Creative tempo: Spatiotemporal dynamics of the default mode network in improvisational musicians.

The intrinsic dynamics of human brain activity display a recurring pattern of anti-correlated activity between the default mode network (DMN), associated with internal processing and mentation, and task positive regions, associated with externally directed attention. In human functional magnetic resonance imaging (fMRI) data, this anti-correlated pattern is detectable on the infraslow timescale (<0.1 Hz) as a quasi-periodic pattern (QPP). While the DMN is implicated in creativity and musicality in traditional time-averaged functional connectivity studies, no one has yet explored how creative training may alter dynamic spatiotemporal patterns involving the DMN such as QPPs. In the present study, we compare the outputs of two QPP detection approaches, sliding window algorithm and complex principal components analysis (cPCA). We apply both methods to an existing dataset of musicians captured with resting state fMRI, grouped as either classical, improvisational, or minimally trained non-musicians. The original time-averaged functional connectivity (FC) analysis of this dataset used improvisation as a proxy for creative thinking and found that the DMN and visual networks (VIS) display higher connectivity in improvisational musicians. We expand upon this dataset's original study and find that QPP analysis detects convergent results at the group level with both methods. In improvisational musicians, dynamic functional correlation in the group-averaged QPP was found to be increased between the DMN-VIS and DMN-FPN for both the QPP algorithm and complex principal components analysis (cPCA) methods. Additionally, we found an unexpected increase in FC in the group-averaged QPP between the dorsal attention network and amygdala in improvisational musicians; this result was not reported in the original seed-based study of this dataset. The current study represents a novel application of two dynamic FC detection methods with results that replicate and expand upon previous seed-based FC findings. The results show the robustness of both the QPP phenomenon and its detection methods. This study also demonstrates the value of dynamic FC methods in reproducing seed-based findings and their promise in detecting group-wise or individual differences that may be missed by traditional seed-based resting state fMRI studies.

Brain signal variability and executive functions across the life span.

Neural variability is thought to facilitate survival through flexible adaptation to changing environmental demands. In humans, such capacity for flexible adaptation may manifest as fluid reasoning, inhibition of automatic responses, and mental set-switching-skills falling under the broad domain of executive functions that fluctuate over the life span. Neural variability can be quantified via the BOLD signal in resting-state fMRI. Variability of large-scale brain networks is posited to underpin complex cognitive activities requiring interactions between multiple brain regions. Few studies have examined the extent to which network-level brain signal variability across the life span maps onto high-level processes under the umbrella of executive functions. The present study leveraged a large publicly available neuroimaging dataset to investigate the relationship between signal variability and executive functions across the life span. Associations between brain signal variability and executive functions shifted as a function of age. Limbic-specific variability was consistently associated with greater performance across subcomponents of executive functions. Associations between executive function subcomponents and network-level variability of the default mode and central executive networks, as well as whole-brain variability, varied across the life span. Findings suggest that brain signal variability may help to explain to age-related differences in executive functions across the life span.

Traditionally, regional variability in brain signals has been viewed as a source of noise in human neuroimaging research. Our study demonstrates that brain signal variability may contain meaningful information related to psychological processes. We demonstrate that brain signal variability, particularly whole-brain variability, may serve as a reliable indicator of cognitive functions across the life span. Global variability and network-level variability play differing roles in supporting executive functions. Findings suggest that brain signal variability serves as a meaningful indicator of development and cognitive aging.

A parsimonious description of global functional brain organization in three spatiotemporal patterns.

Resting-state functional magnetic resonance imaging (MRI) has yielded seemingly disparate insights into large-scale organization of the human brain. The brain's large-scale organization can be divided into two broad categories: zero-lag representations of functional connectivity structure and time-lag representations of traveling wave or propagation structure. In this study, we sought to unify observed phenomena across these two categories in the form of three low-frequency spatiotemporal patterns composed of a mixture of standing and traveling wave dynamics. We showed that a range of empirical phenomena, including functional connectivity gradients, the task-positive/task-negative anti-correlation pattern, the global signal, time-lag propagation patterns, the quasiperiodic pattern and the functional connectome network structure, are manifestations of these three spatiotemporal patterns. These patterns account for much of the global spatial structure that underlies functional connectivity analyses and unifies phenomena in resting-state functional MRI previously thought distinct.

Educating the future generation of researchers: A cross-disciplinary survey of trends in analysis methods.

Methods for data analysis in the biomedical, life, and social (BLS) sciences are developing at a rapid pace. At the same time, there is increasing concern that education in quantitative methods is failing to adequately prepare students for contemporary research. These trends have led to calls for educational reform to undergraduate and graduate quantitative research method curricula. We argue that such reform should be based on data-driven insights into within- and cross-disciplinary use of analytic methods. Our survey of peer-reviewed literature analyzed approximately 1.3 million openly available research articles to monitor the cross-disciplinary mentions of analytic methods in the past decade. We applied data-driven text mining analyses to the "Methods" and "Results" sections of a large subset of this corpus to identify trends in analytic method mentions shared across disciplines, as well as those unique to each discipline. We found that the t test, analysis of variance (ANOVA), linear regression, chi-squared test, and other classical statistical methods have been and remain the most mentioned analytic methods in biomedical, life science, and social science research articles. However, mentions of these methods have declined as a percentage of the published literature between 2009 and 2020. On the other hand, multivariate statistical and machine learning approaches, such as artificial neural networks (ANNs), have seen a significant increase in the total share of scientific publications. We also found unique groupings of analytic methods associated with each BLS science discipline, such as the use of structural equation modeling (SEM) in psychology, survival models in oncology, and manifold learning in ecology. We discuss the implications of these findings for education in statistics and research methods, as well as within- and cross-disciplinary collaboration.

Modeling neural and self-reported factors of affective distress in the relationship between pain and working memory in healthy individuals.

The relationship between pain and cognition has primarily been investigated in patients with chronic pain and healthy participants undergoing experimental pain. Recently, there has been interest in understanding the disruptive effects of non-experimental pain in otherwise healthy individuals. Recent studies suggest that healthy individuals reporting pain also demonstrate decrements in working memory (WM) performance, however factors contributing to this relationship remain poorly understood. The present study examined the association between pain and WM in a large community-based sample of healthy individuals and investigated whether self-reported affective distress and medial frontal cortex activity might help to explain this relationship. To address these research questions, a large publicly available dataset from the Human Connectome Project (N = 416) was sourced and structural equation modeling was utilized to examine relationships between pain intensity experienced over the past 7 days, self-reported affective distress, performance on a WM (n-back) task, and task-related activation in the medial frontal cortex. Examining participants who reported non-zero pain intensity in the past 7 days (n = 228), we found a direct negative association between pain intensity and performance on the WM n-back task, consistent with prior findings. Self-reported affective distress was not associated with WM performance. Additionally, pain intensity was indirectly associated with WM performance via WM task-related activity in the ventromedial prefrontal cortex (vmPFC). Our findings suggest that pain experienced in everyday life by otherwise healthy individuals may directly impact WM performance. Furthermore, WM task-related increases in vmPFC activity may be a factor contributing to this relationship.

Inter-subject phase synchronization differentiates neural networks underlying physical pain empathy.

Recent approaches for understanding the neural basis of pain empathy emphasize the dynamic construction of networks underlying this multifaceted social cognitive process. Inter-subject phase synchronization (ISPS) is an approach for exploratory analysis of task-fMRI data that reveals brain networks dynamically synchronized to task-features across participants. We applied ISPS to task-fMRI data assessing vicarious pain empathy in healthy participants (n = 238). The task employed physical (limb) and affective (face) painful and corresponding non-painful visual stimuli. ISPS revealed two distinct networks synchronized during physical pain observation, one encompassing anterior insula and midcingulate regions strongly engaged in (vicarious) pain and another encompassing parietal and inferior frontal regions associated with social cognitive processes which may modulate and support the physical pain empathic response. No robust network synchronization was observed for affective pain, possibly reflecting high inter-individual variation in response to socially transmitted pain experiences. ISPS also revealed networks related to task onset or general processing of physical (limb) or affective (face) stimuli which encompassed networks engaged in object manipulation or face processing, respectively. Together, the ISPS approach permits segregation of networks engaged in different psychological processes, providing additional insight into shared neural mechanisms of empathy for physical pain, but not affective pain, across individuals.

Ontological Dimensions of Cognitive-Neural Mappings.

The growing literature reporting results of cognitive-neural mappings has increased calls for an adequate organizing ontology, or taxonomy, of these mappings. This enterprise is non-trivial, as relevant dimensions that might contribute to such an ontology are not yet agreed upon. We propose that any candidate dimensions should be evaluated on their ability to explain observed differences in functional neuroimaging activation patterns. In this study, we use a large sample of task-based functional magnetic resonance imaging (task-fMRI) results and a data-driven strategy to identify these dimensions. First, using a data-driven dimension reduction approach and multivariate distance matrix regression (MDMR), we quantify the variance among activation maps that is explained by existing ontological dimensions. We find that 'task paradigm' categories explain more variance among task-activation maps than other dimensions, including latent cognitive categories. Surprisingly, 'study ID', or the study from which each activation map was reported, explained close to 50% of the variance in activation patterns. Using a clustering approach that allows for overlapping clusters, we derived data-driven latent activation states, associated with re-occurring configurations of the canonical frontoparietal, salience, sensory-motor, and default mode network activation patterns. Importantly, with only four data-driven latent dimensions, one can explain greater variance among activation maps than all conventional ontological dimensions combined. These latent dimensions may inform a data-driven cognitive ontology, and suggest that current descriptions of cognitive processes and the tasks used to elicit them do not accurately reflect activation patterns commonly observed in the human brain.

Topography and behavioral relevance of the global signal in the human brain.

The global signal in resting-state functional MRI data is considered to be dominated by physiological noise and artifacts, yet a growing literature suggests that it also carries information about widespread neural activity. The biological relevance of the global signal remains poorly understood. Applying principal component analysis to a large neuroimaging dataset, we found that individual variation in global signal topography recapitulates well-established patterns of large-scale functional brain networks. Using canonical correlation analysis, we delineated relationships between individual differences in global signal topography and a battery of phenotypes. The first canonical variate of the global signal, resembling the frontoparietal control network, was significantly related to an axis of positive and negative life outcomes and psychological function. These results suggest that the global signal contains a rich source of information related to trait-level cognition and behavior. This work has significant implications for the contentious debate over artifact removal practices in neuroimaging.

The situation or the person? Individual and task-evoked differences in BOLD activity.

Investigations of between-person variability are enjoying a recent resurgence in functional magnetic resonance imaging (fMRI) research. Several recent studies have found persistent between-person differences in blood-oxygenated-level dependent (BOLD) activation patterns and resting-state functional connectivity. Conflicting findings have been reported regarding the extent to which (a) between-person or (b) within-person cognitive state differences explain differences in BOLD activation patterns. These discrepancies may arise due to statistical analysis choices, parcellation resolution, and limited sampling of task-fMRI datasets. We attempt to address these issues in a large-scale analysis of several task-fMRI paradigms. Using a novel application of multivariate distance matrix regression, we examine between-person and task-condition variability estimates across varying levels of "resolution", from a coarse region-of-interest level to the vertex-level, and across different distance metrics. These analyses revealed that under most circumstances, differences in task conditions explained a greater amount of variance in activation map differences than between-person differences. However, this finding was reversed when comparing activation maps at a "high-resolution" vertex level. More generally, we observed that when moving from "low" to "high" resolutions, the variance explained by between-person differences increased while variance explained by task conditions decreased. We further analyzed the relationships among subject-level activation maps across all task-conditions using an unsupervised clustering approach and identified a superordinate task structure. This structure went beyond conventional task labels and highlighted those experimental manipulations across task conditions that produce contrasting versus similar whole-brain activation patterns. Overall, these analyses suggest that the question of the subject- versus task-effects on BOLD activation patterns is nontrivial, and depends on the comparison "resolution," choice of distance metric, and the coding of task-conditions.

Disentangling Mathematics from Executive Functions by Investigating Unique Functional Connectivity Patterns Predictive of Mathematics Ability.

What are the underlying neurocognitive mechanisms that give rise to mathematical competence? This study investigated the relationship between tests of mathematical ability completed outside the scanner and resting-state functional connectivity (FC) of cytoarchitectonically defined subdivisions of the parietal cortex in adults. These parietal areas are also involved in executive functions (EFs). Therefore, it remains unclear whether there are unique networks for mathematical processing. We investigate the neural networks for mathematical cognition and three measures of EF using resting-state fMRI data collected from 51 healthy adults. Using 10 ROIs in seed to whole-brain voxel-wise analyses, the results showed that arithmetical ability was correlated with FC between the right anterior intraparietal sulcus (hIP1) and the left supramarginal gyrus and between the right posterior intraparietal sulcus (hIP3) and the left middle frontal gyrus and the right premotor cortex. The connection between the posterior portion of the left angular gyrus and the left inferior frontal gyrus was also correlated with mathematical ability. Covariates of EF eliminated connectivity patterns with nodes in inferior frontal gyrus, angular gyrus, and middle frontal gyrus, suggesting neural overlap. Controlling for EF, we found unique connections correlated with mathematical ability between the right hIP1 and the left supramarginal gyrus and between hIP3 bilaterally to premotor cortex bilaterally. This is partly in line with the "mapping hypothesis" of numerical cognition in which the right intraparietal sulcus subserves nonsymbolic number processing and connects to the left parietal cortex, responsible for calculation procedures. We show that FC within this circuitry is a significant predictor of math ability in adulthood.

Corrigendum: Resting-State Brain Signal Variability in Prefrontal Cortex Is Associated With ADHD Symptom Severity in Children.

[This corrects the article on p. 90 in vol. 12, PMID: 29593515.].

Beyond the evoked/intrinsic neural process dichotomy.

Contemporary functional neuroimaging research has increasingly focused on characterization of intrinsic or "spontaneous" brain activity. Analysis of intrinsic activity is often contrasted with analysis of task-evoked activity that has traditionally been the focus of cognitive neuroscience. But does this evoked/intrinsic dichotomy adequately characterize human brain function? Based on empirical data demonstrating a close functional interdependence between intrinsic and task-evoked activity, we argue that the dichotomy between intrinsic and task-evoked activity as unobserved contributions to brain activity is artificial. We present an alternative picture of brain function in which the brain's spatiotemporal dynamics do not consist of separable intrinsic and task-evoked components, but reflect the enaction of a system of mutual constraints to move the brain into and out of task-appropriate functional configurations. According to this alternative picture, cognitive neuroscientists are tasked with describing both the temporal trajectory of brain activity patterns across time, and the modulation of this trajectory by task states, without separating this process into intrinsic and task-evoked components. We argue that this alternative picture of brain function is best captured in a novel explanatory framework called enabling constraint. Overall, these insights call for a reconceptualization of functional brain activity, and should drive future methodological and empirical efforts.

Inter-subject phase synchronization for exploratory analysis of task-fMRI.

Analysis of task-based fMRI data is conventionally carried out using a hypothesis-driven approach, where blood-oxygen-level dependent (BOLD) time courses are correlated with a hypothesized temporal structure. In some experimental designs, this temporal structure can be difficult to define. In other cases, experimenters may wish to take a more exploratory, data-driven approach to detecting task-driven BOLD activity. In this study, we demonstrate the efficiency and power of an inter-subject synchronization approach for exploratory analysis of task-based fMRI data. Combining the tools of instantaneous phase synchronization and independent component analysis, we characterize whole-brain task-driven responses in terms of group-wise similarity in temporal signal dynamics of brain networks. We applied this framework to fMRI data collected during performance of a simple motor task and a social cognitive task. Analyses using an inter-subject phase synchronization approach revealed a large number of brain networks that dynamically synchronized to various features of the task, often not predicted by the hypothesized temporal structure of the task. We suggest that this methodological framework, along with readily available tools in the fMRI community, provides a powerful exploratory, data-driven approach for analysis of task-driven BOLD activity.

Resting-State Brain Signal Variability in Prefrontal Cortex Is Associated With ADHD Symptom Severity in Children.

Atypical brain function in attention-deficit/hyperactivity disorder (ADHD) has been identified using both task-activation and functional connectivity fMRI approaches. Recent work highlights the potential for another measure derived from functional neuroimaging data, brain signal variability, to reveal insights into clinical conditions. Higher brain signal variability has previously been linked with optimal behavioral performance. At present, little is known regarding the relationship between resting-state brain signal variability and ADHD symptom severity. The current study examined the relationship between a measure of moment-to-moment brain signal variability called mean-square successive difference (MSSD) and ADHD symptomatology in a group of children (7-12 years old) with (n = 40) and without (n = 30) a formal diagnosis of ADHD. A categorical analysis comparing subjects with and without a clinical diagnosis of ADHD showed no differences in MSSD between groups. A dimensional analysis revealed a positive relationship between MSSD and overall ADHD symptom severity and inattention across children with and without an ADHD diagnosis. Specifically, this positive relationship was found in medial prefrontal areas comprising the default mode network. These results demonstrate a link between intrinsic brain signal variability and ADHD symptom severity that cuts across diagnostic categories, and point to a locus of dysfunction consistent with previous neuroimaging literature.

Combining region- and network-level brain-behavior relationships in a structural equation model.

Brain-behavior associations in fMRI studies are typically restricted to a single level of analysis: either a circumscribed brain region-of-interest (ROI) or a larger network of brain regions. However, this common practice may not always account for the interdependencies among ROIs of the same network or potentially unique information at the ROI-level, respectively. To account for both sources of information, we combined measurement and structural components of structural equation modeling (SEM) approaches to empirically derive networks from ROI activity, and to assess the association of both individual ROIs and their respective whole-brain activation networks with task performance using three large task-fMRI datasets and two separate brain parcellation schemes. The results for working memory and relational tasks revealed that well-known ROI-performance associations are either non-significant or reversed when accounting for the ROI's common association with its corresponding network, and that the network as a whole is instead robustly associated with task performance. The results for the arithmetic task revealed that in certain cases, an ROI can be robustly associated with task performance, even when accounting for its associated network. The SEM framework described in this study provides researchers additional flexibility in testing brain-behavior relationships, as well as a principled way to combine ROI- and network-levels of analysis.

Data-Driven Extraction of a Nested Model of Human Brain Function.

Decades of cognitive neuroscience research have revealed two basic facts regarding task-driven brain activation patterns. First, distinct patterns of activation occur in response to different task demands. Second, a superordinate, dichotomous pattern of activation/deactivation, is common across a variety of task demands. We explore the possibility that a hierarchical model incorporates these two observed brain activation phenomena into a unifying framework. We apply a latent variable approach, exploratory bifactor analysis, to a large set of human (both sexes) brain activation maps (n = 108) encompassing cognition, perception, action, and emotion behavioral domains, to determine the potential existence of a nested structure of factors that underlie a variety of commonly observed activation patterns. We find that a general factor, associated with a superordinate brain activation/deactivation pattern, explained the majority of the variance (52.37%) in brain activation patterns. The bifactor analysis also revealed several subfactors that explained an additional 31.02% of variance in brain activation patterns, associated with different manifestations of the superordinate brain activation/deactivation pattern, each emphasizing different contexts in which the task demands occurred. Importantly, this nested factor structure provided better overall fit to the data compared with a non-nested factor structure model. These results point to a domain-general psychological process, representing a "focused awareness" process or "attentional episode" that is variously manifested according to the sensory modality of the stimulus and degree of cognitive processing. This novel model provides the basis for constructing a biologically informed, data-driven taxonomy of psychological processes.SIGNIFICANCE STATEMENT A crucial step in identifying how the brain supports various psychological processes is a well-defined categorization or taxonomy of psychological processes and their interrelationships. We hypothesized that a nested structure of cognitive function, in terms of a canonical domain-general cognitive process, and various subfactors representing different manifestations of the canonical process, is a fundamental organization of human cognition, and we tested this hypothesis using fMRI task-activation patterns. Using a data-driven latent-variable approach, we demonstrate that a nested factor structure underlies a large sample of brain activation patterns across a variety of task domains.

Moment-to-Moment BOLD Signal Variability Reflects Regional Changes in Neural Flexibility across the Lifespan.

Variability of neuronal responses is thought to underlie flexible and optimal brain function. Because previous work investigating BOLD signal variability has been conducted within task-based fMRI contexts on adults and older individuals, very little is currently known regarding regional changes in spontaneous BOLD signal variability in the human brain across the lifespan. The current study used resting-state fMRI data from a large sample of male and female human participants covering a wide age range (6-85 years) across two different fMRI acquisition parameters (TR = 0.645 and 1.4 s). Variability in brain regions including a key node of the salience network (anterior insula) increased linearly across the lifespan across datasets. In contrast, variability in most other large-scale networks decreased linearly over the lifespan. These results demonstrate unique lifespan trajectories of BOLD variability related to specific regions of the brain and add to a growing literature demonstrating the importance of identifying normative trajectories of functional brain maturation.SIGNIFICANCE STATEMENT Although brain signal variability has traditionally been considered a source of unwanted noise, recent work demonstrates that variability in brain signals during task performance is related to brain maturation in old age as well as individual differences in behavioral performance. The current results demonstrate that intrinsic fluctuations in resting-state variability exhibit unique maturation trajectories in specific brain regions and systems, particularly those supporting salience detection. These results have implications for investigations of brain development and aging, as well as interpretations of brain function underlying behavioral changes across the lifespan.

Correspondence between evoked and intrinsic functional brain network configurations.

Much of the literature exploring differences between intrinsic and task-evoked brain architectures has examined changes in functional connectivity patterns between specific brain regions. While informative, this approach overlooks important overall functional changes in hub organization and network topology that may provide insights about differences in integration between intrinsic and task-evoked states. Examination of changes in overall network organization, such as a change in the concentration of hub nodes or a quantitative change in network organization, is important for understanding the underlying processes that differ between intrinsic and task-evoked brain architectures. The present study used graph-theoretical techniques applied to publicly available neuroimaging data collected from a large sample of individuals (N = 202), and a within-subject design where resting-state and several task scans were collected from each participant as part of the Human Connectome Project. We demonstrate that differences between intrinsic and task-evoked brain networks are characterized by a task-general shift in high-connectivity hubs from primarily sensorimotor/auditory processing areas during the intrinsic state to executive control/salience network areas during task performance. In addition, we demonstrate that differences between intrinsic and task-evoked architectures are associated with changes in overall network organization, such as increases in network clustering, global efficiency and integration between modules. These findings offer a new perspective on the principles guiding functional brain organization by identifying unique and divergent properties of overall network organization between the resting-state and task performance. Hum Brain Mapp 38:1992-2007, 2017. © 2017 Wiley Periodicals, Inc.

Graph-Theoretical Study of Functional Changes Associated with the Iowa Gambling Task.

The primary aim of this study was to examine changes in functional brain network organization from rest to the Iowa Gambling Task (IGT) using a graph-theoretical approach. Although many functional neuroimaging studies have examined task-based activations in complex-decision making tasks, changes in functional network organization during this task remain unexplored. This study used a repeated-measures approach to examine changes in functional network organization across multiple sessions of resting-state and IGT scans. The results revealed that global network organization shifted from a local, clustered organization at rest to a more global, integrated organization during the IGT. In addition, network organization was stable across sessions of rest and the IGT. Regional analyses of the Default Mode Network (DMN) and Fronto-Parietal Network (FPN) revealed differential patterns of change in regional network organization from rest to the IGT. The results of this study reveal that global and regional network organization is significantly modulated across states and fairly stable over time, and that network changes in the FPN are particularly important in the decision-making processes necessary for successful IGT performance.