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  • A limitation to be considered in the present study

    2018-10-25

    A limitation to be considered in the present study is whether the seed regions selected for this study were ideal. There is limited precedence for coordinate selection in a fetal sample and a paucity of labeled fetal atlases or analyses tools available (Anderson and Thomason, 2013). Thus, for the present analysis, we adhered tightly to procedures successfully used in premature infants (Smyser et al., 2010) as these best approximate neuroanatomy of our study sample. Another limitation of our study is that we evaluated only 10 XYZ coordinates (i.e., seed regions) all located in the right hemisphere. This was an intentional constraint as we sought to restrict the total number of comparisons to reduce the possibility of introducing type I error (i.e., false positives). By comparison, prior resting-state analyses in preterm infants have tested 5–30 seed regions and have used more relaxed significance thresholds (Doria et al., 2010; Smyser et al., 2010). A final significant concern to be considered in the present study is potential error introduced by fetal motion. Recent studies of the effects of motion on resting-state fMRI have shown that even ‘micro-movement’, as small as 0.2 mm, can impact observed patterns of functional connectivity (Power et al., 2012; Satterthwaite et al., 2013; Van Dijk et al., 2012). Disconcertingly, these investigations show that increased movement can falsely inflate short-range connectivity and decrease long-range connectivity. To mitigate movement related error, we excluded high motion frames across subjects, resulting in similar overall movement across age groups. By intentionally removing equivalent frame numbers in older and younger fetal groups we were also able to assure that fetal participants were matched on total number of frames analyzed. By controlling these variables across groups we limited concern that quality of neuroimaging data may influence observed effects.
    Conclusions Through resting-state evaluation of healthy human fetuses we have identified the earliest forms of neural functional connectivity. Motor, visual, thalamic, DMN, frontal, and temporal networks likely represent immature forms of those described in older populations. We observed temporal coherence across (1) cerebral-cerebellar, (2) cortical-subcortical, (3) intra-hemispheric cortical, and (4) bilateral, cross-hemispheric structures, suggesting many forms of cerebral connectivity are present by the third trimester. We also observed that older fetuses possess significantly more long-range connections than younger fetuses. By evaluating resting-state fMRI in healthy human fetuses we have gained new information about operations in functional AP20187 Supplier circuits in utero. Continued development and use of fetal resting-state fMRI is likely to result in major discoveries for clinical, perinatal and neurological sciences.
    Conflict of interest statement
    Funding This research was supported, in part, by the Merrill Palmer Skillman Institute for Child and Family Development, by the Department of Pediatrics, Wayne State University (WSU) School of Medicine, and by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services. This project was also supported by WSU\'s Perinatology Virtual Discovery Grant (made possible by the W.K. Kellogg Foundation) and WSU\'s President\'s BRAIN Research Enhancement Program awards to MET. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
    Acknowledgements
    Introduction Adolescence is recognized as a period of increased behavioral risk associated with greater mortality (Eaton et al., 2012). Although direct links between real-world risk-taking and brain maturation have yet to be established, research to date suggests that neural systems supporting cognitive control and incentive processing follow different developmental trajectories, which may lead to increased impulsivity in the face of rewarding situations (Casey et al., 2008; Galvan et al., 2006; Luna et al., 2014; Steinberg, 2005). Although initial neurodevelopmental studies have been influential in guiding research toward the interaction of reward processing and cognitive control, there are three limitations in the existing literature. First, in tasks where performance increases with age (e.g., the antisaccade task; Luna et al., 2001), many prior studies have not compared neural activation patterns due to both task performance and age. That is to say, while developmental studies often control performance differences by using tasks that generate equal performance or though analytic models, in the present study we placed both behavior and age into the same model to account for shared vs. unique variance explained by each, allowing for the examination of their interaction. Second, most developmental studies have been cross-sectional in design, limiting implications toward developmental change (Singer and Willett, 2003). We address these limitations by focusing on how incentives, age, and performance, modulate brain activity during inhibitory control throughout middle childhood to young adulthood using an accelerated longitudinal design.