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Biomedical subjects

S J Schiff

Publications and source records attributed to S J Schiff.

At least 19 recordsLinked to original sources

Adaptive electric field control of epileptic seizures.

We describe a novel method of adaptively controlling epileptic seizure-like events in hippocampal brain slices using electric fields. Extracellular neuronal activity is continuously recorded during field application through differential extracellular recording techniques, and the applied electric field strength is continuously updated using a computer-controlled proportional feedback algorithm. This approach appears capable of sustained amelioration of seizure events in this preparation when used with negative feedback. Seizures can be induced or enhanced by using fields of opposite polarity through positive feedback. In negative feedback mode, such findings may offer a novel technology for seizure control. In positive feedback mode, adaptively applied electric fields may offer a more physiological means of neural modulation for prosthetic purposes than previously possible.

Algorithms↗

From generalized synchrony to topological decoherence: emergent sets in coupled chaotic systems.

We consider the evolution of the unstable periodic orbit structure of coupled chaotic systems. This involves the creation of a complicated set outside of the synchronization manifold (the emergent set). We quantitatively identify a critical transition point in its development (the decoherence transition). For asymmetric systems we also describe a migration of unstable periodic orbits that is of central importance in understanding these systems. Our framework provides an experimentally measurable transition, even in situations where previously described bifurcation structures are inapplicable.

Entropy↗

Brain chirps: spectrographic signatures of epileptic seizures.

OBJECTIVE: A chirp is a brief signal within which the frequency content changes rapidly. Spectrographic chirps are found in signals produced from many biological and physical phenomena. In radar and sonar engineering, signals with chirps are used to localize direction and range to the signal source. Although characteristic frequency changes during epileptic seizures have long been observed, the correlation with chirps and chirp technology seems never to have been made. METHODS: We analyzed 19404 s (1870 s of which were from 43 seizures) of intracranially (subdural and depth electrode) recorded digital EEG from 6 patients for the presence of spectral chirps. Matched filters were constructed from methods in routine use in non-medical signal processing applications. RESULTS: We found that chirps are very sensitive detectors of seizures (83%), and highly specific as markers (no false positive detections). The feasibility of using spectral chirps as matched filters was demonstrated. CONCLUSIONS: Chirps are highly specific and sensitive spectrographic signatures of epileptic seizure activity. In addition, chirps may serve as templates for matched filter design to detect seizures, and as such, can demonstrate localization and propagation of seizures from an epileptic focus.

Brain↗

Periodic orbits: a new language for neuronal dynamics.

A new nonlinear dynamical analysis is applied to complex behavior from neuronal systems. The conceptual foundation of this analysis is the abstraction of observed neuronal activities into a dynamical landscape characterized by a hierarchy of "unstable periodic orbits" (UPOs). UPOs are rigorously identified in data sets representative of three different levels of organization in mammalian brain. An analysis based on UPOs affords a novel alternative method of decoding, predicting, and controlling these neuronal systems.

Action Potentials↗

Randomized trial of cerebrospinal fluid shunt valve design in pediatric hydrocephalus.

OBJECTIVE: Forty percent of standard cerebrospinal fluid shunts implanted for the treatment of pediatric hydrocephalus fail within the first year. Two new shunt valves designed to limit excess flow, particularly in upright positions, were studied to compare treatment failure rates with those for standard differential-pressure valves. METHODS: Three hundred-forty-four hydrocephalic children (age, birth to 18 yr) undergoing their first cerebrospinal fluid shunt insertion were randomized at 12 North American or European pediatric neurosurgical centers. Patients received one of three valves, i.e., a standard differential-pressure valve; a Delta valve (Medtronic PS Medical, Goleta, CA), which contains a siphon-control component designed to reduce siphoning in upright positions; or an Orbis-Sigma valve (Cordis, Miami, FL), with a variable-resistance, flow-limiting component. Patients were monitored for a minimum of 1 year. Endpoints were defined as shunt failure resulting from shunt obstruction, overdrainage, loculations of the cerebral ventricles, or infection. Outcome events were assessed by blinded independent case review. RESULTS: One hundred-fifty patients reached an endpoint; shunt obstruction occurred in 108 (31.4%), overdrainage in 12 (3.5%), loculated ventricles in 2 (0.6%), and infection in 28 (8.1%). Sixty-one percent were shunt failure-free at 1 year and 47% at 2 years, with a median shunt failure-free duration of 656 days. There was no difference in shunt failure-free duration among the three valves (P = 0.24). CONCLUSION: Cerebrospinal fluid shunt failure, predominantly from shunt obstruction and infection, remains a persistent problem in pediatric hydrocephalus. Two new valve designs did not significantly affect shunt failure rates.

Adolescent↗

Noninvasive assessment of language dominance in children and adolescents with functional MRI: a preliminary study.

BACKGROUND: Assessment of language organization is crucial in patients considered for epilepsy surgery. In children, the current techniques, intra-carotid amobarbital test (IAT) for language dominance, and cortical electrostimulation mapping (ESM), are invasive and risky. Functional magnetic resonance imaging (fMRI) is an alternative method for noninvasive functional mapping, through the detection of the hemodynamic changes associated with neuronal activation. We used fMRI, to assess language dominance in children with partial epilepsy. METHODS: Eleven right handed children and adolescents performed a word generation task during fMRI acquisition focused on the frontal lobes. Areas where the signal time course correlated with the test paradigm (r = 0.7) were considered activated. Extent and magnitude of signal changes were used to calculate asymmetry indices. Seven patients had IAT, ESM, or surgery outcome available for comparison. RESULTS: fMRI language dominance always agreed with IAT (6 cases) and ESM (1 case), showing left dominance in six and bilateral language in one. fMRI demonstrated left dominance in three additional children, and right dominance in one with early onset of left temporal epilepsy. Four children whose initial studies were equivocal due to noncompliance or motion artifacts were restudied successfully. CONCLUSIONS: fMRI can be used to assess language lateralization noninvasively in children. It has the potential to replace current functional mapping techniques in patients, and to provide important data on brain development.

Adolescent↗

Electric field suppression of epileptiform activity in hippocampal slices.

1. The effects of relatively small external DC electric fields on synchronous activity in CA1 and CA3 from transverse and longitudinal type hippocampal slices were studied. 2. To record neuronal activity during significant field changes, differential DC amplification was employed with a reference electrode aligned along an isopotential with the recording electrode. 3. Suppression of epileptiform activity was observed in 31 of 33 slices independent of region studied and type of slice but was highly dependent on field orientation with respect to the apical dendritic-somatic axis. 4. Modulation of neuronal activity in these experiments was readily observed at field strengths < or = 5-10 mV/mm. Suppression was seen with the field oriented (positive to negative potential) from the soma to the apical dentrites. 5. In vivo application of these results may be feasible.

Action Potentials↗

Quinolinic acid in tumors, hemorrhage and bacterial infections of the central nervous system in children.

A potential mechanism that may contribute to neurological deficits following central nervous system infection in children was investigated. Quinolinic acid (QUIN) is a neurotoxic metabolite of the kynurenine pathway that accumulates within the central nervous system following immune activation. The present study determined whether the levels of QUIN are increased in the cerebrospinal fluid of children with infections of the CNS, hydrocephalus, tumors or hemorrhage. Extremely high QUIN concentrations were found in patients with bacterial infections or the CNS, despite treatment with antimicrobial agents. CSF QUIN levels were also elevated to a lesser degree in patients with hydrocephalus or tumors. CSF L-kynurenine levels increased in parallel to the accumulations in QUIN, which is consistent with increased activity of the first enzyme of the kynurenine pathway, indoleamine-2,3-dioxygenase. The CSF levels of neopterin, a marker of immune and macrophage activation, were also increase in patients with infections. The cytokines tumor necrosis factor-alpha and interleukin-6 were also detected in some patients' samples, and were highest in patients with infection. These results suggest that QUIN is a sensitive marker of the presence of immune activation within the CNS. Further studies of QUIN as a potential contributor to neurologic dysfunction and neurodegeneration in children with CNS inflammation are warranted.

Adolescent↗

Looking for chaos in brain slices.

Many signals measured from the nervous system exhibit apparently random variability that is usually considered to be noise. The development of chaos theory has revealed that such random appearing variability may not, in fact, be random, but rather may be deterministic behavior that can reveal important information about the system's underlying mechanisms. We present some new methods for distinguishing determinism from randomness in experimental data, and we apply these methods to population neural responses recorded from hippocampal tissue slices.

Brain↗

Predictability of EEG interictal spikes.

To determine whether EEG spikes are predictable, time series of EEG spike intervals were generated from subdural and depth electrode recordings from four patients. The intervals between EEG spikes were hand edited to ensure high accuracy and eliminate false positive and negative spikes. Spike rates (per minute) were generated from longer time series, but for these data hand editing was usually not feasible. Linear and nonlinear models were fit to both types of data. One patient had no linear or nonlinear predictability, two had predictability that could be well accounted for with a linear stochastic model, and one had a degree of nonlinear predictability for both interval and rate data that no linear model could adequately account for.

Biophysical Phenomena↗

Periodic pacing an in vitro epileptic focus.

1. The effects of frequency of orthodromic and antidromic stimulation of CA3 on formation of electrographic seizurelike discharges in CA1 was studied in the high potassium hippocampal slice. 2. Within the range of stimulation of CA3 used, 0.1-10.0 Hz, a narrow range was identified between 1.0 and 1.3 Hz, where the tonic phase of seizure generation in CA1 was suppressed. This suppression was observed for both Schaffer collateral and mossy fiber stimulation.

Animals↗

Controlling chaos in the brain.

In a spontaneously bursting neuronal network in vitro, chaos can be demonstrated by the presence of unstable fixed-point behaviour. Chaos control techniques can increase the periodicity of such neuronal population bursting behaviour. Periodic pacing is also effective in entraining such systems, although in a qualitatively different fashion. Using a strategy of anticontrol such systems can be made less periodic. These techniques may be applicable to in vivo epileptic foci.

Action Potentials↗

Time-related patterns of ventricular shunt failure.

Proximal obstruction is reported to be the most common cause of ventriculoperitoneal (VP) shunt failure, suggesting that imperfect ventricular catheter placement and inadequate valve mechanisms are major causes. This study retrospectively examined patterns of shunt failure in 128 consecutive patients with symptoms of shunt malfunction over a 2-year period. Factors analyzed included site of failure, time from shunt placement or last revision to failure, age of patient at time of failure, infections, and primary etiology of the hydrocephalus. One hundred of these patients required revisions; 14 revisions were due to infections. In this series there was a higher incidence of distal (43%) than of proximal (35%) failure. The difference was not statistically significant when the overall series was considered; however, when factoring time to failure as a variable, marked differences were noted regardless of the underlying cause of hydrocephalus or the age of the patient. Of the 49 patients needing a shunt revision or replacement within 2 years of the previous operation, 50% had proximal malfunction, 14% distal, and 10% had malfunctions attributable directly to the valve itself. Also, 12 of the 14 infections occurred during this time interval. In sharp contrast, of the 51 patients having shunt failure from 2 to more than 12 years after the previous procedure, 72% had distal malfunction, 21% proximal, and only 6% had a faulty valve or infection. This difference between time to failure for proximal versus distal failures was statistically significant (P < 0.00001 for both Student's t-test and non-parametric Mann-Whitney U-test).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Fast wavelet transformation of EEG.

Wavelet transforms offer certain advantages over Fourier transform techniques for the analysis of EEG. Recent work has demonstrated the applicability of wavelets for both spike and seizure detection, but the computational demands have been excessive. We compare the quality of feature extraction of continuous wavelet transforms using standard numerical techniques, with more rapid algorithms utilizing both polynomial splines and multiresolution frameworks. We further contrast the difference between filtering with and without the use of surrogate data to model background noise, demonstrate the preservation of feature extraction with critical versus redundant sampling, and perform the analyses with wavelets of different shape. Comparison is made with windowed Fourier transforms, similarly filtered, at different data window lengths. We here report a dramatic reduction in computational time required to perform this analysis, without compromising the accuracy of feature extraction. It now appears technically feasible to filter and decompose EEG using wavelet transforms in real time with ordinary microprocessors.

Brain↗

Stochastic versus deterministic variability in simple neuronal circuits: I. Monosynaptic spinal cord reflexes.

Long time series of monosynaptic Ia-afferent to alpha-motoneuron reflexes were recorded in the L7 or S1 ventral roots in the cat. Time series were collected before and after spinalization at T13 during constant amplitude stimulations of group Ia muscle afferents in the triceps surae muscle nerves. Using autocorrelation to analyze the linear correlation in the time series demonstrated oscillations in the decerebrate state (4/4) that were eliminated after spinalization (5/5). Three tests for determinism were applied to these series: 1) local flow, 2) local dispersion, and 3) nonlinear prediction. These algorithms were validated with time series generated from known deterministic equations. For each experimental and theoretical time series used, matched time-series of stochastic surrogate data were generated to serve as mathematical and statistical controls. Two of the time series collected in the decerebrate state (2/4) demonstrated evidence for deterministic structure. This structure could not be accounted for by the autocorrelation in the data, and was abolished following spinalization. None of the time series collected in the spinalized state (0/5) demonstrated evidence of determinism. Although monosynaptic reflex variability is generally stochastic in the spinalized state, this simple driven system may display deterministic behavior in the decerebrate state.

Afferent Pathways↗

Stochastic versus deterministic variability in simple neuronal circuits: II. Hippocampal slice.

Long time series of Schaffer collateral to CA1 pyramidal cell presynaptic volleys (stratum radiatum) and population spikes (stratum pyramidale) were evoked (driven) in rat hippocampal slices. From the driven CA1 region in normal [K+] perfusate, both population spike amplitude and an input-output function consisting of population spike amplitude divided by the presynaptic volley amplitude were analyzed. Raising [K+] in the perfusion medium to 8.5 mM, slices were induced to spontaneously burst fire in CA3 and long time series of inter-burst intervals were recorded. Three tests for determinism were applied to these series: a discrete adaptation of a local flow approach, a local dispersion approach, and nonlinear prediction. Surrogate data were generated to serve as mathematical and statistical controls. All of the population spike (6/6) and input-output (6/6) time series from the normal [K+] driven circuitry were stochastic by all three methods. Although most of the time series (5/6) from the autonomously bursting high [K+] state failed to demonstrate evidence of determinism, one (1/6) of these time series did demonstrate significant determinism. This single instance of predictability could not be accounted for by the linear correlation in these data.

Algorithms↗