Since initial reports regarding the impact of motion artifact on measures of functional connectivity, there has been a proliferation of participant-level confound regression methods to limit its ...impact. However, many of the most commonly used techniques have not been systematically evaluated using a broad range of outcome measures. Here, we provide a systematic evaluation of 14 participant-level confound regression methods in 393 youths. Specifically, we compare methods according to four benchmarks, including the residual relationship between motion and connectivity, distance-dependent effects of motion on connectivity, network identifiability, and additional degrees of freedom lost in confound regression. Our results delineate two clear trade-offs among methods. First, methods that include global signal regression minimize the relationship between connectivity and motion, but result in distance-dependent artifact. In contrast, censoring methods mitigate both motion artifact and distance-dependence, but use additional degrees of freedom. Importantly, less effective de-noising methods are also unable to identify modular network structure in the connectome. Taken together, these results emphasize the heterogeneous efficacy of existing methods, and suggest that different confound regression strategies may be appropriate in the context of specific scientific goals.
•We evaluate 14 participant-level de-noising pipelines for functional connectivity.•Pipeline performance is markedly heterogeneous.•GSR minimizes the impact of motion but introduces distance dependence.•Censoring reduces motion and improves network identifiability.
The human brain is organized into large-scale functional modules that have been shown to evolve in childhood and adolescence. However, it remains unknown whether the underlying white matter ...architecture is similarly refined during development, potentially allowing for improvements in executive function. In a sample of 882 participants (ages 8–22) who underwent diffusion imaging as part of the Philadelphia Neurodevelopmental Cohort, we demonstrate that structural network modules become more segregated with age, with weaker connections between modules and stronger connections within modules. Evolving modular topology facilitates global network efficiency and is driven by age-related strengthening of hub edges present both within and between modules. Critically, both modular segregation and network efficiency are associated with enhanced executive performance and mediate the improvement of executive functioning with age. Together, results delineate a process of structural network maturation that supports executive function in youth.
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•Structural brain modules become more segregated during youth•Targeted strengthening of hub edges simultaneously promotes network efficiency•Enhanced modular segregation mediates improvements in executive function in youth
Baum et al. apply network analytic techniques to demonstrate that human white matter networks become increasingly modular during adolescent development. Furthermore, targeted strengthening of hub connections facilitates global network integration. This process of network evolution mediates improvements in executive functioning during youth.
As the human brain develops, it increasingly supports coordinated control of neural activity. The mechanism by which white matter evolves to support this coordination is not well understood. Here we ...use a network representation of diffusion imaging data from 882 youth ages 8-22 to show that white matter connectivity becomes increasingly optimized for a diverse range of predicted dynamics in development. Notably, stable controllers in subcortical areas are negatively related to cognitive performance. Investigating structural mechanisms supporting these changes, we simulate network evolution with a set of growth rules. We find that all brain networks are structured in a manner highly optimized for network control, with distinct control mechanisms predicted in child vs. older youth. We demonstrate that our results cannot be explained by changes in network modularity. This work reveals a possible mechanism of human brain development that preferentially optimizes dynamic network control over static network architecture.
The protracted development of structural and functional brain connectivity within distributed association networks coincides with improvements in higher-order cognitive processes such as executive ...function. However, it remains unclear how white-matter architecture develops during youth to directly support coordinated neural activity. Here, we characterize the development of structure–function coupling using diffusion-weighted imaging and n-back functional MRI data in a sample of 727 individuals (ages 8 to 23 y). We found that spatial variability in structure–function coupling aligned with cortical hierarchies of functional specialization and evolutionary expansion. Furthermore, hierarchy-dependent age effects on structure–function coupling localized to transmodal cortex in both cross-sectional data and a subset of participants with longitudinal data (n = 294). Moreover, structure–function coupling in rostrolateral prefrontal cortex was associated with executive performance and partially mediated age-related improvements in executive function. Together, these findings delineate a critical dimension of adolescent brain development, whereby the coupling between structural and functional connectivity remodels to support functional specialization and cognition.
Adolescence is characterized by the maturation of cortical microstructure and connectivity supporting complex cognition and behavior. Axonal myelination influences brain connectivity during ...development by enhancing neural signaling speed and inhibiting plasticity. However, the maturational timing of cortical myelination during human adolescence remains poorly understood. Here, we take advantage of recent advances in high-resolution cortical T1w/T2w mapping methods, including principled correction of B1+ transmit field effects, using data from the Human Connectome Project in Development (HCP-D;
= 628, ages 8-21). We characterize microstructural changes relevant to myelination by estimating age-related differences in T1w/T2w throughout the cerebral neocortex from childhood to early adulthood. We apply Bayesian spline models and clustering analysis to demonstrate graded variation in age-dependent cortical T1w/T2w differences that are correlated with the sensorimotor-association (S-A) axis of cortical organization reported by others. In sensorimotor areas, T1w/T2w ratio measures start at high levels at early ages, increase at a fast pace, and decelerate at later ages (18-21). In intermediate multimodal areas along the S-A axis, T1w/T2w starts at intermediate levels and increases linearly at an intermediate pace. In transmodal/paralimbic association areas, T1w/T2w starts at low levels and increases linearly at the slowest pace. These data provide evidence for graded variation of the T1w/T2w ratio along the S-A axis that may reflect cortical myelination changes during adolescence underlying the development of complex information processing and psychological functioning. We discuss the implications of these results as well as caveats in interpreting magnetic resonance imaging (MRI)-based estimates of myelination.
Myelin is a lipid membrane that is essential to healthy brain function. Myelin wraps axons to increase neural signaling speed, enabling complex neuronal functioning underlying learning and cognition. Here, we characterize the developmental timing of myelination across the cerebral cortex during adolescence using a noninvasive proxy measure, T1w/T2w mapping. Our results provide new evidence demonstrating graded variation across the cortex in the timing of T1w/T2w changes during adolescence, with rapid T1w/T2w increases in lower-order sensory areas and gradual T1w/T2w increases in higher-order association areas. This spatial pattern of microstructural brain development closely parallels the sensorimotor-to-association axis of cortical organization and plasticity during ontogeny.
Executive function is a quintessential human capacity that emerges late in development and displays different developmental trends in males and females. Sex differences in executive function in youth ...have been linked to vulnerability to psychopathology as well as to behaviors that impinge on health, wellbeing, and longevity. Yet, the neurobiological basis of these differences is not well understood, in part due to the spatiotemporal complexity inherent in patterns of brain network maturation supporting executive function. Here we test the hypothesis that sex differences in impulsivity in youth stem from sex differences in the controllability of structural brain networks as they rewire over development. Combining methods from network neuroscience and network control theory, we characterize the network control properties of structural brain networks estimated from diffusion imaging data acquired in males and females in a sample of 879 youth aged 8–22 years. We summarize the control properties of these networks by estimating average and modal controllability, two statistics that probe the ease with which brain areas can drive the network towards easy versus difficult-to-reach states. We find that females have higher modal controllability in frontal, parietal, and subcortical regions while males have higher average controllability in frontal and subcortical regions. Furthermore, controllability profiles in males are negatively related to the false positive rate on a continuous performance task, a common measure of impulsivity. Finally, we find associations between average controllability and individual differences in activation during an n-back working memory task. Taken together, our findings support the notion that sex differences in the controllability of structural brain networks can partially explain sex differences in executive function. Controllability of structural brain networks also predicts features of task-relevant activation, suggesting the potential for controllability to represent context-specific constraints on network state more generally.
•White matter network controllability models ease of locally driven state transitions.•Spatial and developmental patterns of controllability are conserved across sexes.•Regional controllability of white matter networks differs by biological sex.•Sex differences in controllability account for variance in impulsivity.•Activation on a working memory task is partially explained by network controllability.
The spatial distribution of large-scale functional networks on the cerebral cortex differs between individuals and is particularly variable in association networks that are responsible for ...higher-order cognition. However, it remains unknown how this functional topography evolves in development and supports cognition. Capitalizing on advances in machine learning and a large sample imaged with 27 min of high-quality functional MRI (fMRI) data (n = 693, ages 8–23 years), we delineate how functional topography evolves during youth. We found that the functional topography of association networks is refined with age, allowing accurate prediction of unseen individuals’ brain maturity. The cortical representation of association networks predicts individual differences in executive function. Finally, variability of functional topography is associated with fundamental properties of brain organization, including evolutionary expansion, cortical myelination, and cerebral blood flow. Our results emphasize the importance of considering the plasticity and diversity of functional neuroanatomy during development and suggest advances in personalized therapeutics.
•Functional topography is most variable in association cortex in youth•Functional topography is refined during youth and encodes brain maturity•Association network functional topography predicts executive function
Cui et al. demonstrate that individual-specific functional networks are refined during youth in humans. Furthermore, the functional topography of association networks predicts individual differences in executive function.
T1-weighted divided by T2-weighted (T1w/T2w) myelin maps were initially developed for neuroanatomical analyses such as identifying cortical areas, but they are increasingly used in statistical ...comparisons across individuals and groups with other variables of interest. Existing T1w/T2w myelin maps contain radiofrequency transmit field (B1+) biases, which may be correlated with these variables of interest, leading to potentially spurious results. Here we propose two empirical methods for correcting these transmit field biases using either explicit measures of the transmit field or alternatively a ‘pseudo-transmit’ approach that is highly correlated with the transmit field at 3T. We find that the resulting corrected T1w/T2w myelin maps are both better neuroanatomical measures (e.g., for use in cross-species comparisons), and more appropriate for statistical comparisons of relative T1w/T2w differences across individuals and groups (e.g., sex, age, or body-mass-index) within a consistently acquired study at 3T. We recommend that investigators who use the T1w/T2w approach for mapping cortical myelin use these B1+ transmit field corrected myelin maps going forward.
Processing and learning from affective cues to guide goal-directed behavior may be particularly important during adolescence; yet the factors that promote and/or disrupt the ability to integrate ...value in order to guide decision making across development remain unclear. The present study (
N
= 1046) assessed individual difference factors (self-reported punishment and reward sensitivity) related to whether previously-rewarded and previously-punished cues differentially impact goal-directed behavior (response inhibition) in a large developmental sample. Participants were between the ages of 8–21 years (
M
age
= 14.29,
SD
= 3.97, 50.38% female). Previously-
rewarded
cues improved response inhibition among participants age 14 and older. Further, punishment sensitivity predicted overall improved response inhibition among participants aged 10 to 18. The results highlight two main factors that are associated with improvements in the ability to integrate value to guide goal-directed behaviour – cues in the environment (e.g., reward-laden cues) and individual differences in punishment sensitivity. These findings have implications for both educational and social policies aimed at characterizing the ways in which youth integrate value to guide decision making.
Brain networks are expected to be modular. However, existing techniques for estimating a network’s modules make it difficult to assess the influence of organizational principles such as wiring cost ...reduction on the detected modules. Here we present a modification of an existing module detection algorithm that allowed us to focus on connections that are unexpected under a cost-reduction wiring rule and to identify modules from among these connections. We applied this technique to anatomical brain networks and showed that the modules we detected differ from those detected using the standard technique. We demonstrated that these novel modules are spatially distributed, exhibit unique functional fingerprints, and overlap considerably with rich clubs, giving rise to an alternative and complementary interpretation of the functional roles of specific brain regions. Finally, we demonstrated that, using the modified module detection approach, we can detect modules in a
developmental dataset that track normative patterns of maturation. Collectively, these findings support the hypothesis that brain networks are composed of modules and provide additional insight into the function of those modules.
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