Connectomes’ topological organization can be quantified using graph theory. Here, we investigated brain networks in higher dimensional spaces defined by up to 10 graph theoretic nodal properties. These properties assign a score to nodes, reflecting their meaning in the network. Using 100 healthy unrelated subjects from the Human Connectome Project, we generated various connectomes (structural/functional, binary/weighted). We observed that nodal properties are correlated (i.e., they carry similar information) at whole-brain and subnetwork level. We conducted an exploratory machine learning analysis to test whether high-dimensional network information differs between sensory and association areas. Brain regions of sensory and association networks were classified with an 80–86% accuracy in a 10-dimensional (10D) space. We observed the largest gain in machine learning accuracy going from a 2D to 3D space, with a plateauing accuracy toward 10D space, and nonlinear Gaussian kernels outperformed linear kernels. Finally, we quantified the Euclidean distance between nodes in a 10D graph space. The multidimensional Euclidean distance was highest across subjects in the default mode network (in structural networks) and frontoparietal and temporal lobe areas (in functional networks). To conclude, we propose a new framework for quantifying network features in high-dimensional spaces that may reveal new network properties of the brain. Author Summary Nodal properties are of particular importance when investigating patterns in brain networks. Nodal information is usually studied by comparing a few nodal measurements (up to three), resulting in analyses in three-dimensional spaces, at maximum. We offer a new framework to extend these approaches by defining new, up to 10-dimensional, mathematical spaces, called graph spaces, built using up to 10 nodal properties. We show that correlations between nodal properties express differences regarding connectome models (structural/functional, binary/weighted) and brain subnetworks. We provide early application and quantification of machine learning in graph spaces of dimensions 2 to 10, as well as a quantification of single brain regions, and global connectome, Euclidean distance in a 10-dimensional graph space. This provides new tools to quantify network features in high-dimensional spaces.

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.

Clinical network neuroscience, the study of brain network topology in neurological and psychiatric diseases, has become a mainstay field within clinical neuroscience. Being a multidisciplinary group of clinical network neuroscience experts based in The Netherlands, we often discuss the current state of the art and possible avenues for future investigations. These discussions revolve around questions like “How do dynamic processes alter the underlying structural network?” and “Can we use network neuroscience for disease classification?” This opinion paper is an incomplete overview of these discussions and expands on ten questions that may potentially advance the field. By no means intended as a review of the current state of the field, it is instead meant as a conversation starter and source of inspiration to others.

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.