Functional and effective networks inferred from time series are at the core of network neuroscience. Interpreting properties of these networks requires inferred network models to reflect key underlying structural features. However, even a few spurious links can severely distort network measures, posing a challenge for functional connectomes. We study the extent to which micro- and macroscopic properties of underlying networks can be inferred by algorithms based on mutual information and bivariate/multivariate transfer entropy. The validation is performed on two macaque connectomes and on synthetic networks with various topologies (regular lattice, small-world, random, scale-free, modular). Simulations are based on a neural mass model and on autoregressive dynamics (employing Gaussian estimators for direct comparison to functional connectivity and Granger causality). We find that multivariate transfer entropy captures key properties of all network structures for longer time series. Bivariate methods can achieve higher recall (sensitivity) for shorter time series but are unable to control false positives (lower specificity) as available data increases. This leads to overestimated clustering, small-world, and rich-club coefficients, underestimated shortest path lengths and hub centrality, and fattened degree distribution tails. Caution should therefore be used when interpreting network properties of functional connectomes obtained via correlation or pairwise statistical dependence measures, rather than more holistic (yet data-hungry) multivariate models.

Sex steroid hormones have been shown to alter regional brain activity, but the extent to which they modulate connectivity within and between large-scale functional brain networks over time has yet to be characterized. Here, we applied dynamic community detection techniques to data from a highly sampled female with 30 consecutive days of brain imaging and venipuncture measurements to characterize changes in resting-state community structure across the menstrual cycle. Four stable functional communities were identified, consisting of nodes from visual, default mode, frontal control, and somatomotor networks. Limbic, subcortical, and attention networks exhibited higher than expected levels of nodal flexibility, a hallmark of between-network integration and transient functional reorganization. The most striking reorganization occurred in a default mode subnetwork localized to regions of the prefrontal cortex, coincident with peaks in serum levels of estradiol, luteinizing hormone, and follicle stimulating hormone. Nodes from these regions exhibited strong intranetwork increases in functional connectivity, leading to a split in the stable default mode core community and the transient formation of a new functional community. Probing the spatiotemporal basis of human brain–hormone interactions with dynamic community detection suggests that hormonal changes during the menstrual cycle result in temporary, localized patterns of brain network reorganization.

Whole-brain network analysis is commonly used to investigate the topology of the brain using a variety of neuroimaging modalities. This approach is notable for its applicability to a large number of domains, such as understanding how brain network organization relates to cognition and behavior and examining disrupted brain network organization in disease. A benefit to this approach is the ability to summarize overall brain network organization with a single metric (e.g., global efficiency). However, important local differences in network structure might exist without any corresponding observable differences in global topology, making a whole-brain analysis strategy unlikely to detect relevant local findings. Conversely, using local network metrics can identify local differences, but are not directly informative of differences in global topology. Here, we propose the network statistic (NS) jackknife framework, a simulated lesioning method that combines the utility of global network analysis strategies with the ability to detect relevant local differences in network structure. We evaluate the NS jackknife framework with a simulation study and an empirical example comparing global efficiency in children with attention-deficit/hyperactivity disorder (ADHD) and typically developing (TD) children. The NS jackknife framework has been implemented in a public, open-source R package, netjack, available at https://cran.r-project.org/package=netjack.

Optogenetic stimulation has become the method of choice for investigating neural computation in populations of neurons. Optogenetic experiments often aim to elicit a network response by stimulating specific groups of neurons. However, this is complicated by the fact that optogenetic stimulation is nonlinear, more light does not always equal to more spikes, and neurons that are not directly but indirectly stimulated could have a major impact on how networks respond to optogenetic stimulation. To clarify how optogenetic excitation of some neurons alters the network dynamics, we studied the temporal and spatial response of individual neurons and recurrent neural networks. In individual neurons, we find that neurons show a monotonic, saturating rate response to increasing light intensity and a nonmonotonic rate response to increasing pulse frequency. At the network level, we find that Gaussian light beams elicit spatial firing rate responses that are substantially broader than the stimulus profile. In summary, our analysis and our network simulation code allow us to predict the outcome of an optogenetic experiment and to assess whether the observed effects can be attributed to direct or indirect stimulation of neurons.

The contribution of structural connectivity to functional brain states remains poorly understood. We present a mathematical and computational study suited to assess the structure–function issue, treating a system of Jansen–Rit neural mass nodes with heterogeneous structural connections estimated from diffusion MRI data provided by the Human Connectome Project. Via direct simulations we determine the similarity of functional (inferred from correlated activity between nodes) and structural connectivity matrices under variation of the parameters controlling single-node dynamics, highlighting a nontrivial structure–function relationship in regimes that support limit cycle oscillations. To determine their relationship, we firstly calculate network instabilities giving rise to oscillations, and the so-called ‘false bifurcations’ (for which a significant qualitative change in the orbit is observed, without a change of stability) occurring beyond this onset. We highlight that functional connectivity (FC) is inherited robustly from structure when node dynamics are poised near a Hopf bifurcation, whilst near false bifurcations, and structure only weakly influences FC. Secondly, we develop a weakly coupled oscillator description to analyse oscillatory phase-locked states and, furthermore, show how the modular structure of FC matrices can be predicted via linear stability analysis. This study thereby emphasises the substantial role that local dynamics can have in shaping large-scale functional brain states.

Brain connectivity studies of autism spectrum disorder (ASD) have historically relied on static measures of functional connectivity. Recent work has focused on identifying transient configurations of brain activity, yet several open questions remain regarding the nature of specific brain network dynamics in ASD. We used a dynamic coactivation pattern (CAP) approach to investigate the salience/midcingulo-insular (M-CIN) network, a locus of dysfunction in ASD, in a large multisite resting-state fMRI dataset collected from 172 children (ages 6–13 years; n = 75 ASD; n = 138 male). Following brain parcellation by using independent component analysis, dynamic CAP analyses were conducted and k-means clustering was used to determine transient activation patterns of the M-CIN. The frequency of occurrence of different dynamic CAP brain states was then compared between children with ASD and typically developing (TD) children. Dynamic brain configurations characterized by coactivation of the M-CIN with central executive/lateral fronto-parietal and default mode/medial fronto-parietal networks appeared less frequently in children with ASD compared with TD children. This study highlights the utility of time-varying approaches for studying altered M-CIN function in prevalent neurodevelopmental disorders. We speculate that altered M-CIN dynamics in ASD may underlie the inflexible behaviors commonly observed in children with the disorder.

Visual exploration is related to activity in the hippocampus (HC) and/or extended medial temporal lobe system (MTL), is influenced by stored memories, and is altered in amnesic cases. An extensive set of polysynaptic connections exists both within and between the HC and oculomotor systems such that investigating how HC responses ultimately influence neural activity in the oculomotor system, and the timing by which such neural modulation could occur, is not trivial. We leveraged TheVirtualBrain, a software platform for large-scale network simulations, to model the functional dynamics that govern the interactions between the two systems in the macaque cortex. Evoked responses following the stimulation of the MTL and some, but not all, subfields of the HC resulted in observable responses in oculomotor regions, including the frontal eye fields, within the time of a gaze fixation. Modeled lesions to some MTL regions slowed the dissipation of HC signal to oculomotor regions, whereas HC lesions generally did not affect the rapid MTL activity propagation to oculomotor regions. These findings provide a framework for investigating how information represented by the HC/MTL may influence the oculomotor system during a fixation and predict how HC lesions may affect visual exploration.

We test the adequacies of several proposed and two new statistical methods for recovering the causal structure of systems with feedback from synthetic BOLD time series. We compare an adaptation of the first correct method for recovering cyclic linear systems; Granger causal regression; a multivariate autoregressive model with a permutation test; the Group Iterative Multiple Model Estimation (GIMME) algorithm; the Ramsey et al. non-Gaussian methods; two non-Gaussian methods by Hyvärinen and Smith; a method due to Patel et al.; and the GlobalMIT algorithm. We introduce and also compare two new methods, Fast Adjacency Skewness (FASK) and Two-Step, both of which exploit non-Gaussian features of the BOLD signal. We give theoretical justifications for the latter two algorithms. Our test models include feedback structures with and without direct feedback (2-cycles), excitatory and inhibitory feedback, models using experimentally determined structural connectivities of macaques, and empirical human resting-state and task data. We find that averaged over all of our simulations, including those with 2-cycles, several of these methods have a better than 80% orientation precision (i.e., the probability of a directed edge is in the true structure given that a procedure estimates it to be so) and the two new methods also have better than 80% recall (probability of recovering an orientation in the true structure).

The human brain is a dynamic networked system that continually reconfigures its functional connectivity patterns over time. Thus, developing approaches able to adequately detect fast brain dynamics is critical. Of particular interest are the methods that analyze the modular structure of brain networks, that is, the presence of clusters of regions that are densely interconnected. In this paper, we propose a novel framework to identify fast modular states that dynamically fluctuate over time during rest and task. We started by demonstrating the feasibility and relevance of this framework using simulated data. Compared with other methods, our algorithm was able to identify the simulated networks with high temporal and spatial accuracies. We further applied the proposed framework on MEG data recorded during a finger movement task, identifying modular states linking somatosensory and primary motor regions. The algorithm was also performed on dense-EEG data recorded during a picture naming task, revealing the subsecond transition between several modular states that relate to visual processing, semantic processing, and language. Next, we tested our method on a dataset of resting-state dense-EEG signals recorded from 124 patients with Parkinson’s disease. Results disclosed brain modular states that differentiate cognitively intact patients, patients with moderate cognitive deficits, and patients with severe cognitive deficits. Our new approach complements classical methods, offering a new way to track the brain modular states, in healthy subjects and patients, on an adequate task-specific timescale.

Detailed characterization of typical human neurodevelopment is key if we are to understand the nature of mental and neurological pathology. While research on the cellular processes of neurodevelopment has made great advances, in vivo human imaging is crucial to understand our uniquely human capabilities, as well as the pathologies that affect them. Using magnetoencephalography data in the largest normative sample currently available (324 participants aged 6–45 years), we assess the developmental trajectory of resting-state oscillatory power and functional connectivity from childhood to middle age. The maturational course of power, indicative of local processing, was found to both increase and decrease in a spectrally dependent fashion. Using the strength of phase-synchrony between parcellated regions, we found significant linear and nonlinear (quadratic and logarithmic) trajectories to be characterized in a spatially heterogeneous frequency-specific manner, such as a superior frontal region with linear and nonlinear trajectories in theta and gamma band respectively. Assessment of global efficiency revealed similar significant nonlinear trajectories across all frequency bands. Our results link with the development of human cognitive abilities; they also highlight the complexity of neurodevelopment and provide quantitative parameters for replication and a robust footing from which clinical research may map pathological deviations from these typical trajectories.