Dynamic causal modeling: Difference between revisions

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# Model specification. One or more forward models (DCMs) are specified for each subject's data.

#Model estimation. The model(s) are fitted to the data to determine their evidence and parameters.

# Model comparison. Compare theThe evidence for the modelsdata under each model is compared using Bayesian Model Comparison, at the single-subject level or at the group level, and inspect the parameters of the model(s) are inspected.

The key steps are briefly reviewed below.

== Experimental design ==

Functional neuroimaging experiments are typically task-based or examine brain activity at rest ([[Resting state fMRI|resting state]]). In task-based experiments, brain responses are evoked by known deterministic inputs (experimentally controlled stimuli) that embody designed changes in sensory stimulation or cognitive set. These experimental or exogenous variables can change neural activity in one of two ways. First, they can elicit responses through direct influences on specific brain regions. This would include, for example, [[Evoked potential|sensory evoked responses]] in the early visual cortex. The second class of inputs exerts their effects vicariously, through a modulation of the coupling among nodes, for example, the influence of attention on the processing of sensory information. These two types of input - driving and modulatory - are parameterized separately parameterized in DCM. To enable efficient estimation of driving and modulatory effects, a 2x2 [[Factorial experiment|factorial experimental design]] is often used - with one factor modelledserving as the driving input and the other as the modulatory input <ref name=":0" />.

Resting state experiments have no experimental manipulations within the period of the neuroimaging recording. Instead, the interest is in the endogenous fluctuations in brain connectivity during the scan, or in the differences in connectivity between scans or subjects. The DCM framework includes models and procedures for analysing resting state data, described below.

== Model specification ==

Dynamic Causal Models (DCMs) are nonlinear state-space models in continuous time, parameterized in terms of directed effective connectivity between brain regions. Unlike [[Bayesian network|Bayesian Networks]], DCMs can be cyclic, and unlike [[Structural equation modeling|Structural Equation modelling]] and [[Granger causality]], DCM does not depend on the theory of Martingales, i.e., it does not assume that random fluctuations' are serially uncorrelated. All models in DCM have the following basic form:

All models in DCM have the following basic form:

<math>\begin{align}

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\end{align}</math>

The first line describes the change in neural activity <math>z</math> with respect to time <math>\dot{z}</math>. This is the hidden state of the brain, which cannot be directly observed using non-invasive functional imaging. The evolution of neural activity over time is controlled by neural function <math>f</math> with parameters <math>\theta^{(n)}</math> and experimental inputs <math>u</math>. The neural activity in turn causes the timeseries <math>y</math>, written on the second line. This is controlled by observation function <math>g</math> with parameters <math>\theta^{(h)}</math>. ObservationAdditive observation noise <math>\epsilon</math> completes the model. Of key interest to experimenters are the neural parameters <math>\theta^{(n)}</math> which, for example, represent the change in connection strengths due to experimental conditions.

ModelSpecifying specificationa DCM requires selecting models <math>f</math> and <math>g</math> and setting appropriate [[Prior probability|priors]] on the parameters - e.g. selecting which connections should be switched on or off. The choice of modelwhich models to use depends on the hypotheses to bebeing tested and the type of data which is available. For example, with fMRI, <math>f</math> is a simple differential equation model of neuraleffective couplingconnectivity and <math>g</math> is a detailed biophysical model of the [[Haemodynamic response|BOLD response]]. The rest of this section surveys the models which have been developed forusing the DCM framework.

==== Functional MRI ====

The neural model in DCM for fMRI uses a simple mathematical device - a [[Taylor series|Taylor approximation]] - to capture the gross causal causal influences between brain regions and their change due to experimental inputs. This is coupled with a detailed biophysical model of the generation of the BOLD response and the MRI signal, based on the Balloon model of Buxton et al.<ref>{{Cite journal|last=Buxton|first=Richard B.|last2=Wong|first2=Eric C.|last3=Frank|first3=Lawrence R.|date=1998-06|title=Dynamics of blood flow and oxygenation changes during brain activation: The balloon model|url=http://dx.doi.org/10.1002/mrm.1910390602|journal=Magnetic Resonance in Medicine|volume=39|issue=6|pages=855–864|doi=10.1002/mrm.1910390602|issn=0740-3194}}</ref> which wasand extended for use in DCM for fMRI <ref>{{Cite journal|last=Friston|first=K.J.|last2=Mechelli|first2=A.|last3=Turner|first3=R.|last4=Price|first4=C.J.|date=2000-10|title=Nonlinear Responses in fMRI: The Balloon Model, Volterra Kernels, and Other Hemodynamics|url=http://dx.doi.org/10.1006/nimg.2000.0630|journal=NeuroImage|volume=12|issue=4|pages=466–477|doi=10.1006/nimg.2000.0630|issn=1053-8119}}</ref><ref>{{Cite journal|last=Stephan|first=Klaas Enno|last2=Weiskopf|first2=Nikolaus|last3=Drysdale|first3=Peter M.|last4=Robinson|first4=Peter A.|last5=Friston|first5=Karl J.|date=2007-11|title=Comparing hemodynamic models with DCM|url=http://dx.doi.org/10.1016/j.neuroimage.2007.07.040|journal=NeuroImage|volume=38|issue=3|pages=387–401|doi=10.1016/j.neuroimage.2007.07.040|issn=1053-8119}}</ref>. ExtensionsAdditions to the basic neural model enable the inclusion of interactions between excitatory and inhibitory neural populations <ref>{{Cite journal|last=Marreiros|first=A.C.|last2=Kiebel|first2=S.J.|last3=Friston|first3=K.J.|date=2008-01|title=Dynamic causal modelling for fMRI: A two-state model|url=https://doi.org/10.1016/j.neuroimage.2007.08.019|journal=NeuroImage|volume=39|issue=1|pages=269–278|doi=10.1016/j.neuroimage.2007.08.019|issn=1053-8119}}</ref> and non-linear influences of neural populations on the coupling between other populations<ref name=":3">{{Cite journal|last=Stephan|first=Klaas Enno|last2=Kasper|first2=Lars|last3=Harrison|first3=Lee M.|last4=Daunizeau|first4=Jean|last5=den Ouden|first5=Hanneke E.M.|last6=Breakspear|first6=Michael|last7=Friston|first7=Karl J.|date=2008-08|title=Nonlinear dynamic causal models for fMRI|url=https://doi.org/10.1016/j.neuroimage.2008.04.262|journal=NeuroImage|volume=42|issue=2|pages=649–662|doi=10.1016/j.neuroimage.2008.04.262|issn=1053-8119|pmc=PMC2636907|pmid=18565765}}</ref>.

Support for resting state analysis was first introduced in Stochastic DCM<ref>{{Cite journal|date=2011-09-15|title=Generalised filtering and stochastic DCM for fMRI|url=https://www.sciencedirect.com/science/article/pii/S1053811911001406|journal=NeuroImage|language=en|volume=58|issue=2|pages=442–457|doi=10.1016/j.neuroimage.2011.01.085|issn=1053-8119}}</ref>, which estimates both neural fluctuations and connectivity parameters in the time ___domain using a procedure called [[Generalized filtering|Generalized Filtering]]. A faster and more accurate solution for resting state data was introduced which operates in the frequency ___domain, called DCM for Cross-Spectral Densities (CSD) <ref>{{Cite journal|last=Friston|first=Karl J.|last2=Kahan|first2=Joshua|last3=Biswal|first3=Bharat|last4=Razi|first4=Adeel|date=2014-07|title=A DCM for resting state fMRI|url=http://dx.doi.org/10.1016/j.neuroimage.2013.12.009|journal=NeuroImage|volume=94|pages=396–407|doi=10.1016/j.neuroimage.2013.12.009|issn=1053-8119}}</ref><ref>{{Cite journal|last=Razi|first=Adeel|last2=Kahan|first2=Joshua|last3=Rees|first3=Geraint|last4=Friston|first4=Karl J.|date=2015-02|title=Construct validation of a DCM for resting state fMRI|url=https://doi.org/10.1016/j.neuroimage.2014.11.027|journal=NeuroImage|volume=106|pages=1–14|doi=10.1016/j.neuroimage.2014.11.027|issn=1053-8119|pmc=PMC4295921|pmid=25463471}}</ref>. Both of these can be applied to large-scale brain networks by using priors based on functional connectivity<ref>{{Cite journal|last=Seghier|first=Mohamed L.|last2=Friston|first2=Karl J.|date=2013-03|title=Network discovery with large DCMs|url=https://doi.org/10.1016/j.neuroimage.2012.12.005|journal=NeuroImage|volume=68|pages=181–191|doi=10.1016/j.neuroimage.2012.12.005|issn=1053-8119|pmc=PMC3566585|pmid=23246991}}</ref><ref name=":4">{{Cite journal|last=Razi|first=Adeel|last2=Seghier|first2=Mohamed L.|last3=Zhou|first3=Yuan|last4=McColgan|first4=Peter|last5=Zeidman|first5=Peter|last6=Park|first6=Hae-Jeong|last7=Sporns|first7=Olaf|last8=Rees|first8=Geraint|last9=Friston|first9=Karl J.|date=2017-10|title=Large-scale DCMs for resting-state fMRI|url=https://doi.org/10.1162/NETN_a_00015|journal=Network Neuroscience|language=en|volume=1|issue=3|pages=222–241|doi=10.1162/netn_a_00015|issn=2472-1751|pmc=PMC5796644|pmid=29400357}}</ref>. Another recent development for resting state analysis is Regression DCM<ref>{{Cite journal|last=Frässle|first=Stefan|last2=Lomakina|first2=Ekaterina I.|last3=Razi|first3=Adeel|last4=Friston|first4=Karl J.|last5=Buhmann|first5=Joachim M.|last6=Stephan|first6=Klaas E.|date=2017-07|title=Regression DCM for fMRI|url=https://doi.org/10.1016/j.neuroimage.2017.02.090|journal=NeuroImage|volume=155|pages=406–421|doi=10.1016/j.neuroimage.2017.02.090|issn=1053-8119}}</ref> implemented in the Tapas software collection (see [[#Software implementations|Software implementations]]). Regression DCM operates in the frequency ___domain, but linearizes the model under certain simplifications, such as having a fixed (canonical) haemodynamic response function. The enables the model to be invertedrapid rapidlyestimation as a [[General linear model|General Linear Model]], and so can beenabling appliedapplication to large-scale brain networks.

==== EEG / MEG / LFP ====

EEG and MEG data support the estimation of more biologically detailed neural models than fMRI, as their higher temporal resolution provide access to richer neural dynamics. The modelsThese can be classed into phenomenological models, which focus on reproducing particular data features, and physiological models, which recapitulate neural circuity. The physiological models can be further subdivided into two classes - . [http://www.scholarpedia.org/article/Conductance-based_models conductanceConductance-based models], which derive from the equivalent circuit representation of the cell membrane developed by Hodgkin and Huxley in the 1950s<ref name=":5">{{Cite journal|last=Hodgkin|first=A. L.|last2=Huxley|first2=A. F.|date=1952-04-28|title=The components of membrane conductance in the giant axon ofLoligo|url=http://dx.doi.org/10.1113/jphysiol.1952.sp004718|journal=The Journal of Physiology|volume=116|issue=4|pages=473–496|doi=10.1113/jphysiol.1952.sp004718|issn=0022-3751}}</ref> and. convolutionConvolution models, which convolve pre-synaptic input by a synaptic kernel function, derivingderive from work by [[Wilson–Cowan model|Wilson & Cowan]]<ref>{{Cite journal|last=Wilson|first=H. R.|last2=Cowan|first2=J. D.|date=1973-09|title=A mathematical theory of the functional dynamics of cortical and thalamic nervous tissue|url=http://dx.doi.org/10.1007/bf00288786|journal=Kybernetik|volume=13|issue=2|pages=55–80|doi=10.1007/bf00288786|issn=0340-1200}}</ref> and Freeman <ref>{{Cite journal|date=1975|title=Mass Action in the Nervous System|url=http://dx.doi.org/10.1016/c2009-0-03145-6|doi=10.1016/c2009-0-03145-6}}</ref> in the 1970s and involve a convolution of pre-synaptic input by a synaptic kernel function. The specific models are as follows:

* Physiological models:

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*** DCM for LFP (Local Field Potentials) <ref>{{Cite journal|last=Moran|first=R.J.|last2=Kiebel|first2=S.J.|last3=Stephan|first3=K.E.|last4=Reilly|first4=R.B.|last5=Daunizeau|first5=J.|last6=Friston|first6=K.J.|date=2007-09|title=A neural mass model of spectral responses in electrophysiology|url=http://dx.doi.org/10.1016/j.neuroimage.2007.05.032|journal=NeuroImage|volume=37|issue=3|pages=706–720|doi=10.1016/j.neuroimage.2007.05.032|issn=1053-8119}}</ref>. Extends DCM for ERP by added the effects of specific ion channels on spike generation.

*** Canonical Microcircuit (CMC) <ref>{{Cite journal|last=Bastos|first=Andre M.|last2=Usrey|first2=W. Martin|last3=Adams|first3=Rick A.|last4=Mangun|first4=George R.|last5=Fries|first5=Pascal|last6=Friston|first6=Karl J.|date=2012-11|title=Canonical Microcircuits for Predictive Coding|url=http://dx.doi.org/10.1016/j.neuron.2012.10.038|journal=Neuron|volume=76|issue=4|pages=695–711|doi=10.1016/j.neuron.2012.10.038|issn=0896-6273}}</ref>. Used to address hypotheses about laminar-specific ascending and descending signals in the brain, which are thought to underpin [[predictive coding]]. This model splits the single pyramidal cell population from DCM for ERP into deep and superficial populations.

***Neural Field Model (NFM) <ref>{{Cite journal|last=Pinotsis|first=D.A.|last2=Friston|first2=K.J.|date=2011-03|title=Neural fields, spectral responses and lateral connections|url=http://dx.doi.org/10.1016/j.neuroimage.2010.11.081|journal=NeuroImage|volume=55|issue=1|pages=39–48|doi=10.1016/j.neuroimage.2010.11.081|issn=1053-8119}}</ref>. Extends the models above into the spatial ___domain, modelling continuous changes in current across the cortical sheet.

** Conductance models:

***Neural Mass Model (NMM) and Mean-field model (MFM)<ref>{{Cite journal|last=Marreiros|first=André C.|last2=Daunizeau|first2=Jean|last3=Kiebel|first3=Stefan J.|last4=Friston|first4=Karl J.|date=2008-08|title=Population dynamics: Variance and the sigmoid activation function|url=http://dx.doi.org/10.1016/j.neuroimage.2008.04.239|journal=NeuroImage|volume=42|issue=1|pages=147–157|doi=10.1016/j.neuroimage.2008.04.239|issn=1053-8119}}</ref><ref>{{Cite journal|last=Marreiros|first=André C.|last2=Kiebel|first2=Stefan J.|last3=Daunizeau|first3=Jean|last4=Harrison|first4=Lee M.|last5=Friston|first5=Karl J.|date=2009-02|title=Population dynamics under the Laplace assumption|url=http://dx.doi.org/10.1016/j.neuroimage.2008.10.008|journal=NeuroImage|volume=44|issue=3|pages=701–714|doi=10.1016/j.neuroimage.2008.10.008|issn=1053-8119}}</ref>. These models have the same arrangement of neural populations as DCM for ERP, above, but are based on the [[Morris–Lecar model|Morris-Lecar model]] of the barnacle muscle fibre <ref>{{Cite journal|last=Morris|first=C.|last2=Lecar|first2=H.|date=1981-07|title=Voltage oscillations in the barnacle giant muscle fiber|url=http://dx.doi.org/10.1016/s0006-3495(81)84782-0|journal=Biophysical Journal|volume=35|issue=1|pages=193–213|doi=10.1016/s0006-3495(81)84782-0|issn=0006-3495}}</ref>, which in turn derives from the [[Hodgkin–Huxley model|Hodgin and Huxley]] model of the giant squid axon<ref name=":5" />. They enable inference about ligand-gated excitatory (Na+) and inhibitory (Cl-) ion flow, mediated through fast glutamatergic and GABAergic receptors. Whereas DCM for fMRI and the convolution models represent the activity of aeach neural population by a single number - its mean activity - the conductance models include the full density (probability distribution) of activity across the population. The 'mean-field assumption' used in the MFM version of the model has the density of one population's activity depending only on the mean of other neural populations. A subsequent extension to the MFM model added voltage-gated NMDA ion channels<ref>{{Cite journal|last=Moran|first=Rosalyn J.|last2=Stephan|first2=Klaas E.|last3=Dolan|first3=Raymond J.|last4=Friston|first4=Karl J.|date=2011-04|title=Consistent spectral predictors for dynamic causal models of steady-state responses|url=https://doi.org/10.1016/j.neuroimage.2011.01.012|journal=NeuroImage|volume=55|issue=4|pages=1694–1708|doi=10.1016/j.neuroimage.2011.01.012|issn=1053-8119|pmc=PMC3093618|pmid=21238593}}</ref>.

****

* Phenomenological models:

**DCM for phase coupling<ref>{{Cite journal|last=Penny|first=W.D.|last2=Litvak|first2=V.|last3=Fuentemilla|first3=L.|last4=Duzel|first4=E.|last5=Friston|first5=K.|date=2009-09|title=Dynamic Causal Models for phase coupling|url=http://dx.doi.org/10.1016/j.jneumeth.2009.06.029|journal=Journal of Neuroscience Methods|volume=183|issue=1|pages=19–30|doi=10.1016/j.jneumeth.2009.06.029|issn=0165-0270}}</ref>. Models the interaction of brain regions as Weakly Coupled Oscillators (WCOs), in which the rate of change of phase of one oscillator is related to the phase differences between itself and other oscillators .

== Model estimation ==

Model inversion or estimation is implemented in DCM using aan optimisation scheme referred to as [[Variational Bayesian methods|variational BayesianBayes]] optimisationunder schemethe [[Laplace's method|Laplace approximation]]<ref>{{Citation|last=Friston|first=K.|title=Variational Bayes under the Laplace approximation|date=2007|url=http://dx.doi.org/10.1016/b978-012372560-8/50047-4|work=Statistical Parametric Mapping|pages=606–618|publisher=Elsevier|isbn=9780123725608|last2=Mattout|first2=J.|last3=Trujillo-Barreto|first3=N.|last4=Ashburner|first4=J.|last5=Penny|first5=W.}}</ref>. It provides two useful quantities. The log marginal likelihood or model evidence <math>\ln{p(y|m)}</math> is the probability of observing of the given data under the model. This cannot be calculated exactly and in DCM it is approximated by a quantity called the negative variational free energy <math>F</math> , referred to in machine learning as the Evidence Lower Bound (ELBO). Hypotheses are tested by comparing the evidence for different models based on their free energy, a procedure namedcalled Bayesian model comparison.

Model estimation also provides estimates of the parameters <math>p(\theta|y)</math>, for example the connection strengths, which maximise the free energy. Where models differ only in their priors, [[Bayesian model reduction|Bayesian Model Reduction]] can be used to rapidly the derive the evidence and parameters for nested or reduced models from a full model.

== Model comparison ==

Neuroimaging studies typically investigate effects which are conserved at the group level, or which differ between subjects. There are two predominant approaches for group-level analysis: random effects Bayesian Model Selection (BMS) <ref>{{Cite journal|last=Rigoux|first=L.|last2=Stephan|first2=K.E.|last3=Friston|first3=K.J.|last4=Daunizeau|first4=J.|date=2014-01|title=Bayesian model selection for group studies — Revisited|url=http://dx.doi.org/10.1016/j.neuroimage.2013.08.065|journal=NeuroImage|volume=84|pages=971–985|doi=10.1016/j.neuroimage.2013.08.065|issn=1053-8119}}</ref> and Parametric Empirical Bayes (PEB) <ref name=":1">{{Cite journal|last=Friston|first=Karl J.|last2=Litvak|first2=Vladimir|last3=Oswal|first3=Ashwini|last4=Razi|first4=Adeel|last5=Stephan|first5=Klaas E.|last6=van Wijk|first6=Bernadette C.M.|last7=Ziegler|first7=Gabriel|last8=Zeidman|first8=Peter|date=2016-03|title=Bayesian model reduction and empirical Bayes for group (DCM) studies|url=https://doi.org/10.1016/j.neuroimage.2015.11.015|journal=NeuroImage|volume=128|pages=413–431|doi=10.1016/j.neuroimage.2015.11.015|issn=1053-8119|pmc=PMC4767224|pmid=26569570}}</ref>. Random effects BMS posits that subjects differ in terms of which model generated their data - e.g. drawing a random subject from the population, there would be a 25% chance that their databrain wereis generatedstructured bylike model 1 and a 75% chance theirthat datait wereis generatedstructured bylike model 2. The analysis pipeline for the BMS approach procedure follows a series of steps:

# Specify and estimate multiple DCMs per subject, where each DCM (or set of DCMs) embodies a hypothesis.

# Perform random effects BMS to estimate the proportion of subjects whose data were generated by each model

# Perform Bayesian Model Averaging, which is a weighted average over the parameters of the DCMs. This means that models with greater probability contribute more to the average than thosemodels with lower probability.

TheAlternatively, mostthe recently developed PEB approach<ref name=":1" /> is a hierarchical model over parameters (connection strengths). It eschews the notion of different models at the level of individual subjects, and posits that people differ in the (continuous) strength of their individual connections. The PEB approach separates sources of variability in connection strengths across subjects into hypothesised covariates and uninteresting between-subject variability (random effects). The PEB procedure is as follows:

# Specify a single 'full' DCM per subject, which contains all connectivity parameters of interest.

# Specify a Bayesian General Linear Model theto model estimatedthe parameters (the full posterior density) from all subjects using a Bayesian General Linear Model at the group level.

# Test hypotheses by comparing the full group-level model to reduced group-level models where certain combinations of connections have been switched off.

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* Face validity establishes whether the parameters of a model can be recovered from simulated data. This has been performed with the development of each new model (E.g. <ref name=":2" /><ref name=":3" />).

* Construct validity assesses consistency with other analytical methods. - forFor example, DCM has been compared with Structural Equation Modelling <ref>{{Cite journal|last=Penny|first=W.D.|last2=Stephan|first2=K.E.|last3=Mechelli|first3=A.|last4=Friston|first4=K.J.|date=2004-01|title=Modelling functional integration: a comparison of structural equation and dynamic causal models|url=http://dx.doi.org/10.1016/j.neuroimage.2004.07.041|journal=NeuroImage|volume=23|pages=S264–S274|doi=10.1016/j.neuroimage.2004.07.041|issn=1053-8119}}</ref> and other neurobiological computational models <ref>{{Cite journal|last=Lee|first=Lucy|last2=Friston|first2=Karl|last3=Horwitz|first3=Barry|date=2006-05|title=Large-scale neural models and dynamic causal modelling|url=http://dx.doi.org/10.1016/j.neuroimage.2005.11.007|journal=NeuroImage|volume=30|issue=4|pages=1243–1254|doi=10.1016/j.neuroimage.2005.11.007|issn=1053-8119}}</ref>.

* Predictive validity assesses the ability to predict known or expected effects. This has included testing against iEEG / EEG / stimulation <ref>{{Cite journal|last=David|first=Olivier|last2=Guillemain|first2=Isabelle|last3=Saillet|first3=Sandrine|last4=Reyt|first4=Sebastien|last5=Deransart|first5=Colin|last6=Segebarth|first6=Christoph|last7=Depaulis|first7=Antoine|date=2008-12-23|title=Identifying Neural Drivers with Functional MRI: An Electrophysiological Validation|url=http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.0060315|journal=PLOS Biology|language=en|volume=6|issue=12|pages=e315|doi=10.1371/journal.pbio.0060315|issn=1545-7885|pmc=PMC2605917|pmid=19108604}}</ref><ref>{{Cite journal|last=David|first=Olivier|last2=Woźniak|first2=Agata|last3=Minotti|first3=Lorella|last4=Kahane|first4=Philippe|date=2008-02|title=Preictal short-term plasticity induced by intracerebral 1 Hz stimulation|url=https://doi.org/10.1016/j.neuroimage.2007.11.005|journal=NeuroImage|volume=39|issue=4|pages=1633–1646|doi=10.1016/j.neuroimage.2007.11.005|issn=1053-8119}}</ref><ref>{{Cite journal|last=Reyt|first=Sébastien|last2=Picq|first2=Chloé|last3=Sinniger|first3=Valérie|last4=Clarençon|first4=Didier|last5=Bonaz|first5=Bruno|last6=David|first6=Olivier|date=2010-10|title=Dynamic Causal Modelling and physiological confounds: A functional MRI study of vagus nerve stimulation|url=http://dx.doi.org/10.1016/j.neuroimage.2010.05.021|journal=NeuroImage|volume=52|issue=4|pages=1456–1464|doi=10.1016/j.neuroimage.2010.05.021|issn=1053-8119}}</ref><ref>{{Cite journal|last=Daunizeau|first=J.|last2=Lemieux|first2=L.|last3=Vaudano|first3=A. E.|last4=Friston|first4=K. J.|last5=Stephan|first5=K. E.|date=2013|title=An electrophysiological validation of stochastic DCM for fMRI|url=http://dx.doi.org/10.3389/fncom.2012.00103|journal=Frontiers in Computational Neuroscience|volume=6|doi=10.3389/fncom.2012.00103|issn=1662-5188}}</ref> and against known pharmacological treatments <ref>{{Cite journal|last=Moran|first=Rosalyn J.|last2=Symmonds|first2=Mkael|last3=Stephan|first3=Klaas E.|last4=Friston|first4=Karl J.|last5=Dolan|first5=Raymond J.|date=2011-08|title=An In Vivo Assay of Synaptic Function Mediating Human Cognition|url=http://dx.doi.org/10.1016/j.cub.2011.06.053|journal=Current Biology|volume=21|issue=15|pages=1320–1325|doi=10.1016/j.cub.2011.06.053|issn=0960-9822}}</ref><ref>{{Cite journal|last=Moran|first=Rosalyn J.|last2=Jung|first2=Fabienne|last3=Kumagai|first3=Tetsuya|last4=Endepols|first4=Heike|last5=Graf|first5=Rudolf|last6=Dolan|first6=Raymond J.|last7=Friston|first7=Karl J.|last8=Stephan|first8=Klaas E.|last9=Tittgemeyer|first9=Marc|date=2011-08-02|title=Dynamic Causal Models and Physiological Inference: A Validation Study Using Isoflurane Anaesthesia in Rodents|url=http://dx.doi.org/10.1371/journal.pone.0022790|journal=PLoS ONE|volume=6|issue=8|pages=e22790|doi=10.1371/journal.pone.0022790|issn=1932-6203}}</ref>.

== Limitations / drawbacks ==

DCM is a hypothesis-driven approach for investigating the interactions among pre-defined regions of interest. It is not ideally suited for exploratory analyses <ref name=":0" />. Although methods have been implemented for automatically searching over reduced models ([[Bayesian model reduction|Bayesian Model Reduction]]) and for modelling large-scale brain networks<ref name=":4" />, these methods still expect clear hypotheses. Other approaches such as psycho-physical interactions (PPI) analysis may be more appropriate in contexts with less strong hypotheses.

The variational Bayesian methods used for model estimation used approximationsare based on the on the Laplace approximation that the parameters are normally distributed. This approximation can break down in the context of highly non-linear models, such as those used in EEG / MEG analysis, where local minima can preclude the free energy from serving as a closetight lower bound on log model evidence. Sampling approaches provide the gold standard, however are time consuming to run,. andThese have been used to validate variational approximations in DCM <ref>{{Cite journal|last=Chumbley|first=Justin R.|last2=Friston|first2=Karl J.|last3=Fearn|first3=Tom|last4=Kiebel|first4=Stefan J.|date=2007-11|title=A Metropolis–Hastings algorithm for dynamic causal models|url=http://dx.doi.org/10.1016/j.neuroimage.2007.07.028|journal=NeuroImage|volume=38|issue=3|pages=478–487|doi=10.1016/j.neuroimage.2007.07.028|issn=1053-8119}}</ref>.

== Software implementations ==

DCM is implemented in the [[Statistical parametric mapping|Statistical Parametric Mapping]] software package, where itwhich serves as the canonical or reference implementation (http://www.fil.ion.ucl.ac.uk/spm/software/spm12/). It has been re-implemented and further developed in the Tapas software collection (https://www.tnu.ethz.ch/en/software/tapas.html) and the VBA toolbox (http://mbb-team.github.io/VBA-toolbox/).

== References ==