Author Summary 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. Abstract 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.

Author Summary Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with altered patterns of functional brain connectivity. Little is currently known about how moment-to-moment brain dynamics differ in children with ASD and typically developing (TD) children. Altered functional integrity of the midcingulo-insular network (M-CIN) has been implicated in the neurobiology of ASD. Here we use a novel coactivation analysis approach applied to a large sample of resting-state fMRI data collected from children with ASD and TD children to demonstrate altered patterns of M-CIN dynamics in children with the disorder. We speculate that these atypical patterns of brain dynamics may underlie behavioral inflexibility in ASD. Abstract Brain connectivity studies of autism spectrum disorder (ASD) have historically relied on static measures of functional connectivity. Recent work has focused on identifying transient configurations of brain activity, yet several open questions remain regarding the nature of specific brain network dynamics in ASD. We used a dynamic coactivation pattern (CAP) approach to investigate the salience/midcingulo-insular (M-CIN) network, a locus of dysfunction in ASD, in a large multisite resting-state fMRI dataset collected from 172 children (ages 6–13 years; n = 75 ASD; n = 138 male). Following brain parcellation by using independent component analysis, dynamic CAP analyses were conducted and k -means clustering was used to determine transient activation patterns of the M-CIN. The frequency of occurrence of different dynamic CAP brain states was then compared between children with ASD and typically developing (TD) children. Dynamic brain configurations characterized by coactivation of the M-CIN with central executive/lateral fronto-parietal and default mode/medial fronto-parietal networks appeared less frequently in children with ASD compared with TD children. This study highlights the utility of time-varying approaches for studying altered M-CIN function in prevalent neurodevelopmental disorders. We speculate that altered M-CIN dynamics in ASD may underlie the inflexible behaviors commonly observed in children with the disorder.