Biology subjects

Calhoun, V. D.

Publications and source records attributed to Calhoun, V. D..

10 recordsLinked to original sources

bioRxiv2018

Dynamic Functional Network Connectivity In Schizophrenia With MEG And fMRI, Do Different Time Scales Tell A Different Story?

The importance of how brain networks function together to create brain states has become increasingly recognized. Therefore, an investigation of eyes-open resting state dynamic functional network connectivity (dFNC) of healthy controls (HC) versus that of schizophrenia patients (SP) via both fMRI and a novel MEG pipeline was completed. The fMRI analysis used a spatial independent component analysis (ICA) to determine the networks on which the dFNC was based. The MEG analysis utilized a source-space activity estimate (MNE/dSPM) whose result was the input to a spatial ICA, on which the networks of the MEG dFNC was based. We found that dFNC measures reveal significant differences between HC and SP, which depended upon the imaging modality. Consistent with previous findings, a dFNC analysis predicated on fMRI data revealed HC and SP remain in different overall brain states (defined by a k-means clustering of network correlations) for significantly different periods of time, with SP spending less time in a highly-connected state. The MEG dFNC, in contrast, revealed group differences in more global statistics: SP changed between meta-states (k-means cluster states that are allowed to overlap in time) significantly more often and to states which were more different, relative to HC. MEG dFNC also revealed a highly connected state where a significant difference was observed in inter-individual variability, with greater variability among SP. Overall, our results show that fMRI and MEG reveal between-group functional connectivity differences in distinct ways, highlighting the utility of using each of the modalities individually, or potentially a combination of modalities, to better inform our understanding of disorders such as schizophrenia.

neuroscience↗

bioRxiv2018

Relationship between MEG global dynamic functional network connectivity measures and symptoms in schizophrenia

An investigation of differences in dynamic functional network connectivity (dFNC) of healthy controls (HC) versus that of schizophrenia patients (SP) was completed, using eyes-open resting state MEG data. The MEG analysis utilized a source-space activity estimate (MNE/dSPM) whose result was the input to a group spatial independent component analysis (ICA), on which the networks of our MEG dFNC analysis were based. We have previously reported that our MEG dFNC revealed that SP change between cognitive meta-states (repeating patterns of network correlations which are allowed to overlap in time) significantly more often and to states which are more different, relative to HC. Here, we extend our previous work to investigate the relationship between symptomology in SP and four meta-state metrics. We found a significant correlation between positive symptoms and the two meta-state statistics which showed significant differences between HC and SP. These two statistics quantified 1) how often individuals change state and 2) the total distance traveled within the state-space. We additionally found that a clustering of the meta-state metrics divides SP into groups which vary in symptomology. These results indicate specific relationships between symptomology and brain function for SP.

neuroscience↗

bioRxiv2018

Group ICA for Identifying Biomarkers in Schizophrenia: ‘Adaptive’ Networks via Spatially Constrained ICA Show More Sensitivity to Group Differences than Spatio-temporal Regression

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.

neuroscience↗

bioRxiv2018

Spatial dynamics of brain functional domains: A new avenue to study time-varying brain function

The analysis of time-varying activity and connectivity patterns (i.e., the chronnectome) using resting-state magnetic resonance imaging has become an important part of ongoing neuroscience discussions. The majority of previous work has focused on variations of temporal coupling among fixed spatial nodes or transition of the dominant activity/connectivity pattern over time. Here, we introduce an approach to capture spatial dynamics within functional domains (FD), as well as temporal dynamics within and between FD. The approach models the brain as a hierarchical functional architecture with different levels of granularity, where lower levels have higher functional homogeneity and less dynamic behavior and higher levels have less homogeneity and more dynamic behavior. First, a high-order spatial independent component analysis is used to approximate functional units. A functional unit is a pattern of regions with very similar functional activity over time. Next, functional units are used to construct FDs. Finally, functional modules (FMs) are calculated from FDs, providing an overall view of brain dynamics. Results highlight the spatial fluidity within FDs, including a broad spectrum of changes in regional associations from strong coupling to complete decoupling. Moreover, FMs capture the dynamic interplay between FDs. Patients with schizophrenia show transient reductions in functional activity and state connectivity across several FDs, particularly the subcortical domain. Activity and connectivity differences convey unique information in many cases (e.g. the default mode) highlighting their complementarity information. The proposed hierarchical model to capture FD spatiotemporal variation provides new insight into the macroscale chronnectome and identifies changes hidden from existing approaches.

neuroscience↗

bioRxiv2018

Transdiagnostic multimodal neuroimaging in psychosis: structural, resting-state, and task MRI correlates of cognitive control

BackgroundPsychotic disorders, including schizophrenia and bipolar disorder, are associated with impairments in regulation of goal-directed behavior, termed cognitive control. Cognitive control related neural alterations have been studied in psychosis. However, studies are typically unimodal and relationships across modalities of brain function and structure remain unclear. Thus, we performed transdiagnostic multimodal analyses to examine cognitive control related neural variation in psychosis.\n\nMethodsStructural, resting, and working memory task imaging and behavioral data for 31 controls, 27 bipolar, and 23 schizophrenia patients were collected and processed identically to the Human Connectome Project (HCP), enabling identification of relationships with prior multimodal work. Two cognitive control related independent components (ICs) derived from the HCP using multiset canonical correlation analysis + joint independent component analysis (mCCA+jICA) were used to predict performance in psychosis. de novo mCCA+jICA was performed, and resultant IC weights were correlated with cognitive control.\n\nResultsA priori ICs significantly predicted cognitive control in psychosis (3/5 modalities significant). De novo mCCA+jICA identified an IC correlated with cognitive control that also discriminated groups. Structural contributions included insular, somatomotor, cingulate, and visual regions; task contributions included precentral, posterior parietal, cingulate, and visual regions; and resting-state contributions highlighted canonical network organization. Follow-up analyses suggested de novo correlations with cognitive control were primarily influenced by schizophrenia patients.\n\nConclusionsA priori components partially predicted performance in transdiagnostic psychosis and de novo analyses identified novel contributions in somatomotor and visual regions in schizophrenia. Together, results suggest joint contributions across modalities related to cognitive control across the healthy-to-psychosis spectrum.

neuroscience↗

bioRxiv2017

Replicability of time-varying connectivity patterns in large resting state fMRI samples

The past few years have seen an emergence of approaches that leverage temporal changes in whole-brain patterns of functional connectivity (the chronnectome). In this chronnectome study, we investigate the replicability of the human brain's inter-regional coupling dynamics during rest by evaluating two different dynamic functional network connectivity (dFNC) analysis frameworks using 7500 functional magnetic resonance imaging (fMRI) datasets. To quantify the extent to which the emergent functional connectivity (FC) patterns are reproducible, we characterize the temporal dynamics by deriving several summary measures across multiple large, independent age-matched samples. Reproducibility was demonstrated through the existence of basic connectivity patterns (FC states) amidst an ensemble of inter-regional connections. Furthermore, application of the methods to conservatively configured surrogate datasets establishes that the correlation structures in the data do not arise by chance. This extensive testing of reproducibility of similarity statistics also suggests that the estimated FC states are robust against variation in data quality, analysis, grouping, and decomposition methods. We conclude that future investigations probing the functional and neurophysiological relevance of time-varying connectivity assume critical importance.

neuroscience↗

bioRxiv2017

Resting-State fMRI Dynamics and Null Models: Perspectives, Sampling Variability, and Simulations

Studies of resting state functional MRI (rs-fRMI) are increasingly focused on \"dynamics\", or on those properties of brain activation that manifest and vary on timescales shorter than the scans full duration. This shift in focus has led to a flurry of interest in developing hypothesis testing frameworks and null models applicable to the dynamical setting. Thus far however, these efforts have been weakened by a number of crucial shortcomings that are outlined and discussed in this short paper. We focus here on aspects of recently proposed null models that, we argue, are poorly formulated relative to the hypotheses they are designed to test, i.e. their potential role in separating functionally relevant BOLD signal dynamics from noise or intermittent background and maintenance type processes is limited by factors that are fundamental rather than merely quantitative or parametric. In this short position paper, we emphasize that (1) serious care must be exercised in building null models for rs-fMRI dynamics from distributionally stationary univariate or multivariate timeseries, i.e. timeseries whose values are each independently drawn from one pre-specified probability distribution; and (2) measures such as kurtosis that quantify over-concentration of observed values in the far tails of some reference distribution may not be particularly suitable for capturing signal features most plausibly contributing to functionally relevant brain dynamics. Other metrics targeted, for example, at capturing the epochal temporal variation that contributes heavily to dynamic functional connectivity estimates and is and often taken as a signature of brain responsiveness to stimuli or experimental tasks, could play a more scientifically clarifying role. As we learn more about the phenomenon of functionally relevant brain dynamics and its imaging correlates, scientifically meaningful null hypotheses and well-tuned null models will naturally emerge. We also revisit the important concept of distributional stationarity, discuss how it manifests within realizations versus across multiple realizations, and provide guidance on the benefits and limitations of employing this type of stationarity in modeling the absence or functionally relevant temporal dynamics in resting state fMRI. We hope that the discussions herein are useful, and promote thoughtful consideration of these important issues.

neuroscience↗

bioRxiv2017

Salience network dynamics underlying successful resistance of temptation

Self-control and the ability to resist temptation are critical for successful completion of long-term goals. Contemporary models in cognitive neuroscience emphasize the primary role of prefrontal cognitive control networks in aligning behavior with such goals. Here we use gaze pattern analysis and dynamic functional connectivity fMRI data to explore how individual differences in the ability to resist temptation are related to intrinsic brain dynamics of the cognitive control and salience networks. Behaviorally, individuals exhibit greater gaze distance from target location (e.g. higher distractibility) during presentation of tempting erotic images compared with neutral images. Individuals whose intrinsic dynamic functional connectivity patterns gravitate towards configurations in which salience detection systems are less strongly coupled with visual systems resist tempting distractors more effectively. The ability to resist tempting distractors was not significantly related to intrinsic dynamics of the cognitive control network. These results suggest that susceptibility to temptation is governed in part by individual differences in salience network dynamics, and provide novel evidence for involvement of brain systems outside canonical cognitive control networks in contributing to individual differences in self-control.

neuroscience↗

bioRxiv2017

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 decisionmaking 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.

neuroscience↗

bioRxiv2017

Mindfulness and dynamic functional neural connectivity in children and adolescents

BackgroundMindfulness is a non-judgmental, present-centered awareness and acceptance of ones thoughts, feelings, and bodily sensations. Interventions that promote mindfulness consistently show salutatory effects on cognition and psychological wellbeing in adults, and more recently, in children. Understanding the neurobiological mechanisms underlying mindfulness in children may allow for more judicious application of these techniques in clinical and educational settings.\n\nMethodsUsing multi-echo/multi-band fMRI, we measured resting-state connectivity and tested the hypothesis that the association between mindfulness and anxiety in children (N=42) will relate to static and dynamic interactions between large-scale neural networks considered central to neurocognitive functioning and implicated in mindfulness in adults (default mode [DMN], salience and emotion [SEN], and central executive networks [CEN]).\n\nResultsMindfulness was related to dynamic but not static connectivity in children. Specifically, more mindful children transitioned more between brain states over the course of the scan, spent overall less time in a certain connectivity state (state 2), and showed a state-specific reduction in SEN-right CEN connectivity (state 4). Results of a separate measure of present-focused thought during the resting-state were consistent with these results, suggesting state-trait convergence. Finally, the number of state transitions mediated the link between higher mindfulness and lower anxiety, suggesting that flexibility in transitioning between neural states may bridge the well-established link between mindfulness and anxiety in children.\n\nConclusionsResults provide new insights into neural mechanisms underlying benefits of mindfulness on psychological health in children, and suggest that mindfulness relates to functional neural dynamics and interactions between neurocognitive networks, over time.

neuroscience↗