How do tasks impact the reliability of fMRI functional connectivity?

While there is growing interest in the use of functional magnetic resonance imaging-functional connectivity (fMRI-FC) for biomarker research, low measurement reliability of conventional acquisitions may limit applications. Factors known to impact FC reliability include scan length, head motion, signal properties, such as temporal signal-to-noise ratio (tSNR), and the acquisition state or task. As tasks impact signal in a region-wise fashion, they likely impact FC reliability differently across the brain, making task an important decision in study design. Here, we use the densely sampled Midnight Scan Club (MSC) dataset, comprising 5 h of rest and 6 h of task fMRI data in 10 healthy adults, to investigate regional effects of tasks on FC reliability. We further considered how BOLD signal properties contributing to tSNR, that is, temporal mean signal (tMean) and temporal standard deviation (tSD), vary across the brain, associate with FC reliability, and are modulated by tasks. We found that, relative to rest, tasks enhanced FC reliability and increased tSD for specific task-engaged regions. However, FC signal variability and reliability is broadly dampened during tasks outside task-engaged regions. From our analyses, we observed signal variability was the strongest driver of FC reliability. Overall, our findings suggest that the choice of task can have an important impact on reliability and should be considered in relation to maximizing reliability in networks of interest as part of study design.

Functional connectomes become more longitudinally self-stable, but not more distinct from others, across early childhood.

Functional connectomes, as measured with functional magnetic resonance imaging (fMRI), are highly individualized, and evidence suggests this individualization may increase across childhood. A connectome can become more individualized either by increasing self-stability or decreasing between-subject-similarity. Here we used a longitudinal early childhood dataset to investigate age associations with connectome self-stability, between-subject-similarity, and developmental individualization, defined as an individual's self-stability across a 12-month interval relative to their between-subject-similarity. fMRI data were collected during an 18-minute passive viewing scan from 73 typically developing children aged 4-7 years, at baseline and 12-month follow-up. We found that young children had highly individualized connectomes, with sufficient self-stability across 12-months for 98% identification accuracy. Linear models showed a significant relationship between age and developmental individualization across the whole brain and in most networks. This association appeared to be largely driven by an increase in self-stability with age, with only weak evidence for relationships between age and similarity across participants. Together our findings suggest that children's connectomes become more individualized across early childhood, and that this effect is driven by increasing self-stability rather than decreasing between-subject-similarity.

Maturation and interhemispheric asymmetry in neurite density and orientation dispersion in early childhood.

BACKGROUND: The brain's white matter undergoes profound changes during early childhood, which are believed to underlie the rapid development of cognitive and behavioral skills during this period. Neurite density, and complexity of axonal projections, have been shown to change across the life span, though changes during early childhood are poorly characterized. Here, we utilize neurite orientation dispersion and density imaging (NODDI) to investigate maturational changes in tract-wise neurite density index (NDI) and orientation dispersion index (ODI) during early childhood. Additionally, we assess hemispheric asymmetry of tract-wise NDI and ODI values, and longitudinal changes. METHODS: Two sets of diffusion weighted images with different diffusion-weighting were collected from 125 typically developing children scanned at baseline (N = 125; age range = 4.14-7.29; F/M = 73/52), 6-month (N = 8; F/M = 8/0), and 12-month (N = 52; F/M = 39/13) timepoints. NODDI and template-based tractography using constrained spherical deconvolution were utilized to calculate NDI and ODI values for major white matter tracts. Mixed-effects models controlling for sex, handedness, and in-scanner head motion were utilized to assess developmental changes in tract-wise NDI and ODI. Additional mixed-effects models were used to assess interhemispheric differences in tract-wise NDI and ODI values and hemispheric asymmetries in tract-wise development. RESULTS: Maturational increases in NDI were seen in all major white matter tracts, though we did not observe the expected tract-wise pattern of maturational rates (e.g. fast commissural/projection and slow frontal/temporal tract change). ODI did not change significantly with age in any tract. We observed greater NDI and ODI values in the right as compared to the left hemisphere for most tracts, but no hemispheric asymmetry for rate of change with age. CONCLUSIONS: These findings suggest that neurite density, but not orientation dispersion, increases with age during early childhood. In relation to NDI growth trends reported in infancy and late-childhood, our results suggest that early childhood may be a transitional period for neurite density maturation wherein commissural/projection fibers are approaching maturity, maturation in long range association fibers is increasing, and changes in limbic/frontal fibers remain modest. Rightward asymmetry in NDI and ODI values, but no asymmetry in developmental changes, suggests that rightward asymmetry of neurite density and orientation dispersion is established prior to age 4.

Development of human visual cortical function: A scoping review of task- and naturalistic-fMRI studies through the interactive specialization and maturational frameworks.

Overarching theories such as the interactive specialization and maturational frameworks have been proposed to describe human functional brain development. However, these frameworks have not yet been systematically examined across the fMRI literature. Visual processing is one of the most well-studied fields in neuroimaging, and research in this area has recently expanded to include naturalistic paradigms that facilitate study in younger age ranges, allowing for an in-depth critical appraisal of these frameworks across childhood. To this end, we conducted a scoping review of 94 developmental visual fMRI studies, including both traditional experimental task and naturalistic studies, across multiple sub-domains (early visual processing, category-specific higher order processing, naturalistic visual processing). We found that across domains, many studies reported progressive development, but few studies describe regressive or emergent changes necessary to fit the maturational or interactive specialization frameworks. Our findings suggest a need for the expansion of developmental frameworks and clearer reporting of both progressive and regressive changes, along with well-powered, longitudinal studies.

Functional MRI responses to naturalistic stimuli are increasingly typical across early childhood.

While findings show that throughout development, there are child- and age-specific patterns of brain functioning, there is also evidence for significantly greater inter-individual response variability in young children relative to adults. It is currently unclear whether this increase in functional "typicality" (i.e., inter-individual similarity) is a developmental process that occurs across early childhood, and what changes in BOLD response may be driving changes in typicality. We collected fMRI data from 81 typically developing 4-8-year-old children during passive viewing of age-appropriate television clips and asked whether there is increasing typicality of brain response across this age range. We found that the "increasing typicality" hypothesis was supported across many regions engaged by passive viewing. Post hoc analyses showed that in a priori ROIs related to language and face processing, the strength of the group-average shared component of activity increased with age, with no concomitant decline in residual signal or change in spatial extent or variability. Together, this suggests that increasing inter-individual similarity of functional responses to audiovisual stimuli is an important feature of early childhood functional brain development.

Inattentive and hyperactive traits differentially associate with interindividual functional synchrony during video viewing in young children without ADHD.

Inattention and hyperactivity present on a spectrum and may influence the way children perceive and interact with the world. We investigated whether normative variation in inattentive and hyperactive traits was associated with differences in brain function, while children watched clips from an age-appropriate television program. Functional magnetic resonance imaging (fMRI) data and parent reports of inattention and hyperactivity traits were collected from 81 children 4-7 years of age with no parent-reported diagnoses. Data were analyzed using intersubject correlations (ISCs) in mixed effects models to determine if inattentive and hyperactive traits were associated with idiosyncrasy of fMRI response to the video. We hypothesized that pairs of children with higher average inattention and hyperactivity scores would show less interindividual brain synchrony to one another than pairs with lower average scores on these traits. Video watching engaged widespread visual, auditory, default mode and dorsal prefrontal regions. Inattention and hyperactivity were separably associated with ISC in many of these regions. Our findings suggest that the spectrum of inattention and hyperactivity traits in children without ADHD are differentially associated with neural processing of naturalistic video stimuli, which may have implications for understanding how children with different levels of these traits process audiovisual information in unconstrained conditions.

Benchmarking common preprocessing strategies in early childhood functional connectivity and intersubject correlation fMRI.

Preprocessing choices present a particular challenge for researchers working with functional magnetic resonance imaging (fMRI) data from young children. Steps which have been shown to be important for mitigating head motion, such as censoring and global signal regression (GSR), remain controversial, and benchmarking studies comparing preprocessing pipelines have been conducted using resting data from older participants who tend to move less than young children. Here, we conducted benchmarking of fMRI preprocessing steps in a population with high head-motion, children aged 4-8 years, leveraging a unique longitudinal, passive viewing fMRI dataset. We systematically investigated combinations of global signal regression (GSR), volume censoring, and ICA-AROMA. Pipelines were compared using previously established metrics of noise removal as well as metrics sensitive to recovery of individual differences (i.e., connectome fingerprinting), and stimulus-evoked responses (i.e., intersubject correlations; ISC). We found that: 1) the most efficacious pipeline for both noise removal and information recovery included censoring, GSR, bandpass filtering, and head motion parameter (HMP) regression, 2) ICA-AROMA performed similarly to HMP regression and did not obviate the need for censoring, 3) GSR had a minimal impact on connectome fingerprinting but improved ISC, and 4) the strictest censoring approaches reduced motion correlated edges but negatively impacted identifiability.

Videogame exposure positively associates with selective attention in a cross-sectional sample of young children.

There is growing interest in how exposure to videogames is associated with young children's development. While videogames may displace time from developmentally important activities and have been related to lower reading skills, work in older children and adolescents has suggested that experience with attention-demanding/fast-reaction games positively associates with attention and visuomotor skills. In the current study, we assessed 154 children aged 4-7 years (77 male; mean age 5.38) whose parents reported average daily weekday recreational videogame time, including information about which videogames were played. We investigated associations between videogame exposure and children's sustained, selective, and executive attention skills. We found that videogame time was significantly positively associated only with selective attention. Longitudinal studies are needed to elucidate the directional association between time spent playing recreational videogames and attention skills.