We present a didactic introduction to spectral dynamic causal modeling (DCM), a Bayesian state-space modeling approach used to infer effective connectivity from noninvasive 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 modeling 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.

Author Summary We compare bivariate and multivariate methods for inferring networks from time series, which are generated using a neural mass model and autoregressive dynamics. We assess their ability to reproduce key properties of the underlying structural network. Validation is performed on two macaque connectomes and on synthetic networks with various topologies (regular lattice, small-world, random, scale-free, modular). Even a few spurious links can severely bias key network properties. Multivariate transfer entropy performs best on all topologies for longer time series. Abstract 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.

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 parallelization. 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 10,000 time samples. Varying the statistical significance threshold showed a more favorable 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 magnetoencephalography experiments.