Predictability of cortico-cortical connections in the mammalian brain.

Despite a five order of magnitude range in size, the brains of mammals share many anatomical and functional characteristics that translate into cortical network commonalities. Here we develop a machine learning framework to quantify the degree of predictability of the weighted interareal cortical matrix. Partial network connectivity data were obtained with retrograde tract-tracing experiments generated with a consistent methodology, supplemented by projection length measurements in a nonhuman primate (macaque) and a rodent (mouse). We show that there is a significant level of predictability embedded in the interareal cortical networks of both species. At the binary level, links are predictable with an area under the ROC curve of at least 0.8 for the macaque. Weighted medium and strong links are predictable with an 85%-90% accuracy (mouse) and 70%-80% (macaque), whereas weak links are not predictable in either species. These observations reinforce earlier observations that the formation and evolution of the cortical network at the mesoscale is, to a large extent, rule based. Using the methodology presented here, we performed imputations on all area pairs, generating samples for the complete interareal network in both species. These are necessary for comparative studies of the connectome with minimal bias, both within and across species.

Diffusive persistence on disordered lattices and random networks.

To better understand the temporal characteristics and the lifetime of fluctuations in stochastic processes in networks, we investigated diffusive persistence in various graphs. Global diffusive persistence is defined as the fraction of nodes for which the diffusive field at a site (or node) has not changed sign up to time t (or, in general, that the node remained active or inactive in discrete models). Here we investigate disordered and random networks and show that the behavior of the persistence depends on the topology of the network. In two-dimensional (2D) disordered networks, we find that above the percolation threshold diffusive persistence scales similarly as in the original 2D regular lattice, according to a power law P(t,L)∼t^{-θ} with an exponent θ≃0.186, in the limit of large linear system size L. At the percolation threshold, however, the scaling exponent changes to θ≃0.141, as the result of the interplay of diffusive persistence and the underlying structural transition in the disordered lattice at the percolation threshold. Moreover, studying finite-size effects for 2D lattices at and above the percolation threshold, we find that at the percolation threshold, the long-time asymptotic value obeys a power law P(t,L)∼L^{-zθ} with z≃2.86 instead of the value of z=2 normally associated with finite-size effects on 2D regular lattices. In contrast, we observe that in random networks without a local regular structure, such as Erdos-Rényi networks, no simple power-law scaling behavior exists above the percolation threshold.

Neuroscience Needs Network Science.

The brain is a complex system comprising a myriad of interacting neurons, posing significant challenges in understanding its structure, function, and dynamics. Network science has emerged as a powerful tool for studying such interconnected systems, offering a framework for integrating multiscale data and complexity. To date, network methods have significantly advanced functional imaging studies of the human brain and have facilitated the development of control theory-based applications for directing brain activity. Here, we discuss emerging frontiers for network neuroscience in the brain atlas era, addressing the challenges and opportunities in integrating multiple data streams for understanding the neural transitions from development to healthy function to disease. We underscore the importance of fostering interdisciplinary opportunities through workshops, conferences, and funding initiatives, such as supporting students and postdoctoral fellows with interests in both disciplines. By bringing together the network science and neuroscience communities, we can develop novel network-based methods tailored to neural circuits, paving the way toward a deeper understanding of the brain and its functions, as well as offering new challenges for network science.

Neuroscience needs Network Science.

The brain is a complex system comprising a myriad of interacting elements, posing significant challenges in understanding its structure, function, and dynamics. Network science has emerged as a powerful tool for studying such intricate systems, offering a framework for integrating multiscale data and complexity. Here, we discuss the application of network science in the study of the brain, addressing topics such as network models and metrics, the connectome, and the role of dynamics in neural networks. We explore the challenges and opportunities in integrating multiple data streams for understanding the neural transitions from development to healthy function to disease, and discuss the potential for collaboration between network science and neuroscience communities. We underscore the importance of fostering interdisciplinary opportunities through funding initiatives, workshops, and conferences, as well as supporting students and postdoctoral fellows with interests in both disciplines. By uniting the network science and neuroscience communities, we can develop novel network-based methods tailored to neural circuits, paving the way towards a deeper understanding of the brain and its functions.

A continuous-time MaxSAT solver with high analog performance.

Many real-life optimization problems can be formulated in Boolean logic as MaxSAT, a class of problems where the task is finding Boolean assignments to variables satisfying the maximum number of logical constraints. Since MaxSAT is NP-hard, no algorithm is known to efficiently solve these problems. Here we present a continuous-time analog solver for MaxSAT and show that the scaling of the escape rate, an invariant of the solver's dynamics, can predict the maximum number of satisfiable constraints, often well before finding the optimal assignment. Simulating the solver, we illustrate its performance on MaxSAT competition problems, then apply it to two-color Ramsey number R(m, m) problems. Although it finds colorings without monochromatic 5-cliques of complete graphs on N ≤ 42 vertices, the best coloring for N = 43 has two monochromatic 5-cliques, supporting the conjecture that R(5, 5) = 43. This approach shows the potential of continuous-time analog dynamical systems as algorithms for discrete optimization.

The Mouse Cortical Connectome, Characterized by an Ultra-Dense Cortical Graph, Maintains Specificity by Distinct Connectivity Profiles.

The inter-areal wiring pattern of the mouse cerebral cortex was analyzed in relation to a refined parcellation of cortical areas. Twenty-seven retrograde tracer injections were made in 19 areas of a 47-area parcellation of the mouse neocortex. Flat mounts of the cortex and multiple histological markers enabled detailed counts of labeled neurons in individual areas. The observed log-normal distribution of connection weights to each cortical area spans 5 orders of magnitude and reveals a distinct connectivity profile for each area, analogous to that observed in macaques. The cortical network has a density of 97%, considerably higher than the 66% density reported in macaques. A weighted graph analysis reveals a similar global efficiency but weaker spatial clustering compared with that reported in macaques. The consistency, precision of the connectivity profile, density, and weighted graph analysis of the present data differ significantly from those obtained in earlier studies in the mouse.

A multiscale cerebral neurochemical connectome of the rat brain.

Understanding the rat neurochemical connectome is fundamental for exploring neuronal information processing. By using advanced data mining, supervised machine learning, and network analysis, this study integrates over 5 decades of neuroanatomical investigations into a multiscale, multilayer neurochemical connectome of the rat brain. This neurochemical connectivity database (ChemNetDB) is supported by comprehensive systematically-determined receptor distribution maps. The rat connectome has an onion-type structural organization and shares a number of structural features with mesoscale connectomes of mouse and macaque. Furthermore, we demonstrate that extremal values of graph theoretical measures (e.g., degree and betweenness) are associated with evolutionary-conserved deep brain structures such as amygdala, bed nucleus of the stria terminalis, dorsal raphe, and lateral hypothalamus, which regulate primitive, yet fundamental functions, such as circadian rhythms, reward, aggression, anxiety, and fear. The ChemNetDB is a freely available resource for systems analysis of motor, sensory, emotional, and cognitive information processing.

Spatial Embedding and Wiring Cost Constrain the Functional Layout of the Cortical Network of Rodents and Primates.

Mammals show a wide range of brain sizes, reflecting adaptation to diverse habitats. Comparing interareal cortical networks across brains of different sizes and mammalian orders provides robust information on evolutionarily preserved features and species-specific processing modalities. However, these networks are spatially embedded, directed, and weighted, making comparisons challenging. Using tract tracing data from macaque and mouse, we show the existence of a general organizational principle based on an exponential distance rule (EDR) and cortical geometry, enabling network comparisons within the same model framework. These comparisons reveal the existence of network invariants between mouse and macaque, exemplified in graph motif profiles and connection similarity indices, but also significant differences, such as fractionally smaller and much weaker long-distance connections in the macaque than in mouse. The latter lends credence to the prediction that long-distance cortico-cortical connections could be very weak in the much-expanded human cortex, implying an increased susceptibility to disconnection syndromes such as Alzheimer disease and schizophrenia. Finally, our data from tracer experiments involving only gray matter connections in the primary visual areas of both species show that an EDR holds at local scales as well (within 1.5 mm), supporting the hypothesis that it is a universally valid property across all scales and, possibly, across the mammalian class.

Order-to-chaos transition in the hardness of random Boolean satisfiability problems.

Transient chaos is a ubiquitous phenomenon characterizing the dynamics of phase-space trajectories evolving towards a steady-state attractor in physical systems as diverse as fluids, chemical reactions, and condensed matter systems. Here we show that transient chaos also appears in the dynamics of certain efficient algorithms searching for solutions of constraint satisfaction problems that include scheduling, circuit design, routing, database problems, and even Sudoku. In particular, we present a study of the emergence of hardness in Boolean satisfiability (k-SAT), a canonical class of constraint satisfaction problems, by using an analog deterministic algorithm based on a system of ordinary differential equations. Problem hardness is defined through the escape rate κ, an invariant measure of transient chaos of the dynamical system corresponding to the analog algorithm, and it expresses the rate at which the trajectory approaches a solution. We show that for a given density of constraints and fixed number of Boolean variables N, the hardness of formulas in random k-SAT ensembles has a wide variation, approximable by a lognormal distribution. We also show that when increasing the density of constraints α, hardness appears through a second-order phase transition at α_{χ} in the random 3-SAT ensemble where dynamical trajectories become transiently chaotic. A similar behavior is found in 4-SAT as well, however, such a transition does not occur for 2-SAT. This behavior also implies a novel type of transient chaos in which the escape rate has an exponential-algebraic dependence on the critical parameter κ∼N^{B|α-α_{χ}|^{1-γ}} with 0<γ<1. We demonstrate that the transition is generated by the appearance of metastable basins in the solution space as the density of constraints α is increased.

Quantifying randomness in real networks.

Represented as graphs, real networks are intricate combinations of order and disorder. Fixing some of the structural properties of network models to their values observed in real networks, many other properties appear as statistical consequences of these fixed observables, plus randomness in other respects. Here we employ the dk-series, a complete set of basic characteristics of the network structure, to study the statistical dependencies between different network properties. We consider six real networks--the Internet, US airport network, human protein interactions, technosocial web of trust, English word network, and an fMRI map of the human brain--and find that many important local and global structural properties of these networks are closely reproduced by dk-random graphs whose degree distributions, degree correlations and clustering are as in the corresponding real network. We discuss important conceptual, methodological, and practical implications of this evaluation of network randomness, and release software to generate dk-random graphs.

Reducing degeneracy in maximum entropy models of networks.

Based on Jaynes's maximum entropy principle, exponential random graphs provide a family of principled models that allow the prediction of network properties as constrained by empirical data (observables). However, their use is often hindered by the degeneracy problem characterized by spontaneous symmetry breaking, where predictions fail. Here we show that degeneracy appears when the corresponding density of states function is not log-concave, which is typically the consequence of nonlinear relationships between the constraining observables. Exploiting these nonlinear relationships here we propose a solution to the degeneracy problem for a large class of systems via transformations that render the density of states function log-concave. The effectiveness of the method is demonstrated on examples.

Predicting commuter flows in spatial networks using a radiation model based on temporal ranges.

Understanding network flows such as commuter traffic in large transportation networks is an ongoing challenge due to the complex nature of the transportation infrastructure and human mobility. Here we show a first-principles based method for traffic prediction using a cost-based generalization of the radiation model for human mobility, coupled with a cost-minimizing algorithm for efficient distribution of the mobility fluxes through the network. Using US census and highway traffic data, we show that traffic can efficiently and accurately be computed from a range-limited, network betweenness type calculation. The model based on travel time costs captures the log-normal distribution of the traffic and attains a high Pearson correlation coefficient (0.75) when compared with real traffic. Because of its principled nature, this method can inform many applications related to human mobility driven flows in spatial networks, ranging from transportation, through urban planning to mitigation of the effects of catastrophic events.

Cortical high-density counterstream architectures.

Small-world networks provide an appealing description of cortical architecture owing to their capacity for integration and segregation combined with an economy of connectivity. Previous reports of low-density interareal graphs and apparent small-world properties are challenged by data that reveal high-density cortical graphs in which economy of connections is achieved by weight heterogeneity and distance-weight correlations. These properties define a model that predicts many binary and weighted features of the cortical network including a core-periphery, a typical feature of self-organizing information processing systems. Feedback and feedforward pathways between areas exhibit a dual counterstream organization, and their integration into local circuits constrains cortical computation. Here, we propose a bow-tie representation of interareal architecture derived from the hierarchical laminar weights of pathways between the high-efficiency dense core and periphery.

A predictive network model of cerebral cortical connectivity based on a distance rule.

Recent advances in neuroscience have engendered interest in large-scale brain networks. Using a consistent database of cortico-cortical connectivity, generated from hemisphere-wide, retrograde tracing experiments in the macaque, we analyzed interareal weights and distances to reveal an important organizational principle of brain connectivity. Using appropriate graph theoretical measures, we show that although very dense (66%), the interareal network has strong structural specificity. Connection weights exhibit a heavy-tailed lognormal distribution spanning five orders of magnitude and conform to a distance rule reflecting exponential decay with interareal separation. A single-parameter random graph model based on this rule predicts numerous features of the cortical network: (1) the existence of a network core and the distribution of cliques, (2) global and local binary properties, (3) global and local weight-based communication efficiencies modeled as network conductance, and (4) overall wire-length minimization. These findings underscore the importance of distance and weight-based heterogeneity in cortical architecture and processing.

Why data coherence and quality is critical for understanding interareal cortical networks.

Numerous studies have investigated inter-areal cortical networks using either diffusion MRI or axonal tract-tracing. While both techniques have been used in non-human primates only diffusion MRI can be used in human. The advantage of axonal tract-tracing is that unlike diffusion MRI it has a high single-cell resolution, and most importantly gives the laminar origins and terminations of inter-areal pathways. It, therefore, can be used to obtain the weighted and directed cortical graph. Axonal tract tracing has traditionally been collated from multiple experiments in order to determine the large-scale inter-areal network. Collated data of this kind present numerous problems due to lack of coherence across studies and incomplete exploitation. We have therefore developed a consistent data base which uses standardized experimental and parcellation procedures across brains. Here we review our recent publications analyzing the consistent database obtained from retrograde tracer injections in 29 cortical areas in a parcellation of 91 areas of the macaque cortex. Compared to collated data, our results show that the cortical graph is dense. Density is a graph theoretic measure, and refers to the number of observed connections in a square matrix expressed as a percentage of the possible connections. In our database 66% of the connections that can exist do exist which is considerably higher than the graph densities reported in studies using collated data (7-32%). The consistent data base reports 37% more pathways than previously reported, many of which are unidirectional. This latter and unexpected property has not been reported in earlier studies. Given the high density, the resulting cortical graph shows other unexpected properties. Firstly, the binary specificity is considerably higher than expected. As we show, this property is a consequence of the inter-areal connection probability declining with distance. Secondly, small groups of areas are found to receive high numbers of inputs. This is termed a high domination and is analyzed by a graph theoretic procedure known as a minimum dominating set analysis. We discuss these findings with respect to the long-distance connections, over half of which were previously not reported. These so called new found projections display high specificities and play an important integration role across large regions. It is to be expected that the future examination of the 62 remaining areas will disclose further levels of complexity and enable construction of a weighted directed graph revealing the hierarchical complexity of the cortex.

The role of long-range connections on the specificity of the macaque interareal cortical network.

We investigated the influence of interareal distance on connectivity patterns in a database obtained from the injection of retrograde tracers in 29 areas distributed over six regions (occipital, temporal, parietal, frontal, prefrontal, and limbic). One-third of the 1,615 pathways projecting to the 29 target areas were reported only recently and deemed new-found projections (NFPs). NFPs are predominantly long-range, low-weight connections. A minimum dominating set analysis (a graph theoretic measure) shows that NFPs play a major role in globalizing input to small groups of areas. Randomization tests show that (i) NFPs make important contributions to the specificity of the connectivity profile of individual cortical areas, and (ii) NFPs share key properties with known connections at the same distance. We developed a similarity index, which shows that intraregion similarity is high, whereas the interregion similarity declines with distance. For area pairs, there is a steep decline with distance in the similarity and probability of being connected. Nevertheless, the present findings reveal an unexpected binary specificity despite the high density (66%) of the cortical graph. This specificity is made possible because connections are largely concentrated over short distances. These findings emphasize the importance of long-distance connections in the connectivity profile of an area. We demonstrate that long-distance connections are particularly prevalent for prefrontal areas, where they may play a prominent role in large-scale communication and information integration.

The chaos within Sudoku.

The mathematical structure of Sudoku puzzles is akin to hard constraint satisfaction problems lying at the basis of many applications, including protein folding and the ground-state problem of glassy spin systems. Via an exact mapping of Sudoku into a deterministic, continuous-time dynamical system, here we show that the difficulty of Sudoku translates into transient chaotic behavior exhibited by this system. We also show that the escape rate κ, an invariant of transient chaos, provides a scalar measure of the puzzle's hardness that correlates well with human difficulty ratings. Accordingly, η = -log10κ can be used to define a "Richter"-type scale for puzzle hardness, with easy puzzles having 0 < η ≤ 1, medium ones 1 < η ≤ 2, hard with 2 < η ≤ 3 and ultra-hard with η > 3. To our best knowledge, there are no known puzzles with η > 4.

Range-limited centrality measures in complex networks.

Here we present a range-limited approach to centrality measures in both nonweighted and weighted directed complex networks. We introduce an efficient method that generates for every node and every edge its betweenness centrality based on shortest paths of lengths not longer than ℓ=1,...,L in the case of nonweighted networks, and for weighted networks the corresponding quantities based on minimum weight paths with path weights not larger than w(ℓ)=ℓΔ, ℓ=1,2...,L=R/Δ. These measures provide a systematic description on the positioning importance of a node (edge) with respect to its network neighborhoods one step out, two steps out, etc., up to and including the whole network. They are more informative than traditional centrality measures, as network transport typically happens on all length scales, from transport to nearest neighbors to the farthest reaches of the network. We show that range-limited centralities obey universal scaling laws for large nonweighted networks. As the computation of traditional centrality measures is costly, this scaling behavior can be exploited to efficiently estimate centralities of nodes and edges for all ranges, including the traditional ones. The scaling behavior can also be exploited to show that the ranking top list of nodes (edges) based on their range-limited centralities quickly freezes as a function of the range, and hence the diameter-range top list can be efficiently predicted. We also show how to estimate the typical largest node-to-node distance for a network of N nodes, exploiting the afore-mentioned scaling behavior. These observations were made on model networks and on a large social network inferred from cell-phone trace logs (∼5.5×10(6) nodes and ∼2.7×10(7) edges). Finally, we apply these concepts to efficiently detect the vulnerability backbone of a network (defined as the smallest percolating cluster of the highest betweenness nodes and edges) and illustrate the importance of weight-based centrality measures in weighted networks in detecting such backbones.

Complexity of the international agro-food trade network and its impact on food safety.

With the world's population now in excess of 7 billion, it is vital to ensure the chemical and microbiological safety of our food, while maintaining the sustainability of its production, distribution and trade. Using UN databases, here we show that the international agro-food trade network (IFTN), with nodes and edges representing countries and import-export fluxes, respectively, has evolved into a highly heterogeneous, complex supply-chain network. Seven countries form the core of the IFTN, with high values of betweenness centrality and each trading with over 77% of all the countries in the world. Graph theoretical analysis and a dynamic food flux model show that the IFTN provides a vehicle suitable for the fast distribution of potential contaminants but unsuitable for tracing their origin. In particular, we show that high values of node betweenness and vulnerability correlate well with recorded large food poisoning outbreaks.

Centrality scaling in large networks.

Betweenness centrality lies at the core of both transport and structural vulnerability properties of complex networks; however, it is computationally costly, and its measurement for networks with millions of nodes is nearly impossible. By introducing a multiscale decomposition of shortest paths, we show that the contributions to betweenness coming from geodesics not longer than L obey a characteristic scaling versus L, which can be used to predict the distribution of the full centralities. The method is also illustrated on a real-world social network of 5.5 × 10(6) nodes and 2.7 × 10(7) links.