype-dependent effective connectivity of the default mode network in children with combined-type attention deficit hyperactivity disorder (ADHD-C) compared with age-matched, typically developed children (TDC). All 88 children were subtyped according to the occupation times (i.e., dwell times) of the three dominant functional connectivity states, independently of clinical diagnosis. The state-dependent effective connectivity differences between ADHD-C and TDC according to the subtypes and those between the subtypes of ADHD-C were expressed mainly in self-inhibition, magnifying the importance of excitation inhibition balance in the subtyping. These findings provide a clear motivation for decomposing the state-dependent dynamic effective connectivity and state-dependent analysis of the directed coupling in exploring mental diseases.
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Project description:MEG offers dynamic and spectral resolution for resting-state connectivity which is unavailable in fMRI. However, there are a wide range of available network estimation methods for MEG, and little in the way of existing guidance on which ones to employ. In this technical note, we investigate the extent to which many popular measures of stationary connectivity are suitable for use in resting-state MEG, localising magnetic sources with a scalar beamformer. We use as empirical criteria that network measures for individual subjects should be repeatable, and that group-level connectivity estimation shows good reproducibility. Using publically-available data from the Human Connectome Project, we test the reliability of 12 network estimation techniques against these criteria. We find that the impact of magnetic field spread or spatial leakage artefact is profound, creates a major confound for many connectivity measures, and can artificially inflate measures of consistency. Among those robust to this effect, we find poor test-retest reliability in phase- or coherence-based metrics such as the phase lag index or the imaginary part of coherency. The most consistent methods for stationary connectivity estimation over all of our tests are simple amplitude envelope correlation and partial correlation measures.
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Project description:Modern statistical inference techniques may be able to improve the sensitivity and specificity of resting state functional magnetic resonance imaging (rs-fMRI) connectivity analysis through more realistic assumptions. In simulation, the advantages of such methods are readily demonstrable. However, quantitative empirical validation remains elusive in vivo as the true connectivity patterns are unknown and noise distributions are challenging to characterize, especially in ultra-high field (e.g., 7T fMRI). Though the physiological characteristics of the fMRI signal are difficult to replicate in controlled phantom studies, it is critical that the performance of statistical techniques be evaluated. The SIMulation EXtrapolation (SIMEX) method has enabled estimation of bias with asymptotically consistent estimators on empirical finite sample data by adding simulated noise . To avoid the requirement of accurate estimation of noise structure, the proposed quantitative evaluation approach leverages the theoretical core of SIMEX to study the properties of inference methods in the face of diminishing data (in contrast to increasing noise). The performance of ordinary and robust inference methods in simulation and empirical rs-fMRI are compared using the proposed quantitative evaluation approach. This study provides a simple, but powerful method for comparing a proxy for inference accuracy using empirical data.
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Project description:In the past decade, the fast and transient coupling and uncoupling of functionally related brain regions into networks has received much attention in cognitive neuroscience. Empirical tools to study network coupling include functional magnetic resonance imaging (fMRI)-based functional and/or effective connectivity, and electroencephalography (EEG)/magnetoencephalography-based measures of neuronal synchronization. Here we use simultaneously recorded EEG and fMRI to assess whether fMRI-based connectivity and frequency-specific EEG power are related. Using data collected during resting state, we studied whether posterior EEG alpha power fluctuations are correlated with connectivity within the visual network and between the visual cortex and the rest of the brain. The results show that when alpha power increases, BOLD connectivity between the primary visual cortex and occipital brain regions decreases and that the negative relation of the visual cortex with the anterior/medial thalamus decreases and the ventral-medial prefrontal cortex is reduced in strength. These effects were specific for the alpha band, and not observed in other frequency bands. The decreased connectivity within the visual system may indicate an enhanced functional inhibition during a higher alpha activity. This higher inhibition level also attenuates long-range intrinsic functional antagonism between the visual cortex and the other thalamic and cortical regions. Together, these results illustrate that power fluctuations in posterior alpha oscillations result in local and long-range neural connectivity changes.
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Project description:In the past decade, the fusion between diffusion magnetic resonance imaging (dMRI) and functional magnetic resonance imaging (fMRI) has opened the way for exploring structure-function relationships in vivo. As it stands, the common approach usually consists of analysing fMRI and dMRI datasets separately or using one to inform the other, such as using fMRI activation sites to reconstruct dMRI streamlines that interconnect them. Moreover, given the large inter-individual variability of the healthy human brain, it is possible that valuable information is lost when a fixed set of dMRI/fMRI analysis parameters such as threshold values are assumed constant across subjects. By allowing one to modify such parameters while viewing the results in real-time, one can begin to fully explore the sensitivity of structure-function relations and how they differ across brain areas and individuals. This is especially important when interpreting how structure-function relationships are altered in patients with neurological disorders, such as the presence of a tumor. In this study, we present and validate a novel approach to achieve this: First, we present an interactive method to generate and visualize tractography-driven resting-state functional connectivity, which reduces the bias introduced by seed size, shape and position. Next, we demonstrate that structural and functional reconstruction parameters explain a significant portion of intra- and inter-subject variability. Finally, we demonstrate how our proposed approach can be used in a neurosurgical planning context. We believe this approach will promote the exploration of structure-function relationships in a subject-specific aspect and will open new opportunities for connectomics.
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Project description:The amygdala is composed of structurally and functionally distinct nuclei that contribute to the processing of emotion through interactions with other subcortical and cortical structures. While these circuits have been studied extensively in animals, human neuroimaging investigations of amygdala-based networks have typically considered the amygdala as a single structure, which likely masks contributions of individual amygdala subdivisions. The present study uses resting state functional magnetic resonance imaging (fMRI) to test whether distinct functional connectivity patterns, like those observed in animal studies, can be detected across three amygdala subdivisions: laterobasal, centromedial, and superficial. In a sample of 65 healthy adults, voxelwise regression analyses demonstrated positively-predicted ventral and negatively-predicted dorsal networks associated with the total amygdala, consistent with previous animal and human studies. Investigation of individual amygdala subdivisions revealed distinct differences in connectivity patterns within the amygdala and throughout the brain. Spontaneous activity in the laterobasal subdivision predicted activity in temporal and frontal regions, while activity in the centromedial nuclei predicted activity primarily in striatum. Activity in the superficial subdivision positively predicted activity throughout the limbic lobe. These findings suggest that resting state fMRI can be used to investigate human amygdala networks at a greater level of detail than previously appreciated, allowing for the further advancement of translational models.
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Project description:Resting state functional connectivity MRI (fcMRI) has become a particularly useful tool for studying regional relationships in typical and atypical populations. Because many investigators have already obtained large data sets of task-related fMRI, the ability to use this existing task data for resting state fcMRI is of considerable interest. Two classes of data sets could potentially be modified to emulate resting state data. These data sets include: (1) "interleaved" resting blocks from blocked or mixed blocked/event-related sets, and (2) residual timecourses from event-related sets that lack rest blocks. Using correlation analysis, we compared the functional connectivity of resting epochs taken from a mixed blocked/event-related design fMRI data set and the residuals derived from event-related data with standard continuous resting state data to determine which class of data can best emulate resting state data. We show that, despite some differences, the functional connectivity for the interleaved resting periods taken from blocked designs is both qualitatively and quantitatively very similar to that of "continuous" resting state data. In contrast, despite being qualitatively similar to "continuous" resting state data, residuals derived from event-related design data had several distinct quantitative differences. These results suggest that the interleaved resting state data such as those taken from blocked or mixed blocked/event-related fMRI designs are well-suited for resting state functional connectivity analyses. Although using event-related data residuals for resting state functional connectivity may still be useful, results should be interpreted with care.
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Project description:Moral competence (MC) refers to the ability to apply certain moral orientations in a consistent and differentiated manner when judging moral issues. People greatly differ in terms of MC, however, little is known about how these differences are implemented in the brain. To investigate this question, we used functional magnetic resonance imaging and examined resting-state functional connectivity (RSFC) in n=31 individuals with MC scores in the highest 15% of the population and n=33 individuals with MC scores in the lowest 15%, selected from a large sample of 730 Master of Business Administration (MBA) students. Compared to individuals with lower MC, individuals with higher MC showed greater amygdala-ventromedial prefrontal connectivity, which may reflect better ability to cope with emotional conflicts elicited by moral dilemmas. Moreover, individuals with higher MC showed less inter-network connectivity between the amygdalar and fronto-parietal networks, suggesting a more independent operation of these networks. Our findings provide novel insights into how individual differences in moral judgment are associated with RSFC in brain circuits related to emotion processing and cognitive control.
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