Recent resting-state functional connectivity fMRI (RS-fcMRI) research has demonstrated that head motion during fMRI acquisition systematically influences connectivity estimates despite bandpass filtering and nuisance regression, which are intended to reduce such nuisance variability. We provide evidence that the effects of head motion and other nuisance signals are poorly controlled when the fMRI time series are bandpass-filtered but the regressors are unfiltered, resulting in the inadvertent reintroduction of nuisance-related variation into frequencies previously suppressed by the bandpass filter, as well as suboptimal correction for noise signals in the frequencies of interest. This is important because many RS-fcMRI studies, including some focusing on motion-related artifacts, have applied this approach. In two cohorts of individuals (n = 117 and 22) who completed resting-state fMRI scans, we found that the bandpass-regress approach consistently overestimated functional connectivity across the brain, typically on the order of r = .10 – .35, relative to a simultaneous bandpass filtering and nuisance regression approach. Inflated correlations under the bandpass-regress approach were associated with head motion and cardiac artifacts. Furthermore, distance-related differences in the association of head motion and connectivity estimates were much weaker for the simultaneous filtering approach. We recommend that future RS-fcMRI studies ensure that the frequencies of nuisance regressors and fMRI data match prior to nuisance regression, and we advocate a simultaneous bandpass filtering and nuisance regression strategy that better controls nuisance-related variability.

The thalamus is globally connected with distributed cortical regions, yet the functional significance of this extensive thalamocortical connectivity remains largely unknown. By performing graph-theoretic analyses on thalamocortical functional connectivity data collected from human participants, we found that most thalamic subdivisions display network properties that are capable of integrating multimodal information across diverse cortical functional networks. From a meta-analysis of a large dataset of functional brain-imaging experiments, we further found that the thalamus is involved in multiple cognitive functions. Finally, we found that focal thalamic lesions in humans have widespread distal effects, disrupting the modular organization of cortical functional networks. This converging evidence suggests that the human thalamus is a critical hub region that could integrate diverse information being processed throughout the cerebral cortex as well as maintain the modular structure of cortical functional networks. The thalamus is traditionally viewed as a passive relay station of information from sensory organs or subcortical structures to the cortex. However, the thalamus has extensive connections with the entire cerebral cortex, which can also serve to integrate information processing between cortical regions. In this study, we demonstrate that multiple thalamic subdivisions display network properties that are capable of integrating information across multiple functional brain networks. Moreover, the thalamus is engaged by tasks requiring multiple cognitive functions. These findings support the idea that the thalamus is involved in integrating information across cortical networks.

Cognitive control, which continues to mature throughout adolescence, is supported by the ability for well-defined organized brain networks to flexibly integrate information. However, the development of intrinsic brain network organization and its relationship to observed improvements in cognitive control are not well understood. In the present study, we used resting state functional magnetic resonance imaging (RS-fMRI), graph theory, the antisaccade task, and rigorous head motion control to characterize and relate developmental changes in network organization, connectivity strength, and integration to inhibitory control development. Subjects were 192 10–26-y-olds who were imaged during 5 min of rest. In contrast to initial studies, our results indicate that network organization is stable throughout adolescence. However, cross-network integration, predominantly of the cingulo-opercular/salience network, increased with age. Importantly, this increased integration of the cingulo-opercular/salience network significantly moderated the robust effect of age on the latency to initiate a correct inhibitory control response. These results provide compelling evidence that the transition to adult-level inhibitory control is dependent upon the refinement and strengthening of integration between specialized networks. Our findings support a novel, two-stage model of neural development, in which networks stabilize prior to adolescence and subsequently increase their integration to support the cross-domain incorporation of information processing critical for mature cognitive control.

The ability to voluntarily inhibit responses to task-irrelevant stimuli, which is a fundamental component of cognitive control, has a protracted development through adolescence. Previous human developmental imaging studies have found immaturities in localized brain activity in children and adolescents. However, little is known about how these regions integrate with age to form the distributed networks known to support cognitive control. In the present study, we used Granger causality analysis to characterize developmental changes in effective connectivity underlying inhibitory control (antisaccade task) compared with reflexive responses (prosaccade task) in human participants. By childhood, few top-down connectivities were evident with increased parietal interconnectivity. By adolescence, connections from prefrontal cortex increased and parietal interconnectivity decreased. From adolescence to adulthood, there was evidence of increased number and strength of frontal connections to cortical regions as well as subcortical regions. Together, results suggest that developmental improvements in inhibitory control may be supported by age-related enhancements in top-down effective connectivity between frontal, oculomotor, and subcortical regions.

Functional hubs are brain regions that play a crucial role in facilitating communication among parallel, distributed brain networks. The developmental emergence and stability of hubs, however, is not well understood. The current study used measures of network topology drawn from graph theory to investigate the development of functional hubs in 99 participants, 10-20 years of age. We found that hub architecture was evident in late childhood and was stable from adolescence to early adulthood. Connectivity between hub and non-hub ("spoke") regions, however, changed with development. From childhood to adolescence, the strength of connections between frontal hubs and cortical and subcortical spoke regions increased. From adolescence to adulthood, hub-spoke connections with frontal hubs were stable, whereas connectivity between cerebellar hubs and cortical spoke regions increased. Our findings suggest that a developmentally stable functional hub architecture provides the foundation of information flow in the brain, whereas connections between hubs and spokes continue to develop, possibly supporting mature cognitive function.