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AbstractStatic and dynamic functional network connectivity (FNC) are typically studied separately, which makes us unable to see the full spectrum of connectivity in each analysis. Here, we propose an approach called filter-banked connectivity (FBC) to estimate connectivity while preserving its full frequency range and subsequently examine both static and dynamic connectivity in one unified approach.First, we demonstrate that FBC can estimate connectivity across multiple frequencies missed by a sliding-window approach. Next, we use FBC to estimate FNC in a resting-state fMRI dataset including schizophrenia patients (SZ) and typical controls (TC). The FBC results are clustered into different network states. Some states showed weak low-frequency strength and as such were not captured in the window-based approach. Additionally, we found that SZs tend to spend more time in states exhibiting higher frequencies compared with TCs who spent more time in lower frequency states. Finally, we show that FBC enables us to analyze static and dynamic connectivity in a unified way. In summary, FBC offers a novel way to unify static and dynamic connectivity analyses and can provide additional information about the frequency profile of connectivity patterns.

Individuals can be characterized in a population according to their brain measurements and activity, given the inter-subject variability in brain anatomy, structure-function relationships, or life experience. Many neuroimaging studies have demonstrated the potential of functional network connectivity patterns estimated from resting functional magnetic resonance imaging (fMRI) to discriminate groups and predict information about individual subjects. However, the predictive signal present in the spatial heterogeneity of brain connectivity networks is yet to be extensively studied. In this study, we investigate, for the first time, the use of pairwise-relationships between resting-state independent spatial maps to characterize individuals. To do this, we develop a deep Siamese framework comprising three-dimensional convolution neural networks for contrastive learning based on individual-level spatial maps estimated via a fully automated fMRI independent component analysis approach. The proposed framework evaluates whether pairs of spatial networks (e.g., visual network and auditory network) are capable of subject identification and assesses the spatial variability in different network pairs’ predictive power in an extensive whole-brain analysis. Our analysis on nearly 12,000 unaffected individuals from the UK Biobank study demonstrates that the proposed approach can discriminate subjects with an accuracy of up to 88% for a single network pair on the test set (best model, after several runs), and 82% average accuracy at the subcortical domain level, notably the highest average domain level accuracy attained. Further investigation of our network’s learned features revealed a higher spatial variability in predictive accuracy among younger brains and significantly higher discriminative power among males. In sum, the relationship among spatial networks appears to be both informative and discriminative of individuals and should be studied further as putative brain-based biomarkers.

BackgroundA number of studies in recent years have explored whole-brain dynamic connectivity using pairwise approaches. There has been less focus on trying to analyze brain dynamics in higher dimensions over time.MethodsWe introduce a new approach that analyzes time series trajectories to identify high traffic nodes in a high dimensional space. First, functional magnetic resonance imaging (fMRI) data are decomposed using spatial ICA to a set of maps and their associated time series. Next, density is calculated for each time point and high-density points are clustered to identify a small set of high traffic nodes. We validated our method using simulations and then implemented it on a real data set.ResultsWe present a novel approach that captures dynamics within a high dimensional space and also does not use any windowing in contrast to many existing approaches. The approach enables one to characterize and study the time series in a potentially high dimensional space, rather than looking at each component pair separately. Our results show that schizophrenia patients have a lower dynamism compared to healthy controls. In addition, we find patients spend more time in nodes associated with the default mode network and less time in components strongly correlated with auditory and sensorimotor regions. Interestingly, we also found that subjects oscillate between state pairs that show opposite spatial maps, suggesting an oscillatory pattern.ConclusionOur proposed method provides a novel approach to analyze the data in its native high dimensional space and can possibly provide new information that is undetectable using other methods.

Interest in time-resolved connectivity in fMRI has grown rapidly in recent years. The most widely used technique for studying connectivity changes over time utilizes a sliding windows approach. There has been some debate about the utility of shorter versus longer windows, the use of fixed versus adaptive windows, as well as whether observed resting state dynamics during wakefulness may be predominantly due to changes in sleep state and subject head motion. In this work we use an independent component analysis (ICA)-based pipeline applied to concurrent EEG/fMRI data collected during wakefulness and various sleep stages and show: 1) connectivity states obtained from clustering sliding windowed correlations of resting state functional network time courses well classify the sleep states obtained from EEG data, 2) using shorter sliding windows instead of longer non-overlapping windows improves the ability to capture transition dynamics even at windows as short as 30 ​s, 3) motion appears to be mostly associated with one of the states rather than spread across all of them 4) a fixed tapered sliding window approach outperforms an adaptive dynamic conditional correlation approach, and 5) consistent with prior EEG/fMRI work, we identify evidence of multiple states within the wakeful condition which are able to be classified with high accuracy. Classification of wakeful only states suggest the presence of time-varying changes in connectivity in fMRI data beyond sleep state or motion. Results also inform about advantageous technical choices, and the identification of different clusters within wakefulness that are separable suggest further studies in this direction.

Abstract Background Cerebrovascular reactivity (CVR) is an important aspect of brain function, and as such it is important to understand relationship between CVR and functional connectivity. Methods This research studied the role of CVR, or the brain's ability to react to vasoactive stimuli on brain functional connectivity by scanning subjects with blood‐oxygenation‐level‐dependent (BOLD) functional magnetic resonance imaging (fMRI) while they periodically inhale room air and a CO 2‐enriched gas mixture. We developed a new metric to measure the effect of CVR on each intrinsic connectivity network (ICN), which contrasts to voxel‐wise CVR. We also studied the changes in whole‐brain connectivity patterns using both static functional network connectivity (sFNC) and dynamic FNC (dFNC). Results We found that network connectivity is generally weaker during vascular dilation, which is supported by previous research. The dFNC analysis revealed that participants did not return to the pre‐CO 2 inhalation state, suggesting that one‐minute periods of room‐air inhalation is not enough for the CO 2 effect to fully dissipate. Conclusions Cerebrovascular reactivity is one tool that the cerebrovascular system uses to ensure the constant, finely‐tuned flow of oxygen to function properly. Understanding the relationship between CVR and brain dynamism can provide unique information about cerebrovascular diseases and general brain function. We observed that CVR has a wide, but consistent relationship to connectivity patterns between functional networks.

Brain functional connectivity (FC), as measured by blood oxygenation level-dependent (BOLD) signal, fluctuates at the scale of 10s of seconds. It has recently been found that whole-brain dynamic FC (dFC) patterns contain sufficient information to permit identification of ongoing tasks. Here, we hypothesize that dFC patterns carry fine-grained information that allows for tracking short-term task engagement levels (i.e., 10s of seconds long). To test this hypothesis, 25 subjects were scanned continuously for 25 min while they performed and transitioned between four different tasks: working memory, visual attention, math, and rest. First, we estimated dFC patterns by using a sliding window approach. Next, we extracted two engagement-specific FC patterns representing active engagement and passive engagement by using k-means clustering. Then, we derived three metrics from whole-brain dFC patterns to track engagement level, that is, dissimilarity between dFC patterns and engagement-specific FC patterns, and the level of brainwide integration level. Finally, those engagement markers were evaluated against windowed task performance by using a linear mixed effects model. Significant relationships were observed between abovementioned metrics and windowed task performance for the working memory task only. These findings partially confirm our hypothesis and underscore the potential of whole-brain dFC to track short-term task engagement levels. In this study, we hypothesized that whole-brain dynamic functional connectivity (FC) patterns carry fine-grained information that allows for tracking short-term task engagement levels. We derived three task engagement markers from whole-brain dynamic FC pattern, that is, dissimilarity between dynamic FC patterns and high/low-engagement FC patterns, as well as brainwide integration level. We employed a linear mixed effects model to relate those task engagement markers with short-term task performance, and confirmed our hypothesis with the working memory task.

Cognitive impairment is a feature of many psychiatric diseases. Here the authors aimed to identify multimodal neuromarkers that can be used to quantify and predict cognitive performance in individuals with schizophrenia using three different features of MRI and three independent cohorts.

The study of dynamic functional network connectivity (dFNC) has been important to understand the healthy and diseased brain. Recent developments model groups of functionally related brain structures (defined as functional domains) as entities that can send and receive information. A domain analysis starts by detecting a finite set of connectivity patterns known as domain states within each functional domain. Dynamic functional domain connectivity (DFDC) is a novel information theoretic framework for studying the temporal sequence of the domain states and the amount of information shared among domains. In this setting, the information flow among functional domains can be compared to the flow of bits among entities in a digital network. Schizophrenia is a chronic psychiatric disorder which is associated with how the brain processes information. Here, we employed the DFDC framework to analyze a dataset containing resting-state fMRI scans from 163 healthy controls (HCs) and 151 schizophrenia patients (SZs). As in other information theory methods, this study measured domain state probabilities, entropy within each DFDC and the cross-domain mutual information (CDMI) between pairs of DFDC. Results indicate that SZs show significantly higher (transformed) entropy than HCs in subcortical (SC)-SC; default mode network (DMN)-visual (VIS) and frontoparietal (FRN)-VIS DFDCs. SZs also show lower (transformed) CDMI between SC-VIS vs. SC-sensorimotor (SM), attention (ATTN)-VIS vs. ATTN-SM and ATTN-SM vs. ATTN-ATTN DFDC pairs after correcting for multiple comparisons. These results imply that different DFDC pairs function in a more independent manner in SZs compared to HCs. Our findings present evidence of higher uncertainty and randomness in SZ brain function.

Functional connectivity is one of the most widely used tools for investigating brain changes due to schizophrenia. Previous studies have identified abnormal functional connectivity in schizophrenia patients at the resting state brain network level. This study tests the existence of functional connectivity effects at whole brain and domain levels. Domain level refers to the integration of data from several brain networks grouped by their functional relationship. Data integration provides more consistent and accurate information compared to an individual brain network. This work considers two domain level measures: functional connectivity strength and randomness. The first measure is simply an average of connectivities within the domain. The second measure assesses the unpredictability and lack of pattern of functional connectivity within the domain. Domains with less random connectivity have higher chance of exhibiting a biologically meaningful connectivity pattern. Consistent with prior observations, individuals with schizophrenia showed aberrant domain connectivity strength between subcortical, cerebellar, and sensorial brain areas. Compared to healthy volunteers, functional connectivity between cognitive and default mode domains showed less randomness, while connectivity between default mode-sensorial areas showed more randomness in schizophrenia patients. These differences in connectivity patterns suggest deleterious rewiring trade-offs among important brain networks.

Brain functional connectivity has been shown to change over time during resting state fMRI experiments. Close examination of temporal changes have revealed a small set of whole-brain connectivity patterns called dynamic states. Dynamic functional network connectivity (dFNC) studies have demonstrated that it is possible to replicate the dynamic states across several resting state experiments. However, estimation of states and their temporal dynamicity still suffers from noisy and imperfect estimations. In regular dFNC implementations, states are estimated by comparing connectivity patterns through the data without considering time, in other words only zero order changes are examined. In this work we propose a method that includes first order variations of dFNC in the searching scheme of dynamic connectivity patterns. Our approach, referred to as temporal variation of functional network connectivity (tvFNC), estimates the derivative of dFNC, and then searches for reoccurring patterns of concurrent dFNC states and their derivatives. The tvFNC method is first validated using a simulated dataset and then applied to a resting-state fMRI sample including healthy controls (HC) and schizophrenia (SZ) patients and compared to the standard dFNC approach. Our dynamic approach reveals extra patterns in the connectivity derivatives complementing the already reported state patterns. State derivatives consist of additional information about increment and decrement of connectivity among brain networks not observed by the original dFNC method. The tvFNC shows more sensitivity than regular dFNC by uncovering additional FNC differences between the HC and SZ groups in each state. In summary, the tvFNC method provides a new and enhanced approach to examine time-varying functional connectivity.

Brain functional networks identified from fMRI data can provide potential biomarkers for brain disorders. Group independent component analysis (GICA) is popular for extracting brain functional networks from multiple subjects. In GICA, different strategies exist for reconstructing subject-specific networks from the group-level networks. However, it is unknown whether these strategies have different sensitivities to group differences and abilities in distinguishing patients. Among GICA, spatio-temporal regression (STR) and spatially constrained ICA approaches such as group information guided ICA (GIG-ICA) can be used to propagate components (indicating networks) to a new subject that is not included in the original subjects. In this study, based on the same a priori network maps, we reconstructed subject-specific networks using these two methods separately from resting-state fMRI data of 151 schizophrenia patients (SZs) and 163 healthy controls (HCs). We investigated group differences in the estimated functional networks and the functional network connectivity (FNC) obtained by each method. The networks were also used as features in a cross-validated support vector machine (SVM) for classifying SZs and HCs. We selected features using different strategies to provide a comprehensive comparison between the two methods. GIG-ICA generally showed greater sensitivity in statistical analysis and better classification performance (accuracy 76.45 ± 8.9%, sensitivity 0.74 ± 0.11, specificity 0.79 ± 0.11) than STR (accuracy 67.45 ± 8.13%, sensitivity 0.65 ± 0.11, specificity 0.71 ± 0.11). Importantly, results were also consistent when applied to an independent dataset including 82 HCs and 82 SZs. Our work suggests that the functional networks estimated by GIG-ICA are more sensitive to group differences, and GIG-ICA is promising for identifying image-derived biomarkers of brain disease. Keywords: fMRI, Functional network, ICA, Classification, Schizophrenia, GIG-ICA, Spatio-temporal regression

Studies have used resting-state functional magnetic resonance imaging (rs-fMRI) to examine associations between psychopathy and brain connectivity in selected regions of interest as well as networks covering the whole-brain. One of the limitations of these approaches is that brain connectivity is modeled as a constant state through the scan duration. To address this limitation, we apply group independent component analysis (GICA) and dynamic functional network connectivity (dFNC) analysis to uncover whole-brain, time-varying functional network connectivity (FNC) states in a large forensic sample. We then examined relationships between psychopathic traits (PCL-R total scores, Factor 1 and Factor 2 scores) and FNC states obtained from dFNC analysis. FNC over the scan duration was better represented by five states rather than one state previously shown in static FNC analysis. Consistent with prior findings, psychopathy was associated with networks from paralimbic regions (amygdala and insula). In addition, whole-brain FNC identified 15 networks from nine functional domains (subcortical, auditory, sensorimotor, cerebellar, visual, salience, default mode network, executive control and attentional) related to psychopathy traits (Factor 1 and PCL-R scores). Results also showed that individuals with higher Factor 1 scores (affective and interpersonal traits) spend more time in a state with weaker connectivity overall, and changed states less frequently compared to those with lower Factor 1 scores. On the other hand, individuals with higher Factor 2 scores (impulsive and antisocial behaviors) showed more dynamism (changes to and from different states) than those with lower scores. Keywords: Psychopathy, Resting-state fMRI, Dynamic functional network connectivity, Group independent component analysis, K-means clustering

We introduce a novel recurrent neural network (RNN) approach to account for temporal dynamics and dependencies in brain networks observed via functional magnetic resonance imaging (fMRI). Our approach directly parameterizes temporal dynamics through recurrent connections, which can be used to formulate blind source separation with a conditional (rather than marginal) independence assumption, which we call RNN-ICA. This formulation enables us to visualize the temporal dynamics of both first order (activity) and second order (directed connectivity) information in brain networks that are widely studied in a static sense, but not well-characterized dynamically. RNN-ICA predicts dynamics directly from the recurrent states of the RNN in both task and resting state fMRI. Our results show both task-related and group-differentiating directed connectivity.

In the field of neuroimaging, there is a growing interest in developing collaborative frameworks that enable researchers to address challenging questions about the human brain by leveraging data across multiple sites all over the world. Additionally, efforts are also being directed at developing algorithms that enable collaborative analysis and feature learning from multiple sites without requiring the often large data to be centrally located. In this paper, we propose two new decentralized algorithms: (1) A decentralized regression algorithm for performing a voxel-based morphometry analysis on structural magnetic resonance imaging (MRI) data and, (2) A decentralized dynamic functional network connectivity algorithm which includes decentralized group ICA and sliding-window analysis of functional MRI data. We compare results against those obtained from their pooled (or centralized) counterparts on the same data i.e., as if they are at one site. Results produced by the decentralized algorithms are similar to the pooled-case and showcase the potential of performing multi-voxel and multivariate analyses of data located at multiple sites. Such approaches enable many more collaborative and comparative analysis in the context of large-scale neuroimaging studies.

Studies featuring multimodal neuroimaging data fusion for understanding brain function and structure, or disease characterization, leverage the partial information available in each of the modalities to reveal data variations not exhibited through the independent analyses. Similar to other complex syndromes, the characteristic brain abnormalities in schizophrenia may be better understood with the help of the additional information conveyed by leveraging an advanced modeling method involving multiple modalities. In this study, we propose a novel framework to fuse feature spaces corresponding to functional magnetic resonance imaging (functional) and gray matter (structural) data from 151 schizophrenia patients and 163 healthy controls. In particular, the features for the functional and structural modalities include dynamic (i.e., time-varying) functional network connectivity (dFNC) maps and the intensities of the gray matter (GM) maps, respectively. The dFNC maps are estimated from group independent component analysis (ICA) network time-courses by first computing windowed functional correlations using a sliding window approach, and then estimating subject specific states from this windowed data using temporal ICA followed by spatio-temporal regression. For each subject, the functional data features are horizontally concatenated with the corresponding GM features to form a combined feature space that is subsequently decomposed through a symmetric multimodal fusion approach involving a combination of multiset canonical correlation analysis (mCCA) and joint ICA (jICA). Our novel combined analyses successfully linked changes in the two modalities and revealed significantly disrupted links between GM volumes and time-varying functional connectivity in schizophrenia. Consistent with prior research, we found significant group differences in GM comprising regions in the superior parietal lobule, precuneus, postcentral gyrus, medial/superior frontal gyrus, superior/middle temporal gyrus, insula and fusiform gyrus, and several significant aberrations in the inter-regional functional connectivity strength as well. Importantly, structural and dFNC measures have independently shown changes associated with schizophrenia, and in this work we begin the process of evaluating the links between the two, which could shed light on the illness beyond what we can learn from a single imaging modality. In future work, we plan to evaluate replication of the inferred structure-function relationships in independent partitions of larger multi-modal schizophrenia datasets.

As the size of functional and structural MRI datasets expands, it becomes increasingly important to establish a baseline from which diagnostic relevance may be determined, a processing strategy that efficiently prepares data for analysis, and a statistical approach that identifies important effects in a manner that is both robust and reproducible. In this paper, we introduce a multivariate analytic approach that optimizes sensitivity and reduces unnecessary testing. We demonstrate the utility of this mega-analytic approach by identifying the effects of age and gender on the resting state networks of 603 healthy adolescents and adults (mean age: 23.4 years, range: 12 to 71 years). Data were collected on the same scanner, preprocessed using an automated analysis pipeline based in SPM, and studied using group independent component analysis. Resting state networks were identified and evaluated in terms of three primary outcome measures: time course spectral power, spatial map intensity, and functional network connectivity. Results revealed robust effects of age on all three outcome measures, largely indicating decreases in network coherence and connectivity with increasing age. Gender effects were of smaller magnitude but suggested stronger intra-network connectivity in females and more inter-network connectivity in males, particularly with regard to sensorimotor networks. These findings, along with the analysis approach and statistical framework described here, provide a useful baseline for future investigations of brain networks in health and disease.

We examine the coherence in the spontaneous brain activity of sleeping children as measured by the blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) signals. The results are described in terms of resting-state networks (RSN) and their properties. More specifically, in this study we examine the effect of severe prematurity on the spatial location of the visual, temporal, motor, basal ganglia, and the default mode networks, the temporal response properties of each of these networks, and the functional connectivity between them. Our results suggest that the anatomical locations of the RSNs are well developed by 18 months of age and their spatial locations are not distinguishable between premature and term born infants at 18 months or at 36 months, with the exception of small spatial differences noted in the basal ganglia area and the visual cortex. The two major differences between term and preterm children were present at 36 but not 18 months and include: 1) increased spectral energy in the low frequency range (0.01 – 0.06 Hz) for pre-term children in the basal ganglia component, and 2) stronger connectivity between RSNs in term children. We speculate that children born very prematurely are vulnerable to injury resulting in weaker connectivity between resting state networks by 36 months of age. Further work is required to determine whether this could be a clinically useful tool to identify children at risk of developmental delay related to premature birth.

We investigated how the brain integrates motivational and attentional signals by using a neuroimaging paradigm that provided separate estimates for transient cue- and target-related signals, in addition to sustained block-related responses. Participants performed a Posner-type task in which an endogenous cue predicted target location on 70% of trials, while motivation was manipulated by varying magnitude and valence of a cash incentive linked to task performance. Our findings revealed increased detection performance (d’) as a function of incentive value. In parallel, brain signals revealed that increases in absolute incentive magnitude led to cue- and target-specific response modulations that were independent of sustained state effects across visual cortex, fronto-parietal regions, and subcortical regions. Interestingly, state-like effects of incentive were observed in several of these brain regions, too, suggesting that both transient and sustained fMRI signals may contribute to task performance. For both cue and block periods, the effects of administering incentives were correlated with individual trait measures of reward sensitivity. Taken together, our findings support the notion that motivation improves behavioral performance in a demanding attention task by enhancing evoked responses across a distributed set of anatomical sites, many of which have been previously implicated in attentional processing. However, the effect of motivation was not simply additive as the impact of absolute incentive was greater during invalid than valid trials in several brain regions, possibly because motivation had a larger effect on reorienting than orienting attentional mechanisms at these sites.