Bi-variate estimators
Classical methods
Classical estimators of connectivity areNon-linear methods
The most frequently used nonlinear estimators of connectivity are mutual information,Bivariate versus multivariate estimators
Comparison of performance of bivariate and multivariate estimators of connectivity may be found in, where it was demonstrated that in case of interrelated system of channels, greater than two, bivariate methods supply misleading information, even reversal of true propagation may be found. Consider the very common situation that the activity from a given source is measured at electrodes positioned at different distances, hence different delays between the recorded signals. When a bivariate measure is applied, propagation is always obtained when there is a delay between channels., which results in a lot of spurious flows. When we have two or three sources acting simultaneously, which is a common situation, we shall get dense and disorganized structure of connections, similar to random structure (at best some "small world" structure may be identified). This kind of pattern is usually obtained in case of application of bivariate measures. In fact, effective connectivity patterns yielded by EEG or LFP measurements are far from randomness, when proper multivariate measures are applied, as we shall demonstrate below.Multivariate methods based on Granger causality
The testable definition of causality was introduced by Granger. Granger causality principle states that if some series ''Y''(''t'') contains information in past terms that helps in the prediction of series ''X''(''t''), then ''Y''(''t'') is said to cause ''X''(''t''). Granger causality principle can be expressed in terms of two-channel multivariate autoregressive model (MVAR). Granger in his later work pointed out that the determination of causality is not possible when the system of considered channels is not complete. The measures based on Granger causality principle are: Granger Causality Index (GCI), Directed Transfer Function (DTF) and Partial Directed Coherence (PDC). These measures are defined in the framework of Multivariate Autoregressive Model.Multivariate Autoregressive Model
The AR model assumes that ''X''(''t'')—a sample of data at a time ''t''—can be expressed as a sum of ''p'' previous values of the samples from the set of ''k''-signals weighted by model coefficients ''A'' plus a random value ''E''(''t''): The ''p'' is called the model order. For a ''k''-channel process ''X''(''t'') and ''E''(''t'') are vectors of size ''k'' and the coefficients ''A'' are ''k''×''k''-sized matrices. The model order may be determined by means of criteria developed in the framework of information theory and the coefficients of the model are found by means of the minimalization of the residual noise. In the procedure correlation matrix between signals is calculated. By the transformation to the frequency domain we get: ''H''(''f'') is a transfer matrix of the system, it contains information about the relationships between signals and their spectral characteristics. ''H''(''f'') is non-symmetric, so it allows for finding causal dependencies. Model order may be found by means of criteria developed in the framework of information theory, e.g.Granger Causality Index
Granger causality index showing the driving of channel ''x'' by channel ''y'' is defined as the logarithm of the ratio of residual variance for one channel to the residual variance of the two-channel model: GCI''y''→''x'' = ln (''e''/''e''1) This definition can be extended to the multichannel system by considering how the inclusion of the given channel changes the residual variance ratios. To quantify directed influence from a channel ''x''''j'' to ''x''''i'' for ''n'' channel autoregressive process in time domain we consider ''n'' and ''n''−1 dimensional MVAR models. First, the model is fitted to whole ''n''-channel system, leading to the residual variance ''V''''i'',''n''(t) = var(''E''''i'',''n''(''t'')) for signal ''x''''i''. Next, a ''n''−1 dimensional MVAR model is fitted for ''n''−1 channels, excluding channel ''j'', which leads to the residual variance ''V''''i'',''n''−1(t) = var (''E''''i'',''n''−1(''t'')). Then Granger causality is defined as: GCI is smaller or equal 1, since the variance of ''n''-dimensional system is lower than the residual variance of a smaller, ''n''−1 dimensional system. GCI(''t'') estimates causality relations in time domain. For brain signals the spectral characteristics of the signals is of interest, because for a given task the increase of propagation in certain frequency band may be accompanied by the decrease in another frequency band. DTF or PDC are the estimators defined in the frequency domain.Directed Transfer Function
Directed Transfer Function (DTF) was introduced by Kaminski and Blinowska in the form: Where ''Hij''(''f'') is an element of a transfer matrix of MVAR model. DTF describes causal influence of channel ''j'' on channel ''i'' at frequency ''f''. The above equation () defines a normalized version of DTF, which takes values from 0 to 1 producing a ratio between the inflow from channel ''j'' to channel ''i'' to all the inflows to channel ''i''. The non-normalized DTF which is directly related to the coupling strength is defined as: DTF shows not only direct, but also cascade flows, namely in case of propagation 1→2→3 it shows also propagation 1→3. In order to distinguish direct from indirect flows direct Directed Transfer Function (dDTF) was introduced. The dDTF is defined as a multiplication of a modified DTF by partial coherence. The modification of DTF concerned normalization of the function in such a way as to make the denominator independent of frequency. The dDTF''j''→''i'' showing direct propagation from channel ''j'' to ''i'' is defined as: Where ''Cij''(''f'') is partial coherence. The dDTF''j''→''i'' has a nonzero value when both functions ''Fij''(''f'') and ''Cij''(''f'') are non-zero, in that case there exists a direct causal relation between channels ''j''→''i''. Distinguishing direct from indirect transmission is essential in case of signals from implanted electrodes, for EEG signals recorded by scalp electrodes it is not really important. DTF may be used for estimation of propagation in case of point processes e.g. spike trains or for the estimation of causal relations between spike trains and Local Field Potentials.Partial Directed Coherence
The partial directed coherence (PDC) was defined by Baccala and Sameshima in the following form: In the above equation ''Aij''(''f'') is an element of ''A''(''f'')—a Fourier transform of MVAR model coefficients ''A''(''t''), where a''j''(''f'') is ''j''-th column of ''A''(''f'') and the asterisk denotes the transpose and complex conjugate operation. Although it is a function operating in the frequency domain, the dependence of ''A''(''f'') on the frequency has not a direct correspondence to the power spectrum. From normalization condition it follows that PDC takes values from the interval ,1 PDC shows only direct flows between channels. Unlike DTF, PDC is normalized to show a ratio between the outflow from channel ''j'' to channel ''i'' to all the outflows from the source channel ''j'', so it emphasizes rather the sinks, not the sources. The normalization of PDC affects the detected intensities of flow as was pointed out in. Namely, adding further variables that are influenced by a source variable decreases PDC, although the relationship between source and target processes remains unchanged. In other words: the flow emitted in one direction will be enhanced in comparison to the flows of the same intensity emitted from a given source in several directions.Time-varying estimators of effective connectivity
In order to account for the dynamic changes of propagation, the method of adaptive filtering or the method based on the sliding window may be applied to estimators of connectivity. Both methods require multiple repetition of the experiment to obtain statistically satisfactory results and they produce similar results. The adaptive methods, e.g. Kalman filtering, are more computationally demanding, therefore methods based on sliding window may be recommended. In the case of parametric model the number of data points ''kNT'' (''k''—number of channels, ''NT''—number of points in the data window) has to be bigger (preferably by order of magnitude) than the number of parameters, which in case of MVAR is equal to ''k''2''p'' (''p''—model order). In order to evaluate dynamics of the process, a short data window has to be applied, which requires an increase of the number of the data points, which may be achieved by means of a repetition of the experiment. A non-stationary recording may be divided into shorter time windows, short enough to treat the data within a window as quasi-stationary. Estimation of MVAR coefficients is based on calculation of the correlation matrix between channels ''Rij'' of ''k'' signals ''Xi'' from multivariate set, separately for each trial. The resulting model coefficients are based on the correlation matrix averaged over trials. The correlation matrix has the form: The averaging concerns correlation matrices (model is fitted independently for each short data window); the data are not averaged in the process. The choice of window size is always a compromise between quality of the fit and time resolution. The errors of the SDTF may be evaluated by means of bootstrap method. This procedure corresponds to simulations of other realizations of the experiment. The variance of the function value is obtained by repeated calculation of the results for a randomly selected (with repetitions) pool of the original data trials.Applications
The estimation of brain connectivity has found numerous and notable applications, namely when investigating brain changes associated with the treatment of psychopathology like schizophrenia and depression, or following structural damage like in hemorrhage or tumor. The methods applied benefit from a parcellation approach, where regions of the brain are defined fromConclusions
The existence of well defined sources of brain activity connected with particular experimental conditions are well established in fMRI experiments, by means of inverse solution methods and intracortical measurements. This kind of deterministic structure of brain activity should affect functional connectivity, so reported in some works random or barely distinguished from random connectivity structure may be considered as a surprising phenomenon. This kind of results may be explained by methodological errors: 1) unrobust methods of connectivity estimation and, even more important, 2) application of bivariate methods. When multivariate robust measures of connectivity are applied forReferences
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See also
* Resting State fMRI * Dynamic Functional Connectivity * List of Functional Connectivity Software *