Title: Reduced ventral attention network connectivity is linked to the accelerated maturation of adult-like cortical organization in childhood

Across the transition from childhood to adolescence the human brain experiences profound functional changes, shifting from an organizational framework anchored within somatosensory/motor and visual regions into one that is balanced through interactions with later-maturing aspects of association cortex. Here, we provide evidence linking this profile of large-scale functional reorganization to developmental shifts in attention network connectivity. We demonstrate that changes in functional connectivity between childhood and adolescence are preferential to the salience/ventral attention network. Excluding these network-linked vertices from analysis effectively removes developmental changes in cortical organization, while connectivity within the ventral attention network predicts intellectual ability. Children with low ventral attention network connectivity exhibit adolescent-like topographical profiles, suggesting attentional systems may be critically important for understanding how brain functions are refined across development. These data highlight a core role for the ventral attention network in supporting age-dependent shifts in the macroscale organization of cortex across development. Introduction The human brain undergoes a series of staged developmental cascades across childhood and adolescence progressing from unimodal somatosensory/motor and visual regions through the transmodal association cortex territories that support complex cognitive functions. Evidence for the scheduled timing of these neurodevelopmental events has emerged across biological scales, from regional profiles of cellular maturation, synapse formation and dendritic pruning, and intracortical myelination through macro-scale morphological features including folding patterns and associated areal expansion. These processes are imbedded within age dependent anatomical changes across lifespan, particularly the prolonged development of association cortex territories. In parallel, substantial progress has been made characterizing the organization and spatiotemporal maturation of large-scale functional systems across cortex. Here, in vivo imaging work strongly supports the development of a hierarchical axis, or gradient, of cortical organization, with association territories anchored at the opposite end of a broad functional spectrum from primary sensory and motor regions. Despite clear evidence for age-dependent shifts in the macroscale organization of the cortex from childhood through adolescence, the manner and extent to which specific functional networks may contribute to the widespread process of cortical maturation remains elusive. The focused study of discrete functional circuits has provided foundational insights in core maturational processes. For example, discoveries linking hierarchical changes within amygdalaand ventral striatal-medial prefrontal cortex (mPFC) circuitry to the development of emotional and social functioning in adolescence. Yet, the maturational refinement these subcortical-cortical circuits does not occur in isolation. Rather, they are embedded within a broad restructuring of functional systems across the cortical sheet. Here, areal and network boundaries become more clearly defined throughout development, while the predominance of local connectivity patterns in childhood gradually gives way to long distance, integrative, connections in adolescence. This reflects a developmental transition from an anatomically constrained organizational motif to a topographically distributed system. In children, this complex functional architecture is situated within the unimodal cortex, between somatosensory/motor and visual regions. Conversely, adolescents transition into an adult-like gradient, anchored at one end by unimodal regions supporting primary sensory/motor functions and at the other end by the association cortex. While the organizational profiles of large-scale cortical networks are distinct across childhood and adolescence, the extent to which developmental changes within select functional couplings may account for the drastic reorganization in the brain hierarchy remains an open question. By one view, the developmental transition from unimodal though association cortices reflect the coordinated and shared influence of maturational changes across multiple functional systems spanning the entire connectome. An alternative, although not mutually exclusive, possibility is that specific brain networks may play a preferential role in the widespread developmental refinement of cortical connectivity. Individual cortical parcels are functionally organized along a global gradient that transitions from somato/motor and visual regions at one end and multimodal association cortex at the other. The hierarchical nature of these functional relationships reflects a core feature of brain organization in both adolescents and adults. Incoming sensory information undergoes a process of extensive elaboration and attentional modulation as it cascades into deeper layers of cortical processing. Visual system connectivity, as one example, moves along the dorsal and ventral visual streams, eventually converging within aspects of the dorsal and ventral attention networks including the anterior insula, superior parietal cortex, and operculum parietal before eventually filtering through multimodal convergence zones, particularly the default network. Although speculative, these data suggest a possible preferential role for sensory orienting and attentional systems in the integrity of the information processing hierarchies in the human brain. Intriguingly, there is converging evidence to suggest the staged development of a ventral attention network, encompassing aspects of anterior insula, anterior prefrontal cortex and anterior cingulate cortex (see also, cingulo-opercular network and salience network), that follows the age-dependent shifts in cortical organization across childhood and adolescence. The salience/ventral attentional network, together with frontoparietal network, have been proposed to constitute a dual-network system for the ‘top-down’ and ‘bottom-up’ processing necessary for adaptive behavioral responses, supporting the functional propagation of information from primary somato/motor, visual, auditory cortex through the default network. These dissociable attentional and control systems are interconnected in children but later segregate over the course of adolescence to eventually form the parallel architectures that support adaptive behavior in adulthood. This indicates the attention system may play a preferential role in the transformative brain changes occurring throughout childhood and adolescence. As such, characterizing the relationships linking attention network connectivity and age-dependent changes in the macroscale brain organization would provide a tremendous opportunity to understand how the functional architecture of cortex is shaped and sculpted across the human lifespan. In the present study we examined the extent to which specific functional networks may serve to underpin the age-dependent maturation of functional gradient patterns across the cortical sheet. To directly address this open question, we first established the cortical territories exhibiting pronounced functional changes in a longitudinal sample of children and adolescents, revealing the preferential presence of developmental shifts within the ventral attention network. Gradient analyses excluding regions exhibiting the maximal developmental change in children resulted in an accelerated maturation of adolescent-like gradient patterns, suggesting ventral attention territories play a core role in the expression of adolescent-like connectivity gradients. Moreover, children with low ventral attention connectivity exhibited an accelerated profile of cortical maturation that closely resembles prior reports in adolescents and adults. Highlighting the importance of attention network connectivity in cognitive functioning, standardized measures of intelligence linked with reduced attention network degree centrality in children and adolescents. Collectively, these data suggest that ventral attention system functioning in childhood and adolescence may underpin the developmental reorganization and maturation of functional networks across the cortical sheet.