The biomechanics of an overarm throwing task: a simulation model examination of optimal timing of muscle activations.

A series of overarm throws, constrained to the parasagittal plane, were simulated using a muscle model actuated two-segment model representing the forearm and hand plus projectile. The parameters defining the modeled muscles and the anthropometry of the two-segment models were specific to the two young male subjects. All simulations commenced from a position of full elbow flexion and full wrist extension. The study was designed to elucidate the optimal inter-muscular coordination strategies for throwing projectiles to achieve maximum range, as well as maximum projectile kinetic energy for a variety of projectile masses. A proximal to distal (PD) sequence of muscle activations was seen in many of the simulated throws but not all. Under certain conditions moment reversal produced a longer throw and greater projectile energy, and deactivation of the muscles resulted in increased projectile energy. Therefore, simple timing of muscle activation does not fully describe the patterns of muscle recruitment which can produce optimal throws. The models of the two subjects required different timings of muscle activations, and for some of the tasks used different coordination patterns. Optimal strategies were found to vary with the mass of the projectile, the anthropometry and the muscle characteristics of the subjects modeled. The tasks examined were relatively simple, but basic rules for coordinating these tasks were not evident.     

Whole Heart Coronary Imaging with Flexible Acquisition Window and Trigger Delay

Coronary magnetic resonance imaging (MRI) requires a correctly timed trigger delay derived from a scout cine scan to synchronize k-space acquisition with the quiescent period of the cardiac cycle. However, heart rate changes between breath-held cine and free-breathing coronary imaging may result in inaccurate timing errors. Additionally, the determined trigger delay may not reflect the period of minimal motion for both left and right coronary arteries or different segments. In this work, we present a whole-heart coronary imaging approach that allows flexible selection of the trigger delay timings by performing k-space sampling over an enlarged acquisition window. Our approach addresses coronary motion in an interactive manner by allowing the operator to determine the temporal window with minimal cardiac motion for each artery region. An electrocardiogram-gated, k-space segmented 3D radial stack-of-stars sequence that employs a custom rotation angle is developed. An interactive reconstruction and visualization platform is then employed to determine the subset of the enlarged acquisition window for minimal coronary motion. Coronary MRI was acquired on eight healthy subjects (5 male, mean age = 37 ± 18 years), where an enlarged acquisition window of 166–220 ms was set 50 ms prior to the scout-derived trigger delay. Coronary visualization and sharpness scores were compared between the standard 120 ms window set at the trigger delay, and those reconstructed using a manually adjusted window. The proposed method using manual adjustment was able to recover delineation of five mid and distal right coronary artery regions that were otherwise not visible from the standard window, and the sharpness scores improved in all coronary regions using the proposed method. This paper demonstrates the feasibility of a whole-heart coronary imaging approach that allows interactive selection of any subset of the enlarged acquisition window for a tailored reconstruction for each branch region.     

Optimisation of high bar circling technique for consistent performance of a triple piked somersault dismount

The dismount from the high bar is one of the most spectacular skills performed in Men's Artistic Gymnastics. Hiley and Yeadon [2005. Maximal dismounts from high bar. Journal of Biomechanics 38, 2221-2227] optimised the technique in the backward giant circle prior to release using a computer simulation model to show that a gymnast could generate sufficient linear and angular momentum to perform a triple piked backward somersault dismount with a sufficiently large release window (the period of time during which the gymnast could release the bar and successfully complete the dismount). In the present study, it was found that when the timing of the actions at the hip and shoulder joints from the optimum simulation were perturbed by 30ms the resulting simulation could no longer meet the criteria for sufficient aerial rotation and release window. Since it is to be expected that a gymnast's technique can cope with small errors in timing for consistent performance, a requirement of robustness to timing perturbations should be included within the optimisation process. When the technique in the backward giant circle was optimised to be robust to 30ms perturbations, it was found that sufficient linear and angular momentum for a triple piked dismount could be achieved with a realistic release window.     

Coping with perturbations to a layout somersault in tumbling

Tumbling is a dynamic movement requiring control of the linear and angular momenta generated during the approach and takeoff phases. Both of these phases are subject to some variability even when the gymnast is trying to perform a given movement repeatedly. This paper used a simulation model of tumbling takeoff to establish how well gymnasts can cope with perturbations of the approach and takeoff phases. A five segment planar simulation model with torque generators at each joint was developed to simulate tumbling takeoffs. The model was customised to an elite gymnast by determining subject specific inertia and torque parameters and a simulation was produced which closely matched a performance of a layout somersault by the gymnast. The performance of a layout somersault was found to be sensitive to the approach characteristics and the activation timings but relatively insensitive to the elasticity of the track and maximum muscle strength. Appropriate variation of the activation timings used during the takeoff phase was capable of coping with moderate perturbations of the approach characteristics. A model of aerial movement established that variation of body configuration in the flight phase was capable of adjusting for takeoff perturbations that would lead to rotation errors of up to 8%. Providing the errors in perceiving approach characteristics are less than 5% or 5 degrees and the errors in timing activations are less than 7ms, perturbations in the approach can be accommodated using adjustments during takeoff and flight.     

Activation of a distributed somatosensory cortical network in the human brain. A dipole modelling study of magnetic fields evoked by median nerve stimulation. Part I: location and activation timing of SEF sources

Cortical areas responsive to somatosensory inputs were assessed by recording somatosensory evoked magnetic fields (SEF) to electrical stimulation of the left median nerve at wrist, using a 122-SQUID neuromagnetometer in various conditions of stimulus rate, attentional demand and detection task. Source modelling combined with magnetic resonance imaging (MRI) allowed localisation of six SEF sources on the outer aspect of the hemispheres located respectively: (1) in the posterior bank of the rolandic fissure (area SI), the upper bank of the sylvian fissure (parietal opercular area SII) and the banks of the intraparietal fissure contralateral to stimulation, (2) in the SII area ipsilateral to stimulation and (3) in the mid-frontal or inferior frontal gyri on both sides. All source areas were found to be simultaneously active at 70–140 ms after the stimulus, the SI source was the only one active already at 20–60 ms. The observed activation timing suggests that somatosensory input from SI is processed to higher-order areas through serial feedforward projections. However the long-lasting activations of all sources and their overlap in time is also compatible with a top-down control mediated via backward projections.     

Effects of postural muscle fatigue on the relation between segmental posture and movement.

The purpose of this study was to examine whether fatigue of postural muscles might influence the coordination between segmental posture and movement. Seven healthy adults performed series of fifteen fast wrist flexions and extensions while being instructed to keep a dominant upper limb posture as constant as possible. These series of voluntary movements were performed before and after a fatiguing submaximal isometric elbow flexion, and also with or without the help of an elbow support. Surface EMG from muscles Delto?deus anterior, Biceps brachii, Triceps brachii, Flexor carpi ulnaris, Extensor carpi radialis were recorded simultaneously with wrist, elbow and shoulder accelerations and wrist and elbow displacements. Fatigue was evidenced by a shift of the elbow and shoulder muscles EMG spectra towards low frequencies. Kinematics of wrist movements and corresponding activations of wrist prime-movers, as well as the background of postural muscle activation before wrist movement were not modified. There were only slight changes in timing of postural muscle activations. These data indicate that postural fatigue induced by a low-level isometric contraction has no effect on voluntary movement and requires no dramatic adaptation in postural control.     

Cortical Dynamics of Semantic Processing during Sentence Comprehension: Evidence from Event-Related Optical Signals

Using the event-related optical signal (EROS) technique, this study investigated the dynamics of semantic brain activation during sentence comprehension. Participants read sentences constituent-by-constituent and made a semantic judgment at the end of each sentence. The EROSs were recorded simultaneously with ERPs and time-locked to expected or unexpected sentence-final target words. The unexpected words evoked a larger N400 and a late positivity than the expected ones. Critically, the EROS results revealed activations first in the left posterior middle temporal gyrus (LpMTG) between 128 and 192 ms, then in the left anterior inferior frontal gyrus (LaIFG), the left middle frontal gyrus (LMFG), and the LpMTG in the N400 time window, and finally in the left posterior inferior frontal gyrus (LpIFG) between 832 and 864 ms. Also, expected words elicited greater activation than unexpected words in the left anterior temporal lobe (LATL) between 192 and 256 ms. These results suggest that the early lexical-semantic retrieval reflected by the LpMTG activation is followed by two different semantic integration processes: a relatively rapid and transient integration in the LATL and a relatively slow but enduring integration in the LaIFG/LMFG and the LpMTG. The late activation in the LpIFG, however, may reflect cognitive control.     

Cerebral activations related to ballistic, stepwise interrupted and gradually modulated movements in Parkinson patients

Patients with Parkinson’s disease (PD) experience impaired initiation and inhibition of movements such as difficulty to start/stop walking. At single-joint level this is accompanied by reduced inhibition of antagonist muscle activity. While normal basal ganglia (BG) contributions to motor control include selecting appropriate muscles by inhibiting others, it is unclear how PD-related changes in BG function cause impaired movement initiation and inhibition at single-joint level. To further elucidate these changes we studied 4 right-hand movement tasks with fMRI, by dissociating activations related to abrupt movement initiation, inhibition and gradual movement modulation. Initiation and inhibition were inferred from ballistic and stepwise interrupted movement, respectively, while smooth wrist circumduction enabled the assessment of gradually modulated movement. Task-related activations were compared between PD patients (N = 12) and healthy subjects (N = 18). In healthy subjects, movement initiation was characterized by antero-ventral striatum, substantia nigra (SN) and premotor activations while inhibition was dominated by subthalamic nucleus (STN) and pallidal activations, in line with the known role of these areas in simple movement. Gradual movement mainly involved antero-dorsal putamen and pallidum. Compared to healthy subjects, patients showed reduced striatal/SN and increased pallidal activation for initiation, whereas for inhibition STN activation was reduced and striatal-thalamo-cortical activation increased. For gradual movement patients showed reduced pallidal and increased thalamo-cortical activation. We conclude that PD-related changes during movement initiation fit the (rather static) model of alterations in direct and indirect BG pathways. Reduced STN activation and regional cortical increased activation in PD during inhibition and gradual movement modulation are better explained by a dynamic model that also takes into account enhanced responsiveness to external stimuli in this disease and the effects of hyper-fluctuating cortical inputs to the striatum and STN in particular.     

Optimization of backward giant circle technique on the asymmetric bars

The release window for a given dismount from the asymmetric bars is the period of time within which release results in a successful dismount. Larger release windows are likely to be associated with more consistent performance because they allow a greater margin for error in timing the release. A computer simulation model was used to investigate optimum technique for maximizing release windows in asymmetric bars dismounts. The model comprised four rigid segments with the elastic properties of the gymnast and bar modeled using damped linear springs. Model parameters were optimized to obtain a close match between simulated and actual performances of three gymnasts in terms of rotation angle (1.5 degrees ), bar displacement (0.014 m), and release velocities (<1%). Three optimizations to maximize the release window were carried out for each gymnast involving no perturbations, 10-ms perturbations, and 20-ms perturbations in the timing of the shoulder and hip joint movements preceding release. It was found that the optimizations robust to 20-ms perturbations produced release windows similar to those of the actual performances whereas the windows for the unperturbed optimizations were up to twice as large. It is concluded that robustness considerations must be included in optimization studies in order to obtain realistic results and that elite performances are likely to be robust to timing perturbations of the order of 20 ms.     

Temporal aspects of excitation-contraction coupling in airway smooth muscle.

In airway smooth muscle (ASM), ACh induces propagating intracellular Ca2+ concentration ([Ca2+]i) oscillations (5-30 Hz). We hypothesized that, in ASM, coupling of elevations and reductions in [Ca2+]i to force generation and relaxation (excitation-contraction coupling) is slower than ACh-induced [Ca2+]i oscillations, leading to stable force generation. When we used real-time confocal imaging, the delay between elevated [Ca2+]i and contraction in intact porcine ASM cells was found to be approximately 450 ms. In beta-escin-permeabilized ASM strips, photolytic release of caged Ca2+ resulted in force generation after approximately 800 ms. When calmodulin (CaM) was added, this delay was shortened to approximately 500 ms. In the presence of exogenous CaM and 100 microM Ca2+, photolytic release of caged ATP led to force generation after approximately 80 ms. These results indicated significant delays due to CaM mobilization and Ca2+-CaM activation of myosin light chain kinase but much shorter delays introduced by myosin light chain kinase-induced phosphorylation of the regulatory myosin light chain MLC20 and cross-bridge recruitment. This was confirmed by prior thiophosphorylation of MLC20, in which force generation occurred approximately 50 ms after photolytic release of caged ATP, approximating the delay introduced by cross-bridge recruitment alone. The time required to reach maximum steady-state force was >15 s. Rapid chelation of [Ca2+]i after photolytic release of caged diazo-2 resulted in relaxation after a delay of approximately 1.2 s and 50% reduction in force after approximately 57 s. We conclude that in ASM cells agonist-induced [Ca2+]i oscillations are temporally and spatially integrated during excitation-contraction coupling, resulting in stable force production.     

Temporal parameters of male—female sound communication in Leptophyes punctatissima

ABSTRACT. Quantitative information is presented about acoustic communication between the sexes of the speckled bush cricket Leptophyes punctatissima Bosc (Orthoptera: Tettigoniidae). The male song elicits an acoustic response from a receptive female with a net delay (excluding the travelling time of the sound) of about 25 ms depending upon ambient temperature. Only when the female responses fall within the narrow temporal window between 20 and 50 ms after the onset of his song does the male perform phonotaxis. The precise timing of this duet is described, and its advantages and disadvantages are discussed.     

Stance and swing phase detection during level and slope walking in the cat: effects of slope, injury, subject and kinematic detection method

In quadrupeds, there have been limited comparisons of gait timing events detection (e.g., paw contact, PC and paw-off, PO) determined from kinematics and forceplates. The goal of this study was to investigate the effect of different slopes (0, -27, +27°), recovery times after ankle extensor nerve injury and repair (2, 6, 12 weeks), subjects and detection methods on accuracy of kinematically derived PC and PO timings during feline walking. Right hindlimb kinematics and ground reaction forces (GRF) of 4 cats walking along a sloped walkway with embedded forceplates were recorded. A total of 963 walking cycles were analyzed. Gait timings were determined from five kinematic methods based on displacements, velocities or accelerations of hindlimb markers. GRF based 'gold standard' timings for PC and PO were used to determine the systematic and random error of kinematic timing. Systematic errors between the kinematic methods differed significantly (p<0.05). Methods based on vertical paw peak acceleration and velocity gave the smallest systematic errors for PC and PO, respectively. The smallest random errors (standard deviations) for PC and PO were demonstrated by method based on paw horizontal displacement relative to greater trochanter: 13.4ms and 6.6ms, respectively. Effects of slope and subject on systematic errors of kinematic methods were significant, whereas effects of recovery time after nerve injury were not. It was concluded that timing of gait events can be determined consistently using kinematics, although adjustments must be made to account for the systematic error which varies according to subject and slope condition.     

Implicit and Explicit Timing in Oculomotor Control

The passage of time can be estimated either explicitly, e.g. before leaving home in the morning, or implicitly, e.g. when catching a flying ball. In the present study, the latency of saccadic eye movements was used to evaluate differences between implicit and explicit timing. Humans were required to make a saccade between a central and a peripheral position on a computer screen. The delay between the extinction of a central target and the appearance of an eccentric target was the independent variable that could take one out of four different values (400, 900, 1400 or 1900 ms). In target trials, the delay period lasted for one of the four durations randomly. At the end of the delay, a saccade was initiated by the appearance of an eccentric target. Cue&target trials were similar to target trials but the duration of the delay was visually cued. In probe trials, the duration of the upcoming delay was cued, but there was no eccentric target and subjects had to internally generate a saccade at the estimated end of the delay. In target and cue&target trials, the mean and variance of latency distributions decreased as delay duration increased. In cue&target trials latencies were shorter. In probe trials, the variance increased with increasing delay duration and scalar variability was observed. The major differences in saccadic latency distributions were observed between visually-guided (target and cue&target trials) and internally-generated saccades (probe trials). In target and cue&target trials the timing of the response was implicit. In probe trials, the timing of the response was internally-generated and explicitly based on the duration of the visual cue. Scalar timing was observed only during probe trials. This study supports the hypothesis that there is no ubiquitous timing system in the brain but independent timing processes active depending on task demands.     

Performance criteria for generating predictive optimal control simulations of bicycle pedaling

The purpose of this study was to identify one or more performance-based criteria that may be used to generate predictive optimal control simulations of submaximal pedaling. Two-legged pedaling simulations were generated based on minimizing muscle activation, muscle stress, metabolic energy, time derivative of muscle force, and minimizing metabolic energy while pedaling smoothly. The simulations based on minimizing muscle activation and muscle stress most closely matched experimental pedaling data, with the activation criterion better matching experimental muscle activation timing. We conclude that predictive simulations of submaximal pedaling may be generated using a cost function based on minimizing muscle activation.     

Prolactin and delay of implantation in lactating adrenalectomized rats

Adrenalectomy before pregnancy in rats caused the persistence of high blood levels of prolactin (PRL) throughout the ensuing postpartum lactation. The persistence of hyperprolactinaemia was without effect on the (delayed) timing of blastocyst implantation during lactation. The findings indicate that ovarian cycles and pregnancy may continue normally despite the absence of adrenal hormones. They reveal that the enhanced release of pituitary PRL in response to suckling is not dependent on the removal of the adrenals during early lactation. The normal delay of blastocyst implantation through suckling, in the presence of abnormally high concentrations of PRL in blood, throws doubt on the supposed critical role of PRL in determining the length of the period of delay of implantation during lactation.     

Endocardial versus epicardial electrical synchrony during LV free-wall pacing

Cardiac resynchronization therapy has been most typically achieved by biventricular stimulation. However, left ventricular (LV) free-wall pacing appears equally effective in acute and chronic clinical studies. Recent data suggest electrical synchrony measured epicardially is not required to yield effective mechanical synchronization, whereas endocardial mapping data suggest synchrony (fusion with intrinsic conduction) is important. To better understand this disparity, we simultaneously mapped both endocardial and epicardial electrical activation during LV free-wall pacing at varying atrioventricular delays (AV delay 0-150 ms) in six normal dogs with the use of a 64-electrode LV endocardial basket and a 128-electrode epicardial sock. The transition from dyssynchronous LV-paced activation to synchronous RA-paced activation was studied by constructing activation time maps for both endo- and epicardial surfaces as a function of increasing AV delay. The AV delay at the transition from dyssynchronous to synchronous activation was defined as the transition delay (AVt). AVt was variable among experiments, in the range of 44-93 ms on the epicardium and 47-105 ms on the endocardium. Differences in endo- and epicardial AVt were smaller (-17 to +12 ms) and not significant on average (-5.0 +/- 5.2 ms). In no instance was the transition to synchrony complete on one surface without substantial concurrent transition on the other surface. We conclude that both epicardial and endocardial synchrony due to fusion of native with ventricular stimulation occur nearly concurrently. Assessment of electrical epicardial delay, as often used clinically during cardiac resynchronization therapy lead placement, should provide adequate assessment of stimulation delay for inner wall layers as well.     

Glutamate activation of a single NMDA receptor-channel produces a cluster of channel openings.

Activations of the N-methyl-D-aspartate (NMDA) receptor by glutamate were studied in outside-out patches from CA1 cells in rat hippocampal slices. Very low glutamate concentrations (20-100 nM) were used so that individual receptor activations would be well separated. The shut-time distribution contained at least five components, only the longest component being obviously concentration dependent. The three briefest shut-time components had time constants of 56 microseconds, 0.68 ms and 10.1 ms; all of these were independent of glutamate concentration. An individual activation of the receptor therefore produces a long cluster of channel openings that contains longer gaps than have been reported for receptor activations by other fast neurotransmitters. In addition, (i) some activations may contain still longer (mean 78 ms) shut periods generating 'super clusters', and (ii) a significant amount of NMDA current may be carried by prolonged ('high P(open)') periods during which the channel is open for most of the time. Such periods occur intermittently even at these very low glutamate concentrations. It is suggested that the slow time course of the NMDA receptor-mediated synaptic currents may be determined mainly by the channel activation kinetics.     

Shortening of atrioventricular delay at increased atrial paced heart rates improves diastolic filling and functional class in patients with biventricular pacing

Background

Use of rate adaptive atrioventricular (AV) delay remains controversial in patients with biventricular (Biv) pacing. We hypothesized that a shortened AV delay would provide optimal diastolic filling by allowing separation of early and late diastolic filling at increased heart rate (HR) in these patients.

Methods

34 patients (75 ± 11 yrs, 24 M, LVEF 34 ± 12%) with Biv and atrial pacing had optimal AV delay determined at baseline HR by Doppler echocardiography. Atrial pacing rate was then increased in 10 bpm increments to a maximum of 90 bpm. At each atrial pacing HR, optimal AV delay was determined by changing AV delay until best E and A wave separation was seen on mitral inflow pulsed wave (PW) Doppler (defined as increased atrial duration from baseline or prior pacemaker setting with minimal atrial truncation). Left ventricular (LV) systolic ejection time and velocity time integral (VTI) at fixed and optimal AV delay was also tested in 13 patients. Rate adaptive AV delay was then programmed according to the optimal AV delay at the highest HR tested and patients were followed for 1 month to assess change in NYHA class and Quality of Life Score as assessed by Minnesota Living with Heart Failure Questionnaire.

Results

81 AV delays were evaluated at different atrial pacing rates. Optimal AV delay decreased as atrial paced HR increased (201 ms at 60 bpm, 187 ms at 70 bpm, 146 ms at 80 bpm and 123 ms at 90 bpm (ANOVA F-statistic = 15, p = 0.0010). Diastolic filling time (P < 0.001 vs. fixed AV delay), mitral inflow VTI (p < 0.05 vs fixed AV delay) and systolic ejection time (p < 0.02 vs. fixed AV delay) improved by 14%, 5% and 4% respectively at optimal versus fixed AV delay at the same HR. NYHA improved from 2.6 ± 0.7 at baseline to 1.7 ± 0.8 (p < 0.01) 1 month post optimization. Physical component of Quality of Life Score improved from 32 ± 17 at baseline to 25 ± 12 (p < 0.05) at follow up.

Conclusions

Increased heart rate by atrial pacing in patients with Biv pacing causes compromise in diastolic filling time which can be improved by AV delay shortening. Aggressive AV delay shortening was required at heart rates in physiologic range to achieve optimal diastolic filling and was associated with an increase in LV ejection time during optimization. Functional class improved at 1 month post optimization using aggressive AV delay shortening algorithm derived from echo-guidance at the time of Biv pacemaker optimization.     

Timing of Muscle Response to a Sudden Leg Perturbation: Comparison between Adolescents and Adults with Down Syndrome

Movement disturbances associated with Down syndrome reduce mechanical stability, worsening the execution of important tasks such as walking and upright standing. To compensate these deficits, persons with Down syndrome increase joint stability modulating the level of activation of single muscles or producing an agonist-antagonist co-activation. Such activations are also observed when a relaxed, extended leg is suddenly released and left to oscillate passively under the influence of gravity (Wartenberg test). In this case, the Rectus femoris of adults with Down syndrome displayed peaks of activation after the onset of the first leg flexion. With the aim to verify if these muscular reactions were acquired during the development time and to find evidences useful to give them a functional explanation, we used the Wartenberg test to compare the knee joint kinematics and the surface electromyography of the Rectus femoris and Biceps femoris caput longus between adolescents and adults with Down syndrome. During the first leg flexion, adolescents and adults showed single Rectus femoris activations while, a restricted number of participants exhibited agonist-antagonist co-activations. However, regardless the pattern of activation, adults initiated the muscle activity significantly later than adolescents. Although most of the mechanical parameters and the total movement variability were similar in the two groups, the onset of the Rectus femoris activation was well correlated with the time of the minimum acceleration variability. Thus, in adolescents the maximum mechanical stability occurred short after the onset of the leg fall, while adults reached their best joint stability late during the first flexion. These results suggest that between the adolescence and adulthood, persons with Down syndrome explore a temporal window to select an appropriate timing of muscle activation to overcome their inherent mechanical instability.     

Comparison of secretory responses as measured by membrane capacitance and by amperometry.

We have compared capacitance and amperometric measurements in bovine chromaffin cells when secretion was elicited by flash photolysis of caged-calcium or step depolarizations. Total amperometric charge depended linearly on the amount of capacitance increase in both types of experiments. Furthermore, the properties of resolvable amperometric spikes after flashes were comparable to those observed after depolarizations, and their timing was compatible with the rate of capacitance increase. For a more detailed comparison, we used Monte Carlo simulations of multiple amperometric events occurring randomly over the surface of a sphere and summing together, to generate a reference amperometric signal for a given measured capacitance increase. Even after correction for endocytotic processes, the time courses of the integrated experimental records lagged behind the integrated Monte Carlo records by approximately 50 ms in flash and depolarization experiments. This delay was larger by approximately 40 ms than what can be expected from the "pre-foot delay" or the foot duration. Possible sources for the remaining delay could be diffusional barriers like the patch-pipette and the chamber bottom, which are not taken into account in the model. We also applied a novel type of fluctuation analysis to estimate the relative quantum size of an amperometric event. On average the estimates from experimental amperometric traces, in both flash and depolarization experiments, were 3-5 times smaller than estimates from simulated ones. This discrepancy can be due to contributions to the amperometric current from small vesicles, preferred release from cellular regions orientated toward the chamber bottom, or abundance of "foot-only" events. In conclusion, amperometric signals in flash and depolarization experiments displayed similar delayed average time courses and a lower estimate for the relative quantum size compared to the modeled amperometric signals. However, individual amperometric spikes were in agreement with expectations derived from capacitance signals.