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Biomedical subjects

Y Tsau

Publications and source records attributed to Y Tsau.

14 recordsLinked to original sources

Preliminary results of a new method for locating auricular acupuncture points.

Auricular acupuncture is widely used for the treatment of cocaine addiction, and there is an urgent need to conduct controlled clinical research of this intervention. One impediment to this endeavor is the lack of an objective and reliable method for identifying the hypothesized active and control points. In order to address this issue, we conducted two studies employing a constant current electrical device and a novel probing technique. In the first study, we assessed the reliability of our technique for measuring electrical skin resistance points (acupuncture or non-acupuncture) on the body and auricles. In the second study, we analyzed and compared the measurements of skin resistance of auricular acupuncture and control zones in a group of cocaine abusing patients. Findings suggest that our measurement method produced reliable measurements, and that active acupuncture zones revealed a significantly different pattern of electrical skin resistance readings compared to control zones. This method may be useful for locating active and control points in controlled clinical trials of auricular acupuncture.

Acupuncture Points↗

Propagating activation during oscillations and evoked responses in neocortical slices.

Population activity in the cortex is poorly understood. In this report we use voltage-sensitive dye imaging to examine the spatiotemporal patterns of a 7-10 Hz oscillation in neocortical slices from rat somatosensory areas. This oscillation appeared as a component of spontaneous epochs when the preparation was bathed in low [Mg] artificial CSF (ACSF) (Silva et al., 1991). Each epoch started with a synchronized spike, and 3-200 cycles of oscillation emerged afterward. Voltage-sensitive dye imaging revealed that the oscillations in the local field potential recordings were actually caused by a propagating population activation. This activation propagated in a relatively uniform size (not expanding). We call this confined, propagating activation a "dynamic ensemble." During each oscillation cycle, one (occasionally two) dynamic ensemble(s) appeared in the slice and was sustained for 60-200 msec. Dynamic ensembles propagated at approximately 30 mm/sec; the activity could propagate in both directions in cortical slices. The propagation consisted in part of "jumps," the locations of which were not fixed. Dynamic ensembles were distinguishable from the epileptiform spikes that occurred in low [Mg] ACSF. Population events similar to dynamic ensembles were also evoked under conditions of unaltered excitability (slice in normal ACSF) by electrical stimulation that activated a low density of neurons in a large area. Our data suggest that self-sustained, spatially confined, and propagating dynamic ensembles might be related to the epoch oscillations in somatosensory cortex seen in vivo (Nicolelis et al., 1995) and thus resemble one form of population activation in the neocortex.

Animals↗

Epileptiform activity can be initiated in various neocortical layers: an optical imaging study.

The initiation site for triggering epileptiform activity was investigated via optical imaging using voltage-sensitive dyes in the neocortical slice perfused with artificial cerebral spinal fluid containing nominally zero magnesium. The neocortical slices (400-microm thick) were harvested from Sprague-Dawley rats (P21-28). Optical imaging was made by using a high speed photodiode array. Spontaneous epileptiform activity emerged 20-40 min after the preparation was perfused with zero-magnesium solution. There was a good correspondence between electrical and optical signals (n = 46), although the details of the two recordings were somewhat different. The initiation sites were measured optically in 11 preparations. Among them, four were found to be located in superficial layers, two were found in middle layers, and five were found in deep layers. Repeated recordings revealed that these initiation sites were relatively stable; shifting of the initiation site was not observed. Therefore spontaneous epileptiform activity could be initiated in various cortical layers, from layer I to layer VI. The activation started from a small area <0.04 mm(3) and spread smoothly from the initiation site to adjacent cortical areas, suggesting that the initiation site is very confined to one of the cortical layers. The initiation sites were distributed randomly in various cortical areas, and no higher probability was found in a special cortical region. Electrical stimulation delivered via a glass microelectrode filled with 2 M NaCl (2-5 MOhms) could reliably trigger epileptiform activity that had the same characteristics as the spontaneous activity. The cortical neurons activated directly by the stimulation were around the electrode's tip and estimated to be within a 50-microm area, suggesting that only a few neurons were needed to form an initiation site. Because the timing for stimulation was arbitrary and the evoked events were initiated independent of discharges of neurons in any other layers, it is likely that the initiation site for epileptiform activity in various cortical layers is independent of the control of layer V pyramidal neurons. Together these finding suggest that the epileptiform focus is confined and can be formed in several (probably all) neocortical layers and in many cortical areas. The initiating neurons may be of different types because neuronal types in various cortical layers are different.

Animals↗

Urinary epidermal growth factor excretion in children with chronic renal failure.

To investigate the excretion of urinary epidermal growth factor (EGF) in children with chronic renal failure (CRF), we have measured the urinary EGF/creatinine ratio (EGF/Cr) and the 24-hour urine EGF concentration in 19 children with CRF, 11 children with kidney disease and normal creatinine clearance, and 12 healthy children. Children with CRF had a significantly lower daily urine EGF concentration as well as urinary EGF/Cr. In contrast, children with kidney disease and normal renal function had normal daily urine EGF levels and urinary EGF/Cr. Accompanied by no difference in serum EGF between these two groups of patients, these data provide indirect evidence of the kidney as a source of human urinary EGF. There was a positive correlation of urinary EGF/Cr with creatinine clearance in all renal patients (r = 0.608, n = 30, p < 0.001). A much better correlation was found between daily urine EGF and creatinine clearance (r = 0.855, n = 30, p < 0.001). Our results implicate that there is a functional relationship between glomerular filtration and urinary EGF excretion, and that the urinary EGF/Cr may be a reliable indicator of urinary EGF excretion in children with CRF.

Case-Control Studies↗

Voltage-sensitive dyes for monitoring multineuronal activity in the intact central nervous system.

Optical monitoring of activity provides new kinds of information about brain function. Two examples are discussed in this article. First, the spike activity of many individual neurons in small ganglia can be determined. Second, the spatiotemporal characteristics of coherent activity in the brain can be directly measured. This article discusses both general characteristics of optical measurements (sources of noise) as well as more methodological aspects related to voltage-sensitive dye measurements from the nervous system.

Action Potentials↗

Initiation of spontaneous epileptiform activity in the neocortical slice.

Cortical local circuitry is important in epileptogenesis. Voltage-sensitive dyes and fast imaging were used to visualize the initiation of spontaneous paroxysmal events in adult rat neocortical slices. Although spontaneous paroxysmal events could start from anywhere in the preparation, optical imaging revealed that all spontaneous events started at a few confined initiation foci and propagated to the whole preparation. Multielectrode recording over hundreds of spontaneous events revealed that often two or three initiation foci coexisted in each preparation (n = 10). These foci took turns being dominant; the dominant focus initiated the majority of the spontaneous paroxysmal events during that period. The dominant focus and dynamic rearrangement of foci suggest that the initiation of spontaneous epileptiform events involves a local multineuronal process, perhaps with potentiated synapses.

Action Potentials↗

Voltage-sensitive dye recording using retrogradely transported dye in the chicken spinal cord: staining and signal characteristics.

We describe a novel method for retrogradely labeling specific neuronal populations using voltage-sensitive dyes. Styryl dyes were injected into the ventral roots of the isolated embryonic chick spinal cord. After waiting several hours, the dye labeled motoneurons and autonomic preganglionic neurons. Neuronal cell bodies, dendrites and axons were labeled; we presume that the dye traveled either by retrograde transport or by diffusion within the membrane of the axon to which the dyes were initially applied. Using either a photodiode array or a photomultiplier, fluorescence changes could be recorded from motoneurons following antidromic or synaptic activation. Several characteristics of the fluorescence changes were measured indicating that the signals did indeed reflect changes in the motoneuron membrane potential. The best labeling and optical signals were obtained using the relatively hydrophobic dyes di-8-ANEPPQ and di-12-ANEPEQ. In the great majority of cases these dyes responded with an increase in fluorescence of 1-3% (delta F/F) in response to synaptic or antidromic depolarization of the motoneurons. We anticipate that these techniques should be useful in the mapping of activity patterns and connectivity in neural networks within a defined population of neurons.

Action Potentials↗

Dye screening and signal-to-noise ratio for retrogradely transported voltage-sensitive dyes.

Using a novel method for retrogradely labeling specific neuronal populations, we tested different styryl dyes in attempt to find dyes whose staining would be specific, rapid, and lead to large activity dependent signals. The dyes were injected into the ventral roots of the isolated chick spinal cord from embryos at days E9-E12. The voltage-sensitive dye signals were recorded from synaptically activated motoneurons using a 464 element photodiode array. The best labeling and optical signals were obtained using the relatively hydrophobic dyes di-8-ANEPPQ and di-12-ANEPEQ. Over the 24 h period we examined, these dyes bound specifically to the cells with axons in the ventral roots. The dyes responded with an increase in fluorescence of 1-3% (delta F/F) in response to synaptic depolarization of the motoneurons. The signal-to-noise ratio obtained in a single trial from a detector that received light from a 14 x 14 microns2 area of the motoneuron population was about 10:1. Nonetheless, signals on neighboring diodes were similar, suggesting that we were not detecting the activity of individual neurons. Retrograde labeling and optical recording with voltage-sensitive dyes provides a means for monitoring the activity of identified neurons in situations where microelectrode recordings are not feasible.

Animals↗

Measure and statistical test for cross-correlation between paired neuronal spike trains with small sample size.

Recent development of multi-unit recording techniques such as optical recording and multi-electrode arrays makes it possible to record neuronal activities from tens or hundreds of neurons simultaneously. To analyze functional connections between these neurons, cross-correlation analysis has been most commonly applied to the hundreds to thousands of pairs of these neurons. However, conventional cross-correlation data needs statistical tests for significance especially when the sample size of recorded spike trains is small. Here, a multiple hypergeometric model based on a transformation of the cross-correlogram data to a 2 x J table has been suggested. The exact p value for significance can be obtained by the generalized Fisher's method with small sample size and a cross-correlation coefficient for the strength of cross-correlation can be obtained based on the R-square analogue for nominal data. For large sample size, chi 2 test can be applied based on the same transformation. Examples of real spike train data set and simulation show that the methods are applicable to the data of multi-unit activity with only tens of spikes. These methods are especially useful when thousands of cross-correlograms need to be screened quickly and automatically.

Action Potentials↗

Distributed aspects of the response to siphon touch in Aplysia: spread of stimulus information and cross-correlation analysis.

We examined two aspects of the response to siphon stimulation in an attempt to test the hypothesis that the Aplysia CNS functions as a distributed system. First, we estimated the number of central neurons that respond to a light touch to the siphon skin. We made voltage-sensitive dye recordings from the abdominal, pleural, pedal, and cerebral ganglia. From these recordings we estimated that 220 abdominal neurons, 110 pleural neurons, and 650 pedal neurons were affected by the light touch. Thus, the information about this mild and localized stimulus is very widely distributed within the Aplysia CNS. This result allows the possibility that the Aplysia CNS functions as a distributed system. If only a small number of neurons had responded to the touch, it would have supported the conclusion that the gill-withdrawal reflex could be generated by a small, dedicated circuit. Second, we searched for correlations between the spike times of the individual abdominal ganglion neurons. Two time scales were examined: a millisecond time scale corresponding to the duration of a fast synaptic potential and a seconds time scale corresponding to the duration of the gill-withdrawal movement. Neuron pairs with highly correlated spike activity on a millisecond time scale must be connected by (or have a common input that uses) relatively powerful, fast, excitatory synapses. We expected that this kind of synaptic interaction would be relatively rare in nervous systems that functioned in a distributed manner. Indeed, only 0.3% of the neuron pairs had correlation coefficients of 0.15 or greater. These correlations accounted for approximately 2% of the action potentials generated in response to siphon stimulation. Thus, large, fast excitatory synaptic interactions appear to be relatively unimportant. This result is consistent with the hypothesis that the abdominal ganglion functions as a distributed system. When the longer time scale was used for the cross-correlograms, a large fraction of the cell pairs had correlated activity because many neurons are activated by the stimulus. It was not possible to interpret the slow correlations in terms of actual synaptic interactions between individual neurons. Our results are consistent with the possibility that the abdominal ganglion functions in a distributed manner. However, this evaluation is indirect and thus only tentative conclusions can be drawn. Evidence from several sources suggests that the neuronal interactions for generating the Aplysia gill-withdrawal reflex are complex.

Animals↗

Consistency in nervous systems: trial-to-trial and animal-to-animal variations in the responses to repeated applications of a sensory stimulus in Aplysia.

What is the internal noise in a nervous system? We studied this question by determining the trial-to-trial consistency of the neuronal response in the abdominal ganglion of Aplysia californica. Because our voltage-sensitive dye recordings detected the spike activity from a large fraction of the neurons in the ganglion, these results provide a reasonably complete characterization of the consistency of the response to a sensory stimulus. The consistency of each neuron was evaluated by the number and timing of spikes in the response. The variability in the spike count was described using the coefficient of variation. The spike count variations follow a Poisson distribution, indicating that most of these variations were the result of a random process. For each neuron the reliability of the response to touch was measured in two ways; both measures indicated a broad distribution of reliabilities within the neuron population. The time of the maximum response also varied substantially in some animals. These timing variations were in part due to random processes and in part due to systematic effects (changes in activity of many neurons that were highly correlated). The time course of the activity of individual neurons was compared with the time course of the gill withdrawal. In some animals the activity of individual neurons was only poorly correlated with the behavior; in contrast, the summed activity of groups of neurons matched the behavior quite well. This implies that the behavioral output of the system may be a distributed combination of the activity of many neurons. The differences between animals were substantially larger than the trial-to-trial differences in one animal. The responses made by different preparations differed along many dimensions.

Action Potentials↗

Optical measurement of action potential activity in invertebrate ganglia.

With a voltage-sensitive dye and an array of silicon photodiodes we monitored the action potential activity of a large fraction of the cells in the Aplysia abdominal ganglion during the gill-withdrawal reflex. This capability allowed a direct determination of the spread of sensory information within the 1,000 neurons of the ganglion. Surprisingly, approximately 30% of the neurons are activated by a light touch to a small area of siphon skin. It is likely that many other neurons also receive large synaptic potentials, either excitatory or inhibitory, and thus even a very mild and restricted stimulus will have widely distributed effects. It seems to us that these results will force a more pessimistic view of the present understanding of the neuronal basis of apparently simple behaviors.

Action Potentials↗

Normalized power spectrum density function analysis on spike trains. I. Mathematical method and its evaluation.

The mathematical descriptions of normalized power spectrum density function (NPSDF) for rapidly estimating quantitatively the characteristics of frequency domain of neural spike trains were created and the efficient analytical method was thus established. All the tests and practical applications showed that the method reflects the frequency domain accurately and can satisfy most cases of the analysis in both frequency resolution and calculation speed.

Animals↗

Normalized power spectrum density function analysis on spike trains. II. Rhythms of unit activities in the somatosensory cortex of cats.

The normalized power spectrum density function (NPSDF) was used to analyse unit activities in the somatosensory cortex of cats. Thirty-four units from 40 cats were recorded and analysed. Rhythmic activities of 2-5 Hz were found in every unit, the strength increasing with mean firing rate and peripheral stimulation while the frequency remained constant. The results suggested: NPSDF is a better method for studying rhythm of unit activities; 2-5 Hz exists in the unit activities of the somatosensory cortex; and peripheral input may have the action of "phase tuning" in addition to the action of time-locked driven firing.

Animals↗