Bidirectional interactions between neuronal and hemodynamic responses to transcranial direct current stimulation (tDCS): challenges for brain-state dependent tDCS

Transcranial direct current stimulation (tDCS) has been shown to modulate cortical neural activity. During neural activity, the electric currents from excitable membranes of brain tissue superimpose in the extracellular medium and generate a potential at scalp, which is referred as the electroencephalogram (EEG). Respective neural activity (energy demand) has been shown to be closely related, spatially and temporally, to cerebral blood flow (CBF) that supplies glucose (energy supply) via neurovascular coupling. The hemodynamic response can be captured by near-infrared spectroscopy (NIRS), which enables continuous monitoring of cerebral oxygenation and blood volume. This neurovascular coupling phenomenon led to the concept of neurovascular unit (NVU) that consists of the endothelium, glia, neurons, pericytes, and the basal lamina. Here, recent works suggest NVU as an integrated system working in concert using feedback mechanisms to enable proper brain homeostasis and function where the challenge remains in capturing these mostly nonlinear spatiotemporal interactions within NVU during tDCS. Therefore, we propose EEG-NIRS-based whole-head monitoring of tDCS-induced neuronal and hemodynamic alterations for brain-state dependent tDCS

KurSL: model of anharmonic coupled oscillations based on Kuramoto coupling and Sturm–Liouville problem

Physiological signaling is often oscillatory and shows nonlinearity due to complex interactions of underlying processes or signal propagation delays. This is particularly evident in case of brain activity which is subject to various feedback loop interactions between different brain structures, that coordinate their activity to support normal function. In order to understand such signaling in health and disease, methods are needed that can deal with such complex oscillatory phenomena. In this paper, a data-driven method for analyzing anharmonic oscillations is introduced. The KurSL model incorporates two well-studied components, which in the past have been used separately to analyze oscillatory behavior. The Sturm–Liouville equations describe a form of a general oscillation, and the Kuramoto coupling model represents a set of oscillators interacting in the phase domain. Integration of these components provides a flexible framework for capturing complex interactions of oscillatory processes of more general form than the most commonly used harmonic oscillators. The paper introduces a mathematical framework of the KurSL model and analyzes its behavior for a variety of parameter ranges. The significance of the model follows from its ability to provide information about coupled oscillators’ phase dynamics directly from the time series. KurSL offers a novel framework for analyzing a wide range of complex oscillatory behaviors, such as the ones encountered in physiological signals

Dynamical Principles of Emotion-Cognition Interaction: Mathematical Images of Mental Disorders

The key contribution of this work is to introduce a mathematical framework to understand self-organized dynamics in the brain that can explain certain aspects of itinerant behavior. Specifically, we introduce a model based upon the coupling of generalized Lotka-Volterra systems. This coupling is based upon competition for common resources. The system can be regarded as a normal or canonical form for any distributed system that shows self-organized dynamics that entail winnerless competition. Crucially, we will show that some of the fundamental instabilities that arise in these coupled systems are remarkably similar to endogenous activity seen in the brain (using EEG and fMRI). Furthermore, by changing a small subset of the system's parameters we can produce bifurcations and metastable sequential dynamics changing, which bear a remarkable similarity to pathological brain states seen in psychiatry. In what follows, we will consider the coupling of two macroscopic modes of brain activity, which, in a purely descriptive fashion, we will label as cognitive and emotional modes. Our aim is to examine the dynamical structures that emerge when coupling these two modes and relate them tentatively to brain activity in normal and non-normal states

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

Dysconnection in schizophrenia: from abnormal synaptic plasticity to failures of self-monitoring

Over the last 2 decades, a large number of neurophysiological and neuroimaging studies of patients with schizophrenia have furnished in vivo evidence for dysconnectivity, ie, abnormal functional integration of brain processes. While the evidence for dysconnectivity in schizophrenia is strong, its etiology, pathophysiological mechanisms, and significance for clinical symptoms are unclear. First, dysconnectivity could result from aberrant wiring of connections during development, from aberrant synaptic plasticity, or from both. Second, it is not clear how schizophrenic symptoms can be understood mechanistically as a consequence of dysconnectivity. Third, if dysconnectivity is the primary pathophysiology, and not just an epiphenomenon, then it should provide a mechanistic explanation for known empirical facts about schizophrenia. This article addresses these 3 issues in the framework of the dysconnection hypothesis. This theory postulates that the core pathology in schizophrenia resides in aberrant N-methyl-D-aspartate receptor (NMDAR)–mediated synaptic plasticity due to abnormal regulation of NMDARs by neuromodulatory transmitters like dopamine, serotonin, or acetylcholine. We argue that this neurobiological mechanism can explain failures of self-monitoring, leading to a mechanistic explanation for first-rank symptoms as pathognomonic features of schizophrenia, and may provide a basis for future diagnostic classifications with physiologically defined patient subgroups. Finally, we test the explanatory power of our theory against a list of empirical facts about schizophrenia

Critical fluctuations in cortical models near instability

Australian Research Council, the National Health and Medical Research Council, the Brain Network Recovery Group Grant JSMF22002082, and Netherlands Organization for Scientific Research (NWO #451–10-030

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

Generative modelling of the thalamo-cortical circuit mechanisms underlying the neurophysiological effects of ketamine

Cortical recordings of task-induced oscillations following subanaesthetic ketamine administration demonstrate alterations in amplitude, including increases at high-frequencies (gamma) and reductions at low frequencies (theta, alpha). To investigate the population-level interactions underlying these changes, we implemented a thalamo-cortical model (TCM) capable of recapitulating broadband spectral responses. Compared with an existing cortex-only 4-population model, Bayesian Model Selection preferred the TCM. The model was able to accurately and significantly recapitulate ketamine-induced reductions in alpha amplitude and increases in gamma amplitude. Parameter analysis revealed no change in receptor time-constants but significant increases in select synaptic connectivity with ketamine. Significantly increased connections included both AMPA and NMDA mediated connections from layer 2/3 superficial pyramidal cells to inhibitory interneurons and both GABAA and NMDA mediated within-population gain control of layer 5 pyramidal cells. These results support the use of extended generative models for explaining oscillatory data and provide in silico support for ketamine's ability to alter local coupling mediated by NMDA, AMPA and GABA-A

A Novel Approach for Modeling Neural Responses to Joint Perturbations Using the NARMAX Method and a Hierarchical Neural Network

The human nervous system is an ensemble of connected neuronal networks. Modeling and system identification of the human nervous system helps us understand how the brain processes sensory input and controls responses at the systems level. This study aims to propose an advanced approach based on a hierarchical neural network and non-linear system identification method to model neural activity in the nervous system in response to an external somatosensory input. The proposed approach incorporates basic concepts of Non-linear AutoRegressive Moving Average Model with eXogenous input (NARMAX) and neural network to acknowledge non-linear closed-loop neural interactions. Different from the commonly used polynomial NARMAX method, the proposed approach replaced the polynomial non-linear terms with a hierarchical neural network. The hierarchical neural network is built based on known neuroanatomical connections and corresponding transmission delays in neural pathways. The proposed method is applied to an experimental dataset, where cortical activities from ten young able-bodied individuals are extracted from electroencephalographic signals while applying mechanical perturbations to their wrist joint. The results yielded by the proposed method were compared with those obtained by the polynomial NARMAX and Volterra methods, evaluated by the variance accounted for (VAF). Both the proposed and polynomial NARMAX methods yielded much better modeling results than the Volterra model. Furthermore, the proposed method modeled cortical responded with a mean VAF of 69.35% for a three-step ahead prediction, which is significantly better than the VAF from a polynomial NARMAX model (mean VAF 47.09%). This study provides a novel approach for precise modeling of cortical responses to sensory input. The results indicate that the incorporation of knowledge of neuroanatomical connections in building a realistic model greatly improves the performance of system identification of the human nervous system