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.

Whole-Brain Functional Dynamics Track Depressive Symptom Severity.

Depressive symptoms are reported by 20% of the population and are related to altered functional integrity of large-scale brain networks. The link between moment-to-moment brain function and depressive symptomatology, and the implications of these relationships for clinical and community populations alike, remain understudied. The present study examined relationships between functional brain dynamics and subclinical-to-mild depressive symptomatology in a large community sample of adults with and without psychiatric diagnoses. This study used data made available through the Enhanced Nathan Kline Institute-Rockland Sample; 445 participants between 18 and 65 years of age completed a 10-min resting-state functional MRI scan. Coactivation pattern analysis was used to examine the dimensional relationship between depressive symptoms and whole-brain states. Elevated levels of depressive symptoms were associated with increased frequency and dwell time of the default mode network, a brain network associated with self-referential thought, evaluative judgment, and social cognition. Furthermore, increased depressive symptom severity was associated with less frequent occurrences of a hybrid brain network implicated in cognitive control and goal-directed behavior, which may impair the inhibition of negative thinking patterns in depressed individuals. These findings demonstrate how temporally dynamic techniques offer novel insights into time-varying neural processes underlying subclinical and clinically meaningful depressive symptomatology.

Brain Dynamics Underlying Cognitive Flexibility Across the Lifespan.

The neural mechanisms contributing to flexible cognition and behavior and how they change with development and aging are incompletely understood. The current study explored intrinsic brain dynamics across the lifespan using resting-state fMRI data (n = 601, 6-85 years) and examined the interactions between age and brain dynamics among three neurocognitive networks (midcingulo-insular network, M-CIN; medial frontoparietal network, M-FPN; and lateral frontoparietal network, L-FPN) in relation to behavioral measures of cognitive flexibility. Hierarchical multiple regression analysis revealed brain dynamics among a brain state characterized by co-activation of the L-FPN and M-FPN, and brain state transitions, moderated the relationship between quadratic effects of age and cognitive flexibility as measured by scores on the Delis-Kaplan Executive Function System (D-KEFS) test. Furthermore, simple slope analyses of significant interactions revealed children and older adults were more likely to exhibit brain dynamic patterns associated with poorer cognitive flexibility compared with younger adults. Our findings link changes in cognitive flexibility observed with age with the underlying brain dynamics supporting these changes. Preventative and intervention measures should prioritize targeting these networks with cognitive flexibility training to promote optimal outcomes across the lifespan.

Inter-regional BOLD signal variability is an organizational feature of functional brain networks.

Neuronal variability patterns promote the formation and organization of neural circuits. Macroscale similarities in regional variability patterns may therefore be linked to the strength and topography of inter-regional functional connections. To assess this relationship, we used multi-echo resting-state fMRI and investigated macroscale connectivity-variability associations in 154 adult humans (86 women; mean age = 22yrs). We computed inter-regional measures of moment-to-moment BOLD signal variability and related them to inter-regional functional connectivity. Region pairs that showed stronger functional connectivity also showed similar BOLD signal variability patterns, independent of inter-regional distance and structural similarity. Connectivity-variability associations were predominant within all networks and followed a hierarchical spatial organization that separated sensory, motor and attention systems from limbic, default and frontoparietal control association networks. Results were replicated in a second held-out fMRI run. These findings suggest that macroscale BOLD signal variability is an organizational feature of large-scale functional networks, and shared inter-regional BOLD signal variability may underlie macroscale brain network dynamics.

What have we really learned from functional connectivity in clinical populations?

Functional connectivity (FC), or the statistical interdependence of blood-oxygen dependent level (BOLD) signals between brain regions using fMRI, has emerged as a widely used tool for probing functional abnormalities in clinical populations due to the promise of the approach across conceptual, technical, and practical levels. With an already vast and steadily accumulating neuroimaging literature on neurodevelopmental, psychiatric, and neurological diseases and disorders in which FC is a primary measure, we aim here to provide a high-level synthesis of major concepts that have arisen from FC findings in a manner that cuts across different clinical conditions and sheds light on overarching principles. We highlight that FC has allowed us to discover the ubiquity of intrinsic functional networks across virtually all brains and clarify typical patterns of neurodevelopment over the lifespan. This understanding of typical FC maturation with age has provided important benchmarks against which to evaluate divergent maturation in early life and degeneration in late life. This in turn has led to the important insight that many clinical conditions are associated with complex, distributed, network-level changes in the brain, as opposed to solely focal abnormalities. We further emphasize the important role that FC studies have played in supporting a dimensional approach to studying transdiagnostic clinical symptoms and in enhancing the multimodal characterization and prediction of the trajectory of symptom progression across conditions. We highlight the unprecedented opportunity offered by FC to probe functional abnormalities in clinical conditions where brain function could not be easily studied otherwise, such as in disorders of consciousness. Lastly, we suggest high priority areas for future research and acknowledge critical barriers associated with the use of FC methods, particularly those related to artifact removal, data denoising and feasibility in clinical contexts.

Dynamic functional connectivity profile of the salience network across the life span.

The insular cortex and anterior cingulate cortex together comprise the salience or midcingulo-insular network, involved in detecting salient events and initiating control signals to mediate brain network dynamics. The extent to which functional coupling between the salience network and the rest of the brain undergoes changes due to development and aging is at present largely unexplored. Here, we examine dynamic functional connectivity (dFC) of the salience network in a large life span sample (n = 601; 6-85 years old). A sliding-window analysis and k-means clustering revealed five states of dFC formed with the salience network, characterized by either widespread asynchrony or different patterns of synchrony between the salience network and other brain regions. We determined the frequency, dwell time, total transitions, and specific state-to-state transitions for each state and subject, regressing the metrics with subjects' age to identify life span trends. A dynamic state characterized by low connectivity between the salience network and the rest of the brain had a strong positive quadratic relationship between age and both frequency and dwell time. Additional frequency, dwell time, total transitions, and state-to-state transition trends were observed with other salience network states. Our results highlight the metastable dynamics of the salience network and its role in the maturation of brain regions critical for cognition.

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.

Dynamic brain network configurations during rest and an attention task with frequent occurrence of mind wandering.

Mind wandering (MW) has become a prominent topic of neuroscientific investigation due to the importance of understanding attentional processes in our day-to-day experiences. Emerging evidence suggests a critical role for three large-scale brain networks in MW: the default network (DN), the central executive network (CEN), and the salience network (SN). Advances in analytical methods for neuroimaging data (i.e., dynamic functional connectivity, DFC) demonstrate that the interactions between these networks are not static but dynamically fluctuate over time (Chang & Glover, 2010, NeuroImage, 50(1), 81-98). While the bulk of the evidence comes from studies involving resting-state functional MRI, a few studies have investigated DFC during a task. Direct comparison of DFC during rest and task with frequent MW is scarce. The present study applies the DFC method to neuroimaging data collected from 30 participants who completed a resting-state run followed by two runs of sustained attention to response task (SART) with embedded probes indicating a high prevalence of MW. The analysis identified five DFC states. Differences between rest and task were noted in the frequency of three DFC states. One DFC state characterized by negative DN-CEN/SN connectivity along with positive CEN-SN connectivity was more frequently observed during task vs. rest. Two DFC states, one of which was characterized by weaker connectivity between networks, were more frequently observed during rest than task. These findings suggest that the dynamic relationships between brain networks may vary as a function of whether ongoing cognitive activity unfolds in an "unconstrained" manner during rest or is "constrained" by task demands.

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.

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.

Evolution of spatial and temporal features of functional brain networks across the lifespan.

Development and aging are associated with functional changes in the brain across the lifespan. These changes manifest in a variety of spatial and temporal features of resting state functional MRI (rs-fMRI) but have seldom been explored exhaustively. We present a comprehensive study assessing age-related changes in spatial and temporal features of blind-source separated components identified by independent vector analysis (IVA) in a cross-sectional lifespan sample (ages 6-85 years). We show that while large-scale network configurations remain consistent throughout the lifespan, changes persist in both local and global organization of these networks. We show that the spatial extent of the majority of functional networks exhibits linear decreases and both positive and negative quadratic trajectories across the lifespan. Network connectivity revealed nuanced patterns of linear and quadratic relationships with age, primarily in higher order cognitive networks. We also show divergent age-related patterns across the frequency spectrum in lower and higher frequencies. Taken together, these results point to the presence of sophisticated patterns of age-related changes that have previously not been considered collectively. We suggest that established patterns of lifespan changes in rs-fMRI features may be driven by changes in the spectral composition of BOLD signals.

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.

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.

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.

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.

Intrinsic functional connectivity variance and state-specific under-connectivity in autism.

Autism spectrum disorder (ASD) is a neurodevelopmental condition associated with altered brain connectivity. Previous neuroimaging research demonstrates inconsistent results, particularly in studies of functional connectivity in ASD. Typically, these inconsistent findings are results of studies using static measures of resting-state functional connectivity. Recent work has demonstrated that functional brain connections are dynamic, suggesting that static connectivity metrics fail to capture nuanced time-varying properties of functional connections in the brain. Here we used a dynamic functional connectivity approach to examine the differences in the strength and variance of dynamic functional connections between individuals with ASD and healthy controls (HCs). The variance of dynamic functional connections was defined as the respective standard deviations of the dynamic functional connectivity strength across time. We utilized a large multicenter dataset of 507 male subjects (209 with ASD and 298 HC, from 6 to 36 years old) from the Autism Brain Imaging Data Exchange (ABIDE) to identify six distinct whole-brain dynamic functional connectivity states. Analyses demonstrated greater variance of widespread long-range dynamic functional connections in ASD (P < 0.05, NBS method) and weaker dynamic functional connections in ASD (P < 0.05, NBS method) within specific whole-brain connectivity states. Hypervariant dynamic connections were also characterized by weaker connectivity strength in ASD compared with HC. Increased variance of dynamic functional connections was also related to ASD symptom severity (ADOS total score) (P < 0.05), and was most prominent in connections related to the medial superior frontal gyrus and temporal pole. These results demonstrate that greater intraindividual dynamic variance is a potential biomarker of ASD. Hum Brain Mapp 38:5740-5755, 2017. © 2017 Wiley Periodicals, Inc.

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.

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.