Subthreshold Pulses Research Articles

Can transventricular intracardiac impedance measurement discriminate haemodynamically unstable ventricular arrhythmias in human?

To measure changes in transventricular impedance during arrhythmias. Patients were studied during electrophysiological studies. A quadrapolar catheter was positioned at the right ventricular apex (RVA) and a decapolar catheter within the coronary sinus (CS). Transventricular impedance was measured by injecting a subthreshold biphasic rectangular pulse of 600 micro A between poles 1 of the CS catheter and pole 1 of the RVA catheter and the voltage measured between CS pole 10 and RVA catheter pole 4. Stroke impedance (SZ), surface ECG, intracardiac electrogram (IEGM), and invasive femoral artery blood pressure (FAP) were recorded. Twenty-eight patients were analysed, 5 with inducible, haemodynamically unstable ventricular tachycardia (VT) (HUSVT), 5 with stable VT (HSVT). During HUSVT, the SZ value reduced to 22% (range 0.15-0.32 P < 0.001) in comparison with sinus rhythm. For HSVT, the SZ value reduced to 58% (range 0.33-0.88) P < 0.01, significantly different from HUSVT (P < 0.01). There was a good correlation between reduction of SZ and arterial pulse pressure (PP) during arrhythmias (r = 0.95). Changes in SZ strongly correlated with PP amplitude. Transventricular impedance fell significantly during unstable arrhythmias and may be useful as a sensor capable of haemodynamic discrimination.

Modulation of motoneuronal firing behavior after spinal cord injury using intraspinal microstimulation current pulses: a modeling study

We simulated the effects of delivering focal electrical stimuli to the central nervous system to modulate the firing rate of neurons and alleviate motor disorders. Application of these stimuli to the spinal cord to reduce the increased excitability of motoneurons and resulting spasticity after spinal cord injury (SCI) was examined by means of a morphologically detailed computer model of a spinal motoneuron. High-frequency sinusoidal and rectangular pulses as well as biphasic charge-balanced and charge-imbalanced pulses were examined. Our results suggest that suprathreshold high-frequency sinusoidal or rectangular current pulses could inactivate the Na+ channels in the soma and initial segment, and block action potentials from propagating through the axon. Subthreshold biphasic charge-imbalanced pulses reduced the motoneuronal firing rate significantly (up to approximately 25% reduction). The reduction in firing rate was achieved through stimulation-induced hyperpolarization generated in the first node of Ranvier. Because of their low net DC current, these pulses could be tolerated safely by the tissue. To deliver charge-imbalanced pulses with the lowest net DC current and induce the largest reduction in motoneuronal firing rate, we studied the effect of various charge-imbalanced pulse parameters. Short pulse durations were found to induce the largest reduction in firing rate for the same net DC level. Subthreshold high-frequency sinusoidal and rectangular current pulses and low-frequency biphasic charge-balanced pulses, on the other hand, were ineffective in reducing the motoneuronal firing rate. In conclusion, the proposed electrical stimulation paradigms could provide potential rehabilitation interventions for suppressing the excitability of neurons to reduce the severity of motor disorders after injury to the central nervous system.

Augmentation of excitability in the hippocampus of juvenile rat

The short-term plasticity of synaptic transmission has usually been related to neurotransmitter release-dependent processes. In this work, we describe a calcium- and release-independent augmentation of the fiber volley (FVA) that appears during stimulation of the Wistar rat commissural/Schaffer collateral afferents at 10-Hz. Among the possible mechanisms involved in this phenomenon, an increment in sodium channel density or the facilitation of recovery from inactivation does not seem to be responsible for this effect since the depolarization rate of the somatic action potentials (APs) of CA3 pyramidal cells decreases during the 10-Hz stimulation. On the other hand, an increase in the synchronization of the APs can be observed during the very first pulses of the 10-Hz tetanus. However, the major part of the FVA occurs with any increase in synchronization of AP firing. Finally, a strong increase in the firing probability, with kinetics similar to that observed with the FVA, appears at 10-Hz stimulation when APs are induced at threshold intensities. This hyperexcitability seems to be mediated by a residual depolarization that persists for more than 100 ms after the AP. The nature of this post-spike depolarization is uncertain since it persists in the absence of extracellular calcium and was not blocked by the application of phenytoin (100 μM), and this excludes the implication of either calcium or sodium-persistent currents. Additionally, the increase of the stimulation strength did not alter this depolarization, which suggests that the presumed extracellular potassium accumulation produced after the synchronic stimulation of APs is not involved in the depolarization. Interestingly, the slow post-depolarization induced by both supra- and subthreshold pulses is well fitted by a single exponential decay with similar time constants, an indication that the tail depolarization may represent passive discharge of the membrane following an incomplete repolarization of the AP.

Nonlinear evolution of the plasma beat wave: Compressing the laser beat notes via electromagnetic cascading

The near-resonant beat wave excitation of an electron plasma wave (EPW) can be employed for generating the trains of few-femtosecond electromagnetic (EM) pulses in rarefied plasmas. The EPW produces a comoving index grating that induces a laser phase modulation at the difference frequency. As a result, the cascade of sidebands red and blue shifted by integer multiples of the beat frequency is generated in the laser spectrum. The bandwidth of the phase-modulated laser is proportional to the product of the plasma length, laser wavelength, and amplitude of the electron density perturbation. When the beat frequency is lower than the electron plasma frequency, the redshifted spectral components are advanced in time with respect to the blueshifted ones near the center of each laser beat note. The group velocity dispersion of plasma compresses so chirped beat notes to a few-laser-cycle duration thus creating a train of sharp EM spikes with the beat periodicity. Depending on the plasma and laser parameters, chirping and compression can be implemented either concurrently in the same, or sequentially in different plasmas. Evolution of the laser beat wave and electron density perturbations is described in time and one spatial dimension in a weakly relativistic approximation. Using the compression effect, we demonstrate that the relativistic bistability regime of the EPW excitation [G. Shvets, Phys. Rev. Lett. 93, 195004 (2004)] can be achieved with the initially subthreshold beat wave pulse.

Intraoperative Comparison of a Subthreshold Test Pulse with the Standard High‐Energy Shock Approach for the Measurement of Defibrillation Lead Impedance

There are two methods to measure shocking lead impedance: delivery of high-energy shocks that require patient sedation, and the painless measurement of impedance from subthreshold test pulses. The aim of this study was to compare the two methods. The study included 131 patients implanted with a standard DR (n = 71) or VR (n = 60) ICD connected to either single-coil (n = 39) or dual-coil (n = 92) defibrillation leads. The noninvasive high-energy impedance test was done using a 17 J shock after induction of ventricular tachyarrhythmias and compared to a 0.4 microJ test pulse used by the ICD for the subthreshold measurements. Defibrillation lead impedance measurements were not significantly different between patients with the same shocking vector configuration. In patients with a single-coil defibrillation lead the impedance was 62 +/- 9 Omega with the high-energy shock and 62 +/- 8 Omega with the subthreshold test pulses (P = 0.13). Patients with a dual-coil configuration recorded average impedances of 40 +/- 5 Omega from both tests (P = 0.44). While there was no difference in values recorded within each lead configuration, there was a significant difference in impedance between the single-coil and the dual-coil patient groups (P = 0.001). There was no significant difference between shocking lead impedances measured with the high-energy shock or the subthreshold test pulses. This offers the possibility of noninvasive, low-energy serial measurements of shocking lead impedance at follow-up visits and removing the need for sedation.

How could a chirp be more effective than a louder clock-resonant transfer of energy between subthreshold excitation pulses and excitable tissues

By definition, electrical resonance of excitable biomembranes reflects their remarkable ability to select input signals with preferential frequencies as ones that will pass through the chain of information exchange within a coordinated organism. This feature is known to be caused and regulated by the voltage-dependent kinetics of transmembrane ion channels. Knowledge about the resonant behavior of excitable cells may prove crucial toward better underpinning those essential properties of neurons which make them to function as a highly coordinated network. In this work we present novel experimental evidence which strongly supports the paradigm of selective communication between excitable cells, by no more than efficient transfer of energy which takes place when the frequency of subthreshold presynaptic pulses matches the natural, resonant frequency of a target excitable tissue. As a possible direct application, our novel experimental results prove the functional importance of bursting activity of pre-synaptic neurons as an effective physiological mechanism for discriminatory communication between neurons.

Detection of pulses in a colored noise setting

Cortical neurons are exposed to a considerable amount of synaptic background activity, which increases the neurons' conductance and which leads to a fluctuating membrane potential. Here we investigate how the presence and the properties of this background noise influence the ability of a neuron to detect transient inputs, a task that is important for coincidence detection as well as for the detection of synchronous spiking events in a neural system. Using a leaky integrate-and-fire neuron as well as a biologically more realistic Hodgkin-Huxley type point neuron we find that noise enhances the detection of subthreshold input pulses and that the phenomenon of stochastic resonance occurs. When the noise is colored, pulse detection becomes more robust, because the number of false positive events decreases with increasing temporal correlation while the number of correctly detected events is almost unaffected. Therefore, the optimal variance of the noise also changes with the degree of temporal correlations of the background activity. For the integrate-and-fire model these effects can be described using an ansatz by Brunel and Sergi [J. Theor. Biol. 195, 87 (1998)]. Numerical simulations show that the leaky integrate-and-fire model and the Hodgkin-Huxley type point neuron behave qualitatively similarly.

Femtosecond laser-induced damage morphologies of crystalline silicon by sub-threshold pulses

The effect of sub-threshold pulses of circularly polarized Ti:sapphire femtosecond laser system on crystalline (1 0 0) silicon wafer was investigated. Surface damage morphologies were studied by irradiating the test silicon surface with pulses (peak fluence of 0.25 J/cm 2) in succession. These pulses were below the single-pulse surface damage threshold. After the few initial pulses, the observed surface damage morphologies were found to be characterized by a minor phase change region and a major surface damage area at the center, corresponding to the well-known laser-induced periodic surface structure (LIPSS). Further increase in the number of pulses resulted in the formation of new surface morphologies with different features such as ablation, modification, and re-deposited materials. These features were reproducible and more distinguishable at higher number of pulses.

Long-lasting potentiation of excitatory synaptic signaling to the crayfish lateral giant neuron

The neural circuit that underlies the lateral giant fiber (LG)-mediated reflex escape in crayfish has provided findings relating synaptic change to nonassociative learning such as sensitization and habituation. The LGs receive sensory inputs from the primary sensory afferents and a group of mechanosensory interneurons (MSIs). An increase of excitability by suprathreshold repetitive excitation of this circuit, which is similar to Hebbian long-term potentiation (LTP), has been reported. This potentiation was previously thought to result from the enhancement of transmission at cholinergic synapses between primary afferents and MSIs but not the electrical synapses onto LG. In this study, we found that potentiation of synaptic signaling at the electrical synapse onto LG can also be induced when the synapse was activated with subthreshold repetitive pulses or with a few strong suprathreshold shocks. LG LTP was induced in the preparation which had received pulses at limited frequency range. Although whether this LTP is involved in the learning process of escape behavior in crayfish is not clear, the intensity and amount of sensory stimulation used here mimicked those that could easily be produced by a predator trying to catch a crayfish and could be of adaptive significance in life.

Abnormal excitability of premotor-motor connections in de novo Parkinson's disease

The dorsal premotor cortex (PMd) is abnormally active in patients with idiopathic Parkinson's disease. This has been interpreted as a functional correlate of adaptive plasticity within the motor system to compensate for deficient activation of striato-mesial-frontal projections in these patients. Whether abnormal PMd activity influences excitability in the primary motor cortex (M1) in untreated Parkinson's disease patients and how this premotor-motor interaction might be altered by l-dopa is unclear. To this end, we studied the effects of 1 Hz premotor repetitive transcranial magnetic stimulation (rTMS) on M1 excitability in 10 previously untreated non-tremulous Parkinson's disease patients before (day 1) and after (day 8) their first ever l-dopa treatment and compared the results with those of a group of nine age- and sex-matched healthy controls. In each rTMS session, 1200 pulses of 1 Hz rTMS were applied at an intensity of 80% active motor threshold (AMT) to the PMd contralateral to the clinically more affected side in Parkinson's disease patients and to the left PMd in healthy controls. Intracortical paired pulse excitability of ipsilateral M1 was probed using a TMS paired pulse paradigm where subthreshold conditioning pulses (80% of AMT) were given 2-15 ms prior to a suprathreshold test pulse. In Parkinson's disease patients, abnormal baseline intracortical excitability at an interstimulus interval (ISI) of 5 ms was normalized by premotor rTMS. In contrast, rTMS led to an increased excitability at an ISI of 5 ms in healthy controls. Premotor rTMS effects lasted longer (for at least a week) in patients. These results show that the modifiability of premotor-motor connections is abnormal in untreated Parkinson's disease. A single dose of l-dopa reversed, i.e. normalized, the direction of excitability changes in M1 following premotor rTMS in Parkinson's disease patients, suggesting that dopamine depletion directly or indirectly influences premotor-motor interactions in Parkinson's disease. The rTMS conditioning approach described here provides a promising tool to delineate further the excitability changes in frontal motor areas in response to progressive degeneration of nigrostriatal dopaminergic neurons and also to chronic l-dopa treatment in Parkinson's disease.

Experimental evidence of coexisting periodic stochastic resonance and coherence resonance phenomena.

We report evidence of coexisting period stochastic resonance (PSR) and coherence resonance (CR) phenomena in an electrochemical cell. The anodic voltage (V) in the cell is chosen such that the anodic current (I) exhibits excitable fixed point behavior. Subsequently, the anodic voltage is modulated by an external perturbation that is a composite of a subthreshold periodic pulse signal and Gaussian white noise (GWN). As the amplitude of the GWN is increased, the regularity of the invoked dynamics is analyzed using normalized variance curve. The calculated resonance curve shows a double minima, implying the existence of two optimum noise levels where enhanced regularity of the induced spike sequence is detected. Numerical simulations corroborate experimental findings.

Nonlinear stochastic resonance with subthreshold rectangular pulses.

We analyze the phenomenon of nonlinear stochastic resonance (SR) in noisy bistable systems driven by pulsed time periodic forces. The driving force contains, within each period, two pulses of equal constant amplitude and duration but opposite signs. Each pulse starts every half period and its duration is varied. For subthreshold amplitudes, we study the dependence of the output signal-to-noise ratio and the SR gain on the noise strength and the relative duration of the pulses. We find that the SR gains can reach values larger than unity, with maximum values showing a nonmonotonic dependence on the duration of the pulses.

Effects of low frequency and low intensity repetitive paired pulse stimulation of the primary motor cortex

Objective: Following a previous report [Bestmann et al. Clin Neurophysiol 2004;115:755–64] that pairs of subthreshold pulses of transcranial magnetic stimulation (TMS) can show temporal summation, we explored whether repeated application of pairs of stimulation could produce long-lasting after effects on the excitability of the human motor cortex. Methods: Twelve healthy subjects received 25 min repetitive paired pulse magnetic stimulation (paired rTMS) given at a frequency of about 0.6 Hz over the left primary motor cortex (500 paired stimuli in total). The interval between the paired stimuli was 3 ms and the intensity of both stimuli was 80% of active motor threshold. The resting and active motor threshold, MEP recruitment curve, short interval intracortical inhibition (SICI) and facilitation, and the duration of the cortical silent period (SP) were tested for the right first interosseous muscle (FDI) before and two times after the end of 25 min paired rTMS. Results: Prolonged subthreshold paired rTMS produced a significant decrease in excitability in the corticospinal projection to FDI: resting motor threshold was significantly increased and MEP recruitment was significantly decreased, SICI was significantly increased at 2 and 4 ms and the SP was significantly increased in duration. Conclusions: Prolonged low frequency paired rTMS at subthreshold intensity can modulate cortical excitability by producing inhibitory effects that outlast the period of stimulation.

Subthreshold contribution of N-methyl- d-aspartate receptors to long-term potentiation induced by low-frequency pairing in rat hippocampal CA1 pyramidal cells

Long-term potentiation (LTP) is a use-dependent and persistent enhancement of synaptic strength. In the CA1 region of the hippocampus, LTP has Hebbian characteristics and requires precisely timed interaction between presynaptic firing and postsynaptic depolarization. Although depolarization is an absolute requirement for plasticity, it is still not clear whether the postsynaptic response during LTP induction should be subthreshold or suprathreshold for the generation of somatic action potential. Here, we use the whole-cell patch-clamp technique and different pairing protocols to examine systematically the postsynaptic induction requirements for LTP. We induce LTP by changes only in membrane potential while keeping the afferent stimulation constant and at minimal levels. This approach permits differentiation of two types of LTP: LTP induced with suprathreshold synaptic responses (LTP AP) and LTP induced with subthreshold excitatory postsynaptic current (EPSCs; LTP EPSC). We found that LTP AP (>40%) required pairing of depolarization ( V m ≥−40 mV, for 40–60 s) with four to six (0.1 Hz) single synaptically initiated action potentials. LTP EPSC was of smaller magnitude (<30%) and required pairing of depolarization to −50 mV (60 s) with six subthreshold EPSCs. The N-methyl- d-aspartate receptor (NMDAR) antagonists aminophosphonovaleric acid and 7-chlorokynurenic acid consistently blocked LTP EPSC but were ineffective in preventing LTP AP. Robust, NMDAR-independent LTP is obtained by stronger postsynaptic depolarization that converts the EPSCs to suprathreshold somatic action potentials. Purely NMDAR-dependent LTP is obtained by pairing mild somatic depolarization with subthreshold afferent pulses to the postsynaptic cell. Our results indicate that the degree of postsynaptic depolarization in the presence of single afferent pulses determines the type and magnitude of LTP.

Subthreshold contribution of N-methyl--aspartate receptors to long-term potentiation induced by low-frequency pairing in rat hippocampal CA1 pyramidal cells

Long-term potentiation (LTP) is a use-dependent and persistent enhancement of synaptic strength. In the CA1 region of the hippocampus, LTP has Hebbian characteristics and requires precisely timed interaction between presynaptic firing and postsynaptic depolarization. Although depolarization is an absolute requirement for plasticity, it is still not clear whether the postsynaptic response during LTP induction should be subthreshold or suprathreshold for the generation of somatic action potential. Here, we use the whole-cell patch-clamp technique and different pairing protocols to examine systematically the postsynaptic induction requirements for LTP. We induce LTP by changes only in membrane potential while keeping the afferent stimulation constant and at minimal levels. This approach permits differentiation of two types of LTP: LTP induced with suprathreshold synaptic responses (LTPAP) and LTP induced with subthreshold excitatory postsynaptic current (EPSCs; LTPEPSC). We found that LTPAP (>40%) required pairing of depolarization (Vm≥−40 mV, for 40–60 s) with four to six (0.1 Hz) single synaptically initiated action potentials. LTPEPSC was of smaller magnitude (<30%) and required pairing of depolarization to −50 mV (60 s) with six subthreshold EPSCs. The N-methyl-d-aspartate receptor (NMDAR) antagonists aminophosphonovaleric acid and 7-chlorokynurenic acid consistently blocked LTPEPSC but were ineffective in preventing LTPAP. Robust, NMDAR-independent LTP is obtained by stronger postsynaptic depolarization that converts the EPSCs to suprathreshold somatic action potentials. Purely NMDAR-dependent LTP is obtained by pairing mild somatic depolarization with subthreshold afferent pulses to the postsynaptic cell. Our results indicate that the degree of postsynaptic depolarization in the presence of single afferent pulses determines the type and magnitude of LTP.

Transcranial Magnetic Stimulation in Epilepsy.

Transcranial magnetic stimulation (TMS) seems an attractive tool for the study of seizure disorders. It is simple to perform, relatively inexpensive, and generally safe, with the potential to provide noninvasive clinical measurements of neuronal excitability. Applications in patients with epilepsy include investigation of underlying cortical excitability and determination of the effects of antiepileptic drugs (AEDs); preoperative localization of epileptic foci; and functional mapping. Several review articles have been published on the use of TMS for epilepsy (1, 2, 3, 4, 5). Most intriguingly, TMS could become a new seizure treatment modality. The parameters measured by TMS include motor threshold, which is the minimal threshold for motor response in target muscle and motor evoked potential (MEP) amplitude, both measured using single pulses (see Table 1). The cortical silent period (CSP) is a lapse in electromyogram (EMG), when a TMS pulse is given during tonic voluntary muscle contraction; its duration is related to stimulus intensity. Additional parameters are measured with paired-pulse stimulation techniques. For example, intracortical inhibition (ICI), a decrease in MEP amplitude from the first to the second stimulus, is seen when a subthreshold conditioning pulse is followed by a suprathreshold pulse after a 2- to 5-millisecond delay, whereas intracortical facilitation (ICF) occurs when the pulses are 7 to 20 milliseconds apart. TABLE 1 TMS Parameters

Cortical responses to cochlear implant stimulation: channel interactions.

This study examined the interactions between electrical stimuli presented through two channels of a cochlear implant. Experiments were conducted in anesthetized guinea pigs. Multiunit spike activity recorded from the auditory cortex reflected the cumulative effects of electric field interactions in the cochlea as well as any neural interactions along the ascending auditory pathway. The cochlea was stimulated electrically through a 6-electrode intracochlear array. The stimulus on each channel was a single 80- micro s/phase biphasic pulse. Channel interactions were quantified as changes in the thresholds for elevation of cortical spike rates. Experimental parameters were interchannel temporal offset (0 to +/-2000 micro s), interelectrode cochlear spacing (1.5 or 2.25 mm), electrode configuration (monopolar, bipolar, or tripolar), and relative polarity between channels (same or inverted). In most conditions, presentation of a subthreshold pulse on one channel reduced the threshold for a pulse on a second channel. Threshold shifts were greatest for simultaneous pulses, but appreciable threshold reductions could persist for temporal offsets up to 640 micro s. Channel interactions varied strongly with electrode configuration: threshold shifts increased in magnitude in the order tripolar, bipolar, monopolar. Channel interactions were greater for closer electrode spacing. The results have implications for design of speech processors for cochlear implants.

Subthreshold test pulses versus low energy shock delivery to estimate high energy lead impedance in implanted cardioverter defibrillator patients.

The high energy lead impedance is valuable for detecting lead failure in ICDs, but until recently shock delivery was necessary for high energy impedance measurement. This study compared the use of subthreshold test pulses and low energy test shocks to estimate the high energy impedance. Immediately after implantation of Ventak Prizm ICDs in 29 patients, the lead impedance was measured with five subthreshold (0.4 microJ) test pulses, 5 low energy (1.1 J) shocks, and two to three high energy (16 +/- 4.5 J) shocks. The mean impedances measured using high energy shocks, low energy shocks, and subthreshold pulses were 42.0 +/- 7.3 omega, 46.5 +/- 8.1 omega, and 42.4 +/- 7.1 omega, respectively. The impedances measured using high and low energy shocks differed significantly (P < 0.0001), while those obtained by high energy shocks and low energy pulses did not (P = 0.63). According to the Pearson correlation coefficient, the impedance measurements with subthreshold pulses and low energy shocks were both closely correlated (P < 0.0001) with impedance values determined with high energy shocks. However, while the impedance values tended to be higher when measured with low energy shocks, the concordance correlation coefficient (c) was higher for subthreshold test pulse versus high energy shock (c = 0.92) than for low versus high energy shock (c = 0.73). Furthermore, the intraindividual variability of impedance measurements was lower with subthreshold pulse measurements than with low energy shocks. Compared with low energy shocks, impedance measurement with subthreshold pulses has higher reproducibility and a higher correlation with the impedance obtained by high energy shock delivery. Safe and painless high energy impedance estimation with subthreshold pulses might, therefore, help to detect ICD lead failure during routine follow-up.

Ultrashort laser ablation of metals: pump–probe experiments, the role of ballistic electrons and the two-temperature model

The dynamics of laser ablation from metallic surfaces (Ag, Al, Fe and Ni) induced by the combined effect of two 30 fs sub-threshold laser pulses has been examined. In a pump–probe setup the yield of the emitted secondary ions and neutrals has been determined as a function of the delay between the two laser pulses. The instantaneous generation of highly excited (ballistic) electrons by the laser pulse and the thermal properties of the metal, which have been modified to be valid into the regime of high electron temperatures have been found to be determining factors for the ablation process. Unexpectedly, two distinct maxima for particle emission have been observed as a function of the time separation of the pump and the probe pulse. The energy relaxation is discussed within the frame of the two-temperature model (TTM) and it is shown that the measured behavior (in the time domain) of ablated particles can only be explained by taking into account a general expression for the thermal conductivity, valid for a wide range of electron temperatures and in addition a substantial role of hot, ballistic electrons.

Subthreshold test pulse versus shock delivery to evaluate high voltage impedance in ICD patients

Subthreshold test pulse versus shock delivery to evaluate high voltage impedance in ICD patients