Biomedical subjects

D M Durand

Publications and source records attributed to D M Durand.

At least 19 recordsLinked to original sources

PubMed2003

Electric field effects in hyperexcitable neural tissue: a review.

Uniform electric fields applied to neural tissue can modulate neuronal excitability with a threshold value of about 1 mV mm(-1) in normal physiological conditions. However, electric fields could have a lower threshold in conditions where field sensitivity is enhanced, such as those simulating epilepsy. Uniform electrical fields were applied to hippocampal brain slices exposed to picrotoxin, high potassium or low calcium solutions. The results in the low calcium medium show that neuronal activity can be completely blocked in 10% of the 30 slices tested with a field amplitude of 1 mV mm(-1). These results suggest that the threshold for this effect is clearly smaller than 1 mV mm(-1). The hypothesis that the extracellular resistance could affect the sensitivity to the electrical fields was tested by measuring the effect of the osmolarity of the extracellular solution on the efficacy of the field. A 10% decrease in osmolarity resulted in a 56% decrease (n = 4) in the minimum field required for full suppression. A 14% in osmolarity produced an 81% increase in the minimum field required for full suppression. These results show that the extracellular volume can modulate the efficacy of the field and could lower the threshold field amplitudes to values lower than approximately 1 mmV mm(-1).

Action Potentials↗

PubMed2001

Propagation of non-synaptic epileptiform activity across a lesion in rat hippocampal slices.

1. Spontaneous non-synaptic epileptiform activity was induced by bathing rat hippocampal slices in low-Ca(2+) solution. Extracellular recordings from electrodes placed on both sides of a complete cut showed that non-synaptic activity was synchronized across the lesion. 2. Ion-selective electrode recordings showed that each event was accompanied by a transient increase in extracellular potassium that diffused across the lesion. The synchrony was destroyed when a thin film was inserted into the lesion site. 3. Local pressure ejection of KCl evoked an event that subsequently propagated across the lesion. 4. After a complete lesion was made, afterdischarges evoked on one half of a slice were not detected on the other half. 5. Voltage-sensitive dye imaging methods showed that epileptic activity propagated across the mechanical lesion without significant attenuation or additional delays. The velocity of the activity was consistent with that of the slow diffusion of a potassium wave. 6. Since field effects were significantly attenuated across the lesion and all gap junctions and cell processes across the lesion would be cut, these data show that extracellular diffusion, most probably potassium, is sufficient to synchronize populations of neurons and propagate slow frequency epileptiform activity.

Animals↗

PubMed2001

Positive Lyapunov exponents calculated from time series of strange nonchaotic attractors.

Time-series methods for estimating Lyapunov exponents may give a positive exponent when they are applied to the time series of strange nonchaotic systems. Strange nonchaotic systems are characterized by expanding and contracting regions in phase space that result in repeatedly expanding or contracting trajectories. Using time-series methods, the maximum time-series Lyapunov exponent is calculated as an average of the locally most expanding exponents that characterize the divergence of nearby trajectories following a reconstructed attractor over time. A positive exponent is reported by time-series methods for trajectories in an expanding region. While in a converging region, the most expanding dynamics are related to the quasiperiodic driving force. Statistically, a zero exponent related to the quasiperiodic force is obtained through time-series methods within converging regions. As a result, the calculated maximum Lyapunov exponent is positive.

Journal Article↗

PubMed2001

Suppression of epileptiform activity by high frequency sinusoidal fields in rat hippocampal slices.

1. Sinusoidal high frequency (20-50 Hz) electric fields induced across rat hippocampal slices were found to suppress zero-Ca2+, low-Ca2+, picrotoxin, and high-K+ epileptiform activity for the duration of the stimulus and for up to several minutes following the stimulus. 2. Suppression of spontaneous activity by high frequency stimulation was found to be frequency (< 500 Hz) but not orientation or waveform dependent. 3. Potassium-sensitive microelectrodes showed that block of epileptiform activity was always coincident with a stimulus-induced rise in extracellular potassium concentration during stimulation. Post-stimulus inhibition was always associated with a decrease in extracellular potassium activity below baseline levels. 4. Intracellular recordings and optical imaging with voltage-sensitive dyes showed that during suppression neurons were depolarized yet did not fire action potentials. 5. Direct injection of sinusoidal current into individual pyramidal cells did not result in a tonic depolarization. Injection of large direct current (DC) depolarized neurons and suppressed action potential generation. 6. These findings suggest that high frequency stimulation suppresses epileptiform activity by inducing potassium efflux and depolarization block.

Animals↗

PubMed2001

Nonlinear dynamic properties of low calcium-induced epileptiform activity.

The analysis of the dynamic properties of epileptiform activity in vitro has led to a better understanding of the time course of neural synchronization and seizure states. Nonlinear analysis is thus potentially useful for the prediction of seizure onset. We have used nonlinear analysis methods to investigate the development of activity in the low calcium model of epilepsy in brain slices. This model is particularly interesting since neurons synchronize in the absence of synaptic transmission. The dynamic properties calculated from extracellular recordings of activity were used to analyze the transition to synchronous firing and their relation to neuronal excitability. The global embedding dimension, local dimension and the Lyapunov exponent were calculated from time segments corresponding to the onset, transition and fully developed stages of activity. The analysis was repeated for recordings made in the presence of various levels of DC electric fields to modulate neuronal excitability. The global and local dimensions did not change once activity was first initiated, even in the presence of the electric field. The maximum Lyapunov exponents increased during the onset of activity but decreased when the applied hyperpolarizing electric field was large enough to partially suppress the activity. These findings establish a relationship between neuronal excitability and the maximum Lyapunov exponent, and suggest that the Lyapunov exponent may be used to distinguish between various states of the neural network and might be important in seizure prediction and control.

Action Potentials↗

PubMed2001

Selectivity of multiple-contact nerve cuff electrodes: a simulation analysis.

Advances in functional neuromuscular stimulation (FNS) have increased the need for nerve cuff designs that can control multiple motor functions through selective stimulation of selected populations of axons. This selectivity has proved to be difficult to achieve. Recent experiments suggest that it is possible to slowly reshape peripheral nerve without affecting its physiological function. Using computer simulations we have tested the hypothesis that changing the cross section of a nerve from a round to a flat configuration can significantly improve the selectivity of a nerve cuff. We introduce a new index to estimate selectivity to evaluate the various designs. This index is based on the ability of a nerve electrode to stimulate a target axon without stimulating any other axons. The calculations involve a three-dimensional finite element model to represent the electrical properties of the nerve and cuff and the determination of the firing properties of individual axons. The selectivity rating was found to be significantly higher for the Flat Cuff than the Round Cuff. The result was valid with uniform or random distribution of axons and with a random distribution of fascicles diameters. Flattening of individual fascicles also improved the selectivity of the Flat Cuff but only when the number of contacts used was increased to maintain uniform contact density. Therefore, cuff designs that can reshape the nerve into flatter configurations should yield better cuff performance than the cylindrical cuffs but will require higher contact density.

Anisotropy↗

PubMed2001

Toroidal coil models for transcutaneous magnetic stimulation of nerves.

A novel design of coils for transcutaneous magnetic stimulation of nerves is presented. These coils consist of a toroidal winding around a high-permeability material (Supermendur) core embedded in a conducting medium. Theoretical numerical calculations are used to analyze the effect of the design parameters of these coils, such as coil width, toroidal radius, conducting layer thickness and core transversal shape on the induced electric fields in terms of the electric field strength and distribution. Results indicate that stimulation of nerves with these coils has some of the advantages of both electrical and magnetic stimulation. These coils can produce localized and efficient stimulation of nerves with induced electric fields parallel and perpendicular to the skin similar to surface electrical stimulation. However, they retain some of the advantages of magnetic stimulation such as no risk of tissue damage due to electrochemical reactions at the electrode interface and less uncomfortable sensations or pain. The driving current is reduced by over three orders of magnitude compared to traditional magnetic stimulation, eliminating the problem of coil heating and allowing for long duration and high-frequency magnetic stimulation with inexpensive stimulators.

Electric Conductivity↗

PubMed2001

A 3-D differential coil design for localized magnetic stimulation.

A novel three-dimensional (3-D) differential coil has been designed for improving the localization of magnetic stimulation. This new coil design consists of a butterfly coil with two additional wing units and an extra bottom unit, both perpendicular to the plane of the butterfly coil. The wing units produce opposite fields to restrict the spread of induced fields while the bottom unit enhances the induced fields at the excitation site. The peak induced field generated by this new design is located at the center of the coil, providing an easy identification of the excitation site. The field localization of the new coil is comparable with that of much smaller coils but with an inductance compatible to current magnetic stimulators. Numerical computations based on the principles of electromagnetic induction and using a human nerve model were performed to analyze the induced fields and the stimulation thresholds of new coil designs. The localization of the coil design was assessed by a half power region (HPR), within which the magnitude of the normalized induced field is greater than 1/square root of 2. The HPR for a 3-D differential coil built is improved (decreased) by a factor of three compared with a standard butterfly coil. Induced fields by this new coil were measured and in agreement with theoretical calculations.

Axons↗

PubMed2001

Synaptic noise improves detection of subthreshold signals in hippocampal CA1 neurons.

Stochastic resonance (SR) is a phenomenon whereby the detection of a low-level signal is enhanced in a nonlinear system by the introduction of noise. Studies of the effects of SR in neurons have suggested that noise could play a prominent role in improving detection of small signals. Most experimental SR research has focused on the role of noise in sensory neurons using physiological stimuli. Computer simulations show that signal detection in hippocampal neurons is improved by the addition of physiological levels of noise applied extracellularly to synaptic inputs. These results were confirmed experimentally. We now report that endogenous noise sources can also improve signal detection. The noise source was generated by modulating the random synaptic activity on the apical dendrites of CA1 cells in rat hippocampal slices using subthreshold cathodic current. Intracellular recordings of CA1 cells showed that even small increases of synaptic noise are able to greatly improve the detection of an independent, synaptic, subthreshold stimulus as predicted by the simulations. The noise variance in the CA1 cell was compared with the resting variance and with variance changes caused by several endogenous noise sources. In all cases, the increased noise variance was well within the physiological range. These results were supplemented and analyzed with a CA1 computer model. The improved signal detection with small amounts of endogenous noise suggests that the diverse inputs to CA1 are able to improve detection of subthreshold synaptic signals and could provide a means to modulate detection of specific inputs in the hippocampus.

Action Potentials↗

PubMed2000

CMV retinitis recurs after stopping treatment in virological and immunological failures of potent antiretroviral therapy.

OBJECTIVES: To determine predictors of clinical relapse of cytomegalovirus (CMV) end-organ disease in a cohort of 17 HIV-infected patients with healed and treated CMV retinitis (CMVR) who responded to HAART with an increase in CD4 cell counts to above 70 cells/mm3 and discontinued CMV maintenance therapy (MT). DESIGN: Seventeen patients were monitored for reactivation of retinitis. The CD4 cell counts, HIV RNA and peripheral blood mononuclear cell (PBMC) lymphoproliferative assays to CMV at 3 month intervals were compared between patients with and without reactivation of CMVR. Positive lymphoproliferative responses were defined as a stimulation index of 3 or greater. RESULTS: Five out of 17 (29%) patients experienced a recurrence of CMVR a mean of 14.5 months after stopping CMV MT and between 8 days and 10 months after CD4 cell counts fell below 50 cells/mm3. Median CD4 cell counts and plasma HIV RNA at reactivation were 37 cells/mm3 and 5.3 log10 copies/ml. Three patients recurred at a previously active site of the retina, one had contralateral CMVR, and one a recurrence of retinitis and pancreatitis simultaneously. Mean lymphoproliferative responses to CMV were 2.4 in patients with reactivation versus 21.0 stimulation index (SI) in patients without reactivation (P= 0.01). A model incorporating four variables (CD4 cell counts and HIV RNA at maintenance discontinuation, highest CD4 cell count, nadir HIV RNA and median lymphoproliferative responses) identified correctly 88% of patients with and without reactivation. CONCLUSION: CMV disease recurs after virological and immunological failure of HAART if CD4 cell counts drop below 50. In this situation, anti-CMV agents should be resumed before clinical reactivation ensues, because of the risk of contralateral retinal involvement and systemic disease.

AIDS-Related Opportunistic Infections↗

PubMed2000

Prediction of neural excitation during magnetic stimulation using passive cable models.

A method for predicting neural excitation during magnetic stimulation using passive cable models has been developed. This method uses the information of the threshold capacitor voltage for magnetic stimulation coils to determine the equivalent excitation thresholds for the passive transient (PT) and passive steady-state (PSS) cable models as well as for the activating function. The threshold values for the PT, PSS models, and the activating function vary only with the pulsewidth of the stimulus for a variety of coils at different locations and orientations. Furthermore, the excitation threshold for the PSS model is also independent of axon diameter and best fitted to a simple mathematical function. By comparing the transmembrane potential of the PSS model with the corresponding threshold, the prediction of excitation during magnetic stimulation can be made. Similarly, it is also possible to predict excitation using the PT model and the activating function with the corresponding thresholds provided. By taking advantage of the weighted pulsewidth, this method can even predict the excitation for stimuli with various waveforms, greatly simplifying the determination of neural excitation for magnetic stimulation.

Axons↗

PubMed2000

Closed-loop stimulation of hypoglossal nerve in a dog model of upper airway obstruction.

Electrical stimulation of upper airway (UAW) muscles has been under investigation as a treatment method for obstructive sleep apnea (OSA). Particular attention has been given to the electrical activation of the genioglossal muscle, either directly or via the stimulation of the hypoglossal nerve (HG), since the genioglossus is the main tongue protrusor muscle. Regardless of the stimulation site or method, an implantable electrical stimulation device for OSA patients will require a reliable method for detection of obstructive breaths to apply the stimulation when needed. In this paper, we test the hypothesis that the activity of the HG nerve can be used as a feedback signal for closed-loop stimulation of the HG nerve in an animal model of UAW obstruction where a force is applied on the submental region to physically narrow the airways. As an advantage, the method uses a single electrode for both recording and stimulation of the HG nerve. Simple linear filtering techniques were found to be adequate for producing the trigger signal for the electrical stimulation from the HG recordings. Esophageal pressure, which was used to estimate the size of the UAW passage, returned to the preloading values during closed-loop stimulation of the HG nerve. The data demonstrate the feasibility of the closed-loop stimulation of the HG nerve using its activity as the feedback signal.

Airway Obstruction↗

PubMed2000

Measurement of external pressures generated by nerve cuff electrodes.

When external pressures are applied to a peripheral nerve, tissue damage can occur via compression and blood flow occlusion, resulting in degeneration and demyelination of axons. Although many types of nerve electrodes have been designed to avoid or minimize this pressure during stimulation of the nerve or recording of its activity, the measurement of the pressure exerted by these cuffs has not been reported. Currently, only theoretical models are used to predict nerve cuff electrode pressures. We have developed a nerve cuff electrode pressure sensor to measure external pressures exerted by peripheral nerve cuff electrodes. The sensor has a high sensitivity, linear response with little hysteresis and reproducible output. Pressure measurements have been obtained for split-ring and spiral cuff electrodes. The measurements obtained are in agreement with theoretical predictions. Moreover, they indicate that the pressures exerted by cuffs currently used for stimulation generate only a small amount of pressure, which is below the pressure required to occlude blood flow in nerves. The results also suggest that this new sensor can provide reliable measurement of external pressures exerted by nerve electrodes and would be an important tool for comparing various nerve cuff electrode designs.

Bias↗

PubMed2000

Modeling study of peripheral nerve recording selectivity.

Recording of sensory information from afferent fibers can be used as feedback for the closed-loop control of neural prostheses. Clinical applications suggest that recording selectively from various nerve fascicles is important. Current nerve cuff electrodes are generally circular in shape and use a tripolar recording configuration. Preliminary experiments suggest that slowly changing the shape of the nerve to a flatter cross section can improve its selectivity. The objective of this work is to determine the effects of nerve reshaping and other cuff design parameters on the fascicular recording selectivity of a nerve cuff. A finite-element computer model of a multifasciculated nerve with different cuff electrodes was implemented to simulate the recordings. The model included the inhomogeneous and anisotropic properties of peripheral nerves. The recording selectivity was quantified with the use of a Selectivity Index. The results from the model provided information regarding the effect of using monopolar versus tripolar recording configurations, the length of the tripoles in tripolar recordings, the number of contacts that maximize the selectivity index, and the cuff length. Nerve reshaping was found to cause important recording selectivity improvements (106% average). These results provide specific criteria for the design of selectively recording nerve cuff electrodes.

Afferent Pathways↗

PubMed2000

Stochastic resonance improves signal detection in hippocampal CA1 neurons.

Stochastic resonance (SR) is a phenomenon observed in nonlinear systems whereby the introduction of noise enhances the detection of a subthreshold signal for a certain range of noise intensity. The nonlinear threshold detection mechanism that neurons employ and the noisy environment in which they reside makes it likely that SR plays a role in neural signal detection. Although the role of SR in sensory neural systems has been studied extensively, its role in central neurons is unknown. In many central neurons, such as the hippocampal CA1 cell, very large dendritic trees are responsible for detecting neural input in a noisy environment. Attenuation due to the electrotonic length of these trees is significant, suggesting that a method other than passive summation is necessary if signals at the distal ends of the tree are to be detected. The hypothesis that SR plays an important role in the detection of distal synaptic inputs first was tested in a computer simulation of a CA1 cell and then verified with in vitro rat hippocampal slices. The results clearly showed that SR can enhance signal detection in CA1 hippocampal cells. Moreover, high levels of noise were found to equalize detection of synaptic signals received at varying positions on the dendritic tree. The amount of noise needed to evoke the effect is compared with physiological noise in slices and in vivo.

Algorithms↗

PubMed2000

Effects of applied electric fields on low-calcium epileptiform activity in the CA1 region of rat hippocampal slices.

It is well established that exogenous electric fields can suppress activity obtained in different models of epileptiform discharge such as penicillin and high potassium. In the low-calcium model of epilepsy, spontaneous epileptiform bursting is generated in the absence of synaptic transmission. It has been suggested that ephaptic interactions play a critical role in neuronal synchronization and burst propagation in this nonsynaptic model. We, therefore, tested the hypothesis that low-calcium bursting induced in the CA1 region of transverse and longitudinal hippocampal slices should be highly sensitive to exogenous electric fields. Uniform, low amplitude DC electric fields were applied during spontaneous low-calcium epileptiform activity. Modulation and full suppression of epileptiform activity was observed at field strengths between 1 and 5 mV/mm, a value significantly lower than in other in vitro models of epilepsy. We further investigated the hypothesis that the efficacy of electrical fields was related to changes in the extracellular space. Our results suggest that the osmolality of the perfusate can modulate the efficacy of electric fields. It was also observed that the ability of a field to suppress or modulate low-calcium activity was highly dependent on its orientation, polarity, as well as magnitude. Finally, it was observed that the extracellular potassium "waves" that normally accompany individual epileptiform events was abolished when the individual events were suppressed. These results suggest that DC fields modulate and suppress low-calcium activity by directly polarizing CA1 pyramidal cells.

Animals↗

PubMed1999

Effects of oxygen deprivation on parapyramidal neurons of the ventrolateral medulla in the rat.

We characterized the electrophysiological properties and responses of neurons located in the parapyramidal region of the ventral aspect of the rat medulla oblongata (parapyramidal neurons, PP neurons) to oxygen deprivation, in order to understand the mechanisms involved in hypoxia induced respiratory depression. The responses of PP neurons to oxygen deprivation were compared to those of the functionally dissimilar neurons of the dentate gyrus (DG). Neurons from the PP region were found to fire spontaneously with a frequency of 3-3.5 spikes/sec in both adults and neonates and responded to an anoxic insult with a complete loss of spontaneous firing. Discrete metabolite analysis showed a small (about 17%) decrease in tissue adenosine triphosphate (ATP) levels of the PP neurons during an anoxic insult and the decrease was significantly smaller than in the DG cell region (28%). In contrast to the DG neurons, the PP neurons recovered from an anoxic insult lasting more than 30 min, indicating a greater survival capacity of the PP neurons during oxygen deprivation. The PP neurons were also capable of withstanding successive anoxic insults better than the DG cells as demonstrated by their complete recovery following reoxygenation. It is suggested that the PP neurons may depress their electrical activity as an energy conservation mechanism, and thereby survive anoxic insults longer than the dentate neurons, whereas the loss of cellular activity in the DG neurons may be a result of energy depletion.

Adenosine Triphosphate↗

PubMed1999

Neurofuzzy adaptive controlling of selective stimulation for FES: a case study.

A controller was designed for the selective stimulation of the sciatic nerve with a multiple contact cuff electrode to generate a desired torque in the ankle joint of cat. The design integrates three approaches, artificial neural network (ANN) modeling, fuzzy logical adaptation, and geometrical mapping. The geometrical mapping refers to the vector transformation from the joint coordinates to the virtual muscle coordinates which have been conceptually developed to represent the major recruitment features of contact-based functional units in the physical plant. This method reduces the complexity of generating a data set for training the neural network in the feedforward path and implementing the on-line learning algorithm embedded in the feedback loop. The controller was evaluated by computer simulation with the experimental data obtained from the torque generation in five acute cats. The results show that the ANN-based feedforward is capable of predicting 65% of a given desired isometric torque, and the fuzzy logical machine is able to provide suitable gains for feedback modulation to reduce the error from 35 to 8.5% and produce a robust control.

Animals↗