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Abstract: We describe the use of spatial and temporal constraints in dynamic causal modelling (DCM) of magneto- and electroencephalography (M/EEG) data. DCM for M/EEG is based on a spatiotemporal, generative model of electromagnetic brain activity. The temporal dynamics are described by neural-mass models of equivalent current dipole (ECD) sources and their spatial expression is modelled by parameterized lead-field functions. Often, in classical ECD models, symmetry constraints are used to model homologous pairs of dipoles in both hemispheres. These constraints are motivated by assumptions about symmetric activation of bilateral sensory sources. In classical approaches, these constraints are ‘hard’; i.e. the parameters of homologous dipoles are shared. Here, in the context of DCM, we illustrate the use of informed Bayesian priors to implement ‘soft’ symmetry constraints that are expressed in the posterior estimates only when supported by the data. Critically, with DCM one can deploy symmetry constraints in either the temporal or spatial components of the model. This enables one to test for symmetry in temporal (neural-mass) parameters in the presence of non-symmetric spatial expressions of homologous sources (and vice versa). Furthermore, we demonstrate that Bayesian model comparison can be used to identify the best models among a range of symmetric and non-symmetric variants. Our main finding is that the use of ‘soft’ symmetry priors is recommended for evoked responses to bilateral sensory input. We illustrate the use of symmetry constraints in DCM on synthetic and real EEG data. [Copyright &y& Elsevier]

Metastability is a key source of itinerant dynamics in the brain; namely, spontaneous spatiotemporal reorganization of neuronal activity. This itinerancy has been the focus of numerous dynamic functional connectivity (DFC) analyses – developed to characterize the formation and dissolution of distributed functional patterns over time, using resting state fMRI. However, aside from technical and practical controversies, these approaches cannot recover the neuronal mechanisms that underwrite itinerant (e.g., metastable) dynamics—due to their descriptive, model-free nature. We argue that effective connectivity (EC) analyses are more apt for investigating the neuronal basis of metastability. To this end, we appeal to biologically-grounded models (i.e., dynamic causal modelling, DCM) and dynamical systems theory (i.e., heteroclinic sequential dynamics) to create a probabilistic, generative model of haemodynamic fluctuations. This model generates trajectories in the parametric space of EC modes (i.e., states of connectivity) that characterize functional brain architectures. In brief, it extends an established spectral DCM, to generate functional connectivity data features that change over time. This foundational paper tries to establish the model's face validity by simulating non-stationary fMRI time series and recovering key model parameters (i.e., transition probabilities among connectivity states and the parametric nature of these states) using variational Bayes. These data are further characterized using Bayesian model comparison (within and between subjects). Finally, we consider practical issues that attend applications and extensions of this scheme. Importantly, the scheme operates within a generic Bayesian framework – that can be adapted to study metastability and itinerant dynamics in any non-stationary time series. [ABSTRACT FROM AUTHOR]

• We developed neurochemistry-enriched dynamic causal model of resting-state MEG data using MRS measurements of neurotransmitter concentrations. • Neurotransmitter levels, place prior constraints on synaptic connectivity, in the biologically informed model of MEG data. • Comparing evidence of group DCMs using Bayesian model selection procedure reveal synaptic connections that are likely to be informed by MRS data. We present a hierarchical empirical Bayesian framework for testing hypotheses about neurotransmitters' concertation as empirical prior for synaptic physiology using ultra-high field magnetic resonance spectroscopy (7T-MRS) and magnetoencephalography data (MEG). A first level dynamic causal modelling of cortical microcircuits is used to infer the connectivity parameters of a generative model of individuals' neurophysiological observations. At the second level, individuals' 7T-MRS estimates of regional neurotransmitter concentration supply empirical priors on synaptic connectivity. We compare the group-wise evidence for alternative empirical priors, defined by monotonic functions of spectroscopic estimates, on subsets of synaptic connections. For efficiency and reproducibility, we used Bayesian model reduction (BMR), parametric empirical Bayes and variational Bayesian inversion. In particular, we used Bayesian model reduction to compare alternative model evidence of how spectroscopic neurotransmitter measures inform estimates of synaptic connectivity. This identifies the subset of synaptic connections that are influenced by individual differences in neurotransmitter levels, as measured by 7T-MRS. We demonstrate the method using resting-state MEG (i.e., task-free recording) and 7T-MRS data from healthy adults. Our results confirm the hypotheses that GABA concentration influences local recurrent inhibitory intrinsic connectivity in deep and superficial cortical layers, while glutamate influences the excitatory connections between superficial and deep layers and connections from superficial to inhibitory interneurons. Using within-subject split-sampling of the MEG dataset (i.e., validation by means of a held-out dataset), we show that model comparison for hypothesis testing can be highly reliable. The method is suitable for applications with magnetoencephalography or electroencephalography, and is well-suited to reveal the mechanisms of neurological and psychiatric disorders, including responses to psychopharmacological interventions. [ABSTRACT FROM AUTHOR]

Abstract Parkinson's disease (PD) is a neurodegenerative condition in which aberrant oscillatory synchronization of neuronal activity at beta frequencies (15–35 Hz) across the cortico-basal ganglia-thalamocortical circuit is associated with debilitating motor symptoms, such as bradykinesia and rigidity. Mounting evidence suggests that the magnitude of beta synchrony in the parkinsonian state fluctuates over time, but the mechanisms by which thalamocortical circuitry regulates the dynamic properties of cortical beta in PD are poorly understood. Using the recently developed generic Dynamic Causal Modelling (DCM) framework, we recursively optimized a set of plausible models of the thalamocortical circuit (n = 144) to infer the neural mechanisms that best explain the transitions between low and high beta power states observed in recordings of field potentials made in the motor cortex of anesthetized Parkinsonian rats. Bayesian model comparison suggests that upregulation of cortical rhythmic activity in the beta-frequency band results from changes in the coupling strength both between and within the thalamus and motor cortex. Specifically, our model indicates that high levels of cortical beta synchrony are mainly achieved by a delayed (extrinsic) input from thalamic relay cells to deep pyramidal cells and a fast (intrinsic) input from middle pyramidal cells to superficial pyramidal cells. From a clinical perspective, our study provides insights into potential therapeutic strategies that could be utilized to modulate the network mechanisms responsible for the enhancement of cortical beta in PD. Specifically, we speculate that cortical stimulation aimed to reduce the enhanced excitatory inputs to either the superficial or deep pyramidal cells could be a potential non-invasive therapeutic strategy for PD. Highlights • Coupling changes within and between circuit nodes lead to cortical beta enhancement. • Input propagation delays play a crucial role in the up-regulation of cortical beta. • Beta power could be modulated by altering lamina specific inputs. [ABSTRACT FROM AUTHOR]

This technical note introduces adiabatic dynamic causal modelling, a method for inferring slow changes in biophysical parameters that control fluctuations of fast neuronal states. The application domain we have in mind is inferring slow changes in variables (e.g., extracellular ion concentrations or synaptic efficacy) that underlie phase transitions in brain activity (e.g., paroxysmal seizure activity). The scheme is efficient and yet retains a biophysical interpretation, in virtue of being based on established neural mass models that are equipped with a slow dynamic on the parameters (such as synaptic rate constants or effective connectivity). In brief, we use an adiabatic approximation to summarise fast fluctuations in hidden neuronal states (and their expression in sensors) in terms of their second order statistics; namely, their complex cross spectra. This allows one to specify and compare models of slowly changing parameters (using Bayesian model reduction) that generate a sequence of empirical cross spectra of electrophysiological recordings. Crucially, we use the slow fluctuations in the spectral power of neuronal activity as empirical priors on changes in synaptic parameters. This introduces a circular causality, in which synaptic parameters underwrite fast neuronal activity that, in turn, induces activity-dependent plasticity in synaptic parameters. In this foundational paper, we describe the underlying model, establish its face validity using simulations and provide an illustrative application to a chemoconvulsant animal model of seizure activity. [ABSTRACT FROM AUTHOR]

This technical note presents a dynamic causal modelling (DCM) procedure for evaluating different models of neurovascular coupling in the human brain – using combined electromagnetic (M/EEG) and functional magnetic resonance imaging (fMRI) data. This procedure compares the evidence for biologically informed models of neurovascular coupling using Bayesian model comparison. First, fMRI data are used to localise regionally specific neuronal responses. The coordinates of these responses are then used as the location priors in a DCM of electrophysiological responses elicited by the same paradigm. The ensuing estimates of model parameters are then used to generate neuronal drive functions, which model pre- or post-synaptic activity for each experimental condition. These functions form the input to a model of neurovascular coupling, whose parameters are estimated from the fMRI data. Crucially, this enables one to evaluate different models of neurovascular coupling, using Bayesian model comparison – asking, for example, whether instantaneous or delayed, pre- or post-synaptic signals mediate haemodynamic responses. We provide an illustrative application of the procedure using a single-subject auditory fMRI and MEG dataset. The code and exemplar data accompanying this technical note are available through the statistical parametric mapping (SPM) software. • A method is introduced for Bayesian fusion of M/EEG and BOLD fMRI data using dynamic causal modelling. • The key novel contribution is the introduction of neural drive functions, which link models of the two modalities. • Bayesian model comparison is used to select plausible hypotheses about the function of neurovascular coupling. [ABSTRACT FROM AUTHOR]

This paper asks whether integrating multimodal EEG and fMRI data offers a better characterisation of functional brain architectures than either modality alone. This evaluation rests upon a dynamic causal model that generates both EEG and fMRI data from the same neuronal dynamics. We introduce the use of Bayesian fusion to provide informative (empirical) neuronal priors – derived from dynamic causal modelling (DCM) of EEG data – for subsequent DCM of fMRI data. To illustrate this procedure, we generated synthetic EEG and fMRI timeseries for a mismatch negativity (or auditory oddball) paradigm, using biologically plausible model parameters (i.e., posterior expectations from a DCM of empirical, open access, EEG data). Using model inversion, we found that Bayesian fusion provided a substantial improvement in marginal likelihood or model evidence, indicating a more efficient estimation of model parameters, in relation to inverting fMRI data alone. We quantified the benefits of multimodal fusion with the information gain pertaining to neuronal and haemodynamic parameters – as measured by the Kullback-Leibler divergence between their prior and posterior densities. Remarkably, this analysis suggested that EEG data can improve estimates of haemodynamic parameters; thereby furnishing proof-of-principle that Bayesian fusion of EEG and fMRI is necessary to resolve conditional dependencies between neuronal and haemodynamic estimators. These results suggest that Bayesian fusion may offer a useful approach that exploits the complementary temporal (EEG) and spatial (fMRI) precision of different data modalities. We envisage the procedure could be applied to any multimodal dataset that can be explained by a DCM with a common neuronal parameterisation. • Multimodal DCM shows how the same neuronal activity causes multiple measurements. • Bayesian fusion of EEG/fMRI resolves conditional dependencies between parameters. • Information gain quantifies the added benefits of multimodal Bayesian fusion. [ABSTRACT FROM AUTHOR]