No Arabic abstract
Edge-centric functional connectivity (eFC) has recently been proposed to characterise the finest time resolution on the FC dynamics without the concomitant assumptions of sliding-window approaches. Here, we lay the mathematical foundations for the edge-centric analysis and examine its main findings from a quantitative perspective. The proposed framework provides a theoretical explanation for the observed occurrence of high-amplitude edge cofluctuations across datasets and clarifies why a few large events drive the node-centric FC (nFC). Our exposition also constitutes a critique of the edge-centric approach as currently applied to functional MRI (fMRI) time series. The central argument is that the existing findings based on edge time series can be derived from the static nFC under a null hypothesis that only accounts for the observed static spatial correlations and not the temporal ones. Challenging our analytic predictions against fMRI data from the Human Connectome Project confirms that the nFC is sufficient to replicate the eFC matrix, the edge communities, the large cofluctuations, and the corresponding brain activity mode. We conclude that the temporal structure of the edge time series has not so far been exploited sufficiently and encourage further work to explore features that cannot be explained by the presented static null model.
The estimation of causal network architectures in the brain is fundamental for understanding cognitive information processes. However, access to the dynamic processes underlying cognition is limited to indirect measurements of the hidden neuronal activity, for instance through fMRI data. Thus, estimating the network structure of the underlying process is challenging. In this article, we embed an adaptive importance sampler called Adaptive Path Integral Smoother (APIS) into the Expectation-Maximization algorithm to obtain point estimates of causal connectivity. We demonstrate on synthetic data that this procedure finds not only the correct network structure but also the direction of effective connections from random initializations of the connectivity matrix. In addition--motivated by contradictory claims in the literature--we examine the effect of the neuronal timescale on the sensitivity of the BOLD signal to changes in the connectivity and on the maximum likelihood solutions of the connectivity. We conclude with two warnings: First, the connectivity estimates under the assumption of slow dynamics can be extremely biased if the data was generated by fast neuronal processes. Second, the faster the time scale, the less sensitive the BOLD signal is to changes in the incoming connections to a node. Hence, connectivity estimation using realistic neural dynamics timescale requires extremely high-quality data and seems infeasible in many practical data sets.
The brain is organized in a modular way, serving multiple functionalities. This multiplicity requires that both positive (e.g. excitatory, phase-coherent) and negative (e.g. inhibitory, phase-opposing) interactions take place across brain modules. Unfortunately, most methods to detect modules from time series either neglect or convert to positive any measured negative correlation. This may leave a significant part of the sign-dependent functional structure undetected. Here we present a novel method, based on random matrix theory, for the identification of sign-dependent modules in the brain. Our method filters out the joint effects of local (unit-specific) noise and global (system-wide) dependencies that empirically obfuscate such structure. The method is guaranteed to identify an optimally contrasted functional `signature, i.e. a partition into modules that are positively correlated internally and negatively correlated across. The method is purely data-driven, does not use any arbitrary threshold or network projection, and outputs only statistically significant structure. In measurements of neuronal gene expression in the biological clock of mice, the method systematically uncovers two otherwise undetectable, negatively correlated modules whose relative size and mutual interaction strength are found to depend on photoperiod. The neurons alternating between the two modules define a candidate region of functional plasticity for circadian modulation.
We assess electrical brain dynamics before, during, and after one-hundred human epileptic seizures with different anatomical onset locations by statistical and spectral properties of functionally defined networks. We observe a concave-like temporal evolution of characteristic path length and cluster coefficient indicative of a movement from a more random toward a more regular and then back toward a more random functional topology. Surprisingly, synchronizability was significantly decreased during the seizure state but increased already prior to seizure end. Our findings underline the high relevance of studying complex systems from the view point of complex networks, which may help to gain deeper insights into the complicated dynamics underlying epileptic seizures.
A large body of literature has shown the substantial inter-regional functional connectivity in the mammal brain. One important property remaining un-studied is the cross-time interareal connection. This paper serves to provide a tool to characterize the cross-time functional connectivity. The method is extended from the temporal embedding based brain temporal coherence analysis. Both synthetic data and in-vivo data were used to evaluate the various properties of the cross-time functional connectivity matrix, which is also called the cross-regional temporal coherence matrix.
Obsessive-compulsive disorder (OCD) is a common psychiatric disorder with a lifetime prevalence of 2-3 percent. Recently, brain activity in the resting state is gathering attention as a new means of exploring altered functional connectivity in psychiatric disorders. Although previous resting-state functional magnetic resonance imaging studies investigated neurobiological abnormalities of patients with OCD, there are concerns that should be addressed. One concern is the validity of the hypothesis employed. Most studies used seed-based analysis of the fronto-striatal circuit, despite the potential for abnormalities in other regions. A hypothesis-free study is a promising approach in such a case, while it requires researchers to handle a dataset with large dimensions. Another concern is the reliability of biomarkers derived from a single dataset, which may be influenced by cohort-specific features. Here, by employing a recently developed machine-learning algorithm to avoid these concerns, we identified the first OCD biomarker that is generalized to an external dataset. We also demonstrated that the functional connectivities that contributed to the classification were widely distributed rather than locally constrained. Our generalizable classifier has the potential not only to deepen our understanding of the abnormal neural substrates of OCD but also to find use in clinical applications.