Biomedical Engineering - Research Publications

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    Electrical Stimulation of Neural Tissue Modeled as a Cellular Composite: Point Source Electrode in an Isotropic Tissue
    Monfared, O ; Nesic, D ; Freestone, DR ; Grayden, DB ; Tahayori, B ; Meffin, H (IEEE, 2014-01-01)
    Standard volume conductor models of neural electrical stimulation assume that the electrical properties of the tissue are well described by a conductivity that is smooth and homogeneous at a microscopic scale. However, neural tissue is composed of tightly packed cells whose membranes have markedly different electrical properties to either the intra- or extracellular space. Consequently, the electrical properties of tissue are highly heterogeneous at the microscopic scale: a fact not accounted for in standard volume conductor models. Here we apply a recently developed framework for volume conductor models that accounts for the cellular composition of tissue. We consider the case of a point source electrode in tissue comprised of neural fibers crossing each other equally in all directions. We derive the tissue admittivity (that replaces the standard tissue conductivity) from single cell properties, and then calculate the extracellular potential. Our findings indicate that the cellular composition of tissue affects the spatiotemporal profile of the extracellular potential. In particular, the full solution asymptotically approaches a near-field limit close to the electrode and a far-field limit far from the electrode. The near-field and far-field approximations are solutions to standard volume conductor models, but differ from each other by nearly an order or magnitude. Consequently the full solution is expected to provide a more accurate estimate of electrical potentials over the full range of electrode-neurite separations.
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    A Neural Mass Model of Spontaneous Burst Suppression and Epileptic Seizures
    Freestone, DR ; Nesic, D ; Jafarian, A ; Cook, MJ ; Grayden, DB (IEEE, 2013-01-01)
    The paper presents a neural mass model that is capable of simulating the transition to and from various forms of paroxysmal activity such as burst suppression and epileptic seizure-like waveforms. These events occur without changing parameters in the model. The model is based on existing neural mass models, with the addition of feedback of fast dynamics to create slowly time varying parameters, or slow states. The goal of this research is to establish a link between system properties that modulate neural activity and the fast changing dynamics, such as membrane potentials and firing rates that can be manipulated using electrical stimulation. Establishing this link is likely to be a necessary component of a closed-loop system for feedback control of pathological neural activity.
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    INFERRING PATIENT-SPECIFIC PHYSIOLOGICAL PARAMETERS FROM INTRACRANIAL EEG: APPLICATION TO CLINICAL DATA
    Shmuely, S ; Freestone, DR ; Grayden, DB ; Nesic, D ; Cook, M (WILEY-BLACKWELL, 2012-09-01)
    Purpose: Intracranial EEG (iEEG) provides information regarding where and when seizures occur, whilst the underlying mechanisms are hidden. However physiologically plausible mechanisms for seizure generation and termination are explained by neural mass models, which describe the macroscopic neural dynamics. Fusion of models with patient-specific data allows estimation and tracking of the normally hidden physiological parameters. By monitoring changes in physiology, a new understanding of seizures can be achieved. This work addresses model-data fusion for iEEG for application in a clinical setting. Method: Data was recorded from three patients undergoing evaluation for epilepsy-related surgery at St. Vincent's Hospital, Melbourne. Using this data, we created patient-specific neural mass mathematical models based on the formulation of Jansen and Rit (1995). The parameters that were estimated include the synaptic gains, time constants, and the firing threshold. The estimation algorithm utilized the Unscented Kalman Filter (Julier and Uhlmann, 1997). Result: We demonstrate how parameters changed in relation to seizure initiation, evolution and termination. We also show within-patient (across different seizures) and between-patient specificity of the parameter estimates. Conclusion: The fusion of clinical data and mathematical models can be used to infer valuable information about the underlying mechanisms of epileptic seizure generation. This information could be used to develop novel therapeutic strategies
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    INFERRING PATIENT-SPECIFIC PHYSIOLOGICAL PARAMETERS FROM INTRACRANIAL EEG: THEORETICAL STUDIES
    Freestone, DR ; Grayden, DB ; Cook, M ; Nesic, D (WILEY-BLACKWELL, 2012-09-01)
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    PATIENT-SPECIFIC NEURAL MASS MODELING - STOCHASTIC AND DETERMINISTIC METHODS
    Freestone, DR ; Kuhlmann, L ; Chong, MS ; Nesic, D ; Grayden, DB ; Aram, P ; Postoyan, R ; CooK, MJ ; Tetzlaff, R ; Elger, CE ; Lehnertz, K (WORLD SCIENTIFIC PUBL CO PTE LTD, 2013-01-01)
    Deterministic and stochastic methods for online state and parameter estimation for neural mass models are presented and applied to synthetic and real seizure electrocorticographic signals in order to determine underlying brain changes that cannot easily be measured. The first ever online estimation of neural mass model parameters from real seizure data is presented. It is shown that parameter changes occur that are consistent with expected brain changes underlying seizures, such as increases in postsynaptic potential amplitudes, increases in the inhibitory postsynaptic time-constant and decreases in the firing threshold at seizure onset, as well as increases in the firing threshold as the seizure progresses towards termination. In addition, the deterministic and stochastic estimation methods are compared and contrasted. This work represents an important foundation for the development of biologically-inspired methods to image underlying brain changes and to develop improved methods for neurological monitoring, control and treatment.
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    Analytic synchronization conditions for a network of Wilson and Cowan oscillators
    Ahmadizadeh, S ; Nesic, D ; Grayden, DB ; Freestone, DR (IEEE, 2015)
    We investigate the problem of synchronization in a network of homogeneous Wilson-Cowan oscillators with diffusive coupling. Such networks can be used to model the behavior of populations of neurons in cortical tissue, referred to as neural mass models. A new approach is proposed to address local synchronization for these types of neural mass models. By exploiting the linearized model around a limit cycle, we analyze synchronization within a network for weak, intermediate, and strong coupling. We use two-time scale averaging and the Chetaev theorem to analytically check the absence or presence of synchronization in the network with weak coupling. We also utilize the Chetaev theorem to analytically prove synchronization death in a network with strong coupling. For intermediate coupling, we use a recently proposed numerical approach to prove synchronization in the network. Simulation results confirm and illustrate our results.
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    A comparison of open-loop and closed-loop stimulation strategies to control excitation of retinal ganglion cells
    Kameneva, T ; Zarelli, D ; Nesic, D ; Grayden, DB ; Burkitt, AN ; Meffin, H (Elsevier, 2014-11-01)
    Currently, open-loop stimulation strategies are prevalent in medical bionic devices. These strategies involve setting electrical stimulation that does not change in response to neural activity. We investigate through simulation the advantages of using a closed-loop strategy that sets stimulation level based on continuous measurement of the level of neural activity. We propose a model-based controller design to control activation of retinal neurons. To deal with the lack of controllability and observability of the whole system, we use Kalman decomposition and control only the controllable and observable part. We show that the closed-loop controller performs better than the open-loop controller when perturbations are introduced into the system. We envisage that our work will give rise to more investigations of the closed-loop techniques in basic neuroscience research and in clinical applications of medical bionics.
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    On synchronization of networks of Wilson-Cowan oscillators with diffusive coupling
    Ahmadizadeh, S ; Nesic, D ; Freestone, DR ; Grayden, DB (PERGAMON-ELSEVIER SCIENCE LTD, 2016-09-01)
    We investigate the problem of synchronization in a network of homogeneous Wilson-Cowan oscillators with diffusive coupling. Such networks can be used to model the behavior of populations of neurons in cortical tissue, referred to as neural mass models. A new approach is proposed to address conditions for local synchronization for this type of neural mass models. By analyzing the linearized model around a limit cycle, we study synchronization within a network with direct coupling. We use both analytical and numerical approaches to link the presence or absence of synchronized behavior to the location of eigenvalues of the Laplacian matrix. For the analytical part, we apply two-time scale averaging and the Chetaev theorem, while, for the remaining part, we use a recently proposed numerical approach. Sufficient conditions are established to highlight the effect of network topology on synchronous behavior when the interconnection is undirected. These conditions are utilized to address points that have been previously reported in the literature through simulations: synchronization might persist or vanish in the presence of perturbation in the interconnection gains. Simulation results confirm and illustrate our results.
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    Identification of a Neural Mass Model of Burst Suppression
    Jafarian, A ; Freestone, DR ; Nesic, D ; Grayden, D (IEEE, 2019)
    Burst suppression includes alternating patterns of silent and fast spike activities in neuronal activities observable in micro to macro scale 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.
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    Slow-Fast Duffing Neural Mass Model
    Jafarian, A ; Freestone, DR ; Nesic, D ; Grayden, D (IEEE, 2019)
    Epileptic seizures may be initiated by random neuronal fluctuations and/or by pathological slow regulatory dynamics of ion currents. This paper presents extensions to the Jansen and Rit neural mass model (JRNMM) to replicate paroxysmal transitions in intracranial electroencephalogram (iEEG) recordings. First, the Duffing NMM (DNMM) is introduced to emulate stochastic generators of seizures. The DNMM is constructed by applying perturbations to linear models of synaptic transmission in each neural population of the JRNMM. Then, the slow-fast DNMM is introduced by considering slow dynamics (relative to membrane potential and firing rate) of some internal parameters of the DNMM to replicate pathological evolution of ion currents. Through simulation, it is illustrated that the slow-fast DNMM exhibits transitions to and from seizures with etiologies that are linked either to random input fluctuations or pathological evolution of slow states. Estimation and optimization of a log likelihood function (LLF) using a continuous-discrete unscented Kalman filter (CD-UKF) and a genetic algorithm (GA) are performed to capture dynamics of iEEG data with paroxysmal transitions.