Biomedical subjects

Craig S Henriquez

Publications and source records attributed to Craig S Henriquez.

13 recordsLinked to original sources

PubMed2005

Stable ensemble performance with single-neuron variability during reaching movements in primates.

Significant variability in firing properties of individual neurons was observed while two monkeys, chronically implanted with multielectrode arrays in frontal and parietal cortical areas, performed a continuous arm movement task. Although the degree of correlation between the firing of single neurons and movement parameters was nonstationary, stable predictions of arm movements could be obtained from the activity of neuronal ensembles. This result adds support to the idea that movement parameters are redundantly encoded in the motor cortex, such that brain networks can achieve the same behavioral goals through different patterns and relative contribution of individual neuron activity. This has important implications for neural prosthetics, suggesting that accurate operation of a brain-machine interface requires recording from large neuronal ensembles to minimize the effect of variability and ensuring stable performance over long periods of time.

Action Potentials↗

PubMed2005

Cortical ensemble adaptation to represent velocity of an artificial actuator controlled by a brain-machine interface.

Monkeys can learn to directly control the movements of an artificial actuator by using a brain-machine interface (BMI) driven by the activity of a sample of cortical neurons. Eventually, they can do so without moving their limbs. Neuronal adaptations underlying the transition from control of the limb to control of the actuator are poorly understood. Here, we show that rapid modifications in neuronal representation of velocity of the hand and actuator occur in multiple cortical areas during the operation of a BMI. Initially, monkeys controlled the actuator by moving a hand-held pole. During this period, the BMI was trained to predict the actuator velocity. As the monkeys started using their cortical activity to control the actuator, the activity of individual neurons and neuronal populations became less representative of the animal's hand movements while representing the movements of the actuator. As a result of this adaptation, the animals could eventually stop moving their hands yet continue to control the actuator. These results show that, during BMI control, cortical ensembles represent behaviorally significant motor parameters, even if these are not associated with movements of the animal's own limb.

Adaptation, Physiological↗

PubMed2005

Electrotonic influences on action potential duration dispersion in small hearts: a simulation study.

Intrinsic spatial variations in repolarization currents in the heart can produce spatial gradients in action potential duration (APD) that serve as possible sites for conduction block and the initiation of reentrant activity. In well-coupled myocardium, however, electrotonic influences at the stimulus site and wavefront collision sites act to modulate any intrinsic heterogeneity in APD. These effects alter APD gradients over an extent larger than that suggested by the length constant associated with propagation and, thus, are hypothesized to play a greater role in smaller hearts used as experimental models of human disease. This study uses computer simulation to investigate how heart size, tissue properties, and the spatial assignment of cell types affect functional APD dispersion. Simulations were carried out using the murine ventricular myocyte model of Pandit et al. or the Luo-Rudy mammalian model in three-dimensional models of mouse and rabbit ventricular geometries. Results show that the spatial extent of the APD dispersion is related to the dynamic changes in transmembrane resistance during recovery. Also, because of the small dimensions of the mouse heart, electrotonic effects on APD primarily determine the functional dispersion of refractoriness, even in the presence of large intrinsic cellular heterogeneity and reduced coupling. APD dispersion, however, is found to increase significantly when the heart size increases to the size of a rabbit heart, unmasking intrinsic cell types.

Action Potentials↗

PubMed2005

Bistability and correlation with arrhythmogenesis in a model of the right atrium.

Rapid pacing is an important tool for understanding cardiac arrhythmias. A recent experiment involving rapid pacing of sheep atria indicated that the initiation of atrial arrhythmias may be related to the 1:1/2:1 bistability. To elucidate the mechanism of this relation, this study applied the pacing protocol from the sheep study to an idealized model of the right atrium. The model included all major anatomical features, the sino-atrial node, and the regional differences in the action potential duration (APD). A pacing protocol was applied, in which the basic cycle length (BCL) was decreased in steps of 10 ms until the response switched to 2:1, then BCL was increased. The 1:1-to-2:1 transitions occurred at shorter BCLs than the 2:1-to-1:1 transitions yielding a global bistability window of 60ms. As in the sheep study, idiopathic waves were observed at BCLs within or near the bistability window. The model was used to quantify the types, prevalence, and persistence of idiopatic waves, study their initiation and termination, and relate them to the model components. The results demonstrate that idiopatic waveforms move with the shift of the bistability window and that they disappear when bistability is eliminated. Thus, this modeling study supports causal relationship between the 1:1/2:1 bistability and the initiation of arrhythmias.

Action Potentials↗

PubMed2005

An integrative model of mouse cardiac electrophysiology from cell to torso.

AIMS: Although the transgenic mouse has become an important new tool in the study of human diseases and the design of new therapies, a complete picture of cardiac electrophysiology in the mouse, from genome to body surface, is lacking. A computational model of the mouse heart is presented, which is used to study the impact of ion-channel and structural manipulations on the distributions of extracellular potentials on the heart and body surface. METHODS: A model of the mouse heart anatomy, fibre organization and torso geometry was constructed from DTMRI images. An anisotropic bidomain model, with a modified Pandit et al. model for the ionic currents, was used to represent the electrical properties of the tissue. Spatial heterogeneity in the ion currents was introduced by modulating the transient outward current. A sinus beat was simulated in hearts with different tissue and membrane properties and the extracellular potentials were computed at both the heart and body surface. RESULTS: The simulated transmembrane patterns in the heart, and the timing and morphology of the simulated ECG waveforms were consistent with experimental measurements. In addition, the patterns of activation and recovery and the waveforms of the corresponding ECG were found to be relatively insensitive to changes in cell type distribution and tissue anisotropy. CONCLUSION: Because of the small size of the heart, an integrative model of mouse electrophysiology can be simulated from cell to torso, enabling a new tool to study how extracellular signals might be used to detect molecular changes underlying an arrhythmogenic substrate.

Algorithms↗

PubMed2005

A membrane model of electrically remodelled atrial myocardium derived from in vivo measurements.

AIMS: Contemporary ionic-based membrane models are computationally expensive and are not intended to match the properties of a given experimental preparation. The aim of this work was to use measured restitution properties of electrically remodelled atrial tissue to develop a simplified membrane model based on the Fenton-Karma (FK) equations amenable to large-scale simulation of chronic atrial fibrillation (CAF). METHODS: Two membrane models, the FK-CAF and FK-CNTRL parameter sets, were developed to match action potential duration (APD) and conduction velocity (CV) restitution properties of rapid-pacing-induced electrically remodelled sheep atria and healthy atria, respectively. The models were tested by inducing reentry in a two-dimensional anisotropic monodomain and comparing the resulting cycle lengths (CL) with measured CLs. RESULTS: Parameters for the FK models were obtained that reproduced APD and CV restitution properties measured in the CAF and healthy sheep atria. Using the FK-CAF parameters, reentry was sustained in a 2.5 by 2.5 cm sheet with a CL = 91.0 +/- 3.0 ms. Reentry (CL = 113.2 +/- 5.2 ms) could only be sustained in the FK-CNTRL model after the tissue was first activated at a fast rate (136.5 ms). CONCLUSIONS: The FK-CAF model is shown to approximate the restitution properties of remodelled sheep atria and can be used to simulate reentry with short CLs similar to those measured during AF episodes.

Action Potentials↗

PubMed2005

Analytical model of extracellular potentials in a tissue slab with a finite bath.

Extracellular potentials are often used to assess the activation and repolarization of transmembrane action potentials in cardiac tissue under a variety of experimental conditions. An analytical model of the extracellular potentials arising from a planar wavefront propagating in a three-dimensional slab of cardiac tissue with a variably thick adjacent volume conductor or bath is presented. Starting with the transmembrane potential, the model yields the extracellular potentials at various points in the bath and inside tissue. The results show that the analytical model produces signal timecourses with trivial computational costs that are similar to those computed from a full reaction-diffusion bidomain model with different bath thicknesses for tissue with uniform properties and for tissue with an abrupt ionic inhomogeneity.

Algorithms↗

PubMed2005

Finite volume stiffness matrix for solving anisotropic cardiac propagation in 2-D and 3-D unstructured meshes.

The finite volume method (FVM) has been shown recently to be an effective method for discretizing the reaction-diffusion equations that govern wavefront propagation in anisotropic cardiac tissue, as it can naturally handle both complex geometries and no flux boundary conditions without the use of ghost nodes. This communication presents an alternative formulation of FVM for triangle and tetrahedral meshes using the concept of dual basis. An algorithm based on this form is given that leads to an efficient computation of the stiffness matrix, facilitating the incorporation of space adaptive schemes and time varying material properties into numerical simulations of cardiac dynamics.

Action Potentials↗

PubMed2004

A resistor interpretation of general anisotropic cardiac tissue.

This paper describes a spatial discretization scheme for partial differential equation systems that contain anisotropic diffusion. The discretization method uses unstructured finite volumes, or the boxes, that are formed as a secondary geometric structure from an underlying triangular mesh. We show how the discretization can be interpreted as a resistive circuit network, where each resistor is assigned at each edge of the triangular element. The resistor is computed as an anisotropy dependent geometric quantity of the local mesh structure. Finally, we show that under certain conditions, the discretization gives rise to negative resistors that can produce non-physical hyperpolarizations near depolarizing stimuli. We discuss how the proper choice of triangulation (anisotropic Delaunay triangulation) can ensure monotonicity (i.e. all resistors are positive).

Anisotropy↗

PubMed2003

Genesis of the monophasic action potential: role of interstitial resistance and boundary gradients.

The extracellular potential at the site of a mechanical deformation has been shown to resemble the underlying transmembrane action potential, providing a minimally invasive way to access membrane dynamics. The biophysical factors underlying the genesis of this signal, however, are still poorly understood. With the use of data from a recent experimental study in a murine heart, a three-dimensional anisotropic bidomain model of the mouse ventricular free wall was developed to study the currents and potentials resulting from the application of a point mechanical load on cardiac tissue. The applied pressure is assumed to open nonspecific pressure-sensitive channels depolarizing the membrane, leading to monophasic currents at the electrode edge that give rise to the monophasic action potential (MAP). The results show that the magnitude and the time course of the MAP are reproduced only for certain combinations of local or global intracellular and interstitial resistances that form a resting tissue length constant that, if applied over the entire domain, is smaller than that required to match the wave speed. The results suggest that the application of pressure not only causes local depolarization but also changes local tissue properties, both of which appear to play a critical role in the genesis of the MAP.

Action Potentials↗

PubMed2003

Learning to control a brain-machine interface for reaching and grasping by primates.

Reaching and grasping in primates depend on the coordination of neural activity in large frontoparietal ensembles. Here we demonstrate that primates can learn to reach and grasp virtual objects by controlling a robot arm through a closed-loop brain-machine interface (BMIc) that uses multiple mathematical models to extract several motor parameters (i.e., hand position, velocity, gripping force, and the EMGs of multiple arm muscles) from the electrical activity of frontoparietal neuronal ensembles. As single neurons typically contribute to the encoding of several motor parameters, we observed that high BMIc accuracy required recording from large neuronal ensembles. Continuous BMIc operation by monkeys led to significant improvements in both model predictions and behavioral performance. Using visual feedback, monkeys succeeded in producing robot reach-and-grasp movements even when their arms did not move. Learning to operate the BMIc was paralleled by functional reorganization in multiple cortical areas, suggesting that the dynamic properties of the BMIc were incorporated into motor and sensory cortical representations.

Animals↗

PubMed2003

Efficient simulation of three-dimensional anisotropic cardiac tissue using an adaptive mesh refinement method.

A recently developed space-time adaptive mesh refinement algorithm (AMRA) for simulating isotropic one- and two-dimensional excitable media is generalized to simulate three-dimensional anisotropic media. The accuracy and efficiency of the algorithm is investigated for anisotropic and inhomogeneous 2D and 3D domains using the Luo-Rudy 1 (LR1) and FitzHugh-Nagumo models. For a propagating wave in a 3D slab of tissue with LR1 membrane kinetics and rotational anisotropy comparable to that found in the human heart, factors of 50 and 30 are found, respectively, for the speedup and for the savings in memory compared to an algorithm using a uniform space-time mesh at the finest resolution of the AMRA method. For anisotropic 2D and 3D media, we find no reduction in accuracy compared to a uniform space-time mesh. These results suggest that the AMRA will be able to simulate the 3D electrical dynamics of canine ventricles quantitatively for 1 s using 32 1-GHz Alpha processors in approximately 9 h.

Algorithms↗

PubMedDate not supplied

Region specific modeling of cardiac muscle: comparison of simulated and experimental potentials.

This article investigates the quantitative predictive capabilities of region-specific models by comparing experimental electrograms obtained from in vivo mapping of the ventricular free wall with those obtained through simulation of a region specific three-dimensional bidomain model that incorporates measured fiber orientations. Epicardial electrograms were recorded from canine left ventricles during and after unipolar pacing using a 528-channel electrode plaque. Fiber directions throughout the tissue were estimated from diffusion-weighted MRI and from pace mapping. Electrograms were computed in the bidomain model with experimentally derived properties during paced activations at the same spatiotemporal resolution as those recorded experimentally. Epicardial potentials from model and experiment were directly compared, and sensitivities of these comparisons to reference electrode location and to the choice of material properties were analyzed. The comparisons performed here demonstrate, that (1) the stimulus artifact can be used to estimate the in vivo myocardial fiber architecture, (2) the correlation between simulated and experimental electrograms decreases with increasing pacing depth, and (3) the quantitative comparisons between bidomain model and experimental data are sensitive to both the description of the fiber architecture, and the location of the unipolar reference electrode, but relatively insensitive to moderate changes in the bidomain conductivities.

Animals↗