One way to increase the statistical power and generalizability of neuroimaging studies is to collect data at multiple sites or merge multiple cohorts. However, this usually comes with site-related biases due to the heterogeneity of scanners and acquisition parameters, negatively impacting sensitivity. Brain structural connectomes are not an exception: Being derived from T1-weighted and diffusion-weighted magnetic resonance images, structural connectivity is impacted by differences in imaging protocol. Beyond minimizing acquisition parameter differences, removing bias with postprocessing is essential. In this work we create, from the exhaustive Human Connectome Project Young Adult dataset, a resampled dataset of different b -values and spatial resolutions, modeling a cohort scanned across multiple sites. After demonstrating the statistical impact of acquisition parameters on connectivity, we propose a linear regression with explicit modeling of b -value and spatial resolution, and validate its performance on separate datasets. We show that b -value and spatial resolution affect connectivity in different ways and that acquisition bias can be reduced using a linear regression informed by the acquisition parameters while retaining interindividual differences and hence boosting fingerprinting performance. We also demonstrate the generative potential of our model, and its generalization capability in an independent dataset reflective of typical acquisition practices in clinical settings. Author Summary One of the main roadblocks to using multisite neuroimaging data is the effect of acquisition bias due to the heterogeneity of acquisition parameters associated with various sites. This can negatively impact the sensitivity of machine learning models employed in neuroscience. Thus, it is extremely important to model the effect of this bias. In this work, we address this issue at the level of brain structural connectivity, an important biomarker for various brain disorders. We propose a simple linear regression model to minimize this effect using high-quality data from the Human Connectome Project, and show its generalizability to a clinical dataset.

The dynamic repertoire of functional brain networks is constrained by the underlying topology of structural connections. Despite this intrinsic relationship between structural connectivity (SC) and functional connectivity (FC), integrative and multimodal approaches to combine the two remain limited. Here, we propose a new adaptive filter for estimating dynamic and directed FC using structural connectivity information as priors. We tested the filter in rat epicranial recordings and human event-related EEG data, using SC priors from a meta-analysis of tracer studies and diffusion tensor imaging metrics, respectively. We show that, particularly under conditions of low signal-to-noise ratio, SC priors can help to refine estimates of directed FC, promoting sparse functional networks that combine information from structure and function. In addition, the proposed filter provides intrinsic protection against SC-related false negatives, as well as robustness against false positives, representing a valuable new tool for multimodal imaging in the context of dynamic and directed FC analysis.

Author Summary In the present report we asked how signals travel on brain networks and what types of nodes they potentially visit en route. We traced individual path motifs to investigate the propensity of communication paths to explore the putative unimodal-transmodal cortical hierarchy. We find that the architecture of the network promotes signaling via the hierarchy, suggesting a link between the structure and function of the network. Importantly, we also find instances where detours are promoted, particularly as paths traverse attention-related networks. Finally, information about hierarchical position aids navigation in some parts of the network, over and above spatial location. Altogether, the present results touch on several emerging themes in network neuroscience, including the nature of structure-function relationships, network communication and the role of cortical hierarchies. Abstract The wiring of the brain is organized around a putative unimodal-transmodal hierarchy. Here we investigate how this intrinsic hierarchical organization of the brain shapes the transmission of information among regions. The hierarchical positioning of individual regions was quantified by applying diffusion map embedding to resting-state functional MRI networks. Structural networks were reconstructed from diffusion spectrum imaging and topological shortest paths among all brain regions were computed. Sequences of nodes encountered along a path were then labeled by their hierarchical position, tracing out path motifs. We find that the cortical hierarchy guides communication in the network. Specifically, nodes are more likely to forward signals to nodes closer in the hierarchy and cover a range of unimodal and transmodal regions, potentially enriching or diversifying signals en route. We also find evidence of systematic detours, particularly in attention networks, where communication is rerouted. Altogether, the present work highlights how the cortical hierarchy shapes signal exchange and imparts behaviorally relevant communication patterns in brain networks.

Recently, EEG recording techniques and source analysis have improved, making it feasible to tap into fast network dynamics. Yet, analyzing whole-cortex EEG signals in source space is not standard, partly because EEG suffers from volume conduction: Functional connectivity (FC) reflecting genuine functional relationships is impossible to disentangle from spurious FC introduced by volume conduction. Here, we investigate the relationship between white matter structural connectivity (SC) and large-scale network structure encoded in EEG-FC. We start by confirming that FC (power envelope correlations) is predicted by SC beyond the impact of Euclidean distance, in line with the assumption that SC mediates genuine FC. We then use information from white matter structural connectivity in order to smooth the EEG signal in the space spanned by graphs derived from SC. Thereby, FC between nearby, structurally connected brain regions increases while FC between nonconnected regions remains unchanged, resulting in an increase in genuine, SC-mediated FC. We analyze the induced changes in FC, assessing the resemblance between EEG-FC and volume-conduction- free fMRI-FC, and find that smoothing increases resemblance in terms of overall correlation and community structure. This result suggests that our method boosts genuine FC, an outcome that is of interest for many EEG network neuroscience questions. Author Summary In this study, we combine high-density EEG recorded during resting state with white matter connectivity obtained from diffusion MRI and fiber tracking. We leverage the additional information contained in the structural connectome towards augmenting the source-level EEG functional connectivity. In particular, it is known—and confirmed in this study—that the activity of brain regions that possess a direct anatomical connection is, on average, more strongly correlated than that of regions that have no such direct link. We use the structural connectome to define a graph and smooth the source-reconstructed EEG signal in the space spanned by this graph. We compare the resulting “filtered” signal correlation matrices with those obtained from fMRI and find that such “graph filtering” improves the agreement between EEG and fMRI functional connectivity structure. This suggests that structural connectivity can be used to attenuate some of the limitations imposed by volume conduction.

Late human development is characterized by the maturation of high-level functional processes, which rely on reshaping of white matter connections, as well as synaptic density. However, the relationship between the whole-brain dynamics and the underlying white matter networks in neurodevelopment is largely unknown. In this study, we focused on how the structural connectome shapes the emerging dynamics of cerebral development between the ages of 6 and 33 years, using functional and diffusion magnetic resonance imaging combined into a spatiotemporal connectivity framework. We defined two new measures of brain dynamics, namely the system diversity and the spatiotemporal diversity, which quantify the level of integration/segregation between functional systems and the level of temporal self-similarity of the functional patterns of brain dynamics, respectively. We observed a global increase in system diversity and a global decrease and local refinement in spatiotemporal diversity values with age. In support of these findings, we further found an increase in the usage of long-range and inter-system white matter connectivity and a decrease in the usage of short-range connectivity with age. These findings suggest that dynamic functional patterns in the brain progressively become more integrative and temporally self-similar with age. These functional changes are supported by a greater involvement of long-range and inter-system axonal pathways. Author Summary Maturation in human development is represented by changes in both functional dynamics and structural connectivity in the human brain. By constructing a spatiotemporal connectome for a cohort of 81 subjects ranging from 6 to 33 years of age, we demonstrate how these changes can be studied in a unified framework. We do so by defining two new measures of brain dynamics, namely the spatiotemporal diversity, mapping the level of temporal self-similarity of the functional patterns of brain dynamics, and system diversity, quantifying the level of integration/segregation between functional systems. These measures, we argue, represent a novel way of looking at brain dynamics constraints by structural connectivity. Using these measures, we show that dynamic functional patterns in the brain progressively become more integrative and temporally self-similar with age.

Author Summary Sparse structural connectivity data from many subjects can be succinctly represented using appropriate averaging procedures. We show, however, that several popular procedures for doing so generate group-averaged networks with statistics that are dissimilar from the subject-level networks they are intended to represent. These dissimilarities, we argue, arise from the over- and underexpression of short-range and long-distance connections, respectively, in the group-averaged matrix. We present a distance-dependent thresholding procedure that preserves connection length distributions and consequently better matches subject-level networks and their statistics. These findings inform data-driven exploratory analyses of connectomes. Abstract Large-scale structural brain networks encode white matter connectivity patterns among distributed brain areas. These connection patterns are believed to support cognitive processes and, when compromised, can lead to neurocognitive deficits and maladaptive behavior. A powerful approach for studying the organizing principles of brain networks is to construct group-representative networks from multisubject cohorts. Doing so amplifies signal to noise ratios and provides a clearer picture of brain network organization. Here, we show that current approaches for generating sparse group-representative networks overestimate the proportion of short-range connections present in a network and, as a result, fail to match subject-level networks along a wide range of network statistics. We present an alternative approach that preserves the connection-length distribution of individual subjects. We have used this method in previous papers to generate group-representative networks, though to date its performance has not been appropriately benchmarked and compared against other methods. As a result of this simple modification, the networks generated using this approach successfully recapitulate subject-level properties, outperforming similar approaches by better preserving features that promote integrative brain function rather than segregative. The method developed here holds promise for future studies investigating basic organizational principles and features of large-scale structural brain networks.