Neurochemistry-enriched dynamic causal models of magnetoencephalography, using magnetic resonance spectroscopy

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

Computational modelling of movement-related beta-oscillatory dynamics in human motor cortex

Oscillatory activity in the beta range, in human primary motor cortex (M1), shows interesting dynamics that are tied to behaviour and change systematically in disease. To investigate the pathophysiology underlying these changes, we must first understand how changes in beta activity are caused in healthy subjects. We therefore adapted a canonical (repeatable) microcircuit model used in dynamic causal modelling (DCM) previously used to model induced responses in visual cortex. We adapted this model to accommodate cytoarchitectural differences between visual and motor cortex. Using biologically plausible connections, we used Bayesian model selection to identify the best model of measured MEG data from 11 young healthy participants, performing a simple handgrip task. We found that the canonical M1 model had substantially more model evidence than the generic canonical microcircuit model when explaining measured MEG data. The canonical M1 model reproduced measured dynamics in humans at rest, in a manner consistent with equivalent studies performed in mice. Furthermore, the changes in excitability (self-inhibition) necessary to explain beta suppression during handgrip were consistent with the attenuation of sensory precision implied by predictive coding. These results establish the face validity of a model that can be used to explore the laminar interactions that underlie beta-oscillatory dynamics in humans in vivo. Our canonical M1 model may be useful for characterising the synaptic mechanisms that mediate pathophysiological beta dynamics associated with movement disorders, such as stroke or Parkinson's disease

Dynamic causal modelling of electrographic seizure activity using Bayesian belief updating

AbstractSeizure activity in EEG recordings can persist for hours with seizure dynamics changing rapidly over time and space. To characterise the spatiotemporal evolution of seizure activity, large data sets often need to be analysed. Dynamic causal modelling (DCM) can be used to estimate the synaptic drivers of cortical dynamics during a seizure; however, the requisite (Bayesian) inversion procedure is computationally expensive. In this note, we describe a straightforward procedure, within the DCM framework, that provides efficient inversion of seizure activity measured with non-invasive and invasive physiological recordings; namely, EEG/ECoG. We describe the theoretical background behind a Bayesian belief updating scheme for DCM. The scheme is tested on simulated and empirical seizure activity (recorded both invasively and non-invasively) and compared with standard Bayesian inversion. We show that the Bayesian belief updating scheme provides similar estimates of time-varying synaptic parameters, compared to standard schemes, indicating no significant qualitative change in accuracy. The difference in variance explained was small (less than 5%). The updating method was substantially more efficient, taking approximately 5–10min compared to approximately 1–2h. Moreover, the setup of the model under the updating scheme allows for a clear specification of how neuronal variables fluctuate over separable timescales. This method now allows us to investigate the effect of fast (neuronal) activity on slow fluctuations in (synaptic) parameters, paving a way forward to understand how seizure activity is generated

Changes in EEG Power Spectral Density and Cortical Connectivity in Healthy and Tetraplegic Patients during a Motor Imagery Task

Knowledge of brain connectivity is an important aspect of modern neuroscience, to understand how the brain realizes its functions. In this work, neural mass models including four groups of excitatory and inhibitory neurons are used to estimate the connectivity among three cortical regions of interests (ROIs) during a foot-movement task. Real data were obtained via high-resolution scalp EEGs on two populations: healthy volunteers and tetraplegic patients. A 3-shell Boundary Element Model of the head was used to estimate the cortical current density and to derive cortical EEGs in the three ROIs. The model assumes that each ROI can generate an intrinsic rhythm in the beta range, and receives rhythms in the alpha and gamma ranges from other two regions. Connectivity strengths among the ROIs were estimated by means of an original genetic algorithm that tries to minimize several cost functions of the difference between real and model power spectral densities. Results show that the stronger connections are those from the cingulate cortex to the primary and supplementary motor areas, thus emphasizing the pivotal role played by the CMA_L during the task. Tetraplegic patients exhibit higher connectivity strength on average, with significant statistical differences in some connections. The results are commented and virtues and limitations of the proposed method discussed

Tracking slow modulations in synaptic gain using dynamic causal modelling : validation in epilepsy

In thiswork we propose a proof of principle that dynamic causal modelling can identify plausible mechanisms at the synaptic level underlying brain state changes over a timescale of seconds. As a benchmark example for validation we used intracranial electroencephalographic signals in a human subject. These data were used to infer the (effective connectivity) architecture of synaptic connections among neural populations assumed to generate seizure activity. Dynamic causal modelling allowed us to quantify empirical changes in spectral activity in terms of a trajectory in parameter space -identifying key synaptic parameters or connections that cause observed signals. Using recordings from three seizures in one patient, we considered a network of two sources (within and just outside the putative ictal zone). Bayesian model selection was used to identify the intrinsic (within-source) and extrinsic (between-source) connectivity. Having established the underlying architecture, we were able to track the evolution of key connectivity parameters (e.g., inhibitory connections to superficial pyramidal cells) and test specific hypotheses about the synaptic mechanisms involved in ictogenesis. Our key finding was that intrinsic synaptic changes were sufficient to explain seizure onset, where these changes showed dissociable time courses over several seconds. Crucially, these changes spoke to an increase in the sensitivity of principal cells to intrinsic inhibitory afferents and a transient loss of excitatory-inhibitory balance

Bayesian Comparison of Neurovascular Coupling Models Using EEG-fMRI

Functional magnetic resonance imaging (fMRI), with blood oxygenation level-dependent (BOLD) contrast, is a widely used technique for studying the human brain. However, it is an indirect measure of underlying neuronal activity and the processes that link this activity to BOLD signals are still a topic of much debate. In order to relate findings from fMRI research to other measures of neuronal activity it is vital to understand the underlying neurovascular coupling mechanism. Currently, there is no consensus on the relative roles of synaptic and spiking activity in the generation of the BOLD response. Here we designed a modelling framework to investigate different neurovascular coupling mechanisms. We use Electroencephalographic (EEG) and fMRI data from a visual stimulation task together with biophysically informed mathematical models describing how neuronal activity generates the BOLD signals. These models allow us to non-invasively infer the degree of local synaptic and spiking activity in the healthy human brain. In addition, we use Bayesian model comparison to decide between neurovascular coupling mechanisms. We show that the BOLD signal is dependent upon both the synaptic and spiking activity but that the relative contributions of these two inputs are dependent upon the underlying neuronal firing rate. When the underlying neuronal firing is low then the BOLD response is best explained by synaptic activity. However, when the neuronal firing rate is high then both synaptic and spiking activity are required to explain the BOLD signal

Dynamic causal modelling for EEG and MEG

Dynamic Causal Modelling (DCM) is an approach first introduced for the analysis of functional magnetic resonance imaging (fMRI) to quantify effective connectivity between brain areas. Recently, this framework has been extended and established in the magneto/encephalography (M/EEG) domain. DCM for M/EEG entails the inversion a full spatiotemporal model of evoked responses, over multiple conditions. This model rests on a biophysical and neurobiological generative model for electrophysiological data. A generative model is a prescription of how data are generated. The inversion of a DCM provides conditional densities on the model parameters and, indeed on the model itself. These densities enable one to answer key questions about the underlying system. A DCM comprises two parts; one part describes the dynamics within and among neuronal sources, and the second describes how source dynamics generate data in the sensors, using the lead-field. The parameters of this spatiotemporal model are estimated using a single (iterative) Bayesian procedure. In this paper, we will motivate and describe the current DCM framework. Two examples show how the approach can be applied to M/EEG experiments