Multi-spatial-scale dynamic interactions between functional sources reveal sex-specific changes in schizophrenia.

We introduce an extension of independent component analysis (ICA), called multiscale ICA, and design an approach to capture dynamic functional source interactions within and between multiple spatial scales. Multiscale ICA estimates functional sources at multiple spatial scales without imposing direct constraints on the size of functional sources, overcomes the limitation of using fixed anatomical locations, and eliminates the need for model-order selection in ICA analysis. We leveraged this approach to study sex-specific and sex-common connectivity patterns in schizophrenia. Results show dynamic reconfiguration and interaction within and between multi-spatial scales. Sex-specific differences occur (a) within the subcortical domain, (b) between the somatomotor and cerebellum domains, and (c) between the temporal domain and several others, including the subcortical, visual, and default mode domains. Most of the sex-specific differences belong to between-spatial-scale functional interactions and are associated with a dynamic state with strong functional interactions between the visual, somatomotor, and temporal domains and their anticorrelation patterns with the rest of the brain. We observed significant correlations between multi-spatial-scale functional interactions and symptom scores, highlighting the importance of multiscale analyses to identify potential biomarkers for schizophrenia. As such, we recommend such analyses as an important option for future functional connectivity studies.

Dissemination in time and space in presymptomatic granulin mutation carriers: a GENFI spatial chronnectome study.

The presymptomatic brain changes of granulin (GRN) disease, preceding by years frontotemporal dementia, has not been fully characterized. New approaches focus on the spatial chronnectome can capture both spatial network configurations and their dynamic changes over time. To investigate the spatial dynamics in 141 presymptomatic GRN mutation carriers and 282 noncarriers from the Genetic Frontotemporal dementia research Initiative cohort. We considered time-varying patterns of the default mode network, the language network, and the salience network, each summarized into 4 distinct recurring spatial configurations. Dwell time (DT) (the time each individual spends in each spatial state of each network), fractional occupacy (FO) (the total percentage of time spent by each individual in a state of a specific network) and total transition number (the total number of transitions performed by each individual in a specifict state) were considered. Correlations between DT, FO, and transition number and estimated years from expected symptom onset (EYO) and clinical performances were assessed. Presymptomatic GRN mutation carriers spent significantly more time in those spatial states characterised by greater activation of the insula and the parietal cortices, as compared to noncarriers (p < 0.05, FDR-corrected). A significant correlation between DT and FO of these spatial states and EYO was found, the longer the time spent in the spatial states, the closer the EYO. DT and FO significantly correlated with performances at tests tapping processing speed, with worse scores associated with increased spatial states' DT. Our results demonstrated that presymptomatic GRN disease presents a complex dynamic reorganization of brain connectivity. Change in both the spatial and temporal aspects of brain network connectivity could provide a unique glimpse into brain function and potentially allowing a more sophisticated evaluation of the earliest disease changes and the understanding of possible mechanisms in GRN disease.

Tools of the trade: estimating time-varying connectivity patterns from fMRI data.

Given the dynamic nature of the brain, there has always been a motivation to move beyond 'static' functional connectivity, which characterizes functional interactions over an extended period of time. Progress in data acquisition and advances in analytical neuroimaging methods now allow us to assess the whole brain's dynamic functional connectivity (dFC) and its network-based analog, dynamic functional network connectivity at the macroscale (mm) using fMRI. This has resulted in the rapid growth of analytical approaches, some of which are very complex, requiring technical expertise that could daunt researchers and neuroscientists. Meanwhile, making real progress toward understanding the association between brain dynamism and brain disorders can only be achieved through research conducted by domain experts, such as neuroscientists and psychiatrists. This article aims to provide a gentle introduction to the application of dFC. We first explain what dFC is and the circumstances under which it can be used. Next, we review two major categories of analytical approaches to capture dFC. We discuss caveats and considerations in dFC analysis. Finally, we walk readers through an openly accessible toolbox to capture dFC properties and briefly review some of the dynamic metrics calculated using this toolbox.

Discriminating VCID subgroups: A diffusion MRI multi-model fusion approach.

BACKGROUND: Vascular cognitive impairment and dementia (VCID) and Alzheimer's disease are predominant diseases among the aging population resulting in decline of various cognitive domains. Diffusion weighted MRI (DW-MRI) has been shown to be a promising aid in the diagnosis of such diseases. However, there are various models of DW-MRI and the interpretation of diffusion metrics depends on the model used in fitting data. Most previous studies are entirely based on parameters calculated from a single diffusion model. NEW METHOD: We employ a data fusion framework wherein diffusion metrics from different models such as diffusion tensor imaging, diffusion kurtosis imaging and constrained spherical deconvolution model are fused using well known blind source separation approach to investigate white matter microstructural changes in population comprising of controls and VCID subgroups. Multiple comparisons between subject groups and prediction analysis using features from individual models and proposed fusion model are carried out to evaluate performance of proposed method. RESULTS: Diffusion features from individual models successfully distinguished between controls and disease groups, but failed to differentiate between disease groups, whereas fusion approach showed group differences between disease groups too. WM tracts showing significant differences are superior longitudinal fasciculus, anterior thalamic radiation, arcuate fasciculus, optic radiation and corticospinal tract. COMPARISON WITH EXISTING METHOD: ROC analysis showed increased AUC for fusion (AUC = 0.913, averaged across groups and tracts) compared to that of uni-model features (AUC = 0.77) demonstrating increased sensitivity of proposed method. CONCLUSION: Overall our results highlight the benefits of multi-model fusion approach, providing improved sensitivity in discriminating VCID subgroups.

N-BiC: A Method for Multi-Component and Symptom Biclustering of Structural MRI Data: Application to Schizophrenia.

OBJECTIVE: We propose and develop a novel biclustering (N-BiC) approach for performing N-way biclustering of neuroimaging data. Our approach is applicable to an arbitrary number of features from both imaging and behavioral data (e.g., symptoms). We applied it to structural MRI data from patients with schizophrenia. METHODS: It uses a source-based morphometry approach [i.e., independent component analysis of gray matter segmentation maps] to decompose the data into a set of spatial maps, each of which includes regions that covary among individuals. Then, the loading parameters for components of interest are entered to an exhaustive search, which incorporates a modified depth-first search technique to carry out the biclustering, with the goal of obtaining submatrices where the selected rows (individuals) show homogeneity in their expressions of selected columns (components) and vice versa. RESULTS: Findings demonstrate that multiple biclusters have an evident association with distinct brain networks for the different types of symptoms in schizophrenia. The study identifies two components: inferior temporal gyrus (16) and brainstem (7), which are related to positive (distortion/excess of normal function) and negative (diminution/loss of normal function) symptoms in schizophrenia, respectively. CONCLUSION: N-BiC is a data-driven method of biclustering MRI data that can exhaustively explore relationships/substructures from a dataset without any prior information with a higher degree of robustness than earlier biclustering applications. SIGNIFICANCE: The use of such approaches is important to investigate the underlying biological substrates of mental illness by grouping patients into homogeneous subjects, as the schizophrenia diagnosis is known to be relatively nonspecific and heterogeneous.

Resting-state fMRI dynamic functional network connectivity and associations with psychopathy traits.

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.

Novel in silico multivariate mapping of intrinsic and anticorrelated connectivity to neurocognitive functional maps supports the maturational hypothesis of ADHD.

From childhood to adolescence, strengthened coupling in frontal, striatal and parieto-temporal regions associated with cognitive control, and increased anticorrelation between task-positive and task-negative circuits, subserve the reshaping of behavior. ADHD is a common condition peaking in adolescence and regressing in adulthood, with a wide variety of cognitive control deficits. Alternate hypotheses of ADHD emphasize lagging circuitry refinement versus categorical differences in network function. However, quantifying the individual circuit contributions to behavioral findings, and relative roles of maturational versus categorical effects, is challenging in vivo or in meta-analyses using task-based paradigms within the same pipeline, given the multiplicity of neurobehavioral functions implicated. To address this, we analyzed 46 positively-correlated and anticorrelated circuits in a multivariate model in resting-state data from 504 age- and gender-matched youth, and created a novel in silico method to map individual quantified effects to reverse inference maps of 8 neurocognitive functions consistently implicated in ADHD, as well as dopamine and hyperactivity. We identified only age- and gender-related effects in intrinsic connectivity, and found that maturational refinement of circuits in youth with ADHD occupied 3-10x more brain locations than in typical development, with the footprint, effect size and contribution of individual circuits varying substantially. Our analysis supports the maturational hypothesis of ADHD, suggesting lagging connectivity reorganization within specific subnetworks of fronto-parietal control, ventral attention, cingulo-opercular, temporo-limbic and cerebellar sub-networks contribute across neurocognitive findings present in this complex condition. We present the first analysis of anti-correlated connectivity in ADHD and suggest new directions for exploring residual and non-responsive symptoms.

Aberrant functional network connectivity in psychopathy from a large (N = 985) forensic sample.

Psychopathy is a personality disorder characterized by antisocial behavior, lack of remorse and empathy, and impaired decision making. The disproportionate amount of crime committed by psychopaths has severe emotional and economic impacts on society. Here we examine the neural correlates associated with psychopathy to improve early assessment and perhaps inform treatments for this condition. Previous resting-state functional magnetic resonance imaging (fMRI) studies in psychopathy have primarily focused on regions of interest. This study examines whole-brain functional connectivity and its association to psychopathic traits. Psychopathy was hypothesized to be characterized by aberrant functional network connectivity (FNC) in several limbic/paralimbic networks. Group-independent component and regression analyses were applied to a data set of resting-state fMRI from 985 incarcerated adult males. We identified resting-state networks (RSNs), estimated FNC between RSNs, and tested their association to psychopathy factors and total summary scores (Factor 1, interpersonal/affective; Factor 2, lifestyle/antisocial). Factor 1 scores showed both increased and reduced functional connectivity between RSNs from seven brain domains (sensorimotor, cerebellar, visual, salience, default mode, executive control, and attentional). Consistent with hypotheses, RSNs from the paralimbic system-insula, anterior and posterior cingulate cortex, amygdala, orbital frontal cortex, and superior temporal gyrus-were related to Factor 1 scores. No significant FNC associations were found with Factor 2 and total PCL-R scores. In summary, results suggest that the affective and interpersonal symptoms of psychopathy (Factor 1) are associated with aberrant connectivity in multiple brain networks, including paralimbic regions.

Functional brain connectivity in resting-state fMRI using phase and magnitude data.

BACKGROUND: The output of BOLD fMRI consists of a pair of magnitude and phase components. While the magnitude data has been widely accepted for brain function analysis, we can also make use of the phase data (unwrapped) since this is a good representation of the internal magnetic field. In this work, we discuss the use of fMRI phase data for brain function analysis. NEW METHODS: The fMRI phase data taken from 100 subjects are preprocessed using standard SPM approaches. Group independent component analysis (ICA) is applied to the magnitude and phase data separately. We then compare the spatial patterns for both magnitude and phase data using an empirical spatial smoothing procedure. We also evaluate the magnitude and phase functional network connectivity (FC) matrices. RESULTS: We observed the positive/negative correlation-balanced functional connectivity in phase data, which is distinct from the positive correlation prevalence in magnitude data. The phase FC (pFC) structure is quite different from the magnitude FC (mFC) in functional clusters (on-diagonal blocks or cliques) and inter-cluster couplings (off-diagonal blocks). COMPARISON WITH EXISTING: Methods since both the magnitude and phase data of the fMRI signals are generated from the same magnetic source, either can be useful for brain function analysis from different perspective (per different measurements). Herein, we report on making use of resting-state fMRI phase data for brain functional analysis in comparison with magnitude data. This exploration in phase fMRI may provide a new arena for more comprehensive brain function analysis.

Default mode network deactivation to smoking cue relative to food cue predicts treatment outcome in nicotine use disorder.

Identifying predictors of treatment outcome for nicotine use disorders (NUDs) may help improve efficacy of established treatments, like varenicline. Brain reactivity to drug stimuli predicts relapse risk in nicotine and other substance use disorders in some studies. Activity in the default mode network (DMN) is affected by drug cues and other palatable cues, but its clinical significance is unclear. In this study, 143 individuals with NUD (male n = 91, ages 18-55 years) received a functional magnetic resonance imaging scan during a visual cue task during which they were presented with a series of smoking-related or food-related video clips prior to randomization to treatment with varenicline (n = 80) or placebo. Group independent components analysis was utilized to isolate the DMN, and temporal sorting was used to calculate the difference between the DMN blood-oxygen-level dependent signal during smoke cues and that during food cues for each individual. Food cues were associated with greater deactivation compared with smoke cues in the DMN. In correcting for baseline smoking and other clinical variables, which have been shown to be related to treatment outcome in previous work, a less positive Smoke - Food difference score predicted greater smoking at 6 and 12 weeks when both treatment groups were combined (P = 0.005, ß = -0.766). An exploratory analysis of executive control and salience networks demonstrated that a more positive Smoke - Food difference score for executive control network predicted a more robust response to varenicline relative to placebo. These findings provide further support to theories that brain reactivity to palatable cues, and in particular in DMN, may have a direct clinical relevance in NUD.

Spatiospectral Decomposition of Multi-subject EEG: Evaluating Blind Source Separation Algorithms on Real and Realistic Simulated Data.

Electroencephalographic (EEG) oscillations predominantly appear with periods between 1 s (1 Hz) and 20 ms (50 Hz), and are subdivided into distinct frequency bands which appear to correspond to distinct cognitive processes. A variety of blind source separation (BSS) approaches have been developed and implemented within the past few decades, providing an improved isolation of these distinct processes. Within the present study, we demonstrate the feasibility of multi-subject BSS for deriving distinct EEG spatiospectral maps. Multi-subject spatiospectral EEG decompositions were implemented using the EEGIFT toolbox ( http://mialab.mrn.org/software/eegift/ ) with real and realistic simulated datasets (the simulation code is available at http://mialab.mrn.org/software/simeeg ). Twelve different decomposition algorithms were evaluated. Within the simulated data, WASOBI and COMBI appeared to be the best performing algorithms, as they decomposed the four sources across a range of component numbers and noise levels. RADICAL ICA, ERBM, INFOMAX ICA, ICA EBM, FAST ICA, and JADE OPAC decomposed a subset of sources within a smaller range of component numbers and noise levels. INFOMAX ICA, FAST ICA, WASOBI, and COMBI generated the largest number of stable sources within the real dataset and provided partially distinct views of underlying spatiospectral maps. We recommend the multi-subject BSS approach and the selected algorithms for further studies examining distinct spatiospectral networks within healthy and clinical populations.

Schizophrenia Shows Disrupted Links between Brain Volume and Dynamic Functional Connectivity.

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.

Multimodal neural correlates of cognitive control in the Human Connectome Project.

Cognitive control is a construct that refers to the set of functions that enable decision-making and task performance through the representation of task states, goals, and rules. The neural correlates of cognitive control have been studied in humans using a wide variety of neuroimaging modalities, including structural MRI, resting-state fMRI, and task-based fMRI. The results from each of these modalities independently have implicated the involvement of a number of brain regions in cognitive control, including dorsal prefrontal cortex, and frontal parietal and cingulo-opercular brain networks. However, it is not clear how the results from a single modality relate to results in other modalities. Recent developments in multimodal image analysis methods provide an avenue for answering such questions and could yield more integrated models of the neural correlates of cognitive control. In this study, we used multiset canonical correlation analysis with joint independent component analysis (mCCA + jICA) to identify multimodal patterns of variation related to cognitive control. We used two independent cohorts of participants from the Human Connectome Project, each of which had data from four imaging modalities. We replicated the findings from the first cohort in the second cohort using both independent and predictive analyses. The independent analyses identified a component in each cohort that was highly similar to the other and significantly correlated with cognitive control performance. The replication by prediction analyses identified two independent components that were significantly correlated with cognitive control performance in the first cohort and significantly predictive of performance in the second cohort. These components identified positive relationships across the modalities in neural regions related to both dynamic and stable aspects of task control, including regions in both the frontal-parietal and cingulo-opercular networks, as well as regions hypothesized to be modulated by cognitive control signaling, such as visual cortex. Taken together, these results illustrate the potential utility of multi-modal analyses in identifying the neural correlates of cognitive control across different indicators of brain structure and function.

Comparison of IVA and GIG-ICA in Brain Functional Network Estimation Using fMRI Data.

Spatial group independent component analysis (GICA) methods decompose multiple-subject functional magnetic resonance imaging (fMRI) data into a linear mixture of spatially independent components (ICs), some of which are subsequently characterized as brain functional networks. Group information guided independent component analysis (GIG-ICA) as a variant of GICA has been proposed to improve the accuracy of the subject-specific ICs estimation by optimizing their independence. Independent vector analysis (IVA) is another method which optimizes the independence among each subject's components and the dependence among corresponding components of different subjects. Both methods are promising in neuroimaging study and showed a better performance than the traditional GICA. However, the difference between IVA and GIG-ICA has not been well studied. A detailed comparison between them is demanded to provide guidance for functional network analyses. In this work, we employed multiple simulations to evaluate the performances of the two approaches in estimating subject-specific components and time courses under conditions of different data quality and quantity, varied number of sources generated and inaccurate number of components used in computation, as well as the presence of spatially subject-unique sources. We also compared the two methods using healthy subjects' test-retest resting-state fMRI data in terms of spatial functional networks and functional network connectivity (FNC). Results from simulations support that GIG-ICA showed better recovery accuracy of both components and time courses than IVA for those subject-common sources, and IVA outperformed GIG-ICA in component and time course estimation for the subject-unique sources. Results from real fMRI data suggest that GIG-ICA resulted in more reliable spatial functional networks and yielded higher and more robust modularity property of FNC, compared to IVA. Taken together, GIG-ICA is appropriate for estimating networks which are consistent across subjects, while IVA is able to estimate networks with great inter-subject variability or subject-unique property.

Functional network connectivity predicts treatment outcome during treatment of nicotine use disorder.

Altered resting state functional connectivity (rsFC) and functional network connectivity (FNC), which is a measure of coherence between brain networks, may be associated with nicotine use disorder (NUD). We hypothesized that higher connectivity between insula and 1) dorsal anterior cingulate cortex (dACC) and 2) dorsolateral prefrontal cortex (dlPFC) would predict better treatment outcomes. We also performed an exploratory analysis of the associations between FNC values between additional key frontal and striatal regions and treatment outcomes. One hundred and forty four individuals with NUD underwent a resting state session during functional MRI prior to randomization to treatment with varenicline (n=82) or placebo. Group independent component analysis (ICA) was utilized to extract individual subject components and time series from intrinsic connectivity networks in aforementioned regions, and FNC between all possible pairs were calculated. Higher FNC between insula and dACC (rho=0.21) was significantly correlated with lower levels of baseline smoking quantity but did not predict treatment outcome upon controlling for baseline smoking. Higher FNC between putamen and dACC, caudate and dACC, and caudate and dlPFC significantly predicted worse treatment outcome in participants reporting high subjective withdrawal before the scan. FNC between key regions hold promise as biomarkers to predict outcome in NUD.

Resting-State Networks as Simultaneously Measured with Functional MRI and PET.

Functional MRI (fMRI) studies reported disruption of resting-state networks (RSNs) in several neuropsychiatric disorders. PET with 18F-FDG captures neuronal activity that is in steady state at a longer time span and is less dependent on neurovascular coupling. Methods: In the present study, we aimed to identify RSNs in 18F-FDG PET data and compare their spatial pattern with those obtained from simultaneously acquired resting-state fMRI data in 22 middle-aged healthy subjects. Results: Thirteen and 17 meaningful RSNs could be identified in PET and fMRI data, respectively. Spatial overlap was fair to moderate for the default mode, left central executive, primary and secondary visual, sensorimotor, cerebellar, and auditory networks. Despite recording different aspects of neural activity, similar RSNs were detected by both imaging modalities. Conclusion: The results argue for the common neural substrate of RSNs and encourage testing of the clinical utility of resting-state connectivity in PET data.

Chronnectomic patterns and neural flexibility underlie executive function.

Despite extensive research into executive function (EF), the precise relationship between brain dynamics and flexible cognition remains unknown. Using a large, publicly available dataset (189 participants), we find that functional connections measured throughout 56min of resting state fMRI data comprise five distinct connectivity states. Elevated EF performance as measured outside of the scanner was associated with greater episodes of more frequently occurring connectivity states, and fewer episodes of less frequently occurring connectivity states. Frequently occurring states displayed metastable properties, where cognitive flexibility may be facilitated by attenuated correlations and greater functional connection variability. Less frequently occurring states displayed properties consistent with low arousal and low vigilance. These findings suggest that elevated EF performance may be associated with the propensity to occupy more frequently occurring brain configurations that enable cognitive flexibility, while avoiding less frequently occurring brain configurations related to low arousal/vigilance states. The current findings offer a novel framework for identifying neural processes related to individual differences in executive function.

Memory Efficient PCA Methods for Large Group ICA.

Principal component analysis (PCA) is widely used for data reduction in group independent component analysis (ICA) of fMRI data. Commonly, group-level PCA of temporally concatenated datasets is computed prior to ICA of the group principal components. This work focuses on reducing very high dimensional temporally concatenated datasets into its group PCA space. Existing randomized PCA methods can determine the PCA subspace with minimal memory requirements and, thus, are ideal for solving large PCA problems. Since the number of dataloads is not typically optimized, we extend one of these methods to compute PCA of very large datasets with a minimal number of dataloads. This method is coined multi power iteration (MPOWIT). The key idea behind MPOWIT is to estimate a subspace larger than the desired one, while checking for convergence of only the smaller subset of interest. The number of iterations is reduced considerably (as well as the number of dataloads), accelerating convergence without loss of accuracy. More importantly, in the proposed implementation of MPOWIT, the memory required for successful recovery of the group principal components becomes independent of the number of subjects analyzed. Highly efficient subsampled eigenvalue decomposition techniques are also introduced, furnishing excellent PCA subspace approximations that can be used for intelligent initialization of randomized methods such as MPOWIT. Together, these developments enable efficient estimation of accurate principal components, as we illustrate by solving a 1600-subject group-level PCA of fMRI with standard acquisition parameters, on a regular desktop computer with only 4 GB RAM, in just a few hours. MPOWIT is also highly scalable and could realistically solve group-level PCA of fMRI on thousands of subjects, or more, using standard hardware, limited only by time, not memory. Also, the MPOWIT algorithm is highly parallelizable, which would enable fast, distributed implementations ideal for big data analysis. Implications to other methods such as expectation maximization PCA (EM PCA) are also presented. Based on our results, general recommendations for efficient application of PCA methods are given according to problem size and available computational resources. MPOWIT and all other methods discussed here are implemented and readily available in the open source GIFT software.

Dynamic functional network connectivity reveals unique and overlapping profiles of insula subdivisions.

The human insular cortex consists of functionally diverse subdivisions that engage during tasks ranging from interoception to cognitive control. The multiplicity of functions subserved by insular subdivisions calls for a nuanced investigation of their functional connectivity profiles. Four insula subdivisions (dorsal anterior, dAI; ventral, VI; posterior, PI; middle, MI) derived using a data-driven approach were subjected to static- and dynamic functional network connectivity (s-FNC and d-FNC) analyses. Static-FNC analyses replicated previous work demonstrating a cognition-emotion-interoception division of the insula, where the dAI is functionally connected to frontal areas, the VI to limbic areas, and the PI and MI to sensorimotor areas. Dynamic-FNC analyses consisted of k-means clustering of sliding windows to identify variable insula connectivity states. The d-FNC analysis revealed that the most frequently occurring dynamic state mirrored the cognition-emotion-interoception division observed from the s-FNC analysis, with less frequently occurring states showing overlapping and unique subdivision connectivity profiles. In two of the states, all subdivisions exhibited largely overlapping profiles, consisting of subcortical, sensory, motor, and frontal connections. Two other states showed the dAI exhibited a unique connectivity profile compared with other insula subdivisions. Additionally, the dAI exhibited the most variable functional connections across the s-FNC and d-FNC analyses, and was the only subdivision to exhibit dynamic functional connections with regions of the default mode network. These results highlight how a d-FNC approach can capture functional dynamics masked by s-FNC approaches, and reveal dynamic functional connections enabling the functional flexibility of the insula across time. Hum Brain Mapp 37:1770-1787, 2016. © 2016 Wiley Periodicals, Inc.