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R J Sclabassi

Publications and source records attributed to R J Sclabassi.

At least 55 records · Page 3Linked to original sources

A systems theoretic approach to the study of CNS function.

This paper presents a paradigm for using a general systems theoretic approach to study central nervous system function. Neuronal systems are conceptualized as consisting of different populations of neurons, each of which may be treated as a unit with its own dynamic properties. These dynamic properties of each population are determined by fundamental characteristics of its constituent neurons. Different populations interact with each other through the network structure in which they are embedded. We are modeling the linear and nonlinear properties of these systems using a theoretical framework based on two complementary approaches. First, a functional power series is used to characterize the input/output properties of the system. Second, a state-variable approach is used to characterize the internal structure and function of the system and to identify specific relationships among physiological variables. We have extensively investigated the functional power series approach to study the cat somatosensory system and the rabbit hippocampal formation. Both of these systems exhibit nonlinear properties in their response to electrical stimulation, and these nonlinear properties are characterized by the high-order kernels of the functional power series. State-variable models are being formulated to map these input/output properties onto internal models of the systems.

Animals↗

Recording and processing aneurysmal vibration signals in dogs.

A specially designed computerized acoustic aneurysm detection system has been developed and used for recording the acoustic signal produced by aneurysms in dogs. Two transducer types, a modified horn-coupled microphone and a microvascular intra-operative Doppler flowmeter have been used. The results show that the aneurysm signal is time-varying and that a stronger vibration signal can be obtained if a proximal stenosis presents. With direct contact recording, the acoustic signals from aneurysms and parent arteries show different characteristics that can be easily distinguished. The aneurysm signals are processed by spectrograms, and a smoothing technique for suppressing noise is introduced.

Acoustics↗

Nonlinear systems analysis of the hippocampal perforant path-dentate projection. I. Theoretical and interpretational considerations.

1. Nonlinear systems analytic procedures, based on an orthogonalized functional power series approach, were developed for study of the transformational properties of the hippocampal formation. As a testing stimulus, the procedures utilize a train of electrical impulses with randomly varying interimpulse intervals. The specific case was considered of applying such a stimulus to the perforant path, a major afferent to the hippocampal dentate gyrus that arises from the entorhinal cortex. Resulting field potentials evoked within the dentate gyrus are recorded to all impulses in the train. Computational algorithms based on cross-correlations determine the relationship between the interimpulse interval within the random train and amplitude of the evoked dentate potentials. The calculations, which reduce to averaging procedures, were derived for first- and second-order terms, or kernels, of the orthogonalized functional power series. 2. It is proposed that such an approach can be applied to a single component of the complex field potential evoked in the dentate gyrus. This component, the population spike, reflects the action potential discharge of dentate granule cells. Thus, a field potential component for which the underlying neuronal generator is well-known can be analyzed with respect to the transformational characteristics of the network of neurons that influence that generator. Other components of the complex field potential produced by other generators can be ignored. It is shown that this adaptation has the effect of greatly simplifying both the computation and presentation of kernels. 3. As a further consequence of this adaptation, the resulting first- and second-order kernels were shown to have specific interpretations. The first-order kernel represents the average response of the orthodromically driven granule cells to the set of stimuli comprising the random impulse train. The second-order kernel quantitatively characterizes the nonlinearity of the granule cell response, and may be interpreted as a generalized recovery function; i.e., the first input of any pair of stimuli in the train activates the newtork, and the second input tests the modulatory influence of the network excited by the initial input. 4. Most past investigations of nonlinearities of the perforant path-dentate projection have utilized pairs of stimulus impulses. We show here that, for a second-order system, the expected results from paired impulse experiments may be predicted from second-order kernels. Disagreement between the measured and predicted results reflects interactions of a higher order, and thus, greater system complexity.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Nonlinear systems analysis of the hippocampal perforant path-dentate projection. II. Effects of random impulse train stimulation.

1. Nonlinear systems analytic techniques were used to characterize transformational properties of the network of neurons activated by perforant path input to the rabbit hippocampus. Trains of 4,064 impulses with randomly varying interimpulse intervals were used to stimulate perforant path fibers, and amplitudes of evoked dentate granule cell population spikes were measured. Interimpulse intervals of the random stimulus train were determined by a Poisson distribution with a mean interimpulse interval of 500 ms, and with intervals ranging from 1 to 5,000 ms. The response of dentate granule cells to this stimulation was assumed to reflect activity in the larger hippocampal network, because other subpopulations of neurons activated monosynaptically and polysynaptically within the hippocampal formation contribute to granule cell excitability through multiple feedforward and feedback pathways. System properties were characterized both for halothane anesthetized and chronically implanted, unanesthetized preparations. 2. Second-order kernel analysis showed that population spike amplitude was highly dependent on interimpulse interval. When population spikes of all latencies were included in the same analysis, stimulation impulses produced near-total suppression of spike amplitude when they were preceded 10-20 ms by another impulse in the train. Spike suppression extended to approximately 50 ms and was inversely related to length of the interimpulse interval. Suppression of granule cell response to intervals within the range of 10-50 ms was not influenced by halothane anesthesia. 3. Interstimulus intervals greater than approximately 50 ms resulted in a facilitation of population spike amplitude, with maximum facilitation occurring in response to intervals of 90-100 ms. The magnitude of maximum facilitation was significantly greater for anesthetized (129%) than for unanesthetized (74%) preparations. The range of intervals resulting in facilitation for unanesthetized animals could extend to 1,000-1,100 ms (average range, 61-714 ms). This was much greater than observed for population spikes recorded from anesthetized animals (50-364 ms), which exhibited suppression in response to intervals of approximately 300-700 ms. 4. Further analysis revealed that the nature of nonlinearities in population spike amplitude may depend on spike latency. For example, population spikes of "short" latency (3-4 or 4-5 ms, depending on the animal) exhibited only facilitation in response to interstimulus intervals of 1-4 ms.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Nonlinear systems analysis of the hippocampal perforant path-dentate projection. III. Comparison of random train and paired impulse stimulation.

1. The transformational properties of the network of hippocampal neurons activated monosynaptically and polysynaptically by electrical stimulation of the perforant path were analyzed using random impulse train and paired impulse stimuli. In response to both types of input, the amplitudes of granule cell population spikes evoked in the dentate gyrus were used as the measure of network output. The random stimulus train consisted of a series of 4,064 electrical impulses, with interimpulse intervals determined by a Poisson distribution; the mean interimpulse interval of the train was 500 ms, and the range was 1-5,000 ms. Paired impulse stimuli consisted of pairs of impulses separated by 10-1,200 ms; impulses pairs were delivered once every 20 s. The procedures were applied to both anesthetized and chronically implanted, unanesthetized preparations. 2. Nonlinear systems analysis of population spike responses evoked during random train stimulation revealed that dentate granule cell output to any impulse was highly dependent on the interval since a prior impulse. Data from anesthetized animals showed that population spike amplitudes were markedly suppressed in response to intervals less than 50 ms, facilitated in response to intervals of approximately 100 ms, suppressed slightly in response to intervals of 300-700 ms, and unaffected by intervals greater than 700 ms. Data from unanesthetized animals showed similar results except that facilitation rather than suppression of spike amplitude was observed in response to intervals of 300-700 ms, and could extend to intervals as great as 1,000 ms. 3. The results of paired impulse stimulation applied to the same preparations also showed that granule cell response was highly dependent on interimpulse interval. However, nonlinearities observed with paired impulse stimulation differed from those revealed by a random impulse signal. Compared to results of random train stimulation, a paired impulse format produced greater magnitude spike suppression in response to short interimpulse intervals (e.g., 10-20 ms), maximum facilitation in response to shorter interstimulus intervals (50 ms rather than 100 ms), greater magnitude spike facilitation, and greater suppression in response to intervals greater than or equal to 300 ms. Furthermore, there were virtually no differences in the nonlinearities of granule cell response recorded from anesthetized and unanesthetized animals when a paired impulse format was used, whereas several differences were observed with random train stimuli. 4.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Intra-aneurysmal pressure measurements in experimental saccular aneurysms in dogs.

Intra-aneurysmal pressure was studied in an experimental model of saccular aneurysm in dogs, using a vein pouch grafted onto a common carotid arterial bifurcation. The mean and the pulse pressures were recorded simultaneously from within the aneurysm and within the common carotid artery, before and after 50% proximal carotid artery stenosis. These experiments were performed under systemic normotension, hypotension, and hypertension. Normal data suggest that mean intracarotid and intra-aneurysmal pressures are similar and relate in a nearly linear fashion to mean arterial pressure. However, after 50% stenosis, the data had a cubic relationship, the reduction of pressure occurring only in the middle range of mean arterial pressure. Both intra-aneurysmal and intracarotid pulse pressures displayed less dependence on mean arterial pressure. However, sigmoid curves also were observed with the pulse pressures after 50% proximal common carotid artery stenosis. In all cases, after 50% stenosis, the rate of increase of the pulse pressures with mean arterial pressure was greater for higher mean arterial pressures. Our preliminary data indicate that a detailed study of intra-aneurysmal pressure and blood flow in relation to systemic variables such as mean arterial pressure, cardiac output, and peripheral resistance may not only suggest improved means of managing patients with intracranial aneurysms, but also may raise the possibility that, under certain conditions, higher intra-aneurysmal pressures may be induced by downstream stenosis.

Animals↗

Effect of low concentration stable xenon on the EEG power spectrum.

The effect on the central nervous system of inhaled stable xenon, at concentrations of 25%, 30% and 35%, was assessed by evaluating changes in power spectra computed on the electroencephalogram. Ten normal adult subjects were studied in a protocol designed as a repeated measures experiment. Synchronous changes in the EEG power spectra were observed with stable xenon inhalation. These changes were equivalent for symmetrical electrode pairs, but the time history of the changes differed depending on the cortical region being measure. This suggests regional effects of stable xenon inhalation on the mechanisms producing the EEG.

Adult↗

The relationship of the latency of the visual P100 wave to gender and head size.

Six separate recordings of the pattern-reversal visual evoked potentials of 8 male and 8 female healthy adults were made. The average resulting latencies to P100 (LP100) were correlated with head length and circumference as well as with gender and latency to N70 (LN70). There was better correlation of LP100 with head circumference than with gender, and no significant correlation of LP100 with head length or with LN70. Also, using head circumference as a predictor of LP100, the addition of gender to the regression equation did not improve the prediction. These results indicate that a major determinant of differences in LP100 in adults is head size rather than gender. These differences are suggested to be due to differences in the geometry of the head rather than to more general biological differences between males and females.

Adult↗

Neuronet: implementation of an integrated clinical neurophysiology system.

A distributed computing facility that subserves a wide variety of clinical and research neurophysiology functions is described. The backbone of the system is an Ethernet local area network to which are attached a number of "sub"-networks defined by functional requirements. A variety of computer systems are attached to the network, many of which are mounted in portable racks. The capabilities of the overall system are described along with the functions it serves.

Computer Communication Networks↗

An acoustic aneurysm-detector.

Intracranial aneurysms have a high prevalence in the adult population; and if they rupture, significant morbidity almost always ensues. However, pulsatile blood flow through aneurysms produces vibrational sound patterns that may be detected extracranially. Thus, an acoustic aneurysm-detector has been developed to detect the sounds produced by intracranial aneurysms prior to rupture. The design is based on the utilization of a hydrophone for signal detection and computational signal processing for signal extraction. Data are examined in the time domain, the frequency domain, and the time-frequency plane. Examples are presented from an animal model and from a patient with a known aneurysm.

Adult↗

Relationship between hepatic injury status and event related potentials.

Visual, auditory and somatosensory event related potentials were recorded from 58 patients with chronic nonalcoholic liver disease. The results of this study indicate that a significant, although somewhat modest, amount of variance on brainstem auditory, pattern visual and somatosensory ERP latency can be predicted by routinely obtained liver functional measures, albumin, prothrombin time, fasting ammonia level, globulin and especially indocyanine green clearance. Moreover, these associations are present in persons who are not overtly encephalopathic, underscoring the sensitivity of neurophysiologic measurement for detecting hepatic encephalopathy concomitant to only moderate severity of hepatic injury.

Adult↗

The effect of cortical ablation on afferent activity in the cat somatosensory system.

The modulatory influence of primary S1 cortex upon afferent activity in the somatosensory system was examined in acute cats. Modulatory influences due both to prior afferent activity and efferent activity on peripherally evoked neural responses in thalamic n. ventralis posterolateralis (VPL) and the dorsal column nuclei (DCN) were analyzed. The right superficial radial nerve was stimulated with suprathreshold pulses applied randomly in time. Evoked activity was recorded from ipsilateral DCN, contralateral VPL, and contralateral S1 cortex before and after ablation of S1 cortex. The data were analyzed using a modified functional power series. The responses were characterized by first- and second-order kernels computed by cross-correlation. S1 ablation reduced or eliminated the second positive peak in the VPL response. Incomplete S1 ablation produced a graded effect on this peak. In addition, S1 ablation eliminated the negative notch on the leading edge of the response observed in the nucleus cuneatus. The results from VPL suggest that the second VPL positive peak is produced by a tonic S1 influence on another region of the central nervous system that is coupled to VPL, rather than by a direct VPL-cortical-VPL reflex loop. The results from the DCN confirm earlier studies suggesting a cuneate-cortical-cuneate reflex loop.

Afferent Pathways↗

Computerized EEG spectral analysis in elderly normal, demented and depressed subjects.

Computerized spectral analysis of the EEG was performed in 35 patients with Alzheimer's disease and compared to patients with major depression (23) and healthy elderly controls (61). Compared to controls, demented patients had a significant increase in the theta and alpha 1 bandwidths as well as an increased theta-beta difference. The parasagittal mean frequency, beta 1 and beta 2 activity were significantly decreased. Depressed patients differed from demented patients, particularly at the lower end of the spectrum, having significantly less delta and theta activity. Like the demented group, depressed patients also had a decreased parasagittal mean frequency, beta 1 and beta 2 when compared to controls. In demented patients, there was a high correlation between several spectral parameters (parasagittal mean frequency, delta and theta activity, and the theta-beta difference) and the Folstein score, EEG measures used for discriminant analysis were more accurate in identifying demented patients who had lower Folstein scores.

Aged↗

Cardiovascular and electroencephalographic effects of laudanosine in "nephrectomized" cats.

We studied a cat model simulating laudanosine accumulation in the "anephric" patient. Cardiovascular effects were seen only with the bolus doses of laudanosine 2 mg kg-1, and at plasma laudanosine concentrations unlikely to be achieved clinically. Similarly, EEG and power spectra analysis showed no evidence of epileptiform activity at all plasma laudanosine concentrations achieved. The non-specific EEG/power spectra changes observed may reflect a direct CNS activity with neurodepression, since laudanosine was shown by its presence in CSF to cross the blood-brain barrier. These EEG changes were observed at plasma concentrations eight to 10 times those observed in humans during infusion of atracurium. Thus, laudanosine accumulation and related CNS or cardiovascular toxicity seem unlikely following atracurium administration in the anephric patient.

Animals↗

Lysis of intraventricular blood clot with urokinase in a canine model: Part 1. Canine intraventricular blood cast model.

To test the safety and feasibility of using direct instillation of urokinase to induce rapid lysis of intraventricular clots, an animal model of intraventricular blood cast is required. Injections of 11 ml of fresh, unclotted autologous blood into the ventricles of adult mongrel dogs did not produce a solid blood cast in the ventricular system, suggesting that the adult dogs have an unusual ability to clear uncoagulated whole blood from the ventricles and subarachnoid space. Injection of 9 ml of preclotted blood resulted in a subtotal cast of the ventricles, leaving only portions of the occipital horns free of solid clots. This volume of injected clots incurred no mortality and minimal morbidity, whereas injection of 10 to 12 ml resulted in a mortality of 42% and formidable morbidity. The technique of producing this intraventricular blood cast model, as well as that of implanting an indwelling ventricular catheter-reservoir system useful in chronic urokinase administration, is described.

Animals↗

Lysis of intraventricular blood clot with urokinase in a canine model: Part 2. In vivo safety study of intraventricular urokinase.

It was determined from in vitro experiments that the minimal dose of urokinase required to lyse 10 ml of clotted canine blood within a closed space must exceed 10,000 IU. We empirically doubled this minimum effective dose and tested the in vivo safety of injecting 20,000 IU of urokinase every 12 hours for 4 days into the ventricles of six adult mongrel dogs through an implanted catheter-reservoir system. The animals were monitored carefully for local and systemic bleeding by neurological and clinical examination, hematological tests reflecting systemic fibrinolytic status, serial computed tomography, and postmortem histological examinations of the brain, meninges, and peripheral organs. It was found that this intraventricular dose regimen of urokinase did not cause intracranial hemorrhage even though the dogs had recent brain wounds related to transcerebral ventricular catheterization. Mild activation of systemic fibrinolysis, implying passage of the enzyme from ventricle to blood, occurred 4 to 6 hours after each intraventricular injection, but no systemic hemorrhages were seen. This dose regimen also did not cause acute or chronic inflammatory changes in the brain or meninges and did not disturb cerebrospinal fluid circulation.

Animals↗

Lysis of intraventricular blood clot with urokinase in a canine model: Part 3. Effects of intraventricular urokinase on clot lysis and posthemorrhagic hydrocephalus.

Nine millilitres of preclotted autologous blood was injected into the ventricles of 10 adult mongrel dogs (control dogs) to create subtotal ventricular casts with solid clots. The neurological status and systemic fibrinolytic profiles were closely monitored, and the changes in clot and ventricular volumes were measured by serial computed tomography (CT) for 3 months. The control animals showed severe neurological impairment for 7 to 9 days. No visible lysis of the intraventricular clots occurred for 5 to 7 days, after which slow clot lysis occurred at a constant rate. Complete lysis of the 10 clots took 38 to 65 days, indicating that canine cerebrospinal fluid normally possessed limited capacity for in situ fibrinolysis. Of the 10 control dogs, 8 developed progressive ventricular enlargement after a transient initial shrinkage parallel with initial clot lysis. Their final ventricular volume at 3 months was as much as 14 times the base line ventricular volume. Necropsy studies disclosed increased basal subarachnoid fibrosis and extensive ependymal and subependymal damage in the lateral ventricular walls of the hydrocephalic dogs. Ten other dogs (UK dogs) were given similar ventricular clot injections. Six hours later, each UK dog was begun on a regimen of 20,000 IU of intraventricular urokinase every 12 hours until solid clots were no longer seen in the ventricles on CT. In all 10 UK dogs, intraventricular urokinase induced complete lysis in 3 to 6 days without causing local or systemic hemorrhages. The neurological status of all 10 dogs also improved promptly. In 8 UK dogs, the ventricles that were initially distended by clots showed rapid shrinkage parallel with thrombolysis to a final volume at 3 months of less than four times the initial ventricular volume. Only 2 animals had persistently large or expanding ventricles. At necropsy, the ependymal and subarachnoid spaces of the UK dogs were remarkably free of damage and fibrosis. The possible mechanisms by which intraventricular urokinase may prevent posthemorrhagic hydrocephalus are discussed.

Animals↗