Neural Mass Model Research Articles

Dimensional reduction of emergent spatiotemporal cortical dynamics via a maximum entropy moment closure.

Modern electrophysiological recordings and optical imaging techniques have revealed a diverse spectrum of spatiotemporal neural activities underlying fundamental cognitive processing. Oscillations, traveling waves and other complex population dynamical patterns are often concomitant with sensory processing, information transfer, decision making and memory consolidation. While neural population models such as neural mass, population density and kinetic theoretical models have been used to capture a wide range of the experimentally observed dynamics, a full account of how the multi-scale dynamics emerges from the detailed biophysical properties of individual neurons and the network architecture remains elusive. Here we apply a recently developed coarse-graining framework for reduced-dimensional descriptions of neuronal networks to model visual cortical dynamics. We show that, without introducing any new parameters, how a sequence of models culminating in an augmented system of spatially-coupled ODEs can effectively model a wide range of the observed cortical dynamics, ranging from visual stimulus orientation dynamics to traveling waves induced by visual illusory stimuli. In addition to an efficient simulation method, this framework also offers an analytic approach to studying large-scale network dynamics. As such, the dimensional reduction naturally leads to mesoscopic variables that capture the interplay between neuronal population stochasticity and network architecture that we believe to underlie many emergent cortical phenomena.

Dynamical Mechanisms of Interictal Resting-State Functional Connectivity in Epilepsy.

Drug-resistant focal epilepsy is a large-scale brain networks disorder characterized by altered spatiotemporal patterns of functional connectivity (FC), even during interictal resting state (RS). Although RS-FC-based metrics can detect these changes, results from RS functional magnetic resonance imaging (RS-fMRI) studies are unclear and difficult to interpret, and the underlying dynamical mechanisms are still largely unknown. To better capture the RS dynamics, we phenomenologically extended the neural mass model of partial seizures, the Epileptor, by including two neuron subpopulations of epileptogenic and nonepileptogenic type, making it capable of producing physiological oscillations in addition to the epileptiform activity. Using the neuroinformatics platform The Virtual Brain, we reconstructed 14 epileptic and 5 healthy human (of either sex) brain network models (BNMs), based on individual anatomical connectivity and clinically defined epileptogenic heatmaps. Through systematic parameter exploration and fitting to neuroimaging data, we demonstrated that epileptic brains during interictal RS are associated with lower global excitability induced by a shift in the working point of the model, indicating that epileptic brains operate closer to a stable equilibrium point than healthy brains. Moreover, we showed that functional networks are unaffected by interictal spikes, corroborating previous experimental findings; additionally, we observed higher excitability in epileptogenic regions, in agreement with the data. We shed light on new dynamical mechanisms responsible for altered RS-FC in epilepsy, involving the following two key factors: (1) a shift of excitability of the whole brain leading to increased stability; and (2) a locally increased excitability in the epileptogenic regions supporting the mixture of hyperconnectivity and hypoconnectivity in these areas.SIGNIFICANCE STATEMENT Advances in functional neuroimaging provide compelling evidence for epilepsy-related brain network alterations, even during the interictal resting state (RS). However, the dynamical mechanisms underlying these changes are still elusive. To identify local and network processes behind the RS-functional connectivity (FC) spatiotemporal patterns, we systematically manipulated the local excitability and the global coupling in the virtual human epileptic patient brain network models (BNMs), complemented by the analysis of the impact of interictal spikes and fitting to the neuroimaging data. Our results suggest that a global shift of the dynamic working point of the brain model, coupled with locally hyperexcitable node dynamics of the epileptogenic networks, provides a mechanistic explanation of the epileptic processes during the interictal RS period. These, in turn, are associated with the changes in FC.

Transfer Entropy as a Measure of Brain Connectivity: A Critical Analysis With the Help of Neural Mass Models.

Objective: Assessing brain connectivity from electrophysiological signals is of great relevance in neuroscience, but results are still debated and depend crucially on how connectivity is defined and on mathematical instruments utilized. Aim of this work is to assess the capacity of bivariate Transfer Entropy (TE) to evaluate connectivity, using data generated from simple neural mass models of connected Regions of Interest (ROIs).Approach: Signals simulating mean field potentials were generated assuming two, three or four ROIs, connected via excitatory or by-synaptic inhibitory links. We investigated whether the presence of a statistically significant connection can be detected and if connection strength can be quantified.Main Results: Results suggest that TE can reliably estimate the strength of connectivity if neural populations work in their linear regions, and if the epoch lengths are longer than 10 s. In case of multivariate networks, some spurious connections can emerge (i.e., a statistically significant TE even in the absence of a true connection); however, quite a good correlation between TE and synaptic strength is still preserved. Moreover, TE appears more robust for distal regions (longer delays) compared with proximal regions (smaller delays): an approximate a priori knowledge on this delay can improve the procedure. Finally, non-linear phenomena affect the assessment of connectivity, since they may significantly reduce TE estimation: information transmission between two ROIs may be weak, due to non-linear phenomena, even if a strong causal connection is present.Significance: Changes in functional connectivity during different tasks or brain conditions, might not always reflect a true change in the connecting network, but rather a change in information transmission. A limitation of the work is the use of bivariate TE. In perspective, the use of multivariate TE can improve estimation and reduce some of the problems encountered in the present study.

Dynamics and coupling of fractional-order models of the motor cortex and central pattern generators

Objective. Fractional calculus plays a key role in the analysis of neural dynamics. In particular, fractional calculus has been recently exploited for analyzing complex biological systems and capturing intrinsic phenomena. Also, artificial neural networks have been shown to have complex neuronal dynamics and characteristics that can be modeled by fractional calculus. Moreover, for a neural microcircuit placed on the spinal cord, fractional calculus can be employed to model the central pattern generator (CPG). However, the relation between the CPG and the motor cortex is still unclear. Approach. In this paper, fractional-order models of the CPG and the motor cortex are built on the Van der Pol oscillator and the neural mass model (NMM), respectively. A self-consistent mean field approximation is used to construct the potential landscape of the Van der Pol oscillator. This landscape provides a useful tool to observe the 3D dynamics of the oscillator. To infer the relation of the motor cortex and CPG, the coupling model between the fractional-order Van der Pol oscillator and the NMM is built. As well, the influence of the coupling parameters on the CPG and the motor cortex is assessed. Main results. Fractional-order NMM and coupling model of the motor cortex and the CPG are first established. The potential landscape is used to show 3D probabilistic evolution of the Van der Pol oscillator states. Detailed observations of the evolution of the system states can be made with fractional calculus. In particular, fractional calculus enables the observation of the creation of stable modes and switching between them. Significance. The results confirm that the motor cortex and CPG have associated modes or states that can be switched based on changes in the fractional order and the time delay. Fractional calculus and the potential landscape are helpful methods for better understanding of the working principles of locomotion systems.

Theta-Nested Gamma Oscillations in Next Generation Neural Mass Models.

Theta-nested gamma oscillations have been reported in many areas of the brain and are believed to represent a fundamental mechanism to transfer information across spatial and temporal scales. In a series of recent experiments in vitro it has been possible to replicate with an optogenetic theta frequency stimulation several features of cross-frequency coupling (CFC) among theta and gamma rhythms observed in behaving animals. In order to reproduce the main findings of these experiments we have considered a new class of neural mass models able to reproduce exactly the macroscopic dynamics of spiking neural networks. In this framework, we have examined two set-ups able to support collective gamma oscillations: namely, the pyramidal interneuronal network gamma (PING) and the interneuronal network gamma (ING). In both set-ups we observe the emergence of theta-nested gamma oscillations by driving the system with a sinusoidal theta-forcing in proximity of a Hopf bifurcation. These mixed rhythms always display phase amplitude coupling. However, two different types of nested oscillations can be identified: one characterized by a perfect phase locking between theta and gamma rhythms, corresponding to an overall periodic behavior; another one where the locking is imperfect and the dynamics is quasi-periodic or even chaotic. From our analysis it emerges that the locked states are more frequent in the ING set-up. In agreement with the experiments, we find theta-nested gamma oscillations for forcing frequencies in the range [1:10] Hz, whose amplitudes grow proportionally to the forcing intensity and which are clearly modulated by the theta phase. Furthermore, analogously to the experiments, the gamma power and the frequency of the gamma-power peak increase with the forcing amplitude. At variance with experimental findings, the gamma-power peak does not shift to higher frequencies by increasing the theta frequency. This effect can be obtained, in our model, only by incrementing, at the same time, also the stimulation power. An effect achieved by increasing the amplitude either of the noise or of the forcing term proportionally to the theta frequency. On the basis of our analysis both the PING and the ING mechanism give rise to theta-nested gamma oscillations with almost identical features.

Cross frequency coupling in next generation inhibitory neural mass models.

Coupling among neural rhythms is one of the most important mechanisms at the basis of cognitive processes in the brain. In this study, we consider a neural mass model, rigorously obtained from the microscopic dynamics of an inhibitory spiking network with exponential synapses, able to autonomously generate collective oscillations (COs). These oscillations emerge via a super-critical Hopf bifurcation, and their frequencies are controlled by the synaptic time scale, the synaptic coupling, and the excitability of the neural population. Furthermore, we show that two inhibitory populations in a master-slave configuration with different synaptic time scales can display various collective dynamical regimes: damped oscillations toward a stable focus, periodic and quasi-periodic oscillations, and chaos. Finally, when bidirectionally coupled, the two inhibitory populations can exhibit different types of θ-γ cross-frequency couplings (CFCs): phase-phase and phase-amplitude CFC. The coupling between θ and γ COs is enhanced in the presence of an external θ forcing, reminiscent of the type of modulation induced in hippocampal and cortex circuits via optogenetic drive.

Biophysically grounded mean-field models of neural populations under electrical stimulation.

Electrical stimulation of neural systems is a key tool for understanding neural dynamics and ultimately for developing clinical treatments. Many applications of electrical stimulation affect large populations of neurons. However, computational models of large networks of spiking neurons are inherently hard to simulate and analyze. We evaluate a reduced mean-field model of excitatory and inhibitory adaptive exponential integrate-and-fire (AdEx) neurons which can be used to efficiently study the effects of electrical stimulation on large neural populations. The rich dynamical properties of this basic cortical model are described in detail and validated using large network simulations. Bifurcation diagrams reflecting the network's state reveal asynchronous up- and down-states, bistable regimes, and oscillatory regions corresponding to fast excitation-inhibition and slow excitation-adaptation feedback loops. The biophysical parameters of the AdEx neuron can be coupled to an electric field with realistic field strengths which then can be propagated up to the population description. We show how on the edge of bifurcation, direct electrical inputs cause network state transitions, such as turning on and off oscillations of the population rate. Oscillatory input can frequency-entrain and phase-lock endogenous oscillations. Relatively weak electric field strengths on the order of 1 V/m are able to produce these effects, indicating that field effects are strongly amplified in the network. The effects of time-varying external stimulation are well-predicted by the mean-field model, further underpinning the utility of low-dimensional neural mass models.

Evaluation of Resting Spatio-Temporal Dynamics of a Neural Mass Model Using Resting fMRI Connectivity and EEG Microstates.

Resting-state brain activities have been extensively investigated to understand the macro-scale network architecture of the human brain using non-invasive imaging methods such as fMRI, EEG, and MEG. Previous studies revealed a mechanistic origin of resting-state networks (RSNs) using the connectome dynamics modeling approach, where the neural mass dynamics model constrained by the structural connectivity is simulated to replicate the resting-state networks measured with fMRI and/or fast synchronization transitions with EEG/MEG. However, there is still little understanding of the relationship between the slow fluctuations measured with fMRI and the fast synchronization transitions with EEG/MEG. In this study, as a first step toward evaluating experimental evidence of resting state activity at two different time scales but in a unified way, we investigate connectome dynamics models that simultaneously explain resting-state functional connectivity (rsFC) and EEG microstates. Here, we introduce empirical rsFC and microstates as evaluation criteria of simulated neuronal dynamics obtained by the Larter-Breakspear model in one cortical region connected with those in other cortical regions based on structural connectivity. We optimized the global coupling strength and the local gain parameter (variance of the excitatory and inhibitory threshold) of the simulated neuronal dynamics by fitting both rsFC and microstate spatial patterns to those of experimental ones. As a result, we found that simulated neuronal dynamics in a narrow optimal parameter range simultaneously reproduced empirical rsFC and microstates. Two parameter groups had different inter-regional interdependence. One type of dynamics was synchronized across the whole brain region, and the other type was synchronized between brain regions with strong structural connectivity. In other words, both fast synchronization transitions and slow BOLD fluctuation changed based on structural connectivity in the two parameter groups. Empirical microstates were similar to simulated microstates in the two parameter groups. Thus, fast synchronization transitions correlated with slow BOLD fluctuation based on structural connectivity yielded characteristics of microstates. Our results demonstrate that a bottom-up approach, which extends the single neuronal dynamics model based on empirical observations into a neural mass dynamics model and integrates structural connectivity, effectively reveals both macroscopic fast, and slow resting-state network dynamics.

Seizure tracking of epileptic EEGs using a model-driven approach

Objective. As a chronic neurological disorder, epilepsy is characterized by recurrent and unprovoked epileptic seizures that can disrupt the normal neuro-biologic, cognitive, psychological conditions of patients. Therefore, it is worthwhile to give a detailed account of how the epileptic EEG evolves during a period of seizure so that an effective control can be guided for epileptic patients in clinics. Approach. Considering the successful application of the neural mass model (NMM) in exploring the insights into brain activities for epilepsy, in this paper, we aim to construct a model-driven approach to track the development of seizures using epileptic EEGs. We first propose a new time-delay Wendling model with sub-populations (TD-W-SP model) with respect to three aspects of improvements. Then we introduce a model-driven seizure tracking approach, where a model training method is designed based on extracted features from epileptic EEGs and a tracking index is defined as a function of the trained model parameters. Main results. Numerical results on eight patients on CHB-MIT database demonstrate that our proposed method performs well in simulating epileptic-like EEGs as well as tracking the evolution of three stages (that is, from pre-ictal to ictal and from ictal to post-ictal) during a period of epileptic seizure. Significance. A useful attempt to track epileptic seizures by combining the NMM with the data analysis.

The role of coupling connections in a model of the cortico-basal ganglia-thalamocortical neural loop for the generation of beta oscillations

Excessive neural synchronization in the cortico-basal ganglia-thalamocortical circuits in the beta (β) frequency range (12–35 Hz) is closely associated with dopamine depletion in Parkinson’s disease (PD) and correlated with movement impairments, but the neural basis remains unclear. In this work, we establish a double-oscillator neural mass model for the cortico-basal ganglia-thalamocortical closed-loop system and explore the impacts of dopamine depletion induced changes in coupling connections within or between the two oscillators on neural activities within the loop. Spectral analysis of the neural mass activities revealed that the power and frequency of their principal components are greatly dependent on the coupling strengths between nuclei. We found that the increased intra-coupling in the basal ganglia-thalamic (BG-Th) oscillator contributes to increased oscillations in the lower β frequency band (12–25 Hz), while increased intra-coupling in the cortical oscillator mainly contributes to increased oscillations in the upper β frequency band (26–35 Hz). Interestingly, pathological upper β oscillations in the cortical oscillator may be another origin of the lower β oscillations in the BG-Th oscillator, in addition to increased intra-coupling strength within the BG-Th network. Lower β oscillations in the BG-Th oscillator can also change the dominant oscillation frequency of a cortical nucleus from the upper to the lower β band. Thus, this work may pave the way towards revealing a possible neural basis underlying the Parkinsonian state.

Next-generation neural mass and field modeling.

The Wilson-Cowan population model of neural activity has greatly influenced our understanding of the mechanisms for the generation of brain rhythms and the emergence of structured brain activity. As well as the many insights that have been obtained from its mathematical analysis, it is now widely used in the computational neuroscience community for building large-scale in silico brain networks that can incorporate the increasing amount of knowledge from the Human Connectome Project. Here, we consider a neural population model in the spirit of that originally developed by Wilson and Cowan, albeit with the added advantage that it can account for the phenomena of event-related synchronization and desynchronization. This derived mean-field model provides a dynamic description for the evolution of synchrony, as measured by the Kuramoto order parameter, in a large population of quadratic integrate-and-fire model neurons. As in the original Wilson-Cowan framework, the population firing rate is at the heart of our new model; however, in a significant departure from the sigmoidal firing rate function approach, the population firing rate is now obtained as a real-valued function of the complex-valued population synchrony measure. To highlight the usefulness of this next-generation Wilson-Cowan style model, we deploy it in a number of neurobiological contexts, providing understanding of the changes in power spectra observed in electro- and magnetoencephalography neuroimaging studies of motor cortex during movement, insights into patterns of functional connectivity observed during rest and their disruption by transcranial magnetic stimulation, and to describe wave propagation across cortex.

On analysis of inputs triggering large nonlinear neural responses Slow-fast dynamics in the Wendling neural mass model

Many applications in neuroscience, such as electrical and magnetic stimulation, can be modelled as short transient input to non-linear dynamical systems. In excitable systems, small input yields more or less linear responses, while for increasing stimulation strength large non-linear responses may show up suddenly. A challenging task is to determine the transition between the two different response types.In this work we consider such a transition between normal and pathological responses in a model of coupled Wendling neural masses as we encountered in a previous study. First, the different timescales of inhibition in this model allow a slow-fast analysis. This reveals two different dynamical regimes for the systems’ response. Second, the two response types are separated by a high-dimensional stable manifold of a saddle slow manifold. Large pathological responses appear if the fast subsystem escapes from this manifold to another attractor. The typical fast oscillations seen during the pathological responses are explained by the bifurcation diagram of the fast subsystem. Under normal conditions these oscillations are suppressed by slow inhibition. External stimulation temporarily releases the fast subsystem from this slow inhibition. The critical response can be formulated as a boundary value problem with one free parameter and can be used to study the dependency of the transition between the two response types upon the system parameters.

Seizure control in a neural mass model by an active disturbance rejection approach

A closed-loop neuromodulation automatically adjusts stimuli according to brain response in real time. It is viewed as a promising way to control medically intractable epilepsy. A suitable closed-loop modulation strategy, which is robust enough to unknown nonlinearities, dynamics, and disturbances, is in great need in the clinic. For the specialization of epilepsy, the Jansen’s neural mass model is utilized to simulate the undesired high amplitudes epileptic activities, and active disturbance rejection control is designed to suppress the high amplitudes of epileptiform discharges. With the help of active disturbance rejection control, closed-loop roots of the system are far from the imaginary axis. Time domain response shows that active disturbance rejection control is able to control seizure no matter whether disturbances exist or not. At the same time, frequency domain response presents that enough stability margins and a broader range of tunable controller parameters can be obtained. Stable regions have also been presented to provide guidance to choose the parameters of active disturbance rejection control. Numerical results show that, compared with proportional-integral control, more accurate modulation with less energy can be achieved by active disturbance rejection control. It confirms that the active disturbance rejection control-based neuromodulation solution is able to achieve a desired performance. It is a promising closed-loop neuromodulation strategy in seizure control.

Reachability Analysis of Neural Masses and Seizure Control Based on Combination Convolutional Neural Network.

Epileptic seizures arise from synchronous firing of multiple spatially separated neural masses; therefore, many synchrony measures are used for seizure detection and characterization. However, synchrony measures reflect only the overall interaction strength among populations of neurons but cannot reveal the coupling strengths among individual populations, which is more important for seizure control. The concepts of reachability and reachable cluster were proposed to denote the coupling strengths of a set of neural masses. Here, we describe a seizure control method based on coupling strengths using combination convolutional neural network (CCNN) modeling. The neurophysiologically based neural mass model (NMM), which can bridge signal processing and neurophysiology, was used to simulate the proposed controller. Although the adjacency matrix and reachability matrix could not be identified perfectly, the vast majority of adjacency values were identified, reaching 95.64% using the CCNN with an optimal threshold. For cases of discrete and continuous coupling strengths, the proposed controller maintained the average reachable cluster strengths at about 0.1, indicating effective seizure control.

Exploring the Phase-Locking Mechanisms Yielding Delayed and Anticipated Synchronization in Neuronal Circuits.

Synchronization is one of the brain mechanisms allowing the coordination of neuronal activity required in many cognitive tasks. Anticipated Synchronization (AS) is a specific type of out-of-phase synchronization that occurs when two systems are unidirectionally coupled and, consequently, the information is transmitted from the sender to the receiver, but the receiver leads the sender in time. It has been shown that the primate cortex could operate in a regime of AS as part of normal neurocognitive function. However it is still unclear what is the mechanism that gives rise to anticipated synchronization in neuronal motifs. Here, we investigate the synchronization properties of cortical motifs on multiple scales and show that the internal dynamics of the receiver, which is related to its free running frequency in the uncoupled situation, is the main ingredient for AS to occur. For biologically plausible parameters, including excitation/inhibition balance, we found that the phase difference between the sender and the receiver decreases when the free running frequency of the receiver increases. As a consequence, the system switches from the usual delayed synchronization (DS) regime to an AS regime. We show that at three different scales, neuronal microcircuits, spiking neuronal populations and neural mass models, both the inhibitory loop and the external current acting on the receiver mediate the DS-AS transition for the sender-receiver configuration by changing the free running frequency of the receiver. Therefore, we propose that a faster internal dynamics of the receiver system is the main mechanism underlying anticipated synchronization in brain circuits.

How Sensitive Are Conventional MEG Functional Connectivity Metrics With Sliding Windows to Detect Genuine Fluctuations in Dynamic Functional Connectivity?

Despite advances in the field of dynamic connectivity, fixed sliding window approaches for the detection of fluctuations in functional connectivity are still widely used. The use of conventional connectivity metrics in conjunction with a fixed sliding window comes with the arbitrariness of the chosen window lengths. In this paper we use multivariate autoregressive and neural mass models with a priori defined ground truths to systematically analyze the sensitivity of conventional metrics in combination with different window lengths to detect genuine fluctuations in connectivity for various underlying state durations. Metrics of interest are the coherence, imaginary coherence, phase lag index, phase locking value and the amplitude envelope correlation. We performed analysis for two nodes and at the network level. We demonstrate that these metrics show indeed higher variability for genuine temporal fluctuations in connectivity compared to a static connectivity state superimposed by noise. Overall, the error of the connectivity estimates themselves decreases for longer state durations (order of seconds), while correlations of the connectivity fluctuations with the ground truth was higher for longer state durations. In general, metrics, in combination with a sliding window, perform poorly for very short state durations. Increasing the SNR of the system only leads to a moderate improvement. In addition, at the network level, only longer window widths were sufficient to detect plausible resting state networks that matched the underlying ground truth, especially for the phase locking value, amplitude envelope correlation and coherence. The length of these longer window widths did not necessarily correspond to the underlying state durations. For short window widths resting state network connectivity patterns could not be retrieved. We conclude that fixed sliding window approaches for connectivity can detect modulations of connectivity, but mostly if the underlying dynamics operate on moderate to slow timescales. In practice, this can be a drawback, as state durations can vary significantly in empirical data.

Delayed Feedback-Based Suppression of Pathological Oscillations in a Neural Mass Model.

Suppression of excessively synchronous beta frequency (12-35 Hz) oscillatory activity in the basal ganglia is believed to correlate with the alleviation of hypokinetic motor symptoms of the Parkinson's disease. Delayed feedback is an effective strategy to interrupt the synchronization and has been used in the design of closed-loop neuromodulation methods computationally. Although tremendous efforts in this are being made by optimizing delayed feedback algorithm and stimulation waveforms, there are still remaining problems in the selection of effective parameters in the delayed feedback control schemes. In most delayed feedback neuromodulation strategies, the stimulation signal is obtained from the local field potential (LFP) of the excitatory subthalamic nucleus (STN) neurons and then is administered back to STN itself only. The inhibitory external globus pallidus (GPe) nucleus in the excitatory-inhibitory STN-GPe reciprocal network has not been involved in the design of the delayed feedback control strategies. Thus, considering the role of GPe, this paper proposes three schemes involving GPe in the design of the delayed feedback strategies and compared their effectiveness to the traditional paradigm using STN only. Based on a neural mass model of STN-GPe network having capability of simulating the LFP directly, the proposed stimulation strategies are tested and compared. Our simulation results show that the four types of delayed feedback control schemes are all effective, even if with a simple linear delayed feedback algorithm. But the three new control strategies we propose here further improve the control performance by enlarging the oscillatory suppression space and reducing the energy expenditure, suggesting that they may be more effective in applications. This paper may guide a new approach to optimize the closed-loop deep brain stimulation treatment to alleviate the Parkinsonian state by retargeting the measurement and stimulation nucleus.

Leveraging nonlinear dynamic models to predict progression of neuroimaging biomarkers.

Using biomarkers to model disease course effectively and make early prediction is a challenging but critical path to improving diagnostic accuracy and designing preventive trials for neurological disorders. Leveraging the domain knowledge that certain neuroimaging biomarkers may reflect the disease pathology, we propose a model inspired by the neural mass model from cognitive neuroscience to jointly model nonlinear dynamic trajectories of the biomarkers. Under a nonlinear mixed-effects model framework, we introduce subject- and biomarker-specific random inflection points to characterize the critical time of underlying disease progression as reflected in the biomarkers. A latent liability score is shared across biomarkers to pool information. Our model allows assessing how the underlying disease progression will affect the trajectories of the biomarkers, and, thus, is potentially useful for individual disease management or preventive therapeutics. We propose an EM algorithm for maximum likelihood estimation, where in the E step, a normal approximation is used to facilitate numerical integration. We perform extensive simulation studies and apply the method to analyze data from a large multisite natural history study of Huntington's Disease (HD). The results show that some neuroimaging biomarker inflection points are early signs of the HD onset. Finally, we develop an online tool to provide the individual prediction of the biomarker trajectories given the medical history and baseline measurements.

Identification of effective stimulation parameters to abort epileptic seizures in a neural mass model.

Pathological brain activity can be modulated by using electrical stimulation. However, one major challenge is the identification of the optimal parameter values normalizing pathological activity towards more physiological patterns. One possible approach to address this challenge is the use of computational models. Here, we used a validated neural mass model (NMM) to simulate epileptiform activity and its modulation by electrical stimulation. Based on simple features of the simulated signals before and during stimulation within the time and frequency domains, we studied the effectiveness of a given stimulation parameters. Stimulations inducing a membrane polarization greater than 4 mV and a frequency over 25 Hz were identified as common effective parameters for the majority of epileptiform signals. This work provides further evidence for model-guided stimulation parameters optimization as a rationale for neuromodulation therapy refinement.

Identification of A Neural Mass Model of Burst Suppression.

Burst suppression includes alternating patterns of silent and fast spike activities in neuronal activities observable (in micro or macro scale) electro-physiological recordings. Biological models of burst suppression are given as dynamical systems with slow and fast states. The aim of this paper is to give a method to identify parameters of a mesoscopic model of burst suppression that can provide insights into study underlying generators of intracranial electroencephalogram (iEEG) data. An optimisation technique based upon a genetic algorithm (GA) is employed to find feasible model parameters to replicate burst patterns in the iEEG data with paroxysmal transitions. Then, a continuous-discrete unscented Kalman filter (CD-UKF) is used to infer hidden states of the model and to enhance the identification results from the GA. The results show promise in finding the model parameters of a partially observed mesoscopic model of burst suppression.