arXiv subjects

Leonardo Novelli

Publications and source records attributed to Leonardo Novelli.

9 recordsLinked to original sources

arXiv2023

Minimum-phase property of the hemodynamic response function, and implications for Granger Causality in fMRI

Granger Causality (GC) is widely used in neuroimaging to estimate directed statistical dependence among brain regions using time series of brain activity. An important issue is that functional MRI (fMRI) measures brain activity indirectly via the blood-oxygen-level-dependent (BOLD) signal, which affects the temporal structure of the signals and distorts GC estimates. However, some notable applications of GC are not concerned with the GC magnitude but its statistical significance. This is the case for network inference, which aims to build a statistical model of the system based on directed relationships among its elements. The critical question for the viability of network inference in fMRI is whether the hemodynamic response function (HRF) and its variability across brain regions introduce spurious relationships, i.e., statistically significant GC values between BOLD signals, even if the GC between the neuronal signals is zero. It has been mathematically proven that such spurious statistical relationships are not induced if the HRF is minimum-phase, i.e., if both the HRF and its inverse are stable (producing finite responses to finite inputs). However, whether the HRF is minimum-phase has remained contentious. Here, we address this issue using multiple realistic biophysical models from the literature and studying their transfer functions. We find that these models are minimum-phase for a wide range of physiologically plausible parameter values. Therefore, statistical testing of GC is plausible even if the HRF varies across brain regions, with the following limitations. First, the minimum-phase condition is violated for parameter combinations that generate an initial dip in the HRF, confirming a previous mathematical proof. Second, the slow sampling of the BOLD signal (in seconds) compared to the timescales of neural signal propagation (milliseconds) may still introduce spurious GC.

q-bio.NC↗

arXiv2023

Spectral Dynamic Causal Modelling: A Didactic Introduction and its Relationship with Functional Connectivity

We present a didactic introduction to spectral Dynamic Causal Modelling (DCM), a Bayesian state-space modelling approach used to infer effective connectivity from non-invasive neuroimaging data. Spectral DCM is currently the most widely applied DCM variant for resting-state functional MRI analysis. Our aim is to explain its technical foundations to an audience with limited expertise in state-space modelling and spectral data analysis. Particular attention will be paid to cross-spectral density, which is the most distinctive feature of spectral DCM and is closely related to functional connectivity, as measured by (zero-lag) Pearson correlations. In fact, the model parameters estimated by spectral DCM are those that best reproduce the cross-correlations between all measurements--at all time lags--including the zero-lag correlations that are usually interpreted as functional connectivity. We derive the functional connectivity matrix from the model equations and show how changing a single effective connectivity parameter can affect all pairwise correlations. To complicate matters, the pairs of brain regions showing the largest changes in functional connectivity do not necessarily coincide with those presenting the largest changes in effective connectivity. We discuss the implications and conclude with a comprehensive summary of the assumptions and limitations of spectral DCM.

q-bio.NC↗

arXiv2023

Hierarchical Bayesian inference for community detection and connectivity of functional brain networks

Most functional magnetic resonance imaging studies rely on estimates of hierarchically organized functional brain networks whose segregation and integration reflect the cognitive and behavioral changes in humans. However, most existing methods for estimating the community structure of networks from both individual and group-level analysis methods do not account for the variability between subjects. In this paper, we develop a new multilayer community detection method based on Bayesian latent block model (LBM). The method can robustly detect the community structure of weighted functional networks with an unknown number of communities at both individual and group levels and retain the variability of the individual networks. For validation, we propose a new community structure-based multivariate Gaussian generative model to simulate synthetic signal. Our simulation study shows that the community memberships estimated by hierarchical Bayesian inference are consistent with the predefined node labels in the generative model. The method is also tested via split-half reproducibility using working memory task fMRI data of 100 unrelated healthy subjects from the Human Connectome Project. Analyses using both synthetic and real data show that our proposed method is more accurate and reliable compared with the commonly used (multilayer) modularity models.

q-bio.NC↗

arXiv2022

A mathematical perspective on edge-centric brain functional connectivity

Edge time series are increasingly used in brain functional imaging to study the node functional connectivity (nFC) dynamics at the finest temporal resolution while avoiding sliding windows. Here, we lay the mathematical foundations for the edge-centric analysis of neuroimaging time series, explaining why a few high-amplitude cofluctuations drive the nFC across datasets. Our exposition also constitutes a critique of the existing edge-centric studies, showing that their main findings can be derived from the nFC under a static null hypothesis that disregards temporal correlations. Testing the analytic predictions on functional MRI data from the Human Connectome Project confirms that the nFC can explain most variation in the edge FC matrix, the edge communities, the large cofluctuations, and the corresponding spatial patterns. We encourage the use of dynamic measures in future research, which exploit the temporal structure of the edge time series and cannot be replicated by static null models.

q-bio.NC↗

arXiv2021

Assessing the Significance of Directed and Multivariate Measures of Linear Dependence Between Time Series

Inferring linear dependence between time series is central to our understanding of natural and artificial systems. Unfortunately, the hypothesis tests that are used to determine statistically significant directed or multivariate relationships from time-series data often yield spurious associations (Type I errors) or omit causal relationships (Type II errors). This is due to the autocorrelation present in the analysed time series -- a property that is ubiquitous across diverse applications, from brain dynamics to climate change. Here we show that, for limited data, this issue cannot be mediated by fitting a time-series model alone (e.g., in Granger causality or prewhitening approaches), and instead that the degrees of freedom in statistical tests should be altered to account for the effective sample size induced by cross-correlations in the observations. This insight enabled us to derive modified hypothesis tests for any multivariate correlation-based measures of linear dependence between covariance-stationary time series, including Granger causality and mutual information with Gaussian marginals. We use both numerical simulations (generated by autoregressive models and digital filtering) as well as recorded fMRI-neuroimaging data to show that our tests are unbiased for a variety of stationary time series. Our experiments demonstrate that the commonly used $F$- and $χ^2$-tests can induce significant false-positive rates of up to $100\%$ for both measures, with and without prewhitening of the signals. These findings suggest that many dependencies reported in the scientific literature may have been, and may continue to be, spuriously reported or missed if modified hypothesis tests are not used when analysing time series.

stat.ME↗

arXiv2020

Inferring network properties from time series using transfer entropy and mutual information: validation of multivariate versus bivariate approaches

Functional and effective networks inferred from time series are at the core of network neuroscience. Interpreting their properties requires inferred network models to reflect key underlying structural features; however, even a few spurious links can distort network measures, challenging 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 networks 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.

q-bio.NC↗

arXiv2020

Deriving pairwise transfer entropy from network structure and motifs

Transfer entropy is an established method for quantifying directed statistical dependencies in neuroimaging and complex systems datasets. The pairwise (or bivariate) transfer entropy from a source to a target node in a network does not depend solely on the local source-target link weight, but on the wider network structure that the link is embedded in. This relationship is studied using a discrete-time linearly-coupled Gaussian model, which allows us to derive the transfer entropy for each link from the network topology. It is shown analytically that the dependence on the directed link weight is only a first approximation, valid for weak coupling. More generally, the transfer entropy increases with the in-degree of the source and decreases with the in-degree of the target, indicating an asymmetry of information transfer between hubs and low-degree nodes. In addition, the transfer entropy is directly proportional to weighted motif counts involving common parents or multiple walks from the source to the target, which are more abundant in networks with a high clustering coefficient than in random networks. Our findings also apply to Granger causality, which is equivalent to transfer entropy for Gaussian variables. Moreover, similar empirical results on random Boolean networks suggest that the dependence of the transfer entropy on the in-degree extends to nonlinear dynamics.

cs.IT↗

arXiv2019

Large-scale directed network inference with multivariate transfer entropy and hierarchical statistical testing

Network inference algorithms are valuable tools for the study of large-scale neuroimaging datasets. Multivariate transfer entropy is well suited for this task, being a model-free measure that captures nonlinear and lagged dependencies between time series to infer a minimal directed network model. Greedy algorithms have been proposed to efficiently deal with high-dimensional datasets while avoiding redundant inferences and capturing synergistic effects. However, multiple statistical comparisons may inflate the false positive rate and are computationally demanding, which limited the size of previous validation studies. The algorithm we present---as implemented in the IDTxl open-source software---addresses these challenges by employing hierarchical statistical tests to control the family-wise error rate and to allow for efficient parallelisation. The method was validated on synthetic datasets involving random networks of increasing size (up to 100 nodes), for both linear and nonlinear dynamics. The performance increased with the length of the time series, reaching consistently high precision, recall, and specificity (>98% on average) for 10000 time samples. Varying the statistical significance threshold showed a more favourable precision-recall trade-off for longer time series. Both the network size and the sample size are one order of magnitude larger than previously demonstrated, showing feasibility for typical EEG and MEG experiments.

q-bio.NC↗

arXiv2019

IDTxl: The Information Dynamics Toolkit xl: a Python package for the efficient analysis of multivariate information dynamics in networks

The Information Dynamics Toolkit xl (IDTxl) is a comprehensive software package for efficient inference of networks and their node dynamics from multivariate time series data using information theory. IDTxl provides functionality to estimate the following measures: 1) For network inference: multivariate transfer entropy (TE)/Granger causality (GC), multivariate mutual information (MI), bivariate TE/GC, bivariate MI 2) For analysis of node dynamics: active information storage (AIS), partial information decomposition (PID) IDTxl implements estimators for discrete and continuous data with parallel computing engines for both GPU and CPU platforms. Written for Python3.4.3+.

cs.IT↗