fMRI Datasets Research Articles

A Novel Finding in Cerebral Blood Flow in Patients with Sickle Cell Disease Using Bold Functional MRI

Background: Sickle cell disease (SCD) is an inherited blood disorder which is associated with acute and chronic pain, as well as other vascular complications such as arterial steno-occlusion, stroke, and silent cerebral infarction. Alterations of cerebral blood flow have been found to be associated with different painful stages in SCD, thus cerebral blood flow might be correlated with the disease severity determined by varied pain conditions in SCD. Blood oxygen level dependent (BOLD) imaging is a blood-related contrast technology in functional magnetic resonance imaging (fMRI). We have previously demonstrated the feasibility of using low frequency oscillation (LFO) in BOLD fMRI to track the hemodynamic features of the blood flow with maximum cross-correlation coefficient (MCCC) and the Delay Time (i.e., blood arrival time at different brain regions) (Tong et al., JCBFM. 2017). Positive MCCC value was found between the LFO BOLD signals extracted from the global mean (GMean, averaged signal across the whole brain) and the superior sagittal sinus (SSS) in our previous findings (Tong et al., JCBFM. 2018). In this study, we aim to use LFO BOLD signals to explore the cerebral hemodynamic features with MCCCs and their associations with hematological and disease severity related outcomes in patients with SCD. Methods: Ten subjects with SCD aged 14-43 years old (5 HbSS, 3 HbSC, 1 HbSB+, 1 HbB0) and 10 age- and sex-matched controls from a publicly available dataset Human Connectome Project (HCP) (Essen et al., Neuroimage, 2013) were included for data analysis. T1-weighted and resting-state BOLD fMRI (repetition time (TR)=1.05 sec) were collected using a 3T SIEMENS (Prisma) scanner. A BOLD fMRI dataset with TR of 0.72 sec from healthy subjects was used as control. All the BOLD fMRI data were preprocessed using FSL to correct the motion artifact. The SSS region was identified in the T1-weighted image using FSL. The corresponding SSS mask was then applied in the BOLD fMRI image to extract the BOLD fMRI signals in the SSS region. The GMean BOLD signal was averaged across the whole brain. BOLD fMRI Signals were demeaned and band-pass filtered (0.01-0.1 Hz) to acquire the LFO signals. Cross-correlation between the SSS-LFO signal and GMean-LFO signal was performed to calculate the MCCC and their corresponding Delay Time. Correlations between the MCCCs of the two LFO signals (from SSS and GMean) and each hematological index were further performed. Results: Consistent with the healthy control in our previous findings, half of the patients (3 HbSC, 1 HbSB+, and 1 HbSS) presented positive MCCC values. However, interestingly, negative MCCC values were found from another half of the patients (4 HbSS and 1 HbB0, Figure 1, p < 0.05 for all subjects). Notably, all patients with HbSC presented positive MCCC values that are similar to controls whereas 4 out 5 patients with HbSS (80%) were found to have negative MCCC values. More importantly, higher percentages of HbS and lower total Hgb (HbS(%): r=-0.73, p=0.03; Hgb(GM/dL): r=0.69, p=0.03) were found to be significantly associated with the negative MCCC values. Conclusions: We found a never-before-seen negative MCCC signature between the BOLD fMRI signals in the SSS and the GMean in a subset of patients with SCD compared with healthy controls. This might indicate a significant change in cerebral blood flow in a subset of patients with SS disease compared with SC and controls. Importantly, we further observed that this never-before-seen negative MCCC signature is highly associated with the percentage of the HbS and total Hgb that are known to be correlated with disease severity. This might be due to the microvascular shunting (Juttukonda et al., JCBFM, 2019) that exists in patients who have high percentage of HbS. This study is the first to associate BOLD fMRI derived hemodynamic metrics with disease severity related outcomes in SCD. This never-before-seen anti-correlation MCCC signature may have tremendous promise as a novel biomarker for SCD severity and differentiate pain characteristics in different sickle cell phenotypes, and further investigation in larger number of subjects is needed to understand variations between SCD phenotypes and its relationship to clinical outcomes. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Beyond Linear Dynamic Functional Connectivity: A Vine Copula Change Point Model

To estimate dynamic functional connectivity for functional magnetic resonance imaging (fMRI) data, two approaches have dominated: sliding window and change point methods. While computationally feasible, the sliding window approach has several limitations. In addition, the existing change point methods assume a Gaussian distribution for and linear dependencies between the fMRI time series. In this work, we introduce a new methodology called Vine Copula Change Point (VCCP) to estimate change points in the functional connectivity network structure between brain regions. It uses vine copulas, various state-of-the-art segmentation methods to identify multiple change points, and a likelihood ratio test or the stationary bootstrap for inference. The vine copulas allow for various forms of dependence between brain regions including tail, symmetric and asymmetric dependence, which has not been explored before in the dynamic analysis of neuroimaging data. We apply VCCP to various simulation datasets and to two fMRI datasets: a reading task and an anxiety inducing experiment. In particular, for the former dataset, we illustrate the complexity of textual changes during the reading of Chapter 9 in Harry Potter and the Sorcerer’s Stone and find that change points across subjects are related to changes in more than one type of textual attributes. Further, the graphs created by the vine copulas indicate the importance of working beyond Gaussianity and linear dependence. Finally, the R package vccp implementing the methodology from the article is available from CRAN. Supplementary Materials for this article are available online.

Characterizing functional brain networks via Spatio-Temporal Attention 4D Convolutional Neural Networks (STA-4DCNNs)

Characterizing individualized spatio-temporal patterns of functional brain networks (FBNs) via functional magnetic resonance imaging (fMRI) provides a foundation for understanding complex brain function. Although previous studies have achieved promising performances based on either shallow or deep learning models, there is still much space to improve the accuracy of spatio-temporal pattern characterization of FBNs by optimally integrating the four-dimensional (4D) features of fMRI. In this study, we introduce a novel Spatio-Temporal Attention 4D Convolutional Neural Network (STA-4DCNN) model to characterize individualized spatio-temporal patterns of FBNs. Particularly, STA-4DCNN is composed of two subnetworks, in which the first Spatial Attention 4D CNN (SA-4DCNN) models the spatio-temporal features of 4D fMRI data and then characterizes the spatial pattern of FBNs, and the second Temporal Guided Attention Network (T-GANet) further characterizes the temporal pattern of FBNs under the guidance of the spatial pattern together with 4D fMRI data. We evaluate the proposed STA-4DCNN on seven different task fMRI and one resting state fMRI datasets from the publicly released Human Connectome Project. The experimental results demonstrate that STA-4DCNN has superior ability and generalizability in characterizing individualized spatio-temporal patterns of FBNs when compared to other state-of-the-art models. We further apply STA-4DCNN on another independent ABIDE I resting state fMRI dataset including both autism spectrum disorder (ASD) and typical developing (TD) subjects, and successfully identify abnormal spatio-temporal patterns of FBNs in ASD compared to TD. In general, STA-4DCNN provides a powerful tool for FBN characterization and for clinical applications on brain disease characterization at the individual level.

Multimodal analysis demonstrating the shaping of functional gradients in the marmoset brain

The discovery of functional gradients introduce a new perspective in understanding the cortical spectrum of intrinsic dynamics, as it captures major axes of functional connectivity in low-dimensional space. However, how functional gradients arise and dynamically vary remains poorly understood. In this study, we investigated the biological basis of functional gradients using awake resting-state fMRI, retrograde tracing and gene expression datasets in marmosets. We found functional gradients in marmosets showed a sensorimotor-to-visual principal gradient followed by a unimodal-to-multimodal gradient, resembling functional gradients in human children. Although strongly constrained by structural wirings, functional gradients were dynamically modulated by arousal levels. Utilizing a reduced model, we uncovered opposing effects on gradient dynamics by structural connectivity (inverted U-shape) and neuromodulatory input (U-shape) with arousal fluctuations, and dissected the contribution of individual neuromodulatory receptors. This study provides insights into biological basis of functional gradients by revealing the interaction between structural connectivity and ascending neuromodulatory system.

Consistent connectome landscape mining for cross-site brain disease identification using functional MRI.

Many human brain disorders are associated with characteristic alterations in functional connectivity of the brain. A lot of efforts have been devoted to mining disease-related biomarkers for identifying patients with brain disorders from normal controls. However, previous studies show largely inconsistent findings due to variability across numerous study-specific factors such as heterogeneity across different preprocessing pipelines or the use of multi-site data. Also, existing methods usually employ human-engineered features (e.g., graph-theoretical measures) that may be less discriminate for disease identification. To this end, we propose a novel Connectome Landscape Modeling (CLM) method that can mine cross-site consistent connectome landscape and extract data-driven representation of functional connectivity networks for brain disorder identification. Specifically, with functional connectivity networks as input, the proposed CLM model aims to learn a weight matrix for joint cross-site consistent connectome landscape learning, network feature extraction, and disease identification. We impose the row-column overlap norm penalty on the network-based predictor to capture consistent connectome landscape across multiple sites. To capture site-specific patterns, we introduce an ℓ1-norm penalty in CLM. We develop an efficient algorithm based on the Alternating Direction Method of Multipliers (ADMM) to solve the proposed objective function. Experimental results on three real-world fMRI datasets demonstrate the potential use of our CLM in cross-site brain disorder analysis.

A neural signature of the vividness of prospective thought is modulated by temporal proximity during intertemporal decision making

Why do people discount future rewards? Multiple theories in psychology argue that one reason is that future events are imagined less vividly than immediate events, thereby diminishing their perceived value. Here we provide neuroscientific evidence for this proposal. First, we construct a neural signature of the vividness of prospective thought, using an fMRI dataset where the vividness of imagined future events is orthogonal to their valence by design. Then, we apply this neural signature in two additional fMRI datasets, each using a different delay-discounting task, to show that neural measures of vividness decline as rewards are delayed farther into the future.

Effects of face repetition on ventral visual stream connectivity using dynamic causal modelling of fMRI data

Stimulus repetition normally causes reduced neural activity in brain regions that process that stimulus. Some theories claim that this “repetition suppression” reflects local mechanisms such as neuronal fatigue or sharpening within a region, whereas other theories claim that it results from changed connectivity between regions, following changes in synchrony or top-down predictions. In this study, we applied dynamic causal modeling (DCM) on a public fMRI dataset involving repeated presentations of faces and scrambled faces to test whether repetition affected local (self-connections) and/or between-region connectivity in left and right early visual cortex (EVC), occipital face area (OFA) and fusiform face area (FFA). Face “perception” (faces versus scrambled faces) modulated nearly all connections, within and between regions, including direct connections from EVC to FFA, supporting a non-hierarchical view of face processing. Face “recognition” (familiar versus unfamiliar faces) modulated connections between EVC and OFA/FFA, particularly in the left hemisphere. Most importantly, immediate and delayed repetition of stimuli were also best captured by modulations of connections between EVC and OFA/FFA, but not self-connections of OFA/FFA, consistent with synchronization or predictive coding theories, though also possibly reflecting local mechanisms like synaptic depression.

The integrative functional connectivity analysis between seafarer's brain networks using functional magnetic resonance imaging data of different states.

The particularity of seafarers' occupation makes their brain functional activities vulnerable to the influence of working environments, which leads to abnormal functional connectivities (FCs) between brain networks. To further investigate the influences of maritime environments on the seafarers' functional brain networks, the functional magnetic resonance imaging (fMRI) datasets of 33 seafarers before and after sailing were used to study FCs among the functional brain networks in this paper. On the basis of making full use of the intrinsic prior information from fMRI data, six resting-state brain functional networks of seafarers before and after sailing were obtained by using group independent component analysis with intrinsic reference, and then the differences between the static and dynamic FCs among these six brain networks of seafarers before and after sailing were, respectively, analyzed from both group and individual levels. Subsequently, the potential dynamic functional connectivity states of seafarers before and after sailing were extracted by using the affine propagation clustering algorithm and the probabilities of state transition between them were obtained simultaneously. The results show that the dynamic FCs among large-scale brain networks have significant difference seafarers before and after sailing both at the group level and individual level, while the static FCs between them varies only at the individual level. This suggests that the maritime environments can indeed affect the brain functional activity of seafarers in real time, and the degree of influence is different for different subjects, which is of a great significance to explore the neural changes of seafarer's brain functional network.

Diagnostic model optimization method for ADHD based on brain network analysis of resting-state fMRI images and transfer learning neural network.

Introduction: Attention deficit and hyperactivity disorder (ADHD) is a common inherited disease of the nervous system whose cause(s) and pathogenesis remain unclear. Currently, the diagnosis of ADHD is mainly based on clinical experience and guidelines that have laid out some diagnostic standards. Our study aimed to apply a learning-based classification method to assist the ADHD diagnosis based on high-dimensional resting-state fMRI.Methods: Our study selected the ADHD-200 Peking dataset of resting-state fMRI, which has an ADHD patient (n = 142) group and a typically developing control (TDC) healthy control (n = 102) group. We first used Pearson and partial correlation coefficients to perform functional connectivity (FC) analysis between ROIs. Then, the Pearson and partial correlation coefficient matrices were concatenated into a dual-channel feature to build a dual data channel as input to the transfer learning neural network (TLNN) architecture. Finally, we transferred the pretrained model from the auxiliary domain to our target domain and fine-tuned it.Results: Based on the Pearson correlation coefficient, FC between ROIs was detected in 22 brain regions, including the fusiform gyrus, superior frontal gyrus, posterior superior temporal sulcus, inferior parietal lobule, anterior cingulate cortex, and parahippocampal gyrus. Based on the partial correlation coefficient, we found FC in the salient network, default network, sensory-motor network, dorsal attention network, and cerebellum network. With the TLNN architecture, we solved the problem of insufficient training data and improved the sensitivity of the classification method. When the VGG model (fine-tuned transfer strategy, 1,024 fully connected layers) was applied, the accuracy of TLNN classification ultimately reached 82%.Conclusion: Our study suggests that completing the training of the target domain by transferring the prior knowledge of the auxiliary domain is effective in solving the classification problem of small sample datasets. Based on prior knowledge of FC analysis, TLNN classification may assist ADHD diagnosis in a new way.

Multilevel mediation analysis with structured unmeasured mediator-outcome confounding

Mediation analysis usually requires the assumption that there is no unmeasured mediator-outcome confounder. However, this may not hold in many social and scientific studies. Though various parametric and nonparametric mediation methods have been developed, this assumption remains instrumental, without which the causal effects are not identifiable unless alternative assumptions are imposed. To circumvent this, a multilevel parametric structural equation modeling framework is proposed to relax this no unmeasured mediator-outcome confounding assumption under a specific data setting inspired by a real experiment. Using the proposed framework, it is shown that the causal effects are identifiable and consistently estimated. Likelihood-based approaches are proposed with efficient optimization algorithms to estimate the parameters, including the unmeasured confounding effect, instead of performing sensitivity analysis. The asymptotic consistency is established. Using extensive simulations and a functional magnetic resonance imaging dataset, the improvement of the approaches over existing methods is demonstrated. The R package macc for implementation is available on CRAN.

Linear Manifold Modeling and Graph Estimation based on Multivariate Functional Data with Different Coarseness Scales

We develop a high-dimensional graphical modeling approach for functional data where the number of functions exceeds the available sample size. This is accomplished by proposing a sparse estimator for a concentration matrix when identifying linear manifolds. As such, the procedure extends the ideas of the manifold representation for functional data to high-dimensional settings where the number of functions is larger than the sample size. By working in a penalized setting it enriches the functional data framework by estimating sparse undirected graphs that show how functional nodes connect to other functional nodes. The procedure allows multiple coarseness scales to be present in the data and proposes a simultaneous estimation of several related graphs. Its performance is illustrated using a real-life fMRI dataset and with simulated data.

Receptor-informed network control theory links LSD and psilocybin to a flattening of the brain’s control energy landscape

Psychedelics including lysergic acid diethylamide (LSD) and psilocybin temporarily alter subjective experience through their neurochemical effects. Serotonin 2a (5-HT2a) receptor agonism by these compounds is associated with more diverse (entropic) brain activity. We postulate that this increase in entropy may arise in part from a flattening of the brain’s control energy landscape, which can be observed using network control theory to quantify the energy required to transition between recurrent brain states. Using brain states derived from existing functional magnetic resonance imaging (fMRI) datasets, we show that LSD and psilocybin reduce control energy required for brain state transitions compared to placebo. Furthermore, across individuals, reduction in control energy correlates with more frequent state transitions and increased entropy of brain state dynamics. Through network control analysis that incorporates the spatial distribution of 5-HT2a receptors (obtained from publicly available positron emission tomography (PET) data under non-drug conditions), we demonstrate an association between the 5-HT2a receptor and reduced control energy. Our findings provide evidence that 5-HT2a receptor agonist compounds allow for more facile state transitions and more temporally diverse brain activity. More broadly, we demonstrate that receptor-informed network control theory can model the impact of neuropharmacological manipulation on brain activity dynamics.

Local similarity of activity patterns during auditory and visual processing

Neuroimaging studies have shown that brain activity is variable and changes according to stimuli and the environmental context, reflecting brain coding or information representations at different processing levels. However, little is known about activity organization that reflects coding strategies. Here, we explored and compared two different coding approaches, spatial via cross-correlation and intensity-based coding using mutual information. Using two fMRI datasets and different seeds, we searched for the spatial and intensity-based similarities with the seeds in brain activity. Our results showed that, apart from the seed regions, significant regions detected by intensity-based similarity analysis differ completely from those found using cross-correlation. These findings may indicate that information shared through spatial coding differs from that transmitted via non-spatial coding processes. Our results suggest that brain coding is organized in several different ways to optimize information processing.

Domain-specific and domain-general neural network engagement during human-robot interactions.

To what extent do domain-general and domain-specific neural network engagement generalize across interactions with human and artificial agents? In this exploratory study, we analysed a publicly available functional MRI (fMRI) data set (n = 22) to probe the similarities and dissimilarities in neural architecture while participants conversed with another person or a robot. Incorporating trial-by-trial dynamics of the interactions, listening and speaking, we used whole-brain, region-of-interest and functional connectivity analyses to test response profiles within and across social or non-social, domain-specific and domain-general networks, that is, the person perception, theory-of-mind, object-specific, language and multiple-demand networks. Listening to a robot compared to a human resulted in higher activation in the language network, especially in areas associated with listening comprehension, and in the person perception network. No differences in activity of the theory-of-mind network were found. Results from the functional connectivity analysis showed no difference between interactions with a human or robot in within- and between-network connectivity. Together, these results suggest that although largely similar regions are activated when speaking to a human and to a robot, activity profiles during listening point to a dissociation at a lower level or perceptual level, but not higher order cognitive level.

Topographic organization of the human caudate functional connectivity and age-related changes with resting-state fMRI.

The striatum is postulated to play a central role in gating cortical processing during goal-oriented behavior. While many human neuroimaging studies have treated the striatum as an undivided whole or several homogeneous compartments, some recent studies showed that its circuitry is topographically organized and has more complex relations with the cortical networks than previously assumed. Here, we took a gradient functional connectivity mapping approach that utilizes the entire anatomical space of the caudate nucleus to examine the organization of its functional relationship with the rest of the brain and how its topographic mapping changes with age. We defined the topography of the caudate functional connectivity using three publicly available resting-state fMRI datasets. We replicated and extended previous findings. First, we found two stable gradients of caudate connectivity patterns along its medial-lateral (M-L) and anterior-posterior (A-P) axes, supporting findings from previous tract-tracing studies of non-human primates that there are at least two main organizational principles within the caudate nucleus. Second, unlike previous emphasis of the A-P topology, we showed that the differential connectivity patterns along the M-L gradient of caudate are more clearly organized with the large-scale neural networks; such that brain networks associated with internal vs. external orienting behavior are respectively more closely linked to the medial vs. lateral extent of the caudate. Third, the caudate's M-L organization showed greater age-related reduction in integrity, which was further associated with age-related changes in behavioral measures of executive functions. In sum, our analysis confirmed a sometimes overlooked M-L functional connectivity gradient within the caudate nucleus, with its lateral longitudinal zone more closely linked to the frontoparietal cortical circuits and age-related changes in cognitive control. These findings provide a more precise mapping of the human caudate functional connectivity, both in terms of the gradient organization with cortical networks and age-related changes in such organization.

Accelerated functional brain aging in major depressive disorder: evidence from a large scale fMRI analysis of Chinese participants

Major depressive disorder (MDD) is one of the most common mental health conditions that has been intensively investigated for its association with brain atrophy and mortality. Recent studies suggest that the deviation between the predicted and the chronological age can be a marker of accelerated brain aging to characterize MDD. However, current conclusions are usually drawn based on structural MRI information collected from Caucasian participants. The universality of this biomarker needs to be further validated by subjects with different ethnic/racial backgrounds and by different types of data. Here we make use of the REST-meta-MDD, a large scale resting-state fMRI dataset collected from multiple cohort participants in China. We develop a stacking machine learning model based on 1101 healthy controls, which estimates a subject’s chronological age from fMRI with promising accuracy. The trained model is then applied to 1276 MDD patients from 24 sites. We observe that MDD patients exhibit a +4.43 years (p < 0.0001, Cohen’s d = 0.31, 95% CI: 2.23–3.88) higher brain-predicted age difference (brain-PAD) compared to controls. In the MDD subgroup, we observe a statistically significant +2.09 years (p < 0.05, Cohen’s d = 0.134525) brain-PAD in antidepressant users compared to medication-free patients. The statistical relationship observed is further checked by three different machine learning algorithms. The positive brain-PAD observed in participants in China confirms the presence of accelerated brain aging in MDD patients. The utilization of functional brain connectivity for age estimation verifies existing findings from a new dimension.

Dynamic functional connectivity estimation for neurofeedback emotion regulation paradigm with simultaneous EEG-fMRI analysis.

Joint Analysis of EEG and fMRI datasets can bring new insight into brain mechanisms. In this paper, we employed the recently introduced Correlated Coupled Tensor Matrix Factorization (CCMTF) method for analysis of the emotion regulation paradigm based on EEG frontal asymmetry neurofeedback in the alpha frequency band with simultaneous fMRI. CCMTF method assumes that the co-variations of the common dimension (temporal dimension) between EEG and fMRI are correlated and not necessarily identical. The results of the CCMTF method suggested that EEG and fMRI had similar covariations during the transition of brain activities from resting states to task (view and upregulation) states and these covariations followed an increasing trend. The fMRI shared spatial component showed activations in the limbic system, DLPFC, OFC, and VLPC regions, which were consistent with the previous studies and were linked to EEG frequency patterns in the range of 1–15 Hz with a correlation value close to 0.75. The estimated regions from the CCMTF method were then used as the candidate nodes for dynamic functional connectivity (dFC) analysis, in which the changes in connectivity from view to upregulation states were examined. The results of the dFC analysis were compared with a Normalized Mutual information (NMI) based approach in two different frequency ranges (1–15 and 15–40 Hz) as the NMI method was applied to the vectors of dFC nodes of EEG and fMRI data. The results of the two methods illustrated that the relation between EEG and fMRI datasets was mostly in the frequency range of 1–15 Hz. These relations were both in the brain activations and the dFCs between the two modalities. This paper suggests that the CCMTF method is a capable approach for extracting the shared information between EEG and fMRI data and can reveal new information about brain functions and their connectivity without solving the EEG inverse problem or analyzing different frequency bands.

Aberrant dynamic minimal spanning tree parameters within default mode network in patients with autism spectrum disorder.

The altered functional connectivity (FC) level and its temporal characteristics within certain cortical networks, such as the default mode network (DMN), could provide a possible explanatory framework for Autism spectrum disorder (ASD). In the current study, we hypothesized that the topographical organization along with its temporal dynamics of the autistic brain measured by temporal mean and variance of complex network measures, respectively, were significantly altered, which may further explain the autistic symptom severity in patients with ASD. To validate these hypotheses, the precise FCs between DMN regions at each time point were calculated using the resting-state functional magnetic resonance imaging (fMRI) datasets from the Autism Brain Imaging Data Exchange (ABIDE) project. Then, the minimal spanning tree (MST) technique was applied to construct a time-varying complex network of DMN. By analyzing the temporal mean and variance of MST parameters and their relationship with autistic symptom severity, we found that in persons with ASD, the information exchange efficiencies between cortical regions within DMN were significantly lower and more volatile compared with those in typical developing participants. Moreover, these alterations within DMN were closely associated with the autistic symptom severity of the ASD group.

A spatio-temporal decomposition framework for dynamic functional connectivity in the human brain

Much recent attention has been directed toward investigating the spatial and temporal organization of brain dynamics, but the rules which constrain the variation of spatio-temporal organization in functional connectivity under different brain states remain unclear. Here, we developed a novel computational approach based on tensor decomposition and regularization to represent dynamic functional connectivity as a linear combination of dynamic modules and time-varying weights. In this approach, dynamic modules represent co-activating functional connectivity patterns, and time-varying weights represent the temporal expression of dynamic modules. We applied this dynamic decomposition model (DDM) on a resting-state fMRI dataset and found that whole-brain dynamic functional connectivity can be decomposed as a linear combination of eight dynamic modules which we summarize as ‘high order modules’ and ‘primary–high order modules’, according to their spatial attributes and correspondence with existing intrinsic functional brain networks. By clustering the time-varying weights, we identified five brain states including three major states and two minor states. We found that state transitions mainly occurred between the three major states, and that temporal variation of dynamic modules may contribute to brain state transitions. We then conceptualized the variability of weights as the flexibility of the corresponding dynamic modules and found that different dynamic modules exhibit different amounts of flexibility and contribute to different cognitive measures. Finally, we applied DDM to a schizophrenia resting-state fMRI dataset and found that atypical flexibility of dynamic modules correlates with impaired cognitive flexibility in schizophrenia. Overall, this work provides a quantitative framework that characterizes temporal variation in the topology of dynamic functional connectivity.

WHOCARES: WHOle-brain CArdiac signal REgression from highly accelerated simultaneous multi-Slice fMRI acquisitions

Objective. To spatio-temporally resolve cardiac signals in functional magnetic resonance imaging (fMRI) time-series of the human brain using neither external physiological measurements nor ad hoc modelling assumptions. Approach. Cardiac pulsation is a physiological confound of fMRI time-series that introduces spurious signal fluctuations in proximity to blood vessels. fMRI alone is not sufficiently fast to resolve cardiac pulsation. Depending on the ratio between the instantaneous heart-rate and the acquisition sampling frequency (, with TR being the repetition time), the cardiac signal may alias into the frequency band of neural activation so that its removal through spectral filtering techniques is generally not possible. In this paper, we show that it is feasible to temporally and spatially resolve cardiac signals throughout the brain even when cardiac aliasing occurs by combining fMRI hyper-sampling with simultaneous multislice (SMS) imaging. The technique, which we name WHOle-brain CArdiac signal REgression from highly accelerated simultaneous multi-Slice fMRI acquisitions (WHOCARES), was developed on 695 healthy subjects selected from the Human Connectome Project and its performance validated against the RETROICOR, HAPPY and the pulse oxymeter signal regression methods. Main results. WHOCARES is capable of retrieving voxel-wise cardiac signal regressors. This is achieved without employing external physiological recordings nor through ad hoc modelling assumptions. The performance of WHOCARES was, on average, superior to RETROICOR, HAPPY and the pulse oxymeter regression methods. Significance. WHOCARES holds basis for the reliable mapping of cardiac activity in fMRI time-series. WHOCARES can be employed for the retrospective removal of cardiac noise in publicly available fMRI datasets where physiological recordings are not available. WHOCARES is freely available at https://github.com/gferrazzi/WHOCARES.