To investigate how extracellular electric field modulates neuron activity, a reduced two-compartment neuron model in the presence of electric field is introduced in this study. Depending on neuronal geometric and internal coupling parameters, the behaviors of the model have been studied extensively. The neuron model can exist in quiescent state or repetitive spiking state in response to electric field stimulus. Negative electric field mainly acts as inhibitory stimulus to the neuron, positive weak electric field could modulate spiking frequency and spike timing when the neuron is already active, and positive electric fields with sufficient intensity could directly trigger neuronal spiking in the absence of other stimulations. By bifurcation analysis, it is observed that there is saddle-node on invariant circle bifurcation, supercritical Hopf bifurcation and subcritical Hopf bifurcation appearing in the obtained two parameter bifurcation diagrams. The bifurcation structures and electric field thresholds for triggering neuron firing are determined by neuronal geometric and coupling parameters. The model predicts that the neurons with a nonsymmetric morphology between soma and dendrite, are more sensitive to electric field stimulus than those with the spherical structure. These findings suggest that neuronal geometric features play a crucial role in electric field effects on the polarization of neuronal compartments. Moreover, by determining the electric field threshold of our biophysical model, we could accurately distinguish between suprathreshold and subthreshold electric fields. Our study highlights the effects of extracellular electric field on neuronal activity from the biophysical modeling point of view. These insights into the dynamical mechanism of electric field may contribute to the investigation and development of electromagnetic therapies, and the model in our study could be further extended to a neuronal network in which the effects of electric fields on network activity may be investigated.
In this paper, we investigate the abatement of spike-and-wave discharges in a thalamocortical model using a closed-loop brain stimulation method. We first explore the complex states and various transitions in the thalamocortical computational model of absence epilepsy by using bifurcation analysis. We demonstrate that the Hopf and double cycle bifurcations are the key dynamical mechanisms of the experimental observed bidirectional communications during absence seizures through top-down cortical excitation and thalamic feedforward inhibition. Then, we formulate the abatement of epileptic seizures to a closed-loop tracking control problem. Finally, we propose a neural network based sliding mode feedback control system to drive the dynamics of pathological cortical area to track the desired normal background activities. The control system is robust to uncertainties and disturbances, and its stability is guaranteed by Lyapunov stability theorem. Our results suggest that the seizure abatement can be modeled as a tracking control problem and solved by a robust closed-loop control method, which provides a promising brain stimulation strategy.
Based on a reduced two-compartment model, the dynamical and biophysical mechanism underlying the spike initiation of the neuron to extracellular electric fields is investigated in this paper. With stability and phase plane analysis, we first investigate in detail the dynamical properties of neuronal spike initiation induced by geometric parameter and internal coupling conductance. The geometric parameter is the ratio between soma area and total membrane area, which describes the proportion of area occupied by somatic chamber. It is found that varying it could qualitatively alter the bifurcation structures of equilibrium as well as neuronal phase portraits, which remain unchanged when varying internal coupling conductance. By analyzing the activating properties of somatic membrane currents at subthreshold potentials, we explore the relevant biophysical basis of spike initiation dynamics induced by these two parameters. It is observed that increasing geometric parameter could greatly decrease the intensity of the internal current flowing from soma to dendrite, which switches spike initiation dynamics from Hopf bifurcation to SNIC bifurcation; increasing internal coupling conductance could lead to the increase of this outward internal current, whereas the increasing range is so small that it could not qualitatively alter the spike initiation dynamics. These results highlight that neuronal geometric parameter is a crucial factor in determining the spike initiation dynamics to electric fields. The finding is useful to interpret the functional significance of neuronal biophysical properties in their encoding dynamics, which could contribute to uncovering how neuron encodes electric field signals.
To investigate the abnormal brain activities in the early stage of Parkinson's disease (PD), the electroencephalogram (EEG) signals were recorded with 20 channels from non-dementia PD patients (18 patients, 8 females) and age matched healthy controls (18 subjects, 8 females) during the resting state. Two methods based on the ordinal patterns of the recorded series, i.e., permutation entropy (PE) and order index (OI), were introduced to characterize the complexity of the cortical activities for two groups. It was observed that the resting-state EEG of PD patients showed lower PE and higher OI than healthy controls, which indicated that the early-stage PD caused the reduced complexity of EEG. We further applied two methods to determine the complexity of EEG rhythms in five sub-bands. The results showed that the gamma, beta and alpha rhythms of PD patients were characterized by lower PE and higher OI, i.e., reduced complexity, than healthy subjects. No significant differences were observed in theta or delta rhythms between two groups. The findings suggested that PE and OI were promising methods to detect the abnormal changes in the dynamics of EEG signals associated with early-stage PD. Further, such changes in EEG complexity may be the early markers of the cortical or subcortical dysfunction caused by PD.
Thalamocortical (TC) relay cells exhibit different temporal patterns of activity, including tonic mode and burst mode, to transmit sensory information to the cortex. Our aim was to quantify the metabolic cost of different temporal patterns of neural activity across a range of average firing rates. We used a biophysically-realistic model of a TC relay neuron to simulate tonic and burst patterns of firing. We calculated the metabolic cost by converting the calculated ion fluxes into the demand for ATP to maintain homeostasis of intracellular ion concentrations. Most energy was expended on reversing Na + entry during action potentials and pumping Ca 2+ out of the cell. Average firing rate determined the ATP cost across firing patterns by controlling the overall number of spikes. Varying intraburst frequency or spike number in each burst influenced the metabolic cost by altering the interactions of inward and outward currents on multiple timescales, but temporal pattern contributed substantially less to the metabolic demand of neural activity as compared to average firing rate. These predictions should be considered when interpreting findings of functional imaging studies that rely of estimates of neuronal metabolic demand, e.g., functional magnetic resonance imaging.
The results reveal that synaptic inputs, stimulus frequency, and electrode position regulate antidromic activation of the cell body during extracellular stimulation. These findings provide a biophysical basis for interpreting the widespread inhibition/activation of target nuclei during DBS.
To explore the effects of manual acupuncture (MA) on brain activities, we design an experiment that acupuncture at acupoint ST36 of right leg with four different frequencies to obtain electroencephalograph (EEG) signals. Many studies have demonstrated that the complexity of EEG can reflect the states of brain function, so we propose to adopt order recurrence quantification analysis combined with discrete wavelet transform, to analyze the dynamical characteristics of different EEG rhythms under acupuncture, further to explore the effects of MA on the complexity of brain activities from multi-scale point of view. By analyzing the complexity of five EEG rhythms, it is found that the complexity of delta rhythm during acupuncture is lower than before acupuncture, and for alpha rhythm that is higher, but for beta, theta and gamma rhythms there are no obvious changes. All of those effects are especially obvious during acupuncture with frequency of 200 times/min. Furthermore, the determinism extracted from delta, alpha and gamma rhythms can be regarded as a characteristic parameter to distinguish the state acupuncture at 200 times/min and the state before acupuncture. These results can provide a theoretical support for selecting appropriate acupuncture frequency for patients in clinical, and the proposed methods have the potential of exploring the effects of acupuncture on brain activities.
Responses of different neurons to electric field (EF) are highly variable, which depends on intrinsic properties of cell type. Here we use multi-compartmental biophysical models to investigate how morphologic features affect EF-induced responses in hippocampal CA1 pyramidal neurons. We find that the basic morphologies of neuronal elements, including diameter, length, bend, branch, and axon terminals, are all correlated with somatic depolarization through altering the current sources or sinks created by applied field. Varying them alters the EF threshold for triggering action potentials (APs), and then determines cell sensitivity to suprathreshold field. Introducing excitatory postsynaptic potential increases cell excitability and reduces morphology-dependent EF firing threshold. It is also shown that applying identical subthreshold EF results in distinct polarizations on cell membrane with different realistic morphologies. These findings shed light on the crucial role of morphologies in determining field-induced neural response from the point of view of biophysical models. The predictions are conducive to better understanding the variability in modulatory effects of EF stimulation at the cellular level, which could also aid the interpretations of how applied fields activate central nervous system neurons and affect relevant circuits.
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