Isolated effective coherence (iCoh): causal information flow excluding indirect paths

A problem of great interest in real world systems, where multiple time series measurements are available, is the estimation of the intra-system causal relations. For instance, electric cortical signals are used for studying functional connectivity between brain areas, their directionality, the direct or indirect nature of the connections, and the spectral characteristics (e.g. which oscillations are preferentially transmitted). The earliest spectral measure of causality was Akaike's (1968) seminal work on the noise contribution ratio, reflecting direct and indirect connections. Later, a major breakthrough was the partial directed coherence of Baccala and Sameshima (2001) for direct connections. The simple aim of this study consists of two parts: (1) To expose a major problem with the partial directed coherence, where it is shown that it is affected by irrelevant connections to such an extent that it can misrepresent the frequency response, thus defeating the main purpose for which the measure was developed, and (2) To provide a solution to this problem, namely the "isolated effective coherence", which consists of estimating the partial coherence under a multivariate auto-regressive model, followed by setting all irrelevant associations to zero, other than the particular directional association of interest. Simple, realistic, toy examples illustrate the severity of the problem with the partial directed coherence, and the solution achieved by the isolated effective coherence. For the sake of reproducible research, the software code implementing the methods discussed here (using lazarus free-pascal "www.lazarus.freepascal.org"), including the test data as text files, are freely available at: https://sites.google.com/site/pascualmarqui/home/icoh-isolated-effective-coherenceComment: 2014-02-21 pre-print, technical report, KEY Institute for Brain-Mind Research, University of Zurich, et a

Information flow between resting state networks

The resting brain dynamics self-organizes into a finite number of correlated patterns known as resting state networks (RSNs). It is well known that techniques like independent component analysis can separate the brain activity at rest to provide such RSNs, but the specific pattern of interaction between RSNs is not yet fully understood. To this aim, we propose here a novel method to compute the information flow (IF) between different RSNs from resting state magnetic resonance imaging. After haemodynamic response function blind deconvolution of all voxel signals, and under the hypothesis that RSNs define regions of interest, our method first uses principal component analysis to reduce dimensionality in each RSN to next compute IF (estimated here in terms of Transfer Entropy) between the different RSNs by systematically increasing k (the number of principal components used in the calculation). When k = 1, this method is equivalent to computing IF using the average of all voxel activities in each RSN. For k greater than one our method calculates the k-multivariate IF between the different RSNs. We find that the average IF among RSNs is dimension-dependent, increasing from k =1 (i.e., the average voxels activity) up to a maximum occurring at k =5 to finally decay to zero for k greater than 10. This suggests that a small number of components (close to 5) is sufficient to describe the IF pattern between RSNs. Our method - addressing differences in IF between RSNs for any generic data - can be used for group comparison in health or disease. To illustrate this, we have calculated the interRSNs IF in a dataset of Alzheimer's Disease (AD) to find that the most significant differences between AD and controls occurred for k =2, in addition to AD showing increased IF w.r.t. controls.Comment: 47 pages, 5 figures, 4 tables, 3 supplementary figures. Accepted for publication in Brain Connectivity in its current for

Causal structure learning from time series: Large regression coefficients may predict causal links better in practice than small p-values

In this article, we describe the algorithms for causal structure learning from time series data that won the Causality 4 Climate competition at the Conference on Neural Information Processing Systems 2019 (NeurIPS). We examine how our combination of established ideas achieves competitive performance on semi-realistic and realistic time series data exhibiting common challenges in real-world Earth sciences data. In particular, we discuss a) a rationale for leveraging linear methods to identify causal links in non-linear systems, b) a simulation-backed explanation as to why large regression coefficients may predict causal links better in practice than small p-values and thus why normalising the data may sometimes hinder causal structure learning. For benchmark usage, we detail the algorithms here and provide implementations at https://github.com/sweichwald/tidybench . We propose the presented competition-proven methods for baseline benchmark comparisons to guide the development of novel algorithms for structure learning from time series

Information transfer and criticality in the Ising model on the human connectome

We implement the Ising model on a structural connectivity matrix describing the brain at two different resolutions. Tuning the model temperature to its critical value, i.e. at the susceptibility peak, we find a maximal amount of total information transfer between the spin variables. At this point the amount of information that can be redistributed by some nodes reaches a limit and the net dynamics exhibits signature of the law of diminishing marginal returns, a fundamental principle connected to saturated levels of production. Our results extend the recent analysis of dynamical oscillators models on the connectome structure, taking into account lagged and directional influences, focusing only on the nodes that are more prone to became bottlenecks of information. The ratio between the outgoing and the incoming information at each node is related to the the sum of the weights to that node and to the average time between consecutive time flips of spins. The results for the connectome of 66 nodes and for that of 998 nodes are similar, thus suggesting that these properties are scale-independent. Finally, we also find that the brain dynamics at criticality is organized maximally to a rich-club w.r.t. the network of information flows

The Thalamus and Brainstem Act As Key Hubs in Alterations of Human Brain Network Connectivity Induced by Mild Propofol Sedation

Despite their routine use during surgical procedures, no consensus has yet been reached on the precise mechanisms by which hypnotic anesthetic agents produce their effects. Molecular, animal and human studies have suggested disruption of thalamocortical communication as a key component of anesthetic action at the brain systems level. Here, we used the anesthetic agent, propofol, to modulate consciousness and to evaluate differences in the interactions of remote neural networks during altered consciousness. We investigated the effects of propofol, at a dose that produced mild sedation without loss of consciousness, on spontaneous cerebral activity of 15 healthy volunteers using functional magnetic resonance imaging (fMRI), exploiting oscillations (<0.1 Hz) in blood oxygenation level-dependent signal across functionally connected brain regions. We considered the data as a graph, or complex network of nodes and links, and used eigenvector centrality (EC) to characterize brain network properties. The EC mapping of fMRI data in healthy humans under propofol mild sedation demonstrated a decrease of centrality of the thalamus versus an increase of centrality within the pons of the brainstem, highlighting the important role of these two structures in regulating consciousness. Specifically, the decrease of thalamus centrality results from its disconnection from a widespread set of cortical and subcortical regions, while the increase of brainstem centrality may be a consequence of its increased influence, in the mildly sedated state, over a few highly central cortical regions key to the default mode network such as the posterior and anterior cingulate cortices

Parasympathetic-sympathetic causal interactions assessed by time-varying multivariate autoregressive modeling of electrodermal activity and heart-rate-variability

Objective: Most of the bodily functions are regulated by multiple interactions between the parasympathetic (PNS) and sympathetic (SNS) nervous system. In this study, we propose a novel framework to quantify the causal flow of information between PNS and SNS through the analysis of heart rate variability (HRV) and electrodermal activity (EDA) signals. Methods: Our method is based on a time-varying (TV) multivariate autoregressive model of EDA and HRV time-series and incorporates physiologically inspired assumptions by estimating the Directed Coherence in a specific frequency range. The statistical significance of the observed interactions is assessed by a bootstrap procedure purposely developed to infer causalities in the presence of both TV model coefficients and TV model residuals (i.e., heteroskedasticity). We tested our method on two different experiments designed to trigger a sympathetic response, i.e., a hand-grip task (HG) and a mental-computation task (MC). Results: Our results show a parasympathetic driven interaction in the resting state, which is consistent across different studies. The onset of the stressful stimulation triggers a cascade of events characterized by the presence or absence of the PNS-SNS interaction and changes in the directionality. Despite similarities between the results related to the two tasks, we reveal differences in the dynamics of the PNS-SNS interaction, which might reflect different regulatory mechanisms associated with different stressors. Conclusion: We estimate causal coupling between PNS and SNS through MVAR modeling of EDA and HRV time-series. Significance: Our results suggest promising future applicability to investigate more complex contexts such as affective and pathological scenarios

Altered Effective Connectivity Network of the Amygdala in Social Anxiety Disorder: A Resting-State fMRI Study

The amygdala is often found to be abnormally recruited in social anxiety disorder (SAD) patients. The question whether amygdala activation is primarily abnormal and affects other brain systems or whether it responds “normally” to an abnormal pattern of information conveyed by other brain structures remained unanswered. To address this question, we investigated a network of effective connectivity associated with the amygdala using Granger causality analysis on resting-state functional MRI data of 22 SAD patients and 21 healthy controls (HC). Implications of abnormal effective connectivity and clinical severity were investigated using the Liebowitz Social Anxiety Scale (LSAS). Decreased influence from inferior temporal gyrus (ITG) to amygdala was found in SAD, while bidirectional influences between amygdala and visual cortices were increased compared to HCs. Clinical relevance of decreased effective connectivity from ITG to amygdala was suggested by a negative correlation of LSAS avoidance scores and the value of Granger causality. Our study is the first to reveal a network of abnormal effective connectivity of core structures in SAD. This is in support of a disregulation in predescribed modules involved in affect control. The amygdala is placed in a central position of dysfunction characterized both by decreased regulatory influence of orbitofrontal cortex and increased crosstalk with visual cortex. The model which is proposed based on our results lends neurobiological support towards cognitive models considering disinhibition and an attentional bias towards negative stimuli as a core feature of the disorder

Graph analysis of functional brain networks: practical issues in translational neuroscience

The brain can be regarded as a network: a connected system where nodes, or units, represent different specialized regions and links, or connections, represent communication pathways. From a functional perspective communication is coded by temporal dependence between the activities of different brain areas. In the last decade, the abstract representation of the brain as a graph has allowed to visualize functional brain networks and describe their non-trivial topological properties in a compact and objective way. Nowadays, the use of graph analysis in translational neuroscience has become essential to quantify brain dysfunctions in terms of aberrant reconfiguration of functional brain networks. Despite its evident impact, graph analysis of functional brain networks is not a simple toolbox that can be blindly applied to brain signals. On the one hand, it requires a know-how of all the methodological steps of the processing pipeline that manipulates the input brain signals and extract the functional network properties. On the other hand, a knowledge of the neural phenomenon under study is required to perform physiological-relevant analysis. The aim of this review is to provide practical indications to make sense of brain network analysis and contrast counterproductive attitudes